Measuring effects of ivermectin-treated cattle on malaria vectors in Vietnam: a village-randomized trial

Abstract

Background: Malaria elimination using current tools has stalled in many areas. Ivermectin (IVM) is a broad-antiparasitic drug and mosquitocide that has been proposed as a tool for reaching malaria elimination. Under laboratory conditions, IVM has been shown to reduce the survival of Anopheles populations that have fed on IVM-treated mammals. Treating cattle with IVM has been proposed as an important contribution to malaria vector management, however, the impacts of IVM in this animal health use-case had been untested in field trials in Southeast Asia. Methods: Through a randomized village-based trial, this study aimed to quantify the effect of IVM-treated cattle on anopheline populations in treated vs. untreated villages in Central Vietnam. Local zebu cattle in six rural villages were included in this study. Cattle were treated with IVM at established veterinary dosages in three villages and in three additional villages, cattle were untreated as controls. The mosquito populations in all villages were sampled using cattle-baited traps for six days before, and six days after a 2-day treatment IVM-administration (intervention) period. Vector species were characterized using taxonomic keys. The impact of the intervention was analyzed using a difference-in-differences (DID) approach with generalized estimating equations (Poisson distribution with bootstrapped errors). Results: Across the treated villages, 1,112 of 1,527 censused cows (73% overall; range 67% to 83%) were treated with IVM. In both control and treated villages, there was a 30% to 40% decrease in total anophelines captured in the post-intervention period as compared to the pre-intervention period. In the control villages, there were 1873 captured pre-intervention and 1079 captured during the post-intervention period. In the treated villages, there were 1594 captured pre-intervention, and 1101 captured during the post-intervention period. The DID model analysis comparing total captures between arms was not statistically significant (p = 0.67). Secondary outcomes of vector diversity found that in four villages (two treated and two control) there were statistically significant changes in the anopheline population diversity (p < 0.05) based on Shannons diversity index. Two villages (one treated and one control) had a statistically significant increase in diversity and two villages (one treated and one control) had a significant decrease in population diversity (p < 0.05). There were no clear trends in treated or untreated vector population evenness or richness estimates. Conclusions: Unexpectedly large decreases in trapping counts post-intervention across all study villages impacted the ability of this study to quantify any differential impacts. As such, the results of this study do not provide evidence that treating cattle in villages with IVM reduces nightly captures from cattle-baited traps of female anopheles mosquitoes when compared to control villages. The lack of differential impacts may be due to several factors including the short half-life of IVM, crossover in mosquito populations between treated and control villages, feeding preferences of the mosquitoes, and mass-action effects from extensive mosquito trapping. Future studies should plan to treat at least 80% of the cattle in the village and evaluate the relationship between dose-density and mosquito prevalence. Additional studies should investigate whether IVM differentially impacts vector species at a population level.