Dengue Virus Blocker Works Even Better In The Field Than The Lab

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The history of medicine is filled with treatments and vaccines that worked beautifully under test conditions in the lab, but failed for unexpected reasons when put out to wider trial. So it’s a bit of a shock when something actually works better in the “real world” than in the laboratory, but that’s what happened when a dengue fever prevention mechanism got tested in Vietnam.

The dengue virus kills an estimated 13,600 people a year, but that is just one part of the damage. Although often mild, and gone within a week, the disease can be so painful that it’s also called breakbone fever, and physical or psychological after-effects sometimes last a lifetime. Besides hydration, it cannot be treated and the only approved vaccine is expensive and not fully protective.

Most attempts to fight the disease rely on trying to control the Aedes aegypti mosquito, which spreads it, but these are either expensive or provide only temporary benefits before the mosquito rises again, resistant to whatever method was used to fight it. Dr Lauren Carrington of the University of Melbourne is part of one of several teams working on a different approach, using the Wolbachia bacterium.

Wolbachia comes in many varieties and infects a wide array of insects. Some strains appear harmless to their hosts, while others shorten their lives or make them sterile. If we can get the right strain of Walbachia to spread through A. aegypti populations, there are a multitude of ways to stop dengue’s spread.

Carrington is working with the wMel strain, which is apparently harmless to the mosquito, but reduces their susceptibility to dengue infection. This greatly reduces the risk of induced resistance compared to a lethal variety. In the Proceedings of the National Academy of Sciences, Carrington acknowledges that the reasons the wMel strain stops dengue from infecting many A. aegypti are not fully understood. However, it also appears to block the Zika and chikungunya viruses as well, not only providing added benefits, but strengthening theories it both primes the immune system and competes for resources these viruses need.

When lab-raised mosquitoes infected with wMel fed on the blood of 141 dengue patients, they were 68 percent less likely to have the virus in their saliva when caught subsequently than uninfected mosquitoes. That might be enough to disrupt the transmission of the virus, but it’s clearly far from ideal. However, when the experiment was done in the wild wMel reduced dengue infection by 86 percent.

The reasons field trials outperformed lab experiments are unclear, although Carrington suspects it has to do with wild mosquitoes not getting the same nutrients as their pampered lab counterparts. Irrespective of the cause, however, the finding raises hopes wMel could make a major difference to the spread of this awful disease.

Carrington told IFLScinece field trials of other strains of Wolbachia have had the opposite outcome, proving less effective than lab tests had suggested. For example, Carrington said one version that shortened the lives of mosquitoes so they don’t have time for the virus to develop to the point where it can be transmitted; “Also reduced the fitness of its host in other ways,” making it unlikely to succeed in the wild. 

We can’t directly catch and infect enough mosquitoes to make Wolbachia widespread, but the bacterium has not been catching a ride on insects for millions of years without learning a trick or two itself. When an infected male and uninfected female mate, they produce eggs that don’t hatch. As a result, infected females, who pass wMel on to the next generation, have a reproductive advantage. “Over a number of generations, the frequency of infected mosquitoes will increase in the population,” Carrington told IFLScience. 

Trials are now taking place in a number of countries where dengue is widespread, and Carrington hopes that if these produce similarly positive results, we may soon see dengue cases fall in those regions.

Read more: http://www.iflscience.com/health-and-medicine/dengue-virus-blocker-works-even-better-in-the-field-than-the-lab/