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441 © 2 017 Indian Journal of Cancer | Pulished by Wolters Kluwer - MedknowCancer and cure: A critical analysis
Roy PS, Saikia BJ
Department of Medical Oncology, Dr. B. Borooah Cancer Institute, Guwahati, Assam, India
Correspondence to: Dr. Roy PS, E‑mail: drpsr.roy@rediffmail.com
Abstract
Cancer is one of the most dreaded diseases of the 20th century and spreading further with continuance and increasing incidence in the 21st century. 
The situation is so alarming that every fourth person is having a lifetime risk of cancer. India registers more than 11 lakh new cases of cancer 
every year, whereas, this figure is above 14 million worldwide. Is cancer curable? The short answer to this question is “Yes.” In fact, all cancers 
are curable if they are caught early enough. Cancer cells continue to grow unless one of four things occur: (1) The cancerous mass is removed 
surgically; (2) using chemotherapy or another type of cancer‑specific medication, such as hormonal therapy; (3) using radiation therapy; or (4) the 
cancer cells shrink and disappear on their own.
Key Words:  Cancer, carcinogenesis, targeted therapy
Introduction
A hundred years ago, cancer was not so common; however, 
since the last couple of decades, its incidence has been rising 
alarmingly , probably due to our changing lifestyle, habits, 
and increased life expectancy . Cancer is one of the most 
dreaded diseases of the 20th century and spreading further


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since the last couple of decades, its incidence has been rising 
alarmingly , probably due to our changing lifestyle, habits, 
and increased life expectancy . Cancer is one of the most 
dreaded diseases of the 20th century and spreading further 
with continuance and increasing incidence in the 21st century . 
The situation is so alarming that every fourth person is 
having a lifetime risk of cancer.[1] India registers more than 
11 lakh new cases of cancer every year, whereas, this figure 
is above 14 million worldwide. We are constantly exposed 
to a variety of cancer causing agents, known as carcinogens.
What is cancer? Put simply; cancer is the abnormal growth 
of cells. Cancers arise from any organ or body structure and 
are composed of tiny cells that have lost the ability to stop 
growing. Occasionally , cancer may be detected “incidentally” by 
a laboratory test or radiological routine test or for an entirely 
different reason. In general, cancer must reach a size of 1 
cm, or be comprised of 1 million cells, before it is detected. 
At this point, it may be referred to as a “‘mass,” a “growth,” 
a “tumor,” a “nodule,” a “lump,” or a “lesion.” Exceptions 
to this general rule include cancers of the blood and bone 
marrow (leukemia’s and lymphomas) – which frequently do 
not produce a “mass,” but will be evident on laboratory tests.
Transformation of a normal cell into a cancerous cell is 
probably not such a critical event in the genesis of cancer;


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marrow (leukemia’s and lymphomas) – which frequently do 
not produce a “mass,” but will be evident on laboratory tests.
Transformation of a normal cell into a cancerous cell is 
probably not such a critical event in the genesis of cancer; 
rather it is the inability of immune cells of the body to 
identify and destroy the newly formed cancer cells when 
they are a few in numbers.[2] The risk of cancer is multiplied 
in those persons, whose immune system is suppressed due 
to any factor including chronic stress, old age, chronic 
debilitating disease, previous use of chemotherapy , and abuse 
of drugs such as analgesics, antibiotics, and corticosteroids.
Multidisciplinary Aspects
Cancer cells continue to grow unless one of four things 
occur:  (1) The cancerous mass is removed surgically; 
(2) using chemotherapy or another type of cancer -specific medication, such as hormonal therapy; (3) using radiation 
therapy; or (4) the cancer cells shrink and disappear on their 
own. This last event, while extremely rare, can occur with 
some melanomas or some kidney cancers.
Surgery , radiotherapy , and chemotherapy from the 
conventional approaches are used to treat cancer. Surgery 
was the first modality used successfully in the treatment of 
cancer. It is the only curative therapy for many common 
solid tumors. The most important determinant of a successful 
surgical therapy is the absence of distant metastases and 
no local infiltration. Chemotherapy is the administration


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cancer. It is the only curative therapy for many common 
solid tumors. The most important determinant of a successful 
surgical therapy is the absence of distant metastases and 
no local infiltration. Chemotherapy is the administration 
of cytotoxic agents (orally or intravenously , usually in 
combinations) resulting in cytotoxicity to both resting and 
dividing cells. The objective of cancer chemotherapy is to 
prevent cancer cells from multiplying, invading, metastasizing, 
and killing the patient. Systemic chemotherapy is the main 
treatment available for disseminated malignant diseases. 
Radiation therapy is a local modality used in the treatment of 
cancer. Other conventional techniques used in the treatment 
of cancer including bone marrow transplantation, peripheral 
stem cell transplantation, hormone therapy , photodynamic 
therapy , cryosurgery , immunotherapy , and gene therapy .
Is cancer curable? The short answer to this question is “Y es.” In 
fact, all cancers are curable if they are caught early enough. That 
is the justification for screening tests (such as mammograms, 
colonoscopies, and Pap smear examination). When cancers are 
caught early , they tend to be smaller; they are thus either easier 
to remove surgically or more likely to shrink in response to 
chemotherapy or radiation therapy . When cancer is localized, it 
can be totally removed by surgery but in most of the cases, it 
is practically impossible to detect cancer at such an early stage.


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chemotherapy or radiation therapy . When cancer is localized, it 
can be totally removed by surgery but in most of the cases, it 
is practically impossible to detect cancer at such an early stage. 
Early detection is often the key to surviving any form of cancer.
The diagnosis and treatment of cancer have come a long way 
in the last 50 years. In the past, cancer, the “C-word,” was a 
death sentence. Today , we can treat and cure several types of 
cancer; however, it is evident that these cancers need to be 
found at an early stage. More than 7 out of 10 children are 
cured of cancer. Testicular cancer, Hodgkin’s lymphoma and 
How to cite this article: Roy P, Saikia B. Cancer and cure: A 
critical analysis. Indian J Cancer 2016;53:441‑2.This is an open access article distributed under the terms of the Creative Commons 
Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix, 
tweak, and build upon the work non‑commercially, as long as the author is credited 
and the new creations are licensed under the identical terms.
For reprints contact:  reprints@medknow.comReview 
Article
Access this article online
Quick Response Code:Website: 
www.indianjcancer.com
DOI: 
10.4103/0019‑509X.200658 
PMID: 
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Roy and Saikia: Cancer and cureIndian Journal of Cancer | July-September 2016 | Volume 53 | Issue 3 442many cases of leukemia can all be cured in adults with current 
treatments. Most skin cancers are cured with surgery . Moreover, 
many cases of thyroid cancer and cancer of the larynx are cured 
with radiotherapy . Many other types of cancer are also cured 
if they are found early enough  – for example, 75% of breast 
cancers found at an early stage. Of course, there is still a long 
way to go before we can cure most cancers. The difficulty is 
that different cancers are caused by different things, so there 
is not one strategy that can prevent them. They also respond 
to different treatments, so not one kind of treatment can cure 
them all. Even though we can cure several types of cancers, it 
is important to maintain vigilance about screening for cancer.
Some forms of cancer are curable no matter when they 
are detected, and some are only curable if they are caught 
at any early stage. For example, acute leukemia and some 
types of lymphoma can be curable with chemotherapy . 
Certain lymphomas such as Hodgkin’s disease require 
radiation therapy for a cure. Other common cancers such 
as colon cancer, breast cancer, prostate cancer, lung cancer, 
and pancreatic cancer are all curable, but only if they are 
detected in early stages (Stage I or II).
Some cancers have high survival rates with early detection. 
Six highly treatable cancers among others are – cancers of


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and pancreatic cancer are all curable, but only if they are 
detected in early stages (Stage I or II).
Some cancers have high survival rates with early detection. 
Six highly treatable cancers among others are – cancers of 
breast, skin (nonmelanomas), colon, prostate, testes, and 
cervix. Most of the childhood malignancies (both solid and 
hematolymphoid) are curable.
Breast cancer is the most common nonskin cancer among 
women, as one out of every eight women will be diagnosed 
in her lifetime. In patients whose breast cancer is detected 
while still in localized form have a 5-year survival rate of 
98%, compared with a survival rate of 72% by Stage III 
and just 22% by Stage IV .[3,4]
Skin cancers (basal cell carcinoma and squamous cell 
carcinoma) are the most common form of all human cancers, 
and if found early , skin cancer is nearly 100% treatable. 
Likewise, diagnosing cervical cancer while the lesions are 
precancerous leads to a near 100% survival rate, but the 
rate drops to just 32% if diagnosed in Stage III and 16% if 
diagnosed at Stage IV . Testicular cancer is treatable in 99% 
of the time when detected early , but only 73% are cancer -free 
after 5 years if diagnosed in advanced stages. Similarly , 5-year 
survival rate when colon cancer is detected early is 90%, yet 
only 39% of cases are diagnosed before cancer has begun to 
spread. According to the Surveillance, Epidemiology , and End 
Results Program, it is 98% survivable for 5 or more years


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survival rate when colon cancer is detected early is 90%, yet 
only 39% of cases are diagnosed before cancer has begun to 
spread. According to the Surveillance, Epidemiology , and End 
Results Program, it is 98% survivable for 5 or more years 
if prostate cancer diagnosed at stages when the disease is 
confined to the prostate gland (Stage I and II).[1] The survival 
rate drops to about 28% if diagnosed at Stage IV .
Cancers cells not only have mutations that result in 
dysregulated expression of oncogenes and tumor suppressor 
genes, but these changes result in the alteration of expression 
of hundreds of genes. Looking at this, we have various forms 
of “targeted” therapy directed at specific single molecular 
targets or a class of molecular targets in cancer cells. With 
targeted therapy , the specific mechanism of action of the drug 
results in an increase in its therapeutic index. Currently , the 
two major classes of targeted therapy are the small molecule tyrosine kinase inhibitors and monoclonal antibodies (MABs). 
Imatinib, for instance, has been amazingly successful as a 
targeted agent directed against several members of a class of 
enzyme known as tyrosine kinases, and by that mechanism, 
it has been phenomenally successful as a treatment of chronic 
myeloid leukemia and gastrointestinal stromal tumors. 
Tamoxifen is a targeted therapy directed at the estrogen 
receptor (ER), and it still remains a mainstay of treatment for


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it has been phenomenally successful as a treatment of chronic 
myeloid leukemia and gastrointestinal stromal tumors. 
Tamoxifen is a targeted therapy directed at the estrogen 
receptor (ER), and it still remains a mainstay of treatment for 
ER-positive breast cancers, along with a newer class of drugs 
known as aromatase inhibitors.
Cancer researchers work on developing new and more 
effective surgery techniques, radiotherapy and chemotherapy 
drugs all the time. Biological therapies such as MABs, 
cancer vaccines, and gene therapies are all active areas of 
research. There are various anti-angiogenic drugs that can 
stop cancers from growing the blood vessels that they need. 
Research is also looking into developing cost-effective ways 
of screening for the different common cancers so they can 
be diagnosed early enough to be cured.
Avoiding immune destruction is now considered a hallmark 
of cancer, and the immunotherapy arena has exploded 
with the recent advances demonstrating an improvement 
in survival and a durability of response in patients with 
different cancer types, like in melanoma, which translates 
into an improved overall survival benefit.[5] To name those 
immunotherapeutic strategies that include the adoptive 
transfer of ex vivo activated T cells, immunomodulatory 
MABs, and cancer vaccines. Advances in molecular 
pathology will provide the means to identify the targets 
and will be used to subtype tumors and will provide predict


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transfer of ex vivo activated T cells, immunomodulatory 
MABs, and cancer vaccines. Advances in molecular 
pathology will provide the means to identify the targets 
and will be used to subtype tumors and will provide predict 
response to therapy and provide prognostic information.[6]
Conclusion
Unfortunately , although we do fairly well  (and in some cases 
very well) against early stage cancer, we do not do so well 
against Stage IV metastatic disease, particularly solid tumors. 
There is still a long way to go before we can cure most cancers.
Financial support and sponsorship
Nil.
Conﬂicts of interest
There are no conflicts of interest.
References
1. Mackay J, Jemal A, Lee NC, Parkin DM. The Cancer Atlas. Atlanta: 
American Cancer Society; 2006.
2. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 
2011;144:646-74.
3. Reeves GK, Beral V, Green J, Gathani T, Bull D; Million Women Study 
Collaborators. Hormonal therapy for menopause and breast -cancer risk 
by histological type: A cohort study and meta -analysis. Lancet Oncol 
2006;7:910-8.
4. Cuzick J, DeCensi A, Arun B, Brown PH, Castiglione M, Dunn B, et al.  
Preventive therapy for breast cancer: A consensus statement. Lancet 
Oncol 2011;12:496-503.
5. Couzin -Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. 
Science 2013;342:1432-3.
6. Bennett WP, Hussain SP, Vahakangas KH, Khan MA, Shields PG, 
Harris CC. Molecular epidemiology of human cancer risk: Gene -environment


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5. Couzin -Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. 
Science 2013;342:1432-3.
6. Bennett WP, Hussain SP, Vahakangas KH, Khan MA, Shields PG, 
Harris CC. Molecular epidemiology of human cancer risk: Gene -environment 
interactions and p53 mutation spectrum in human lung cancer. J Pathol 
1999;187:8-18.
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LECTURE NOTES 
 
For Health Officers 
 
 
 
 
Internal Medicine 
 
 
 
  
 
  
 
Editors 
Getachew Tizazu, M.D. . 
Jimma University 
Tadesse Anteneh, M.D., M.P.H. 
Hawassa University 
 
2006 
 
In collaboration with the Ethiopia Public Heal th Training Initiative, The Carter Center, 
the Ethiopia Ministry of Health, and the Ethiopia Ministry of Education


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Funded under USAID Cooperative Agreement No. 663-A-00-00-0358-00. 
 
 
Produced in collaboration with the Ethiopia Pu blic Health Training Initiative, The Carter 
Center, the Ethiopia Ministry of Health, and the Ethiopia Ministry of Education. 
   
 
   
 
Important Guidelines for Printing and Photocopying Limited permission is granted free of charge  to print or photocopy all pages of this 
publication for educational, not-for-profit use by health care workers, students or faculty. All copies must retain all author credits and copyright notices included in the 
original document. Under no circumstances is it permissible to sell or distribute on a 
commercial basis, or to claim authorship of, copies of material reproduced from this 
publication.  
 ©2006 by Getachew Tizazu, Tadesse Ante neh, Yoseph Mamo, Zenebe Assefa, 
Abere Bekela, Woldnecherkos Abebe, Fetih Mohammed, Tesfaye H/Tsion, 
Girma Tesfaye, and Dejuma Yadeta  All rights reserved. Except as expressly provided above, no part of this publication may 
be reproduced or transmitted in any form or by any means, electronic or mechanical, 
including photocopying, recording, or by any information storage and retrieval system, without written permission of the author or authors. 
 
 
 
 
This material is intended for educational use only by practicing health care workers or 
students and faculty in a health care field.


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i  
PREFACE 
 
Internal medicine is a vast and complicated fiel d that is based on strong scientific and clinical 
foundations. Moreover it is rapidly evolving and one needs periodic updating and catching up with the 
state of the art knowledge.   
Providing a comprehensive review of internal medici ne is not only difficult but almost impossible, as 
the field is vast and extensive. Despite this limitation, the authors have tried to provide a basic 
framework for working knowledge of Internal medicine. Essential topics are included as much as possible, and some chapters and topics are dealt extensively, such as Infectious diseases in general and Acute febrile illnesses, Tuberculosis, and HIV/AIDS in particular, as these are known to be the commonest causes of morbidity and mortality in developing countries, like ours.  
Even though a number of individuals have contributed in the original document of this lecture note, as 
more than 3 years have elapsed, most of the topics are reviewed, and some topics are completely 
rewritten, to include new developments and the state of the art scientific knowledge. 
This lecture note has been written primarily for Health officer students; however it can also be used by 
medical students and all other health science students who deal with patients, who have medical 
illnesses. 
         G e t a c h e w  T i z a z u  
 & 
         Tadesse Anteneh


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ii  
ACKNOWLEDGMENTS 
 
The editors are very grateful to all the medical professionals from Jimma, Hawassa, and Haramaya 
Universities, who have contributed in different ways to help develop this lecture note.  
Our special thanks go to the contributing authors, who took time from their very tight schedules, to 
prepare the draft lecture notes, in different topics. We sincerely appreciate the effort of the reviewers who have given their valuable comments and inputs during the initial within University review, and the subsequent joint reviews conducted at the Carter center, in Addis Ababa. 
We are mostly indebted to Dr. Akilu Azaje, Assistant professor of Internal medicine, in the department 
of Internal Medicine at the Medical faculty of A ddis Ababa University, who has reviewed the first draft 
lecture note, for his guidance and outstanding comments and valuable inputs. 
We would like to thank Dr. Tekabe Abdosh, who reviewed some topics of this lecture note.  
We also thank all the staff of the Carter center, Ethiopia for their hospitable hosting and assistance 
during the development of the lecture note.  
Last but not least our deepest gratitude extended to Ato Aklilu Mulugeta, for his tremendous effort, 
close follow-up and contribution in facilitating the completion of this lecture note.  
         G e t a c h e w  T i z a z u ,  M . D .  
          &           Tadesse Anteneh, M.D.


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iiiCONTRIBUTORS 
 
Contributors   Chapters or Topics contributed  
Getachew Tizazu, M.D. 
Assistant professor of internal medicine  
Faculty of medical sciences,  Jimma University  ( Currently working for Columbia University ICAP – 
Ethiopia Program) Infectious diseases 
Diseases of Metabolism and the Endocrine 
System 
Diseases of the connective tissue and  
Joints 
Diseases of the Nervous system Diseases of the Cardiovascular system 
Tadesse Anteneh, MD , MPH 
Assistant professor of Internal medicine ,  
Health sciences Faculty ,  
Hawassa University  Infectious diseases 
Diseases of the Respiratory system Diseases of the Gastrointestinal system 
Hematologic diseases 
Yoseph Mamo, M.D. 
Associate professor of Internal medicine ,  
Faculty of Medical sciences,  Jimma University  Diseases of Metabolism and the Endocrine 
System 
 
Zenebe Assefa, M.D.  
Assistant professor of Internal medicine ,  
Faculty of Medical sciences ,  Jimma University  Diseases of the Nervous system  
Abera Bekele, M.D. Assistant professor of Internal medicine ,  Faculty of Medical sciences ,  Jimma University  Diseases of the Kidneys


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iv 
Woldecherkos Abebe, M.D. 
Assistant professor of Internal medicine ,  
Faculty of Medical sciences ,  
Jimma University Diseases of the Cardiovascular System 
Fetih Mohammed, M.D.  
Assistant professor of Internal medicine ,  
Health sciences Faculty,  Jimma University  Disease of the Respiratory System Tuberculosis HIV/AIDS  
Tesfaye H/ Tsion M.D. 
Lecturer in the department of  Internal medicine ,  
Faculty of Medical sciences , Jimma University  Sexually transmitted Infections  HIV/AIDS 
Girma Tesfaye, M.D.  Lecturer in the department of  Internal medicine   Hematologic diseases 
Dejuma Yadeta, M.D. 
Lecturer in the department of Internal medicine ,  
Health sciences Faculty , Hawassa University Gastrointestinal diseases


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vTable of Contents  
 
Prefece ................................................................................................................... .... ......i 
Acknowledgement ............................................................................................................ii 
Table of Contents ............................................................................................................. i ii 
List of tables ................................................................................................................ ....vi 
Abbreviation .................................................................................................................. .. vii 
Chapter I. Infectious diseases.............................................................................. .........1  
1. Introduction  to infectious diaseses ......................................................... .........1 
2. Acute Febrile Ilnesses ............................................................................. .........4 
2.1.  Malaria  ......................................................................................... .........4  
2.2. Typhoid (enteric) fever ................................................................... .......17  
2.3. Relapsing fever  ............................................................................. .......22


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2.2. Typhoid (enteric) fever ................................................................... .......17  
2.3. Relapsing fever  ............................................................................. .......22 
      2.4  Typhus fever  ................................................................................. .......29    3. Helmenthiasis and Parasitic Diseases..................................................... .......34 
3.1 Intestinal Nematodes ...................................................................... .......34 3.2 Tissue Nematodes  ......................................................................... .......41 3.3 Filariasis & Related Infections ......................................................... .......43 3.4 Trematodes : Schistosomiasis  ....................................................... .......47 
3.5 Cestodes ......................................................................................... .......53 
3.6 Leishmaniasis ................................................................................. .......56 
4 Tuberculosis ............................................................................................. .......64  5 Human Immunodeficiency Virus and AIDS............................................... .......79 
6 Sexualy Transmited Diseases ................................................................. .....130


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6 Sexualy Transmited Diseases ................................................................. .....130 
7 Other infectious diaseses ......................................................................... .....145 
7.1 Tetanus........................................................................................... .....145 7.2 Rabies ............................................................................................ .....150 7.3 Anthrax .......................................................................................... .....153 
7.4 Brucellosis ...................................................................................... .....156 
 
Chapter II. Disease of the respiratory System .................................................... .....159 
1. Common Symptoms of respiratory system ............................................ .....159 
2. Upper Respiratory Tract Infection .......................................................... .....164


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vi3. Pneumonia............................................................................................. .....169 
4. Bronchial Asthma................................................................................... .....177 
5. Chronic obstructive pulmonary diseases  ............................................. .....185 
6. Suppurative lung diseases .................................................................... .....191  
6.1 Bronchiectasis................................................................................. .....191 6.2 Lung Abscess ................................................................................. .....193 
7. Pleurisy and pleural effusion.................................................................. .....195 8. Neoplasms of the lung .......................................................................... .....198 
 Chapter III. Diseases of the Cardiovascular System.......................................... .....203 
1. Rhehumatic Fever ................................................................................ .....205 
2. Congestive heart failure........................................................................ .....210


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1. Rhehumatic Fever ................................................................................ .....205 
2. Congestive heart failure........................................................................ .....210   
3. Valvular Heart Diaseses ...................................................................... .....218 4. Infective Endocarditis .......................................................................... .....228 5. Cardiomypathies .................................................................................. .....238 
6. Myocarditis .......................................................................................... .....246 
7. Hypertension ....................................................................................... .....251 8. Pericarditis and Pericardial effussion .................................................. .....266 9. Ischemic Heart Diseases and Myocardial Infarction ............................ .....271 
10. Cardiac Arrythemias ............................................................................ .....285 
  
Chapter IV. Diaseses of the Kidneys .................................................................. .....292 
1. Introduction to renal diseases ............................................................... .....292 
2. Acute nephritic syndrome  .................................................................... .....297


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1. Introduction to renal diseases ............................................................... .....292 
2. Acute nephritic syndrome  .................................................................... .....297 
3. Nephrotic Syndrome ............................................................................. .....301 4. Acute Renal Failure .............................................................................. .....305 5. Chronic Renal Failure ........................................................................... .....316 6. Urinary Tract Infection ........................................................................... .....327 
 
Chapter V. Disease of the Gastrointestinal system............................................ .....337 
1. Approach to patients with GI disorders ....................................................... .....337 
2. Gastritis and Peptic Ulcer Diseases ............................................................ .....342 
3. Malabsorption ............................................................................................. .....354 
4. Pancreatic Diseases ................................................................................... .....359 5. Hepatitis ...................................................................................................... .....365


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vii 6. Chronic Liver Diseases Cirrhosis and Hepatoma ....................................... .....373 
7. Diarrheal Diseases ...................................................................................... .....382 
 Chapter VI. Hematologic Diseases ...................................................................... .....389 
1. Anemia ........................................................................................................ .....389 2. Lukemias ..................................................................................................... .....405 
3. Lymphoma .................................................................................................. .....420 
4. Disorders of Hemostasis ............................................................................. .....425 
 
Chapter VII. Disease of Metabolism and Endocrine System ............................ .....433 
 
    1.  Introduction to Diseases of the Endocrine System ..................................... .....433     2. Diabetes Mellitus  ........................................................................................ .....435     3.  Thyroid diseases ......................................................................................... .....455     4.  Diseases of the Adrenal Gland ................................................................... .....474


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5.  Diseases of the Pituitary Gland .................................................................. .....480 
 Chapter VIII. Diseases of the Nervous System ................................................... .....491 
1. Headache .................................................................................................... .....491 
2. Diseases of the Spinal Cord ........................................................................ .....500 
3. Cerebrovascular diseases /Stroke .............................................................. .....507 
4. Impairment of Consciousness and Coma.................................................... .....515 5. Seizures  and Epilepsy ................................................................................ .....523 6. Parkinson’s diseases and other movement disorders ................................. .....536 
7. Peripheral Neuropathy................................................................................. .....547 
8. CNS infections : Meningitis and Encephalitis............................................... .....555 
 
Chapter XI. Connective Tissue Diseases and Diseases of Joints .................... .....562 
1. Systemic Lupus Erythromatous ( SLE ) ....................................................... .....562 2. Rheumatoid Arthritis .................................................................................... .....566


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1. Systemic Lupus Erythromatous ( SLE ) ....................................................... .....562 2. Rheumatoid Arthritis .................................................................................... .....566 
3. Other connective tissue diseases : Systemic Sclerosis , Mixed connective 
      tissue disorders ........................................................................................... .....573 4. Gout ............................................................................................................ .....576


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viiiLIST OF TABLES 
TableI-2.1-1 The basic characteristics of the two transmission types of malaria .... .........6 
Table I-2.1-2 Types of plasmodium and their clinical features ............................... .........9 Table I-2.3 -1 The basic characteristics of the two types of borreliae...................... .......25 Table I-3.6-1: Important causes of cutaneous leishmaniasis................................... .......61 
Table I- 4 -1: Tuberculosis Treatment Category...................................................... .......74 
Table I- 4-2: Anti TB drugs are classified in to two groups ..................................... .......76 Table I-4-3: Side Effects of common Anti TB drugs and Treatment of side effects ......77  Table I-5-1. Manifestations of Tuberculosis in early and advanced HIV.................. .....100 
Table I-5-2. Stages of ADIS dementia complex ...................................................... .....109 
Table I-5-3. Revised classification system for HIV infection (CDC Classification)... .....122 Table I-5-4. WHO Clinical Staging System for HIV/AIDS ........................................ .....122 Table II-4-1 Comparison of the two major types of Asthma .................................... .....178 Table II-4-2. Step wise approach for managing Asthma in adults .......................... .....183 
Table II-5-1 Summary of clinical manifestations of Chronic Bronchitis and Emphysema188


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Table II-5-1 Summary of clinical manifestations of Chronic Bronchitis and Emphysema188 
Table III -1-1 Jones criteria for the diagnosis of acute rheumatic fever ................... .....207 Table III -2-1:New York Heart Association Heart Failure Symptom Classification                         System.............................................................................................. .... .213 
Table III-4-1: Frequencies of Occurrence of prominent Clinical and Laboratory                        Manifestations in Endocarditis........................................................... .....233 Table III -4-2  The Duke Criteria for the Clinical Diagnosis of Infective Endocarditis ....234 Table III-5-1 Clinical classification of Cardiomyopathies ........................................ .....239 Table III-7-1 Classification of blood pressure for adults and older children ............ .....252 
Table –III-8-1.  Classification of Pericarditis ........................................................... .....267 
Table V-1-1 Main differences between exudative and transudative ascetic fluids . .....339 Table V-2-1 Some differences in the clinical manifestations between DU and GU .....347 Table V-2-2 Regimens recommended for eradication of H. pylori infection ........... .....350 
Table V -5-1 Comparisons of   some features of hepatitis A, B, and C .................. .....368


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Table V -5-1 Comparisons of   some features of hepatitis A, B, and C .................. .....368 
Table V-6-1 Stages of chronic hepatic encephalopathy and their manifestations .. .....379 Table VI-1-1 Criteria of anemia in adults at sea level ............................................. .....389 Table VI-1-2 Difference in between Cobalamine and Folate physiology and daily                      Requirement ....................................................................................... .....401  
Table VI-2-1 Showing the main features of acute leukemic cells ........................... .....411 Table VIII-2-3 The treatment of acute leukemias (Cytotoxic drugs & phases of treatment)412


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ix Table VI-4-1  Correlation of coagulation factor activity and severity in hemophiliac  
                       and factor IX deficiency ................................................................... .....430 
Table VI-4-2 Comparison between different coagulation disorders ........................ .....431 
Table VII-2-1 Criteria for the Diagnosis of Diabetes Mellitus .................................. .... 440 Table VII-4- 2 Interpretations of Water deprivation test .......................................... .....489 Table VIII-3-1 Characteristic features of different types of stroke ........................... .....510 
Table VIII-4-1 Glasgow coma Scale ....................................................................... .....517 
Table VIII-5-1 Selection of antiepileptic drugs ........................................................ .....530 Table VIII-7-1 Etiologies of neuropathies based the predominant symptoms or signs .547   Table VIII-8-1 CSF analysis findings in different types of meningitis ...................... .....558


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x ABBREVIATIONS AND ACRONYMS 
 
ABC  – Airway, Breathing, and Circulation 
ABG  - Arterial blood gas 
ACTH – Adrenocorticotrophic hormone 
ADH  – Antiduiretic hormone 
AFB – Acid fast bacilli 
AIDS  – Acquired Immunodeficiency Syndrome 
ALT/SGPT  – Alanine aminotransferase 
AMI – acute myocardial infarction 
ANC  – Antenatal care 
APOC  – African Programme for Onchocerciasis Control 
ARDS – Adult respiratory distress syndrome 
ARF – Acute rheumatic fever/acute renal failure 
ARTs  – Antiretroviral therapies 
ASO titer  – Antistreptolysin O titer 
AST/SGOT  - Aspartate aminotransferase   
AV - Atrioventricular or arteriovenous 
BCG – Bacille Calmette Guerin  
BF – Blood film 
BID – Twice a day 
BLCM  – Below left costal margin 
BM – Bone marrow 
BMI – Body mass index 
BP - Blood pressure 
BPH - Benign prostatic hypertrophy 
BS – Blood sugar 
BUN – Blood Urea Nitrogen 
CAD – Coronary artery disease 
CBC  – Complete blood count 
CHF - Congestive heart failure 
CNS – Central nervous system


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xi CPK  - Creatine phosphokinase   
CR – Creatinine 
CRF - Chronic renal failure 
CRH – Corticotrophic hormone 
CSF – cerebrospinal fluid 
CT – Computerized Tomogram 
CTLs – Cytotoxic T Lymphocytes  
CVD  – Cerebrovascular diseases 
CVS – Cardiovascular system 
CXR  – Chest x-ray 
DAT – Direct agglutination test 
DDI – Didanosine 
D4T- Stavudin 
DIC – Disseminated intravascular coagulopathy 
Direct IF  – direct Immunoflourescent  
DKA  – diabetic ketoacidosis 
DM – diabetes mellitus 
DNA - Deoxyribonucleic acid   
DOTS  – Directly Observed TB treatment Short course 
DW - dextrose in water 
EBV- Epstein-Barr virus  
ECF – Extracellular fluid 
ECG  – Electrocardiogram 
EFV – Efavirenz  
ELISA  – Enzyme linked immunosorbent assay 
EPTB  – extrapulmonary tuberculosis 
ESR - Erythrocyte sedimentation rate 
ESRD – End stage renal disease 
ETB – Ethambutol 
FBC – Full blood count 
FBS – Fasting blood glucose 
FSH – follicle stimulating hormone


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xii GAS – Group A Streptococci 
GDM - Gestational onset diabetes mellitus 
GH – Growth hormone 
GHRH  – Growth hormone releasing hormone 
GI - Gastrointestinal 
GIT – Gastrointestinal tract 
GnTH  - Gonadotrophic hormone 
GTT - glucose tolerance test 
HAART  – Highly active antiretroviral treatment 
HAV  - Hepatitis A virus 
HBV – Hepatitis B virus 
HCV – hepatitis C virus 
HDL - high-density lipoprotein 
Hgb – hemoglobin  
HHV-8  – Human Herpes Virus-8 
HIV –Human Immunodeficiency Virus 
Hx – Clinical history 
ICF – Intracellular fluid 
ICU – Intensive care unit 
IGT- Impaired glucose tolerance 
IHD – ischemic heart disease 
IM - Intramuscular 
INH – Isoniazid 
IV - intravenous 
IVDU  – Intravenous drug use 
JHR – Jarisch Herxheimer reaction 
JVP - Jugular venous pressure 
KS – Kaposi Sarcoma 
KUB –Kidney Ureter Bladder 
LBRF – Louse borne relapsing fever 
LDH - Lactate dehydrogenase  
LDL - low-density lipoprotein


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xiiiLH - Luetenizing hormone 
LP – Lumbar puncture 
LVH – left ventricular hypertrophy 
MAC – Mycobacterium avium complex 
MDR – Multidrug resistance 
MODY 1, 2, 3  – Maturity onset diabetes of the young 1,2,3 
MRI – Magnetic Resonant Imaging 
MTCT – Mother to Child transmission 
N/S – Normal saline   
NCTs  – Nerve conduction test 
NK cells  – Natural killer cells 
NNN – Nichole MacNeal Novy medium 
NSAIDs  - Non-steroidal anti-inflammatory drugs 
OEPA – Onchocerciasis Eliminati on Programme for Americas 
OIs – Opportunistic infections 
OMs – Opportunistic malignancies 
P/E – Physical examination 
PaO2 – partial pressure of arterial oxygen 
PCP – Pneumocystis carinii pneumonia 
PCR  – Polymerase Chain Reaction 
PFT – pulmonary function test 
PLWHA  – People living with HIV/AIDS 
PML - Progressive multifocal leukoencephalopathy   
PMTCT - prevention of Mother  to Child transmission 
PO – Per os (orally) 
PPD – Purified protein derivative 
PTB - pulmonary tuberculosis 
PTU - Propylthiouracil 
PZA - Pyrazinamide 
QD – once a day 
QID – four times a day 
R/O – rule out


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xivRBC  - Red blood cells 
RF – relapsing fever/Rheumatic fever 
RHD – Rheumatic heart disease 
RIF - Rifampicin 
RNA – Ribonucleic acid 
RPR – Rapid  plasma reagin 
S1 - First heart sound 
S2 - Second heart sound 
S3 - third heart sound 
S4 – Fourth heart sound 
SC - Subcutaneously 
Stat - Once 
STDs  – Sexually transmitted diseases 
TB – Tuberculosis 
TBRF – Tick borne relapsing fever 
TID – Three times a day 
TLCP – TB leprosy control programme 
TRH – Thyroid releasing hormone 
U/S - Ultrasound 
UTI – Urinary tract infection 
VDRL  – Venereal Disease Research Laboratory 
WBC – white blood cells 
WHO – World Health Organization 
ZDV – Zudovudine 
CMV  – cytomegalovirus 
UV-B  – Ultraviolet B 
UVA  – Ultraviolet A


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Internal Medicine 
 
 1CHAPTER ONE 
INFECTIOUS DISEASES 
 
1. Introduction to infectious diseases 
 
Generally infectious diseases resu lt from bacteria, viruses, fungi, and parasites. Despite decades of 
dramatic progress in their treatment and prevention,  infectious diseases remain a major cause of 
death and are responsible for worsening the living conditions of many millions of people around the 
world especially in the developing countries. Infecti ons frequently challenge the clinician’s diagnostic 
skill and must be considered in the differential di agnosis of syndromes affecting a multitude of organ 
systems. Infectious diseases often do not occur in isolated cases; rather they spread through a group exposed from a point source (e.g. a water supply cont aminated with cholera) or from individual to 
individual (e.g. via respiratory droplets spreading tuberculosis). Many factors affect the likelihood of 
acquiring infections which include, host, environmental   microbial factors. 
 
Host and Environmental Factors     
For any infectious process to occur, the parasite and the host must first encounter each other. Factors 
such as geography (e.g. altitude and malaria), environment (e.g. mosquito breeding site and malaria), 
disease vectors and host behavior (e.g. sexual behavior and sexually transmitted diseases) thus 
influence the likelihood of infection. Many Host Factors  such as age, immunization, prior illness,


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disease vectors and host behavior (e.g. sexual behavior and sexually transmitted diseases) thus 
influence the likelihood of infection. Many Host Factors  such as age, immunization, prior illness, 
nutritional status, pregnancy, coexisting illnesses and emotional status all have some impact on the 
risk of infection after exposure to a particular pathogen. 
 
Medical care itself can increase the patient’s risk of acquiring an infection. This can occur in several ways: through contact with the pathogens during hospitalization, through injections, surgical incisions, via mucosal surfaces by end tracheal tubes and bladder catheters, through the introduction of foreign 
bodies, through alteration of the natural flora with antibiotics, and through treatment with suppressive 
drugs such as steroids.
 
 
Microbial Factors    
Infection involves complicated interaction of parasites and host and inevitably affects both. In most 
cases a pathogenic process consisting of several steps is required for the development of infections.


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Internal Medicine 
 
 2Since the competent host has a complex series of defense mechanisms in place to prevent infection, 
the successful parasite must utilize specific strategies at each of these steps. The specific strategies used by bacteria, viruses, and parasites have some si milarities, but the details are unique not only for 
each class of organism but also for individual species within a class;                               
Invasion;  
Microorganisms attached to mucosal surface use specific mechanisms to invade deeper structures. 
For example, meningococci and gonococci penetrate  and traverse mucosal epithelial cells by 
transcytotic mechanism. 
Tropism; 
In order to infect a host successfully, many pathogens occupy highly specific place within the host and 
thus are tropic to a particular body site or cell type. For example, malaria sporozoites are rapidly 
cleared from the blood into the hepatocyts, where they undergo maturation and release into the 
circulation; trophozoites in turn can infect only the erythrocytes.  
Microbial virulence strategies;  
Microbes have developed a variety of strategies for escaping the immunity. For example, some 
pathogenic organisms elaborate toxins and enzymes that facilitate the invasion of the host and are often responsible for the disease state and many bacteria are encapsulated with polysaccharides that allow them to invade and deposit in the absence of specific antibodies.
 
 
Immune response:


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Immune response:  
Is a defense mechanism developed by the host for recognizing and responding to microorganisms.   It 
is divided I to two major classes. Innate and Acquired Immunity.  
Innate immunity (Natural Immunity) :  
Is first line of defense and serves to protect the host with out prior exposure to the infectious agent. 
This immune response is nonspecific and has no memo ry. Examples of Innate immunity include skin 
and mucous mebrane, phagocytoses by macrophages and nutrophils, complement system etc 
 
Acquired (Adaptive) Immunity :  
Is specific immune mechanism developed against a particular organism. It takes time to develop and 
it has long standing memory.  It has two major arms:


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Internal Medicine 
 
 3• Cellular immunity : comprising T- lymphocytes, NK cells  
• Humeral Immunity : comprises of B-Lymphocytes and antibodies produced by plasma cells. 
 
Laboratory diagnosis 
The lab diagnosis of infections requires the demonstration, either  
1.  Direct microscopic visualization of pathogens in clinic al material (e.g. Plasmodium species in 
blood films) or the growth of microorganisms in the laboratory (e.g. culture) or 
2.   Indirect (e.g. antibody / serology test for HIV), of viral, bacterial, mycotic, or parasitic agents in 
tissues, fluids, or excreta of the host.  
Treatment; 
Optimal therapy for infectious diseases requires a broad knowledge of medicine and careful clinical judgment. Life threatening infections such as bacteria l meningitis and sepsis require urgent   initiation 
of therapy often before a specific infective organism  is identified. Antimicrobial agents must be chosen 
empirically and must be against the range of potential infectious agents consistent with the clinical 
condition. In contrast, good clinical judgment sometimes dictates withholding of antimicrobials in a self 
limited process or until a specific diagnosis is made.  Certain infections (e.g. peritonitis, necrotizing 
fascitis, and abscess) require surgery as a primary m eans of cure; in these conditions, antibiotics play 
only as an adjunctive role.  
References: 
1. Kasper L., Braunwald E., Harrison’s principles of  Internal medicine, 16th Edition, Intruducion to


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only as an adjunctive role.  
References: 
1. Kasper L., Braunwald E., Harrison’s principles of  Internal medicine, 16th Edition, Intruducion to 
infectious diseases, pages 695-700.


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Internal Medicine 
 
 42. Acute Febrile Illnesses 
 
2.1. Malaria 
Learning Objective :  At the end of this unit the student will be able to  
1) Define Malaria  
2) List the etiologies of the different types of malarias 
3) Describe the mode of transmission & the life cycle of malaria   
4) Mention the epidemiology of malaria. 5) Explain the pathogenesis malaria 6) Identify the clinical features of the different malarial diseases 7) List the common complications of malaria. 
8) Describe the most commonly used tests for the diagnosis of malaria 
9) Make an accurate diagnosis of malaria 10) Treat malaria at the primary care level with  appropriate drugs   11) Design appropriate methods of prevention & control of malaria 
 
Definition 
Malaria is a protozoal disease transmitted to man by the bite of the female anopheles mosquitoes. 
Etiology of Malaria 
Malaria is caused by the protozoan genus plasmodium . Four species are known to cause disease in 
man 
P. falciparum :  also called malignant malaria 
P. vivax            :  tertian malaria   
P. ovale            :  tertian malaria 
P. malariae      :  quartan malaria 
N.B. Almost all deaths are caused by falciparum malaria 
 Epidemiology of malaria 
• Malaria is one of the commonest infectious diseases of man having a global distribution with 
prevalence of 500 million people affected ever y year and about 2 million people die of 
malaria/year.  40 % of the world population livi ng in tropical/subtropical climates are exposed


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prevalence of 500 million people affected ever y year and about 2 million people die of 
malaria/year.  40 % of the world population livi ng in tropical/subtropical climates are exposed 
to malaria. The prevalence of malaria is increasing because of the emergence of DDT 
resistant Anopheles mosquitoes, drug resistant plasmodia and global whether changes.


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Internal Medicine 
 
 5• Malaria is common in both low and high land areas and epidemics are commonly observed in 
the latter with elevations between 1600 to 2150 meters during the months between September 
and December. The disease is prevalent in 75% of the country with over 40 million people at 
risk.   
• All human malarial parasites are found in Ethiopia, but P. falciparum and P. vivax  are the 
commonest, accounting for 60% and 40% respectively. However P. ovale  and P . malariae  
account for less than 1% of all cases, 
• Endemicity of malaria is defined based on spleenic rates (palpable spleen) in children 
between 2 & 9 years.  Depending on this, region s are classified in to 4 endemicity areas:- 
o Hypo endemic  - Where < 10% children have enlarged spleen 
o Meso-endemic  - Where 10-50% children have enlarged spleen 
o Hyper-endemic  - Where 51-75% of children have enlarged spleen 
o Holo-endemic -   Where > 75% of children have enlarged    " 
 
• In Holo - and H yper  endemic areas there is an intense transmission of P. falciparum people 
can sustain more than one infectious mosquito bit per day – people are infected repeatedly in their lives. Is such places, morbidity and mortal ity are considerable during childhood. Immunity 
against disease is hard won and during adulthood most infections are asymptomatic. This frequent round-year transmission is termed Stable transmission .


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against disease is hard won and during adulthood most infections are asymptomatic. This frequent round-year transmission is termed Stable transmission .   
• In Hypo  and Meso  endemic areas the transmission of malaria is low, erratic or focal, full 
protective immunity is not acquired and symptomatic disease may occur at all ages .This is termed as Unstable transmission .


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Internal Medicine 
 
 6   TableI-2.1-1 The basic characteristics of the two transmission types  of malaria   
   
 Stable  Unstable  
Mosquito life  
long   
short 
Mosquito bites Frequent Rare 
 
Human immunity High Low 
 
Epidemics             No (only with rainy Season 
& migration of non- immunes to the area Yes 
Eradication/ control Difficult  Possible 
 Infant parasite rate  is percentage of infants with positive blood smears for malaria. It is the most 
sensitive index of transmission of malaria to a locality.  
 Transmission 
• Malaria is transmitted by the bite of the female anopheles mosquitoes or inoculation of 
blood.  The female anopheles mosquitoes carry the plasmodium parasite and discharge into human body during feeding on a blood meal.   
 
• Transmission of malaria requires high environmental temperature and collected water 
body, both of which are ideal conditions for breeding of mosquitoes.  Therefore, 
transmission is common in lowlands during rainy season, especially with migration of non-immuned individuals to these areas. Rare cases of congenital transmission are known. 
 
  Life Cycle and Pathogenesis  
• The life cycle of plasmodium is divided in to two, namely asexual and sexual cycles. 
• Sexual cycle occurs inside the  anopheles mosquitoes (definitive host)  
• Asexual cycle occurs in human body which has two phases, namely  
‐ Liver phase (pre & exoerythrocytic phase) and 
‐ Erythrocytic phase


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Internal Medicine 
 
 7• Human infection begins with inoculation of  plasmodium sporozoites by female anopheles 
mosquito   during blood meal. The sporozoites are transported to the liver by the blood 
where they invade liver cells and undergo as exual reproduction. In this phase a single 
sporozoite produces thousands (10,000 – 30,000) of merozoites. The swollen liver cells rupture and discharge merozoites into the blood stream which then invade RBCs and multiply 6-20 fold every 48 to 72 hrs. When the parasites reach certain density in the 
blood, the symptomatic stage begins. In P. vivax  and P. ovale  some of these liver forms 
remain dormant (called hypnozoites) for months to years. These dormant forms 
(hypnozoites) are causes of relapses that characterize infection in these two species. 
• After entry into the blood stream, merozoites invade red blood cells and become 
trophozoites. The trophozoites enlarge, develop pigment and then become amoeboid in shape and occupy most of the red cells consum ing nearly all hemoglobin by the end of 48 
hr of life in the RBC. It is now called schizont .Then multiple divisions give rise to several 
merozoites, which are released in to the blood stream when infected RBCs rupture and 
repeat the same cycle by invading other new RBC.  This explains the anemia in malaria 
which is largely due to the destruction of RBC. 
• During this process the infected RBC & sometimes uninfected ones are removed from the


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repeat the same cycle by invading other new RBC.  This explains the anemia in malaria 
which is largely due to the destruction of RBC. 
• During this process the infected RBC & sometimes uninfected ones are removed from the 
circulation by the spleen clearance function and contribute its share to the anemia. This immunologic function of the spleen causes enlargement of the organ. 
• In P. falciparum infected RBC containing mature forms adhere to small blood vessels 
(called cytoadherence ) and also with uninfected RBC forming rosettes ( called 
Rosetting ) , both of which result in sequestration of RBCs in vital organs like the brain 
and the heart and interfere with the micro circulation and metabolism and contribute to its 
severity. This makes detection of mature forms difficult, and only ring forms and 
gametocytes can be found on peripheral blood films. Sequestration is not a feature of other species of malaria and all stages of the parasite can be seen in the peripheral blood film.  
• After a serious of asexual cycles some of the parasites develop in to morphologically 
distinct, long lived sexual forms (gametocytes) that can transmit malaria.  During a blood meal gametocytes are taken by the female anopheles mosquito, the male and female gametocytes form zygotes, in the   insect’s  midgut the zygotes mature in to ookinetes 
which then develop to oocystes and which divide to liberate several motile sporozoites.


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Internal Medicine 
 
 9Clinical features  
The incubation period varies between 10-14 days in P. vivax , P. ovale, & P.falciparum, and 
18days to six weeks in P. malariae. 
 
Table I-2.1-2Types of plasmodium:and their clinical features  
Type of malaria Incubation period Pattern of fever Recurrence 
A) Benign form: 
 
Plasmodium malaria 
 
Pl. vivax / ovale (dormant hypnocytes may stay in liver and cause later relapse)   21 – 42 days 
 
10 – 21 days   no fever for 2 days 
 
no fever for 1 day (both irregular at first)   no relapses 
 
relapses possible for up to 5 years 
B) Malignant form: 
may lead to death 
within days, causes almost all of deaths 
due to malaria 
Pl. falciparum 7 – 20 days (Longer in 10 %) Irregular rhythm of fever due to unsynchronized replication of 
parasites no relapses 
• Early symptoms are non- specific- malaise, fatigue, headache, muscle pain and 
abdominal discomfort followed by fever, nausea and vomiting is common. 
• Classically malaria manifests in regular paroxysms of high grade fever, chills and 
rigor, occurring every 2 days in P. vivax and P.ovale, and every 3rd day in P. 
malariae, but irregularly in P.falciparum. Malarial febrile paroxysms (which are due 
to rupture of schizonts and release of pyrogens) typically have 3 stages 
¾ The “cold stage” the patient feels intensely cold & has shivering. This lasts 
for 30 minutes to 1hour.It is characterized by vasoconstriction of vessels & the temperature rises rapidly.


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¾ The “cold stage” the patient feels intensely cold & has shivering. This lasts 
for 30 minutes to 1hour.It is characterized by vasoconstriction of vessels & the temperature rises rapidly. 
¾ The” hot stage” The patient feels hot & uncomfortable, & become delirious. 
This stage lasts for 2-6 hours. 
¾ The “sweating stage” patient will have profuse sweating & become very 
much exhausted


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Internal Medicine 
 
 10Physical Findings 
Uncomplicated infection has few physical findings except fever, malaise, and mild anemia, a 
palpable spleen and liver and mild jaundi ce e especially in children.  
 
Severe and complicated Malaria 
Is defined as life threatening malaria caused by P. falciparum, and the asexual form of the parasite demonstrated in a blood film.  Clinical Criteria for diagnosing of sever and complicated falciparum malaria in adults (the 
presence of one criteria already defines a complicated malaria) 
• Cerebral malaria: is a state of unarousable coma lasting for more than 30 minutes and other causes of coma ruled out. 
• Change of level of consciousness less maked than unarousable coma 
• Generalized tonic clonic sezure  (> 2/day) 
• Severe Normocytic  anemia (Hgb < 5 g/dl) 
• Acute renal failure (Oliguria of < 400 ml/24 h and/or creatinine > 3 mg/dl) 
• Pulmonary edema or ARDS 
• Hypoglycaemia (BS < 40 mg/dl) is multi factorial 
o The parasite consumes glucose 
o Catabolic state increases glucose demand  of the host 
o Anorexia associated with the illness 
o Drugs like quinine can cause hypoglycaemia 
• Metabolic acidociis  (  lactic acidosis ) (pH < 7.25; plasma bicarbonate < 15 mmol/l) 
• Circulatory collapse, shock  ,septicaemia ( “ Algid Malaria “ ): systolic BP < 80 
mmHg, core vs. skin temperature difference > 10°C) 
• Spontaneous bleeding / Disseminated Intravascular coagulation ( DIC) 
• Hemoglobinuria 
• Jaundice, bilirubine > 3 mg/dl


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mmHg, core vs. skin temperature difference > 10°C) 
• Spontaneous bleeding / Disseminated Intravascular coagulation ( DIC) 
• Hemoglobinuria 
• Jaundice, bilirubine > 3 mg/dl 
• Hyperparasitemia (>5 % of erythrocytes affected by plasmodium or > 100.000 plasmodium/µl) 
• P. falciparum malaria in pregnant women is also considered as sever because it is 
associated with adverse out comes to the mother and the foetus 
These sever complications may occur singly, or, more commonly, in combination in the same patient


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Internal Medicine 
 
 11Who is at risk of developing severe malaria in high transmission areas ? 
o Young Children 
o Visitors from non Endemic areas of any age 
o Pregnant women 
Laboratory  
Symptoms and signs of the disease are not specific to malaria, and resemble many types of 
febrile illnesses. Therefore confirmation of infection with laboratory investigations is essential. 
1. Demonstration of the parasite by blood film  (thin & thick) stained by Giemsa or Wright’s 
stain  
• Thin blood film  is methanol fixed; you can see intact RBC with parasites inside it 
Advantage : species identification is simple; percentage of RBC parasitized can be 
estimated  
• Thick blood film,  not methanol fixed, RBC are lysed during staining, parasites are seen 
free from RBC 
Advantage : concentrates the parasite 20-40 times, this helps to determine parasite 
concentration.  
NOTE: A single blood film examination doesn’t rule out malaria, and it should be repeatedly 
done possibly during febrile episodes. However, studies have shown that BF can be negative in 
small percentage of patients with malarias 
 
Other Lab Tests  
• Hemoglobin- anemia can be detected 
• Blood glucose 
• Peripheral morphology- Normocytic normochromic anemia - Low or normal WBC 
• LP and CSF analysis ( when indicated to R/O Meningitis )  
• BUN/ Cr,  SGOT ,  SGPT , Serum electrolytes etc 
 
Treatment  
Depends on the type of malaria and the severity of the diseases


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• LP and CSF analysis ( when indicated to R/O Meningitis )  
• BUN/ Cr,  SGOT ,  SGPT , Serum electrolytes etc 
 
Treatment  
Depends on the type of malaria and the severity of the diseases  
A. Benign forms of malaria (Plasmodium malariae, vivax, ovale): 
Chloroquine is effective  
Dose : Initial dose is 600 mg PO followed by 300mg after 6, 24 and 48 h subsequently.


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Internal Medicine 
 
 12N.B Cloroquine is no effect on the exoerythrocytic liver form (= reservoir). To protect 
from later recurrences, chloroquine therapy should be followed by:- 
Primaquine:  (dose: 15 mg/day over 2 weeks), which is effective against liver forms 
and gametocytes. 
 
B. Treatment of P.Falciparum malaria  
• The high treatment failure rates of chlor oquine for the treatment  of uncomplicated 
P.falciparum malaria as docum ented through a nationwide study conducted in 1997/98 in 
Ethiopia, led to a treatment  policy change that recommends  the use of Sulfadoxine-
Pyrimethamine as first line drug for the treatment of uncomplicated falciparum malaria and 
chloroquine for the treatment of vivax malaria.   
• In subsequent years, however, unpublished re ports from isolated st udies indicated higher 
treatment failure rates. Accordingly, a nati onwide study on the therapeutic efficacy of 
Sulfadoxine-Pyrimethamine for the treatment of uncomplicated falciparum malaria was 
conducted in 11 sentinel sites from October – December 200 3. Results obtained from the 
study showed a mean treatment failure rate of 35.9% on the 14-days follow-up and 71.8% on 
the 28-days follow-up.  
• This level of treatment failure rate is mu ch higher than the cut-off point recommended by 
WHO for a treatment policy change. In-vivo therapeutic efficacy and safety baseline study on 
artemether-lumefantrine was also  conducted in 4 sites by enro lling 213 subjects and after a


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WHO for a treatment policy change. In-vivo therapeutic efficacy and safety baseline study on 
artemether-lumefantrine was also  conducted in 4 sites by enro lling 213 subjects and after a 
follow-up period of 14 days, no treatment failu re cases and drug side effects were reported 
 
i) Treatment of uncomplicated falciparum malaria : oral drugs are used can be used  
 In most tropical countries since resistance to chloroquine and Sulfadoxine-pyrimethamine is 
well documented other drugs are recommended. 
a) Aritemisinin and its derivatives  were developed originally in China, have proved to 
be highly effective in adults and children. 
There are different preparations like, Artes unate PO, or IV), Artemether (PO, IM)  
• Artemether-Lumefantrine: (Coartem 20/120): is most widely used in Ethiopia.  
Tablet containing 20 mg Artemether plus 120 mg  Lumefantrine in a fix ed dose combination.  
Adult Dosage:   < 35 kg: 3 tabs PO BID for 3 days  
      > 35 Kg:  4 tabs PO BID for 3 days  
Side effects: Dizziness and fatigue, anorexia, nausea, vomiting, abdominal pain, palpitations, 
myalgia, sleep disorders, arthralgia, headache and rash.


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Internal Medicine 
 
 13Contra-indications:  
 As malaria  prophylaxis either alone or in combination.  
 Persons with a previous history of reaction after using the drug  
 Pregnant women, mothers with infants less than three months of age and Infants less 
than 5 kg  
b) Quinine:  
Adult dose :  600 mg PO TID for 5 – 7 days alone or in combination with + Tetracycline 500 
mg PO QID or Doxycycline 100mg PO /day for the same period 
Side effects: 
 Cinchonism: Tinnitus, hearing loss, dizziness, tremor, nausea, resteleness, blurring 
 Hypogycemia  : is the commonest adverse effect  
c) Mefloquine  : Structurally ressembles Quinine. It is effective against all malarial specious 
including multi-drug resistant P.falciparum. Howe ver some resistance strains of P.falciparum 
for Mefloquine are reported in some tropical countries. 
Dose:   15mg/kg followed by second dose of 10mg/kg after 8-12 hr 
Side Effects : Nausea, abdominal cramp, vertigo, insomnia, sometimes acute psychosis and 
convulsion  
d) Sulfadoxine-pyrimethamine (oral) e.g. Fansidar -3 tablets stat as a single dose. (1 tablet = 
500mg sulfadoxine + 25 mg pyrimethamine). Cont raindicated in children less than one year. 
Due to high prevalence of resistance to this combination, it is not recommended for treatment of 
P.faciparum in most tropical countries including Ethiopia. 
–5 days (e.g 4 mg /kg for 3 days) in combination with Mefloquine 25 mg/kg 
Treatment of Severe and comp licated falciparum malaria:


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P.faciparum in most tropical countries including Ethiopia. 
–5 days (e.g 4 mg /kg for 3 days) in combination with Mefloquine 25 mg/kg 
Treatment of Severe and comp licated falciparum malaria:   
NB: Patients should be admitted and treated in a Hospital setting  A)  Drug Treatment: 
i) Quinine : is drug of choice for severe and complicated malaria. 
Dosage and Adminstration:   
Where IV administration of quinine is possible  
Loading dose:  Quinine 20 mg salt/kg of body weight by infusion over 4 hours, in 5 % 
dextrose in saline (5-10 ml/kg of body weight depending on the patient's overall fluid 
balance).  
Maintenance does: Twelve hours after the start of the loading dose, give quinine 10 mg 
salt/kg of body weight in dextrose saline over 4 hours. Repeat the same dose of quinine 
(i.e. 10 mg salt/kg) every 8 hours until the patient can take oral medication.


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Internal Medicine 
 
 14  Wherever IV administration of quinine is not possible.  
Quinine dihydrochloride 20 mg salt per kg loading dose intramuscularly divided in to two 
sites, anterior thigh). Then quinine dihydrochloride 10 mg salt per kg IM every 8 hours 
until patient can swallow. 
ii) Artesunate injection (if available) : 2.4 mg/kg IV or IM stat followed by 1.2 mg/kg at 12 
and 24 hrs and then daily.  
B)  Supportive treatment:  
• Bring down fever (cold sponges,  paracetamol)  
• Administer glucose IV or PO to prevent hypoglycaemia and encourage early PO intake 
of food  
• Ensure adequate fluid intake, check input and output and control water and electrolyte 
balance (beware of pulmonary edema due to fluid overload).  
• Consider transfusion in severe falciparum malaria with high parasitemia (> 20% of 
erythrocytes affected by plasmodium)  
• Check renal function tests and blood sugar (beware of hypoglycemia).  
• For  comatose or unconscious  patients proper nursing care is mandatory 
 Position the patient on his/her sides; turn every 2 hours to avoid bed sores. 
 Catheterize the bladder, monitor input-output. 
 Avoid fluid overload 
 Monitor blood glucose regularly 
 Ensure adequate nutrition 
Chronic Complications of Malaria 
Tropical Splenomegaly Syndrome (Hyp erreactive malarial Splenomegaly) 
It is a syndrome resulting from an abnormal immunologic response to repeated infection. Is 
seen is some residents of malaria endemic area in tropical Africa and Asia


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Tropical Splenomegaly Syndrome (Hyp erreactive malarial Splenomegaly) 
It is a syndrome resulting from an abnormal immunologic response to repeated infection. Is 
seen is some residents of malaria endemic area in tropical Africa and Asia  
It is characterized by 
 Huge spleen ( > 10 cm BLLCM ) with or with out hepatomegaly 
 Hyperspleenism (anaemia, pancytopenia ) 
 Marked elevation of serum IgM and anti malarial antibody 
 Hepatic Sinusoidal lymphocytes  
 Peripheral B-Cell lymphocytosis 
Clinical Feature:


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Internal Medicine 
 
 15
 Abdominal mass or dragging sensation in the left upper quadrant and sometimes                        
abdominal pan 
 Anaemia and sometimes Pancytopenia  Æ susceptibility to Infection 
 The parasite may not be detected in peripheral blood film 
Treatment 
• Antimalarial prophylaxis for a long time , usually for the duration of malaria 
exposure.  
• Drugs commonly used are chloroquine or mefloquine.  
• The enlarged spleen and liver usually regress over a period of months with effective 
Antimalarial prophylaxis. 
• Splenectomy is only indicated for those with failure of antimalarial prophylaxis at least 
given for 6months. 
Prevention of Malaria  
A. General measures  
Mechanical Barriers/Methods 
• Draining water collections and swampy areas 
• Use of chemical impregnated mosquito nets around beds 
• Wire mesh across windows 
• Staying indoors at night  
• Use of long sleeved shirts and long trousers 
  Insecticides or Chemicals 
• Use insecticide spray aerosols (permethrin, deltamethrin and chlorinated 
hydrocarbons) 
• Application of insect repellents to exposed skin (e.g. diethyltoluamide) 
• DDT sprayed in the interior of houses is effective in killing the adult mosquito for many 
months. 
 B. Drug prophylaxis  
It is indicated for   
• Pregnant women in endemic areas because of   their increased risk of severe malaria 
• Children between 3 months and 4 years in endemic area (born to non-immune mother)


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Internal Medicine 
 
 16• Travelers to malarious areas  they should start taking drugs 1 week before traveling to 
these areas & for 4 weeks after the individual left the endemic area. 
 
Drugs available for prophylaxis  
In Areas where there is chloroquine resistant P. falciparum 
• Mefloquine 250mg/week orally, effective against multi drug resistant p. falciparum, 
safe during pregnancy 
• Doxycycline 100mg daily orally , not us ed for children < 8 years& during pregnancy 
• Maloprim (Pyrimethamine+ dapson) 1 tab orally/wk 
• Chloroquine+ proguanil combination alternative to mefloquine and doxycycline. 
 
In areas where there is for chloroquine sensitive P.falciparum  and other” benign” malarias:                    
• Chloroquine 2 tabs of 150 mg tablet orally every week  
• Chloroquine+ proguanil combination can be used as an alternative 
References: 
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, 
Salmonellosis, pages 1218-1232. 
2) Gordon c cook and Alimuddin Zumla, Manson’s Tropical Diseases, 21st edition, 2003, 
pages 937 – 949. 
3)  Management of severe and complicated ma laria in Ethipoa , Federal MOH , 2005


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Internal Medicine 
 
 172.2 Typhoid (Enteric) Fever 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define Typhoid fever    
2. List the etiologies of typhoid fever    3. Describe the epidemiology of typhoid fever   . 
4. Explain the pathogenesis typhoid fever    
5. Describe the clinical features of typhoid fever    6. List the common complications typhoid fever   . 7. Describe the most commonly used tests for the diagnosis of typhoid fever    8. Make an accurate diagnosis of typhoid fever    
9. Treat typhoid fever with  appropriate antibiotics   
10. Design appropriate methods of prevention and control of typhoid fever    
 
Definition:  Typhoid fever is a systemic infection characterized by fever and abdominal pain 
caused by dissemination of Salmonella typhi and occasionally by S. paratyphi A and B and 
S.typhimarium, all of which are non capsulated, gram negative motile bacteria. 
 
Epidemiology 
• Human beings are the only hosts for S. typhi and S.paratyphi. Thus enteric fever is 
transmitted only thorough close contact with acutely infected individuals or chronic 
carriers through ingestion of contaminated food or water.  
• Chronic carriers are the source of infection harboring the organisms in their gall bladder 
(especially in the presence of gall stones) and rarely at other sites.  It affects people of all ages and both sexes. Enteric fever is endemic in most developing countries.


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(especially in the presence of gall stones) and rarely at other sites.  It affects people of all ages and both sexes. Enteric fever is endemic in most developing countries.  
• Currently the disease is observed at a great frequency in AIDS  patients than the general 
population. 
 
Pathogenesis 
Following ingestion of the organism in contaminated food or drink, Salmonella typhi passes the 
gastric barrier and reach the upper small inte stine where the bacilli invade the intestinal 
epithelium and they are engulfed by phagosoms which reside in the Peyer’s patches. The bacilli multiply and enter the blood stream and cause transient bacteremia. At this stage the


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Internal Medicine 
 
 18Salmonellae disseminate throughout the body in macrophages via lymphatic and colonize 
reticuloendothilial tissue (liver, spleen, lymph nodes, and bone marrow). Patients have relatively fewer or no signs and symptoms during this initial incubation period. Signs and symptoms, 
including fever and abdominal pain result when a critical number of bacteria have replicated. 
During weeks after initial colonization, further inflammation of the Peyer’s patches may result enlargement and necrosis which may result intestinal hemorrhage and perforation. Infection may become persistent and invade the gall bladder. The clinical phase of the disease depends 
on host defense and bacterial multiplication.  
 
Clinical Manifestation 
The incubation period varies from 3-60 days.  The manifestation is dependent on inoculum size, 
state of host defense and the duration of the disease. The Severity of the illness may range 
from mild, brief illness to acute, severe diseas e with central nervous system involvement and 
death.   
First week   
• Fever is high grade, with a daily increase in a step-ladder pattern for the 1
st one 
week and then becomes persistent.  
• Headache , malaise , Abdominal pain 
• Initially diarrhea or loss stole followed by constipation in adults, diarrhea is dominate 
feature in children 
• Relative bradycardia  
• Splenomegally  Hepatomegaly   
• “Rose spots” not commonly seen in black pat ients. In whites it appears as small,


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feature in children 
• Relative bradycardia  
• Splenomegally  Hepatomegaly   
• “Rose spots” not commonly seen in black pat ients. In whites it appears as small, 
pale red, blanching macules commonly over chest & abdomen, lasting for 2-3 days.  
• Epistaxis 
Second week 
• Fever becomes continuous 
• The patient becomes very ill and withdrawn confused, delirious and sometimes 
may be even comatose


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Internal Medicine 
 
 19Third Week 
• The patient goes to a pattern of “typhoidal state" characterized by extreme toxemia, 
disorientation, and “pea-soup” diarrhea and sometimes may be complicated by intestinal 
perforation and hemorrhage.  
Fourth Week 
• Fever starts to decrease and the patient may deferveresce with resolution of symptoms.  
At this point patient may lose weight.  
• Relapse may occur in 10% of cases.  
 Complications  of Typhoid fever  
• Gastrointestinal perforation and hemorrhage: are late complications that may occur in 
the 3rd or 4th week. May develop despite c linical improvement. These complications are 
life threatening and need immediate medical and surgical interventions 
• Other Less common complications  
 Hepatitis                                                  
 Meningitis                                             .  
 Arthritis, osteomyelitis 
 Parotitis and  orchitis  
 Nephritis   
 Myocarditis  
 Bronchitis and pneumonia     
N.B these complications can be prevented by prompt diagnosis and treatment 
 
Chronic Carriers  
• Approximately 1- 5 % of patient with Enteric fever become asymptomatic chronic carriers 
• They shed S.typhi  in either urine or stool for  > 1 year 
• Incidence of Chronic carriage is high in women and among patients with biliary 
abnormality (e.g. gall stone, carcinoma of gall bladder) and other GI malignancies.  
Diagnosis 
Can be suggested by the presence of 
 Persistent fever


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• Incidence of Chronic carriage is high in women and among patients with biliary 
abnormality (e.g. gall stone, carcinoma of gall bladder) and other GI malignancies.  
Diagnosis 
Can be suggested by the presence of 
 Persistent fever 
 Relative bradycardia, which was found to occur in 86% of Ethiopians. 
 Rose spots, which occurs in 70% of whites and 20% of Ethiopians.


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Internal Medicine 
 
 20
 Leucopenia 
But definitive diagnosis of the disease requires laboratory tests. 
1. Isolation of the organism  by blood, stool or urine culture is diagnostic. 
o The yield of recovery of the organism differs depending on the specimen cultured 
and the duration of clinical disease; 
o Blood culture  -mostly (up to 90%) patients have positive culture in the 1st week, 
and only 50% by the 3rd week. The yield is much lower if patient has taken 
antibiotics prior to the test. 
o Stool culture  is negative in the first week and becomes positive in 75% of 
patients in the 3rd week. Urine culture parallels stool culture. 
Widal test for O and H antigens 
• The O (somatic) antigen shows active infection whereas the H (flagellar) antigen could 
be indicative of past infection or immunization for typhoid. 
• Widal test has certain limitations, and to make a diagnosis of current infection a 4X (fold) 
rise in titer on paired sera taken during the acute and convalescence phases is 
necessary. 
Limitations of Widal test 
• It is non specific and a positive test could be due to 
 Infection by other salmonellae (as the antigen used for the test is also 
shared by other salmonellae) 
 Recent vaccination for typhoid 
 Past typhoid (already treated)  
• The demonstration of 4- fold rise in titer on paired sera is not useful for the treatment of 
acute cases, as this requires waiting for the convalescence phase of the disease and at


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Past typhoid (already treated)  
• The demonstration of 4- fold rise in titer on paired sera is not useful for the treatment of 
acute cases, as this requires waiting for the convalescence phase of the disease and at 
this stage if the patient is lucky recovery will occur.    
 
Treatment   
Antibiotic therapy is curative. These drugs can be given either orally or intravenous, depending on patient condition (able to take orally or not),  severity of the disease. One should note that 
fever may persist for 4-6 days despite effective antibiotic treatment


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Internal Medicine 
 
 21Oral drugs 
First Line  
Nowadays 4-amino quinolones are the drugs of choice because of their effectiveness on 
multidrug resistant typhoid, and low relapse and carrier rates. Ciprofloxacin, norfloxacin, 
ofloxacin, and pefloxacin are all equally effective. 
• Ciprofoxacin: 500mg PO BID for 10 days 
• Ceftriaxone 1-2 gm IM or IV for 10 -14 days  
4- amino quinolones are not recommended for use in children and pregnant women because of 
their observed potential damaging effect on cartilage of the growing animals. However, in 
severe infections especially by MDR strains,  we have to outweigh the benefits and the potential 
risks. 
 Alternative  
• Azithromycine   1 gm PO daily for 5 days  
• Chloramphenicol   500 mg Po QID for 14 days 
• Norfloxacin  400mg twice daily   for 10 days 
Chloramphenicol is very cheap and also quit e effective with initia l doses of 3 - 4 g/d 
for adults, with clinical response observed in  24 - 48hrs after initiation. Dose should 
be reduced to 2g/d when fever starts to decrease (usually after 5 - 6 days), and 
continued to complete 2 weeks treatment.  
 Intravenous drugs  are recommended for critically sick patients who are admiited or for patients 
who are unable to take oral drugs 
• Ceftriaxone 2-4gm once a day for 3 days and t hen 1- 2gm IV/IM for a total of 10- 14 
days. 
• Intravenous Chloramphenical  1gm IV QID for 2-3 days and then start PO medication


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who are unable to take oral drugs 
• Ceftriaxone 2-4gm once a day for 3 days and t hen 1- 2gm IV/IM for a total of 10- 14 
days. 
• Intravenous Chloramphenical  1gm IV QID for 2-3 days and then start PO medication 
as soon as the patient can take oral medication.  This is a drug of choice for patients 
that need parenteral therapy especially in Ethiopia (mainly for cost reason). 
Problems of antibiotic treatment 
• Multidrug resistant (MDR) S.typhi  is reported in different parts of the world, especially 
Indian subcontinent and Southeast Asia. Hence if resistance is suspected in an area, the preferred treatment would be with quinolones, azithromycin or third generation 
cephalosporins


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Internal Medicine 
 
 22• Early use of antibiotics is associated with high rate of relapse (up to 20%) as compared 
to untreated cases (where the relapse rate is 5 - 10%). This is due to inhibition of 
adequate development of immune response by early therapy. 
• Eradication of chronic carrier state  requires prolonged treatment with 
 Ciprofloxacin for 4 weeks is effective and  much better than the other drugs  
 Ampicillin or Amoxicillin 100mg/kg/d ta ken with Probenecid 30mg/kg/day for 6 
weeks. 
 Co-trimexazole (160/800mg twice a day) plus Rifampicin 600mg orally/d for 6 
weeks.. 
 N.B. Drug treatment does not eradicate infection in 40% of the chronic carriers. Hence surgical 
resection of the gall bladder may sometimes be necessary. 
 Prevention and  control 
• Improve environmental sanitation 
• Identification and treatment of Chronic carriers 
• Avoid food handling by chronic carriers 
• Vaccination for travelers to endemic areas 
o Live oral vaccine (TY21a) 3 doses can be given to those over 6 years. Protective 
for several years 
o Purified Vi polysaccharide vaccine given in a single dose to those over 2 years 
and HIV positives, is as effective as live vaccine. 
 References: 
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, 
Salmonellosis, pages 897 - 902 . 
2) Gordon c cook and Alimuddin Zumla, Manson’s Tropical Diseases, 21
st edition, 2003, 
pages 937 – 949.


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Internal Medicine 
 
 232.3 Relapsing Fever 
 
 Learning Objective :  At the end of this unit the student will be able to  
1. Define relapsing fever  2. List the etiologies of the two major types of relapsing fever 3. Describe the mode of transmission relapsing fever 
4. Mention the epidemiology of relapsing fever 
5. Describe the pathophysiology of relapsing fever 6. Identify the different features of the two types of borrelia and their clinical manifestations  7. List the complications of relapsing fever 8. Describe the most commonly used tests for the diagnosis of relapsing fever 
9. Make an accurate diagnosis of relapsing fever 
10.  Manage relapsing fever at the primary care level with  appropriate drugs   11.  Design appropriate methods of prevention and control of relapsing fever 
 
Definition 
Relapsing fever is an acute febrile illness caused by Borrelia species, presenting with 
recurrence of characteristic febrile periods last ing for days alternating with afebrile periods.  
Relapsing fever describes two distinct diseases: 
• Louse borne (Endemic) relapsing fever (LBRF):- transmitted by body louse Pediculus 
humanis var corporis  
• Tick borne (Epidemic) relapsing fever (TBRF)- transmitted by tick (Ornithodoros)  
 Etiology 
Relapsing fever is caused by Borrelia species,  which are spirochetal gram negative helical 
bacteria. 
• B. recurrentis  is the only species that cause LBRF 
• B. duttoni  is the commonest causes of TBRF in sub-Saharan Africa.


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Etiology 
Relapsing fever is caused by Borrelia species,  which are spirochetal gram negative helical 
bacteria. 
• B. recurrentis  is the only species that cause LBRF 
• B. duttoni  is the commonest causes of TBRF in sub-Saharan Africa. 
Borrelia  demonstrates remarkable antigenic variation and strain heterogeneity which help the 
parasite to escape the immune response of the host and result in recurrence of febrile episodes.


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Internal Medicine 
 
 24Transmission :  
LBRF : Body lice become infected by B. recurrentis while  feeding  on spirochetemic human 
blood, the only reservoir of infection. Humans acquire infection when infected body lice are 
crushed and their fluids contaminate mucous membrane or breaks in the skin (such as 
abrasions caused by scratching of pruritic louse bites)  LBRF is now an important disease only in the northeastern Africa, specially the highlands of 
Ethiopia where an estimated 10,000 case occur annually. In Ethiopia the diseases affects 
mostly homeless men living crowded together in  very unhygienic circumstances especially 
during rainy seasons. Some of the risk factors for LBRF are over crowding like in military 
camps, civilian population disrupted by war and other disasters.  
TBRF : Rodents are the primary hosts and vector ticks become infected when they feed 
spirochetemic rodents.  Ticks transmit the borreliae vertically over several generations. TBRF is 
most highly endemic in sub-Saharan Africa  but also is found in Mediterranean and Middle 
eastern countries.   
 
Pathophysiology 
In humans, borreliae after entering the body multiply in the blood and circulate in great number 
during febrile periods.  They are also found in  the spleen, liver, central nervous system, bone 
marrow, and may be sequestered in these organs during periods of remission.  Severity is 
related to spirocheatal density in blood but systemic manifestations are related to release of


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marrow, and may be sequestered in these organs during periods of remission.  Severity is 
related to spirocheatal density in blood but systemic manifestations are related to release of 
various cytokines.  The disease is characterized by sub capsular and parenchymal hemorrhage with infarcts of 
spleen, liver, heart and brain is seen.  Thus, patients will have enlarged spleen and liver with 
variable edema and swelling of brain, lung and kidneys. Relapsing fever in pregnancy can result abortion, still birth and fatal neonatal infection Death from TBRF is rare. In contrast fatality rate of LBRF may reach up to 20 % during out beaks mainly among malnourished and stressed population. 
 
Clinical Features 
• The manifestation of both LBRF and TBRF are similar.   
• Incubation period is 7 days (ranging from 2-18 days).


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Internal Medicine 
 
 25• The onset is sudden with high grade irregular fever, headache, chills, myalgias, 
arthralgias, and insomnia.   
• Patient will be withdrawn, disinterested to food and other stimuli and thirsty.  Patient will 
have delirium associated with high grade fever, tachycardia and  dry tongue, injected 
conjunctiva and photophobia 
• Summation gallop , occasionally resulting from myocardial involvement 
• Upper abdominal tenderness with hepatosplenomegally,  
• Scattered petechiae over the trunk, extremities and mucous membrane in 1/3 LBRF and 
fewer TBRF 
• Symptoms and signs of meningial irritation may be seen in some patients.   
• Icteric sclera may be found in late stage of the disease.  
 Complications :-  
Life threatening complications are unusual in otherwise healthy persons if the disease is diagnosed and treated early. Complications are common in late disease in untreated patients.  
 Epistaxis, blood streaked sputum other bleeding tendencies 
 Neurologic manifestations like iridocyc litis, meningitis, coma, isolated cranial 
nerve palsies, 
 Pneumonitis,  
 Myocarditis  
 Spleenic rupture of spleen etc.  . 
 Without treatment, symptoms intensify over 2-7 days period and subside with spontaneous 
crisis during which borrelia disappear from the circulation.  Such cycles of febrile periods alternating with afebrile periods may recur several times.   
Table I-2.3-1 Basic characteristics of the two types of borreliae    
    
  
    LBRF  TBRF


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crisis during which borrelia disappear from the circulation.  Such cycles of febrile periods alternating with afebrile periods may recur several times.   
Table I-2.3-1 Basic characteristics of the two types of borreliae    
    
  
    LBRF  TBRF  
Causes B. recurrent is B. dutt oni + many others(all zoonotic 
Parasite in the vector   Found in endolymph of  lice Found in all tissues, including  salivary 
glands & ovaries


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Internal Medicine 
 
 26 
Transmission Contamination of mucous 
membrane or breaks or abrasions 
on the skin by body fluids of lice, 
released during crushing         -  
Not transmitted by the bite of lice 
or inoculation of louse feces By bite of tick during blood meal  (organisms in the  saliva & coaxal fluid 
of borrelia) 
Vertical transmission 
(Tran Ovarian) No Yes 
Distribution East Africa-Eth iopia Sub-Saharan Africa,  
Mediterranean littoral, middle east, Russia, India, China, USA 
Occurrence Epidemics are frequent in 
homeless people living in 
unhygienic  crowded 
condition 
 Sporadic or in small often familial 
clusters 
Vector longevity Short life span Lives over 10 Yrs 
Jarisch – Herxheimer Reaction More sever Less sever 
Eradication Easy Difficult because of: 
- the  night biting habit &  painless 
nature of the bite of ticks 
- vertical transmission/trans-ovarian/ 
-  long life span. 
 
Diagnosis 
• Diagnosis of relapsing fever is made based on demonstration of the organisms in blood, 
bone marrow, CSF etc  
Blood Film:   
• Giemsa or Wright stained peripheral blood smear is the most commonly done laboratory 
test in Ethiopia, and an ideal test in the resource limited setting.   
• Spiral organisms can be demonstrated on peripheral blood taken during febrile period 
preceding the crisis.  This is positive in more than 70% of LBRF and in lower percentage 
of patients with TBRF.


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Internal Medicine 
 
 27 Other Tests  
• Dark field microscopy of unstained blood/CSF  
• Serologic tests 
 
Treatment  
Relapsing fever is treated with antibiotics.  In LBRF single dose of erythromycin, tetracycline, 
doxycycline or chloramphenical, produces rapid clearance of borrelia from the blood & 
remission of symptoms.  TBRF is less sensitive to these antibiotics and requires a 7 days course of treatment. 
 
 
 
Adult Dosage  
Medication     LBRF (single dose)  TBRF (7 day schedule) 
Oral 
• Erythromycin  500mg   500mg every 6 hrs 
• Tetracycline  500mg   500mg every 6 hrs 
• Doxycycline  100mg   100mg every 12 hrs 
• Chloramphenicol  500mg   500mg every 6 hrs 
Parenteral  
Penicillin G (procaine)   600,000 I.M stat        600,000 IM daily 
Delousing of patients with Relapsing fever is important to prevent transmission and recurrence  
Jarisch- Herxheimer Reaction (JHR )  
• Rapidly acting antibiotics regularly precipitate JHR within 1- 4 hrs of 1st dose 
• More sever in patients with LBRF than TBRF 
• It is more sever when high numbers of spirochetes are circulating in the blood 
• Jarisch- Herxheimer Reaction has three phases 
Chill phase:-  lasts for 10- 30 minutes  
• Rigor, hyperventilation, high cardiac output,  
• High body Temperature ( > or = 41 Co)  accompanied by , agitation , confusion  
Flush phase:  
• Fall in body temperature, drenching sweating, Potential dangerous fall in Systemic blood 
pressure  ( as  peripheral vascular resistance falls )


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Internal Medicine 
 
 28• Clinical and ECG evidence of myocarditis may be seen , S 3 gallop and prolonged QT 
interval  
• Vitals signs must be monitored closely during this time which usually lasts for <or = 8 hrs  
Recovery (Deferverescence) phase 
• Vital signs slowly come to normal  
• The Patients is exhausted ,  
Treatment of JHR 
• Close monitoring of vital signs 
• Care full fluid management  
• Control high body Temperature 
• Short term digoxin I.V administration in pat ients with evidence of myocardial dysfunction  
Prevention and Control of Relapsing Fever 
• Avoiding over crowding  
• Apply hygienic practices that reduce the number of body lice (washing clothes) 
• Elimination of ticks  
• Health education  
• Early case detection and treatment of infected persons and close contacts 
• In out breaks of LBRF, empirical single dose treatment with doxycycline  
• Eradication of Rodents to control TBRF: ( Rodenticides )  
 
References  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th  Edition, Relapsing 
fever, pages 991-994. 
2) Gordon c cook and Alimuddin Zumla, Manson’s Tropical Diseases, 21st edition, 2003, 
pages 937 – 949 .


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Internal Medicine 
 
 292.4 Rickettisial diseases: ( Epidemic and Endemic Typhus)   
  
Learning Objective :  At the end of this unit the student will be able to  
1. Define rickettsial diseases with Special Emphasis on Epidemic and Endemic Typhus 2. Classify  rickettsial diseases 
3. List the etiologies of the different types of rickettsial diseases   
4. Describe the mode of transmission rickettsial diseases  5. Explain the epidemiology of rickettsial diseases 6. Describe the pathophysiology of rickettsial diseases 7. Identify the clinical manifestations of the different types of rickettsial diseases  8. List the complications of rickettsial diseases 
9. Describe the most commonly used tests for the diagnosis of rickettsial diseases 
10. Make an accurate diagnosis of rickettsial diseases  11. Refer complicated  cases of rickettsial diseases to hospitals for better management  12. Design appropriate methods of prevention and control of rickettsial diseases 
 Definition:   
Rickettisiae are small intracellular bacteria that  are spread to man by arthropod vectors, namely 
human body lice, fleas, ticks & larval mites. Th e organisms inhabit the gastrointestinal tract of 
these arthropods & spread to human host by the direct bite of the vector or the inoculation of the 
organism contained in the feces of the vector by bite induced body itching. These infections are 
characterized by persistence in the body, wides pread vasculitis (invading endothelial cells of


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organism contained in the feces of the vector by bite induced body itching. These infections are 
characterized by persistence in the body, wides pread vasculitis (invading endothelial cells of 
small blood vessels) & multi-system involvem ent. Except in louse borne typhus humans are 
accidental hosts in most rickettisial diseases. 
 
 Classification 
Rickettsial diseases are classified into five general groups 
• Tick  and mite borne spotted fever group 
• Flea and louse borne typhus group 
• Chigger borne scrub typhus  
• Ehrlichiosis 
• Q-fever


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Internal Medicine 
 
 30Etiology and Epidemiology of Epidemic and Endemic Typhus  :  
Epidemic Typhus (Louse born ) : is caused by  R.prowazekii and  transmitted by human body 
louse (Pediculus humanus corporis).  Lice acquire the rickettsia while ingesting a blood meal 
from an infected patient, the rickettsia multiply in the midgut epithelial cells of the louse and are 
excreted via louse faeces. The infected louse defecates during a blood meal and the patient autoinoculates the organisms by scratching. It is commonly associated with poverty, cold 
weather, war and natural disasters. The disease is prevalent in mountainous areas of Africa, 
South America, and Asia. 
 Endemic Typhus (Flea born) / Murine Typhus: is cause by R. thyphi which is transmitted by 
fleas. R.typhi  is maintained in mammalian host/flea cycles, with rats. Fleas acquire R.thyphi 
from rikettsemic rats and carry the organism th roughout the rest of their life span.  . Humans 
and rats are infected when rickettsia –laden fleas are scratched in to pruritic bite lesions. 
 
Pathophysiology 
In man rickettsia multiply in the endothelial cells of capillaries causing lesions in the skin, brain, 
lung, heart, kidneys and skeletal muscles. Endothelial proliferation coupled with peri-vascular 
reaction causes thromboses and small hemorrhages. However, tissue and organ injury is


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lung, heart, kidneys and skeletal muscles. Endothelial proliferation coupled with peri-vascular 
reaction causes thromboses and small hemorrhages. However, tissue and organ injury is 
commonly due to increased vascular permeability with resulting edema, hypovolemia and organ ischemia. This leads to multi-system involvem ent with complications such as non-cardiogenic 
pulmonary edema, cardiac dysrhythemia, encepha litis, renal and hepatic failure and bleeding.  
 
Clinical Features 
Signs and symptoms:   
• Incubation period of 1 week 
• Abrupt onset of illness with prostration, severe headache and rapidly rising fever of 38.8 
to 40.0 °C 
• Cough s seen in 70 % of patients , myalgia may also occur which may be severe 
• Rash, begins on upper trunk around 5th day and then becomes generalized, involving 
the entire body except face, palms and soles;  at first, rash is macular, becoming 
maculopapular, petechial and confluent without treatment, although in black people, rash 
may be absent ( spotless epidemic typhus ) 
• Photophobia, with conjunctival injection and eye pain; frequent


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 31• Tongue may be dry, brown, furred 
• The signs of central nervous system involvement, commonly as meningo-encephalitis, 
appear towards the end of the 1st week progressing to seizure and coma .  
 
Brill-Zinsser disease  (recrudescent typhus) : This is a mild form of epidemic typhus caused 
by reactivation of dormant R. prowazekii  in the body (in the lymph nodes) as a result of 
immunosuppression or old age. Occurs after several years of acute infection .  The 
manifestation of the disease is similar to  acute epidemic typhus but milder. The organisms 
may infect other people in the presence of vectors (body lice).  
Endemic typhus (Flea borne typhus)  
• Epidemic typhus (also known as muri ne typhus) is a relatively milder.  
• The incubation period is 1 - 3 weeks and followed by sudden onset of fever, 
rigors, frontal headache, pain in the back and limbs, constipation and cough (due 
to bronchitis). 
• The fever becomes constant after the third day and associated with conjunctivitis 
and orbital pain.  
• Rash appears on the fifth day initially as blanching macules at the anterior axillary 
folds, which subsequently spread to involve other parts of the body (sparing the face & the neck) and become purpuric.  
• During the second week symptoms worsen and additional manifestations, such 
as sore lips, dry brown tremulous tongue, feeble pulse, enlarged spleen & delirium appear.   
Complications of Endemic and Epidemic Typhus


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• During the second week symptoms worsen and additional manifestations, such 
as sore lips, dry brown tremulous tongue, feeble pulse, enlarged spleen & delirium appear.   
Complications of Endemic and Epidemic Typhus  
 Skin necrosis, gangrene of digits,  
 Venous thrombosis 
 Interstitial pneumonia in severe cases 
 Myocarditis   
 Oliguric renal failure  
 Parotitis  
Diagnosis of rickettsial diseases is based on 
History, clinical course of the disease and epidemiologic of the disease may give a clue for 
diagnosis.


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 32Laboratory investigations ;  
Serologic tests :   
• Indirect fluorescent antibody test 
• Weil-Felix agglutination test : This is widely used by many of the hospitals and the 
private clinics in this country, is not specific or sensitive. 
Isolation of the organism by inoculation  into laboratory animals is possible, it is time 
consuming and technically demanding.  
 
Treatment of rickettsial diseases 
Endemic Typhus  
 Doxycycline 100mg bid PO for 7-15 days 
 Chloramphenicol 500mg QID PO for7-15 days 
Epidemic typhus 
 Doxycycline 200mg as single dose  PO until the patient is afebrile for 24 hours.  
 Delousing louse borne typhus    
Supportive Therapy 
 Attention to fluid balance, prevention of bed sores,  
 Treat agitation with diazepam 
 Steroid treatment (prednisolone 20 mg  daily for adults) in severe cases 
 
Prognosis:  Untreated disease is fatal in 7 to 40 % of cases, depending on condition of host. 
In untreated survivors, renal insuffici ency, multiorgan involvement and neurologic 
manifestations (12 %) are common.  However, endemic typhus has better prognosis with a 
mortality of only 1 – 2%. Serious neurological, renal and other complications are unusual.  
 
Prevention 
For flea borne typhus 
 Elimination of fleas on clothing & bedding using insecticides like 1% Malathion powder 
 Apply residual insecticide powder on the floor & bedding to kill hatching fleas.  
 Rodent control using chemicals (e.g. warfarin) 
For louse borne typhus


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Elimination of fleas on clothing & bedding using insecticides like 1% Malathion powder 
 Apply residual insecticide powder on the floor & bedding to kill hatching fleas.  
 Rodent control using chemicals (e.g. warfarin) 
For louse borne typhus    
Eradicate all lice on clothing & bedding using insecticides (1% Malathion powder) 
including all family contacts. DDT is not useful as the lice are often resistant to it


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Internal Medicine 
 
 33
 Wash the patient with soap and water & apply insecticides all over & disinfect clothing 
with insecticides in a bag or sterilize by autoclaving. 
 Protective wearing smeared with insect repellents is recommended for nurses and 
other attendants 
Chemoprophylaxis: Doxycycline 100mg weekly will protect those at risk. 
 
References:   
1) Kasper L., Braunwald E. , Harrison’s principles of Internal medicine, 16th  Edition, 
Rikettsial diseases, pages 999 - 1007 .


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Internal Medicine 
 
 343. Helminthic Infections  
• Intestinal Nematodes 
• Tissue Nematodes  
• Filariasis and Related Infections 
• Schistosomiasis & Other Trematodes 
• Cestodes 
 
3.1 Intestinal Nematodes 
Learning Objective :  At the end of this unit the student will be able to  
1. Define intestinal nematodes  
2. List the etiologies of intestinal nematodes 
3. Describe the mode of transmission of intestinal nematodes 
4. Mention the epidemiology of intestinal nematodes  5. Describe the pathophysiology of intestinal nematodes  6. Identify the clinical manifestations of intestinal nematodes 
7. List the complications of intestinal nematodes 
8. Describe the most commonly used tests to identify intestinal nematodes 9. Manage intestinal nematodes at the primary care level with appropriate drugs   10. Design appropriate methods of prevention and control of intestinal nematodes 
 
Nematodes  are elongated, symmetric round worms.  These can be classified as intestinal or 
tissue nematodes. Some of the intestinal nematode species are Strongyloides stercoralis, 
Enterobius vermicularis, Trichuris trichuira, Ascaris lumbricoides, Necator americanus and 
Ancylostoma  duodenale . More than a billion people worldwide are infected with one or more 
species of intestinal nematodes.  They are most common in regions with poor sanitation, 
especially in developing countries.   
 
3.1.1 Ascariasis 
Definition:  Ascariasis is an infection caused by Ascaris Lumbricoides.


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species of intestinal nematodes.  They are most common in regions with poor sanitation, 
especially in developing countries.   
 
3.1.1 Ascariasis 
Definition:  Ascariasis is an infection caused by Ascaris Lumbricoides. 
Epidemiology  - Ascariasis has a worldwide distribution particularly in regions with poor 
sanitation.  Children frequently acquire ascariasis by the ingestion of embryonated eggs.   
Development:- The adult live in the lumen of the small intestine, especially in the jejunum.  
Eggs reach the external environment with the feces. After ingestion these eggs hatch in the


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Internal Medicine 
 
 35intestine, liberating minute larvae that rapidly penetrate blood or lymph vessels in the intestinal 
wall.  Some larvae reach the portal circulation & are carried to the liver; others pass through the thoracic duct.  They then reach the lung (lung phase), filtered out of blood stream.  After 
increasing in size they migrate to the epiglottis and then down the esophagus to reach the 
intestine where mating takes place.  
 Clinical Features :  
• During the lung phase patients may develop an irritating nonproductive cough and 
burning substantial discomfort. Fever is usual during this phase.  Chest x-ray may show evidence of pneumonitis (Leoffler's syndrome).  
• In established infections, patients are often asymptomatic.  
• In heavy infections, particularly in children, large bolus of worms may cause pain and 
small-bowel obstruction, or they could have chronic abdominal discomfort and growth retardation.  A large worm can enter and occlude the billiary tree, causing biliary colic, cholecystits & pancreatitis. 
 Diagnosis:   Most cases of ascariasis can be diagnosed by the microscopic detection of 
characteristic Ascaris eggs in feces.  Treatment:  Mebendazole 100 mg twice daily for 3 days 
Piperazine 75mg/kg (max. 3.5g) single dos e daily for two days Pyrantel pamoate 
single dose of 10mg/kg Albendazole in a single dose of 400mg is also effective.


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Piperazine 75mg/kg (max. 3.5g) single dos e daily for two days Pyrantel pamoate 
single dose of 10mg/kg Albendazole in a single dose of 400mg is also effective.                        
N.B Mebendazole and albendazole are contraindicated in pregnancy; but pyrantel pamoate and piperazine are safe. 
 
3.1.2 Hookworm 
 
Definition:- It is infection caused by two hookworm species Ankylostoma duodenale  and 
Necator americanus . 
Epidemiology:  It is prevalent worldwide. But older children have the greatest incidence and 
intensity of hookworm infection. It is prevalent in  areas with poor sanitary conditions, particularly 
in relation to human waste disposal. Adults are usually infected when walking or walking bare


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Internal Medicine 
 
 36footed. Hookworm is one of the most common contributing factors for the development of iron 
deficiency anemia in developing countries. 
 
Etiology and development :  The adults are pink or creamy white.  The oval buccal capsule 
contains two pairs of fused teeth.  The male are 8-11mm long; the females, between 10 and 13mm.  The adult hookworms live attached to the mucosa of the small intestine.  Females liberate eggs into the lumen, which are eliminated with the feces.  Under optimum conditions of 
moisture and temperature they hatch within 24 - 48 hours.  They then develop to become 
infective (or filariform) larvae.  When these come into contact with unprotected human skin (usually bare foot), they penetrate the skin layers, enter the blood stream and are transported to the lungs.  Then they migrate up the bronchi and trachea and down the esophagus to reach the small intestine where maturity is attained. 
Clinical features:   
• Most hookworm infections are asymptomatic. 
• Infective larvae may provoke pruritic skin lesion at the site of penetration, as well as at 
subcutaneous migration.  
• Infected people may rarely present with mild transient pneumonitis.   
• In the early intestinal phase, there may be epigastria pain, inflammatory diarrhea or 
other GI symptoms.   
• The major consequence of chronic hookworm infection is iron deficiency because worms 
suck blood from the intestine.  Anemia usual ly develops if there is preexisting iron


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other GI symptoms.   
• The major consequence of chronic hookworm infection is iron deficiency because worms 
suck blood from the intestine.  Anemia usual ly develops if there is preexisting iron 
deficiency states like malnutrition and pregnancy. 
 
Diagnosis:   Diagnosis is established by the finding of characteristic oval hookworm eggs in 
the feces.  Eggs of the two species are not distinguishable.  Anemia of blood loss with Hypochromic microcytic picture is seen in hookworm disease. 
 
Treatment: Several drugs can be used to eradicate hookworm. Commonly used drugs are:  
• Mebendazole 100mg twice daily for 3 days  
• Albendazole 400mg in a single dose.    
• Mild iron-deficiency anemia often can be treated with oral iron alone (ferrous 
sulphate tabs), until anemia is resolved.


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Internal Medicine 
 
 373.1.3 Strongyloidiasis 
 
Definition:-   Strongyloidiasis is an infection by the nematode stronyloides stercoralis, the 
female of which usually is embedded in the mucosa of the small intestine of humans. 
 
Epidemiology:  Mainly distributed in tropical areas, particularly in South East Asia, sub-Saharan 
Africa, and Brazil.  
Etiology and development:   The parasitic adult female lays eggs that hatch in the intestine.  
Rhabditiform larvae passed in feces can transform in to infectious filariform larvae outside of the 
host.  Humans acquire strongloidiasis when fila riform larvae in faecally contaminated soil 
penetrate the skin or mucous membranes.  The larvae then travel to the lungs from the blood 
stream to reach the epiglottis. They are then swallowed to the small intestine.  The minute 
(2mm-long) parasitic adult female worms reproduc e by themselves, parasitic adult males do not 
exist. 
 Eggs hatch locally in the intestinal mucosa, releasing rhabditiform larvae that pass with the 
feces into soil or the rhabditiform larvae in the bow el can develop directly into filariform larvae 
that penetrate the colonic wall or perianal skin and enter the circulation to repeat the migration 
that establishes internal re-infection, called autoinfection. This allows the infection to persist for decades.  
Clinical features : 
• Mild infections are usually asymptomatic.   
• Recurrent urticaria, often involving the buttocks and wrists, is the most common


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Clinical features : 
• Mild infections are usually asymptomatic.   
• Recurrent urticaria, often involving the buttocks and wrists, is the most common 
cutaneous manifestation.   
• Adult parasites burrow into the duodeno-jejunal mucosa and can cause abdominal 
(usually midepigastric) pain, which resembles peptic ulcer pain.  Nausea, diarrhea, GI 
bleeding, mild colitis and weight loss can occur. 
The autoinfection cycle of strongyloidiasis is normally contained by unknown factors of the 
host's immune system.   Strongyloidiasis in immune compromised hosts  . 
• There will be hyper-infection with colitis, enteritis or mal-absorption.


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Internal Medicine 
 
 38• In disseminated disease larvae invade not only the GIT and lung, but also the CNS, 
peritoneum, liver and  kidneys.   
• Bacteremia may develop from enteric bacteria entering through the disrupted intestinal 
mucosa. 
Diagnosis:  In uncomplicated stongyloidiasis, the fi nding of rhabditiform larvae in feces is 
diagnostic.  Serial stool examination may be necessary to detect the larvae.  Eggs are almost 
never seen in stool because they hatch in the intestines. 
 
Treatment: -  Even asymptomatic patients should be treated.   
• Thiabendazole , which is still the drug of choice, is given in a dose of 25mg/kg BID (max. 
3g/day) for 3 days. There are however common side effects like nausea, vomiting, 
diarrhea, dizziness and neuropsychiatric disturbances.   
• Ivermectin  200μg/kg as a single dose daily for 1 or 2 days is better tolerated.  
Disseminated cases should be treated for 5-7 days. 
• Albendazole  400 mg can also be used in simple infections and produces 80% reduction 
in egg count and 200mg/day oral dose for 3 days gives 100% cure.. 
 
3.1.4 Trichuriasis (Whi p-worm infection) 
 
Definition: Trichuriasis is an infection of the hum an intestinal tract caused by the nematode 
Trichuris trichiura. 
Epidemiology:- It is distributed worldwide, but is most abundant in the warm, moist regions of 
the world, the tropics and subtropics. 
Etiology and development:- The parasites have a characteristic whip like shape.  The anterior


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Epidemiology:- It is distributed worldwide, but is most abundant in the warm, moist regions of 
the world, the tropics and subtropics. 
Etiology and development:- The parasites have a characteristic whip like shape.  The anterior 
portion is long and thread like; the posterior portion is broader and comprises about 2/5 of the worm.  The females are slightly longer than the males, 35-50mm long. 
The adult worms reside in the colon and caecum, the anterior portions threaded into the 
superficial mucosa.  Thousands of eggs are laid daily and pass with the feces.  They mature in the soil.  After ingestion, infective eggs hatch in the duodenum, releasing larvae that mature before migrating to the large bowel.  The adult worms may live for several years. 
 
Clinical features: Most infections are asymptomatic.  Large worm burden may be associated, 
especially in children, with diarrhea of long duration, dysentery, mucoid stools, abdominal pain


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Internal Medicine 
 
 39and tenderness, dehydration, anemia, weight loss and weakness.  Rectal prolapse may occur, 
particularly in children. Diagnosis: - Diagnosis is reached by demonstration of characteristic lemon-shaped whip 
worm eggs.  Adult worms, which are about 3-5cm long, can be seen on proctoscopy.  Treatment: -  Trichuriasis can be effectively treated with mebendazole or albendazol. 
 Mebendazole 100mg twice daily for 3 days or 
 Albendazole 4mg/kg as a single dose  
 
3.1.5 Enterobiasis (Pinworm) 
 
Definition:- Enterobiasis is an infection of the human in testinal tract by the pin worm Enterobius 
vermicularis. 
Epidemiology: Enterobiasis is found all over the world.  It is more common in temperate 
countries than tropics. 
Tiology and development:- Enterobius vermicularis is a spindle-shaped parasite of humans.  
The female is 8-13mm long; the male, 2-5mm.  Females lay embryonated eggs, which are 
flattened on one side. 
 The gravid female worm migrates nocturnally out into the perianal region and releases upto 
10,000 immature eggs.  The eggs are rapidly in fective and are transmitted by hand-to-mouth 
passage.  The larvae hatch and mature entirely within the intestine.  Self-infection results from 
perianal scratching and transport of eggs to the hands or nails and then to mouth. Pinworm 
infections are very common among family members.


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passage.  The larvae hatch and mature entirely within the intestine.  Self-infection results from 
perianal scratching and transport of eggs to the hands or nails and then to mouth. Pinworm 
infections are very common among family members. 
 
Clinical fearures: While pinworm infection may be asymptomatic, the most common symptom is the intense nocturnal pruritus ani.  This is because of the cutaneous irritation in the perianal region produced by the migrating gravid females and the presence of eggs.  Intense pruritus may lead to dermatitis, eczema and severe secondary bacterial infections of the skin.  Rarely, pinworms may invade the female genital tract, causing vulvovaginits and pelvic granulomas. 
 
Diagnosis:-  Eggs are not found in the stool because they are released in the perineum.  
Therefore, eggs deposited in the perianal region are detected by the application of clear


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 40cellulose tape to the perianal region in the morning.  The tape is then transferred to slide to be 
seen under a microscope. Treatment: Keeping personal hygiene is part of the treatment; patients should keep their 
nails short and wash hands with soap and water after defecation. A single dose of mebendazole 100mg, or pyrantel pamoate10mg/kg, both repeated afte r 2 weeks is effective. An alternative is 
piperazine 65mg/kg for 7 days with repeat course after 2 weeks. It is advisable to treat all household contacts.


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Internal Medicine 
 
 413.2 Tissue Nematodes 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define tissue nematodes  2. List the etiologies of tissue nematodes 3. Describe the mode of transmission of tissue nematodes 
4. Mention the epidemiology of tissue nematodes 
5. Describe the pathophysiology of tissue nematodes 6. Identify the clinical manifestations of tissue nematodes  7. List the complications of tissue nematodes  8. Describe the most commonly used tests to identify tissue nematodes  
9. Manage tissue nematodes at the primary care level with appropriate drugs   
10. Design appropriate methods of prevention and control of tissue nematodes    
 
Tissue nematodes include Trichinosis , Visceral and Ocular larva migrans , Cutaneous larva 
migrans , Cerbral angiostrogliasis  and Gnathostomiasis . 
 
3.2.1 Trichinosis  
Definition:- Disease caused by the parasite Trichinella spiralis,  characterized by an acute and 
rapid course with fever, gastrointestinal symptoms, myalgia and eosinophilia. Epidemiology:- It is widely spread throughout the temperate regions of the world wherever pork 
or pork products are eaten.  It is enzootic in wild life in Africa and man is involved sporadically by 
eating fresh or inadequately cooked pork.  Etiology:- The trichina worm, T.spiralis is a white round worm just visible to the naked eye.  
Adult male ranges from 1.4 - 1.6mm in length by 40 - 60 μm in diameter; the female is 3-4mm


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eating fresh or inadequately cooked pork.  Etiology:- The trichina worm, T.spiralis is a white round worm just visible to the naked eye.  
Adult male ranges from 1.4 - 1.6mm in length by 40 - 60 μm in diameter; the female is 3-4mm 
long and about one and one - half times as broad as the male. Development:- The worm gains entrance to the digestive tract as larvae encysted in muscle 
tissue.  By the time they reach the small intest ine they are freed from their cysts, penetrate the 
duodenum epithelium and mature within a few days.  The female are fertilized and produce between 1000 and 1500 larvae during the 3-16 week period they parasitizes man.  The larva 
circulates in the blood.  They then invade different tissues mainly the muscles. 
Clinical features : -


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 42Twenty-four hours following ingestion of larvae, signs of GI disturbance like nausea, vomiting, 
diarrhea and abdominal pain may occur. With muscular infiltration there may be periorbital 
edema, myalgia and persistent fever up to 40.5oc.  The last stage is characterized by neurologic 
symptoms and sometimes myocarditis.  
 Diagnosis:-  Blood eosinophilia develops in > 90% between 2-4 weeks after infection.  Serum 
levels of IgE and muscle enzymes including creatine phosphokinase, lactate dehydrogenase 
and aspartate aminotransferase are elevated in most symptomatic patients.  A presumptive 
diagnosis can be made based on fever, eosinophilia, periorbital edema and myalgias after a suspected meal.  Diagnosis is confirmed by incr easing titers of parasite specific antibody or 
muscle biopsy demonstrating the larvae. Treatment:- Current antihelminthics are not effective.  Most lightly infected patients recover 
with bed rest, antipyretics and analgesics.  Thia bendazole 25-50mg/kg/day for 2-5 days brings 
down fever and eosinophilia. Mebendazole 300mg daily for 7 days is an alternative. Glucocorticoids (e.g. prednisolone 1mg /kg) are helpful for severe myositis and myocarditis.  
3.2.2 Cutaneous Larva Migrans


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down fever and eosinophilia. Mebendazole 300mg daily for 7 days is an alternative. Glucocorticoids (e.g. prednisolone 1mg /kg) are helpful for severe myositis and myocarditis.  
3.2.2 Cutaneous Larva Migrans 
Cutaneous Larva Migrans ("creeping eruption") is skin eruption caused by burrowing larvae of animal hookworms, usually the dog and cat hookworm (Ancylostoma braziliense).  Larvae hatch from eggs passed in dog and cat feces and mature in the soil.  Humans become infected after skin contact with soil by penetration.  It is prevalent among children and in regions with warm humid climates. 
 
After larvae penetrate the skin, erythematous lesions form along the tortuous tracts of their migration through the dermal-epidermal junction.  The larvae advance several centimeters a day.  Intensely pruritic lesions occur any w here on the body.  The adult worm will die without 
treatment in several weeks.   Diagnosis is readily made clinically.  
 
Treatment  is with thiabendazole orally 25mg/kg bid or albendazol 200mg bid for 2 days or 
topically petroleum jelly for 2-5 days.


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Internal Medicine 
 
 433.3 Filariasis 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define filariasis 2. List the etiologies of filariasis 3. Describe the mode of transmission of filariasis  
4. Mention the epidemiology of filariasis  
5. Describe the pathophysiology of filariasis 6. Identify the clinical manifestations of filariasis  7. List the complications of filariasis 8. Describe the most commonly used tests to identify filariasis 
9. Manage filariasis at the primary care level with appropriate drugs   
10. Design appropriate methods of prevention and control of filariasis 
 
3.3.1 Lymphatic filariasis 
Lymphatic filariasis is caused by Wuchereria bancrofti , Brugia malayi  or Brugia timori .  While the 
later two are found in Asia, the former is prevalent in the tropics and subtropics.  Therefore, 
W.bancrofti  is discussed below. 
 
Definition: Filariasis (bancrofti) is due to the presence of adult W.bancrofti  in the lymphatic 
system or connective tissues of man.  Many species of Anopheles, Culex, Mansonia and Aedes 
are vectors. 
 
Epidemiology: It is widespread throughout much of the tropics and subtropics.  It is also found 
in some Far East countries.  Complete development of the larval forms has been found to occur in many species of mosquitoes.  Generally, W. bancrofti larvae are in lesser number (scarce) in 
the peripheral blood by day and increase at night.


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in some Far East countries.  Complete development of the larval forms has been found to occur in many species of mosquitoes.  Generally, W. bancrofti larvae are in lesser number (scarce) in 
the peripheral blood by day and increase at night. 
 Clinical features: The most common presentations of the lymphatic filariasis are asymptomatic 
(or subclinical) microfilaremia, hydrocel e, acute adenolymphangitis and chronic lymphatic 
disease.  Most of infected individuals have few symptoms despite large numbers of circulating 
microfilaria in the peripheral blood.  But sub-clinical disease is common with microscopic 
hematuria and/or proteinuria and in men scrotal lymphangiectasia.  Only few patients progress


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 44to the acute and chronic stages of infection.  Patients may present acutely with high-grade 
fever, lymphangitis, and transient local edema.  Later patients may have lymphedema (upper and lower extremities) and scrotal swelling. 
 
Diagnosis:- Difficult because microfilaria may not easily be identified.  Definitive diagnosis is by 
demonstration of microfilaria from blood, hydrocele fluid or other body fluids at night.  
Treatment: Diethyl carbamazepine (DEC, 6mg/kg daily fo r 12 days is) the treatment of choice.  
Albendazol 400mg twice daily for 21 days has been shown to have microfilaricidal activity. 
 
3.3.2 Onchocerciasis 
 
Definition: Onchocerciasis ("river blindness") is caused by the filarial nematode Onchocerca 
volvulus.  Etiology:  The living parasites are white or cream colored and transparent.  The males are 19-
42 mm long and the females 33 – 50 cm. 
 
Epidemiology:- Infection in humans begins with deposition infective larvae on the skin by the 
bite of an infected black fly.  The larvae develop into adult in subcutaneous tissue and form nodules.  About 7 months to 3 years after infection the gravid female releases microfilariae that migrate out of the nodule and through out the tissues.  Infection is transmitted to other persons 
when a female black fly ingests microfilariae from the host’s skin and these microfilariae then 
develop into infective larvae. 
 
Clinical features:


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when a female black fly ingests microfilariae from the host’s skin and these microfilariae then 
develop into infective larvae. 
 
Clinical features:  
• Following the bite of an infected fly, there is an incubation period of several months 
before nodules appear. The subcutaneous nodules, onchocercomata,  are the most characteristic lesions of onchocerciasis. They usually app ear on coccyx, sacrum, thigh 
and bony prominences.     
• But the most frequent manifestations of onchocerciasis are pruritus and rash.


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 45• The skin lesions are characterized by wrinkling of skin and epidermal atrophy that can 
more often lead to hypopigmentation than hyperpigmentation. Eczematous dermatitis 
and pigmentary changes are more common in the lower extremities.   
• Visual impairment is the most serious complication of onchocerciasis.  This is due to 
intense inflammation that surrounds the dying mi crofilaria. Early lesions are conjuctivitis 
with photophobia; sclerosing keratitis occurs in minority of patients, which leads to blindness. Inflammation in the interior eye cause iridocyclitis. 
• Patients could have enlarged inguinal lymph nodes (hanging groin). 
• Heavily infected patients could have severe wasting. 
 
Diagnosis:- Diagnosis depends on demonstration of the microfilariae in the skin snip or nodules. 
Microfilariae are rarely found in blood smear, but may be seen in urine.  
Treatment:  Chemotherapy is the main treatment.   
• Ivermectin orally in a single dose of 150mg/kg, y early or semiannually is the treatment 
of choice.  No agent so far eradicates the adult worm.  The drug is microfilaricidal and 
has many advantages: no severe ocular reaction and prevents blindness due to optic 
nerve disease by 50%, the drug is taken ora lly only once every 6 – 12 months & inhibits 
the production of microfilariae by adult female worms for some months. 
• Ivermectin is contraindicated if there is co-infection with loa loa, inn pregnant or lactating


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the production of microfilariae by adult female worms for some months. 
• Ivermectin is contraindicated if there is co-infection with loa loa, inn pregnant or lactating 
women and children under the age of 5 years.  
• Antihistamines should be given for the pruritus. 
 
Prevention 
• Personal exposure in endemic areas can be reduced by avoiding black fly localities and 
by protective clothing. Repellents are of value only for short periods as they are washed 
off by sweat. 
• Control programmes (2 in Africa and one in America) have covered over 99% of all 
population living in endemic areas.  
The control of onchocerciasis today is based on 2 strategies:  
• Vector control by spraying insecticides. Onchocerciasis control Programme in West-
Africa used this strategy


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 46• Large scale Ivermectin chemotherapy is the ma in strategy being used by Onchocerciasis 
Elimination Programme in the Americas (OEPA) and African Programme for 
Onchocerciasis control (APOC)


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Internal Medicine 
 
 473.4 Trematodes 
 
Trematodes or flatworms are a group of morphologically and biologically heterogeneous 
parasitic helminthes that belong to the phylum platyhelminthes.  Human trematode infections are classified according to the site they involv e; the adult flukes may in volve blood, biliary tree, 
intestines and lungs.  Blood flukes are schistosoma mansoni, S.haematobium, S.japonicum, S. 
intercalatum, and S. mekongi.  Biliary (hepatic ) flukes are opisthorchis viverini, clonorchs 
sinensis and fasciola hepatica.  Intestinal flukes are Fasciolopsis buski, and Heterophyes.  
Finally, lung flukes are paragonimus westermani.  Because of its public health importance, only schistosomiasis is discussed here. 
 
3.4. 1 Schistosomiasis 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define schistosomiasis 
2. List the etiologies of the different types of schistosomiasis 
3. Describe the mode of transmission & the life cycle of schistosomiasis  4. Explain the risk behavior of transmission of schistosomiasis 5. Mention the epidemiology of schistosomiasis 6. Explain the pathogenesis of schistosomiasis 
7. Identify the clinical features of the different schistosomiasis 
8. List the common complications of schistosomiasis. 9. Describe the most commonly used tests for the diagnosis of schistosomiasis 10. Make an accurate diagnosis of schistosomiasis  
11. Manage schistosomiasis at the primary care level with  appropriate drugs


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11. Manage schistosomiasis at the primary care level with  appropriate drugs   
12. Design appropriate methods of prevention & control of schistosomiasis  
 
Definition   
Schistosomiasis (also known as Biliharziasis) is a group of diseases caused by the genus 
Schistosoma affecting mainly the gastrointestinal and genitourinary organs.


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Internal Medicine 
 
 48    Etiology and life cycle: Schistosomiasis  in man is caused by five species of Schistosoma  
      S. mansoni 
S. haematobium 
S. japonicum- in southeast Asia 
S. makongi- in southeast Asia (makongi valley   Laos, Cambodia) S. intercalatum - endemic in Congo basin 
The first three are common causes of schistosomiasis. S. haematobium is the cause of urinary 
schistosomiasis and all the rest cause intestinal schistosomiasis.  
Life cycle 
 
Man is the definitive host where sexual reproduc tion takes place after cercarial entry by skin 
penetration and snails are intermediate hosts in which asexual regeneration continues. Each species of Schistosoma has a specific snail host i.e.   S. mansoni   -Biomphalaria species 
S. haematobium  - Bulinus species 
S. japonicum                - Onchomelania species 
 
Life cycle of Schistosomiasis


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 49Epidemiology 
 
• Distribution is world wide where appropriate snails are present. S. mansoni  is reported 
from Africa, Asia, Central and S. America and Europe, and S. haematobium  is endemic 
in most Africa and West Asia. The other three species have localized distribution. In 
Ethiopia, only S. mansoni  and S . haematobium  are endemic. S. mansoni has a wider 
distribution in the lower highland areas of Ethiopia between 1000- 2000 meter altitude. S. haematobium  is endemic in low lands of Ethiopia. 
• It is transmitted by cercarial skin penetration which requires contact with water bodies 
containing cercaria escaping from appropria te snail host. This is encouraged by limited 
sanitary facilities (lack of safe and adequate H
2O supply and latrines) substandard 
hygienic practices, use of water for i rrigation, ignorance, poverty and population 
movements. 
 
Clinical manifestations 
Intestinal schistosomiasis is caused by all human Schistosoma except S. haematobium , 
which is the only cause for urinary schistosomiasis. It affects the large bowel, the liver(in the 
intestinal form), distal colon and  rectum, and manifestations are dependent on the stages of infection. The 1
st two stages are the same for all species of Schistosoma:- 
a) Stege1 . Swimmer’s itch (stage of Invasion) : This is the first clinical sign of acute infection


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st two stages are the same for all species of Schistosoma:- 
a) Stege1 . Swimmer’s itch (stage of Invasion) : This is the first clinical sign of acute infection 
appearing soon after exposure, usually with in 24 – 48 hrs, and characterized by itching at sites of cercarial entry commonly known as swimmer’s itch . It is seen in new comers and 
not common in indigenous people. 
b)  Stege2. Acute stage  (also called toxemia stage/ Katayama syndrome  in Asia)  
It is an early allergic manifestation to egg deposition (3 – l0 wks) in response to massive antigenic stimulus of eggs and include fever, headache, chills, myalgias malaise, profuse 
diarrhea, nausea and vomiting. Patient may have generalized lymphadenopathy, hepatosplenomegally, urticaria and leucocytosis  with marked eosinophilia. Severity depends 
on intensity of infection, and tends to be mild in indigenous population. 
c) Stage 3 &4  (Chronic stage ) occurs 3 months to several years later, coincides with 
deposition of eggs in the tissues. The clinical picture represents the effect of the pathologic lesions caused by the eggs on the urinary and gastrointestinal systems. Thus urinary and 
intestinal Schistosomiasis are different in  their manifestations, as described below.


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 50d) Stages 3&4 intestinal Schistosomiasis   
The disease is very light and symptom-less for months, and then presenting with recurrent 
diarrhea with blood and lethargy. They may have intestinal polyps, and progressive fibrosis of 
the intestinal wall leading to formation of strictures but intestinal obstruction is very rare. 
Moreover, granulomatous hepatitis followed by pr ogressive peri-portal fibrosis (also called 
pipe stem fibrosis) may develop resulting in portal hypertension with associated splenomegally, ascites and esophageal varices that occasionally may bleed. 
e) Stages 3 and 4 urinary Schistosomiasis 
Deposition of eggs in the wall of the urinary bladder induces the formation of pseudo tubercles and epithelial hyperplasia, with subsequent fibrosis and calcification causing dribbling, incontinence, frequency, dysuria and hematuria. Chronic infection leads to obstructive uropathy, hydronephrosis, chronic pyelonephritis, renal failure and contraction of 
the bladder. 
In rare instances gonads, CNS (brain, spinal cord), lungs and endocrine organs can be involved. 
 
Laboratory Diagnosis   
• Identification of the characteristic ova 
In stool or urine by 
 Direct smear method; easy but light infection can be missed  
 Sedimentation / Concentration method 
 In rectal snip/bladder biopsy sample if it cannot be detected in the stool or urine. 
• Seroimmunological diagnosis lacks specificity,  
  Clinical diagnosis


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Sedimentation / Concentration method 
 In rectal snip/bladder biopsy sample if it cannot be detected in the stool or urine. 
• Seroimmunological diagnosis lacks specificity,  
  Clinical diagnosis 
• For intestinal Schistosomiasis  
 Sigmoidoscopy and rectal snip identifies lesions and  ova of the parasite 
 Ultrasound of liver and spleen to demonstrate  peri-portal fibrosis and  spleen 
enlargement 
 Liver biopsy  
• For urinary schistosomiasis 
 Cystoscopy - demonstrates fibrosis and calcification of the bladder 
 Bladder biopsy and histology demonstrates ova in biopsy sample 
 Radiological


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 51o Plain abdominal X- ray may detect calcification of bladder 
o Intravenous Pyelogram-to see for the presence of obstructive uropathy 
o Ultrasound of the kidneys and ureter 
 
Treatment  
Drug treatment is both safe and effective, 
• Praziquantel : has wide spectrum, effective against all species of Schistosoma, single 
oral dose, has high cure rate  
         Dose:     S. mansoni and S. haematobium = 40mg/kg orally once 
                      S. japonicum  = 60mg/kg orally once 
• Metrifonate  is effective against S. haematobium.  
          Dose :  7.5 – 10mg/kg in 3 doses at 2 wks interval  
• Oxaminoquine  is effective against S. mansoni 
    Dose : 15mg/kg orally once for sensitive strains  
                  In Ethiopia 40mg/kg orally once 
 
Prevention and control requires multidisciplinary approach  
• Environmental sanitation avoidance of pollution of surface water 
 Provision of latrine and sanitary waste disposal  
 Prevention of human contact with infected water 
 Provision of safe and adequate water 
 Protective clothing when contact is unavoidable 
 Health education to reduce contact with infected water bodies 
• Elimination of the disease in the reservoir by chemotherapy 
 Case finding and treatment and mass (community) treatment in selected 
population 
• Snail control  
 Physical control-alteration of habitat,eg removal of vegetation, drainage of   
swamps etc 
 Chemical control (moluscicides) Yuri min, Frescon, “Endod“ (phytholacca


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population 
• Snail control  
 Physical control-alteration of habitat,eg removal of vegetation, drainage of   
swamps etc 
 Chemical control (moluscicides) Yuri min, Frescon, “Endod“ (phytholacca 
dedocandra) 
 Biological control- Fish or other snails that feed on vector snails


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 52References: 
1. Schistosomiasis in Ethiopia , Patho Biology Department AAU 
2. Kasper L., Braunwald E. , Harrison’s principles of Internal medicine, 16th  Edition, 
Schistosomiasis  , pages 1266-1271.


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Internal Medicine 
 
 533.5 Cestodes 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define cestodes 2. List the types of cestodes and their etiologies  3. Describe the mode of transmission of cestodes 
4. Explain the risk behavior for the transmission of cestodes 
5. Mention the epidemiology of cestodes 6. Identify the clinical features of cestodes 7. List the common complications of infection by cestodes 8. Describe the most commonly used tests for the diagnosis of cestodes 
9. Make an accurate diagnosis of cestodes  
10. Manage cestodes at the primary care level with appropriate drugs   11. Design appropriate methods of prevention and control of cestodes 
 Cestodes or tapeworms are segmented worms .  The tapeworms can be divided into two.   
• In one group the definitive hosts are humans, these include Taenia saginata, 
Diphyllobothrium, Hymenolepsis and Dipylidium Canium.   
• In the other group, humans are intermediate hosts.  These are Echinococcosis, 
Sparganosis and Coenurosis.   
• Humans can be a definitive or intermediate host to T.solium. 
 
3.5.1 Taeniasis saginata 
Definition:- Taeniasis saginata or beef tapeworm infection is caused by the presence of the 
adult beef tapeworm, T.Saginata, in the intestine of humans. 
Distribution:- It is found all over the world.  It occurs in all countries where raw meat is


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Definition:- Taeniasis saginata or beef tapeworm infection is caused by the presence of the 
adult beef tapeworm, T.Saginata, in the intestine of humans. 
Distribution:- It is found all over the world.  It occurs in all countries where raw meat is 
ingested.  It is prevalent in sub-Saharan Africa and the Middle East. Ethiopia is one of the heavily affected countries. Etiology and Epidemiology: T.Saginata is a large tapeworm usually 5-10 meters in length.  
The scolex carries four round suckers.  Behind the scolex there is a short neck from which proglottids (segments) form.  As each proglottid ma tures, it is displaced further back from the 
neck by the formation of new, less mature segments.  Humans are the only definitive host.  Eggs deposited on vegetation can persist for months or years, until ingested by cattle.  Embryo


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 54from cattle intestine migrates to the muscle and transform into cysticercus.  When eaten raw or 
undercooked, this infects humans. Clinical features : Usually patients are asymptomatic.  Often infection is detected when 
patients pass proglottids with stool or alone.  Proglottids are motile and this causes perianal discomfort during discharge.  Mild abdominal pain, nausea, anorexia and weight loss can occur.  Diagnosis: The diagnosis is reached by demonstrating the eggs or proglottids in the stool. 
Treatment:  Treatment of choice is prazequantel 5 -10 mg/kg in a single dose. 
            Niclosamide as a 2 g single morning dose before breakfast is an alternative.  
 
3.5.2 Taeniasis Solium:   
It is caused by T.solium from eating raw or undercooked pork. 
Etiology: The adult tapeworm resides in the upper jejunum, similar to taenia saginata.  Its 
scolex attaches to intestinal wall by both sucking disk and two rows of hooklets.  Life cycle is 
similar to beef tapeworm.  However, both the adult tapeworm and the larvae (Cysticerca) infect 
people. Clinical features : Mostly patients are asymptomatic; but they could have epigastric discomfort, 
nausea and weight loss. Patients may note passage of proglottids.  When infected with 
cysticerica (cysticercosis), they are distribute d all over the body.  The major manifestations 
come from the CNS with seizures, headache, raised intracranial pressure, mental changes etc.


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cysticerica (cysticercosis), they are distribute d all over the body.  The major manifestations 
come from the CNS with seizures, headache, raised intracranial pressure, mental changes etc. 
Diagnosis: The diagnosis of intestinal T.solium infection is made by the detection of eggs or 
proglottides.  Diagnosis is difficult in cysticercosis, which is done by different clinical and laboratory criteria. 
Treatment: Intestinal T.solium  infection is treated with a single dose of prazequantel 5-10 
mg/kg, this treatment may be complicated by dev elopment of CNS inflammation if cysticercosis 
co-exist. If patients develop CNS symptoms, refer them to a hospital. 
 
3.5.3 Hymenolepis nana (Dwarf tapeworm) 
Etiology: Dwarf tapeworm is 25-40mm in length by 1mm in breadth.  The scolex bears four 
small suckers.   Epidemiology: It is distributed all over the world.  
This tapeworm doesn't require intermediate host.  Hatching of eggs occurs in the small intestine where they penetrate the villus and become cysticercoid.


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 55Eventually the parasites breakout in to the lumen of the gut and reach maturity.  Infection is 
prevalent in children. Clinical features: Most infections are asymptomatic.  Severe infections may manifest with 
abdominal pain, anorexia and diarrhea. Diagnosis: Diagnosis is based upon demonstration of the eggs in the stool. 
Treatment: -  The treatment of choice is praziquantel 25 mg/kg as single dose. 
  A course of niclosamide for 7 days is also effective. 
 
3.5.4 Diphyllobothriasis (fish tape worm):-  
Diphyllobothriasis is infection caused by adult Diphyllobothrium latum. It is acquired from eating 
raw fish. Etiology: It is mostly found in Europe and Northern hemisphere.  It is the longest tapeworm 
reaching up to 25 meters. Clinical: Many people are asymptomatic.  But pati ents could have abdominal pain, loss of 
appetite, anorexia, nausea, diarrhea or loss of weight.  Since this tapeworm consumes a lot of vitamin B12 and interferes with its absorption, it can cause vitamin B12 deficiency; and some patients develop megaloblastic anemia. 
 
Diagnosis: Diagnosis is reached by demonstration of characteristic eggs in the stool. 
Treatment: 
• Praziquantel 5-10 mg/kg once is very effective.  
• Vitamin B12 deficiency should be treated if present. 
 
N.B further reading Module on  intestinal parasitosis, by Health Science College, 
Hawassa University


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 563.6 Leishmaniasis 
 
 Learning Objective :  At the end of this unit the student will be able to  
1. Define leishmaniasis 
2. Classify leishmaniasis 3. List the etiologies & animal reservoirs of the different types of leishmaniasis 4. Describe the mode of transmission leishmaniasis 
5. Explain the epidemiology of leishmaniasis 
6. Describe the pathophysiology of visceral leishmaniasis 7. Identify the clinical manifestations of the different types of leishmaniasis  8. List the complications of visceral leishmaniasis  9. Describe the most commonly used tests for the diagnosis of leishmaniasis 
10. Make a presumptive diagnosis of leishmaniasis  
11. Refer suspected cases of leishmaniasis to hospitals for investigation & treatment  12. Design appropriate methods of prevention andcontrol of leishmaniasis 
 
Definition : is an infectious disease caused by the protozoa called Leishmania 
Classification of leishmaniasis There are three major clinical forms of leishmaniasis : 
• Visceral leishmaniasis   
• Cutaneous leishmaniasis   
• Mucocutaneous leishmaniasis   
 
Etiologic Agents 
The different clinical forms of leishmaniasis (listed above) are caused by different species of 
leishmanial parasites which are listed under each of these diseases. The parasites are seen in 
two forms 
• Leishmanial form:-  ( amastogote )  this is non flagellate form seen in man and extra 
human vertebrate reservoir


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leishmanial parasites which are listed under each of these diseases. The parasites are seen in 
two forms 
• Leishmanial form:-  ( amastogote )  this is non flagellate form seen in man and extra 
human vertebrate reservoir 
• Leptomonad forms (also called promastigotes) are flagellated forms  
The parasite is transmitted by the bite of vectors of the species phlebotomus, Sand flies


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 57Life Cycle of Leshimaniasis  
• Transmitted by the bite of an infected female phlebotomine Sand fly, the leishmaniases 
are globally widespread diseases. Sand flies are primarily infected by animal reservoir 
hosts, but humans are also a reservoir for some forms. Animal Reservoirs: include 
Rodents - Commonly in East Africa, Ethiopia, the Sudan and Kenya and Canines - Mediterranean and Asia. 
• The life-cycle starts when a parasitized female  sandfly takes a blood meal from a human 
host. As the sandfly feeds, promastigote forms of the leishmanial parasite enter the human host via the proboscis. Within the human host, the promastigote forms of the parasite are ingested by macrophage where they metamorphose into amastigote forms 
and reproduce by binary fission. They increase in number until the cell eventually bursts, 
then infect other phagocyctic cells and continue the cycle. 
• The infected host is bitten by another female sandfly. Parasites are picked up by the fly 
during the blood meal. The parasites are transformed inside the fly and delivered to a 
new host, and the life-cycle continues 
 
Fig 3.6.1 Life cycle of Leshimania


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 58Visceral Leishmaniasis (Kala Azar) 
 
Visceral leishmaniasis is a chronic systemic disease caused by L. donovani.   It is characterized 
by chronic irregular fever, profound wasting, debility and hepatosplenomegally. 
 Epidemiology  
Visceral leishmaniasis affects many countries in Africa, mainly Ethiopia and the Sudan the 
Middle East, Southern soviet union, India and S. America.  It is endemic in low land Ethiopia 
mainly North Western Ethiopia (Metema, Humera), Gikawo (Gambella), lower Omo river basin 
and in the south Woito and Segan river basin, Moyale and lower Genale river.  The disease is becoming a common opportunistic infection in HIV/AIDS.  
Transmission 
The commonest way of transmission is by inoculation of promastigotes into humans by the bite of sand flies which breed in termite hills and forests. The source of the aflagellate forms may be either humans or extra human vertebrate reservoirs, and the disease may have life cycles that involve humans and sand flies only, or humans, sand flies and extra human 
vertebrate reservoirs together. Rarely transmission may occur via blood transfusion and injections.  
Pathogenesis 
The common site of entrance is the skin where primary cutaneous lesion appears at the sites of 
sand fly bite.  The lesion is tiny and may pass unnoticed.  This is also called primary


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Pathogenesis 
The common site of entrance is the skin where primary cutaneous lesion appears at the sites of 
sand fly bite.  The lesion is tiny and may pass unnoticed.  This is also called primary 
leishmanioma.  Here a cellular reaction by lymphocytes and plasma cells develop around the amasitigote-filled histiocytes in the dermis.  As immune response develops epitheloid and giant 
cells appear, to be followed in some by healing. 
 
In others usually 4-6 months later amastigotes escape to the blood in macrophages, hematogeneous spread occurs and colonize the cells of reticuloendothelial system, where they multiply further and released after rupture of the cells and transported to new cells.  The cells affected include that of spleen, liver, bone marrow and lymphatic glands, where the parasite 
multiplies and cause overcrowding of cells and as a result these organs are enlarged.


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 59The spleen is grossly enlarged with smooth capsule initially, which become thickened & nodular 
as disease progresses.  The involvement of the bone marrow leads to the development of pancytopenia.  The liver with its Kuppfer cells packed with amastigotes is enlarged & progress 
to cirrhosis. The lymphatic glands are enlarged & congested especially the mesenteric group. 
 
Clinical Features 
• Incubation period usually varies from weeks to months but can be as long as years.   
• Visceral infections remain sub clinical or become symptomatic with acute, sub acute or 
chronic course.   
• The onset is often gradual but can also be sudden with high grade fever (intermittent or 
remittent) lasting for 2-6 weeks and occasionally longer.  Waves of fever are separated 
by afebrile periods.   
• In those with gradual onset in endemic areas discomfort below the left costal margin is 
common due to enlarged spleen and have cough, epistaxis and diarrhea.   
• The patient will be markedly emaciated, with hepatosplenomegally, generalized 
peripheral lymphadenopathy and marked pallor in the late stage of the disease.   
• Edema of the legs, brittle dry hair, hemorrhages from any site (gum, skin etc) with 
purpura and petechiae of the skin may occur. 
• Some patients develop post - Kala- Azar derma  leishmaniasis after months or years of 
treatment for VL. 
 
Diagnosis 
• Definitive diagnosis is based on demonstration of the Parasite


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purpura and petechiae of the skin may occur. 
• Some patients develop post - Kala- Azar derma  leishmaniasis after months or years of 
treatment for VL. 
 
Diagnosis 
• Definitive diagnosis is based on demonstration of the Parasite 
- Giemsa stained smear of peripheral blood (in Indian form) and tissue touch 
preparation of organ aspirates and examined by light microscopy. 
- Culture of tissue aspirates taken from the spleen,  BM, liver or lymph node with 
the corresponding yield of 95%, 85%, 75%, 60% respectively, using different media (NNN or Schneider insect media) 
• Serologic diagnosis  - ELISA or DAT, both 100% sensitive & specific 
• Montenegro skin test  - negative in visceral leishmaniasis, becomes positive 6-8 wks 
after recovery. 
• CBC  - Pancytopenia (anemia, leucopoenia, thrombocytopenia)


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 60Management 
Patients need hospitalization for proper treatment and follow up. 
• Supportive treatment 
 Blood transfusion to correct anemia 
 Treat any additional infection 
 Correct malnutrition 
• Definitive treatment 
Pentostam / Sodium Stibogluconate :  IV, IM 20mg sb/kg per day for 28 days  
For relapse or incomplete cure the same drug can be used for 40-60 day 
If resistant to the above drug use alternative drugs  
Amphotercine B lipid formulation:   IV 2- 5mg/kg per day 5-25 weeks 
Petntamidine:  IV, IM 4 mg/kg per day for 3-4 weeks  
Prevention measures should include  
• Reduction of human contact with sand flies by using  
 Insecticide impregnated bed nets  
 Wearing protective clothing and covering as much skin as possible 
 Chemical repellents applied on exposed skin before hours of sandfly activity 
(dusk and night) are effective. 
 Combustion of permethrin containing mosquito coils is also effective 
   Screening windows and doors 
• Reduction of sand fly population by using insecticides  DDT, Malathion 
• Control of reservoir - dogs rodent 
• Construct huts and camps away from breeding sites (termite hills and forests).   
• Destroy sand fly breeding sites 
 
Cutaneous Leishmaniasis (oriental sore) 
 
The skin is one of the organs commonly affected by leishmania. Following the bite of sand flies, 
leishmania multiply in the macrophages of the skin.  Single or multiple painless nodules occur


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Cutaneous Leishmaniasis (oriental sore) 
 
The skin is one of the organs commonly affected by leishmania. Following the bite of sand flies, 
leishmania multiply in the macrophages of the skin.  Single or multiple painless nodules occur 
on exposed areas (mainly the face) within one week to 3 months of the bite.  The nodules may enlarge and ulcerate with erythematous raised border and overlying crust which may spontaneously heal over months to years.  Different clinical patterns are described depending on the etiologic agents as follows:-


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 61Table I- 3.6-1: Important causes of cutaneous leishmaniasis 
           
In the Old World 
  
Leishmani
a Species  Distribution  Reservoir  Clinical Pattern  
L.major & 
L.tropica Russia & Eastern Europe middle east, the 
Mediterranean sub-Saharan& west Africa. 
           Desert rodent for 
L.major dog& 
humans for L.tropica Spontaneous healing with 
scaring 
L. ethiopica Highlands of Ethiopia    & 
Kenya Hyrax Spontaneous healing with 
in 6 mo 
In the New World 
  
L. amazonensis   Diffuse cutaneous 
leishmaniasis resembling 
lepromatous leprosy (but spares the nasal septum) 
L. peruviana Cooler climates( Andes)  Single or multiple 
ulcers(Uta),heal 
spontaneously 
L. mexicana  Mexico, Guatemala  
Brazil, Venezuela & 
Panama    Infection of Pinna 
(chiclero's ear) Causes destruction of Pinna lesion 
persisting for more  than 
20 yrs. 
 
Investigation for Diagnosis 
• Giemsa staining of smear from a split skin :  This demonstrates leishmania in 80% of 
cases 
• Culture followed by smear


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 62• Leishmanin skin test is positive in over 90% of cases although it is negative in diffuse 
cutaneous leishmaniasis. 
 
Treatment  
Small lesions don't require treatment.  However la rge lesions or those on cosmetically important 
sites require treatment either 
• Locally - by surgery, curettage, cryotherapy or hyperthermia (40-420c) or 
• Systemic therapy:   with drugs like Pentostam.  
 N.B. Treatment is less successful than visceral leishmaniasis as antimonials are 
poorly concentrated in the skin L. ethiopica is resistant to antimonials. 
 
Mucocutaneous Leishmaniasis  
• It is caused by  L. braziliensis , and commly seen Latin America (Brazil, Ecuador. Bolivia, 
Uruguay and Northern Argentina)  
• In the early stage it affects the skin, but in secondary stage of the disease it involves the 
upper respiratory mucosa.  
• Initially painful, itchy nodules appear on the lower limbs and then ulcerate with 
lymphangitis.  Tue lesion may heal spontaneously in 6 months.   
• In about 40% of patients, secondary lesions appear several years later at the 
mucocutaneous junctions of nesopharynx.  This leads to nasal obstruction, ulceration, 
septal perforations and destruction of the nasal cartilage called Espundia. 
Diagnosis  is difficult as there are a few leishmania in the lesions 
  
• Leishmanin skin test is often positive 
• Antibody tests (DAT, ELISA) are often positive


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septal perforations and destruction of the nasal cartilage called Espundia. 
Diagnosis  is difficult as there are a few leishmania in the lesions 
  
• Leishmanin skin test is often positive 
• Antibody tests (DAT, ELISA) are often positive 
 
Treatment:  Requires systemic antimonials (Pentostam) but relapses are common.  
Amphotericin is sometimes used. Death usually occurs from secondary  bacterial infection


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 63References:  
1. Kasper L., Braunwald E. , Harrison’s principles of Internal medicine, 16th  Edition, 
Leshimaniasis  , pages 1233-1237.


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 644.  Tuberculosis 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define Tuberculosis 
2. List the etiologic agents for Tuberculosis 3. Describe the mode of transmission of Tuberculosis   
4. Understand the epidemiology of Tuberculosis  
5. Describe the pathophysiology of Tuberculosis  6. Identify the clinical manifestations of Tuberculosis   7. List the complications of  Tuberculosis  8. Describe the most commonly investigations for the diagnosis of Tuberculosis  
9. Make an accurate diagnosis of Tuberculosis  
10. Understand the different treatment categories of Tuberculosis be able to categorize any 
type of Tuberculosis  
11. Understand the different case definitions of tuberculosis 
12. Manage most cases of tuberculosis appropriately  
13. Refer complicated  cases of Tuberculosis diseases to hospitals for better management  14. Design appropriate methods of prevention and control of Tuberculosis  
 Definition: Tuberculosis is a Chronic necrotizing disease caused by Mycobacterium 
tuberculosis complex.  It usually affects the lung s but almost all organs can be affected. Thus it 
is conveniently classified into:  
• Pulmonary TB (PTB) : accounts for 80% of all TB cases. 
Smear-positive PTB: 75-80% of all PTB cases Smear-negative PTB: 20-25% of all PTB cases 
• Extra-pulmonary TB (EPTB) : accounts for 20% of all TB cases. 
 Etiologic Agent:  Mycobacterium belongs to the myc obacteriaceae family.  The species


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Smear-positive PTB: 75-80% of all PTB cases Smear-negative PTB: 20-25% of all PTB cases 
• Extra-pulmonary TB (EPTB) : accounts for 20% of all TB cases. 
 Etiologic Agent:  Mycobacterium belongs to the myc obacteriaceae family.  The species 
commonly involved are M. tuberculosis, M.bovis, M. africanum and M.microti.  But of all, 
M.tuberculosis is by far the commonest.  M. tuberculosis is a rod-shaped, non-spore-forming, 
thin aerobic bacterium measuring about 0.5 μm by 3μm.  The bacterium is demonstrated by acid 
fast staining technique.


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Internal Medicine 
 
 65Epidemiology:- 
• Tuberculosis is one of the most prevalent diseases in the world.  About one-third of the 
world’s population is infected with tuberculosis and thus at risk of developing active 
disease (TB). It is estimated that 8.4 million people develop active TB every year and 2.3 
million die. More than 90 % of TB cases and deaths occur in developing countries and 75 % of cases are in the most economically productive age group. 
• TB has been recognized as major cause of morbidity and mortality in Ethiopia. 
According to a report from Ministry of health TB is 3
rd leading cause of hospitalization 
and 1st leading cause of Hospital death. WHO Estimates Incidence of TB in Ethiopia is   
356 per 100,000 /yr and the incidence Smear positive TB is 155 per 100,000/year. 
• In the year 2001 the TB leprosy control program (TLCP) registered 94,957 cases of TB 
from DOTS implementing areas.  
• Coinfection with HIV significantly increases the risk of developing Active TB and HIV has 
become the most important risk factor to develop active TB. In HIV- infected persons the 
risk of developing TB is increased by more than 10 times compared to those who are 
HIV negative. It is estimated that about 40% of adult TB cases in urban areas are HIV-positive. The incidence and prevalence of tubercu losis, in recent years has doubled or


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HIV negative. It is estimated that about 40% of adult TB cases in urban areas are HIV-positive. The incidence and prevalence of tubercu losis, in recent years has doubled or 
tripled because of the HIV pandemic, especially in developing countries. It is also shown that active tuberculosis can result in rapid progression of HIV infection in a patient. 
• Multi-drug resistant TB which often results from poor management is becoming a serious 
concern in many countries. 
 
Transmission  
Adults with smear positive TB such as cavi tory TB and Laryngeal TB are the sources of 
infection. Patients who are culture-negative pulmonary TB and extra pulmonary disease are not 
infectious. 
M. tuberculosis is commonly transmitted from a patient with infectious tuberculosis to a healthy 
individual through  
• Inhalation of droplets excreted via coughing, sneezing or speaking.          
• Un-boiled milk could also transmit M. bo vis, but the incidence seems to be decreasing 
because of health education on boiling or pasteurizing milk.


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Internal Medicine 
 
 66Factors that facilitate transmission of pulmonary tuberculosis are 
• Infectivity of the contact  ( patients with heavy bacterial load) 
• Environment: overcrowding  
• Duration of contact  ( prolonged exposure ) 
• Intimacy ( how close the source and the subject are )   
 
Patients who acquire the infection may not develop the disease.  The rate of clinical disease is highest during late adolescence and early adulthood, but the reasons are not clear.  Especially young women are affected more than men.   
 The presence some disease conditions increase the likely hood of developing active TB 
(Clinically over disease).   
• The commonest is co-infection with HIV, which suppresses cellular immunity.   
• Hematologic and other malignancies : lymphoma, leukemia, malignancies,  
• Chronic renal failure 
• Diabetes mellitus 
• Immune suppressive drugs like long-term corticosteroids (e.g. prednisolone)  
• Old age because of decreased immunity.  
• Malnutrition is a very important factor for the development of disease. 
 
Pathogenesis  
M. tuberculosis enters the body mostly via respiratory tract through coughed out droplets from 
an infectious patient.


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• Malnutrition is a very important factor for the development of disease. 
 
Pathogenesis  
M. tuberculosis enters the body mostly via respiratory tract through coughed out droplets from 
an infectious patient. 
 
M. tuberculosis interacts with host immune system immediately after entry.  Activated alveolar macrophages ingest the bacilli; after which they release chemicals to activate other immune system components and try to control the infection or multiplication of bacilli. This process will bring about cell - mediated immune response.  These activated cells aggregate around the 
lesion and the center becomes necrotic, soft cheese like material called caseous necrosis .  
The center, however, may still contain live bacteria that become dormant.  These bacteria will 
flare up and multiply when the person's immunity  is depressed. But if the bacteria inside the 
macrophage multiply rapidly, they will kill the macrophage and are released but to be taken up


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Internal Medicine 
 
 67by other macrophages again. If this process is not arrested, patients may develop disseminated 
infection.  
Clinical Manifestations  
 Pulmonary Tuberculosis : - This can be classified as primary or post primary (Secondary). 
Primary disease: Clinical illness directly after infection is called primary tuberculosis; this is 
common in children <4 years of age. Thus, it results from an initial infection.  
• Frequently it involves the middle and lower lung zones.   
• In the majority it heals spontaneously leaving a healed scar on the lung called Ghon 
lesion .  
• It may be contained by immunity into dormant stage only to flare up in immuno-
compromised state.  
• In children or in immune compromised individuals the disease is usually rapid involving 
the lungs, pleura and mediastinal lymph nodes.  It may disseminate into the blood 
stream and cause milliary tuberculosis or TB meningitis that may be rapidly fatal. 
 
Post primary disease:  -If no clinical disease is developed after the primary infection, dormant 
bacilli may persist for years or decades before being reactivated, when this happens, it is called 
secondary (or post primary) tuberculosis. There fore this is from endogenous reactivation of 
latent infection.   
• It is more common in adults, and typically in volves the apical lobes.  But any portion of 
the lungs may be involved.  The disease could extend from small infiltrates to large


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latent infection.   
• It is more common in adults, and typically in volves the apical lobes.  But any portion of 
the lungs may be involved.  The disease could extend from small infiltrates to large 
cavitory lesions.  Patients with cavitory lesion expectorate tuberculosis bacilli with 
sputum.   
• Early in the course patients may have intermittent fever, night sweats, weight loss, 
anorexia and weakness.  Most patients have cough, which may be dry at first, but later 
becomes productive of whitish sputum; it is frequently blood streaked.  Patients may have exertional dyspnea.   
• Physical examination  may reveal a chronically sick patient with pallor and clubbing. 
Inspiratory crepitations are seen in some cases.


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Internal Medicine 
 
 68• Laboratory findings  may include raised ESR, anemia or leukocytosis. Sputum 
examination may be positive for AFB. Chest x -ray findings are non-specific; infiltrations, 
consolidation or cavitory lesions may be present. 
 
Extra-pulmonary Tuberculosis :-Commonly affected organs are lymph nodes, pleura, 
meninges, genitourinary tract, bones and joints, and peritoneum. 
 
Lymph-node tuberculosis (TB lymphadenitis):-   
• It is seen more in HIV patients.   
• The commonest sites are cervical and supraclavicular.  
• Lymphnodes are typically matted and firm, sometimes pus may be discharging.  
• The diagnosis is made by fine needle aspiration and/or lymph node biopsy.  
 Pleural tuberculosis:-   
• Pleural involvement may be asymptomatic or  patients could have fever, pleuritic chest 
pain and dyspnea.   
• On physical examination, typically ther e will be decreased tactile fremitus, dullness and 
decreased breath sounds on the affected side.   
• Fluid should be aspirated from pleural space (thoracentesis) and analyzed.  
• Chest x-ray is also helpful in diagnosis; it may show homogenous opacity with meniscus 
sign.  
• Empyema (pus in the pleural space) may complicate tuberculosis occasionally. 
 Genitourinary tuberculosis:   
• It can involve any part of the system.   
• Dysuria, intermittent hematuria and flank pain are common presentations.  But it may be 
asymptomatic for a long period of time.


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Genitourinary tuberculosis:   
• It can involve any part of the system.   
• Dysuria, intermittent hematuria and flank pain are common presentations.  But it may be 
asymptomatic for a long period of time.   
• Urinalysis shows pyuria and hematuria without bacteria in majority of cases (commonly 
called sterile pyuria). Diagnosis may be reached by culturing urine repeatedly for 
M.tuberculosis.   
• It affects more females and may present as infertility or pelvic pain.


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Internal Medicine 
 
 69Skeletal Tuberculosis:-   
• It is usually reactivation of hematogenous site  or extension from a nearby lymph node.  
The most common sites are spine, hips and knees.   
• Spinal tuberculosis is called Pott's disease  or tuberculous spondylitis.  In adults, 
lower thoracic and lumbar vertebrae are commonly affected.  Patients may present with 
swelling and pain on the back with or without paraparesis or paraplegia due to cord compression.   
• Tuberculosis in other bones or joints usually present with pain and swelling. 
• Joint tuberculosis: - Any joint can be affected but weight bearing joints; particularly the 
hip and knee joints are commonly involved. Patients present with progressive joint 
swelling, usually with pain and limitation of movement. If left untreated, the joint may be 
destroyed.   
 Tuberculosis Meningitis:-   
• It is commonly seen in children and immuno-compromised people particularly patients 
with HIV.   
• More than half have evidence of disease in the lungs.   
• Patients with TB meningitis present with headache, behavioral changes and nuchal 
rigidity for about two weeks or more.  Patients may have cranial nerve paralysis and 
seizure.  
• Cerebra spinal fluid analysis  is the most important modality to diagnose TB meningitis. 
CSF examination shows increased WBC c ount, predominantly lymphocytes, and high 
protein and low glucose content. But any of theses could be normal in the presence of


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CSF examination shows increased WBC c ount, predominantly lymphocytes, and high 
protein and low glucose content. But any of theses could be normal in the presence of 
the disease. AFB can be seen in sediment CSF in only 20% of cases; this percentage increases if examined CSF volume is increased. Culture may be positive in about 80%, but it takes 4 to 6 weeks to grow.  
• Patients should be referred to a hospital if TB meningitis is suspected.     
 Gastro Intestinal Tuberculosis:-  
• Tuberculosis can affect anywhere from the mouth to the anus.   
• Bacteria could reach GI by swallowing sputum, hematogenously or by ingesting raw 
milk.  The commonest sites are terminal ileum and cecum.


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 70• Abdominal pain, diarrhea, symptoms of intestinal obstruction and hematochezia (frank 
blood on stool) may be the presenting symptoms.  There could be associated fever, 
night sweats, weight loss and anorexia.  There could be a palpable mass in the abdomen.  Patient could have involvement  of the peritoneum, liver and spleen. 
• Tuberculos peritonitis  arises from ruptured abdominal lymph node or hematogenous 
dissemination. Patients usually present with abdominal swelling and pain, weight loss, fever and night sweating. Aspiration of perit oneal fluid (paracenthesis) reveals exudative 
fluid with many WBC, predominantly lympho cytes. AFB is rarely positive and culture 
positivity is very low. 
• Involvement of the liver and spleen is part of disseminated tuberculosis. Patients will 
present with hepatomegaly and/or splenomegaly. There could be evidence of 
involvement of other organs.  
Pericardial Tuberculosis (TB pericarditis):   
• It is frequently seen in patients with HIV.   
• Patients usually present with fever, retro-sternal pain, cough, dyspnea and generalized 
edema because of pericardial effusion.  Cardiac tamponade may appear later  
• Constrictive pericarditis may develop as a complication of TB pericarditis even after 
treatment and patients can present with symptoms and signs of right sided heart failure. 
• Diagnosis is usually reached by analyzing the pericardial effusion, which is always done


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treatment and patients can present with symptoms and signs of right sided heart failure. 
• Diagnosis is usually reached by analyzing the pericardial effusion, which is always done 
in hospitals. It may show lymphocytos is, but yield for AFB is low.  
• Chest x-ray may show enlarged heart shadow , which suggests effusion. Ultrasound 
should be done when available and it demonstrates effusion.    
Milliary tuberculosis: - 
• This is secondary to hematogenous dissemination of the bacilli.   
• It is more common in children and immuno-compromised patients.   
• Manifestations are nonspecific with fever, night sweats, anorexia, weakness, and weight 
loss.  Patients may or may not have respiratory symptoms.   
• Physical examination findings include seriously sick patient with hepatomegaly, 
splenomegaly and lymphadenopathy.   
• Since symptoms and signs are not specific, high index of suspicious is required for the 
diagnosis.   
• Chest x-ray usually shows milliary pattern of infiltration bilaterally (milliate like lesions, 
“dagussa” in Amharic).


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Internal Medicine 
 
 71Diagnosis 
Clinical suspicion is very important for the diagnosis of tuberculosis.  Patients who have 
suggestive symptoms and signs for tuberculosis should undergo further tests.   
• AFB Microscopy : 
AFB is found on microscopy from specimens like sputum, pleural, peritoneal and cerebrospinal fluid and body discharges, but the yield is different. However, definitive diagnosis depends on detection of M. tuberculosis  from a culture of specimen.  
Sputum examination  is extremely important in patients who have sputum production.  
 AFB stain should be done 3 times in 2 consecutive days (spot - early morning - 
spot).  
 Sputum smear is said to be positive when at least 3 AFB are seen.  
 Smear positive TB is diagnosed when at  least 2 smears are positive or one 
smear positive plus suggestive chest x-ray finding.  
 If all 3 sputum smears are negative and t he patient has suggestive clinical and 
chest x-ray findings, first the patient should be treated with broad spectrum antibiotics to rule out other bacterial causes. If the patient doesn’t respond, 
smear negative pulmonary TB can be strongly considered. 
• Mycobaterial culture  is the gold standard for making diagnosis. However the bacillus is 
slowly multiplying and it takes several weeks to grow the bacilli in a culture media. May 
be used for drug sensitivity tests. 
• Chest x-ray  presentations of tuberculosis are varied.  Although any radiographic finding


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slowly multiplying and it takes several weeks to grow the bacilli in a culture media. May 
be used for drug sensitivity tests. 
• Chest x-ray  presentations of tuberculosis are varied.  Although any radiographic finding 
is possible, typically there will be nodular infiltrates and cavities in the upper lobe; pleural effusion is also common. Chest x-ray findings do not confirm diagnosis of TB.     
• Raised ESR  is a very important clue for the diagnosis even though this is nonspecific. 
There could also be anemia of chronic illness. 
• PPD skin  test is widely used to screen tuberculosis in developed countries where the 
prevalence of TB is low.   Positive reactions are obtained when patients have the infection but do not have active disease or they have received BCG for immunization.  
Therefore, it is not a good method of screening in our country.   
 Standardized case Definition of Tuberculosis 
After making diagnosis of TB proper case Definition should be made to decide on appropriate 
treatment. The definition of TB case depend on the following points


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Internal Medicine 
 
 721. Site of TB ( Pulmonary Vs Extrapulmonary  ) 
• Pulmonary tuberculosis (PTB) refers to disease involving the lung parenchyma. 
Therefore tuberculous intrathoracic lym phadenopathy (mediastinal and/or hilar) or 
tuberculous pleural effusion, without radiographic abnormalities in the lungs, constitutes 
a case of extrapulmonary TB. A patient with both pulmonary and extrapulmonary TB should be classified as a case of pulmonary TB.  Miliary tuberculosis is classified as pulmonary TB because there are lesions in the lungs. 
•  Extrapulmonary tuberculosis (EPTB) refers to tuberculosis  of organs other than the 
lungs, e.g. pleura, lymph nodes, abdomen, genitourinary tract, skin, joints and bones, meninges. Diagnosis should be based on one cult ure-positive specimen, or histological 
or strong clinical evidence consistent with active EPTB, followed by a decision by a clinician to treat with a full course of tuberculosis  chemotherapy. The case definition of 
an extrapulmonary TB case with several sites affecte
d depends on the site representing 
the most severe form of disease . 
2. Bacteriology ( result of sputum smear ) : Smear positive Vs Smear negative 
Identification of smear-positive cases is impor tant, because they are the most infectious 
cases and usually have higher mortality;


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the most severe form of disease . 
2. Bacteriology ( result of sputum smear ) : Smear positive Vs Smear negative 
Identification of smear-positive cases is impor tant, because they are the most infectious 
cases and usually have higher mortality;  
• Pulmonary tuberculosis, sputum smear-positive (PTB+) a) Two or more initial sputum smear examinations positive for AFB, or b) One sputum smear examination positive for AFB plus radiographic abnormalities 
consistent with active PTB as determined by a clinician, or 
c) One sputum smear positive for AFB plus sputum culture positive for M. tuberculosis.  
• Pulmonary tuberculosis, sputum smear-negative (PTB-)  
Case of PTB that does not meet the above definition for smear-positive TB. 
This group includes cases without smear result, which should be exceptional in adults 
but are relatively more frequent in children. 
Note . In keeping with good clinical and public health practice, diagnostic criteria for PTB-should 
include: 
• A at least three sputum specimens negative for AFB, and 
• A radiographic abnormalities consistent with active PTB, and  
• No response to a course of broad-spectrum TB antibiotics, and 
• Decision by a clinician to treat with a full course of ant tuberculosis chemotherapy.


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Internal Medicine 
 
 73• In health facilities where microscopy laboratory services are available and diagnostic 
criteria are properly applied, PTB smear-positive cases represent at least 65% of the 
total of PTB cases in adults, and 50% or more of all TB cases. 
• Note that these proportions may be lower in high HIV-incidence populations. 
• It is apparent from the above definitions that in the absence of culture, standard chest 
radiography is necessary to document  cases of smear-negative PTB.  
3. History of previous treatment of TB In order to identify those patients at increased risk of acquired drug resistance and to prescribe appropriate treatment, a case should be defined according to whether or not the patient has previously received TB treatment.  The following definitions are used: 
• New:  a patient who has never had treatment fo r TB or who has taken ant tuberculosis 
drugs for less than 1 month.  
• Relapse:  a patient previously treated for TB who has been declared cured or treatment 
completed, and is diagnosed with bacteriologically positive (smear or culture) tuberculosis.  
• Treatment after failure: a patient who is started on a re-treatment regimen after having 
failed previous treatment.  
• Treatment after default. A patient who returns to treatment, positive bacteriologically, 
following interruption of treatment for 2 months or more.  
• Transfer in. A patient who has been transferred from another TB register to continue 
treatment .


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following interruption of treatment for 2 months or more.  
• Transfer in. A patient who has been transferred from another TB register to continue 
treatment . 
• Other.  All cases that do not fit the above definitions. This group includes  
 Chronic case, a patient who is sputum-positive at the end of a re-treatment 
4. Severity of the diseases  
Bacillary load, extent of disease and anatomical site are considerations in determining TB 
disease severity and therefore the appropriate treatment. Involvement of an anatomical site results in classification as severe disease if there is a significant acute threat to life (e.g. pericardial TB), a risk of subsequent severe handicap (e.g. spinal TB), or both (e.g. 
meningeal TB). 
Case definitions  
• Tuberculosis suspect. Any person who presents with symptoms  or signs suggestive of TB, in 
particular cough of long duration (more than 2 weeks)


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Internal Medicine 
 
 74• Case of tuberculosis. A patient in whom TB has been bacterio logically confirmed or diagnosed by a 
clinician.  
• Definite case of tuberculosis: a patient with positive culture for the M.tuberculosis complex.  
Based on the above criteria and case definitions, a TB patient falls in to one of the four 
categories of treatment. This categorization helps in prioritizing patients and in selecting the type regime to be used in a patient. 
 Table I- 4 -1: Tuberculosis Treatment Category  
TB treatment 
category  
Patients Recommended 
Treatment /Regimen 
 Category  1  • New smear positive PTB 
• Smear –ve PTB with extensive 
TB 
• Sever forms of extra 
pulmonary TB   DOTs short course  HRZE/S for 2 months                +  
HR 4 MO or HE 6 MO Or  H3R3 for 4 MO 
 Category  2   • Relapse  
• Treatment Failure  
• Return after Default  Retreatment  2HRZES/ 1HRZE                +  
            5ERH 
 Category  3   
  
• Smear negative PTB with 
limited  
• EPTB less ever form 
• Children between 7 and 14 
years old with any type of 
TB, who are not seriously ill  
  2HRZ or 2H3R3E3                  + 
HR 4 MO or HE 6 MO 
Or  H3R3 for 4 MO 
 Category  4    
• Chromic cases  2
nd Line Anti TB drugs


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Internal Medicine 
 
 75Anti Tuberculosis Chemotherapy 
Aim of Treatment of Tuberculosis   
• To cure the patient from the diseas es and prevent death and complications  
• To decrease transmission of Tuberculosis  
Treatment of tuberculosis has two phases, 
• The intensive (initial) phase : combination of 3 or more drugs is given for 2 
months. In the retreatnment regimen it continued for 3 months. This is to decrease 
the bacterial load and make the patient non-infectious rapidly. 
• Continuation phase:   Two or three drugs used for 4 -5 months.  This phase follows 
the intensive phase and the aim is to achieve complete cure.   
♦ During the intensive phase of DOTS, the drugs must be collected daily and must be 
swallowed under the direct observation of a health worker. During the continuation 
phase, the drugs must be collected every month and self-administered by the patient. 
♦ For category 2 pateints put on re-treatment, the whole duration of re-treatment, including 
the continuation phase, the drugs must be taken under the direct observation of a health worker. Streptomycin should not be included in the re-treatment for pregnant 
women.


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Internal Medicine 
 
 76Table I- 4-2: Anti TB drugs ar e classified in to two groups  
 
First Line Drugs (Essential Anti 
tuberculosis drugs): There are five drugs 
in use currently  Second Line Drugs (reserve Anti TB drugs) are used only in Chronic case of 
TB  
• Streptomycin (S) in 1gm vial : the 
only drug given IM 
• Ethambutol  (E) in 400mg tablet,  
• Isoniazeid (H) in 100mg and 300 
mg tablet,  
• Rifampicin (R) in 150mg and 
300mg tablets and  
• Pyrazinamide (Z) in 500mg tablets. 
Fixed drug combinations  
• RIF , INH , PZA(RHZ) 
150/75/400mg 
• ETH and INH (EH) 400/150mg 
• RIF and INH (RH) 150/75mg 
• RIF, INH, PZA, ETB (RHZE) 
150/75/400/225  • AMINOGLYCOSIDES  
 Kanamycin and Amikacin 
 Capreomycin (polypeptide) 
• THIOAMIDES  
 Ethionamide 
 Protionamide 
• FLUOROQUINOLONES  
 Ofloxacin 
 Ciprofloxacin 
• CYCLOSERINE (AND TERIZIDONE)  
•  P-AMINOSALICYCLIC ACID 
Side Efects of common Anti TB Drugs : Anti-tuberculosis drugs cause different side 
effects.  These may be Minor w here the drugs are continued or Major in which case the 
drugs should be discontinued and the patient referred


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Internal Medicine 
 
 77Table I-4-3: Side Effects of common Anti TB drugs and Treatment of side effects  
 
 
Anti TB Drug   
Severity of the 
adverse effect  
Side Effects  
Treatment of Side 
Effects 
Minor  Burning Sensation in the Feet  (Peripheral neuropathy) Pyridoxine 100 mg PO daily  
 Isoniazide  
Major  Jaundice /Hepatitis  Stop INH 
Minor  Orange or red discoloration of urine 
Nausea , abdominal pain  Reassurance  
Take drug with small 
meal  
Rifampicine  
 
Major  Hepatitis , Acute renal failure shock , purpura  Stop Rifampcin 
 
Minor  None    
Ethambutol 
Major  Optic neuritis : Visual impairment  Stop Ethambutol 
 Minor  Mild skin rash  
Perioral parasthesia Symptomatic treatment  
 Streptomycine  
 Major  Ototoxicity :  Vertigo and hearing impairment  Stop Streptomycin 
Minor  Joint pain  Analgesics like Aspirin 
  Pyrazinamide 
Major  Hepatotoxicity / jaundice   Stop Pyrazinamide 
 
Important points to consider in the treatment of tuberculosis: 
• Streptomycin should not be given to pregnant woman, and patients with renal 
failure and ear problems.  It should be replaced by Ethambutol.  Streptomycin 
dose should not be more than 750mg if the patient's age is > 50 years. 
• Children who are 6 years or below should not be given Ethambutol because of 
damage to the eyes and children may not complain of it. 
• Patients should be strictly followed after initiation of the drugs.


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Internal Medicine 
 
 78• All sputum-positive patients on DO TS must have one sputum specimen 
examined at the end of the 2nd, 5th and 7th month. If sputum is negative at the 
end of 8 weeks, the continuation phase can be started. 
• Corticosteroids are added to the anti-TB in TB meningitis, pericarditis, and spinal 
TB. Adrenal TB patients should have replacement therapy. 
Tuberculosis and HIV is dealt on HIV section 
 
Refernces: 
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, 
Tuberculosis, pages 953-965.    
2) National TB Treatmnet guidline for Ethiopia  
3) Treatment of Tuberculosis : Guidline for National programmes , Third edition , 
WHO- Geneva 2003 
4) TB/HIV , a clinical manual , Second edition , WHO-Geneva , 2004


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Internal Medicine 
 
 795. Human Immuno Deficiency Virus – HIV/AIDS 
 
Learning Objectives : At the end of the th is Unit the student will be able to  
1. Define HIV disease and AIDS  
2. Understand the basic virology of the etiologic agent  
3. Describe the mode of transmission of HIV   4. Understand the epidemiology of HIV   5. Describe the pathophysiology of HIV/AIDS  
6. Identify the clinical manifestations of HIV/AIDS    
7. List the complications and Organ systems affected by HIV/AIDS  8. Describe the most commonly investigations for the diagnosis of HIV  9. Make an appropriate diagnosis of the common manifestations of HIV/AIDS  and different 
opportunistic infections  
10. Make appropriate WHO clinical staging of HIV/AIDS   11. Manage common opportunistic infections  12. Understand the basics of Antiretroviral drugs and HAART including indications /eligibility 
criteria for the initiation of ART  
13. Initiate ART for most patients and follow patients on ART   14. Refer complicated  cases of HIV/AIDS  diseases to hospitals for better management  
 
Definition:  HIV disease is a chronic infe ctious disease caused by the Human Immuno 
Deficiency Virus, which is characterized by spec trum starting from primary infection, with or 
without the acute syndrome, followed by a relatively long period of asymptomatic stage after 
which in most patient’s progress to advanced and life threatening disease (AIDS)  
 
Historical Back Ground


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without the acute syndrome, followed by a relatively long period of asymptomatic stage after 
which in most patient’s progress to advanced and life threatening disease (AIDS)  
 
Historical Back Ground  
1981:  AIDS was first recognized in USA among Homosexual males 
 PCP was seen among 5 homosexuals  
 Kaposi’s sarcoma was diagnosed in 26 homosexuals with  1983: HIV virus was isolated from a patient with lymphadenopathy 
1984:  HIV virus was clearly demonstrated to be the causative agent for AIDS


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 80Epidemiology  
♦ According to UNAIDS report at the end of 2006 about 39.5 million people were living 
with HIV/AIDS, out of which 2.3 million were children and 17.7 million were women. In 
2006 there were about 4.3 million new infections out of which 530, 000 were children < 15 years. There were about 2.9 million deaths out of which 380,000 were children. 
♦ Sub-Saharan Africa is the worst affected by the pandemic with 25.7 million living with 
HIV, Out of which 2.1 million are children < 15 years. The overall adult prevalence in this region is 5.9 %. There were about 2.1 million deaths due to HIV/AIDS in 2006. 
♦ Our country Ethiopia is the second most populous country in Sub-Saharan African 
suffering from the brunt of HIV/AIDS. In Ethiopia HIV was first detected in collected sera in 1984. The first two AIDS cases were reported to the Ministry of Health in1986.  
♦ National HIV prevalence rate according to AIDS in Ethiopia 6ht report is 3.5% (the 
prevalence is different in Urban and Rural areas 10.1 % and 1.9 % respectively.) There are about 1.3 million people living with HIV/AIDS out of which 134,586 were children. There were nearly 128, 988 new infections in 2006 of which 12, 9196 are children. There 
were about 134, 450 deaths in 2006 among these 20,929 were children.  
 
Mode of Transmission of HIV  
1. Sexual Transmission:  
 Is the major mode of transmission worldwide ( 90 % )


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were about 134, 450 deaths in 2006 among these 20,929 were children.  
 
Mode of Transmission of HIV  
1. Sexual Transmission:  
 Is the major mode of transmission worldwide ( 90 % ) 
 The virus is found in high quantities in the sexual fluids (seminal and vaginal 
fluid) of people with HIV infection  with in infected monocytes and in cell-free 
state 
 Anal sex appears to be the sexual practice carrying the highest risk of 
transmitting HIV. The reasons being rectal mucosa is thin and fragile and there are susceptible cells ( Langerhans cells  ) in the rectal mucosa  
 Vaginal sex is also an effective from of transmission.   
 The presence of other STDs like Syphilis , Gonorrhea etc increase the risk of 
acquiring or transmitting HIV infection by several fold, as the quantity of the virus in seminal or vaginal fluid significant ly increase and the number of infected 
monocytes is high around the genital area in patients with STDs.. 
 Oral sex may have some risk however there are no reports so far attributable to 
oral sex.


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 812. Transmission through blood and blood products  
 IV drug abusers who share needles and syringes have high risk .This is the main 
mode of transmission in Eastern Europe. 
 Blood or blood products transfusion from infected donors (the risk of infection is 
90-100 %). Currently the risk is very minimal as blood and blood products are 
screened carefully using antibody and p24 antigen testing to identify donors in the widow period. 
 Transmission through sharp instruments, injection needles etc. There may be a 
risk of transmission from one patient to another or from an infected patient to health care provider  
3. Mother to Child Transmission  
 Without any intervention, the risk of mother to child  transmission is  30-45%  in 
the developing world and 15-30% in the developed world , 
 HIV may be transmitted from infected mothers to children during  
i. Pregnancy:-10 % before the 3
rd Trimester  
ii. Labor and Delivery:- 70 % late pregnancy and during labor 
iii. Breast Feeding :- 10-15 % 
  MTCT is by far the largest source of HIV infection in children under 15 
 
Factors Influencing MTCT 
Maternal Factors 
 Maternal viral Load: The higher the viral load, the higher is the risk of MTCT  
 Woman becomes infected with HIV during pregnancy 
 Severe immune deficiency  
 Clinical and immunological state 
 Use of ART during pregnancy and postpartum to mother and newborn


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 Woman becomes infected with HIV during pregnancy 
 Severe immune deficiency  
 Clinical and immunological state 
 Use of ART during pregnancy and postpartum to mother and newborn 
 Viral, bacterial, and parasitic placental infection (especially malaria)  
 Nutritional status, particularly vitamin A 
 
 Labor and Delivery 
 Prolonged rupture of membranes (>4 hours) 
 Acute chorioamnionitis  
 Invasive fetal monitoring or delivery techniques


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 82 Mixing of maternal and fetal body fluids 
 Episiotomy 
 First infant in a multiple birth 
Fetal Conditions 
 Premature delivery 
 Immature immune status  
 First-born twin 
Infant Feeding Practices/Breastfeeding 
 Mother becomes infected with HIV while breastfeeding (risk increases up to 20%)  
 Mixed feeding (breast milk and other foods) increases risk 
 Breast pathologies (lesions, infections) 
 Advanced disease in the mother 
 Poor maternal nutritional status 
 Breastfeeding during the first 4–6 months  
 The longer mother breastfeeds, the greater the risk 
 HIV is not spread via non-sexual everyday casual contact between people like kissing, 
hugging and sharing common utensils, baths etc. 
 HIV infected people are considered most infectious soon after acquiring the infection and 
during the AIDS (symptomatic) phase.  However, remember that it is possible to transmit HIV any time during the disease.
 
 
Etiologic agent: 
HIV is a retrovirus which belongs to the sub family of lente virus. HIV virus is cytopathic virus. There are 2 main Types of the virus  HIV- 1:   is the most common cause of HIV Disease throughout the world and  it has several 
groups and subtypes; 
 M group  which comprises 9 subtypes: A,B,C,D,F,G,H,J,K, as well as growing 
number of major circulating recombinant forms   ( CRFs )  e.g. AE ,  AG etc  
• O group (outliers) : relatively rare seen in Cameron and Gambia  
 N group:  (reported only in Cameroon)


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number of major circulating recombinant forms   ( CRFs )  e.g. AE ,  AG etc  
• O group (outliers) : relatively rare seen in Cameron and Gambia  
 N group:  (reported only in Cameroon)   
Global Pattern of HIV -1 distribution 
• Africa:  > 75 % of strains recovered to date have been subtypes A, C and D with C 
being the most common 
• Europe and Americas : subtype B is the predominant strain


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 83• Asia: recombinant forms such AE account of the infections in south East Asia while 
subtype C is prevalent in India. Subtype B is also seen in Asia.  
HIV - 2:  Was first identified in West Africa and it is mostly confined to West Africa, however a 
number of cases which can be traced to West Africa are found worldwide. 
 
Morphology of the Virus  
 
 
♦ HIV is Spherical shaped virus. The most important parts of the virus are:- 
 Its viral envelop has many small spikes  which consists of two important 
glycopropteins gp41 and gp120 which play an important role when the virus 
attaches to its host cells 
 The viral capsid ( core )  which contains two single stranded viral RNA and an 
important enzyme for the virus called reverse transcriptase enzyme  
 The reverse transcriptase enzyme plays an important step in the life cycle of the 
virus. It converts the single stranded viral RNA into double stranded DNA  ( this 
process is called reverse transcription ) 
 Characteristics of HIV 
 HIV infect cells that express CD4 receptor molecules 
 The CD
4 receptors are present on various types of blood cells including 
lymphocytes, macrophages, monocytes, tissue cells (e.g. Dendirtic cells in the genital tract and ano-rectal region) and glial cells of brain Successful entry of the virus to a target cell also requires cellular co-receptors  
 A fusion co-receptor is designated CXCR5 for T-cell tropic stain and CCR4 for 
monocyte -macrophage tropic strains


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 84 The receptor and co-receptors of CD4 cells interact with HIV’s gp-120 and gp-41 
proteins during entry into a cell  
 
Life Cycle of HIV: Replication 
1) Attachment /binding  and fusion of the virus to the host cells 
 The receptor and co-receptors of CD4 cells interact with HIV’s gp-120 and gp-41 
proteins during entry into a cell 
2) Uncoatting  of the viral capsid and release of Viral RNA into the cytoplasm of the host 
cell 
3) Reverse transcription:  Viral RNA is concerted in to Double stranded DNA by reverse 
transcriptase enzyme 
4) Translocation :  viral DNA is Imported to cell nucleus 
5) Integration of proviral DNA to host-cell DNA 
6) Cellular activation causes transcription (copying) of HIV DNA back to RNA 
 Some RNA translated to HIV proteins 
 Other RNA moved to cell membrane 
7) Viral Assembly  :HIV assembled under cell membrane and buddes from cell 
8) Maturation :  viral Proteases enzymes cleave longer proteins in to important viral 
proteins and help to convert immature viral particle into and  infectious HIV 
  
 
 
Life cycle of the virus and Sites of action for antiretroviral drugs


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 85Pathogenesis :  
CD 4 positive T-Lymphocytes (also known as T helper  cells) play central role in the defense 
mechanism of the body against infection. They mainly coordinate the Cell mediated immune 
system and also assist the antibody mediated immune system .  
 
♦ HIV virus has special affinity to CD 4 T-cells and infects them 
♦ HIV infection is  characterized by a pr ofound immunodeficiency from progressive decline 
of T-helper cells 
♦ The pathogenetic mechanism of HIV disease is multi-factorial and multiphasic and it 
differs in different stage of the disease 
 
Mechanism of CD 4 Cell Depletion  
• HIV-mediated direct cytopathicity (single cell killing) – infected CD 4 cells die 
• HIV-mediated syncytia formation 
• Defect in CD4 T-cell regeneration in relation to the rate of destruction 
• Maintenance of homeostasis of total T-lymphocytes (decreased CD4, increased 
CD8) 
• HIV-specific immune response (killing of virally infected and innocent cells) 
• Auto-immune mechanism 
• Programmed cell death (apoptosis) 
  Qualitative abnormalities (even the existing CD4 cells are dysfunctional)  
• Impaired expression of IL-2 
• Defective IL-2 and INF-Alfa production 
• Decreased help to B-cells in production of immunogloblins 
 Peculiar Characteristics of HIV and reasons for Persistent Viremia   HIV is a unique infection in that, though the body reacts by producing antibodies to destroy the


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• Decreased help to B-cells in production of immunogloblins 
 Peculiar Characteristics of HIV and reasons for Persistent Viremia   HIV is a unique infection in that, though the body reacts by producing antibodies to destroy the 
virus, the virus is not cleared, except partially in the early period of infection A chronic infection is established, and it persists with varying degrees of viral replication. Viral replication is continuous in all stages (early infection, during the long period of clinical latency, and in advanced stage.)  There is no virological latency.


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 86 
Despite robust immune reaction, HIV evades elim ination by the immune system and a chronic 
infection is established. Some of the mechanisms are: 
 High level of viral mutation – HIV has an extraordinary ability to mutate 
 Large pool of latently infected cells that cannot be eliminated by viral-specific CTLs 
 Virus homes in lymphoid organs, while antibody is in the circulation  
 Exhaustion of CD8 T-lymphocytes by excessive antigen stimulation  
 HIV attacks CD-4 T-cells, which are central to both humeral and-cell mediated immunity 
 HIV seeds itself in areas of the body where sufficient antibodies might not reach, e.g., 
the central nervous system 
 
Progression of HIV is different in different individuals  
Rapid progressors: After the initial infection patients progress fast and develop OIs and die 
within 2-3 years. Account for 15 % of all patients  
Normal Progressors: After the initial primary infection patients remain health for 6- 8 years 
before they start having overt clinical manife stations: account for 80 % of all patients  
 
Long term survivors: Patients who remain alive for 10-15 years after initial infection. In most 
the diseases might have progressed and there may be evidences of immunodeficiency. 
 
Long term non progressors: This is individuals who have been infected with HIV for > 10 
years. Their CD4 count may be in the normal range and they may remain clinically stable for 
several years


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Long term non progressors: This is individuals who have been infected with HIV for > 10 
years. Their CD4 count may be in the normal range and they may remain clinically stable for 
several years  
 What affects disease progression in HIV Infected individuals  
 Viral set point: The level of steady-state viremia (set-point) at six months to one year 
after infection, has an important prognostic implication for progression of HIV disease 
o Those with a high viral set-point have faster progression to AIDS, if not treated 
 Immune response 
o High CD8 slow progression  
o Low CD8 rapid decline  
 Viral type ; HIV 2 slow course  
 Concomitant conditions 
o Malnutrition hastens the progression of HIV


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 87o Chronic infectious conditions e.g. Tuberculosis  
 
Diagnosis and Laboratory monitoring of HIV  
1. Serologic Tests :  
a. HIV antibody tests :- detect antibodies formed by the immune system against 
HIV 
i. ELISA : used to be standard screening test for HIV  
 Tests for a number of antibody proteins in combination 
 A very sensitive  test ( . 99.5 % ), but not very specific 
 A positive result  needs to be confirmed by Western blot for confirmation  
 The test need skilled personnel  , takes several hours  
ii. Western blot: is an excellent confirmatory test. 
 It has high specificity but relatively poor sensitivity   
 It should not be used for screening purpose 
iii. Rapid HIV antibody testes  
Advantages:   Rapid tests have reasonably good sensitivity and specificity ( >99 % ) 
 Easy logistically , does not need continuous water or electric supply 
 Can be done by less skilled personnel and the interpretation of results is 
easy 
 Test result can be made available in < 30 minutes 
 Because of these advantages of rapid tests WHO has recommend a serious of Rapid HIV antibody testes to be done to diagnose HIV infection.


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 88 
 
 
 
 
   
 
  
  
 
   
 
• When the 1
st test is non-reactive, then the client can receive negative HIV result  
• When both tests are reactive, the final HIV result is positive.  Test Sample: 
 
NEGATIVE:  
Client receives 
negative result POSITIVE:  
Do 2nd confirmatory 
test 
NEGATIVE:  
Use 3rd test to 
confirm POSITIVE:  
Client receives Positive result 
NEGATIVE  
Client receives negative result  
 POSITIVE:  
Client receives positive
 result   Test Al gorithm for HIV Dia gnosis
Pre Test counseling  
1st Screening test  
 
Determine®:  
3rd    Tie breaker test  
 
Uni-Gold ® 2nd Confirmatory test  
 
CApillus ®


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 89• If one test is reactive and the other is non-reactive, then a third test known as a 
tiebreaker is performed.  
• The tie-breaker determines the final result – if the tiebreaker is reactive, then the 
final HIV result is positive; if the tiebreaker is non-reactive, then the final HIV result 
is negative.  
        
b. HIV antigen assays ( Tests ) 
i. P24 antigen capture assay: this test detects p24 viral protein in the blood of HIV 
infected individuals. This viral protein can be detected during early infection, before seroconversion. Thus this test is us ed to detect blood donors during the Window 
period  
2. DNA – PCR : Viral replication  
 Is an extremely sensitive test -can detect 1-10 copies of HIV proviral DNA per ml of 
blood  
 It uses PCR technology to amplify proviral DNA  
 This test is costly and needs sophisticated instruments and highly skilled 
professional  
 It is highly sensitive and the chance of false positivity is high. hence it should not be used for making initial diagnosis of HIV infection  
 It is often used  
i. To make early diagnosis of HIV in HIV exposed infants as serology tests are 
unable to diagnose HIV till the infant is 18 months old 
ii. To diagnose or confirm virologic failure in patients who are not responding to ART 
iii. When there is indeterminate serology  
3. CD
4  T cell count : as CD4 cells play a crucial role in the body defense mechanism ,


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ii. To diagnose or confirm virologic failure in patients who are not responding to ART 
iii. When there is indeterminate serology  
3. CD
4  T cell count : as CD4 cells play a crucial role in the body defense mechanism , 
measuring the amount of CD4 cells is an important indicator of the level of immune 
suppression  that a patient infected with HIV has  
 The average CD4 count of a normal person is in the range of 1000-1200 
/mm3.  Studies have shown the average CD4 count of normal Ethiopians is 
low 
 In patients with HIV CD4 count drops by an average of 50 - 100 cells per 
year  
 Tells you the level of immune damage inflicted by HIV


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 90
 It should never used to make diagnosis of HIV 
 CD4 count may be variable depending on circumstances 
o Diurnal variation; High evening low at midnight 
o Inter current infection, use of steroids and stress could affect CD4 
count  
 Following the trend in CD4 count is us full in clinical decision  making  
 Percentage of CD4 count is useful in children below 6 years 
 Importance’s  of CD4 count  
o To decide eligibility of a patient for ART 
o To follow the progress of a patient on ART 
o To diagnose immunologic failure in patients who are not responding 
well to ART  
4. Additional  tests  that should be done is patients with HIV infection include:  
 HBV , HCV  
 FBP and ESR 
 SGOT/AST and  SGPT/ALT 
 Serum Creatinine 
 Syphilis serology: RPR  
 AFB chest X-Ray where possible 
 Stool examination for parasites 
 Malaria blood slide 
 Pregnancy test for women in child bearing age  
 
Natural History and Clinical Manifestations of HIV infection  
The clinical consequences of HIV infection encompass a spectrum ranging from an acute syndrome associated with primary infection to a prolonged asymptomatic state to advanced 
disease 
 
1. Primary HIV Infection : Acute HIV syndrome and Seroconversion  
2. Asymptomatic stage – Clinical latency 3. Early Symptomatic Diseases – mild immunodeficiency 4. AIDS defining illnesses : Advanced immunodeficiency


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 91
 
 
1. Primary HIV Infection : Acute HIV syndrome and Seroconversion  
Acute HIV syndrome: 
• Some patients are asymptomatic but 50 – 70% of HIV infected individuals experience 
an acute clinical syndrome 3 – 6 weeks after primary infection 
• A flue like syndrome in which symptoms persist from 1 –several weeks and gradually 
subside  
• The typical clinical features includes  
 Fever 
 Pharyngitis, lymphadenopathy,  
 Headache, artheralgia, myalgia, malaise,  
 GI symptoms : Anorexia, nausea vomiting, diarrhea,  
 Erythematous maculopapular rash and mucocutaneous ulceration 
 Neurological symptoms: HIV in CSF, aseptic meningoencephalitis 
Encehphalitis, peripheral neuropathy  
Most patients (> 90%) recover spontaneously 10 % manifest a fulminate course of immunologic 
and clinical deterioration  
 2. Asymptomatic stage – Clinical latency  
 In most  ( 90 ) of patients, primary infection with or without the acute syndrome is 
followed by a prolonged period of clinical latency


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 92
 The length of time from initial infection to the development of clinical disease varies 
greatly (median is 7-10 years.) 
 Viral replication continues during this period of clinical latency. So there is no 
virologic latency  
 The rate of disease progression is directly correlated with HIV RNA levels.  Patients 
with high levels of HIV RNA progress to symptomatic disease faster than do 
patients with low levels of HIV RNA 
 The CD 4 cell count fall progressively during this stage at an average rate of 50 
cells/μl/year,  
3. Early Symptomatic Diseases – mild immunodeficiency   
 Patients begin to develop sign and symptoms of clinical illness , when CD 4 cell 
count falls below 500/ μl,  
 Most of the manifestations are due to minor opportunistic infections ( not AIDS 
defining illnesses )  or direct effect of long standing HIV  
The clinical findings include: 
a) Generalized lymphadenopathy  
o Definition: enlarged lymph nodes (> 1cm) in  ≥ 2 extra-inguinal sites for more than 3 
months without an obvious cause. 
o It is often the earliest symptom of HIV infection after primary infection 
b) Oral lesions: 
• Are usually indicative of fairly advanc ed immunologic decline, generally occurring in 
patients with CD4 count < 300 / μl.                                                                       
            i. Oral thrush: 
o Appears as a white, cheesy exudates, often on an erythematous mucosa


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patients with CD4 count < 300 / μl.                                                                       
            i. Oral thrush: 
o Appears as a white, cheesy exudates, often on an erythematous mucosa 
(most commonly seen on the soft palate) which gives an erythematous or 
bleeding surface on scraping  
o When it involves the esophagus, patients complain of difficulty and/or pain 
on swallowing  
o Is due to Candida infection  
o Confirmatory diagnosis is by direct examination of a scraping for 
pseudohyphal elements  
o Treatment  -   Apply 0.25% Gential Violet BID and/or 
         Nystatin tablets or suspension 500,000 IU every 6 hr


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 93If pharynx or esophagus involved; Ketoconazole 200 mg PO BID for 2 
weeks or Miconazole oral gel. 
            ii. Oral hairy leukoplakia: 
o Appears as a filamentous white lesion, generally along the lateral borders of 
the tongue. 
o Is presumed due to Epstein – Barr virus infection 
            iii.   Apthous ulcer: 
o Ulcer on the oral cavity or pharynx of unknown etiology 
o Usually are painful and may interfere in swallowing  
  c)  Herpes zoster (shingles) 
o Seen in 10 – 20% of patients with HIV infection 
o It is a reactivation syndrome of varicella zoster virus  
o Indicates a modest decline in immune function and is often the first clinical 
indication of immunodeficiency 
o Lesions are usually localized to a single dermatome, but may extend over 
several dermatomes and frank cutaneous dissemination may be seen. 
o It has a relapse rate of 20% 
      d) Thrombocytopenia: 
o Thrombocytopenia in HIV infection has immunologic base (is due to auto 
immune destruction of platlets).  
o It is very similar to IPT (idiopathic thrombocytopenic purpura) 
o Since most patients have platelet count of >50,000/ μl serious clinical 
problem are seen rarely.  
o In some patients, when the platelet count falls < 10,000/ μl, clinical symptoms 
such as bleeding of the gums, extremity petechiae, and easy bruisability are 
common presenting features. 
o Bone marrow examination is normal or may show increased 
megakaryocytes


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such as bleeding of the gums, extremity petechiae, and easy bruisability are 
common presenting features. 
o Bone marrow examination is normal or may show increased 
megakaryocytes  
       e)  Other clinical conditions seen in patients during early stage of HIV: 
o Molluscum contagiosum  
o Recurrent bouts of oral or genital herpes simplex 
o Condylomata accuminata.


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 94HIV/AIDS associated illnesses affecting different Organ Functions  
 
Opportunistic infections: are infections that develop as a result of HIV −inflicted damage 
to the immune system. 
 OIs are leading causes of morbidity and mortality in HIV-infected persons 
 Most of the common OIs are preventable as well as treatable 
 In resource-limited settings, it may be difficult to diagnose and manage OIs 
 Most opportunistic infections and complications of HIV develop when the CD4 count 
drops below 200cells /ml 
 Opportunistic malignancies: are neaoplastic conditions which tend to occur more 
frequently in patients with underlining immunodeficiency.  
 
Disease of the Respiratory system associated with HIV infection 
♦ The Respiratory system  is the most common site of HIV-associated 
complications/illnesses. 
♦ Respiratory problems are the leading cause of morbidity & mortality in persons 
infected with HIV. 
♦ Many of the respiratory problems are both Preventable & Treatable. 
♦ Therefore, Prevention, evaluation, and treatment of pulmonary disease is an 
essential part of managing patients with HIV infection 
There is a wide spectrum of Pulmonary Manifestations. 
Opportunistic Infection  
 Bacterial: Streptococal, H.infleunza, gram negatives , Staphylococcal 
 Mycobacterial: M. tuberculosis, M. kansasi, M. aveum intracellularie  
 Fungal: PCP, Cryptococcus neofrmans, Histoplasmosis, Coccidiodeoco 
mycosis, Aspergillosis


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 Bacterial: Streptococal, H.infleunza, gram negatives , Staphylococcal 
 Mycobacterial: M. tuberculosis, M. kansasi, M. aveum intracellularie  
 Fungal: PCP, Cryptococcus neofrmans, Histoplasmosis, Coccidiodeoco 
mycosis, Aspergillosis 
 Viral: Cutomegaovirus, Herpes simplex infection  
 Parasitic pathogens: Toxoplasmosis, Strongliodosis  
Opportunistic Malignancies    
 Pulmonary Kaposi’s sarcoma 
 Non Hodgkin’s Lymphoma 
♦ The type of OIs or OMs that a patient develops depend on the degree of 
immunosupression i.e. each of the OIs and OMs typically develop at or


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 95below a characteristic CD4 cell count range. Therefore CD4 cell count is an 
excellent indicator of the risk of developing a specific OI or OM. 
♦ Knowing the stage of the disease will be useful in limiting the differential 
diagnosis. 
♦ In the advanced stage of HIV infection, a person may be infected by more 
than one pathogen.  
Respiratory manifestations which may occur at any CD4 level 
 Upper respiratory tract infection (URI) :Sinusitis , Pharyngitis 
 Acute bronchitis 
 Bacterial pneumonia 
 Tuberculosis 
 Non-Hodgkin's lymphoma               
Respiratory manifestations which may occur when CD4 level is <500/mm3 
 Bacterial Pneumonia 
 Pulmonary TB 
Respiratory manifestations which may occur when CD4 level is <200/ mm3 
 Pneumocystis carinii pneumonia 
 Cryptococcus neoformans pneumonia 
 Bacterial pneumonia (associated with bacteremia/sepsis) 
 Disseminated or extrapulmonary tuberculosis  
Respiratory manifestations which may occur when CD4 level is <100/ mm3 
 Pulmonary Kaposi's sarcoma 
 Bacterial pneumonia (Gram-negativ e bacilli and   Staphylococcus 
aureus increased) 
 Toxoplasma pneumonitis  
Respiratory manifestati ons which may occur wh en CD4 level is <50/  mm3 
 Disseminated Histoplasma capsulatum 
 Disseminated Coccidioides immitis 
 Cytomegalovirus pneumonitis 
 Disseminated Mycobacterium avium complex 
 Disseminated mycobacterium (nontuberculous) 
 Aspergillus species pneumonia


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 96Knowledge of the relative frequencies of these pulmonary diseases is IMPORTANT. 
Bacterial Pneumonia 
 Common etiological agents: S. pneumoniae 
 As the degree of immunosuppressioin worsens pneumonia may be recurrent  and 
associated with sepsis  
 Clinical presentation: Abrupt onset with fever, cough, production of purulent 
sputum, dyspnea, and pleuritic chest pain 
 Recommended Investigations : Chest X-ray, blood culture, FBC, gram stain of 
sputum, sputum culture and sensitivity 
 Common findings: X-ray may show pneumonic consolidation, infiltrates, or pleural 
effusion; leukocytosis; blood cultures may be positive 
 Treatment: 
Antibiotics : Penicillin (procaine Pen/Crystalinne Pen), Amoxicillin 
fluoroquiolones Supplemental Oxygen 
 
Pneumocystis carinii Pneumonia (P . jiroveci  pneumonia)  
Etiologic agent: P. jiroveci  is fungus which is the etiologic agent for PCP 
 Epidemiology 
 One of the commonest OIs in industrialized countries. However the incidence has 
declined over the years due to HAART and use of CPT Prophylaxis 
 Used to be considered rare in Africa ( Early studies in 1990s showed  4-15% 
prevalence , however recent studies show a prevalence of 25-52% 
 In Ethiopia: though PCP is commonly seen in clinical practice there is only limited 
published information. Study done by G. Aderaye (et al AIDS 2003, 17: 435-440) 
shows  30.3% prevalence of P. carinii among expectorated sputum samples of


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 In Ethiopia: though PCP is commonly seen in clinical practice there is only limited 
published information. Study done by G. Aderaye (et al AIDS 2003, 17: 435-440) 
shows  30.3% prevalence of P. carinii among expectorated sputum samples of 
HIV+/PTB- Pts. This suggests that  PCP may be an important differential diagnosis 
amongst HIV + patients 
 50% of patients experience at least one bout of PCP during the course of their Life 
time.  
 Transmitted from human to human, or fr om environmental reservoirs to human


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 97Clinical Presentation 
 Mode of presentation- PCP has indolent course characterized by weeks of vague 
symptoms prior to presentation or diagnosis.  Median duration of symptom is 28 
days.  
 Dyspnea and fever are cardinal symptoms  
 Cough with scanty sputum in > 2/3 of cases 
Signs:  Findings on physical examination are minimal, and the usual findings for 
pneumonia may not be noted.  
 Respiratory distress ± Cyanosis  
 Little abnormality on chest examination rhonchi or wheeze may be heard, 
especially in patients with some other underlying pulmonary disease, findings of 
consolidation are usually absent. 
 P. carinii appears to be capable of hematogenic spread and seeding a variety of 
organ systems as well as causing a primary infection of the ear. 
 Diagnostic Work-up 
1) Chest x-ray is helpful 
Could be normal. Diffuse bilateral alveolar/interstitial infiltrates is the usual findings 
2) LDH is elevated in > 90% of cases : Has a very high negative predictive value i.e. if 
LDH level is low in a patient the diagnosis of PCP is less likely  
3) Definitive Dx  –demonstration of the trophozoite or cyst from the organisms in 
samples obtained from Induced sputum in which the yield is 60% or Brocho-alveolar 
lavage in which the yield is 95% . Staining: Wright-Giemsa, Methenamine silver, 
Direct IF, nPCR 
4) Other tests: Gallium 67 Scan, PFT, ABG 
 Management (Treatment)  
1) Antibiotics :


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lavage in which the yield is 95% . Staining: Wright-Giemsa, Methenamine silver, 
Direct IF, nPCR 
4) Other tests: Gallium 67 Scan, PFT, ABG 
 Management (Treatment)  
1) Antibiotics :  
o The gold standard for therapy of PCP at present is co-trimoxazole IV/PO  
o It is effective in > 90% of patients.  
o Usual dose, 15 mg/kg/day (trimethoprim) in 3-4 divided doses (3-4 480 mg 
tabs 4X/day) 
o Duration of Rx - 21 days ( 3 weeks )


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 98o The major disadvantage is the relatively high incidence of side effects rash, 
fever, leucopenia 10% (HIV -ve) Vs 50% (HIV +ve) 
o Response to treatment may not occur until the end of first week and the 
patient may get worse during the first few days owing to the inflammatory 
response resulting from the death of large number of organisms in the lungs. 
♦ Alternative Regimens : 
• Clindamycin 600 mg IV q8h or 300-400 mg PO q6h + primaquine 15-30 
mg base/day x 21 days 
• Pentamidine 4mg/kg/day IVX21 days 
• Atovaquone 750 mg PO bid with meal x 21 days 
2) Adjuvant Treatment:  
o Supplemental O 2      
o Steroids:  reduces mortality by 50% and the need for mechanical ventilation. 
Steroids reduce the inflammatory response and its adverse clinical consequences.  Start within 72 hours of presentation 
♦ Indications are if the patient is in: 
•  Moderate / severe respiratory distress or cyanotic 
• Pa O
2   < 70mmHg 
Dose : Prednisone 40 mg PO bid x 5 days 
40 mg daily for 5 days 
20 mg daily for 11 days 
PCP - preventive therapies 
Primary Prophylaxis is strongly recommended for HIV infected person with 
evidence of significant immune deficiency:  
♦ CD4+ count < 200/ μl (CD 4 cell percentage of less than 15% in 
children ) 
♦ HIV associated thrush 
♦ Unexplained fever 
Secondary prophylaxis  is indicated for patients with prior episode of PCP 
PCP - preventive therapies drugs/regimens: 
o TMP-SMX two tablets/day (single strength)


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children ) 
♦ HIV associated thrush 
♦ Unexplained fever 
Secondary prophylaxis  is indicated for patients with prior episode of PCP 
PCP - preventive therapies drugs/regimens: 
o TMP-SMX two tablets/day (single strength) 
o TMP-SMX two tablets three times per week


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Internal Medicine 
 
 99Alternative regimens: 
♦ Dapsone 100 mg PO daily 
♦ Dapsone 50 mg PO daily, plus pyri methamine 50 mg PO weekly, plus 
leucovirin25 mg Po weekly 
♦ Aerosolized Pentamidine 300 mg monthly via nebulizer 
♦ Atovaqoune 1500 mg daily 
N.B. The prevention of PCP may also be beneficial in reducing the risk of having other HIV 
associated infections such as CNS toxoplasmosis and other bacterial infections.  
 
HIV and Tuberculosis 
TB is the leading OI in developing countries  
HIV             TB 
 
Impact of HIV on tuberculosis  
HIV affects almost all aspects of TB. 
 
Effect of HIV on Epidemiology of TB 
♦ Increases incidence and prevalence of TB .Life time risk of developing TB is 
50%among HIV positives compared to 5-10% in HIV negative patients 
♦ HIV is the most potent factor known to increase risk of progression from M. 
tuberculosis  infection to active disease. 
♦ The seroprevalence of HIV among TB patients may range from 30 % - 60 % 
 Effect of HIV Clinical Manifestations of TB and it Diagnosis: 
Clinical Presentation depends on degree of immunosupression


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Internal Medicine 
 
 100Table I-5-1. Manifestaions of Tunerculosis in early and advanced HIV 
 
 
 
 Early stage of HIV 
Infection :when CD 4 
count >200 cells/mm3 
 Late stage of HIV Infection  when CD
4 
count <200 cells/mm3 
 
 Clinical 
Presentation  Similar to non HIV infected 
with  productive cough  
Pulmonary manifestations 
dominate  Atypical presentation :  
Extrapulmonary TB is more 
common  
TB tends to be disseminated 
(involving different organs like 
meningitis, pleura, pericardium, 
Lymph nodes etc)  
Laboratory 
Diagnosis  Sputum smear   
PPD  
Often positive  
 
Often reactive with >10mm  Often negative  
 
Often negative or annergic  
 
Chest X-ray  
In the setting of an 
HIV epidemic, it is 
no longer possible 
to look at a CXR 
and say that it is TB 
or it is not TB! 
 Typical CXR findings of TB 
Upper lobe and or bilateral 
infiltrates 
Cavitations 
Pulmonary fibrosis 
 Atypical CXR findings  
CXR may show interstitial infiltrates especially in lower zones 
with no features of cavitation and 
fibrosis 
Negative CXR can be associated 
with sputum AFB+ (12% with 
pulmonary disease) 
In the setting of an HIV epidemic, 
it is no longer possible to look at a 
CXR and say that it is TB or it is 
not TB!  
 
Treatment of TB in HIV infected patients  
♦ When TB and HIV are coexisting TB is more life threatening and it should be treated 
first and patients should be stabilized  
♦ The same Combination anti-TB drugs are given  based on the treatment category


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 101♦ Close follow-up of patients on DOTs is required   
♦ Complete cure from TB may be achieved in six to eight months 
 
Most patients who have TB-HIV co infection are eligible for ART  
When to start ART in patients on Anti Tb Medication depends on CD4 count and the clinical condition of the patient  
 CD4 < 50 /mm
3: start ART as soon as the patient tolerates the Anti Tb medication  
 CD4 count between 50 – 200 mm3  start anti TB after completion of intensive phase 
of DOTs 
 CD4 > 200 mm3 ART can be initiated after compilation of Anti-TB treatment  
 
Challenges / Problems in treatment of TB/HIV co infected patients  
 Increased morbidity, mortality and high case fatality rate 
 Increased drug toxicity 
 Decreased Drug absorption 
 High pill burden which may decrease adherence to treatment  
 Drug Interaction between Anti TB drugs and ARTs  
 
Impact of TB on HIV 
 TB hastens the rate of HIV progression. 
 Tuberculosis is the leading cause of illness and death among PLWHAs. 
 
INH Preventive Therapy 
 Rationale: Life time risk  of having active TB in patients with HIV is  50%  with Annual 
risk  of 7 - 9% ( compared to only 5-10 % life time risk in non HIV infected ) 
 It is advisable to give INH prophylaxis for HIV infected patents  
 Patients should be screening for active TB before they are given preventive therapy  
 
Treatment  
 INH 300mg/d for 6-9 months. 
 Alternatively, Rifampicin for 4 months can be used


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Internal Medicine 
 
 102Neurological Manifestations of HIV/AIDS 
    
• The nervous system is the second commonl y affected organ system by HIV next to 
the respiratory system  
• Common cause of Morbidity & Mortality 
• Occur at any stage of HIV infection  
• All levels of the neuro-axis are involved 
• Clinical manifestations are variable  
 
Pathogenetic Mechanisms for Neurologic manifestations  
1. Directly related to HIV 
• Aseptic Meningitis 
• AIDS dementia complex 
• Myelopathy 
• Peripheral Neuropathy: AIDP( Acute demy linating distal polyneuropathy), MNM ( 
mononuritis multiplex ), DSPN ( distal sensory ply neuropathy ) 
•  Myopathy 
•  Vasculitis  
2. Secondary to Immunodeficiency  
A. Opportunistic Infections 
• CNS Toxoplasmosis 
• Cryptococcal Meningitis 
• Tuberculos Meningitis/Tuberculoma 
• PML 
• Neuro-syphilis 
• CMV polyradiculopathy/Encephalitis 
B. Opportunistic Malignancies 
• Primary CNS Lymphoma 
 
3. ART related 
• Peripheral Neuropathy :d4T, DDI 
• Myopathy :ZDV 
• EFV related – Psychiatric Manifestations


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Internal Medicine 
 
 103Epidemiology 
High incidence of neurological disease among HIV patients:  
• 7-20% of initial AIDS diagnoses,  
• 30-70% prevalence among inpatients 
• >90% in post mortem studies 
 
Aseptic meningitis:   
• It may occur at any time in the course of HIV infection, most commonly at the 
time of acute HIV infection. However it becomes increasingly rare following the 
development of AIDS. 
• Patients experience a syndrome of headache, photophobia, sometimes frank-
encephalitis and cranial nerve involvement,  (commonly VII cranial nerve is affected ) 
 CSF findings -    lymphocyte pleocytosis 10-100 cells/ μl 
                -   Increased protein level protein< 100mg/dl,  
                   -   Normal glucose level 
 The syndrome usually resolves spontaneously with in 2-4 weeks.              
Diagnosis of HIV :  HIV serology may be negative if it occurs during the primary HIV infection. 
To confirm the diagnosis of HIV p24 atg or DNA PCR may be done or Repeat HIV serology after 
few weeks 
 
CNS TOXOPLASMOSIS  
Etiology:  Toxoplasmosis is caused by protozoa, Toxoplasma gondii 
Epidemiology 
 Zoonotic infection cats are the definite hosts and excrete the oocysts in their feces and 
can be transmitted from animals to humans.  
 T. gondii cysts are also found in under-cooked meat. 
 Prevalence of latent Toxoplasma infection in the general population is high - 80% in 
Ethiopia


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can be transmitted from animals to humans.  
 T. gondii cysts are also found in under-cooked meat. 
 Prevalence of latent Toxoplasma infection in the general population is high - 80% in 
Ethiopia 
 Toxoplasmosis gondii is the most common cause of secondary CNS infection in patients 
with AIDS.


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Internal Medicine 
 
 104 It is generally a late complication of HIV infection and usually occurs when the CD 4 cell 
count is less than 100/mm3. 
 It is thought to represent a reactivation syndrome of prior infection. 
 
Clinical Features 
• Onset - Subacute 
• Fever, Headache, Hemiparesis, Seizures and altered mentation 
• Over 90% present with Focal neurologic deficits  
• 10% of patients present with encephalitis picture – confusion or comma and become 
more toxic  
• Commonly  affected areas – Basal ganglia, brain stem and cerebellum 
• Extra-cranial manifestation: 
o Retinitis 
o Myocarditis  
o Pneumonitis (lung) 
 
Diagnosis 
Clinical (Hx + P/E) + Neuro-imaging + Therapeutic Trial +/--Histology - Biopsy 
Neuroimaging (CT/MRI):  
• Multiple ring enhancing lesions are the findings in most patients (90%) with mass 
effect and edema 
• Preferential location: basal ganglia, grey-white junction, white matter 
Serologic assays: Limited value, a negative toxoplasma antibody test makes the diagnosis less likely Histology: brain biopsy – In patients with treatment failure (not possible in our country) 
 
Treatment Regimen 1  
Loading dose of pyrimethamine 50-75mg/ day for 2-3 days, followed by 
Pyrimethamine 25-50 mg/day, plus sulfadiazine 2 - 4 gm/d in divided doses, PO, plus folinic 
acid 10-20mg/d Regimen 2  
Pyrimethamine and leucovorin plus clindamycin 450 mg q8hrs


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 105Duration of Rx: 6 weeks, or 3 weeks after complete resolution of lesions on CT 
Continue suppressive Rx for life: pyri methamine 25mg/day + sulfadiazine2g/day + 
folinic acid 5-10mg/day  
High rate of adverse reactions 
Regimen 3 
Fansidar PLUS Folinic Acid ( Pyrimethamine 25 mg +Sulfadoxin 500mg ) 
N.B. As the other preparations are not available in Ethiopia, Fansidar is a drug which is widely 
used  
Dose:  Fansidar 525 mg tabs 2 tabs PO BID for 2 days and then 1 tab PO/day 
If the patient is very critical, add Doxycycline 100mg PO BID 
Side effects: 
 Leukopenia is the main side effect of the treatment. A higher dose of fansidar (2 
tab/day) has been found to be associated with frequent incidence of fatal 
hemorrhage.  
 Check for bleeding tendency such as gum bleeding, epistaxis, hematuria  
 Do Hgb, WBC and platelet count once per week.  
 To prevent these side effects, give folinic  10mg PO per day or advice to take cream 
cake daily. 
 If there is bleeding tendency, stop Fansider and start Doxycycline 100mg PO BID.   
 Alternatives:  
Co-trimoxazole, or Clindamycin+Pyrimethamine/Primaquine,  
 Azithromycin,Clarithromycin,      
Doxycycline 
Indication for Steroids and dose :  
 Evidence of marked increase in Intra cranial pressure and altered mentation 
 Dose : administer Dexamethasone 8 mg IV stat and then 4 mg IV QID till the  
Suppressive/Maintenance therapy: Fansidar 1 tab per day should be continued.


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 Evidence of marked increase in Intra cranial pressure and altered mentation 
 Dose : administer Dexamethasone 8 mg IV stat and then 4 mg IV QID till the  
Suppressive/Maintenance therapy: Fansidar 1 tab per day should be continued. 
• Suppressive therapy (secondary prophylaxis ) can be stopped when the CD4 
count is more than 200 for 6 months  
Preventive Therapy Indications:  
 CD4+ count < 100cells/ μl 
Regimens 
 TMP-SMX two tablets per day


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Internal Medicine 
 
 106 TMP-SMX two tablets 3 times per week 
Alternative Regimens  
 Dapsone plus Pyrimetham ine plus leucovirin 
N.B. Primary prophylaxis can be stopped if CD4 count >200cells/ml for more than three months 
following HAART 
 
Cryptococcal Meningitis 
Etiology:  Cryptococcus neoformans, which is yeast - like fungus. 
Pigeon droppings commonly contain serotypes A or D  
Infection is acquired through inhalation  
Epidemiology: 
 Is the leading cause of meningitis in patients with AIDS  
 Is the initial AIDS defining illness in 2 % of patients 
 Particularly common in patients with AIDS is Africa 
Clinical Features 
 Occurs late in the course of HIV/AIDS – when CD4 count is, 100/mm3  
 CNS and meningial involvement is seen in 67-85 % of patients  
 Low grade fever n nausea , vomiting , headache  ,  
 Both fever and nuchal rigidity are often mild or lacking  
 Papilledema is seen in one third of patients 
 Neck stiffness , Photophobia – Meningial signs are seen in 30% of patients  
 Late manifestations : Confusion , altered state of consciousness Æ comma  
Other organ systems affected  
 Extra cranial manifestations : Occasionally appears as pulmonary or disseminated 
disease that includes the skin (10%). 
 Cutaneous Cryptococcosis: centrally umblicated multiple lesions on the face (look very 
much like Molluscum contagiosum.) 
 Pulmonary disease 
 Fungemia 
 Lymphadenopathy 
 The prostate gland may be a reservoirs for smoldering infection


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Internal Medicine 
 
 107Diagnosis 
LP – CSF Analysis 
 Opening pressure is high  
 WBC with differential, Protein, Glucose  is normal in 1/3 of patients  
 Indian Ink – Positive in 60-80% 
 CSF Cryptococcal Antigen – Positive in   95-99% 
 Cryptococcal Culture – Gold Standard  
Treatment 
Induction 
Amphotericin B (with or without flucytosine) 
 0. 7-1 mg/kg for two to three weeks followed by consolidation. 
Consolidation 
Fluconazole 400 mg, PO, daily for 8-10wks OR until CSF is sterile 
Maintenance :( suppressive ) 
Fluconazole, 200 mg, PO, daily life long 
Adjunct treatment   
• Management of raised intracranial pressure ; 
o If CSF opening pressure- CSF drainage until CSF pressure is < 200 mm 
H2O; repeat LP daily until stable OR CSF pressure normalizes  
• There is no place for  Dexamethsone  
• Discontinue maintenance or secondary prophylaxis when CD4 count rises to > 200 
/mm3 for more than 6 months after completion of treatment following in patients who are taking HAART 
 
Progressive Multifocal Leukoencephalopathy (PML) 
Epidemiology of PML 
 Reactivation of JC Virus It is seen in 2-4% of AIDS Pts 
Clinical presentation 
• Occurs late in the course of HIV when the CD4 counts< 100/ μl  
• Subacute onset  
• The patient is afebrile, alert no headache 
• Multifocal neurologic deficit 
• Variable presentation: “Classic triad’: dementia, hemiparesis, and hemianopsia.


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 108• Serology: 90% adults are seropositive for JC virus 
Diagnosis - PML 
 CSF is often non-diagnostic , JCV PCR or brain biopsy may help to make diagnosis c 
PML Treatment 
No effective treatment. But initiation of HAART increases survival to  
 
Primary CNS Lymphoma 
Clinical Presentation Occurs late in the course of HIV when the CD4+ counts: < 100/ μl 
Occurs in 2-4% of AIDS patients 
Symptoms and signs 
 - Confusion, lethargy, memory loss; 57% 
 - Hemiparesis or aphasia 40%  - Seizures 14%  - Cranial nerve palsy 9%  - Headaches only 3% 
 - No fever  unless concomitant infection 
Neuroimaging 
 CT/MRI: multiple lesions as frequent as single lesion. (Irregular and solid enhancement, 
subependymal enhancement more specific, variable mass effect. Localization mainly periventricular 
CSF : Epstein-barr virus DNA PCR – CSF ( sensitivity: 85-100% ,specificity: 98-100% ) 
Histology: Diffusely infiltrating, multicentric tumor of B cell lineage with the presence of EBV 
genome in ~100% Treatment 
 Cytotoxic chemotherapy is not effective  
 Radiotherapy can help some patients 
 Response to steroids variable 
 
HIV- associated Dementia Co mplex /HIV encephalopathy / HIV-1 associated 
Dementia Complex 
 First AIDS defining illness in up to 5-10% 
 Major cause of dementia in young people


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 109 A major feature of this entity is the development of dementia, which is defined as a 
decline in cognitive ability from a previous level. 
 TRIAD : cognitive, motor and behavioral dysfunction 
 
Table I-5-2. Stages of ADIS dementia complex  
 
 
  Cognition   Behavior   Motor 
Early Inability to 
Concentrate Altered personality  
 Middle Mental Slowing Forgetfulness 
 Social 
withdrawal Poor coordination 
Late  Global dementia  Apathy    Paraparesis 
Diagnosis : 
 Neuropsychological tests 
 Mini-mental test 
 It is often a diagnosis of  Exclusion  
Treatment: 
 HAART – most patients improve with HAART with possible benefit from ARV agents 
that penetrate the CNS (AZT, d4T, ABC, Nevarpine)  
 Supportive care 
 
Peripheral Neuropathies 
Occurs in 1/3 of pts with AIDS 
Type: 
 Mono neuropathy e.g. Bell’s palsy 
 Mononuritis multiplex  
 Distal sensory peripheral polyneuropathy (DSPN) 
DSPN: Is the most common.  
 It may be cause by HIV infection or ART mainly d4T and DDI


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Internal Medicine 
 
 110 It presents with symmetric bilateral painful burning sensation parasthesia and  tingling of  
the feet and lower extremities ,  
Diagnosis: Clinical, Nerve conduction study, Exclusion of other causes 
Treatment: Symptomatic treatment and discontinuation or changing the drug which is causing it 
when symptoms are sever, 
 
Seizure 
 Seizure is a relatively frequent complication of HIV infection. 
 May be a consequence of opportunistic infections, neoplasms, or HIV encephalitis.  
 The seizure threshold is often lower than normal in patients with HIV infection owing to 
the frequent presence of electrolyte abnormalities. 
 It may be the presenting clinical symptom of HIV disease. 
Common causes of Seizure in HIV patients  
 CNS toxoplasmosis 15-40 % of patients  
 Primary CNS lymphoma15-35% of patients  
 Cryptococcal meningitis 8% of patients  
 HIV encephalopathy 7-50 % of patients  
Treatment  
 Most of the time patients will have 2 or more seizures suggesting that anticonvulsant 
therapy is indicated in all patients with HIV infection and seizures, unless a rapidly 
correctable cause is found. 
 While Phenytoin (100 mg PO TID) remains the initial treatment of choice, Phenobarbital 
(100mg PO every night) or Valproic acid are also alternatives. 
 
Gastrointestinal diseases in p atients infected with HIV 
 
Candidiasis 
Caused by Candida albicans 
Oral Candidiasis Oral thrush:


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(100mg PO every night) or Valproic acid are also alternatives. 
 
Gastrointestinal diseases in p atients infected with HIV 
 
Candidiasis 
Caused by Candida albicans 
Oral Candidiasis Oral thrush: 
 Appears as a white, cheesy exudates, often on an erythematous mucosa (most 
commonly seen on the soft palate) which gives an erythematous or bleeding surface on 
scraping


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Internal Medicine 
 
 111 Erythematous Form : there is predominantly erythema rather that white patches 
Esophageal Candidiasis 
 Usually coincides with CD4 count of < 50 /µl 
 Causes substantial pain or a sense of obstruction on swallowing 
 Most lesions occur on the distal third of the esophagus and appear on endoscopy as 
redness, edema and focal white patches or ulcers 
 If and HIV infected person has oral thrush and substernal pain up on  swallowing  
presumed diagnosis of Esophageal Candidiasis can be made s 
 Endoscopy would prove the diagnosis, but is unnecessary if the patient responds to 
antifungal therapy 
 Linear ulcerations of the esophagus may be seen on barium x-ray. 
 
Treatment 
Oral candidiasis  
 Nystatin IU/ml suspension 2.5-5 ml gargled 5X   daily 
 2% Miconazole oral gel applied 2-3 x daily 
 Amphotericin B lozenges 
 Fluconazole 100mg –200mg PO /day for 7-14days in severe and persistent cases 
 Oral hygiene, discontinue  steroids and antibiotics if the patient is taking any  
 
Esophageal Candidiasis   
First line : Fluconazole 200mg/day PO ( up to 400mg/day) for 14-21 days 
Alternately  
 Ketoconazole 200-400mg for 14-21 days 
 Itraconazole 200mg/day for 14-21 days 
 
Diarrhea in HIV positive patients 
 Is a common clinical condition in HIV infected patients (>50%) 
 May be acute or chronic , watery , mucoid or  bloody 
 May or may not be associated with fever  
 Spectrum may depend on the degree of immunodeficiency state


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 Is a common clinical condition in HIV infected patients (>50%) 
 May be acute or chronic , watery , mucoid or  bloody 
 May or may not be associated with fever  
 Spectrum may depend on the degree of immunodeficiency state 
 Pathogens may be: Bacterial, Viral, Protozoal, Fungal  ,Spirochetal ,Mycobacterial 
,Metazoal , Others (malignancies)


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Internal Medicine 
 
 112Mechanism of diarrhea 
 Adhesion to mucosal surface 
 Enterotoxin  
 Entero-invasion 
 Atrophy of mucosal surface 
 
Chronic Diarrheas 
Definition – Diarrhea lasting for more than two weeks with a single watery bowel motion and or 
three or more loose stools per day 
 Diarrhea occurs in 30-90% HIV-positive cases in Europe and USA and in 90% of cases 
in the developing countries 
 Frequency of diarrhea increases as the CD4 count falls 
 With HAART, incidence of chronic diarrhea decreases  
 
Protozoa that cause chronic Diarrhia in HIV patients:   
 Cryptosporidia 
 Isospora belli  
 Microsporidium  
HIV enteropathy: (AIDS enteropathy) 
 Chronic diarrheal syndrome for which no etiologic agent other than HIV can be identified  
 It is most likely a direct result of HIV infection  
 
 Clinical features  
 Early stage : intermittent self limiting diarrhea however in advanced stage, persistent life 
threatening diarrhea  
 Copious amount of stool several times per/day associated with abdominal cramp. 
nausea and vomiting may also be present  
 Significant weight loss ( wasting ) may occur due to the associated malabsorption  
 Fluid and electrolyte depletion  
Diagnostic investigation  
 Stool Microscopy 
 Culture 
 Intestinal biopsy 
 Special stains: Modified AFB stain


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 113Treatment  
1. General treatment of chronic diarrhea 
 Hydration: oral , parentaral with electrolyte replacement  
 Symptomatic treatment : Anti-diarrheal agents 
 Loperamide 2-4 mg QID 
 Lomotil 5 mg QID 
 Tincture of opium 0.3 ml QID 
 Codeine tablets 
2. Specific treatment  
 Cryptosporidium 
 Nitazoxanide 0.5 – 1.0 gm bid or  
 Paromomycin 1 gm bid + azithromycin 600 mg qd 
Isospora  
 Cotrimoxazole 2 tabs   QID for x 10 d, then bid for 3 weeks OR Pyrimethamine 75 mg + 
folinic acid 10 
 Chronic suppression (secondary prevention): Cotrimoxazole 2 tabs /day OR 
pyrimethamine 25 mg + folinic acid 5 mg qd 
Problem:  malabsorption of drugs 
Strongyloidias  
 Parasitic infection caused by Strongyliod stercolaris  
 Acquired through skin penetration of its larva form  
 Auto infection is common  
 In its life cycle there is transition via the lungs and settles in the GI tract, primarily small 
intestine free-living or parasitic 
 Usually a mild disease in immunocopetent individuals 
 Disseminated infection common in immuno-compromised hosts, 
 Systemic manifestation may mimic sepsis 
Clinical Manifestation 
 Asymptomatic to mild symptoms in i mmuno-competent indivi duals with occasional 
severe pruritis .It may manifest with mild diarrhea, epigastric pain  
 In Immunocopromised patients large amount of filariform larva are released and may 
invade : 
o GI tract : causing enteritis with severe diarrhea and malabsorption


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severe pruritis .It may manifest with mild diarrhea, epigastric pain  
 In Immunocopromised patients large amount of filariform larva are released and may 
invade : 
o GI tract : causing enteritis with severe diarrhea and malabsorption 
o Lungs:  manifest with cough, shortness of breath 9 Loffler’s’ pneumonia.


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Internal Medicine 
 
 114o CNS , peritoneum and liver may also be invaded  
 Severe systemic symptoms are comm only seen in disseminated infections 
 May be complicated by Gram negative sepsis 
 
Drug Treatment 
 Ivermectine 200 µg 1-2 days  
 Thiabendazole 75 mg/kg bid for 3 days 
 Albendazole 400mg/day for 5 days 
 
Skin Manifestations of HIV  
 80-90 % of HIV patients have skin manifestation 
 Skin problems could be the first organ system affected  
 Various type of skin disease occur 
Classification of cutaneous conditions associated with HIV/AIDS  
 INFECTIONS: Bacterial  infections   
 INFESTATIONS 
 INFLAMMATORY CONDITIONS 
 MALIGNANCY 
Staphylococcus auresus 
A common pathogenic causes infection  
Common manifestations are  
 Bullous Impetigo Ecthyma      
 Folliculitits 
 Furuncle  
 Carbuncle  , Cellulitis  
 
Treatment:  
Topical Antibiotics or Systemic antibiotics depending on severity of the diseases  
 
Syphilis (Treponema pallidum)in HIV infected patients  
• Syphilis has atypical presentations in HIV patients  
• Primary chancre usually painless can be tender 
• Latent period before development of meningovascular syphilis is shorter


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 115• Rapidly progresses to tertiary syphilis 
• Relapses without re-exposure 
• Pleomorphic skin lesions reported 
• VDRL can be negative-due to high titer antibody level 
DIAGNOSTIC TESTS  
• Screening Tests-VDRL/RPR 
• Specific Test- FTA-ABS -fluorescent treponemal antibody absorption 
Treatment 
• Benzathin penicillin 2.4 mega unit IM weekly three doses 
• Penicillin IV / 2 to 4 mega unit every 4 hours for 10 to 14 days.(with CNS involvement) 
• Azithromycin + Benzathin penicillin + Amoxicillin 
• Follow up at intervals of 1, 2, 3, 6, 9 and 12 months. 
Viral disease associated with HIV  
• Herpes simplex 
• Varicella-zoster virus 
• Human papiloma virus 
• Moluscum contagiosum 
Herpes simplex virus 
• Is due to reactivation of latent virus 
• The usual manifestations are grouped vesicle with erythematous base 
• In HIV infected patients however : 
o Atypical presentation 
o Chronic non healing deep ulcer 
o Verrucous erosion 
o Mixed infection are common  
o High frequency of reactivation 
o Widespread local extension 
o Higher incidence of dissemination 
o Viremic spread to visceral organs, which is life threatening 
Treatment 
• Systemic acyclovir 2oo mg.5 X a day 5-10 days 
• Acyclovir 50 mg /kg every 8 hours where absorption is poor 
• Acyclovir 400 mg 2 X a day in frequent relapse


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 116• Famcyclovir 125 mg 2 x daily for 5 days 
• Valacyclovir 1 gm 2 x daily for 10 days 
 
Varicella-zoster virus (HZ) 
• There is increased incidence of HZ in patients with HIV infection  
• It is one of the earliest opportunistic infection to occur  
• The clinical presentations are atypical presentation 
o Hemorrhagic necrotic lesion 
o Chronic verrucous lesion 
o Multiple dermatomal involvement 
o Tendency to be generalized 
o It may occur recurrently 
 
Treatment 
Primary varicella -acyclovir IV 10mg /kg ev ery 8 hours for 7 to 10 days 
Herpes zoster 
• Acyclovir 800 mg 5 X a day for 7 – 10 days 
• Famcyclovir 500 mg 5 x /day for 7 days 
• Valacyclovir 1 gm 3 x a day for 7 days 
 
Humna papiloma virus 
Wart is common infection in HIV 
It is refractory to treatment 
Complications are neoplastic changes and increased risk of cervical carcinoma Treatment 
• Podophyllin 20 % or 5-Fluorouraacil 
• Cryotherapy or Excision of big tumors 
 
Moluscum contagiosum(MC) 
Cause by pox virus 
It occurs in HIV patients with low CD4 count 
Atypical presentations are common  
• It is commonly seen in children but can infect immunocopromised adults


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 117• It tends to be Generalized 
• Giant Moluscum contagiosum  
• Secondary infection 
Treatment 
• Cryosugery or  Curettage or Electrosurgery 
• Podophyllin or Cantaridine or 5-fluorouracil 
 
Pruritic papular eruption (PPE) 
• It Chronic itchy condition commonly seen in HIV infected patients  
• Symmetrical non-follicular papules on trunk and extensors of extremities 
• The most common cutaneous manifestation in HIV- prevalence 11-46 % 
 
Diagnosis : Biopsy 
Treatment  
Topical : Antipruritic lotion, Corticostroid, Oatmeal bath 
Systemic: Antihistamin, coricosterroid, Phototherapy, UV-B, UVA + Psoralen 
 
Cytomegalovirus (CMV)  
• Cytomegalovirus (CMV) 
• Herpes virus 
• High incidence  
o 30 - 40% in general population are positive antibody for CMV 
o 90% or more in IV Drug abusers have positive antibody for CMV 
o 20-30 % of patients with AIDS had CMV reactivation prior to the era of HAART 
• Able to establish a latent infection that can reactivate 
• Late-stage AIDS illness (CD+4 < 100) 
Clinical manifestations : retinitis, esophagitis, colitis 
CMV Retinitis;  
• Clinical presentation:Visual disturbances – floaters , flashes of light photophobia and 
blurring of vision ,painless, gradual loss of vision  ,usually bilateral 
Diagnosis confirmed by retinal exam  
CMV GI Disease Esophageal ulcers


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 118• Pain and difficulty in swallowing 
• Diagnosis by tissue biopsy 
Colitis 
• Abdominal pain, watery diarrhea, sometimes bloody, rarely perforation 
• Fever 
• Diagnosis by tissue biopsy 
Hepatitis and acalyculus cholecystitis  
Treatment for CMV  
• Valganciclovir  (PO) 
• Ganciclovir (IV)  
• Ganciclovir Intra-ocular Implant  
• Foscarnet (IV) 
• Cidofovir (IV) 
18% in IV Ganciclovir   
 
Visceral Leishmaniasis and HIV Co-infection  
• Visceral Leishmaniasis is Caused by L.donovanii  
• VL has become an important OI among persons infected with HIV-1 
• Most co-infected patients with clinically evident leishmania have CD4 cell less than 
200/µl. 
• The infections affect the same cell lines, causing cumulative deficiency of the immune 
response  
• Leishmania parasite suppresses Th1 activity  
• Visceral Leishmaniasis Clinical Manifestation  
• Patients present with fever, organomegaly, anemia or pancytopenia  
• Presentation could be atypical, but VL should be suspected in those with travel history to 
endemic areas 
Diagnosis 
• Serology less sensitive in immunocompromised  
• Parasite could be detected in peripheral blood in immuno -compromised patients  
• Bone marrow aspirate 
• Splenic aspirate most sensitive


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 119Treatment 
First line – Pentavalent antimonials (Sb) 
Alternatives- Pentamidine, Amphotericin B  
Relapse and toxicity are common in patients co-infected with HIV  
Opportunistic Malignancies  
• Kaposi’s Sarcoma  
• Lymphoma  
• Cervical cancer 
 
Kaposi’s sarcoma  
Etiology/pathogenesis: multi-factorial 
• Vascular neoplasm affecting skin and mucosa 
• Immunosuppression increases risk of KS 400-500 times higher than general population 
• Presence of Human Herpes Virus 8 (HHV8) found in all types of KS 
• HIV virus Tat protein potentiates the milieu conducive to KS growth 
Transmission 
• Studies have shown that HHV-8 which is the etiologic agent for KS is believed to be 
transmitted sexually. The risk factors are multiple partners, history of STD, and being 
HIV positive.  
• More common in homosexual men  
• Multiple heterosexual contacts is a risk factor for HHV-8 in Africa 
• Parentral: frequent IVDU 
• Oral: via saliva: HHV-8 titers 2-3 times higher in saliva than in semen, anorectal or 
prostate fluid samples 
 Epidemiology 
• Is the most  common Opportunistic malignancy among  HIV positive patients  
• With use of HAART, KS incidence has declined by 66%  
Clinical Manifestations • Can affect almost any organ system 
• Most common sites include


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 120o Skin: flat to nodular lesions; can progress to significant infiltration of skin and 
necrosis 
o Oral cavity: flat to invasive lesions 
o GI tract: can have KS anywhere in GI tract, which can cause intestinal blockage and 
bleeding 
o Pulmonary: can spread along bronchi and vessels. 
Diagnosis 
• Skin and oral lesions can be diagnosed by visual exam even though skin biopsy is most 
accurate to make diagnosis 
• Lung and GI-tract lesions would need endoscopy and biopsy for accuracy 
• Resolution of skin lesions with HAART can give a presumptive diagnosis 
• Testing for HHV-8 is more research than clinically applicable 
 
Treatment Primary treatment  is antiretroviral drugs (HAART). Lesions significantly regress with HAART  
Local therapy for skin lesions 
• Alitretinoin gel (35-50% response),Local radiation (20-70% response) 
• Intralesional vinblastine/vincristine (70-90% response) 
• Cryotherapy (85% response), Photodynamic therapy or Surgical excision 
 
Systemic Treatment :  
Immunotherapy -interferon-alfa: immunomodulatory antiviral and antiangiogenic. This treatment 
may have superior efficacy if combined with HAART. 
Chemotherapy : Indicated for rapidly progressive oral or visceral disease 
• Liposomal doxorubicin/daunorubicin is superior to conventional chemo with less toxicity  
 
Lymphomas  
• Lymphomas occur with increased frequency in immunoi deficiency states and there are 
120X increased incidence of Lymphoma among HIV patients.


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Lymphomas  
• Lymphomas occur with increased frequency in immunoi deficiency states and there are 
120X increased incidence of Lymphoma among HIV patients. 
• 6% of all AIDS patients develop lymphoma at sometime in the course of their illness 
• As HIV diseases progress the risk of Lymphoma increases. 
• The incidence of lymphoma hasn’t shown dram atic decrease even after HAART is being 
widely used by HIV patients worldwide.


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 121• It is a late manifestation which often occurs when the CD4count falls below 200/mm3 
 
Three main categories seen with HIV 
• Grade III or IV Immunoblastic lymphoma (60%) 
• Burkitt’s lymphoma(20%)- associated to EBV 
• Primary CNS lymphoma 
 Treatment 
1. In patients with high  CD4 count – Intensive Chemotherapy 
In patients with low Cd4 count – low dose Chemotherapy  
2. Palliative measures : to decrease the size of the lesion and associated edema  
• Radiotherapy 
• Glucocorticoides  :  
 
Cervical cancer 
• There is a five-fold risk of developing cervical c.a. in women with AIDS 
• Is associated with human papilloma virus infection 
• Invasive c.a. of the Cervix is an AIDS defining illness. 
• Abnormal PAP smear is seen in 60%of HIV infected women 
• Anorectal c.a. may also be seen in homosexual men 
Clinical Staging of HIV/AIDS 
 There are different types of staging systems.  The most common are: 
• The WHO clinical staging system  
• The CDC staging system 
 WHO Clinical Staging System for HIV/AIDS 
• It is a system designed for estimating the degree of immuno-suppression on clinical 
criteria 
• Intended for use in patients known to have HIV (i.e. HIV+ antibody test) 
• It is widely used in recourse limited settings to make decisions as to when to start 
patients on ART 
• According to this staging system there are 4 clinical stages


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 122Table I-5-3. Revised classification system for HIV infection ( CDC Classification) 
 
Clinical category 
  
CD4 category 
 
Asymptomatic /Primary HIV Symptomatic Not A or C conditions  AIDS indicator conditions 
1.  > 500/mm3
 A1 B1 C1 
2.  200-499 
/mm3    
  
A2 B2 C2 
3.  < 200 /mm3
 A3 B3 C3 
 
The shaded portion indicates the expanded AIDS surveillance case definition. 
Comparison: WHO vs. CDC Classification 
• WHO classification does not require CD4 count and hence is more appropriate to use in 
resource limited settings with high HIV prevalence. 
• CDC clinical categories more dependent on expensive laboratories and the staging is 
not adapted to resource poor settings 
 
Table I-5-4. WHO Clinical Staging System for HIV/AIDS 
 
 
Stage 1 Asymptomatic 
 Stage 2 Minor Symptoms 
 Stage 3 Moderate Symptoms 
 
Stage 4 AIDS defining illnesses


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 123Clinical Stage 1 
• Asymptomatic  
• Persistent generalized lymphadenopathy (PGL)(PGL-is defined as the presence of 
lymph node  > 1cm, in two extra inguinal sites and persisting for more than three 
months)  
Clinical Stage 2 s 
• Unexplained moderate weight loss  ( < 10 % of body weight ) 
• Recurrent upper respiratory tract infections ( sinusitis , tonsillitis , otitis media , and 
pharyngitis ) 
• Minor mucocutaneous manifestations (seborrheic dermatitis, fungal nail infections, 
recurrent oral ulcerations, angular chelitis) 
• Herpes zoster within the past 5 years (single dermatome) 
Clinical Stage 3  
• Unexplained sever weight loss (>10% of body weight ) 
• Unexplained chronic diarrhea longer than 1 month 
• Unexplained prolonged fever > 1 month 
• Persistent Oral candidiasis (thrush) 
• Oral hairy leukoplakia  
• Pulmonary tuberculosis  
• Severe bacterial infection (pneumonia, pyom yositis, empyema, meningitis, bateremia) 
• Acute necrotizing ulcerative stomatitis, ginigivitis, or periodentitis  
• Unexplained anemia (< 8 gm/dl), neutropenia 500/mm3, and or chronic 
thrombocythopenia ( < 50, 000/mm ) 
Clinical Stage 4 
• HIV wasting syndrome 
• Pneumocystis carinii pneumonia 
• CNS toxoplasmosis 
• Cryptosporidiosis or Isosporosis related  watery diarrhea > 1 month ,  
• Extrapulmonary cryptococcosis  
• Cytomegalovirus (CMV) disease of an organ other than liver, spleen, or lymph nodes 
(e.g. retinitis)


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• CNS toxoplasmosis 
• Cryptosporidiosis or Isosporosis related  watery diarrhea > 1 month ,  
• Extrapulmonary cryptococcosis  
• Cytomegalovirus (CMV) disease of an organ other than liver, spleen, or lymph nodes 
(e.g. retinitis) 
• Chronic Herpes simplex ( HSV) infection – orolabial, genital anorectal lasting for more 
than 1 month


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 124• Any disseminated endemic mycosis (e.g. histoplasmosis, coccidiodomycosis) 
• Esohagial Candidiasis ( involving  esophagus, trachea, bronchi or lungs ) 
• Recurrent Bacterial pneumonia 
• Recurrent septicemia  
• Disseminated atypical mycobacterium 
• Extrapulmonary tuberculosis 
• Lymphoma ( cerebral or B- cell Non Hodgkin’s lymphoma ) 
• Invasive cervical carcinoma 
• Kaposi’s sarcoma 
• HIV encephalopathy 
• Symptomatic HIV associated neuropathy. 
 
Antiretroviral Drugs (ARTs) 
ARTs are the corner stone of medical management of HIV infection.  
Classes of Antiretroviral Drugs 
1) Nucleoside reverse transcriptase inhibitors  ( NRTIs)  
Lamivudine (3TC)   Stavudine ( d4t ) 
Zidovudine (AZT     Abacavir ( ABC)  
Didanosine (DDI )   Zalcitabin ( DDC )  
Emtricitabine (FTC)   Tenofovir (TDF ),  
Mechanism of Action : Structurally these drugs resemble naturally occurring nucleosides and 
break the formation of viral DNA by breaking the chain ( chain breakers ) 
Zidovudine (AZT )  
• Dosage :300mg PO  BID  
• Side effects : Anemia, Myalgias, bone Marrow Suppression  
 Lamivudine (3TC): 
• Dosing : 150mg BID or 300mg QD 
• Side effects :Headache , occasional nausea 
Stavudine (d4T) • Dosing : 40 mg BID for weight > 60 kg , 30 mg BID for weight < 60 kg  
• Side effects  :Peripheral Neuropathy (5-15%)  ,Lactic acidosis, Pancreatitis


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 125Abacavir (ABC) 
• Dosing : 1 x 300mg tablet BID 
• Toxicity:  Allergic reaction (Hypersensitivity reacti on) which occurs within first 6 weeks of 
initiation of therapy. Never re challenge the patient again with ABC 
Tenofevir (TDF ):  is a ctually, a nucleoTIDE  
Dosing:  1 x 300mg tablet QD 
Toxicity : Headache, Nausea, Diarrhea, Lactic acidosis 
Didanosine (ddI) 
Dosing  
1 x 400mg enteric coated capsule QD (if <60kg: 250mg QD) 
Or  
2 x 100mg buffered tab BID or 4 x 100mg QD (if <60kg: 125 mg BID or 250mg QD) 
NOTE : If use buffered tablets, 2 or more tablets must be used at each dose to provide adequate 
buffer . 
Or   
250mg of reconstituted buffered powder BID (if <60kg: 167mg BID) 
Didanosine (ddI) (2) 
Food Interactions: take on empty stomach  Toxicity : Peripheral Neuropathy, Nausea, abdominal pain, Pancreatitis, Lactic acidosis 
2) Non-nucleoside reverse transcriptase inhibitors ( NNRTIs)  
• Nevirapine (NVP, Nevipan
®) 
• Efavirenz (EFV, Stocrin®) 
• Delavirdine (DLV, Rescriptor®), rarely used  
Mechanism of Action:  inhibit the active site of Reverse transcriptase enzyme  
Nevirapine (NVP, Nevipan®) 
Dosing:  200 mg QD x 2 weeks, then 200 mg BID  
Toxicity : 
• Skin rash (17%)   may be  
o Milder form (dry rash )  : erythematous, maculopapular rash  
 Treatment: continue medication with close observation antihistamins may be 
administered 
o Severe form (wet rash) : with mucous membrane involvement, Steven’s Johnson


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o Milder form (dry rash )  : erythematous, maculopapular rash  
 Treatment: continue medication with close observation antihistamins may be 
administered 
o Severe form (wet rash) : with mucous membrane involvement, Steven’s Johnson 
Syndrome and Toxic epidermal necrolysis (TEN) 
 Rx:- Discontinue medication, never re-challenge


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 126• Hepatitis : 
Efavirenz (EFV, Stocrin®) 
Dosing : 3 x 200mg capsules or 600mg P.O. /d 
Food Interactions : Take with low-fat meal because high-fat meals increase absorption by 50% 
Æ increases side effects  
Toxicity 
• CNS Changes  (52%) - Insomnia, nightmares, poor concentration, mood change, dizziness, 
disequilibrium, depression, psychosis  
• Skin Rash  (15-27%)- usually does not require discontinuation 
• Nausea 
CONTRAINDICATED DURING PREGNANCY  
3) Protease Inhibitors 
Lopinavir + Ritonavir (Kaletra®)    Nelfinavir (Viracept®) 
Saquinavir-SGC (Fortovase®)    Saquinavir-HGC (Invirase®) Indinavir (Crixivan®)    Amprenavir (Agenerase®) Fosamprenavir (Lexiva®)    Atazanavir (Reyataz®) 
Ritonavir (Norvir®)   
Mechanism of Action : Inhibit viral assembly by blocking the  
• PIs are mainly used as second line drugs in recourse limited settings as these drugs are 
expensive and most formulations need refrigeration. 
Common side effects of PIs  • Glucose intolerance (in some patients may cause Diabetes mellitus ) 
• Lipid abnormalities :hypertriglyceridemia , low HDL and  high LDL 
• Lipodystrophy-– Morphologic Changes ,fat accumulation in the lower part of the body and 
atrophy of facial fat   
Goals of ART: (HAART  = Highly Active Antiretroviral Therapy) 
1) Improve the length and quality of the patient’s life 2) Increase total lymphocyte count (TLC) and CD4 cell count, allowing preservation or 
improvement of immune function


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Goals of ART: (HAART  = Highly Active Antiretroviral Therapy) 
1) Improve the length and quality of the patient’s life 2) Increase total lymphocyte count (TLC) and CD4 cell count, allowing preservation or 
improvement of immune function 
3) HIV RNA < 400 copies/ml or “undetectable”    within 4-6 months of ART initiation  
4) Reduce HIV-related morbidity and mortality 
 Is not a cure for HIV. If treatment is stopped, the virus will continue to replicate  
 It cannot eliminate HIV completely from the body.


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 127What does HAART require to be effective ?  
• Strict adherence to this regimen 
• Proper monitoring of side effects and disease progression 
• Recognition and treatment of co-morbidities 
• Recognition of drug interactions 
The Baseline Assessment before initiation of HAART 
 Baseline medical history 
 Physical examination 
 Clinical staging 
 Laboratory testing 
 Development of the patient care plan 
 
WHO Criteria to Initiate ART in Adults and adolescents  
 
 
WHO clinical 
stage  
CD4 testing not available   
CD4 testing available 
 
1  
Don’t treat 
 
2  
ART may be started if TLC is < 
1200/mm3  Start ART only  if CD4 
count is < 200/mm3  
 
3  
If symptomatic initiate ART 
irrespective of TLC Start ART if CD4 is< 
350/mm3 and initiate 
before CD4 drops 
<200/mm3 
 
4 Start ART irrespective of TLC Start ART irrespective of 
CD4 count  
 
Note: ART should be initiated in WHO clinical stage 3 patients with CD4 <350/mm3 if patients 
have: 
o Pulmonary TB 
o Sever bacterial infections


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 128o Oral candidiasis  
Do not start ARVs if: 
• The patient is not motivated 
• Without intensive counseling 
• If treatment cannot be continued 
• If asymptomatic and no information about CD4+ count 
• If the patient has active OI ( first treat the OI which may be an immediate danger to the 
life of the patient before initiating ART ) 
• If the patient has serious psychiatric illness and there is no care giver  
  
First-Line ARV Regimen for Ethiopia  
  
 
 
 
   
 
       
 
Four combinations can be made from these first line drugs  
• AZT/3TC/NVP or 
• AZT/3TC/NVP or 
• D4T/3TC/EFV or 
• D4T/3TC/EFV  
 
Second Line drugs for Ethiopia  
ABC or TDF or ZDV (if not taken)/+ Didianosin (ddI) + Kaletra® LPV/r or SQV/r or NFV          The indications for changing from First line to Second line regime is when there is evidence of 
treatment failure  Zidovudine 
(AZT ) 
Efavirenze  
(EFV )Stavudine 
 (d4t) Nevirapine  
( NVP )
Lamivudine 
(3TC)


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 129• Clinical failure 
• Immunological failure 
• Virological failure  
 
References :  
1) Anthony S. Fauci, Harrison’s Principles of Internal Medicine, Volume 1 pages 1076 -
1139 
2) WHO case definition of HIV for surveillance and Revised Clinical staging, 2006 
3) WHO, Antiretroviral therapy for HIV infection for adolescents and adults in resource -
limited setting, 2006.  
4) Hoffman Ch., HIV medicine, 2006. 
5) AIDS in Ethiopia, Federal MOH Ethiopia, June 2006


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 1306.  Sexually transmitted Infections 
 
Learning objectives: At the end of this lesson students are expected to  
1. Define Sexually transmitted diseases ( STDs or STIs )  
2. Understand the common etiologic agent for STIs 3. Understand the epidemiology of different STIs    
4. Describe the pathophysiology of common STIS  
5. Identify the clinical manifestations of different STIs     6. List the complications and Organ systems affected by STIs  7. Describe the most commonly investigations for the diagnosis of STIs   8. Make an appropriate diagnosis of Different STIs   
9. Understand the syndromic approach for the management of different STIs  
 
Definition: 
Sexually transmitted diseases (STD’S) are a di verse group of infections, caused by different 
types of microbial agents, that are frequently transmitted by sexual contact, and for which 
sexual transmission is epidemio logically important, are considered sexually transmitted 
diseases. “Sexual” includes the full range of he terosexual or homosexual behavior, including 
genital, oral-genital, oral-anal, and genital-anal contact.  
• At present there are more than 20 known causes of STD. No single STD can be 
regarded as an isolated problem because multiple infections are common and because the presence of one STD denotes high-risk sexual behavior that is often 
associated with other, more serious infection.  
• Most STDs are rarely if ever transmitted by fomites, food, flies, or casual contact.


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associated with other, more serious infection.  
• Most STDs are rarely if ever transmitted by fomites, food, flies, or casual contact.   
• At least one sexual partner is always infected; the apparent exceptions usually can 
be attributed to prolonged sub-clinical infection in one or both partners.  Therefore, 
risk assessment (including elicitation of a sexual history) and management of sexual partners are of paramount importance. 
Epidemiology of STIs 
• STIs are major public health problems in all countries, but are especially in developing 
countries where access to adequate diagnostic and treatment facilities is very limited or 
nonexistent. There is limited information on the incidence and prevalence of STIs is


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 131Ethiopia. FMOH compiled 58,632 and 27,947cases from all regions in 2002 and 2003 
respectively. 
• A large proportion of STIs are symptomatic  and most symptomatic patients seek 
treatment from traditional healers , pharmacists , drug vendor shops and market places 
• STDs can be classified and managed in two different ways ( approaches ) 
1. Etiologic approach  
• Advantages:  Accurate diagnosis, accurate treatment, proper use of antibiotics 
(decreases over treatment and antibiotic resistance). It is the better way to diagnose and treat asymptomatic infections  
• Disadvantages : Needs lab support and expertise , expensive (cost may be 
incurred due to lab tests ) and it is time consuming 
2. Syndromic approach   
• Advantages:   Treatment can be given immediately, mixed infection may exist 
and may be adrsessed, there is no need for laboratory diagnosis and the treatment can be given by middle level health professionals. Hence this approach may be a good alternative for in resource limited settings. 
Disadvantages:  over treatment with antibiotics, there is risk of creating antibiotic 
resistance and decreased compliance. There is also increased cost of drugs. Moreover asymptomatic infection missed. 
N.B – In general, an overall approach to the management of a patient with sexually 
transmitted disease begins with 
 
Risk assessment of : 
• Sexual orientation and practice 
• Number of recent and current sexual partners 
• History


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N.B – In general, an overall approach to the management of a patient with sexually 
transmitted disease begins with 
 
Risk assessment of : 
• Sexual orientation and practice 
• Number of recent and current sexual partners 
• History
 of STD in the patient  
• Recent history  of STD of the partner 
• Sociodemographic and other markers of high risk   
Clinical assessment : elicitation of information on specific current symptoms and signs of 
STDs. 
 Laboratory tests : If available, confirmatory diagnostic or screening tests may then be ordered.


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 132Comprehensive Case Management : is vital approach for controlling STIs. So health care 
providers should undertake the following measures besides treating individual patients   
1. Partner notification and management  
2. Condom promotion and supply 
3. Health education and risk reduction counseling  4. Linkage with HIV counseling and testing  5. Follow-up visits for patients with STI 
STI Syndromes 
• Urethral discharge Syndrome 
• Vaginal discharge 
• Genital ulcer 
• Inguinal bubo 
• Scrotal swelling 
• Lower abdominal pain 
• Neonatal conjunctivitis 
 
1. Urethral discharge : 
Urethral discharge is the most common presenting compliant of men with STD.  In urethral 
discharge, exudate is present in the anterior urethra and the discharge is often accompanied 
by dysuria or urethral discomfort. It may lead to epididymitis and complications such as infertility and urethral stricture.  
Etiology 
For practical purposes, STD-related urethritis is divided into  
• Gonococcal urethritis: caused by  Nisseria gonorrhea 
o Has a short incubation period (2-3days 
o Vast majority of cases present with abundant and purulent discharge 
o Tend to produce more severe urinary tract infection symptoms like 
dysuria, urgency and frequency. 
• Nongonococcal urethritis (NGU):  usually caused by Chlamydia trachomatis or 
U.urealyticum. 
o Has scanty to moderate, white, mucoid or serous discharge. 
o Mild urinary tract infection symptoms


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dysuria, urgency and frequency. 
• Nongonococcal urethritis (NGU):  usually caused by Chlamydia trachomatis or 
U.urealyticum. 
o Has scanty to moderate, white, mucoid or serous discharge. 
o Mild urinary tract infection symptoms 
o Has long incubation period (1-3 weeks).


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 133The quantity and appearance of the discharge can be used to distinguish accurately gonococcal 
and nongonococcal urethritis in about 75-80% of patients who have not urinated recently.  It can’t, of course, be used to diagnose dual infection with N.gonorrhea and C.trachomatis. Milking 
of the urethra may be necessary to get a good amount of discharge sample. 
Laboratory  
• Microscopy of urethral discharge stained with methylene blue or safranin or Gram’s 
stain shows pus cells with characteristic intracellular coffee bean shaped diplococci 
Æ N.gonorrhea. 
• Pus cells without intracellular diplococci = NGU. 
Treatment: When the accurate etiologic diagnosis is made  
• Gonococcal Urethritis :   
Ceftriaxone 250mg IM stat  
OR  
Ciprofloacin 500mg PO stat  
OR  
Spectinomycin 2mg IM stat. 
• NGU : Doxycycline 100mg PO BID for 7 days or Tetracycline 500mg PO QID for 7 days 
OR Erythromycin 500mg PO QID for 7 days if the patent has contraindication for TTC.. 
When there is no Etiologic diagnosis: Treatment should cover both gonococccal and 
chlamydial infections (combine the above treatments)  
 
2.  Vaginal Discharge:  
 Etiology 
1. N.gonorrhea  
2. Chlamydia trachomatis  
3. Trichomonas vaginalis,  
4. Gardnerella vaginalis  5. Candida albicans 6. Vaginal anaerobes (“bacteria vaginosis”) 
• The first three are sexually acquired and the last three are endogenous infections. 
• The first two cause cervicitis while the last four cause vaginitis.


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 134• Bacterial vaginosis  (Gardnerella vaginalis) is the leading cause of vaginal discharge 
in Ethiopia followed by Candidiasis, Trichomoniasis, and Gonococcal and Chlamydial 
cervicitis.  
• As urethritis in males, co-infection with C.trachomatis is common in women with 
gonorrhea (~ 50%). 
Clinical feature: 
Many women have a small amount of vaginal discharge (physiologi c leukorrhea), which is clear 
and odourless. It becomes abnormal if the woman notes a change in  the amount , colour or 
odour of the discharge . In general, most women with this syndrome will complain of: 
• Excessive secretions and soiling of undergarments  
• Changes in colour and/or odour of discharge 
• Associated itching, dysuria, dysparunia 
• Redness of vulva 
• Sometimes may be accompanied by lower abdominal pain 
The initial assessment of a patient who has vaginal discharge includes risk assessment and clinical evaluation with spec ulum examination to determine the site of infection. 
 
Vaginitis : bacterial vaginosis, vaginal candidiasis and /or trichomoniasis are the usual causes 
of vaginitis.  
• Bacterial vaginosis and trichomoniasis are more frequent among sexually active women 
while vaginal candidiasis occurs when there is impairment of local or systemic defense 
mechanism. 
• The discharge in bacterial vaginosis is homogenous with a typical fishy odour due to the 
presence of volatile amines and this may e apparent during examination or when the


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mechanism. 
• The discharge in bacterial vaginosis is homogenous with a typical fishy odour due to the 
presence of volatile amines and this may e apparent during examination or when the 
discharge is mixed with 10 % KOH.  
• Trichomonads present with profuse, runny, mal-odorous discharge. Yeasts (Candida) 
often present with white, curd-like discharge and pruritus. 
Speculum examination : in isolated vaginitis the cervix looks healthy and discharge is not 
coming from the cervical opening. 
Cervicitis:  The presence of purulent exudates from the cervical os indicates infection with 
N.gonorrhea  and C.trachomatis. 
Risk factors for STI related cervicitis in Ethiopia ( one or more of the following ) 
• Multiple sexual partners in the last 3 months


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 135• New sexual partners in the last 3 months  
• Age less than 25 years  
• Having ever traded sex  
Cervicitis is frequently asymptomatic. It may be detected on routine pelvic examination or during 
evaluation of a patient with vaginal discharge  
Complications of Cervicitis and Vaginitis  
• PID 
• Premature rapture of membrane  
• Preterm labour  
• Infertility  
• Chronic pelvic pain  
Laboratory:  
It is used mainly for the diagnosis of trichom oniasis, bacterial vaginosis and candidiasis 
T.vaginalis : characteristic jerky motility of the parasite with many leukocytes. 
B.vaginosis : 
• The typical fishy odour will be enhanced by the addition of 1- 2 drops of KOH to the 
specimen of vaginal discharge (“sniff test”) 
• Number of epithelial cells per microscopic field exceeds the number of leukocytes.  
• “Clue cells” =cornified squamous epithe lial cells covered by coccobacilli.  
Candidiasis:  Look for yeast (10% KOH may improve diagnostic sensitivity). 
N.B. In general, Gram stains are not helpful in diagnosing gonorrhea in females (low sensitivity). 
Treatment  
 When accurate Diagnosis is made  
T.vaginalis  : Metronidazole 2gm PO stat 
B. Vaginosis  
• Only symptomatic women need treatment. 
• Metronidazole 500mg PO BID for 7 days or Metronidazole 2 gm as single dose 
and repeat after 48hr. 
 
Vulvovaginal candidiasis 
Topical antifungal agents:  Nystatin 100,000-1,000, 000 IU, intravaginally daily for 14 days.


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• Metronidazole 500mg PO BID for 7 days or Metronidazole 2 gm as single dose 
and repeat after 48hr. 
 
Vulvovaginal candidiasis 
Topical antifungal agents:  Nystatin 100,000-1,000, 000 IU, intravaginally daily for 14 days. 
                Miconazole or clotrimazole 200mg intravaginally daily for 3 days                      
Mucopurulent discharge from the cervix  : treat for gonorrhea and chlamydial infection.


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 136When Specific diagnosis could not be made manage as vaginal discharge syndrome 
 
 
Recommended treatment for Vaginal Discharge  
Risk Assessment Positive  Risk Assessment Negative  
Ciprofloxacin 500 mg PO stat Or 
Spectinomycin 2gm IM stat  
Plus 
Doxycycline 100 mg PO BID for 7 
days  
Plus 
Metronidazole 500mg Po ID for 7 days  
 Metronidazole 500mg Po ID for 7 
days  
Plus 
Clotrimazole vaginal tabs 200mg 
at bed time for 3 days  
 
3. Genital Ulcer: 
A genital ulcer is a loss of continuity of the skin of the genitalia. Genital ulcers may be painful or painless and are frequently accompanied by inguinal lymphadenopatly. 
Common Etiology agents: 
• Treponema pallidum (syphilis) 
• Haemophilus ducreyi (chancroid) 
• Calymmatobacterium granulomatis (granuloma inguinale) 
• C.trachomatis serovar L
1-L3   (Lymphogranuloma venereum or LGV) 
• Herpes virus 1 or 2 (Herpes simplex virus or HSV) 
Syphilis  
• Genital ulcer occurs in the primary stage of the diseases 
• It starts as a small popular lesion that rapidly ulcerates to produce a non tender 
indurated lesion with a clean base and raised margins known as chancre 
• Chancres may appear at any point of contact :genitals, anus, mouth, lips 
• Heal without treatment in 1 to 6 weeks 
• Swollen lymph nodes may appear


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 137Complications  
o Secondary syphilis 
o Aortitis with valvulitis  
o Neurosyphilis 
Genital Herpes: 
• HSV virus has two types 
o HSV-2 causes dominantly genital disease 
o HSV-1 causes dominantly oral disease 
• Worldwide the most common cause of genital ulcer 
• Latency and frequent recurrence characterizes genital herpes , producing a lifelong 
infection /persistent 
• Herpetic ulcers  
o Are usually painful and multiple 
o Starts as clear vesicle and becomes pustule, which later erodes to an ulcer and 
then crusts 
o Heals spontaneously after 2-3 weeks  
o Recurrence possible but milder (number of vesicles are fewer)  
• It tends to be aggressive in HIV patients with extensive tissue involvement and chronic 
ulceration. It may also be dissemination to CNS, skin etc 
Complications: 
o Recurrence  
o Aseptic meningitis and enchephalitis  
Chancroid 
• Caused by Haemophilus ducreyi   
• Is one of the commonest causes of genital ulcer in most developing countries, however it 
was not found to be a common cause of genital ulcer in Ethiopia. 
• Incubation period: 3 -15 days 
• Ulcer on the penile shaft or prepuce  
• It is painful progressing from a small papule to pustule and then ulcer with soft margins 
described as soft chancre  , yellow gray exudative covering and erythema 
• Inguinal adenopathy that becomes necrotic and fluctuant ( bubo ) follows the ulcer within 
1-2 weeks  
Complication :  penile autoamputaion


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 138Lymphogranuloma Venereum (LGV) 
• Caused by L1, L2 and L3 serovars of Chlamydia trachomatis  
• There is little evidence on the prevalence of LGV in Ethiopia 
• Major pathology occurs in the lymphatic system  
• Primary stage  is marked by a painless vesiculo-papular ulceration at the site of 
inoculation  
– Located in the penis in men  
– On the labia and posterior vagina in women. 
• Primary lesion usually not noticed. 
• The secondary stage  is described as the inguinal syndrome 
o  A painful inguinal lymphadenitis with constitutional symptoms   
o In men infection usually spreads through the lymphatics causing inguinal and 
femoral lymphadenitis. 
o In women upper vaginal and cervical infection results in enlargement of the 
obturator and iliac nodes. (sometimes pelvic nodes) 
• Inguinal adenopathy is usually unilateral (2/3 of cases) 
• Nodes initially discreet later becomes fluctuant and suppurative developing multiple 
draining fistulas 
• Bubo may be grooved by the inguinal ligament ("groove sign" of LGV)  
• External genitalia may be oedematous and swollen  
• May lead to anatomical distortion and irregularity, particularly of the penis  
• Spontaneous healing after several months possible  
Late complications include  
o Genital elephantiasis  
o Adhesion 
o Stricture and fistula of the penis,  urethra and the rectum 
 
Granuloma Inguinale (Donovanosis) 
• Chronic: progressively destructive bacterial infection of the genital region without


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o Genital elephantiasis  
o Adhesion 
o Stricture and fistula of the penis,  urethra and the rectum 
 
Granuloma Inguinale (Donovanosis) 
• Chronic: progressively destructive bacterial infection of the genital region without 
systemic symptoms 
• Etiology: Calymmatobacterium granulomatis  a gram-negative intra-cellular bacteria 
• Transmission –sexual and non-sexual contact


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 139• Distribution –mainly in Australia, Caribbean, India, and southern Africa. Little information 
about its prevalence in Ethiopia 
Clinical Manifestation 
• Incubation period – usually1 to 4 weeks may be as long as a year 
• The patient usually presents with a non suppur ative genital lesion which develops from a 
small firm papule to painless ulcer with a beefy-red appearance and non-purulent base  
• Lesion bleeds easily, expand gradually  
• Extra inguinal in 6% of cases 
• 50% women have lesion on cervix  
Complications  
o Genital pseudo-elephantiasis of labia 
o Adhesion  
o Urethral , vaginal or rectal stenosis  
Management of Genital Ulcer 
1. When specific Etiologic diagnosis is made 
Syphilis: 
• Benzanthine penicillin 2.4million IU IM stat OR  
• Procaine penicillin 1.2milli on IU daily IM for 10 days. 
• In penicillin allergic patients, doxycycline 100mg PO BID for 15 days or Tetracycline 500mg 
PO QID for 15 days. 
Genital Herpes: 
• Acyclovir 200 mg 5X per day for 10 days or Acyclovir 400 mg Po TID for 10 days  
Treatment of chancroid: 
• Ceftriaxone 250mg 1M stat or 
• Erythromycin 500mg PO TID for 7 days  
Treatmen  of LGV: 
• Doxycycline 100mg PO BID for 14 days or  
• Tetracycline 500mg PO QID for 14 days 
Treatment  of Granuloma inguinale  
• Cotrimoxazole 02 tab PO BID for 14 days  
      N.B – Tetracycline is contraindicated during pregnancy


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 1402. When specific Etiologic diagnosis is not made – Syndromic approach  
Recommended treatment for non-vesicular genital ulcer 
Benzanthine penicillin 2.4million IU IM stat  
Or (in penicillin allergic patients) 
Doxycycline 100mg PO BID for 14 days 
Plus  
Ciprofloxacin 500 mg PO for 3 days or 
Erythromycin 500mg PO QID for 7 days  
        Recommended treatment for Vesicular, multiple or recurrent genital ulcer 
Acyclovir 200 mg 5X per day for 10 days or 
Acyclovir 400 mg Po TID for 10 days  
       Recommended treatment for  
 Recurrent Infection : Acyclovir 400 mg Po TID for 5 days  
 Suppressive therapy : Acyclovir 400 mg PO BID continuously 
 
4. Lower abdominal pain: 
Lower abdominal pain in women is associated with pelvic inflammatory disease (PID).PID 
denotes pelvic infections in women (e.g. salphingitis, endometritis, parametritis, oopheritis) 
caused by microorganisms which generally ascend from the lower genital tract to invade the 
endometrium, fallopian tubes, ovaries, other adjacent tissues and peritoneum 
Etiology:  
• Commonly N.gonorrhea and C.trachomatis which are sexually transmitted  
• PID if often polymicrobial and may be associated with Mycoplasma , Bacteriods , 
Streptococcus , E.Coli , H .Influenza which may or may not be sexually transmitted  
Risk factors : 
• The occurrence of vaginal discharge may be an antecedent event  
• STD 
• postpartum and postabortal ascending infections 
• Intra uterine device ( IUD)


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 141Clinical feature:  
• Mild to severe bilateral lower abdominal pain is the most common complaint, which may 
first be noticed during or shortly after the menses and which is sometimes associated 
with fever.  
• The presence of vaginal discharge supports the diagnosis of PID and pain during 
intercourse or urination may also be present 
Physical examination  
• Lower abdominal and adenexal tenderness toget her with cervical excitation tenderness 
may be indicative of PID. 
• A tender pelvic mass together with fever, nausea or vomiting can also be detected. 
• Vaginal discharge, genital ulcer, presence of IUD, open cervix (abortion tissue seen or 
felt) support the diagnosis of PID. 
Diagnosis :  
• Is often difficult. Over diagnosis and treatment may be justified in order to prevent 
complications. 
• Rule out other cause of lower abdominal pain in women such as appendicitis , ectopic 
pregnancy and Cholecystitis 
Laboratory : Direct wet mount microscopy of a vaginal specimen is necessary.  The presence of 
pus cells in numbers exceeding those of epithelial cells suggests infection of the lower genital 
tract. Complications   
• Peritonitis and intra-abdominal abscess 
• Adhesion and Intestinal obstruction  
• Ectopic Pregnancy 
• Infertility  
Treatment Most patients with mild to moderate PID can be treated as an out patient  
Some patients need hospital admission: Indications for admission are  
 Uncertain diagnosis  
 Pelvic abscess suspected


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• Ectopic Pregnancy 
• Infertility  
Treatment Most patients with mild to moderate PID can be treated as an out patient  
Some patients need hospital admission: Indications for admission are  
 Uncertain diagnosis  
 Pelvic abscess suspected 
 Pregnant patients  
 Co infection with HIV


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Internal Medicine 
 
 142• As the infection is poly-microbial in nature instead of single, combination of antibiotics 
should be prescribed. The spectrum of activity of the antimicrobial agents should cover 
the following organisms: N.gonorrhea, C. trachamatis, aerobic and anaerobic bacteria.  
• Antibiotics should be initiated empirically even before the microbiological report is 
available.   
 
 Recommended treatment for PID 
Out patient   In patient  
Ciprofloxacin 500 mg PO stat 
Or 
Spectinomycin 2gm IM stat  
Plus 
Doxycycline 100 mg PO BID for 14 days  
Plus 
Metronidazole 500mg Po ID for 14 
days  
 
Admit the patient if there is no improvement within 72 hours  Metronidazole 500mg Po ID for 7 days  
Plus 
Clotrimazole vaginal tabs 200mg 
at bed time for 3 days  
 
Non Specific : Adequate bed rest, analgesic,  
 If there are any obstetric or surgical complications, refer the patient as early as possible. 
5. Inguinal bubo: 
• Inguinal bubo is an enlargement of the lymph glands in the groin area. 
• Etiology: The common sexually transmitted pathogen associated with Inguinal bubo 
include  
o C.trachomatis serovar L 1-L3   (Lymphogranuloma venereum or LGV) 
o Haemophilus ducreyi (chancroid) 
o Calymmatobacterium granulomatis (granuloma inguinale) 
o Treponema pallidum (syphilis) may sometimes cause inguinal bubo


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Internal Medicine 
 
 143• Except in case of LGV, a bubo is rarely a sole manifestation of STD and is usually found 
together with the etiologically related genital ulcer.  Non-sexually transmitted local or 
systemic infections can also  cause inguinal lymphadenopathy.  
Clinical feature: 
• Usually patients complain of unilateral or bilateral painful swelling in the groin, but 
buboes can be painless. 
• It is important to ask for any history of associated genital ulcer. 
 Treatment: 
 
Recommended treatment for Inguinal Bubo 
Ciprofloxacin 500 mg PO BID  for 3 days  
                                PLUS Doxycycline 100 mg PO BID for 14 days OR Erythromycin 500 mg PO BQID for 14 days   
 
• Fluctuant buboes require aspiration through adjacent healthy skin (don’t incise for 
drainage). 
• If genital ulcers are present, treat with the etiologically related cause of the ulcer. 
 
6. Scrotal Swelling Syndrome 
The cause of scrotal swelling depend on the age of the patient 
For those younger than 35 years  
• N.gonorrhoeae 
• C.tracomatis  
For those older than 35 years  
• Gram negative organisms 
• Tuberculosis 
• Other cause include : Brucellosis , Mumps , Onchocerciasis , Wuchereria 
buncrofti  
It is important to exclude other causes of scrotal swelling which may require urgent surgical 
evaluation and management


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 144• Testicular Torsion  
• Trauma   
• Incarcerated inguinal hernia  
 
Complications of Scrotal Swelling: caused by STI include  
• Epididymitis 
• Infertility  
• Impotence  
• Prostatitis  
Treatment of Scrotal swelling suspected of STI origin is similar to Urethral discharge. 
 
 Recommended treatment for Scrotal swelling  
Ciprofloxacin 500 mg PO stat OR Spectinomycin 2gm IM stat                                  PLUS 
Doxycycline 100 mg PO BID for 7 days OR Tetracycline 500 
mg PO QID for 7 days  
 
Supportive Treatment : Analgesia and scrotal support may be indicated if the patient has 
severe pain   References: 
1. National guideline for Syndromic aproch of Sexualy transmited infections, Federal MOH, 
2005. 
2. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, Sexualy 
transmited diseases, overview, pages 762-774


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Internal Medicine 
 
 1457. Other Important Infectious Diseases  
 
7.1. Tetanus 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define tetanus  
2. Classify tetanus 
3. Mention the etiology of tetanus 4. Describe the mode of transmission of tetanus 5. Explain the epidemiology of tetanus 6. Describe the pathophysiology of tetanus 
7. Identify the clinical manifestations of tetanus 
8. Describe the most commonly used method for the diagnosis of tetanus 9. Make a diagnosis of tetanus 10. Refer cases of tetanus to hospitals for better care and close follow up 
11. Design appropriate methods of prevention for tetanus  
 
Definitions 
Tetanus is a neurologic disease characterized by increased muscle tone and spasms caused by 
toxin released from the bacteria Clostridium tetani.  
 
Etiologic Agent 
• Clostridium tetani  is an anaerobic, motile Gram-positive rod that forms an oval, colorless, 
terminal spore, which looks like a tennis racket or a drumstick.  It is found worldwide in soil. 
• Spores may survive for years in  soil.  They are also resistant to different disinfectant and 
even to boiling for less than 20 minutes. 
 
Epidemiology 
• Tetanus occurs sporadically and almost always affects non-immunized persons.  
Partially immunized persons or fully immunized individuals who fail to maintain adequate immunity are also affected. 
• Tetanus is more prevalent in developing countries like India, Bangladesh, Pakistan,


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Partially immunized persons or fully immunized individuals who fail to maintain adequate immunity are also affected. 
• Tetanus is more prevalent in developing countries like India, Bangladesh, Pakistan, 
eastern Mediterranean, South America and Africa including Ethiopia.


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Internal Medicine 
 
 146• Tetanus is more common in rural areas where there is frequent contact with soil.  It also 
occurs more frequently in warmer climates, during summer months and in males.  
Neonates and young children are affected more in developing countries where immunization programs are not comprehensive.  Development of severe illness is seen more in the elderly.  Most cases of tetanus follow injuries especially during farming, gardening or other outdoor activities.  Tetanus may also be associated with surgery, 
otitis media, abortion or delivery. 
 
Pathogenesis  
• Although C. tetani frequently contaminates wounds, germination and toxin production, 
however, takes place in wounds with necrotic tissue, foreign bodies or infection that is active. Often the wound is trivial or could seem to be healed from outside. 
• Tetanospasmin, a toxin produced by the bacteria in the wound binds to peripheral motor 
neuron terminals, enters the axon and is taken to spinal cord and brainstem by 
retrograde transport.  The toxin then inhibits release of inhibitory neurotransmitter and γ-
aminobutyric acid (GABA) with diminished inhibition, there will be increased excitation 
spasm and rigidity.  Tetanospasmin may also block neurotransmitter release at the 
neuromuscular junction and produce weakne ss or paralysis.  Generalized tetanus 
occurs when toxin enters into blood stream and lymphatic to affect distant nerve 
endings. 
  Clinical Manifestations


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neuromuscular junction and produce weakne ss or paralysis.  Generalized tetanus 
occurs when toxin enters into blood stream and lymphatic to affect distant nerve 
endings. 
  Clinical Manifestations 
• The incubation period  (time between the injury and first symptom) of tetanus is about 7 
– 10 days but it may range from 1 day to 2 months.  
• The period of onset  (time between the first symptom and spasm) ranges 1 – 7 days.  
The shorter the incubation period and period of onset, the more severe the disease becomes. There are different forms of tetanus: neonatal, generalized and localized tetanus.  The most common form is generalized tetanus.  
 
Generalized Tetanus  
• The median time of onset after injury is seven days; but could occur as early as with in 
three days. Usually the fist symptom is increased tone in the masseter muscle (trismus, or lockjaw) and patient is unable to open his mouth.


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Internal Medicine 
 
 147• Immediately after this the patient develops dysphagia, stiffness in the neck and back. 
• Then the patient develops contraction of facial muscles to produce rhesus sardonicus  
(sneer or grimace). 
• There may be arched back (opisthotonos), generalized muscle spasm triggered by 
stimulus such as light or noise.   
• Deep tendon reflexes may be exaggerated.   
• There may be dysphagia or paralytic ileus. 
Localized tetanus:  is a rare form of tetanus.  
• It presents with rigidity and spasm around the portal of entry.  
• While most localized tetanus have good prognosis, cephalic tetanus has high mortality. It 
comes after head injury, injury to the face or ear infection. 
Patients may come with wide ranges of wound severity, although most have trivial or healed 
wound. In fact 15% – 20 % of patients may not give history of injury. Neonatal tetanus :  
• Occurs in neonates of non-immunized mother and those delivered in unhygienic 
condition. 
• It is a very severe form of tetanus with more than 90% mortality. 
• Neonates should be referred urgently to a near-by hospital if there is suspicion of clinical 
tetanus. 
Tetanus may be graded according to severity. Grading is helpful in prognosis and 
management . 
• Grade I (mild) : moderate trismus, generalized spasticity 
• Grade II (moderate)  : Moderate trismus, mild to moderate but short lasting spasms, 
tachypnea – RR 30-35/min and mild dysphagia


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management . 
• Grade I (mild) : moderate trismus, generalized spasticity 
• Grade II (moderate)  : Moderate trismus, mild to moderate but short lasting spasms, 
tachypnea – RR 30-35/min and mild dysphagia  
• Grade III (severe)  : Severe trismus, generalized spasticity, prolonged spasms, 
respiratory embarrassment RR >40/min, apnoeic spells, tachycardia >120/min and 
severe dysphagia 
• Grade IV (very severe)  : Features of grade III plus severe autonomic disturbance of 
CVS. It includes episodes of hypertension and tachycardia alternating with relative hypotension and bradycardia or severe persistent hypertension (DBP >110 mmHg) or 
severe persistent hypotension (SBP <90mmHg).


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Internal Medicine 
 
 148Poor prognostic factors in Tetanus : 
• Patients with higher grades 
• Short incubation period and period of onset 
• Cephalic tetanus and  
• Patients with comorbidities have poor prognosis.     
Diagnosis 
The diagnosis of tetanus rests entirely on clinical grounds.  But wounds should be cultured for 
C.tetani or superinfection. CSF analysis is normal. 
Treatment 
The goals of treatment are  
• To eliminate source of toxin 
• Neutralize unbound toxin and  
• Prevent muscle spasm. 
General measures :  
• Patients should be admitted to a quiet room in an ICU, where frequent monitoring is 
possible.   
• If there are wounds, they should be explored and cleaned. 
• Respiratory care:   Intubation and tracheostomy may be required and should be done 
as early as possible if indicated.  Thes e procedures are required for hypoventilation 
caused by laryngospasm or over sedation or to avoid aspiration. 
• Autonomic dysfunction : No definitive treatment has so far been outlined.  But 
hypotension requires fluid expansion and vasopressor agents. 
• Other measures:   hydration should be maintained.  Naso-gastric tube can be inserted 
for nutrition.  Physiotherapy should be instituted as soon as possible to avoid 
contracture.  Input and output should be monitored.  Bedsores and other infections 
should be prevented.  Recovering patients should start active immunization against tetanus. 
Specific Treatment ;


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contracture.  Input and output should be monitored.  Bedsores and other infections 
should be prevented.  Recovering patients should start active immunization against tetanus. 
Specific Treatment ; 
Antibiotic treatment : This helps to eradicate the vegetative bacteria, not the toxin.  
• Crystalline penicillin 3 million units IV 6X a day for 10 days is used but metronidazole 
500mg every 6 hrs or 1g every 12 hours can also be used.  Erythromycin and 
clindamycin are alternatives in patients allergic to penicillins. 
Antitoxin:  - This neutralizes only circulating toxins which are not bound.


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 149• Human tetanus immune globulin (TIG) is the choice and if available should be given 
early.  
• But tetanus antitoxin (TAT), which is available in our setup, can be given in doses of 
10,000 IU intravenous and 10,000 IU intra-muscular. 
Control of muscle spasms :  
• Diazepam and Chlorpromazine are given 6 hourly, alternatively.   
• If spasms are not controlled by the above medication, neuromuscular blockers and 
mechanical ventilation can be used. 
 
 
References: 
1. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, Tetanus,  pages 840-841


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Internal Medicine 
 
 1507.2. Rabies 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define rabies  2. Mention the etiology of rabies 3. Describe the mode of transmission of rabies 
4. Explain the epidemiology of rabies  
5. Describe the pathophysiology of rabies  6. Identify the clinical manifestations of rabies 7. Describe the most commonly used method for the diagnosis of rabies  8. Make a diagnosis of rabies  
9. Refer people who were bitten by rabied animals to hospitals for post exposure 
prophylaxis 
10. Design appropriate methods of prevention and control of rabies 
 
Definition:  Rabies in an acute central nervous system  disease that is caused by rabies virus, 
an RNA virus, which is transmitted by infected secretions. Etiology : - The rabies virus is a single stranded RNA virus which belongs to the rhabdovirus 
family. 
 Epidemiology:   
• Rabies is found in animals in most regions of the world.  Source of infection could be 
domestic or wild animals.  
• Human infection occurs through contact with un-immunized domestic animals or 
exposure to wild animals in the periphery. Humans are occasionally infected by wild 
animals like foxes and bats, but domestic dogs are responsible for more than 90% of 
human cases worldwide. 
• The incubation period of rabies is very variable, which ranges from as early as 7 days to 
as late as more than one year, but the mean incubation period is 1 to 2 months.


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human cases worldwide. 
• The incubation period of rabies is very variable, which ranges from as early as 7 days to 
as late as more than one year, but the mean incubation period is 1 to 2 months. 
 
Pathogenesis:   Rabies virus enters the body through skin or mucous membrane.  There is 
initial replication of virus at the muscles around port of entry.  The virus then ascends to the 
CNS through the neuromuscular junction.  Once in the CNS, the virus replicates in the gray


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Internal Medicine 
 
 151matters.  The virus then passes to other organs like kidneys, salivary glands, heart, and skin, 
following the autonomic nervous system. Passage of the virus into salivary gland facilitates further transmission. 
 
Clinical manifestations:   
Clinical manifestations can be divided into four stages. 
• Prodromal stage:  usually it lasts less than 4 days; it is manifested by fever, headache, 
malaise, and anorexia and vomiting.  
• Encephalitis phase:  starts with excitation and agitation but later there will be confusion, 
hallucination, aggressive behavior, muscle spasms, meningismus, opisthotonus, seizure and focal paralysis.  Patients may have fever, irregular pupils, salivation, perspiration and postural hypotension. 
• Brainstem dysfunction:  begins soon after the encephalitis phase.  There will be 
multiple cranial nerve deficits. Excessive salivation and inability to swallow results drooling of saliva.  Hydrophobia is seen in about 50% of cases. 
• Death:  Patients rapidly develop coma and death is usually caused due to respiratory 
failure (by apnea).  
 
Laboratory Findings:   Early in the course, routine investigations are normal.  Later the white 
cell count is usually moderately elevated, but it may as well be normal. 
However, the diagnosis of rabies rests on identification of the virus or serologic tests. 
Treatment 
Once clinical disease appears, mortality is almost 100%. So far only 6 cases have recovered


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However, the diagnosis of rabies rests on identification of the virus or serologic tests. 
Treatment 
Once clinical disease appears, mortality is almost 100%. So far only 6 cases have recovered 
from disease in the world. Therefore anyone with history of domestic or wild animal bite should 
be taken seriously.   
Post exposure prophylaxis:  should be considered in people who had physical contact with 
saliva or secretions of infected animals or bitten by unprovoked animal e.g. a dog may likely have rabies.  Post exposure pr ophylaxis of rabies includes: 
• Rigorous cleansing and treatment of the wound  
• Administration of rabies vaccine together with anti-rabies immunoglobulin.   
• As the incubation period of rabies is variable, post exposure prophylaxis should be 
initiated as long as there is no clinical evidence of rabies.


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 152Pre-exposure Prophylaxis:  people who are at risk of contact with rabies like veterinarians, 
laboratory workers and animal handlers should receive pre exposure prophylaxis. 
 
Reference 
1. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, Rabis 
virus,  pages 1155-1160


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Internal Medicine 
 
 1537.3. Anthrax 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define anthrax  2. Classify anthrax 3. Mention the etiology of anthrax 
4. Describe the mode of transmission of anthrax  
5. Explain the epidemiology of anthrax  6. Describe the pathophysiology of anthrax   7. Identify the clinical manifestations of anthrax  8. Describe the most commonly used tests for the diagnosis of anthrax  
9. Make a diagnosis of anthrax  
10. Treat anthrax at the primary care level 
11. Design appropriate methods of prevention and control of anthrax   
 Definition:  anthrax is an infection that is caused by Bacillus anthracis. It mainly affects 
herbivorous animals but humans are infected by contact with the causative agent from infected 
animals, by contact, ingestion or inhalation. 
Etiology:  Bacillus anthracis  is a large, aerobic, spore-forming, gram-positive rod, which is 
encapsulated and non-motile. Epidemiology:  Anthrax is more common in herbivorous animals like cattle, sheep and goats.  
They are infected while grazing on contaminated grass.  Humans may acquire anthrax from agricultural sites through contact with animals like butchering and feeding or industrial sites through exposure to contaminated hides, wool or bones. 
Pathogenesis:    
• Cutaneous anthrax is initiated when spores of B. anthracis  are introduced through 
abrasions of the skin or insect bite.


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Pathogenesis:    
• Cutaneous anthrax is initiated when spores of B. anthracis  are introduced through 
abrasions of the skin or insect bite.  
• Inhalation anthrax is acquired by directly inhaling the agent to the alveoli.   
• Gastrointestinal form usually occurs after i ngestion of raw or partially cooked meat that is 
contaminated.  
B. anthracis  goes to the blood stream and replicates rapidly.  It is resistant to phagocytosis.  It 
also produces anthrax toxin, which causes edema and inhibition of polymorphonuclear 
leucocyte function.  Moreover, it causes release of cytokines, shock and death.


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 154Clinical Manifestations 
About 95% of anthrax is cutaneous form. 5% is inhalation, and that of gastrointestinal (GI) is 
very rare. GI form is more common in areas where raw meat is ingested. 
Cutaneous anthrax :  
• The lesions are more common on exposed areas like face, neck and extremities.  
• In the beginning, a small red macule develops within days.  This will become papular 
and pustular which then forms a central necrotic ulcer (black eshcar) with surrounding 
edema; it is painless.  
• Usually there is associated painful regional lymphadenopathy and fever is uncommon.   
• Most patients recover spontaneously but about 10% develop progressive infection, 
bacteremia, high grade fever and rapid death. 
Inhalational anthrax (wool sorter’s disease):   
• This form resembles severe viral respiratory disease and thus diagnosis is difficult.   
• This form may be used as biological warfare.  
• Within 3 days of infection patients develop fever, dyspnea, stridor, hypoxemia, 
hypotension and may die within 24 hours once patients become symptomatic. 
Gastrointestinal anthrax:  Patients may have nausea, vomiting, abdominal pain, bloody 
diarrhea, and fever; they may develop ascites. 
 Treatment 
Cutaneous anthrax   
• Can be treated with crystalline penicillin 2 million units 6 hourly until edema subsides 
then oral penicillin for 7-10 days.   
• For allergic patients, ciprofloxacin, erythromycin, TTC or chloramphenicol may be given.


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Cutaneous anthrax   
• Can be treated with crystalline penicillin 2 million units 6 hourly until edema subsides 
then oral penicillin for 7-10 days.   
• For allergic patients, ciprofloxacin, erythromycin, TTC or chloramphenicol may be given.   
• Wound should be cleaned, debrided and dressed.   
Inhalation or GI form   
• Should be treated with high dose penicillin 8-12 million units per day, divided into 4-6 
doses. 
Mortality rate  
• Cutaneous Anthrax is 10-20%,  for and almost. 
• GI Anthrax can 50% 
• Inhalational anthrax 100% for


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Internal Medicine 
 
 155Prevention: 
• Mass vaccination of animals 
• Avoiding feeding on infected cattle 
• Proper disposal of dead animals and  
• Keeping personal hygiene. 
 
Reference: 
1. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, Anthrax 
,  pages 1280-1-83


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Internal Medicine 
 
 1566.4 Brucellosis 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define brucellosis 2. List the etiologies of brucellosis 3. Describe the mode of transmission of brucellosis 
4. Explain the epidemiology of brucellosis  
5. Describe the pathophysiology of brucellosis  6. Identify the clinical manifestations of brucellosis 7. Describe the most commonly used tests for the diagnosis of brucellosis  8. Make a diagnosis of brucellosis  
9. Treat brucellosis at the primary care level 
10. Design appropriate methods of prevention and control of brucellosis 
 
Definition:  Brucellosis is a zoonotic disease caused by Brucella species , which is characterized 
by remittent type of fever and multi-organ involvem ent.  It is transmitted to humans from infected 
animals. 
 
Etiology : It is caused by four different types of Brucella. They are small aerobic gram-negative 
bacilli; they are non-motile and facu ltative intracellular parasites. 
• Brucella melitensis (the most common and most virulent type) acquired from goats, 
sheep and camels. 
• Brucella abortus from cattle 
• Brucella suis from hogs  
• Brucela canis from dogs 
 
Epidemiology:   
• It is found worldwide, but the true incidence is not known.  In communities where 
brucellosis is endemic, it occurs in children and family members of infected persons are at risk.  Commonly affected are farmers, meat-processing workers, veterinarians, and 
laboratory workers.


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Internal Medicine 
 
 157• Brucella organism is transmitted commonly through the ingestion of untreated milk or 
milk products; raw meat and bone marrow have been implicated.  But it can also be 
transmitted by inhalation from close contact with animals. 
Pathogenesis:  In the blood Brucella is ingested by polymorphonuclear leukocytes and 
macrophages but they resist intracellular phagocytosis.  Severity of the disease is largely determined by the outcome of pathogen-phagocyte interaction.  The organisms multiply, reach 
blood stream via lymphatics, and then reside in different organs, the liver, spleen, bones, 
kidneys, lymph nodes, heart valves, nervous system and testes.  In infected organs there will be 
inflammatory responses or noncaseating granulomas. Serum IgM will appear within a week and later IgG and IgA will develop. 
 Clinical manifestations and complications:    
• Brucellosis is a systemic ill ness and its manifestations mimic other febrile illnesses.   
• The incubation period is about 1-3 weeks.  The  illness may begin suddenly or it could be 
gradual.  
• The most common symptoms are fever, chills, diaphoresis, headache, myalgia, fatigue, 
anorexia, joint and low back-pain, weight loss, constipation, sore throat and dry cough.   
• Patients may look well with no findings or may exhibit physical findings related to the 
organ affected. 
• Fever of brucellosis has no distinctive features but it occurs in late afternoons or 
evenings.


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• Patients may look well with no findings or may exhibit physical findings related to the 
organ affected. 
• Fever of brucellosis has no distinctive features but it occurs in late afternoons or 
evenings.   
• Patients may have reactive asymmetric polyart hritis involving larger joints; and lumbar 
vertebral osteomyelitis.  
• Cardiovascular complications of Bruce llosis include endocarditis, myocarditis, 
pericarditis, thrombophlebites and pulmonary embolism.   
• Brucella can have respiratory manifestations like sore throat, tonsillitis, dry cough and 
even pneumonia and lung abscess.   
• Gastrointestinal manifestations are generally mild and include nausea, vomiting, 
abdominal pain and diarrhea; there is hepatosplenomegaly in about 15-20% of patients.   
• Patients may have genitourinary infection and present with epididymoorchitis, prostatitis, 
amenorrhea, tubo-ovarian abscess, salphingitis, acute pyelonephritis and 
glomerulonephritis.


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Internal Medicine 
 
 158• Nervous system involvement is unco mmon but when involved patients may have 
meningitis, meningoencephalitis, brain abscess, hemiplegia and cranial nerve deficit.   
• Other manifestations are conjunctivitis, retinopathy, skin involvement, abortion, anemia, 
leukopenia and thrombocytopenia. 
 
Diagnosis  
The combination of history of exposure, clinical  features and significantly raised levels of 
Brucella agglutinin confirms the diagnosis of active brucellosis. 
Treatment   
• The combination of doxycycline and aminoglycoside (gentamicin, or streptomycin) for 4 
weeks followed by the combination of doxycycline and rifampin for 4 to 8 weeks is the most effective treatment modality. 
• Alternative regimen is combination of doxycycline and rifampin given for 8 to 12 weeks. 
• Patients with serious illness and complication need admission for treatment with 
intravenous medications and possible surgical intervention. 
 
Prevention  - Immunization of animals, boiling or pasteurizing milk are important in preventing 
the disease.  
 
Reference: 
1. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, 
Brucellosis , 914-917


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Internal Medicine 
 
 159CHAPTER TWO 
DISEASES OF THE RESPIRATORY SYSTEM 
 
1. Common Symptoms of Respiratory System 
 
Learning Objective :  At the end of this unit the student will be able to  
1. List the common symptoms of diseases of the respiratory system 
2. Characterize each of the symptoms 
3. Describe the pathophysiology of each symptom 4. Identify disease conditions associated with each symptom 5. Describe the most commonly used investigations of the respiratory system 
 
Cough  
Cough is an explosive expiration that provides  a protective mechanism for clearing the 
trachiobronchial tree of secretions and foreign material.  However, when excessive, it is one of 
the commonest presentations (complaint).  As a protective mechanism against foreign or noxious material, cough can be initiated by a variety of airway irritants, which enter the trachiobronchial tree by inhalation (smoke, dust, 
fumes) or by aspiration (upper airway secretions, gastric contents, foreign bodies). 
 Any disorder resulting in inflammation, constriction, infiltration, or compression of airways can be associated with cough.   Inflammation commonly results from airway infections, ranging from. 
Some causes of cough are: 
• Inflammation-infection (viral  ,bacterial etc )  , bronchitis , bronchiectasis,  asthma etc  
• Constriction - asthma (it is reversible)  
• Infiltration – tuberculosis, neoplasm, granuloma, or sarcoidosis


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Some causes of cough are: 
• Inflammation-infection (viral  ,bacterial etc )  , bronchitis , bronchiectasis,  asthma etc  
• Constriction - asthma (it is reversible)  
• Infiltration – tuberculosis, neoplasm, granuloma, or sarcoidosis  
Examples of parenchymal lung disease potentially producing cough include pneumonia, 
interstitial lung disease, and lung abscess. Patients with congestive heart failure may have cough, because of interstitial edema.


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Internal Medicine 
 
 160Approach to the Patient with cough 
A detailed history frequently provides the most valuable clues for etiology of the cough.  
Particularly important questions include: 
• Is the cough acute or chronic? Factors influencing it? 
• Were there associated symptoms suggestive of a respiratory infection? 
• Is it seasonal or associated with wheezing? Dyspnea? 
• Is there nasal discharge or gastroesophageal reflux (heartburn)? 
• Is there fever or sputum?  If sputum is present, what is its character? 
• Does the patient have any associated disease or risk factors for disease (e.g. Cigarette 
smoking, risk for HIV, environmental exposures eg. pollution)? 
 The general physical exam  may point to a non-pulmonary cause of cough, such as heart 
failure, malignancy, or AIDS. 
• Auscultation of the chest may demonstrate: inspiratory stridor (indicative of upper airway 
disease), respiratory wheezing (indicating lower airway disease) or inspiratory crepitations (process involving the pulmonary parenchyma, such as interstitial lung disease, pneumonia, tuberculosis or pulmonary edema). 
Complications of cough: may precipitate syncope, fracture of the ribs etc 
Definitive treatment of cough  depends on determining the underlying cause and then initiating 
specific therapy. Different cough suppressants can be used in addition to specific therapy to decrease the duration of cough.  
Chest Discomfort/pain


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Definitive treatment of cough  depends on determining the underlying cause and then initiating 
specific therapy. Different cough suppressants can be used in addition to specific therapy to decrease the duration of cough.  
Chest Discomfort/pain 
Chest discomfort is one of the most frequent complaint for which patients seek medical attention. There is little relation between the severity of chest discomfort and the gravity of its cause. 
 
Causes of Chest Discomfort Pleuritic chest pain  – It is usually a brief, sharp, knifelike pain that is precipitated by inspiration 
or coughing. It is very common and generally results from inflammation of parietal pleura. Typical example is pneumonia.


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Internal Medicine 
 
 161Myocardial ischemia:   
• Angina pectoris is usually described as a heaviness, pressure, squeezing or sensation of 
strangling or constriction in the chest, but it also may be described as an aching or 
burning pain or even as indigestion.  
• Typically, angina pectoris develops during emotion or physical exertion. The pain 
typically resolves within 5-30 minutes. The pain is   more prolonged in myocardial 
infarction (MI). 
Chest pain due to pericarditis: -  
• The pain arises from parietal pericardium and adjacent parietal pleura. Infectious 
diseases and inflammation are the main causes of pain.  
• Pericarditis can cause pain in several locations like the tip of the shoulder and the neck 
more often the pain is located in the anterior part of the chest and is relieved by bending forward; but pain may also be in the upper part of abdomen or at corresponding region of the back.  
• Pericardial pain commonly has a pleuritic component; i.e. it is aggravated by cough and 
deep inspiration, because of pleural irritation. Sometimes there may be steady substernal discomfort that mimics acute myocardial infarction. 
Vascular causes of chest pain:  –  
• Pain due to acute dissection of the aorta usually begins abruptly, reaches an extremely 
sever peak rapidly.  
• It is felt in the center of the chest and/ or the back, lasts for hours and requires unusually


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Vascular causes of chest pain:  –  
• Pain due to acute dissection of the aorta usually begins abruptly, reaches an extremely 
sever peak rapidly.  
• It is felt in the center of the chest and/ or the back, lasts for hours and requires unusually 
large amounts of analgesics for relief of pain. Pain is not aggravated by changes in position or respiration. Usually there is associated low blood pressure. 
Chest pain due to pulmonary embolism: -  
• The pain resulting from pulmonary embolism may resemble that of acute MI, because in 
massive embolism pain is located substernally.  
• In patients with smaller emboli, pain is located more laterally, is pleuritic in nature, and 
sometimes is associated with hemoptysis.  
Gastrointestinal causes of chest discomfort: -  
• Esophageal pain commonly presents as a deep thoracic burning pain, which is the 
hallmark of acid-induced pain. Esophageal spasm has acute pain that may be indistinguishable from MI.


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Internal Medicine 
 
 162• Other diseases like PUD, biliary disease, pancreatitis, and cholecystits may present as 
chest discomfort or pain. 
 
Emotional cause of chest pain  - Usually, the discomfort is experienced as a sense of 
"tightness", sometimes called "aching".  It is confused with myocardial   ischemia. Ordinarily, it 
lasts for half an hour or more.  There is usually associated emotional strain or fatigue. 
 
Hemoptysis; is defined as expectoration of blood from the respiratory tract, which could be 
scanty and mixed with sputum or large amount of frank blood. Massive hemoptysis is defined as 
expectoration of >600 ml of blood in 24 hours. Hemoptysis can have different causes. Some of the causes are: 
1) Tracheobronchial source 
• Neoplasm    
• Bronchitis , Bronchiectasis 
• Foreign body   
• Airway trauma 
2) Pulmonary parenchymal source 
• Pneumonia, tuberculosis 
• Lung abscess 
• Lung congestion 
3) Primary vascular source 
• Mitral stenosis  
• Pulmonary embolism 
4)  Sources other than the lower respiratory tract 
• Upper airway (nasopharyngeal) bleeding 
• GI bleeding 
 Tuberculosis and pneumonia are the commonest causes of hemoptysis in developing 
countries. But bronchitis and bronchogenic ca are common in developed regions. Up to 
30% of patients may not have identifiable cause even after complete investigation.


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Internal Medicine 
 
 163Approach to the patient with hemoptysis 
History:   
• Blood streaked, mucopurulent sputum suggests bronchitis.  
• If it is associated with fever pneumonia should be suspected.  
• If sputum smell is putrid, lung abscess is likely.  
• Hemoptysis that occurs suddenly with  chest pain and dyspnea suggests pulmonary 
embolism.  
• Previous history of renal disease, SLE, or malignancy is all important for suggesting 
DDX.   
Physical examination : may reveal 
• Pleural friction rub, Localized or diffuse crackles Æ lung paranchymal damage.  
• Wheezing ÆAirflow obstruction (chronic bronchitis).  
• Cardiac examination may reveal pulmonary hypertension, mitral stenosis or heart failure 
Diagnostic evaluation  :  
• Chest X-ray which may show mass lesion suggestive of bronchiectasis, pneumonia.  
• Sputum examination for Gm and AFB stain. 
• CBC, coagulation profile, urine analysis,  
• BUN and creatinine and  
• If possible bronchoscopy is useful in localizing and managing the site of bleeding 
Treatment : the rapidity of bleeding and its effects on gas exchange determine the urgency of 
management. 
• If there is only blood streaking sputum with mid hemoptysis, first establish diagnosis. Put 
the patient at rest and Giving cough suppressant may help to subside the bleeding  
• If massive hemoptysis urgent treatment is necessary to stop bleeding and patients


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the patient at rest and Giving cough suppressant may help to subside the bleeding  
• If massive hemoptysis urgent treatment is necessary to stop bleeding and patients 
should be referred to a hospital. Massive hemoptysis may require endotracheal intubation and mechanical ventilation. If the bleeding side is known position the patient 
so that the source of bleeding is placed in dependent position to protect suffocation of 
the unaffected lung.


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Internal Medicine 
 
 164   2. Upper Respiratory Tract Infections  
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define upper respiratory infections 
2. List the etiologies of upper respiratory infections  3. Describe the mode of transmission of upper respiratory infections  4. Explain the epidemiology of upper respiratory infections   
5. Describe the pathophysiology of upper respiratory infections  
6. Identify the clinical manifestations of upper respiratory infections  7. Describe the most commonly used method of diagnosis of upper respiratory infections  8. Make a diagnosis of upper respiratory infections  9. Give supportive therapy at the primary care level 
10. Design appropriate methods of prevention of upper respiratory infections  
 
2.1 The Common Cold (Acute coryza) 
It is an acute, usually afebrile, viral infection of the respiratory tract, with inflammation in any or 
all airways, including the nose, paranasal sinuses, throat, larynx, and often trachea and bronchi. 
Etiology  - Many viruses cause the common cold including Picornavirus (rhinoVirus), Influenza 
and parainfluenza viruses, Respiratory syncytial virus, Corona- and adeno virus group.  Infections may be facilitated by excessive fatigue, emotional distress, or allergic naso 
pharyngeal disorders and during the mid-phase of the menstrual cycle. 
Symptoms and signs  - onset is abrupt after a short (1 to 3 days) incubation period.  Illness


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pharyngeal disorders and during the mid-phase of the menstrual cycle. 
Symptoms and signs  - onset is abrupt after a short (1 to 3 days) incubation period.  Illness 
generally begins with nasal or throat discomfort followed by sneezing, rhinorrhea, and malaise.  
The disease is afebrile and pharyngitis is usually present. Nasal secretions, watery and profuse 
during 1
st or 2nd day of symptoms, become more mucous and purulent. Hacking cough 
associated with scanty sputum often lasts into the 2nd week. When no complications occur, 
symptoms normally resolve in 4 to 10 days. 
Diagnosis - Symptoms and signs are nonspecific. Bacterial infections, allergic rhinorrhea, and 
other disorders also cause upper respiratory tract symptoms at onset.  Differentiation depends 
on the season and the course of the Symptoms. Fever more severe symptoms usual indicate influenza.


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Internal Medicine 
 
 165Prophylaxis - Immunity is virus type-specific.  Because of numerous types and strains of known 
viruses causing URT, it is difficult to produce a useful vaccine. 
Treatment 
• A Warm, comfortable environment and measures to prevent direct spread of infection 
are recommended for all persons.  
• Antipyretics and analgesics are given to control fever and malign.  
• Nasal decongestants are used if patients have nasal congestion. Steam inhalation is 
also used in nasal congestions to help mobilize secretions and relieve chest tightness. 
• Treat persistent cough with cough suppressants. 
• Ascorbic acid or high doses of citrus juices have no scientific benefit. 
• Antibiotics are not effective against viruses, so they are not recommended unless a 
specific bacterial complication develops. 
2.2 Influenza 
Influenza is a specific acute viral respirator y disease characterized by fever, coryza, 
cough, headache, and malaise and inflamed re spiratory mucous membranes. It usually 
occurs as an epidemic in rainy seasons.  
Etiology : It is caused by influenza viruses, which are classified as orthomyxovirus.  There are 
types A, B & C 
Epidemiology :  
• Influenza type A virus is the most frequent single cause of clinical influenza; other 
causes include influenza B, paramyxovirus, pneumonia-virus and (rarely in adults) rhino and echoviruses.  
• Spread is by person - to - person contact; airborne droplets spray infects people and


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causes include influenza B, paramyxovirus, pneumonia-virus and (rarely in adults) rhino and echoviruses.  
• Spread is by person - to - person contact; airborne droplets spray infects people and 
contaminates articles with viruses that can transmit infection.  
• Persons of all ages are affected, but prevalence is highest in school children.  
• Persons at highest risk of developing severe disease are those with chronic pulmonary 
disease and those with valvular heart disease, pregnant women, the elderly, the very young and the bed ridden. 
• Infection with influenza A is associated with significant morbidity and mortality.  
Symptoms and Signs:  
• During the 48-hour incubation period, transient asymptomatic viremia occurs.  
• Then there is chills and fever up to 39 to 39.5 
0c developing over 24 hr.


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Internal Medicine 
 
 166• Generalized aches and pains (most pronounced in the back and legs) appear early.  
• Headache is prominent. 
• Respiratory tract symptoms may be mild initially but become prominent later.  
• The soft palate, posterior hard palate, and tonsillar pillars may be reddened. Usually 
after 2 to 3 days, acute symptoms rapidly subside and fever ends.  
• Weakness, sweating and fatigue may persist for several days or occasionally for weeks.  
• In severe cases, hemorrhagic bronchitis and pneumonia are frequent and can develop 
within hours.  
• Fulminant, fatal viral pneumonia may occur and death may follow as soon as 48 hr after 
onset. This is usually during a pandemic caused by a new virus or in high-risk people. 
Complication:   
• Secondary bacterial infection of the bronchus and pneumonia. With pneumonia, cough 
worsens and purulent or bloody sputum is produced.  Crepitations can be detected over 
affected segment. 
• Encephalitis, myocarditis, and myoglobinuria may occur as complications of influenza, 
usually during convalescence.  
Diagnosis:   
• Clinical influenza is a common experienc e and can easily diagnosed. Chest examination 
is usually normal in mild cases and may look like common cold. Pulmonary symptoms may be similar to those of bronchitis or atypical pneumonia. Fever and severe constitutional symptoms differentiate influenza from the common cold 
• The leukocyte count is normal in uncomplicated cases.


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• The leukocyte count is normal in uncomplicated cases.  
• Isolating the virus can make specific diagnosis of influenza. Serologic tests are also 
used. 
 
Prognosis:  Recovery is the rule in uncomplicated influenza. Viral pneumonia may cause death. 
Prophylaxis:  Vaccines that include the prevalent strains of influenza viruses effectively reduce 
the incidence of infection. Amantadine 100mg orally bid (for adults) can be used prophylactically 
against influenza A. 
 
Treatment: 
• Amantadine has a beneficial effect on fever and respiratory symptoms if given early in 
uncomplicated influenza.


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Internal Medicine 
 
 167• Basic treatment for most patients is symptomatic with bed rest, antipyretics, nasal 
decongestants & steam inhalation.  
 
2.3 Acute Bronchitis 
It is an acute inflammation of the tracheobronchial tree, generally self-limiting and with eventual 
complete healing and return to normal function. It could be caused by infections or irritants.  
Etiology:   
• Acute infectious bronchitis  is often part an acute upper respiratory tract infection (URTI). 
It may develop after a common cold or other viral infection of the nasopharynx, throat or 
tracheobronchial tree, often with secondary bacterial infection.  
• Acute irritative bronchitis  is caused by various mineral and vegetable dusts, volatile 
solvents, tobacco or other smoke.  
Symptoms and signs :  
• Acute infectious bronchitis is often preceded by symptoms of URTI, coryza, malaise, 
chilliness, slight fever, back and muscle pain and sore throat.  
• The onset of cough usually signals onset of bronchitis. Cough is initially dry but 
progresses to be productive.  Purulent sputum suggests bacterial superinfection.  
• In uncomplicated case, fever to 38.80c may be present upto 3-5 days, following which 
acute symptoms subside (though cough may continue for several weeks).   
• Persistent fever may suggest complication like pneumonia.  
• Pulmonary signs are few in uncomplicated acute bronchitis. Scattered rhonchi and


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acute symptoms subside (though cough may continue for several weeks).   
• Persistent fever may suggest complication like pneumonia.  
• Pulmonary signs are few in uncomplicated acute bronchitis. Scattered rhonchi and 
wheezes may be heard, as well as occasional crepitations at the bases.  Serious complications are usually seen only in patients with an underlying chronic respiratory 
disorder. 
Diagnosis :  
• It is usually based on the symptoms and signs.  
• Chest X-ray is taken only to rule out serious conditions like pneumonia.  
• In persons who do not respond to antibio tics, gram stain and sputum culture is 
necessary. 
Treatment : 
• General Management  
• Rest until fever subsides.  
• Oral fluids should be taken more:- this  facilitates sputum expectoration.


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Internal Medicine 
 
 168• Antipyretics and analgesics (like aspirin or par acetamol) are given if there is fever or 
myalgia.  
• Symptomatic treatment of cough may shorten the duration of cough.                    
• Specific Treatment  
• Antibiotics should be given when purulent sputum and persistent fever are present.                        
TTC or ampicillin can be given for 7 – 10 days.


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Internal Medicine 
 
 1693. Pneumonia 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define Pneumonia  2. List the etiologic agents of Pneumonia occurring in different settings  3. Describe the mode of transmission of Pneumonia    
4. Understand the epidemiology of Pneumonia.  
5. Describe the pathophysiology of Pneumonia  6. Identify the clinical manifestations of Pneumonia    7. List the complications of  Pneumonia  8. Describe the most commonly investigations for the diagnosis of Pneumonia   
9. Make an accurate diagnosis of Pneumonia   
10. Manage most cases of Pneumonia  appropriately  11. Refer complicated  cases of Pneumonia  
 
Pneumonia is an acute infection of lung parenchyma  including alveolar spaces and interstitial 
tissue. 
• Involvement may be confined to an entire lobe -Lobar pneumonia 
• A segment of a lobe-Segmental or lobular pneumonia  
• Alveoli contiguous to bronchi -  Bronchopneumonia  
• Interstitial tissue - Interstitial pneumonia  
These distinctions are generally based on x-ray observations. Predisposing factors for pneumonia  include:- 
• Preceding respiratory viral infections 
• Alcoholism 
• Cigarette smoking 
• Underlying diseases such as Heart failure, COPD  
• Age extremes 
• Immunosuppressive therapy and disorders 
• Decreased consciousness, comma , seizure etc  
• Surgery and aspiration of secretions


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Internal Medicine 
 
 170The usual mechanisms to develop pneumonia are either to inhale droplets small enough to 
reach the alveoli, or to aspirate secretions from the upper airways.  Other means include 
hematogenous dissemination, via the lymphatics, or directly from contiguous infections. 
Microbial Pathogen that cause Pneumonia: depend on the setting in which pneumonia is 
acquired 
1. Community-acquired  pneumonia 
o Streptococcus pneumoniae ( pneumococcal pneumonia ) commonest cause  
o Mycoplasma pneumoniae  
o Chlamydia pneumoniae 
o Haemophilus influenza  
o Oral anaerobic bacteria  
o Staphylococcus aureus  
o Legionella pneumophila 
o Mycobacterium tuberculosis 
2. Aspiration pneumonia: This occurs when large amount of oropharyngeal or gastric 
contents are aspirated into the lower respiratory tract. Aspiration occurs more frequently 
in patients with: 
• Decreased level of consciousness (alcoholism, seizure, strokes or general 
anesthesia)  
• Neurologic dysfunction of oropharynx and swallowing disorders.  
• People with periodontal disease are affected more.  
Common Etiologic agents of Aspiration pneumonia: It is often polymicrobial 
o Anerobic organisms in the oral cavity  
o Enterobateriacae 
o S. pneumoniae 
o S.aureus 
 Patients present with cough and foul smelling sputum. The cough may be chronic


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Common Etiologic agents of Aspiration pneumonia: It is often polymicrobial 
o Anerobic organisms in the oral cavity  
o Enterobateriacae 
o S. pneumoniae 
o S.aureus 
 Patients present with cough and foul smelling sputum. The cough may be chronic 
forming lung abscess and may resemble TB. There will be signs of cavity on physical exam and CXR. It is treated with crystalline penicillin and metronidazole IV for several 
weeks if lung abscess develops.   
3. Community acquired Pneumonia in Immunocompromised hosts: 
Immunocompromised hosts such as transplant recipients, HIV infected patients, and 
patients on Chemotherapy etc. are prone to develop pneumonia. The etiologic agents are


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Internal Medicine 
 
 171o Common bacterial causes of CAP : St. Pnumoniae , H.influenzae, 
Mycoplasma  
o Gram negative organisms : enterobacteriaceae 
o Funguses such as Pneumocystis carinii ( jerovecii ), C. neoformans , 
Histoplasmosis , Aspergillus 
o Mycobaterium tuberculosis  
o Viruses : HSV , CMV 
4. Hospital-acquired pneumonia: a patient is said to have hospital acquired pneumonia if the 
symptoms begin 48 hours after hospital admission and not incubating at the time of 
admission. Common organisms that cause hospital-acquired pneumonia are:- 
o Gram-negative bacilli including  Pseudomonas aeroginosa , K.pneumoniae  
o Staphylococcus aureus ( may ne drug resistant ) 
o Oral anaerobes. 
Clinical Presentation of community acquired pneumonia 
• Community acquired pneumonia can have typical or atypical presentations. This 
classification is less distinct but it may have diagnostic value. More commonly patients have “typical” presentation and it is mainly caused by S.Pneumonae .  But other 
organisms like H. influenza  and oral flora can be causes.  
• Pneumonia is often preceded by a URTI. 
The “typical” Community acquired pneumonia:  is characterized by:- 
• Sudden onset with a single shaking chill. This is followed by high grade fever (upto 
40.5
0c ) 
• Cough productive of purulent, blood streaked or rusty sputum 
• Pleurtic chest pain on the involved side worsened during inspiration and coughing  
• Daphnia ( shortness of Breath )


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40.5
0c ) 
• Cough productive of purulent, blood streaked or rusty sputum 
• Pleurtic chest pain on the involved side worsened during inspiration and coughing  
• Daphnia ( shortness of Breath ) 
• Headache , myalgia , arthralgia and fatigue   
Physical findings  
• The Patient will have tachycardia (pulse 100 to 140/min)and  tachypnea (RR > 20/min).  
• There will be pulmonary signs of consolidation (lobar pneumonia), which are  
 Increased tactile fremitus and vocal fremitus , dullness on  percussion  
 Bronchial breath sound, egophony, wispering pectoriloquy, crackles and pleural 
friction rub.


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 172The “atypical” pneumonia present with: 
• Atypical” pneumonia is usually caused by M. pneumoniae , C.pneumoniae , oral 
anaerobes  and P. carinii (usually in HIV patients), as well as S. Pneumoniae. Some 
viruses like influenza virus, Varicella zoster virus and cytomegalovirus may cause 
“atypical” pneumonia. Tuberculosis could also present in this form.   
• More gradual onset of symptoms, dry cough, shortness of breath. 
• Prominence of systemic symptoms like headache, malign, fatigue, nausea, vomiting and 
diarrhea.  
• Chest findings on physical examination are minimal even though X-ray changes are 
marked.  
Complications:   
• Local : Parapneumonic effusion or pus in the pleural space (empyema).  
• Distant complications : include septic arthritis and meningitis. Pneumonia can progress 
to sepsis, sometimes with septic shock.   
Laboratory findings:  
1) CBC : leucocytosis with increased neutrophils is seen in most cases.  
2) Gram stains from sputum  may show a predominant pathogen like Gram-positive 
diplococci. 
3) Chest x-ray shows  pulmonary infiltrates or homogeneous opacity indicating lobar 
pneumonia. Very early in the course, it may be normal.  
Diagnosis: 
• Pneumonia should be suspected in patients with acute febrile illness, associated with 
chest pain, dyspnea and cough.  
• Presumptive diagnosis can be made from hi story, changes on chest x-ray, blood and


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Diagnosis: 
• Pneumonia should be suspected in patients with acute febrile illness, associated with 
chest pain, dyspnea and cough.  
• Presumptive diagnosis can be made from hi story, changes on chest x-ray, blood and 
sputum culture and sputum Gram stains. An absolute diagnosis requires demonstration 
of S. pneumoniae or other etiologic agents in pleural fluid, blood, lung or transtracheal 
aspirate. 
Prognosis:  The overall mortality rate is low, if treated early.  Factors that herald a poor 
prognosis include the following:-  
• Extremes of age, especially < 1 yr or >60yrs,  
• Positive blood culture 
• Involvement of more than one lobe  
• Peripheral WBC < 5000/ml


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Internal Medicine 
 
 173• Presence of associated diseases (e.g. cirrhosis, CHF, immunosuppression) 
• Development of extrapulmonary complicat ions like meningitis and endocarditis. 
Management: 
Mild form of CAP 
Patients with uncomplicated “typical” pneumonia can be treated at OPD   
• Amoxicillin 500 mg PO TID or  Ampicillin 500 mg PO QID for 7 to 10 days  OR.  
• Procaine penicillin 600,000 IU IM every 12 hrs. 
If “atypical” pneumonia is suspected,   
• Erythromycin 500 mg PO QID for 7-10 days or Doxycycline100 mg PO BID  
Supportive Therapy : Patients should also get bed rest, adequate fluids and analgesics for 
pleuritic chest pain and fever.  Response  – In mildly ill patients who are treated early, fever subsides in 24 to 48 hrs. Others 
may require 4 days to respond. 
• If Patients are allergic to penicillins, cephalosporins, erythromycin, and clindamycin can 
be given. TTC are less predictable and should not be used in seriously ill patients.  
• If a patient does not improve, the following factors should be considered:  
 Wrong etiologic diagnosis 
 Adverse drug reaction 
 Far advanced case or superinfection 
 Inadequate host defenses due to associated condition 
 Non-compliance to the drug regimen in outpatients 
 Antibiotic resistance of the strain and  
 Complications like empyema requiring drainage, or metastatic foci of infection 
requiring higher doses (e.g. meningitis, endocarditis or septic arthritis).


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Antibiotic resistance of the strain and  
 Complications like empyema requiring drainage, or metastatic foci of infection 
requiring higher doses (e.g. meningitis, endocarditis or septic arthritis). 
 
• Persistent cough and infiltration on chest x-ray for more than 6 weeks after therapy 
suggests possibility of an underlying bronchogenic neoplasm or tuberculosis. 
Severe forms of CAP 
If patients are seriously ill they shoul d be admitted and treated as inpatient. 
Criteria for Hospitalization of patients with Pneumonia are:  
1) Respiratory rate of  >28/min ( Tachypnea ) tachycardia >140/min 
2) Systolic blood pressure <90mm Hg (hypotension 
3) Hypoxemia (arterial PO 2 < 60mm Hg) while breathing room air or O 2 saturation < 90 %


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Internal Medicine 
 
 1744) New onset of confusion or impaired level of consciousness . 
5) Unstable /Significant co-morbidity (e.g. Heart faiure , uncontrolled diabetes, Chronic 
Renal insufficiency ,alcoholism , immunosuppresion ) 
6) Multilobar pneumonia  is Hypoxemia is present 7) Pleural effusion and with analysis showing characteristics of  complication 
 Other conditions in which inpatient management may be advisable  
• Elderly patient >65 yrs of age 
• Leukopenia <5000 WBC/ml 
• Pneumonia caused by St. aureus or Gram negative bacilli 
• Suppurative complications e.g. empyema, arthritis, meningitis, endocarditis 
• Failure of Outpatient treatment  
• Inability to take oral medication or persistent vomiting 
Management of CAP 
Supportive management   
• Ensure adequate oxygenation to patients with cyanosis, significant hypoxemia, sever 
dyspnea, circulatory disturbance or delirium.  
• Patients should be well hydrated 
• Fever and pain should be managed 
Antibiotic Therapy 
• Admitted patients should be started on antibiotics empirically  
• High dose of crystalline penicillin 3-4 million IU IV every 4-6 hours  
• Alternatives are Ceftriaxone 1gm IV daily or  2X /day or Ampicillin 500 mg IV QID Or 
Cefotaxime 
• In severely ill patients erythromycin or a flouroquinolone can be added. 
• Choice of Antibiotics may be modified based on culture and sensitivity results, if 
available.


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Cefotaxime 
• In severely ill patients erythromycin or a flouroquinolone can be added. 
• Choice of Antibiotics may be modified based on culture and sensitivity results, if 
available.   
• If the patient improves, IV treatment can be changed to oral after 3-4 days to complete a   
7-10 days course. 
Prevention 
• Cessation of smoking and alcoholism  
• Vaccines : Influenza an Pneumococcal vaccines ( available in developed countries )


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Internal Medicine 
 
 175Pneumonia in the Compromised Host 
• Immunocompromised hosts include patients with AIDS, acute leukemia, cancer 
chemotherapy, diabetes, sickle cell disease, Hodgkin's disease, and corticosteroid 
treatment. 
• The potential pathogens in compromised hosts are many, as it has been stated above.  
• Pathogens like Streptococcus pneumonia, which cause pneumonia in immunocompetent 
people, are still responsible for the majority of pneumonia in compromised patients.  
Diagnosis:   
• Sputum examination and culture are used but they are not specific.   
• Transtracheal aspirate, bronchoscopy and biopsy have high accuracy; however these 
are done only in specialized hospitals.  
• High index of suspicion from clinical pr esentation is important to diagnose pneumonia in 
immunocompromised hosts.  
Treatment :  
• Acutely ill patients who have suspected bacterial infections are often treated with 
antibiotics selected on the basis of probabilities and the findings with sputum gram stain 
and culture. Later treatment is adjusted on the basis of more definitive diagnostic 
evaluation.  
• In patients with HIV infection and “atypical” pneumonia, PCP should be considered and 
treated with high dose of co-trimoxazole ( 3 tablets every 6 hours for 3 weeks) if clinically considered. 
 
Hospital acquired Pneumonia (HAP)  
The definition of HAP includes the presence of a new or progressive infiltrates of Chest X-ray ,  
plus at least two of the following


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Hospital acquired Pneumonia (HAP)  
The definition of HAP includes the presence of a new or progressive infiltrates of Chest X-ray ,  
plus at least two of the following  
• Fever >37.8 oC 
•  Leukocytosis > 10,000/mm3 
• Production of purulent sputum 
Other findings: dyspnea, hypoxemia and chest pain 
Treatment  
Antibiotics: Should be initiated empirically which latter on may be modified based on culture and 
sensitivity result.


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Internal Medicine 
 
 176The selection of drugs should be guided by an understanding of local patterns of antibiotics 
resistance  Antibiotics should cover at least gram negatives and S. aureus  
• Ceftriaxone 1gm IV daily or BID plus Cloxacillin or meticillin Or 
• Levofloxacin 500 mg IV /day  
When resistant organisms are suspected  
• Cefotaxime 750 mg IV TID plus Vancomycin 1gm IV BID  
Prevention 
• Strict hand washing protocols by health care providers  
• Extubate an entubated patient as soon as the patient is stable  
• Remove NG tubes when the patient is stable 
• Proper aseptic handling of IV lines 
 
References: 
4) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, 
Pneumonia,      pages 1528-1540


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Internal Medicine 
 
 1774. Bronchial Asthma 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define bronchial asthma  2. Understand the epidemiology of bronchial asthma. 3. Describe the etiology of bronchial asthma.     
4. Understand the pathophysiology of bronchial asthma .   
5. Identify the clinical manifestations of bronchial asthma.     6. List the signs of severity of bronchial asthma.   7. Make an accurate diagnosis of bronchial asthma.   8. Manage most cases of bronchial asthma.  
9. Refer complicated cases of bronchial asthma.   
 
Definition : Bronchial asthma is defined as chronic inflammatory disease of airways 
characterized by increased responsiveness of t he tracheobronchial tree to a multiplicity of 
stimuli. It is associated with widespread airway obstruction that is reversible (but not completely in some patients), either spontaneously or with treatment 
Epidemiology:   
• Asthma is a common disease The prevalence of asthma is rising in different parts of the 
world.  
• It can occur at any age; but it usually starts early in life. About 50% of patients develop 
asthma before the age of 10 and another 35% before the age of 40.  
• Males are affected twice as common as females in early life; this sex difference 
equalizes by age 30. Most cases of asthma are associated with personal or family history of allergic disease such as eczema, rhinitis and urticaria.


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• Males are affected twice as common as females in early life; this sex difference 
equalizes by age 30. Most cases of asthma are associated with personal or family history of allergic disease such as eczema, rhinitis and urticaria.  
Etiology Asthma is a heterogeneous disease and genetic ( atopic )  and environmental factors 
such as viruses , occupational exposure and allegens contribute to its initiation and continuance 
. Atopy is the single most important risk factor for asthma 
 Asthma can be classified in to 3 types Allergic (atopic) , Nonallergic ( idiosyncratic ) and Mixed


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Internal Medicine 
 
 178Table II-4-1 Comparison of the two major types of Asthma  
 
 Allergic 
(Atopic) 
asthma   Non Allergic 
(idiosyncratic )  
Age of onset  Early in life  Late in life 
Family or personal history of 
allergy: rhinitis , urticaria eczemaPresent  Absent  
Skin test with intradermal injection of allergens  Positive wheal-and -flare skin test Negative skin test 
Serum IgE level  Elevated  Normal 
Response to inhalation provocative test positive  Negative  
 
Many patients have disease that doesn’t fit into either of the 2 categories, but instead fall into a 
mixed group with some features from each group. In general asthma which has its onset early in life tends to have strong allergic component, where as  asthma that develops late in life tends to 
be nonallergic or to have mixed etiology.  
Factors important for the genesis of asthma 
• Genetic factors  
o Asthma has strong genetic predisposition or familial tendency 
Stimuli that incite Asthma  
• Allergens :  Seasonal allergens such as pollen green 
 Non seasonal animal feathers , dust mites , molds  
• Pharmacologic stimuli : Aspirin , Tatrazin (coloring agent), Beta blockers such as 
Propranolol etc 
• Environmental and air pollution : in industrial and heavily populated areas. The 
common pollutants are ozone, nitrogen dioxide and sulfur dioxide. 
• Infections : Respiratory infections are the most common of the stimuli that evoke acute


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• Environmental and air pollution : in industrial and heavily populated areas. The 
common pollutants are ozone, nitrogen dioxide and sulfur dioxide. 
• Infections : Respiratory infections are the most common of the stimuli that evoke acute 
exacerbation of asthma. Respiratory viruses are the major factors.


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Internal Medicine 
 
 179• Exercise: is  a very common precipitant of acute episodes of asthma  
• Emotional stress: psychological factors can worsen or ameliorate asthma  
Pathophysiology:  
Asthma results from a state of persistent subacute inflammation of the airways.  The airways 
obstruction in asthma is due to a combination of factors. The cells thought to play important part 
in the inflammatory response are mast cells, eosinophils, lymphocytes and airway epithelial cells. These cells release inflammatory mediators which may result  
• Bronchoconstriction  (spasm of airways smooth muscles ) 
• Vascular congestion and edema of airways mucosa 
• Increased mucus production  
• Injury and desquamation of the airways epi thelium and impaired muco-ciliary transport  
Symptom and Signs 
• The symptoms of each asthmatic patient differ greatly in frequency and degree.   
• Some asthmatics are symptom free, with an occasional episode that is mild and brief; 
others have mild coughing and wheezing much of the time, punctuated by severe exacerbations of symptoms following exposure to known allergens, viral infection, exercise etc. Psychological factors particularly those associated with crying, screaming 
or hard laughing may precipitate symptoms. 
• An attack usually begins acutely with paroxysms of wheezing, coughing, and shortness 
of breath, or insidiously with slowly increasing manifestations of respiratory distress.


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or hard laughing may precipitate symptoms. 
• An attack usually begins acutely with paroxysms of wheezing, coughing, and shortness 
of breath, or insidiously with slowly increasing manifestations of respiratory distress.  
• The asthmatic first notices dyspnea, tachypnea, cough and tightness in the chest and 
may even notice audible wheezes.  
On physical examination  –  
• Varying degrees of respiratory distress tachypnea, tachycardia, and audible wheezes 
are often present.  
• Dehydration may be present because of sweating and tachypnea.  
• Chest examination shows a prolonged expira tory phase with relatively high pitched 
wheezes throughout inspiration and most of expiration.  
• In more severe episodes, patients may be unable to speak more than a few words 
without stopping for breath.  
• Cyanosis is usually a late sign of hypoxia.  
• Confusion and lethargy may indicate the onset of progressive respiratory failure.


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Internal Medicine 
 
 180• Less wheezing (silent chest) might indicate mucous plug or patient fatigue with less 
airflow. And it is a sign of impending respiratory failure. 
• The presence, absence, or prominence of wheezes does not correlate precisely with the 
severity of the attack.   
• The most reliable clinical signs include the degree of dyspnea at rest, cyanosis, difficulty 
in speaking and use of accessory muscles of respiration.  This is confirmed by arterial 
blood gas analysis. 
• Between acute attacks, breath sounds may be normal during quiet respiration. However, 
low grade wheezing maybe heard at any time in some patients, even when they claim to be completely asymptomatic. 
Complications during an Acute Attack of Asthma 
• Pneumothorax : It may present as sudden worsening of respiratory distress, 
accompanied by sharp chest pain and on examinat ion, hyperresonant lung with a shift of 
mediastinum. Chest x-ray confirms the diagnosis.  
• Mediastinal and subcutaneous emphysema  due to alveolar rupture 
• Atelectasis due to obstruction 
• Dilated right heart chambers  (Corpulmonale) : from ch ronic hypoxemia and pulmonary 
hypertension  
• Respiratory failure  
 
Laboratory Findings 
• Eosinophilia  is a common finding.  
• Sputum  is tenacious, rubbery and whitish or may be yellowish; eosinophils are present 
in the sputum. 
• Chest x-ray:  varies from normal to hyperinflation.  Atelectasis and pneumothorax may 
be seen in complicated cases.


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• Sputum  is tenacious, rubbery and whitish or may be yellowish; eosinophils are present 
in the sputum. 
• Chest x-ray:  varies from normal to hyperinflation.  Atelectasis and pneumothorax may 
be seen in complicated cases.  
• Pulmonary function tests  are valuable in differential diagnosis and in known patients to 
assess the degree of airways obstruction. 
 
Diagnosis 
Asthma should be considered in anyone who wheezes. A family history of allergy, rhinitis or 
asthma can be elicited in most asthmatics.


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Internal Medicine 
 
 181Differential diagnosis includes :  
• In children : foreign body obstruction, viral URTI involving the epiglottis (croup), and 
bronchiolitis (RSV infection);  
• In adults : COPD, heart failure, endobronchial TB, and malignancies. Physical 
examination should search for heart failure and signs of chronic hypoxemia (clubbing). 
Unilateral wheezes usually indicate obstruction by foreign bodies or tumor. 
Prevention of attacks 
• The role of environmental factors (e.g. animal dander, dust, airborne moulds, and 
pollens) in acute exacerbations is clear. Allergens that can be controlled by avoidance 
should be eliminated. 
• Nonspecific exacerbating factors (e.g. cigarette smoke, odors, irritant fumes, and change 
in temperature, atmospheric pressure, and humidity) should also be investigated and avoided if possible. 
 
Treatment 
General principles 
• Assessing the severity of the attack is paramount in deciding management 
• Bronchodilators should be used in orderly progression 
• Decide when to start corticosteroids 
Treatment of the Acute Attack 
Mild acute asthmatic attack: Most patients can be managed as an outpatient 
• Salbutamol aerosol (Ventolin®) two puffs every 20 minutes for three doses is the 1st line 
of treatment.  
• Adrenaline 1:1000 can be given in doses up to a maximum of 0.2 ml in children and 0.3 
ml in adults, repeated once or twice in 20 to 30 min (if there is no hypertension or any other contra indication).


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of treatment.  
• Adrenaline 1:1000 can be given in doses up to a maximum of 0.2 ml in children and 0.3 
ml in adults, repeated once or twice in 20 to 30 min (if there is no hypertension or any other contra indication).  
• If the initial treatment fails, Aminophylline 250 mg IV diluted in dextrose in water should 
be given slowly over 10-15 minutes, once.  
• If the patient does not respond to one dose of aminophylline IV, then the patient is 
declared to have severe asthma, and should be admitted and managed as in-patient.


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Internal Medicine 
 
 182In patient management  
Patients who are diagnosed to have severe and life threatening asthma need in patient 
management. Some may even need admission to ICU. 
 Signs of Severity of acute asthmatic attack 
1) Tachycardia HR > 120/min , Tachypnea RR.30 min 
2) Presence of pulsus paradoxus 3) Use of accessory muscles of  respiration 
4) Cyanosis 
5) Altered state of consciousness ( confusion , drowsiness ) 6) Silent chest  7) Paradoxical movement of the chest and the abdomen  8) Presence of complications : Pneumothorax , atelectasis 
9) Unable to finish a sentence with single breath ( frequent interruption of speech to take a 
breath ) 
10) Laboratory parameters 
o PEFR < 50 % or FEV
1 < 60 % 
o PaO 2   < 60mmof Hg or SaO 2  < 90 % 
o PaCO 2 > 42 mmHg 
 
Specific drug Treatment  
• Aminoplylline in doses of 1mg/kg/hr in a continuous IV infusion should be given.  
• Corticosteroids  should also be given IV e.g. Hydrocortisone 4mg/kg IV every 4 hrs. 
When the patient improves the hydrocorti sone be changed to Prednisolone PO and the 
dosage should be tapered up on discharge. 
• Patients who do not respond to aggressive drug therapy are candidates for endotracheal 
intubation and Mechanical Ventilation for which they should be admitted to an ICU. 
• Respiratory tract infections precipitating acute asthmatic attack are predominantly viral; 
but if patients expectorate yellowish, green or brown sputum, antibacterial therapy is


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• Respiratory tract infections precipitating acute asthmatic attack are predominantly viral; 
but if patients expectorate yellowish, green or brown sputum, antibacterial therapy is 
indicated. Ampicillin is the first line; alternat ives are TTC, erythromycin or cotrimoxazole. 
Chest x-ray is taken if there is suspicion of pneumonia or complications.


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Internal Medicine 
 
 183Supportive Treatment  
• O 2 therapy is always indicated for hospitalized patients 
• Fluid and electrolyte balance requires special attention because of frequent occurrence 
of dehydration during   acute asthmatic attack. However, over hydration may cause 
pulmonary edema and one should be cautious in fluid administration.  
• Anxiety is common in patients with severe acute asthmatic attack. However this can be 
overcome when underlying hypoxia and feeling of asphyxiation is treated. Health personnel should be considerate and reassure the patient. 
 
Maintenance Therapy for Asthma (Chronic Treatment) 
Goal of Therapy : To achieve a stable, asymptomatic state with the best pulmonary function, 
using the list amount of medication .Drug selection is based upon the severity of illness. 
 
Table II-4-2. Step wise approach for managing Asthma in adults  
 
Severity Symptoms 
day/night  Medication  Alternative 
treatment in 
resource limited setting 
Mild 
intermittent  ≤ 2 days/wk and ≤ 2 
nights /month  No daily medication needed  
Treat when there is acute exacerbation   
Mild Persistent  > 2days /week but < 1 per day and > 2 
nights/month Low dose inhaled steroids 
or 
Cromolyn  Theophedrine tablets 
or Salbutamol tabs 
Moderate Persistent  Daily symptoms and more than 1 night /wkLow-medium does inhaled steroid and long acting B-agonist inhaler 
 Theophylline sustained release  Salbutamol Tabs  
Prednisolone tablets 
(low dose


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or Salbutamol tabs 
Moderate Persistent  Daily symptoms and more than 1 night /wkLow-medium does inhaled steroid and long acting B-agonist inhaler 
 Theophylline sustained release  Salbutamol Tabs  
Prednisolone tablets 
(low dose  
Sever Persistent  Continual daily symptoms and High dose inhaled steroid and long acting inhaled B-Theophylline sustained release


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Internal Medicine 
 
 184frequent night 
symptoms agonists and Oral steroids (if needed ) Salbutamol Tabs  Prednisolone tablets (high dose) or 
Celestamine tabs 
 
 
References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition,  Asthma,     
pages 1508-1515 
2) Myers R. Allen , National Medical Series for independent Study ( NMS ) 3rd edition 
Medicine, Asthma, pages 75-78


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Internal Medicine 
 
 1855. Chronic obstructive pulmonary diseases (COPD) 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define chronic obstructive pulmonary diseases (COPD 2. List the etiologies of COPD 3. Explain the epidemiology of COPD 
4. Describe the pathophysiology of COPD 
5. Identify the clinical manifestations of COPD 6. Outline the main differences between c. bronchitis and emphysema  7. Describe the most commonly used tests for the diagnosis of COPD  8. Make a diagnosis of COPD 
9. Give therapy to COPD at the primary care level 
10. Design appropriate methods of prevention of COPD  
 
Definition : Chronic obstructive pulmonary diseases are conditions characterized by chronic 
irreversible airway obstruction causing an increas ed resistance to outflow of air due to chronic 
bronchitis and emphysema. Both these diseases occur together in the same individual in a 
variable proportion but the manifestations of one often predominates the clinical picture.  1) Chronic bronchitis : is a condition associated with excessive tracheobronchial mucus 
production sufficient to cause cough with expectoration of sputum for at least 3 months in a 
year for over 2 consecutive years.  
2) Pulmonary emphysema : is distension of the airspaces distal to the terminal bronchioles, 
accompanied by destructive changes of the alveolar septa. 
Etiology 
• Emphysema : Any factor leading to chronic alveolar inflammation would encourage


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2) Pulmonary emphysema : is distension of the airspaces distal to the terminal bronchioles, 
accompanied by destructive changes of the alveolar septa. 
Etiology 
• Emphysema : Any factor leading to chronic alveolar inflammation would encourage 
development of an emphysematous lesion. Smoking has adverse effects on lung 
defenses, leading to emphysematous change. Congenital enzyme defects such as α
1- 
antitrypsin deficiency are also risk factors for the disease.  
• Chronic bronchitis : with sufficient exposure to bronchial irritants, particularly cigarette 
smoke, most persons develop some degree of chronic bronchitis with signs of 
inflammation of the airways. In developing countries household smoke from fire wood is said to be a major contributing factor.


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Internal Medicine 
 
 186Prevalence :  
• COPD is a major health problem especially in western societies because of the effect 
of cigarette smoking and aging.   
• Males are affected more than females which could be attributed to the higher 
prevalence of smoking in males. Nowadays, the incidence of this disease in females is 
increasing because of the increasing smoking habit.  
 Pathological changes and pathophysiology  
• Chronic bronchitis is characterized by hypertrophy of mucus glands in both large and 
small airways with thickening of walls and accompanying excess production of mucus 
and narrowing of airway lumen. In C. bronchitis, alveoli are often spared, and no vessel 
loss and lung perfusion remains normal but ventilation is very much reduced. This 
leads to abnormal V/Q (arteriovenous shunt) and patients usually suffer from hypoxemia (manifested with cyanosis) and acidosis, which causes pulmonary 
hypertension and right heart failure in the long term.  
• On the other hand emphysema is characterized by destruction of alveolar septa and 
distension of alveoli resulting in reduced surface area and loss of vessels, the later causing reduced perfusion. Moreover, emphysema causes mucus production and airway narrowing with accompanying reduction in ventilation. This leads to retention of 
carbon dioxide in the blood and severe dyspnea from reduced tissue perfusion. 
However, these patients don’t suffer from hypoxia and acidosis, and have less chance


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carbon dioxide in the blood and severe dyspnea from reduced tissue perfusion. 
However, these patients don’t suffer from hypoxia and acidosis, and have less chance 
of development of pulmonary hypertension and cor-pulmonale. However, patients 
usually have a mixed picture of em physema and chronic bronchitis. 
Clinical features:   
• COPD is thought to begin early in adult life but significant symptoms and disability do 
not appear until middle age.  
• A mild "smoker's cough" is often present many years before onset of exertional 
dyspnea. Gradual progressive exertional dyspnea is the most common presenting complaint.  
• Cough, wheezing, recurrent respiratory infections or, occasionally weakness, weight 
loss, or reduced libido may also be initial manifestations.  
Physical findings : in COPD are very variable especially in early stages.


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Internal Medicine 
 
 187• A consistent abnormality is obstruction to expiratory airflow manifested by prolonged 
forced expiration (normally < 4 seconds). 
• Typical findings including gross pulmonary hyperinflati on, prolonged expiration during 
quiet breathing, pursed-lip breathing, stooped posture, and marked use of accessory 
muscles of respiration are seen in later stages of COPD.  
• Other findings are rhonchi, diminished vesicular breath sounds, tachycardia, distant 
heart sounds, and decreased diaphragmatic excursion.  
• The chest may be remarkably "quiet" in adv anced stages of emphysema but is usually 
"noisy" in patients with chronic bronchitis.  
• In advanced cases, frank cyanosis may be there from hypoxemia; a plethoric 
appearance associated with secondary erythrocytosis and, signs of right-sided heart 
failure in patients with cor-pulmonale.  Mild edema may be there even without heart failure. 
Chest x-ray findings :- are very variable.   
• In early stages it is normal.  
• Hyperinflation (e.g. depressed diaphragm, generalized radio-lucency of the lung fields) 
is common usually late in the disease process.  
• In patients with recurrent chest infections, a variety of non-descriptive post-
inflammatory abnormalities (referred to as “dirty lung”) may be noted on the chest film. 
Diagnosis:  
• COPD should be suspected in any patient with chronic productive cough and/or 
exertional dyspnea of uncertain etiology, or whose physical examination reveals


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Diagnosis:  
• COPD should be suspected in any patient with chronic productive cough and/or 
exertional dyspnea of uncertain etiology, or whose physical examination reveals 
evidence of prolonged forced expiration. 
• Pulmonary function tests (spirometric testing) are done at specialized hospitals to 
determine the type of pulmonary obstruction.  
• Red cell counts may reveal erythrocytos is and elevated hematochrit in chronic 
hypoxemic patients.  
• The pattern of physiologic abnormality in each patient depends to some extent on the 
relative severity of intrinsic bronchial disease and emphysema. In patients with severe 
emphysema, resting hypoxemia is usually m ild (i.e. no or less cyanosis). In patients 
with chronic bronchitis, severe hypoxemia may be noted relatively early.


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Internal Medicine 
 
 188Table II-5-1 Summary of clinical manifestations of Chronic Bronchitis and Emphysema 
 
  
Predominant emphysema  Predominant C. 
bronchitis 
Age  60 +/-  50+/- 
Body habitus Thin obese 
Cough  After dyspnea  Before dyspnea  
Sputum  Scanty, mucoid Copious, purulent 
Appearance  Pink, tachypneic (pink puffers)  Cyanosed, normal RR 
(blue bloaters) 
P/E ↑AP diameter, 
Use of accessory muscles of respiration Silent chest, Hyperresonant 
Decreased cardiac dullness +/- use of accessory muscles of respiration  
No hyperresonance  Rhonchi (changing)  Wheezing with cough 
CXR Long, narrowed tubular heart,  Low diaphragm (flat diaphragm) Dark lung fields (translucent) 
with loss of peripheral vascular 
markings Enlarged heart  Large pulmonary artery  Increased bronchovascular markings 
 
Hematology  Normal Hct Increased Hct 
Blood gases PaO 2  =65– 75mmH  
PaCO 2 = 35 – 40mmHg PaO 2 = 40 – 60mmHg 
PaCO 2 = 50 – 60mmHg 
Complications  Less bronchial infection Terminal respiratory insufficiency 
+/- cor-pulmonale Frequent bronchial infection  Repeated respiratory insufficiency 
Frequent cor-pulmonale


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Internal Medicine 
 
 189Course and Prognosis 
In the early stage of COPD, some reversal of airway obstruction and considerable 
symptomatic improvement can often be obtained with therapy, but the long-term prognosis is less favorable in such patients.  
Treatment:  so far no curative treatment.  
• Therapy is directed at relieving symptoms, controlling potentially fatal exacerbations, 
and slowing of the progression of the disorder.  
• Avoidance of bronchial irritants, especially cessation of smoking, is of primary 
importance.  
Thus, the treatment is outlined as follows:  
1) Treatment of infection : COPD patients with purulent sputum should be treated with a 
broad spectrum antibiotic. Commonly used drugs include co-trimoxazole 980mg POBID or TTC or Ampicillin 250 - 500mg four times a day for 10 days. The course can be repeated at the first sign of recurrence of bronchial infection.  
2) Control of bronchospasm : β-agonists like salbutamol, or one of the theophyllines can 
be used. Corticosteroids do not have a major role in maintenance treatment. 
3) Facilitation of drainage of bronchial secretion : adequate hydration with oral fluids is 
essential to prevent drying of secretions.  Inhalation of mist, postural drainage, and chest exercise may help. 
4) Hypoxemia:  this will lead to cor-pulmonale in patients with predominant c.bronchitis. 
Oxygen should be given in such patients with hypoxia, and in severe cases a portable


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4) Hypoxemia:  this will lead to cor-pulmonale in patients with predominant c.bronchitis. 
Oxygen should be given in such patients with hypoxia, and in severe cases a portable 
oxygen therapy ( 16 hrs /day) for home use is recommended.                                 
5) Control of heart failure : the most important measures are correction of hypoxemia, 
administration of diuretics and restriction of sodium intake. 
6) Exercise : prolonged inactivity leads to exercise intolerance. Regular exercise as long 
as there is no severe heart disease is recommended. 
7) Depression : The nature of the disease should be well understood by both the patient 
and the family. Psychological support is very important. Antidepressants may be 
necessary but they should be used cautiously to avoid sedation. 
8) Treatment of exacerbation : exacerbation requires prompt treatment. If sputum 
becomes purulent, a course of broad-spectrum antibiotics should be given.  
9) Phlebotomy:  hematochrit is usually high because of the chronic hypoxemia 
(polycythemia) especially in patients with predominant chronic bronchitis. Phlebotomy


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Internal Medicine 
 
 190should be done when the hematocrit level is very high (above 55%) and patients are 
symptomatic. 
 
References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition,  Chronic 
obstructive pulmonary diseases, pages 1547-1553 
2) Myers R. Allen , National Medical Series for independent Study ( NMS ) 3rd edition 
Medicine, Chronic obstructive pulmonary diseases , 70-74


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Internal Medicine 
 
 1916. Suppurative lung diseases  
 
6.1 Bronchiectasis   
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define bronchiectasis  
2. List the etiologies of bronchiectasis  3. Explain the epidemiology of bronchiectasis  4. Describe the pathophysiology of bronchiectasis  5. Identify the clinical manifestations of bronchiectasis 
6. Describe the most commonly used tests for the diagnosis of bronchiectasis   
7. Make a diagnosis of bronchiectasis 8. Give treatment for bronchiectasis at the primary care level 9. Design appropriate methods of prevention of bronchiectasis   
Definition:  It is a pathologic, irreversible destruction and dilatation of the wall of bronchi and 
bronchioles, usually resulting from suppurative infection in an obstructed bronchus. 
Etiology and pathogenesis:   
• Small bronchi of children are susceptible to recurrent infections and obstruction by 
foreign body, lymph node, or impacted secretions, all of which lead to persistent 
infection and the development of bronchiectasis. However, bacterial pneumonia is the 
commonest cause of bronchiectasis. Pr edisposing conditions include congenital 
disorders (e.g. bronchial stenosis) and immunosuppressive disorders.  
Clinical features 
• Chronic cough productive of copious and of fensive purulent sputum is the cardinal 
feature of bronchiectasis. The sputum typically forms three layers when collected in a


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Clinical features 
• Chronic cough productive of copious and of fensive purulent sputum is the cardinal 
feature of bronchiectasis. The sputum typically forms three layers when collected in a 
glass container: the upper layer is foam (mucus), the middle one is liquid and the lower 
one is sediment.  
• In the early stage of the disease cough and sputum production are related to cold 
exposure, with occasionally hemoptysis.  
• In advanced disease patients have progressive dyspnea, massive hemoptysis and 
cough occurs at any time of the day and produces large volume of khaki colored 
sputum with accompanying cyanosis and clubbing.


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Internal Medicine 
 
 192• Complications in advanced cases include recurrent hemoptysis, cor-pulmonale, 
respiratory failure, amyloidosis and recurrent pneumonia. 
Diagnosis 
• Diagnosis is largely based on clinical features. Obtaining a history of recurrent 
pulmonary infections ultimately followed by chronic recurrent cough and production of 
copious purulent sputum may suggest a diagnosis of bronchiectasis.  
• Physical examination of the chest may s how only rales in early stages. Additional 
findings like cyanosis, clubbing and signs of right heart failure appear late.  
• Pulmonary function test may be normal in early disease.  
• Chest x-ray usually shows peribronchial  fibrosis or it can have a honeycomb 
appearance. Segmental lung collapse may be observed in parts of the lung affected by 
bronchiectasis. 
• Definitive diagnosis of bronchiectasis is made by bronchography.  
• CT scanning often identifies the lesions, eliminating the need for bronchoscopy and 
contrast studies. 
Treatment 
Generally, patients should avoid smoking and exposure to dust. Living in warm & dry 
climatic condition is advisable. However, m edical therapy is the mainstay of treatment 
and include  
 
1) Control of respiratory infections  : 
a. Broad spectrum antibiotics that shou ld be given whenever signs of pulmonary 
infection appear and symptoms are exacerbated (Ampicillin, tetracycline or 
erythromycin),  
b. Immunization for influenza and S. pneumoniae  if available


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a. Broad spectrum antibiotics that shou ld be given whenever signs of pulmonary 
infection appear and symptoms are exacerbated (Ampicillin, tetracycline or 
erythromycin),  
b. Immunization for influenza and S. pneumoniae  if available 
2) Improve drainage of secretion : using postural drainage, liquefaction and 
bronchodilators. 
3) O 2 therapy:  may be given in patients with hypoxemia. 
4) Surgical resection  of the affected part is indicated when bronchiectasis is localized, 
and in those with recurrent massive hemoptysis that fails to respond to conservative 
treatment. This is effective if done early in life.


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Internal Medicine 
 
 1936.2 Lung abscess 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define lung abscess  2. List the etiologies of lung abscess  3. Explain the risk factors for lung abscess   
4. Identify the clinical manifestations of lung abscess 
5. Describe the most commonly used methods for the diagnosis of lung abscess 6. Make a diagnosis of lung abscess  7. Identify the complications of lung abscess 8. Give treatment for lung abscess at the primary care level 
9. Design appropriate methods of prevention of lung abscess   
 
Definition:  lung abscess is defined as collection of pus within a destroyed portion of the lung. 
It may develop following necrotizing infections of  the lung (bacterial pneumonia, TB, fungi), 
loss of blood supply to a part of the lung causing cavitary infarction due to septic or bland 
embolism, obstruction to airways or cavitations of malignancy. The anaerobic abscess is the 
commonest and usually follows periodontal diseases (gingivitis, pyorrhea) or aspiration of oro-
pharyngeal/gastric contents. 
Etiology:   
• Lung abscess is commonly caused by pyogenic bacteria: S.aureus, Klebsiella , mixed 
anaerobes, and Nocardia.   
• Common risk factors include alcoholism, immunodeficiency, loss of consciousness, 
and periodontal diseases 
Clinical features:   
• In the early stage manifestations of lung abscess may resemble that of pneumonia.


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anaerobes, and Nocardia.   
• Common risk factors include alcoholism, immunodeficiency, loss of consciousness, 
and periodontal diseases 
Clinical features:   
• In the early stage manifestations of lung abscess may resemble that of pneumonia.  
• The development of features of lung abscess within 1-2 weeks after bacterial 
pneumonia, possible aspiration or bronchial obstruction is usually reported.  
• Patients will have cough with sudden expectoration of massive purulent and foul 
smelling sputum, high grade fever, and sweating with occasional hemoptysis.   
Diagnosis :  
When patients present with the typical manifestations outlined above, the diagnosis of lung 
abscess may not difficult.  However, it should be confirmed by chest x-ray by


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Internal Medicine 
 
 194demonstrating parenchymal infiltrates with cavity  containing air-fluid level. Gram stain and 
culture of the sputum help to make etiologic diagnosis. 
Complications include   
• Metastatic brain abscess 
• Fatal hemoptysis 
• Empyema 
• Secondary amyloidosis 
Treatment  
Medical therapy is the main stay of treatment. Admit patients to hospitals and  the 
following modalities of therapy can be given:  
1) Antibiotics  – start empirical antibiotics until laboratory results are available and adjust 
drugs accordingly. Start both crystalline penicillin and chloramphenicol high doses IV 
and treatment should be given for 4 – 8 weeks. 
2) Drainage of abscess  – postural drainage can be effective but bronchoscopic drainage 
may be used when airway obstruction by fo reign body or mass hinders drainage of pus 
by postural means. Bronchoscopes and experts who can do such procedures are 
available only in specialized hospitals. 
3) Surgical treatment of lung abscess may be indicated in patients with  
• Persistent or massive hemoptysis 
• Empyema or bronchopleural fistula 
• Failure of medical treatment  
• Lung cancer 
 
References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition,  
Bronchiectasis, pages 1541-1542. 
2) Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition Medicine, 
Bronchiectasis, 78-80.


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Internal Medicine 
 
 1957. Pleurisy and Pleural Effusion 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define pleurisy and pleural effusions 2. Classify pleural effusions 3. List the etiologies of pleural effusions 
4. Describe the pathophysiology of pleural effusions 
5. Identify the clinical manifestations of pleural effusions  6. Describe the most commonly used method of diagnosis of pleural effusions  7. Make a diagnosis of pleural effusions  8. Give treatment for pleural effusions at the primary care level 
 
Definition: pleural effusion is the presence of excess fluid in the pleural space. Normally 10– 
20 ml of fluid is spread in a thin layer between the two layers of pleurae. Pleural effusions are 
classified as transudates and exudates based on laboratory analysis of the fluid.  
Transudative effusion:  results from elevations in hydrostatic pressure or decrease in oncotic 
pressure. The following are some of the causes:-  
• Heart failure 
• Cirrhosis of the liver 
• Nephrotic syndrome  
• Myxoedema  
• Hypoproteinemia  
Exudative effusion: is  due to pleural inflammation (pleurisy) with an increased permeability of 
the pleural surface to protein. Pleurisy commonly occurs in infections such as pneumonia, 
infections of the esophagus, mediastinum or s ub-diaphragmatic areas, traumatic injuries, and 
extension of infections from adjacent organs. Initially pleurisy tends to be dry but fluid starts to


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infections of the esophagus, mediastinum or s ub-diaphragmatic areas, traumatic injuries, and 
extension of infections from adjacent organs. Initially pleurisy tends to be dry but fluid starts to 
collect subsequently. It is found in association with:-  
• Parapneumonic effusions 
• Empyema 
• Pulmonary embolism 
• Neoplasms  
• Systemic lupus erythematosis and rheumatoid pleural effusion 
• Sub-diaphragmatic abscess


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Internal Medicine 
 
 196• Pancreatitis 
• Uremic pleural effusion 
• Hemothorax 
• Chylothorax (thoracic duct injury) 
• Radiation and drugs.  
Clinical findings and diagnosis  
• Pleuritic chest pain and dyspnea are the most common symptoms, but many pleural 
effusions are asymptomatic and discovered on physical examination or chest x-ray.  
• Underlying causes should be suspected from the history.  
• Physical examination on the affected side discloses the presence of decreased chest 
motion, absent tactile fremitus, percussion dullness, and decreased or absent breathes 
sounds.  
Diagnosis and laboratory findings  
• The diagnosis of pleural effusion can be suspected from a properly done physical 
examination. 
• Chest x-ray is the most precise way to confirm the physical findings. It demonstrates 
the presence of pleural fluid as homogenous opacity with a meniscus-sign and 
obliteration of the costophrenic angle. Large pleural effusions may result in complete 
opacification of the hemithorax and mediastinal shift to the opposite side. The best way 
to identify and localize a loculated pleural effusion is with ultrasonography. 
• Pleural thoracenthesis (aspiration of fluid) should be performed to confirm the presence 
of fluid and to determine its characteristics, including color and consistency.  
o Clear yellow fluid is described as serous 
o Bloody or blood-tinged fluid as sanguineous or serosanguineous. Some of the


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of fluid and to determine its characteristics, including color and consistency.  
o Clear yellow fluid is described as serous 
o Bloody or blood-tinged fluid as sanguineous or serosanguineous. Some of the 
causes include pulmonary infarction and pleural carcinomatosis 
o Translucent or opaque, thick fluid as purulent.  
• Microscopic examination of the fluid is important including Gram stain and culture (if 
possible).  
• Total and differential cell counts should be obtained.  
o The predominance of polymorphonuclear leukocytes suggests an underlying 
pneumonia with a parapneumonic effusion.  
o The presence of many small mature lymphocytes, particularly with few 
mesothelial cells, strongly suggests tuberculosis.


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Internal Medicine 
 
 197• It is important to determine whether pleural fluid is an exudate or a transudate; this 
gives a clue to the underlying cause. Ex udative effusions have at least one of the 
following characteristics, whereas transudates have none of these: 
o Pleural fluid protein/ serum protein > 0.5    
o Plural fluid LDH/serum LDH > 0.6 
o Pleural fluid LDH more than 2/3 normal upper limit for serum 
• If effusion is exudative, gross description of fluid, glucose level, amylase level, WBC 
and differential count, microbiologic st udies, and cytology should be obtained. 
Treatment:   
• Therapeutic thoracenthesis should be done in massive effusion to relieve respiratory 
distress. Removal should be limited to 1200 to 1500 ml at a time.  
• Definitive treatment of pleural effusion requires identifying the underlying condition and 
administration of specific therapy.  
o Tuberculous effusion is treated with a course of anti tuberculous drugs.  
o Parapneumonic effusions and other bacterial infections in the pleural space 
should be treated with long course of antibiotics.  
o Empyema (purulent fluid in the pleural cavity) is treated with high doses of 
parenteral antibiotics coupled with surgical drainage (Chest tube insertion).  
 
References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, 
Disorders of the pleura, pages 1565-1568. 
2) Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition


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References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, 
Disorders of the pleura, pages 1565-1568. 
2) Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition 
Medicine, Diseases of the pleura, 88-91.


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Internal Medicine 
 
 1988. Neoplasms of the lung 
 
Learning Objective :  At the end of this unit the student will be able to  
1. Classify lung neoplasms 
2. List the etiologies of lung neoplasms 3. Identify the clinical manifestations of lung neoplasms 
4. Describe the most commonly used method of diagnosis of lung neoplasms 
5. Make a diagnosis of lung neoplasms 6. Refer patients with lung neoplasms to hospitals for further investigations and treatment  
 
• Metastatic tumors are more common than primary tumors of the lungs; the commonest 
primary sites being the breasts, stomach, prostate, and ovary.  
• Majority (90 – 95%) of primary lung tumors are malignant epithelial tumors collectively 
called bronchogenic carcinomas. The remaining are bronchial carcinoids, mesenchymal tumors (lymphomas, sarcomas, liomyomas, lipomas, fibromas, liomyosarcomas) and bronchial hemartomas, the last being benign tumors with 
aberrant differentiation of the bronchial tissues. The disease is common between the 
age ranges 65 – 75 years, and affects men more than women, with M: F ratio of 2:1. 
Etiology : A number of factors have been found to be associated with lung cancer and include 
• Cigarette smoking  - cigarettes contain at least 55 carcinogens and the risk of lung 
cancer increases to 20 fold for people who smoke more than 40 cigarettes/d. Smokers have 10 times more risk of dyi ng from lung cancer than non-smokers.


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• Cigarette smoking  - cigarettes contain at least 55 carcinogens and the risk of lung 
cancer increases to 20 fold for people who smoke more than 40 cigarettes/d. Smokers have 10 times more risk of dyi ng from lung cancer than non-smokers. 
• Exposure to Radon in underground miners  (occupational) or indoors  
• Exposures to other carcinogens :Ni, Co , Cr, Asbestos, Polycyclic aromatic 
hydrocarbons, Silica , Mustard gas (world war I) 
Pathologic features of bronchogenic carcinomas: originate from the bronchial 
epithelium and have 4 histological types  
• Adenocarcinoma (including bronchoalveolar carcinoma) account for 30 -
35% of bronchogenic ca 
• Squamous cell carcinoma accounts for  25 -30% 
• Small cell (Oat cell) carcinoma  accounts for 15 – 25% 
• Large cell carcinoma accounts for 10 – 15%


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Internal Medicine 
 
 199• Mixed cell type (Squamous & sm all cell or squamous cell & 
adenocarcinoma) account for 5 - 10% 
• Pleomorphic carcinoma (mixed carci noma & sarcomatoid pattern) 0.5%  
Differentiation between small cell and non-sma ll cell carcinoma (Adenocarcinoma, Squamous 
cell ca, large cell ca) is very important becaus e small cell carcinoma is responsive (at least 
initially) to chemotherapeutic treatment.  
All lung neoplasms are very aggressive, invasi ve and widely metastasizing commonly to liver, 
adrenals brain and bones; they also produce bioactive hormones and other products.  Cigarette smoking is closely linked to squamous cell ca, small cell ca and large cell ca but not 
to adenocarcinoma Adenocarcinoma 
• More common in women than men & develop in the periphery of the lung 
• Commonest lung cancer in non-smokers 
• Some adenocarcinoma arise from an area of pulmonary fibrosis/scar (old infarcts, 
asbestosis, or on healed TB scars) which are referred to as  scar cancers 
• Distant organ metastases occurs in over 50% of cases, especially to the brain 
• Have poor prognosis – 5 year survival is 10 -12% 
 
Squamous cell carcinoma 
• More common in males than females 
• Strongly associated with cigarette smoking 
• Arise centrally in the major or  segmental bronchi & spread to hilar lymph nodes  
in 70 – 90% of cases or to distant nodes in 50 -60% of cases or to viscera 
• Has poor prognosis – 5 year survival  is only 5 – 8% 
Small cell carcinomas


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• Arise centrally in the major or  segmental bronchi & spread to hilar lymph nodes  
in 70 – 90% of cases or to distant nodes in 50 -60% of cases or to viscera 
• Has poor prognosis – 5 year survival  is only 5 – 8% 
Small cell carcinomas 
• Very aggressive and early metastasizing 
• More common in males than females 
• Strongly associated to cigarette smoking 
• Centrally located 
• Commonly associated with paraneoplastic syndromes 
• Poor prognosis – 5 year survival  is only 5 – 8% 
Large cell carcinomas 
• Anaplastic (undifferentiated) tumors, and occur in smokers


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Internal Medicine 
 
 200• Central or peripheral locations 
• Metastasizes very rapidly and widely 
 
Clinical features of lung carcinomas are variable.  
• Some may present with local pulmonary symptoms. Others present with symptoms 
referable to metastasis before local pulmonary symptoms.  
• About 10 - 15% of lung tumors are detected by chance (a coin shaped lesion on chest 
x-ray). Manifestations could be related to local obstruction, local tumor invasion, distant 
metastasis or ectopic hormone secretions by tumor cells (paraneoplastic syndromes).  
• Local symptoms depend on the location of the tumor. When tumors are endobronchial 
cough, hemoptysis, stridor, wheezes, dyspnea, and nonresolving pneumonia may predominate. Pleuritic chest pain is common with peripheral  tumors.   
Local tumor invasion and obstruction  may result in  
 Recurrent laryngeal nerve palsy causing hoarseness of voice 
 Phrenic nerve paralysis with diaphragm paralysis 
 Esophageal obstruction causing dysphagia 
 Superior vena cava obstruction  presenting with edema of the face 
 Pancoast syndrome is said to exist when apical lung tumors infiltrate the spinal 
nerves (C8 – T1) and cause shoulder pain, & cervical sympathetic nerves causing Horner’s syndrome which is characterized by  absence of sweating, eyelid drooping and 
pupillary constriction on the affected side.  Pericardial or pleural effusions, and bronchial obstruction leading to atelectasis, 
pneumonia, and lung abscess


