- Author: Kathy Keatley Garvey
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.
- Author: Kathy Keatley Garvey
Fischer, a member of the Mosquito Research Group, Department of Ecology, Genetics and Evolution, will speak on "The Recent Expansion of Aedes aegypti Distribution: Are the Populations Adapting to Colder Climate Regions?" at 4:10 p.m., Pacific Time. The Zoom link is https://ucdavis.zoom.us/j/99515291076.
She will be introduced by UC Davis doctoral student Erin Taylor Kelly of the laboratory of medical entomologist-geneticist Geoffrey Attardo.
"The mosquito Aedes aegypti, vector of dengue and other arboviruses, has recently expanded its distribution towards colder climate regions," Fischer says in her abstract. "This might be favored by an adaptation of the populations to local conditions. We explore the larval tolerance to low temperatures and the photo period-induced embryonic diapause as possible mechanisms occurring in temperate Argentina."
"My main research interest is on mosquito ecology, and my current project aims to analyze the effects of environmental conditions (photo period, temperature, humidity) and resources (larval food) on the fitness of Aedes aegypti," she writes on ResearchGate. "I am also interested in human caused environmental change and its consequences on vector borne diseases."
Fischer recently co-authored a research paper on Behavior of Aedes albifasciatus (Diptera: Culicidae) larvae from eggs with different dormancy times and its relationship with parasitism by Strelkovimermis spiculatus (Nematoda: Mermithidae).
Kelly, seminar host, researches the A. aegypti in the Attardo lab. She won a first-place award at the Entomological Society of America meeting last November with her poster, “Metabolic Snapshot: Using Metabolomics to Compare Near-Wild and Colonized Aedes aegypti.” She competed in the Physiology, Biochemistry and Ecology Section. (See https://bit.ly/3HJR0IF).
Fischer's talk meshes with the work of the Geoffrey Attardo laboratory. In one of his research projects, Attardo investigates the threat of these invasive mosquitoes, which have gained a foothold and spread throughout the state, putting California at risk for Aedes-vectored diseases such as dengue, chikungunya, Zika and yellow fever. Attardo studies the prevalence and physiology of insecticide resistance in Californian populations and evaluates the use of genetic markers to predict insecticide resistance and to track movement of genetically independent populations of aegypti throughout the state. Attardo and his lab are also currently developing novel biochemically oriented methods of insecticide resistance quantification to identify compounds that mosquito abatement districts can use for monitoring, and to define the biochemical pathways required to maintain this problematic adaptation.
The department's weekly seminars, held at 4:10 p.m. on Wednesdays, are coordinated by nematologist Shahid Siddique, who may be emailed at ssiddique@ucdavis.edu with any technical questions.
- Author: Kathy Keatley Garvey
“It's an issue of great concern, especially as current control methods do not appear to be working well,” said Cornel, who does research on the mosquito in Clovis, Fresno County, where it was discovered in June 2013. Simultaneously, the insect was found in the cities of Madera and San Mateo.
“This ongoing widespread invasion and establishment proves that this is no longer a regional issue and has affected many cities and towns in California,” he wrote Feb. 8 in F1000 Research, http://f1000research.com/slides/5-149.
But Cornel is optimistic that the pest management intervention strategies and surveillance and control tactics now underway will help control its spread. Infected Aedes aegypti can transmit dengue, yellow fever, Zika and chikungunya viruses.
The Zika virus, now spreading throughout the Western hemisphere, is an emerging mosquito-borne virus that was first identified in Uganda in 1947 in rhesus monkeys, according to the World Health Organization. It was subsequently identified in humans in 1952 in Uganda and the United Republic of Tanzania. Outbreaks of Zika virus disease have been recorded in Africa, the Americas, Asia and the Pacific.
Despite the mosquito's invasion in parts of the United States, there are no reported cases of locally transmitted Zika virus in California or in the contiguous United States, according to the Centers for Disease Control and Prevention. The cases have all involved travelers returning home from countries plagued with disease outbreaks.
Cornel works with the Consolidated Mosquito Abatement District, based in Fresno County, to tackle the spread of the mosquito there. The district covers 1,058 square miles, including part of Kings County.
How far north in California will the mosquito, commonly known as yellow fever mosquito, spread?
“I don't want to exclude the possibility that it may spread as far north as Sacramento,” said Cornel, who collects, rears and researches mosquitoes from all over the world, including the United States, Mali, Cameroon, Comoros, Tanzania, South Africa and Brazil. “We need to see if it overwinters as eggs or adults or both.”
It's troubling that the mosquito is becoming more and more resistant to pesticides, Cornel said. “We have found that the Aedes aegypti have insecticide resistance genes which likely explains why their ultra-low volume and barrier spray applications have not worked as well as expected.”
At Clovis, Cornel and his colleagues trap mosquitoes in gravid or ovitraps; study overwintering and flight dispersal; and employ mark-release-capture trials to estimate dispersal and population size, needed to plan biological (Wolbachia) and chemical auto-dissemination control strategies. They also engage in “recruiting” mosquitoes to kill other mosquitoes. “We have mosquitoes spread insecticides for us, that is, we turn them into mosquito-control workers through the use of insect growth regulators and biopesticides.”
Their 27-slide document, “Surveillance and Control of Aedes aegypti Mosquito in Clovis, Calif.,” published in F1000 Research details their research with text and maps. It is work of Cornel and Yoosook Lee of UC Davis; Stephen Dobson of the University of Kentucky; Corey Bansfield of MosqMate Inc. and Jodi Holeman, Mark Amireno, Charles Smith and Stephen Mulligan III of the Consolidated Mosquito Control District. In the document, Mulligan, director of the Consolidated Mosquito Control District, describes Aedes aegypti as “the rat of the mosquitoes.”
The California team works with University of Kentucky scientists to develop novel control strategies. One trial involves coating male mosquitoes with insect growth regulators, which are passed on to the females. Males are also infested with a biopesticide or “a good bacteria-like organism,” Wolbachia. “The male transfers it to the female, which affects the ovaries and negatively affects immature development,” Cornel explained. “It's not new, but it's not been employed in large trials.”
Regarding flight dispersal, Cornel has found that “males can fly well over 200 meters in one night from their breeding site. We previously thought it was no more than 60 to 100 meters.”
“The Aedes aegypti fly predominantly during cooler periods of the day,” the medical entomologist said. “When it's too hot, they hang around the shade.” When residents walk at dusk, both male and female mosquitoes can follow them. “Only the females bite but the males will hang around your ankle waiting for the females to arrive.”
The researchers target mosquito breeding sites, primarily yard drains. “Despite the drought and the elimination of visible bodies of water, such as bird baths, pet bowls and flower pots, there's a major issue: yard drains,” Cornel said. “Yard drains installed in new home developments empty into the gutter or street and are cryptic breeding sites for mosquitoes.” He speculates that these mosquitoes are breeding underground.
“These drains are not easily accessible and we can't see the mosquitoes,” Cornel pointed out. “We need to blow out the water and plug these yard drains to eliminate these breeding sites.” He suggests that cities everywhere address this public safety issue and “redesign the yard drains.”
Cornel works with the Consolidated Mosquito Abatement District in setting gravid or “killing traps” in the front yards of homes in Clovis. The traps, which look like five-gallon buckets, contain orchard grass and water. “When the orchard grass decomposes, it releases a plume of chemicals that attracts female Aedes aegypti to lay their eggs in,” Cornel said. A screen prevents them from reaching the water to lay their eggs. The insects adhere to black sticky paper.
It's crucial for the public to become involved, Cornel said. “We have to focus on public education. We have to get the message across to eliminate mosquito breeding sites. We can't go to every house. We must rely on the public to eliminate the breeding sites.”
It's possible—but he hopes not—that what is now a “mosquito nuisance” will result in a disease outbreak.
Related Links:
- Anthony Cornel: Mosquito Man UC Davis Department of Entomology and Nematology
- Anthony Cornel, Kearney Agricultural Research and Extension Center
- Yoosook Lee, UC Davis Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine
- F1000 Research
- Traps Tested in Clovis (UC ANR)
- Aedes aegypti, California Department of Public Health, Aedes aegypti
- Consolidated Mosquito Control District, based in Fresno County