When Google’s Debug project made headlines this spring for seeking permission to release genetically engineered mosquitoes in California and Florida, it raised a question that public health researchers also have been studying: Can technology solve a problem as old and stubborn as mosquito-borne disease? The Yale School of Public Health (YSPH) has its own experts at the forefront of that work. Dr. Albert Ko, MD, Raj and Indra Nooyi Professor of Public Health and professor of epidemiology (microbial diseases) and of medicine (infectious diseases), and Dr. Chantal Vogels, PhD, assistant professor of epidemiology, (microbial diseases), are both faculty in the Department of Epidemiology of Microbial Diseases — and both are studying new strategies to stop mosquitoes from spreading deadly viruses.
Dr. Ko, who is also a collaborating researcher at the Oswaldo Cruz Foundation-Brazilian Ministry of Health, co-leads the EVITA trial, a large National Institutes of Health (NIH)-funded randomized controlled trial in Brazil testing whether releasing mosquitoes infected with a naturally occurring bacterium called Wolbachia can protect communities from dengue, Zika, and chikungunya. Vogels studies the genetic diversity of viruses and how that variation affects the effectiveness of mosquito control strategies. Together, their research offers insights that extend beyond the tropics — including for West Nile virus, a mosquito-borne disease that continues to sicken and kill people across the United States each year. We asked them what they’ve learned, and what it means for the future of vector control.
1. What role can technology play in fighting mosquito-borne diseases, and what are the risks of leaving public health out of that conversation?
Dr. Vogels: Technological innovation can help overcome some of today’s most pressing public health challenges. Not only do we need new solutions to mitigate the impact of infectious diseases on public health, but we also need more sustainable and cost-effective solutions. In the context of mosquito-borne virus control, I see a role for partnerships between public health, big tech, and communities to identify new targets for control and to drive the broader-scale implementation of control interventions, such as Wolbachia-based strategies.
In the context of Wolbachia-based control, large numbers of mosquitoes need to be reared in the laboratory for release in the field. Technological advancement can help to automize mosquito mass rearing and sorting of male and female mosquitoes, which are used for different interventions: Male Wolbachia-carrying mosquitoes are released for mosquito population suppression (due to reproductive incompatibility with wildtype mosquitoes), whereas female Wolbachia-carrying mosquitoes are used for mosquito population replacement (replacing wildtype with Wolbachia-carrying mosquitoes).
Several factors affect how well Wolbachiacan prevent dengue virus infection. In our recent study, we look at how genetic differences in dengue virus impact Wolbachia’sability to block it. We tested two Wolbachiastrains against 60 different dengue virus samples from all four serotypes. We found that both the Wolbachiastrains and dengue virus samples varied in how well they worked together — some pairs inhibiting more effectively than others
This matters for real-world dengue control. When planning Wolbachia-based interventions, we need to account for dengue virus diversity. Genetic differences in the virus may explain why Wolbachiaworks well in some regions but not in others
We’ve shared this manuscript as a preprint so the scientific community can see our findings before formal peer review. We’ve also discussed this work with key stakeholders — public health officials, academics, industry partners, and government agencies. This broad conversation is important; leaving out any stakeholders risks hindering dengue control efforts
Before releasing Wolbachia-carrying mosquitoes, we need to clearly communicate the public health benefits to build awareness and public support
2. Describe the large National Institutes of Health (NIH) cluster randomized controlled trial in Brazil
Dr. Ko: The EVITA trial seeks to understand whether releasing Wolbachia-infected Aedes aegypti mosquitoes can protect people from being infected with viruses of public health importance such as dengue, Zika, and chikungunya
For the intervention we are evaluating we released Wolbachia-infected male and female mosquitoes. Rather than reduce native populations by releasing sterile males as they are doing in Debug (population suppression), our approach replaces the native mosquito population with Wolbachia-infected mosquitoes (population replacement), which are resistant to dengue, Zika, and chikungunya viruses
The advantage of this approach is that you only release mosquitoes once and don’t have to continuously release mosquitoes which can be costly and challenging to do in much of the Global South. The Debug strategy works in a small wealthy country such as Singapore, which spends greater than $20 million for vector control, but will be difficult if not impossible to implement in countries such as Brazil where urban centers have marginalized informal communities or rural regions are far from mosquito factories.
The EVITA trial, which was supported by the NIH and the Brazilian Ministry of Health, has just ended and we expect to disseminate the results by the end of the year
3. What can your research tell us about controlling West Nile Virus?
Dr. Ko: The population replacement approach, which we are evaluating in the EVITA trial and is now being rolled out throughout Brazil, is an intervention specific to preventing diseases transmitted by Aedes aegypti. Research is being done to see whether this would be a feasible approach for West Nile Virus, which is transmitted by another mosquito (Culexspecies). But it’s a more complex issue since Culexalready carries Wolbachiaso approaches are seeing if other improved strains of Wolbachia would work.
Dr. Vogels:Wolbachiais a promising intervention for mosquito-borne viruses with transmission cycles that primarily involve a single mosquito vector species (e.g., targeting Aedes aegyptifor dengue control). For these viruses, targeting a single mosquito species has the potential to make a significant impact on disrupting virus transmission. In contrast, West Nile virus has a much more complex transmission cycle that involves many mosquito species that can serve as vectors. This complex ecology makes it more challenging to use Wolbachia, because targeting a single mosquito species may not result in effective control, as other species may continue to contribute to virus transmission.
