Worldwide, between 50 and 100 million cases of dengue fever-an acute febrile disease found primarily in the tropics and Africa-occur each year. Spread by Aedes aegypti, a mosquito that prefers to feed on humans, dengue fever and dengue hemorrhagic fever are a major public health problem. Nicole Achee, Ph.D., Assistant Professor in the Uniformed Services University of the Health Sciences (USU) Department of Preventive Medicine and Biometrics, and her team comprised of U.S. and international researchers are undertaking an innovative research project to prevent dengue in Thailand and Peru. Their efforts will be supported by a new $3.5 million grant from the Bill & Melinda Gates Foundation to the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF).
Achee and colleagues at USU, including Don Roberts, Ph.D., USU professor emeritus and world-renowned authority on vector control, have devoted the last several years to analyzing vector control approaches. Much of this work has focused on quantifying the repellant, irritant and toxicant effects of chemicals used for vector control, including DDT, deltamethrin and several novel compounds. Among their findings, the team has shown that DDT can be an extremely effective repellant at application levels below what's currently being used in the field-levels that are non-toxic. Additionally, these studies have shown a significant repellent response even among resistant mosquitos. The group's work played a role in the World Health Organization's 2006 decision to actively promote DDT for public health use.
The team is taking a long-term approach to vector control, attempting to find an effective strategy that does not focus on the toxic actions of chemicals, which in the past has been the prevalent strategy. A purely toxic approach to vector control tends to accelerate the development of resistant populations. Research shows that killing the insects may not be necessary for effective vector control; initiating repellent and irritant responses may be sufficient by preventing house entry and/or causing an escape response prior to the mosquitos' biting humans indoors. In addtion, the integration of an outdoor trap in the peridometstic environment to capture these repelled/irritated mosquitoes may have an additive effect in reducing pathogen transmission. Such a "Push-Pull" approach is being evaluated in the current Project.
Translating laboratory results to a real-life setting requires on-site field validation in those countries from which test mosquito populations originate. This will provide a best-estimate approach to the applicability of the proposed vector control strategy. Peru and Thailand were chosen as field sites for the research program based on the importance of dengue and dengue hemorrhagic fever in both countries.
Iquitos, Peru Field Site
Team members from NAMRU-6 and UCDavis are conducting field validation of USUHS laboratory results using a mark-release-recapture experimental hut design. Experiments include quantifying indoor Ae. aegypti resting behavior preferences to identify optimal placement of chemical treatment (see Project Presentations). In addition, teams are evaluating the hut entry and exit behavioral responses upon exposure to chemical irritants and repellents. Personnel from Queensland Health and the local Department of Health (DISA) are currently optimizing traps for the reduction of host-seeking Ae. aegypti females in the peridomestic environment within the local cemetery. Focus group studies have been performed by Tulane University and USUHS Project participants in Iquitos to create awareness of program objectives and goals, determine social acceptance of the trap design, and guide further modifications to the Push-Pull strategy components based on qualitative data generated from the local population.
Kanchanaburi, Thailand Field Site
Team members from Kasetsart University are also conducting field validation of USUHS laboratory results using a mark-release-recapture experimental hut design. Test populations of Aedes aegypti are reared in an on-site insectary. Both resting pattern and entry/exit movement pattern studies are being evaluated following similar protocols used at the Peru field site (see Project Publications).
A 10 x 40 m screen house has been constructed at the Thai site to facilitate optimization studies for the peridomestic trap. Participants from both Kasetsart University and Colorado State University have explored changes in trap efficacy based on varying mosquito populations as well as following exposure to spatial repellent chemicals. Social scientists from the Thai Ministry of Health (MOH) have also conducted focus group discussions in two disease endemic populations within Thailand to identify challenges to acceptability and sustainability of the Push-Pull strategy during post-project development.
USU Laboratory Activities
Our team at USU has been responsible for designing and optimizing a novel behavioral assay system, what we call the Box Assay, for detailed quantification of resting behavior as well as SR and CI thresholds based on varying chemicals, concentration and treatment surface area coverage (see Box Laboratory Assay SOP). Outcome measures include the location of resting, the number of Ae. aegypti responding (not entering / escaping) along with knockdown and 24h mortality rates. We conduct the assays in a temperature/humidity controlled environment and use standard chemical compounds currently registered by WHO for vector control. Assay test populations are female Ae. aegypti mosquitoes from the F1-F4 generation ranging in age from 4-7DO. We acquire our mosquito eggs from the Peru and Thailand sites and routinely refresh our colonies with field material to maintain natural behavioral characteristics. Both colony and assay populations are maintained through membrane feeding in the USU insectary (see Insectary SOPs).