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Item type:Publication, Efficacy of a spatial repellent for control of Aedes-borne virus transmission: a cluster randomized trial in Iquitos, Peru(Cold Spring Harbor Laboratory, 2021-03-05)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 (ABV) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases is 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 ABV 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% (1-sided 95% CI lower limit, 6·9%; 1-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 the first conclusive statistical evidence from a pre-planned cluster randomized controlled clinical trial with a pre-defined effect size on the primary endpoint that was appropriate powered to prospectively quantify and statistically test for a difference in the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo. Significance Statement Vector interventions are needed for Aedes -borne viral diseases (dengue, Zika, chikungunya, and yellow fever) prevention, but their application is hindered by the lack of evidence proving they prevent infection or disease. Our research reports the first conclusive statistical evidence from a pre-planned, prospective cluster-randomized, controlled clinical trial (cRCT) of significant protective efficacy (34.1% hazard estimate) against human Aedes -borne virus (ABV) infection by a chemical-based vector control intervention, the most commonly used intervention category among all ABV World Health Organization recommendations. A previous trial against malaria in Indonesia indicated a positive trend but did not detect a significant effect. Results from our ABV study will help guide public health authorities responsible for operational management and world-wide prevention of ABV, and incentivize new strategies for disease prevention. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Efficacy of a spatial repellent for control of Aedes-borne virus transmission: A cluster-randomized trial in Iquitos, Peru(National Academy of Sciences, 2022-06-28)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. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Quantifying Heterogeneities in Arbovirus Transmission: Description of the Rationale and Methodology for a Prospective Longitudinal Study of Dengue and Zika Virus Transmission in Iquitos, Peru (2014–2019)(Public Library of Science, 2023-02-01)Current knowledge of dengue virus (DENV) transmission provides only a partial understanding of a complex and dynamic system yielding a public health track record that has more failures than successes. An important part of the problem is that the foundation for contemporary interventions includes a series of longstanding, but untested, assumptions based on a relatively small portion of the human population; i.e., people who are convenient to study because they manifest clinically apparent disease. Approaching dengue from the perspective of people with overt illness has produced an extensive body of useful literature. It has not, however, fully embraced heterogeneities in virus transmission dynamics that are increasingly recognized as key information still missing in the struggle to control the most important insect-transmitted viral infection of humans. Only in the last 20 years have there been significant efforts to carry out comprehensive longitudinal dengue studies. This manuscript provides the rationale and comprehensive, integrated description of the methodology for a five-year longitudinal cohort study based in the tropical city of Iquitos, in the heart of the Peruvian Amazon. Primary data collection for this study was completed in 2019. Although some manuscripts have been published to date, our principal objective here is to support subsequent publications by describing in detail the structure, methodology, and significance of a specific research program. Our project was designed to study people across the entire continuum of disease, with the ultimate goal of quantifying heterogeneities in human variables that affect DENV transmission dynamics and prevention. Because our study design is applicable to other Aedes transmitted viruses, we used it to gain insights into Zika virus (ZIKV) transmission when during the project period ZIKV was introduced and circulated in Iquitos. Our prospective contact cluster investigation design was initiated by detecttion of a person with a symptomatic DENV infection and then followed that person’s immediate contacts. This allowed us to monitor individuals at high risk of DENV infection, including people with clinically inapparent and mild infections that are otherwise difficult to detect. We aimed to fill knowledge gaps by defining the contribution to DENV transmission dynamics of (1) the understudied majority of DENV-infected people with inapparent and mild infections and (2) epidemiological, entomological, and socio-behavioral sources of heterogeneity. By accounting for factors underlying variation in each person’s contribution to transmission we sought to better determine the type and extent of effort needed to better prevent virus transmission and disease. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Direct Mosquito Feedings on Dengue-2 Virus-Infected People Reveal Dynamics of Human Infectiousness(Public Library of Science, 2023-09-01)Dengue virus (DENV) transmission from humans to mosquitoes is a poorly documented, but critical component of DENV epidemiology. Magnitude of viremia is the primary determinant of successful human-to-mosquito DENV transmission. People with the same level of viremia, however, can vary in their infectiousness to mosquitoes as a function of other factors that remain to be elucidated. Here, we report on a field-based study in the city of Iquitos, Peru, where we conducted direct mosquito feedings on people naturally infected with DENV and that experienced mild illness. We also enrolled people naturally infected with Zika virus (ZIKV) after the introduction of ZIKV in Iquitos during the study period. Of the 54 study participants involved in direct mosquito feedings, 43 were infected with DENV-2, two with DENV3, and nine with ZIKV. Our analysis excluded participants whose viremia was detectable at enrollment but undetectable at the time of mosquito feeding, which was the case for all participants with DENV-3 and ZIKV infections. We analyzed the probability of onward transmission during 50 feeding events involving 27 participants infected with DENV-2 based on the presence of infectious virus in mosquito saliva 7–16 days post blood meal. Transmission probability was positively associated with the level of viremia and duration of extrinsic incubation in the mosquito. In addition, transmission probability was influenced by the day of illness in a non-monotonic fashion; i.e., transmission probability increased until 2 days after symptom onset and decreased thereafter. We conclude that mildly ill DENV-infected humans with similar levels of viremia during the first two days after symptom onset will be most infectious to mosquitoes on the second day of their illness. Quantifying variation within and between people in their contribution to DENV transmission is essential to better understand the biological determinants of human infectiousness, parametrize epidemiological models, and improve disease surveillance and prevention strategies.