The studies that assess malaria transmission blocking assays and gametocyte carriage rates in Bancoumana, Mali (NIAID Protocol 11-I-N143) have continued, and this year an additional modality called Experimental Huts was implemented to measure transmission in wild-caught mosquitoes. The study completed enrollment of 250 children and adults in July 2011, and has now been extended through this year. Participants are followed monthly to determine parasite carriage rates. Some gametocyte positive volunteers participate in mosquito feeding assays (direct skin feeds;membrane feeds;Experimental Hut studies) to provide data on parasite transmission to mosquito using various laboratory methods. Vaccines that block transmission of malaria to mosquitoes have the potential to be critical tools in the drive to eliminate or eradicate malaria. Clinical development of such vaccines requires expertise in vaccinology, parasitology, and entomology, which is continuously being developed and strengthened as part of 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, and is continuing into the 2014 season. The Phase 1 clinical protocol (13-I-N109) for Pfs25-EPA/Alhydrogel transmission-blocking vaccine trial continues at the Bancoumana site. After a dose escalation trial in the US determined this to be a safe and immunogenic vaccine, vaccinations were initiated in Bancoumana and surrounding villages in May 2013. The vaccine is given at 0, 2, and 4 months, after which transmission-blocking activity was assessed during the ensuing malaria season. A 4th and final dose will be given in Sep 2014 after which transmission-blocking activity will again be assessed during the 2014 transmission season. The DSMB review in 2014 has deemed the vaccine product sufficiently safe and immunogenic based on ELISA data to continue the study. The primary goal of the trial is to assess safety, and the primary measure of vaccine activity will be measured by performing direct skin feeds of mosquitoes on all volunteers each week for 6 weeks after the 4th vaccine dose. The LMIV epidemiologic study of malaria infection and disease in Malian infants and pregnant women continues in Ouelessebougou, Mali. This study has thus far enrolled nearly 1900 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 offspring. The results from these studies have been submitted for 2 presentations at the ASTMH meeting in Nov 2014. During FY14, the ICER/MRTC facilities in the village of Doneguebougou were upgraded to support whole organism vaccine trials. A Phase 1 trial of the PfSPZ Vaccine product developed by Sanaria, Inc, was initiated in Jan 2014 to assess its safety, immunogenicity, and efficacy in a naturally exposed Malian populations. This is the first-ever field trial of a whole organism vaccine. All 5 doses of the vaccine have been administered, and the study participants are now being followed to assess the degree of activity that the vaccine has to prevent infection with naturally circulating wild-type parasites in Mali. Clinical Laboratory. During FY12, the clinical lab transitioned to a core facility to support other DIR activities at MRTC. During FY14, LMIV studies continued as the major customer and supporter for the clinical laboratory, and the clinical laboratory is currently supporting all the studies listed here including the Phase 1 clinical trials. This is the first clinical lab in West or North Africa to achieve CAP certification. Quality assurance processes are ongoing, and certification is actively maintained. Immunology Laboratory. During FY14, LMIV supported the efforts of DIR to establish a new core Immunology lab, drawing from the staff and facilities that previously supported HIV and TB studies. We successfully integrated the new core activities into our vaccine trials, for purposes of processing and storing PBMC samples. This interaction has expanded the assay expertise in the immunology lab, and has also given the lab experience in supporting a Phase 1 interventional trial, which is new to the group. Over the past year, we convened the second West African Regional Training Workshop on Protozoan Pathogens for young scientists. The workshop brought together 22 young scientists from across the west African region, together with a west African and international faculty. The theme of the 2-week workshop was Infection of the Pregnant Host, and emphasized hands on activities, journal clubs, student participation, and research proposal development. The feedback from the young scientists about the quality of their experience and knowledge gained was uniformly very high.
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