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University of Nebraska Medical Center

Down With Dengue

Science

Today’s post is not exactly chemical per se, but it’s very promising news on the anti-infectives front. Dengue fever is a viral disease whose range has been extending in recent years, very likely as a result of changes in the climate (it was formerly considered more of a tropical disease). It’s yet another mosquito-carried one, and it has been difficult to come up with either small-molecule drugs against it or effective vaccines.

The latter tactic has been made more difficult by there being four distinct serotypes of dengue, and (famously) the first vaccine marketed (Dengevaxia) causes antibody-dependent enhancement of disease (ADE). That is, if you’ve had dengue before the vaccine can be useful, but if you immune system has never been exposed to it, vaccination with Dengevaxia can actually make your first exposure worse. Which is a very bad outcome, needless to say. In people who’ve had confirmed dengue in the past, the vaccine is around 76% effective, though. It was approved in 2018 in the EU and 2019 in the US. More recently, another vaccine (Qdenga) was approved last year in Indonesia and then the EU. It does not appear to cause ADE, but on the other hand it seems to be notably less effective against three of the serotypes and more effective against DENV2.

So it would be desirable to have some other way to knock this disease down, and now there may be one coming on. For some time, there’s been interest in using Wohlbachia bacteria to infect Aedes aegypti mosquitos, because insects so infected appear to be far less likely to harbor and transmit viruses in general – not only dengue, but also zika, chikungunya, and yellow fever. Wohlbachia infection is common in many insect species, but not in wild-type A. aegypti. (The mosquitoes do not infect humans with Wohlbachia, in case you’re wondering). A particular feature is that if Wohlbachia-carrying male mosquitos mate with an uninfected female, the resulting eggs do not even hatch. Meanwhile, female mosquitoes (the ones that do all the biting), if infected with Wohlbachia, transmit the bacteria to their eggs and larvae. So this holds out the possibility of making a virus-resistant mosquito population.

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