Could Building a Better Mosquito Cut Incidence of Dengue?

NATIONAL HARBOR, Md. -- In various parts of the world where Aedes aegypti mosquitoes were bred with the naturally occurring bacteria Wolbachia and then released into the wild, there was a reduced incidence of dengue infection, a researcher said here.

Large-scale deployments of these mosquito programs in Australia, Indonesia, Vietnam, and Brazil produced field evidence of reduced dengue incidence, even up to several years after deployment, reported Katie Anders, PhD, of Monash University in Melbourne, Australia.

At a presentation at the annual meeting of the American Society of Tropical Medicine & Hygiene, Anders discussed this real-world evidence for the effectiveness of these programs.

"Even given the well-understood limitations, even with imperfect data, we are still seeing a signal [of these programs] across multiple sites," she said. "We have field evidence that these Wolbachia deployments can reduce dengue transmission."

As described on the World Mosquito Program website, this not-for-profit initiative seeks to breed mosquitoes that carry Wolbachia bacteria, which is not naturally occurring in A. aegypti mosquitoes. But the presence of Wolbachia decreases the mosquito's ability to be infected by dengue, chikungunya, yellow fever, and even Zika viruses, which they can then pass on to humans. The programs then release these mosquitoes into the wild to breed with other mosquitoes. The idea is that eventually, the Wolbachia mosquitoes will overtake the wild-type mosquitoes -- meaning that a mosquito with less ability to infect humans will be predominant in the areas.

It's not just a theory either. Anders pointed to a mathematical modeling study that looked at simulations up to 10 years post-release of Wolbachia mosquitoes, and estimated a more than 95% reduction in symptomatic dengue incidence.

The World Mosquito Program has operations in 12 countries, and deployments in 10 countries, including Australia, Latin America, countries in the Pacific, as well as planned programs in India and Sri Lanka in 2020, Anders said.

North Queensland, Australia, has the longest program, as releases of Wolbachia mosquitoes started as early as 2011 in towns such as Cairns and Townsville. Anders reported that there have been no outbreaks of dengue in northern Queensland for the past 5 years, and estimated a 96% reduction (95% CI 84%-99%) in the incidence of locally acquired dengue, based on dengue-notified cases from January 2001 to September 2019.

Likewise, a quasi-experimental study in Yogyakarta, Indonesia examined dengue case notifications following the release of Wolbachia mosquitoes, and found a 76% reduction (95% CI 60%-86%) in notified dengue incidence. Similar results were seen following deployment in Niteroi, a city near Rio de Janeiro in Brazil (73% reduction in notified dengue incidence).

Anders also pointed to anecdotal evidence in Vinh Luong, a small community in Vietnam, which showed an 86% reduction (95% CI 76%-92%) in notified dengue incidence following deployment of Wolbachia mosquitoes. She added that there was no increase in dengue incidence in this town despite a record year in Nha Trang, a large urban area adjacent to Vinh Luong.

And actual clinical trials are underway in both Yogyakarta, Indonesia and in the city of Medellin in Colombia. In Yogyakarta, a cluster-randomized trial where 24 clusters will be randomized to either Wolbachia deployments or routine dengue control. A test-negative design will examine febrile patients at outpatient clinics -- both virologically confirmed dengue cases and arbovirus-negative controls. The trial is ongoing until the end of 2020.

Medellin's "pragmatic approach" will combine an interrupted time series analyses of dengue case notifications and a case-control study with a test-negative design, though Anders noted the area has experienced low dengue transmission since the 2016 epidemic there.

"We will apply a time series analysis to see if we continue to get replication of this signal across project sites," she said.