With 50 million cases in the tropics each year, dengue fever is humanity's most common insect-borne viral infection. Killing the mosquitoes that carry it is the only way to fight it, but now a large-scale survey in Thailand has revealed that this can make the deadliest form of dengue more prevalent.
Known as "breakbone fever", dengue is painful but normally not fatal the first time around - the real threat is the second infection.
There are four varieties, or serotypes. Say you get bitten by a mosquito carrying serotype A, and then a year later by one carrying serotype B. The antibodies you made in response to A bind to the B virus but do not destroy it.
Instead these pairs overstimulate the immune system, causing a potentially fatal disease called dengue haemorrhagic fever. DHF kills 12,000 people a year, mainly children.
However, for a few weeks after you contract dengue, you have a kind of immunity that does destroy other serotypes.
If you get serotype B during these weeks, you will not develop DHF but will develop antibodies to both A and B. If you get infected by all the serotypes during such a window of cross-immunity, you can end up with antibodies to all of them and won't develop DHF.
This led Yoshiro Nagao and colleagues at the London School of Hygiene and Tropical Medicine to an unusual hypothesis. They figured that when there are lots of mosquitoes about, people are more likely to catch another serotype during the brief cross-immunity period, leading to less DHF.
However, if the number of mosquitoes is reduced, people are infected less frequently and so are less likely to catch another serotype during this crucial window. This led the team to the counter-intuitive idea that fewer mosquitoes could result in more cases of DHF.
To test the hypothesis, they combined the incidence of DHF in Thailand with a huge Thai survey that sampled water containers in a million homes across the country, from 2002 to 2004, looking for larvae of the dengue-carrying Aedes mosquito.
The evidence supported the team's hypothesis: as mosquito infection rates climbed towards 30% of houses, DHF cases also increased. But once over the 30% threshold, the relationship was reversed and DHF cases dropped off as infection rates climbed.
In some villages, 70% of homes had Aedes larvae. A mathematical model based on the survey showed that cutting this to 30% would increase DHF cases by more than 40%. Infestation had to be cut to less than 10% to reduce DHF cases, but achieving such an extensive reduction might be difficult, the researchers warn.
The World Health Organization encourages mosquito control - such as spraying insecticide - as a means of fighting dengue. But as this may increase the number of DHF cases, such measures should be "subject to ethical discussion", says Nagao.
Axel Kroeger, a WHO dengue expert, says even if this new discovery is confirmed, it is worth fighting dengue by controlling mosquitoes. This is because some developing countries have achieved far less than 30% infestation, while higher levels often reflect a neglect of mosquito control.
Journal reference: PLoS Neglected Tropical Diseases (DOI: 10.1371/journal.pntd.0000263)
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