Every year, 50-100 million people are infected with the dengue fever virus, which is transmitted to humans through the bites of female Aedes aegypti mosquitoes, mainly in South East Asia and South America. With no vaccine and no specific treatment, serious complications arise in around 500, 000 cases and 22, 000 deaths. It is a leading cause of hospitalisation and death among young children and it can place a considerable financial strain on middle to low income families.
So the development of a new control to stop the virus comes as welcome news. Two studies published in Nature show that the spread of dengue fever through a wild mosquito population could be prevented by infecting mosquitoes with a common bacterium called Wolbachia pipientis.
“The presence of the Wolbachia in the mosquito completely blocks the ability of the dengue virus to be able to grow. If it can’t grow in the mosquito, then it can’t be transmitted between people,” said Scott O’Neill, a co-author of the studies, from the University of Queensland, Australia.
In the first study, the researchers transferred a strain of the Wolbachia bacteria from fruit flies to mosquitoes. They discovered that the bacteria inhibited the growth of the dengue fever virus and had very little effect on the mosquito otherwise in terms of health and lifespan.
The next stage of the research involved the release of 300, 000 mosquitoes infected with the bacteria into the wild in two remote towns in Australia. After five weeks, the researchers found that almost all of the wild mosquitoes were infected with the bacteria.
“There has been intense interest in developing and disseminating mosquitoes that cannot transmit dengue, but the roadblock to this approach has been that mosquitoes modified to resist dengue tend to have lower fitness than wild type mosquitoes and to die out when mixed with wild type mosquito,” said Kathryn Hanley, an associate professor of biology, who was not involved in either study, from the New Mexico State University, USA.
“In this context, the development of a Wolbachia strain that both limits dengue transmission and spreads through a natural population is extremely significant,” she said.
It is uncertain how the Wolbachia is able to suppress the virus but the researchers believe that the bacteria might boost the immune system of the mosquito to help it to fight off the virus or that the bacteria competes for key molecules, such as fatty acids, that the virus needs to replicate. “The jury is still out on which of those two mechanism is critical, or it might be a combination of both,” said O’Neill.
“These studies mark the first time that a deliberate Wolbachia-mediated population- replacement strategy has been attempted in nature, and herald the beginning of a new era in the control of mosquito-borne diseases,” said Jason Rasgon, who is based at the Johns Hopkins Bloomberg School of Public Health, USA, in an commentary published in Nature.
He wrote that the “groundbreaking” approach could be applied to other diseases transmitted by mosquitoes, such as malaria, and has the advantage of not having any negative effects on the ecosystem because the mosquito population is changed rather than eliminated.
Whether the spread of Wolbachia in “the highly variable world-wide range of dengue virus” is possible and able to “provide consistent protection against viral strains of different genetic make up” remains to be seen, he said. To determine these, the researchers will need to test the Wolbachia-infected mosquitoes in endemic areas, he added.
But Hanley does not believe that this approach alone will be enough to eliminate dengue fever. “The best efforts of the public health community in vector control have never been sufficient to globally eradicate a microbial pathogen, though they have been sufficient to eliminate pathogens regionally,” she said.
Her belief is that eradication of dengue fever will only be possible with the development of a vaccine. “The Wolbachia strain would have to be combined with an efficacious dengue vaccine, something that I’m hopeful will become available in the next ten to twenty years,” she said. (There is a promising vaccine development in progress, read my article published in the Bulletin of the World Health Organization).
She also highlighted the inability of the Wolbachia to entirely prevent the replication of the virus in the mosquito as a potential problem: ”It is equivalent, in some ways, to vaccinating the mosquitoes with what is known as an ‘imperfect vaccine’ – one that limits but does not eliminate pathogen replication. This approach, if used broadly, may impose selection for higher replication and therefore higher virulence in dengue virus. The Wolbachia itself is a living organism and may evolve in unexpected way.”
The researchers acknowledge that more work needs to be carried out to determine whether this method can work to eliminate the virus on a global scale. ”There are a number of hurdles we still need to overcome before we get to the stage where Wolbachia can control dengue,” said Ary Hoffman, a co-author of the studies, based at the University of Melbourne, Australia. “These are early days. But at the moment, we are very hopeful.”
The researchers plan to test the new approach in endemic countries, such as, Vietnam, Thailand, Indonesia and Brazil over the next year.
This is a longer version of my article published on the COSMOS magazine website.
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