Controlling dengue from within

Dengue fever is a mosquito-borne viral disease that’s becoming an increasing problem in tropical and subtropical regions. It is an infection that causes a severe influenza-like illness, and sometimes a deadly complication called dengue haemorrhagic fever. Some of the symptoms of dengue include sudden onset of high fever which may last 2 to 7 days, joint and muscle pain, weakness, and skin rashes, among others. In the Philippines alone, some 29,000 cases were reported between 1 January and 10 July 2010, an increase of 34.7% during the same period in 2009 according to the Department of Health.

A traditional measure to control the spread of the disease is to reduce the population of the mosquitoes, Aedes aegypti, which carries the virus. But this has had little success in reducing the incidence of dengue, and therefore more effective alternatives are urgently needed. In a recent issue of the journal Nature (25 August 2011), two papers[1,2] showed that the bacteria called Wolbachia can be used to control the infection of mosquitoes with the dengue virus by infecting them with a strain of the bacteria. The research team also demonstrated that Wolbachia infection can be spread effectively to natural mosquito populations when infected mosquitoes were released into the wild, ensuring the spread of dengue-resistant mosquitoes.

According to Wikipedia, Wolbachia is “one of the world’s most common parasitic microbes and is possibly the most common reproductive parasite in the biosphere. Within arthropods, it is notable for significantly altering the reproductive capabilities of its hosts.” One particular reproductive phenotype by Wolbachia is called cytoplasmic incompatibility. It is the inability of infected males to successfully reproduce with uninfected females or females infected with another Wolbachia strain. On the other hand, infected females are not affected by this phenomenon, resulting in a reproductive advantage over uninfected females. Since the bacteria are maternally transmitted, this phenomenon essentially kills the non-infected offspring, while offspring of infected females receiving the bacteria survive and thus, facilitating the rapid spread of infection within the population. However, successful population invasion still requires that the infected hosts overcome incomplete maternal transmission as well as some fitness costs.

Aside from being able to rapidly invade wild insect populations, Wolbachia also have the capacity to influence the insect’s ability to transmit pathogens either indirectly by reducing the insect’s lifespan or directly by reducing the viruses’ or other pathogens’ ability to spread within the insect.

Utilizing this characteristic effect of the Wolbachia bacteria, a research team from Australia demonstrated the bacteria’s potential in stopping the transmission of the dengue virus in mosquitoes. In the first paper entitled “The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations,” Walker and colleagues reported a strain of Wolbachia, called wMel, that significantly reduces dengue virus carriage in mosquitoes with small host fitness costs. The strain was grown and extracted from Drosophila (fruit flies), and then injected into the embryos of the Aedes aegypti, the mosquito that carries dengue. Their results showed that infected lab mosquitoes did not transmit dengue. Moreover, the team was able to demonstrate that the wMel strain could also effectively invade wild-type population in a contained field-cage experiments.

In the second paper entitled “Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission,” Hoffmann and colleagues demonstrated how the wMel Wolbachia infection introduced into Aedes aegypti successfully invaded two natural A. aegypti populations in a controlled field trial in two towns near Cairns in north-eastern Australia. They showed that within only a  few months after the initial release, between 80 and 100 percent of the tested mosquitoes found in the city already carried the bacteria.

Although the studies were not able to assess the effectiveness of the strategy in decreasing the incidence of dengue due to the fact that there were only sporadic cases of the disease in the towns tested, the findings demonstrate that Wolbachia-based strategies can be deployed as a practical approach to dengue suppression. This would be highly useful for developing countries such as the Philippines due to its relatively simple deployment system. A concerted effort from the government and the research sector would do well to adapt these techniques or else look into other feasible and practical ways to curb the particularly high incidence of dengue infection in the country. Finally, the findings of the said studies also open the possibility for using the same strategy to suppress other mosquito-borne diseases such as malaria, where research has already shown reduction in malaria transmission with Wolbachia infection.

References:
[1]  T. Walker, etl al., The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations, Nature 476 (2011) pp 450-453 (doi:10.1038/nature10355)
[2] A. A. Hoffmann, et. al., Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission, Nature 476 (2011) pp 454-457 (doi:10.1038/nature10356)