Dengue Incidence Down by Three Fourths in Wolbachia-Treated Areas in Indonesia

By Rob Goodier

November 30, 2020

NEW YORK (Reuters Health) - The incidence of dengue appears to have dropped by 77% in areas of Yogyakarta City, Indonesia, that were treated with Wolbachia-infected mosquito eggs in a new cluster-randomized trial, according to new research.

When mosquitoes are infected with Wolbachia bacteria, their ability to transmit RNA viruses such as dengue is reduced.

"In fact, the 77% reduction in dengue incidence that we observed in Wolbachia-treated areas was much larger than the 50% effect size that we powered the trial to detect," said Dr. Katherine Anders of the World Mosquito Program at Monash University in Melbourne, Australia.

"We expect that after Wolbachia deployments are completed throughout the untreated areas of Yogyakarta by the end of this year, we are likely to see an even greater impact on dengue transmission - and are optimistic that this may even result in local elimination of dengue for years to come," she told Reuters Health by email.

The findings were presented November 18 at the virtual annual meeting of the American Society of Tropical Medicine and Hygiene.

Dr. Anders and colleagues conducted what may be the first randomized controlled trial of this type of intervention. The study divided 312,000 people in an area of 26 square kilometers (10 square miles) of Yogyakarta into 24 clusters. Half of the clusters were randomized to receive batches of Aedes aegypti mosquito eggs infected with Wolbachia, and the entire region received standard mosquito control measures.

Coronavirus lockdowns cut the trial short in March 2020 after it had run for more than two years. Using a test-negative design, the researchers enrolled 8,144 participants, including 385 with virologically confirmed dengue infections and 5,921 test-negative controls.

The primary endpoint was efficacy in reducing confirmed dengue caused by any dengue virus serotype. In the intention-to-treat (ITT), the researchers compared the odds of residence in a Wolbachia-treated area between cases and test-negative controls.

"This design allowed them to directly compare the risk of dengue infection in communities that were very near to each other yet exposed to either the natural mosquitoes or the Wolbachia-infected mosquitoes," explained Dr. Stephanie Yanow, a professor of global health at the University of Alberta in Edmonton, Canada, who was not involved in the research.

"This is a powerful approach to assess the effects of the intervention on risk of infection in populations with similar characteristics and at close geographical proximity," she said.

The efficacy of Wolbachia deployments in preventing confirmed dengue was 77.1% (95% confidence interval, 65.3 to 84.9), and the data suggested the intervention was similarly effective against all four dengue virus serotypes.

"This gives us great confidence in continuing our work to scale up, and to make this effective intervention available to tens of millions more people living in areas at risk of dengue over the next few years," Dr. Anders said.

The intervention is considered sustainable in part because the infection, once introduced, tends to spread unaided through mosquito populations and eventually outnumber the non-infected mosquitoes.

Infected females can successfully mate whether or not the male is infected, and the eggs she lays will be infected. Non-infected females, however, will not produce eggs if they are fertilized by an infected male.

Infected females tend to produce fewer eggs, but that reproductive disadvantage is not enough to prevent the spread of the infection, according to recent research.

The World Mosquito Program (WMP) first released Wolbachia-infected mosquitoes into the wild in Australia in 2011, and the bacterium remains in those mosquito populations.

"Unlike other vector-control interventions that need to be reapplied regularly in order to achieve sustained suppression of the mosquito population, WMP's Wolbachia method is self-sustaining for years following a single period of releases. Wolbachia levels remain high in the local mosquito populations in northern Australia now nine years post-release, and in Indonesia now more than three years post-release, making this an effective and long-term solution to reducing the burden of Aegypti-borne diseases," Anders said.

SOURCE: American Society of Tropical Medicine and Hygiene 2020 annual meeting, presented November 18, 2020.