The protocol to develop malaria transmission blocking assays and to estimate gametocyte carriage rates has been continued in Bancoumana, Mali (NIAID Protocol 11-I-N143), and the protocol was renewed to allow another year of followup. Vaccines which block infectivity of malaria in mosquitoes have the potential to be critical tools in the drive to eliminate or eradicate malaria. Clinical development of such vaccines will require expertise in vaccinology, parasitology, and entomology, uniquely available in this collaboration. Assays to estimate the potential benefit of these vaccines need to be standardized and validated in malaria exposed populations. Baseline data from this protocol was used to plan for the first ever field trial of a transmission blocking vaccine, which was initiated in 2013. The study completed enrollment of 250 children and adults in July 2011, and the initial followup of this cohort was completed in June 2012, and has now been extended for a third year. Participants are followed monthly to determine parasite carriage rates. Some gametocyte positive volunteers participate in mosquito feeding assays (both direct skin feeds and membrane feeds) to provide data on mosquito infectivity using various laboratory methods. The results of feeding experiments will be presented at the ASTMH Conference in November 2013 in one oral presentation and one poster presentation. The Phase 1 clinical protocol for Pfs25-EPA/Alhydrogel transmission-blocking vaccine project was approved and the trial has been initiated. After a dose escalation trial in the US determined this to be a safe and immunogenic vaccine, this trial was designed to recruit 120 volunteers in Mali and randmize these to receive either the study vaccine or the comparator. Vaccinations were iniatied in Bancoumana and surrounging villages in Mali in May 2013 and volunteers continue to be followed. The vaccine is given at 0, 2, and 4 months, after which transmission-blocking activity will be assessed during the ensuing malaria season;and then a 4th and final dose will be given at 14 months after which transmission-blocking activity will again be assessed. he DSMB review thus far has deemed the vaccine product sufficiently safe to continue the study. Epidemiologic study of malaria infection and disease in Malian infants and pregnant women continues in Ouelessebougou, Mali. This study has thus far enrolled 1500 pregnant women as well as their newborns after delivery, and also several hundred children under 5 years of age, for longitudinal followup. Data are being collected on the frequency of clinical malaria and asymptomatic parasitemia, and samples are being collected for immunoparasitologic and host factor analyses, to determine the molecular bases for malaria pathogenesis and immunity. Our results thus far show that pregnancy malaria increases the risks of stillbirth and premature delivery, as well as the risk of malaria in the offsrping. The results from these studies have been accepted for one oral presentation and two poster presentations the ASTMH meeting in Nov 2013. During FY13, ICER/MRTC facilities were also upgraded and plans developed to initiate whole organism vaccine trials in Mali. These trials envision using whole sporozoite vaccine products developed by Sanalria, Inc, and to assess their safety, immunogenicity, and efficacy in naturally exposed populations in Mali. Clinical Laboratory. The clinical lab achieved certification by the College of American Pathologists in April, 2010, and has subsequently been re-certified. This is the first clinical lab in West or North Africa to achieve CAP certification. Quality assurance processes are ongoing, and the lab continues to provide critical support for study activities for LMIV. During FY12, the clinical lab transitioned to a core facility to support other DIR activities at MRTC, and is currently supporting all the studies listed here including the Phase 1 clinical trial.

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