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Selassie Majola Kumordjie Sawyer.
PHD Candidate
Project Title
Plasmodium falciparum genetic variations, helminths co-infection and acquisition of immunity to malaria.
 
Executive Summary

Plasmodium falciparum (Pf) malaria contributes significantly to morbidity and mortality in Ghana and is responsible for about 38% of all outpatient illnesses, 36% of all admissions, and 33% of all deaths in children under 5 years 1. Each year, the public health facilities alone receive between 3.1 and 3.5 million malaria cases, with about 900,000 cases being in children under 5 years 1. Long term sustainability of current intervention measures against malaria is threatened by both vector and parasite resistance to the chemical agents used and thus, vaccine development remains the most promising alternative. The diverse polymorphic nature of the Pf expressed surface proteins has been a major hindrance to the development of an effective vaccine although a few candidates are in different stages of preclinical and clinical studies 2-6. In sub-Saharan Africa helminth co-infection in malaria is a common occurrence 7,8 . Chronic helminth infection may induce a Th2 immune response that modulates the host immune reaction to other antigens and is thought to have detrimental effects in reducing the efficacy of protective immune responses 7. Several studies have investigated the consequences of Pf and helminth co-infection in relation to malaria however, the conclusions have been inconsistent 7-10.
The overall aim of this study is to assess the dynamics of Pf genetic variations that underlie the acquisition of immunity to malaria and determine if helminth co-infection in malaria contributes to Pf molecular evolution and virulence through immune modulation.

 
    Objective
    • Assess polymorphisms in genes that encode parasite proteins necessary for invasion of erythrocytes (MSP1, AMA1, Rh5, EBA 175), transmission (Pfs 25, Pfs 48/45,Pfs 230), cytoadherence (PfEMP1-DBL2β, CIDR1α domains) and the vaccine candidate antigens GLURP and MSP3 in a longitudinal cohort study (LCS) of Ghanaian children.
    • Measure expression profiles of genes that encode parasite cytoadherence proteins (PfEMP1-DBL2β, CIDR1α domains) in children who develop severe malaria.
    • Compare polymorphisms in isolates from symptomatic and asymptomatic carriers to ascertain unique differences
    • Determine if repeated malaria episodes are associated with identical strains through microsatellite genotyping
    • Determine the effect of co-infection of helminths and malaria in relation to evolution of virulence




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