A novel route to battle dengue carrying mosquitoes

Published in The Hindu on August 25, 2011

Aedes aegypti

Wolbachia bacterium lives inside the Aedes aegypti cells, thus  making the mosquitoes resistant to dengue virus. — Photo: Wikimedia Commons

Nearly 50 million people get infected with dengue fever every year in more than 100 countries, India included. And the severity of the outbreaks is showing an upward trend. All conventional methods have so far failed to prevent people from getting infected. Humans get infected with dengue when Aedes aegypti mosquitoes carrying the dengue virus bite them.

It is against this backdrop that two groups of scientists have taken a totally different route to fight the battle. They have made the Aedes aegypti mosquitoes completely resistant to dengue virus infection.

The result: the manipulated A. aegypti mosquitoes are no longer the carriers of the dengue virus. Thus the transmission of the virus to humans is blocked. Their work is reported in two papers published today (August 25) in Nature.

The mechanism

So how did they make the A. aegypti mosquitoes resistant to dengue infection? They introduced Wolbachia bacterium, a common bacterium which even in nature infects insects and mosquitoes, into A. aegypti. Since the bacterium lives inside the host’s cells, it makes the mosquitoes resistant to dengue virus.

Incidentally, studies done already have shown that mosquitoes become resistant to West Nile virus when an avirulant strain of Wolbachia bacterium is introduced into them. These papers come at a time when earlier studies had shown that the ability of the Wolbachia-infected mosquitoes to block dengue transmission came at the cost of fitness of the mosquitoes.

The highlight is that the bacterium is maternally inherited and hence the offspring carry the bacterium. That is, the embryos die when Wolbachia-infected males mate with uninfected females. On the other hand, the embryos are not destroyed when Wolbachia-infected females mate with either infected or uninfected males. Thus in principle, the bacterium can spread through the A. aegypti population in the field.

While the first team led by T. Walker of The University of Queensland, Brisbane, restricted itself to laboratory and caged studies, the second team led by A.A. Hoffmann of The University of Melbourne, Victoria, went a step further. They released the genetically modified mosquitoes in the field in two locations near Cairns in north-eastern Australia in January this year.

Laboratory studies

Walker’s team compared the various important attributes of mosquitoes with both virulent (wMelPop-CLA) and avirulent (wMel) strains of the bacterium. Hoffmann’s team used only mosquitoes with avirulant (wMel) strains for the field study.

The avirulent wMel mosquito strains outclassed the virulent wMelPop-CLA on most counts. The wMel strains could successfully invade a small wild-type population of mosquitoes much more effectively than the other strain.

The other most important parameter is the survival ability of embryos. wMel strains showed a very strong ability to destroy embryos produced by uninfected females mated with infected males. A 90 per cent embryo survival rate was seen in the case of infected female mosquitoes.

The viability of eggs was better in the case of the avirulent wMel mosquito strains. While the lifespan of the avirulent strains was reduced by only 10 per cent, there was a 40 per cent drop in the case of the virulent strains.

The wMelPop-CLA strains showed greater ability to suppress dengue virus transmission. But such high transmission disruption comes at the cost of survival of the infected mosquitoes.

“The ability of wMel to provide protection against dengue virus in A. aegypti is unlikely to be transient,” the authors conclude. They also state that dengue can be controlled by releasing a relatively small number of Wolbachia-infected mosquitoes.

Field studies

The first release happened in January this year and continued for 9-10 weeks in both locations. The number of mosquitoes released per week varied between 10,000 and 22,000. Cairns in north-eastern Australia was hit by a severe cyclone during the trial period, and the effects of that is not completely known.

But despite the cyclone, after the seventh release the mosquitoes carrying the Wolbachia increased and “reached near fixation 5 weeks after releases stopped.”

The proof

The field studies showed that wild mosquito populations’ ability to act as carriers of the dengue virus can be reduced by releasing Wolbachia-infected mosquitoes.

Nature news notes the advantage of such population-replacement approach. “Once established, they are self-propagating. And since the mosquito population is simply changed rather than eliminated, effects on the ecosystem should be minimal,” it states.