Browsing by Author "Schmidt, Nathan"

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    Examine gut microbiota between and as a potential cause of severe versus asymptomatic malaria.
    (Kamuzu University of Health Sciences, 2020-06-15) Schmidt, Nathan
    i] Type of Research Studies Gut microbiota and human malaria: Examine gut microbiota between and as a potential cause of severe versus asymptomatic malaria Case-control cohort study. ii] Problem to be Studied The majority of Plasmodium falciparum infections are asymptomatic. While some infections progress to clinical uncomplicated malaria, which is debilitating in its own right, a small percentage of infections progress to clinical forms of severe malaria (e.g., severe malarial anemia and cerebral malaria), which are responsible for P. falciparum related deaths. To date, it is not fully understood what factors contribute towards the susceptibility of P. falciparum infection progressing to clinical uncomplicated malaria or severe malaria. This knowledge gap hinders discovery of new strategies to prevent this evolution. iii] Objectives 1. compareCompare gut microbiota compositions and functions between children with strictly defined asymptomatic P. falciparum parasitemia and life-threatening P. falciparum cerebral malaria and determine the effect of gut microbiota differences on both the host humoral immune response and severity of disease.Characterize gut microbiota in participants with asymptomatic P. falciparum compared to participants with life-threatening cerebral malaria. 2.1. Examine biomarkers, including plasma cytokines, circulating antibodies, and immune cell populations, of the humoral immune response to P. falciparum in children with asymptomatic infections compared to children with cerebral malaria. 3.2. Determine the ability of gut microbiota in the stool of donors to impact the severity of malaria by Use stool samples collected from participants with asymptomatic infections and cerebral malaria to colonizinge germ-free mice with patient stool samples followed by infection with rodent malaria. to determine ability of gut microbiota in the stool donors to impact the severity of malaria. iv] Methodology We propose to conduct a case-control cohort study in the catchment area of Queen Elizabeth Central Hospital, Blantyre, Malawi. 1. Cerebral malaria cases – These will consist of children aged 12-96 months presenting to the Pediatric Research Ward at Queen Elizabeth Central Hospital in Blantyre, Malawi. Children must meet the WHO classification for cerebral malaria (Blantyre Coma Score ≤ 2, peripheral P. falciparum parasitemia, and no other discernible cause for coma) as well as be retinopathy positive. These cases will be recruited from a larger ongoing study investigating the pathogenesis of cerebral malaria. COMREC P.09/16/2024 (PI Taylor). A venipuncture sample and stool sample will be collected for a detailed analysis of the host and parasite factors leading to the persistent asymptomatic infection 2. Asymptomatic controls – Children will be recruited into this group upon escorting of cerebral malaria cases home post-discharge. They will be from adjacent households to the cerebral malaria case and will thus be matched in geographic location to the cerebral malaria cases. Twelve participants within one year in age and of the same sex will be chosen to match with each cerebral malaria case. This will be necessary to increase the likelihood of obtaining a child that is asymptomatically infected. Finger prick samples of blood will be collected onto filter paper monthly for two months from asymptomatic children, aged 12-96 16-Sep-2020 Gut microbiota and human malaria: Examine gut microbiota between Version 1.25 and as a potential cause of severe versus asymptomatic malaria 24 April15 June 2020 4 months. PCR analysis of filter papers will be carried out on a monthly basis, and when a participant has two consecutive positive samples (whilst asymptomatic), a venipuncture sample and stool sample will be collected for a detailed analysis of the host and parasite factors leading to the persistent asymptomatic infection. v] Expected Findings and Dissemination We anticipate finding that gut microbiota will be different between children with cerebral malaria and asymptomatic infections, which will alter the host immune response to Plasmodium and collectively be a contributing factor to determining the severity of malaria disease. Results will be disseminated in peer-reviewed journals, international conferences, the University of Malawi College of Medicine Research Dissemination Conference, and will be provided to COMREC and community leaders.