The number of dengue cases reported to the World Health Organization (WHO) has increased eight-fold since 2000, from 500,000 cases to 4.2 million in 2019. Wolbachia-infected Aedes mosquitoes are bringing hope; they reduced dengue case numbers by 77 per cent during a World Mosquito Program (WMP) trial in Indonesia. We spoke with Dr Katie Anders, Director of Impact Assessment at WMP.

The trial divided the city of Yogyakarta into 24 communities and randomly selected 12 to receive the Wolbachia-infected mosquitoes; the other 12 showed what would have happened in the absence of Wolbachia. “We’re excited about the results of our randomised controlled trial in Yogyakarta,” Dr Anders told us. “While the study supports what we see elsewhere, it is the first time we have generated solid evidence of the true impact of Wolbachia-infected Aedes mosquitoes on dengue.”

The study was specifically designed to stand up to scientific rigour. In addition to the control communities, the study confirmed dengue case numbers in laboratories, whereas previous trials had relied on health facilities notifying authorities of patients with the disease. Also, previous trials had struggled to exclude factors such as natural fluctuations in dengue dynamics.

The results are likely to be a conservative estimate of the Wolbachia effect. “The movement of people and mosquitoes across our randomly allocated communities may have diluted the result,” said Dr Anders.

Dr Anders goes on to explain how, equally importantly, the study showed that you don’t need to deploy Wolbachia-infected mosquitoes to every last square hundred metres of a city because “any holes left fill themselves in over time”.

Big cities targeted for Wolbachia-infected mosquitoes

WMP is currently prioritising big cities with a massive burden of disease, expanding interventions in Colombia, Brazil, Mexico and Indonesia. “The impact of Wolbachia might be even higher deploying across a whole city,” said Dr Anders. “In cities seeing tens of thousands of dengue cases, Wolbachia offers a huge potential benefit.” It aims to reach more than 75 million people over the next five years, from 5 million people to date.

The team plans to release mosquitoes for a second randomised controlled trial in Belo Horizonte in Brazil later this year. The trial is being run by a US-based academic group and funded by the US National Institutes of Health.

However, overall WMP is shifting focus from evidence generation to scaled implementation and cost-effectiveness. “We’re aiming operational deployments where we can achieve the biggest impact for the lowest cost,” Dr Anders explains.

Costs come down when regions manufacture their own mosquitoes at scale to supply countries within the region. With that in mind, Dr Anders shared WMP innovations since we last spoke in May of last year: “We are innovating for production at scale, quality assurance, a longer mosquito egg shelf-life, and to distribute eggs efficiently to cover larger areas faster and more cost-effectively.”

Its focus includes:

• producing large quantities of high-quality mosquito eggs for cost-effective deployment over large cities
• optimising the supply chain in distributing mosquito eggs from large regional manufacturing centres to partner countries
• involving the community more directly, replacing the army of field officers it uses today
• using drones to release measured numbers of mosquitoes, following a successful pilot in Fiji
• finding new approaches to reaching big cities and complex environments

The impact of COVID-19

For WMP, the COVID-19 pandemic has affected operations. While WMP paused face-to-face interaction for distributing eggs, releases are now resuming. Sites have developed contact-free methods for setting mosquito containers and for receiving the mosquitoes collected to monitor Wolbachia establishment.

Data-gathering is being impacted too. Trials reliant on surveillance systems may be underestimating dengue case numbers as people are less likely to present at a health facility, and government are sometimes delaying data notifications.

On a global scale, community-based activities for mosquito control have paused. And people are spending more time at home, where the risk of dengue transmission is high. The pandemic may be fuelling dengue outbreaks. “Singapore is facing its largest dengue epidemic on record this year,” said Dr Anders. “Thailand and Malaysia have also had big years. And they’re also dealing with COVID-19. Dengue and COVID-19 combined could overwhelm health systems.”

What’s more, COVID-19 is diverting both attention and funding away from dengue and other diseases. Nevertheless, dengue-endemic countries are recognising how dengue has been a problem for decades, is a problem now and is going to continue being a problem. “WMP is still getting a lot of interest from communities and governments in dengue-endemic countries,” she says. “They see there’s still a massive need for effective control because dealing with COVID-19 and dengue is a double burden on their health systems.”

The exciting results from the Yogyakarta trial serve only to strengthen WMP as it engages prospective partners. We’re looking forward to seeing how WMP operations expand operations in the coming months and years.