Examine gut microbiota between and as a potential cause of severe versus asymptomatic malaria.
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Date
2020-06-15
Authors
Journal Title
Journal ISSN
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Publisher
Kamuzu University of Health Sciences
Abstract
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
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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.