Dataset Information

Efficacy of a spatial repellent for control of Aedes-borne virus transmission: A cluster-randomized trial in Iquitos, Peru.

ABSTRACT: Over half the world's population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABVs by releasing active ingredients into the air that disrupt mosquito-human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate, and parity status through mixed-effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34.1% (one-sided 95% CI lower limit, 6.9%; one-sided P value = 0.0236, z = 1.98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28.6 (95% CI 24.1%, ∞); z = -9.11) and 12.4% (95% CI 4.2%, ∞); z = -2.43), respectively. Our trial provides conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

SUBMITTER: Morrison AC

PROVIDER: S-EPMC9245620 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Efficacy of a spatial repellent for control of Aedes-borne virus transmission: A cluster-randomized trial in Iquitos, Peru.

Morrison Amy C AC Reiner Robert C RC Elson William H WH Astete Helvio H Guevara Carolina C Del Aguila Clara C Bazan Isabel I Siles Crystyan C Barrera Patricia P Kawiecki Anna B AB Barker Christopher M CM Vasquez Gissella M GM Escobedo-Vargas Karin K Flores-Mendoza Carmen C Huaman Alfredo A AA Leguia Mariana M Silva Maria E ME Jenkins Sarah A SA Campbell Wesley R WR Abente Eugenio J EJ Hontz Robert D RD Paz-Soldan Valerie A VA Grieco John P JP Lobo Neil F NF Scott Thomas W TW Achee Nicole L NL

Proceedings of the National Academy of Sciences of the United States of America 20220623 26

Over half the world's population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical ...[more]

PMID: 35737833

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Project description:BackgroundEmpiric evidence shows that Aedes aegypti abundance is spatially heterogeneous and that some areas and larval habitats produce more mosquitoes than others. There is a knowledge gap, however, with regards to the temporal persistence of such Ae. aegypti abundance hotspots. In this study, we used a longitudinal entomologic dataset from the city of Iquitos, Peru, to (1) quantify the spatial clustering patterns of adult Ae. aegypti and pupae counts per house, (2) determine overlap between clusters, (3) quantify the temporal stability of clusters over nine entomologic surveys spaced four months apart, and (4) quantify the extent of clustering at the household and neighborhood levels.Methodologies/principal findingsData from 13,662 household entomological visits performed in two Iquitos neighborhoods differing in Ae. aegypti abundance and dengue virus transmission was analyzed using global and local spatial statistics. The location and extent of Ae. aegypti pupae and adult hotspots (i.e., small groups of houses with significantly [p<0.05] high mosquito abundance) were calculated for each of the 9 entomologic surveys. The extent of clustering was used to quantify the probability of finding spatially correlated populations. Our analyses indicate that Ae. aegypti distribution was highly focal (most clusters do not extend beyond 30 meters) and that hotspots of high vector abundance were common on every survey date, but they were temporally unstable over the period of study.Conclusions/significanceOur findings have implications for understanding Ae. aegypti distribution and for the design of surveillance and control activities relying on household-level data. In settings like Iquitos, where there is a relatively low percentage of Ae. aegypti in permanent water-holding containers, identifying and targeting key premises will be significantly challenged by shifting hotspots of Ae. aegypti infestation. Focusing efforts in large geographic areas with historically high levels of transmission may be more effective than targeting Ae. aegypti hotspots.

Project description:During the last 50 years, the geographic range of the mosquito Aedes aegypti has increased dramatically, in parallel with a sharp increase in the disease burden from the viruses it transmits, including Zika, chikungunya, and dengue. There is a growing consensus that vector control is essential to prevent Aedes-borne diseases, even as effective vaccines become available. What remains unclear is how effective vector control is across broad operational scales because the data and the analytical tools necessary to isolate the effect of vector-oriented interventions have not been available. We developed a statistical framework to model Ae. aegypti abundance over space and time and applied it to explore the impact of citywide vector control conducted by the Ministry of Health (MoH) in Iquitos, Peru, over a 12-year period. Citywide interventions involved multiple rounds of intradomicile insecticide space spray over large portions of urban Iquitos (up to 40% of all residences) in response to dengue outbreaks. Our model captured significant levels of spatial, temporal, and spatio-temporal variation in Ae. aegypti abundance within and between years and across the city. We estimated the shape of the relationship between the coverage of neighborhood-level vector control and reductions in female Ae. aegypti abundance; i.e., the dose-response curve. The dose-response curve, with its associated uncertainties, can be used to gauge the necessary spraying effort required to achieve a desired effect and is a critical tool currently absent from vector control programs. We found that with complete neighborhood coverage MoH intra-domicile space spray would decrease Ae. aegypti abundance on average by 67% in the treated neighborhood. Our framework can be directly translated to other interventions in other locations with geolocated mosquito abundance data. Results from our analysis can be used to inform future vector-control applications in Ae. aegypti endemic areas globally.

Project description:BackgroundKnowledge of spatial patterns of dengue virus (DENV) infection is important for understanding transmission dynamics and guiding effective disease prevention strategies. Because movement of infected humans and mosquito vectors plays a role in the spread and persistence of virus, spatial dimensions of transmission can range from small household foci to large community clusters. Current understanding is limited because past analyses emphasized clinically apparent illness and did not account for the potentially large proportion of inapparent infections. In this study we analyzed both clinically apparent and overall infections to determine the extent of clustering among human DENV infections.Methodology/principal findingsWe conducted spatial analyses at global and local scales, using acute case and seroconversion data from a prospective longitudinal cohort in Iquitos, Peru, from 1999-2003. Our study began during a period of interepidemic DENV-1 and DENV-2 transmission and transitioned to epidemic DENV-3 transmission. Infection status was determined by seroconversion based on plaque neutralization testing of sequential blood samples taken at approximately six-month intervals, with date of infection assigned as the middate between paired samples. Each year was divided into three distinct seasonal periods of DENV transmission. Spatial heterogeneity was detected in baseline seroprevalence for DENV-1 and DENV-2. Cumulative DENV-3 seroprevalence calculated by trimester from 2001-2003 was spatially similar to preexisting DENV-1 and DENV-2 seroprevalence. Global clustering (case-control Ripley's K statistic) appeared at radii of ?200-800 m. Local analyses (Kuldorf spatial scan statistic) identified eight DENV-1 and 15 DENV-3 clusters from 1999-2003. The number of seroconversions per cluster ranged from 3-34 with radii from zero (a single household) to 750 m; 65% of clusters had radii >100 m. No clustering was detected among clinically apparent infections.Conclusions/significanceSeroprevalence of previously circulating DENV serotypes can be a predictor of transmission risk for a different invading serotype and, thus, identify targets for strategically placed surveillance and intervention. Seroprevalence of a specific serotype is also important, but does not preclude other contributing factors, such as mosquito density, in determining where transmission of that virus will occur. Regardless of the epidemiological context or virus serotype, human movement appears to be an important factor in defining the spatial dimensions of DENV transmission and, thus, should be considered in the design and evaluation of surveillance and intervention strategies.

Project description:Dengue is one of the most important vector-borne diseases, resulting in an estimated hundreds of millions of infections annually throughout the tropics. Control of dengue is heavily dependent upon control of its primary mosquito vector, Aedes aegypti. Innovative interventions that are effective at targeting the adult stage of the mosquito are needed to increase the options for effective control. The use of insecticide-treated curtains (ITCs) has previously been shown to significantly reduce the abundance of Ae. aegypti in and around homes, but the impact of ITCs on dengue virus (DENV) transmission has not been rigorously quantified. A parallel arm cluster-randomized controlled trial was conducted in Iquitos, Peru to quantify the impact of ITCs on DENV seroconversion as measured through plaque-reduction neutralization tests. Seroconversion data showed that individuals living in the clusters that received ITCs were at greater risk to seroconverting to DENV, with an average seroconversion rate of 50.6 per 100 person-years (PY) (CI: 29.9-71.9), while those in the control arm had an average seroconversion rate of 37.4 per 100 PY (CI: 15.2-51.7). ITCs lost their insecticidal efficacy within 6 months of deployment, necessitating re-treatment with insecticide. Entomological indicators did not show statistically significant differences between ITC and non-ITC clusters. It's unclear how the lack of protective efficacy reported here is attributable to simple failure of the intervention to protect against Ae. aegypti bites, or the presence of a faulty intervention during much of the follow-up period. The higher risk of dengue seroconversion that was detected in the ITC clusters may have arisen due to a false sense of security that inadvertently led to less routine protective behaviors on the part of households that received the ITCs. Our study provides important lessons learned for conducting cluster randomized trials for vector control interventions against Aedes-transmitted virus infections.

Project description:The importance of mosquitoes in human pathogen transmission has motivated major research efforts into mosquito biology in pursuit of more effective vector control measures. Aedes aegypti is a particular concern in tropical urban areas, where it is the primary vector of numerous flaviviruses, including the yellow fever, Zika, and dengue viruses. With an anthropophilic habit, Ae. aegypti prefers houses, human blood meals, and ovipositioning in water-filled containers. We hypothesized that this relatively simple ecological niche should allow us to predict the impacts of insecticidal control measures on mosquito populations. To do this, we use Skeeter Buster 2 (SB2), a stochastic, spatially explicit, mechanistic model of Ae. aegypti population biology. SB2 builds on Skeeter Buster, which reproduced equilibrium dynamics of Ae. aegypti in Iquitos, Peru. Our goal was to validate SB2 by predicting the response of mosquito populations to perturbations by indoor insecticidal spraying and widespread destructive insect surveys. To evaluate SB2, we conducted two field experiments in Iquitos, Peru: a smaller pilot study in 2013 (S-2013) followed by a larger experiment in 2014 (L-2014). Here, we compare model predictions with (previously reported) empirical results from these experiments. In both simulated and empirical populations, repeated spraying yielded substantial yet temporary reductions in adult densities. The proportional effects of spraying were broadly comparable between simulated and empirical results, but we found noteworthy differences. In particular, SB2 consistently over-estimated the proportion of nulliparous females and the proportion of containers holding immature mosquitoes. We also observed less temporal variation in simulated surveys of adult abundance relative to corresponding empirical observations. Our results indicate the presence of ecological heterogeneities or sampling processes not effectively represented by SB2. Although additional empirical research could further improve the accuracy and precision of SB2, our results underscore the importance of non-linear dynamics in the response of Ae. aegypti populations to perturbations, and suggest general limits to the fine-grained predictability of its population dynamics over space and time.

Project description:BackgroundOver the past decades, several viral diseases transmitted by Aedes mosquitoes-dengue, chikungunya, Zika-have spread outside of tropical areas. To limit the transmission of these viruses and preserve human health, the use of mosquito traps has been developed as a complement or alternative to other vector control techniques. The objective of this work was to perform a systematic review of the existing scientific literature to assess the efficacy of interventions based on adult mosquito trap to control Aedes population densities and the diseases they transmit worldwide.Methods and findingsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted using the PubMed and Scopus databases. Among the 19 selected papers, lethal ovitraps were used in 16 studies, host-seeking female traps in 3 studies. Furthermore, 16 studies focused on the control of Ae. aegypti. Our review showed great heterogeneity in the indicators used to assess trap efficacy: e.g., the number of host-seeking females, the number of gravid females, the proportion of positive containers, the viral infection rate in female mosquitoes or serological studies in residents. Regardless of the type of studied traps, the results of various studies support the efficacy of mass trapping in combination with classical integrated vector control in reducing Aedes density. More studies with standardized methodology, and indicators are urgently needed to provide more accurate estimates of their efficacy.ConclusionsThis review highlights gaps in the demonstration of the efficacy of mass trapping of mosquitoes in reducing viral transmission and disease. Thus, further large-scale cluster randomized controlled trials conducted in endemic areas and including epidemiological outcomes are needed to establish scientific evidence for the reduction of viral transmission risk by mass trapping targeting gravid and/or host-seeking female mosquitoes.

Dataset Information

Efficacy of a spatial repellent for control of Aedes-borne virus transmission: A cluster-randomized trial in Iquitos, Peru.

Publications

Efficacy of a spatial repellent for control of <i>Aedes</i>-borne virus transmission: A cluster-randomized trial in Iquitos, Peru.

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