Vaccines that block transmission of malaria to mosquitoes have the potential to be critical tools in the drive to eliminate or eradicate malaria. Assays to estimate the potential benefit of these vaccines need to be standardized and validated in malaria exposed populations. This year, the studies that assess malaria transmission blocking assays and gametocyte carriage rates in Bancoumana, Mali under NIAID Protocol 11-I-N143 were completed. An additional study under NIAID Protocol 14-I-N159 was initiated to has allow further evaluation of a modality called Experimental Huts that was implemented to measure transmission in wild-caught mosquitoes, and is continuing. The Protocol 11-I-N143 completed enrollment of 248 children and adults in July 2011. In July 2012, 238 additional participants were recruited. The study had been extended through this year as a platform to assess malaria transmission assays; the last study visits were completed in Aug 2015, and the protocol is now in the process of being closed. Participants were followed monthly to determine parasite carriage rates. Some gametocyte positive volunteers participated in mosquito feeding assays (direct skin feeds; membrane feeds; Experimental Hut studies) to provide data on parasite transmission to mosquito using various laboratory methods. Data on gametocyte carriage and mosquito infectivity from these protocols were used to determine the design of a Phase 1 study in malaria-exposed adults of Pfs25-EPA/Alhydrogel, which was completed this past year. This is the first field trial of a transmission blocking vaccine. In additional to safety and immunogenicity, the trial has provided an opportunity to further develop feeding assays, with the ultimate goal of validating an assay which can be used as an efficacy surrogate. A key goal over the past 2 years has been to assess the parameters under which feeding assays are performed, in order to optimize the rate of mosquito infections. In these studies, we have made the following conclusions: 1. Feeding mosquitoes on the arms versus calves versus ankles of study participants did not significantly differ in infection rates, though feeding on arms generally yielded higher infection rates 2. Feeding mosquitoes at dusk versus dawn did not significantly differ in infection rates, though feeding at dawn generally yielded higher infection rates 3. Optimal mosquito ages and duration of starvation were identified Another signficant finding this year is that our design for Experimental Hut studies is a reliable method to capture wild mosquitoes that have fed on local residents in Mali. This method entails having a single family member sleep in a hut under study, which is encased in exit traps to retain bloodfed wild mosquitoes. Thus far, we find that all evaluable mosquitoes captured had fed on the subject staying in the hut. This provides a basis to extend these studies an additional year. We have also used data from these studies to understand host factors that influence malaria transmission. Hemoglobinopathies modify the clinical expression of malaria infection but their effect on the reservoir of falciparum parasites remains largely unexplored. Based on the transmission studies, we observed that hemoglobin C heterozygotes are more likely to carry parasites including transmissible gametocytes, while hemoglobin S heterozygotes are less likely to carry parasites, compared to hemoglobin AA individuals. Hemoglobin C heterozygotes disproportionately maintain the parasite reservoir throughout the dry season.
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