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Scott, T.

Publications and source records attributed to Scott, T..

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Vertical transmission of Zika virus from orally infected Aedes aegypti produces infectious adult progeny.

Vertical transmission, or pathogen transfer from mother to offspring, can facilitate persistence of emerging arboviruses, such as Zika virus (ZIKV), in mosquito populations. Understanding vertical transmission and the different environmental and temporal conditions that affect it is important to assess whether new outbreaks could occur without reintroduction of the virus. To determine the rate of vertical transmission for ZIKV, Aedes aegypti females were fed on ZIKV infected blood, maintained under three temperature conditions (27{degrees}C, 30{degrees}C, and 33{degrees}C), and allowed to oviposit three times. Progeny were tested for virus presence at 3, 7, and 14 days after adult emergence. The overall vertical transmission rate was 6.5% (3.9 - 9.9). Vertical transmission was observed across all maternal temperature conditions and was detected in adult progeny as young as 3 days and as late as 14 days post-emergence. In total, 3.4% (1.6 - 6.2) of adult progeny produced saliva with detectable ZIKV, indicating their capacity to transmit ZIKV to humans. To our knowledge, this is the first evidence that vertical transmission occurs from orally-infected female Aedes aegypti to their adult progeny at a range of temperatures, and proof that Zika virus can persist in the saliva of those progeny throughout their lifetimes. These results suggest that the virus may be maintained in Ae. aegypti populations without a vertebrate host, allowing for human infections to occur without consistent re-introductions of ZIKV.\n\nAuthor SummaryIn 2015, Zika virus spread to over 50 countries. However, it is not known whether the virus persisted in the outbreak areas or became locally extinct. One way mosquito-borne viruses, like Zika, could become established is by transferring directly between mosquito generations rather than circulating between mosquitoes and humans. This is known as vertical transmission, and happens when the virus infects the developing eggs of infected maternal mosquitoes. As with other mosquito-borne diseases, like dengue, in order to infect humans the virus must be present in the saliva of infected mosquito progeny during blood feeding. We found vertical transmission occurred throughout the infected mothers reproductive lifetime and across a range of temperature conditions. Vertically infected progeny had Zika virus in their saliva as early as three days after adult emergence, implying that they could infect a person even during their first bloodmeal. Importantly, this work indicates that Zika virus could establish itself in the mosquito population even when human to mosquito transmission is not actively occurring.

epidemiology

Estimating the impact of city-wide Aedes aegypti population control: An observational study in Iquitos, Peru

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.\n\nAuthor SummaryDespite the growing threat of arboviruses, there is a dearth of best practices for the primary vector control tools used in the field. In the absence of cluster randomized control trials, evidence on the utility (or lack thereof) of vector control interventions must be gleaned from ongoing control programs. Motivated by 12 years of household-level Ae. aegypti abundance surveys and neighborhood-level space-spray campaign data from Iquitos, Peru, we developed a new framework to model mosquito abundance. In spite of significant spatial and temporal heterogeneity, we identified a statistically significant and practically important impact of the local Ministry of Health space-spray campaign, specifically, a reduction of mosquito abundance of 67% when coverage was optimal. Our framework can be directly applied to other locations with geolocated mosquito abundance data and our findings can be used to both optimize resources within Iquitos as well as inform future vector-control interventions in Ae. aegypti endemic areas globally.

ecology

Statistical and biological uncertainties associated with vaccine efficacy estimates and their implications for dengue vaccine impact projections

Given the limited effectiveness of strategies based solely on vector control to reduce dengue virus (DENV) transmission, it is expected that an effective vaccine could play a pivotal role in reducing the global disease burden of dengue. Of several dengue vaccines under development, Dengvaxia(R) from Sanofi Pasteur recently became the first to become licensed in select countries and to achieve WHO recommendation for use in certain settings, despite the fact that a number of uncertainties about its profile complicate projections of its public health impact. We used a stochastic, agent-based model for DENV transmission to perform simulations of the public health impact of dengue vaccines in light of two key uncertainties: (1) \"statistical uncertainty\" about the numerical value of the vaccines efficacy against disease, and (2) \"biological uncertainty\" about the extent to which its efficacy against disease derives from the amelioration of symptoms, blocking of DENV infection, or some combination thereof. Simulations of a generic dengue vaccine showed that the proportion of disease episodes averted following 20 years of routine vaccination of nine-year olds at 80% coverage was sensitive to both the numerical value of vaccine efficacy and to the extent to which efficacy derives from blocking of DENV infection. Simulations of a vaccine resembling Dengvaxia(R) took into account that vaccine trial results substantially reduced statistical uncertainty but did not address biological uncertainty, resulting in the proportion of disease episodes averted being more sensitive to biological uncertainty than to statistical uncertainty. Taken together, our results indicate limitations associated with the use of symptomatic disease as the primary endpoint of dengue vaccine trials and highlight the importance of considering multiple forms of uncertainty in projections of a vaccines public health impact.

epidemiology