The parallel, cluster-randomized, controlled trial revealed that a spatial repellent, currently under review by the World Health Organization (WHO), reduced human Aedes-borne virus infection by 34.1 percent.
“That is a significant statistical and public health reduction,” said Scott, an internationally recognized medical entomologist who retired from the UC Davis Department of Entomology and Nematology in 2015 but continues his scientific research on the ecology and epidemiology of dengue, a mosquito-borne viral infection transmitted mainly by A. aegypti. Dengue, one of the most rapidly increasing vector-borne infectious diseases, infects some 400 million people a year, with 4 billion people at risk annually.
The clinical study results mean that spatial repellents have “the potential to reduce a variety of vector-borne diseases, augment existing public health efforts, and can be an effective component in vector control intervention strategies,” Scott said.
The newly published research, “Efficacy of a Spatial Repellent for Control of Aedes-borne Virus Transmission: A Cluster-Randomized Trial in Iquitos, Peru,” appears in the Proceedings of the National Academy of Sciences (PNAS). The Bill and Melinda Gates Foundation funded the research in a grant to the University of Notre Dame (UND). Medical entomologist Nicole Achee, a research professor at UND, served as the project leader.
“To have shown a substantial public health impact at an endemic site, is rewarding,” said Scott, now a resident of Luck, Wis. “Our results provide valuable new data on mosquito control that will help to fill long-standing knowledge gaps and improve guidance for development of enhanced public health policy. Because literally billions of people around the globe are at risk of infection and disease from these viruses we are encouraged that results from our trial will contribute to improved health and well-being of so many people.”
Epidemiologist Amy Morrison, a 1996-2018 project scientist with the UC Davis Department of Entomology and Nematology and now with the UC Davis School of Veterinary Medicine's Department of Pathology, Microbiology and Immunology, served as the lead author of the PNAS paper. “This trial was the most logistically challenging field project I've ever participated in,” she said. “I led the field efforts in Iquitos, Peru where I have resided since 1998. Our research team continued to amaze me; they had to replace more than 20,000 products in more than 2,000 houses every 15 days and managed 80 percent coverage of participating houses. This type of vector control trial is very difficult to carry out so demonstrating protective efficacy is very gratifying.”
Achee said the Peru study outcomes “are a critical component to achieving our goals for supporting a WHO policy endorsement for spatial repellents. The reduction in Aedes-borne virus infection in at-risk participants seen in trial results have fundamentally contributed to the WHO encouraging further consideration for the use of this product class in public health worldwide. This is a historical milestone that was led by the UC Davis implementing team and I am thrilled to have been part of the collaborative effort."
Spatial repellents are “devices that contain volatile active ingredients that disperse in air,” the authors explained. “The active ingredients can repel mosquitoes from entering a treated space, inhibit attraction to human host cues, or disrupt mosquito biting and blood-feeding behavior and, thus, interfere with mosquito–human contact. Any of these outcomes reduce the probability of pathogen transmission.”
More than half of the world population is at risk for infection with viruses transmitted by Aedes mosquitoes, including include dengue, Zika, chikungunya, and yellow fever, the scientists wrote.
Vector interventions are needed for Aedes-borne viral (ABV) disease prevention “but their application is hindered by the lack of evidence proving they prevent infection or disease," they wrote. "Results from our ABV study will help guide public health authorities responsible for operational management and worldwide ABV disease control and incentivize new strategies for disease prevention.”
“The primary mosquito vector, Aedes aegypti, thrives in modern tropical urban environments. Despite decades of effort to control Ae. aegypti populations and prevent disease, the geographic range of illness and the viruses this mosquito transmits continue to expand,” they related. “Rigorously proven vector control interventions that measure protective efficacy against Aedes-borne viruses are limited to Wolbachia in a single trial in Indonesia and do not include any chemical interventions. Spatial repellents, a new option for efficient vector control, are designed to decrease human exposure to Aedes-borne viruses by releasing active ingredients into the air that disrupt mosquito–human contact and, thus, reduce the risk of human infection.”
The Iquitos trial is one of two trials recommended by WHO for assessing public health value and developing global health policy for the intervention class of spatial repellents. “Fully integrating vector control into Aedes-borne viral disease prevention programs requires quantitative guidance based on quantitative measures of the impact from each intervention component,” the authors wrote. “Ministries of Health, local to national governments, and nongovernmental organizations can use the Peru trial results as an evidence base for informed application of spatial repellents. Considering the growing public health threat from Aedes-borne viral disease, difficulties of developing vaccines against multiple viruses, and past poorly informed vector control failures, enhanced Aedes-borne viral disease prevention will benefit greatly from interventions, like the Peru trial, with proven public health value.
Thomas Scott. Scott, a member of three WHO committees and one of the world's Highly Cited Researchers for the third consecutive year, co-chairs a Lancet Commission that focuses on how prevention of viruses transmitted by Aedes mosquitoes. He served on the faculty of the Department of Entomology, University of Maryland, from 1983 to 1996 before joining the UC Davis entomology faculty as a professor of entomology and director of the Vector-Borne Disease Laboratory. Highly honored by his peers, Scott won the coveted Harry Hoogstraal Medal from the American Society of Tropical Medicine and Hygiene in 2018. He is a fellow of the American Society of Tropical Medicine and Hygiene, Entomological Society of America, and the American Association for the Advancement of Science. He holds bachelor and master's degrees from Bowling Green (Ohio) State University and a doctorate in ecology in 1981 from Pennsylvania State University.
Amy Morrison. Morrison, who holds a doctorate in public health from Yale University, with a concentration in epidemiology of infectious diseases, and a master's degree in public health from UCLA, has served as the principal investigator, co-principal investigator and a collaborator on a number of federally funded grants. She specializes in the epidemiology of tropical vector-borne diseases, with an emphasis on (1) arthropod vector ecology and dengue virus transmission dynamics and (2) spatial and temporal analyses using Geographic Information Systems.
As a project scientist, Morrison supervises multiple studies on A. aegypti and dengue virus transmission dynamics, including longitudinal cohort studies evaluating A. aegypti control interventions, and the role of human movement in dengue transmission dynamics in Iquitos, funded by National Institutes of Health, Military Infectious Disease Research Program and Bill and Melinda Gates Foundation. She is an active member of the American Mosquito Control Association, American Association for the Advancement of Science, Entomological Society of America, American Society of Tropical Medicine and Hygiene, and the Society of Vector Ecologists.
Nicole Achee. Achee is a research associate professor in the Department of Biological Sciences, UND, and holds a joint associate professor appointment in the Eck Institute for Global Health, UND. She worked as a medical entomologist in the international settings of Belize, Indonesia, Mexico, Nepal, Peru, South Korea, Suriname, Tanzania and Thailand. Her curriculum vitae includes principal investigator for large scale clinical trials in Peru and Indonesia. Both studies aimed “to generate evidence of the protective efficacy of spatial repellents for prevention of malaria and dengue human infections for use toward full World Health Organization public health policy recommendations,” she says on her website. Achee holds a doctorate in medical entomology from the Uniformed Services University of the Health Science, Bethesda, Md.
In addition to the Bill and Melinda Gates Foundation, the Iquitos project drew support from the Defense Threat Reduction Agency, Military Infectious Disease Research Program and the U.S. National Institute of Allergy and Infectious Diseases.