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Analysis of immune responses, genetic polymorphism and prevalence of molecular markers for drug resistance in Plasmodium falciparum in different endemic areas of Zimbabwe

Posted on:2007-08-09Degree:Ph.DType:Dissertation
University:The Johns Hopkins UniversityCandidate:Mlambo, GodfreeFull Text:PDF
GTID:1454390005485727Subject:Biology
Abstract/Summary:
Previously, malaria endemicity in Zimbabwe has been described based on passive case detection and altitudinal analysis since data on entomological inoculation rates is not available. However, it is not known whether passive case detection and altitudinal analysis are accurate and stable indices for describing the epidemiology of malaria in Zimbabwe. We therefore examined samples from patients presenting at health centers from three locations (Bindura, Chiredzi and Kariba) previously described to differ in malaria endemicity based on altitudinal analysis. We investigated whether immune markers such as antibodies could be reliably used to describe and predict differences in malaria endemicity and malaria transmission in these areas. Of the antigens tested i.e AMA-1, EBA-175, CSP, MSP-1 and Pfg27, IgG and IgM antibodies measured by ELISA were higher for Bindura, an area previously described to be hypo-endemic compared to Kariba and Chiredzi (with the exception of IgG and IgM to AMA-1 and EBA-175 which were similar between Chiredzi and Bindura), areas that have been described to be of hyper- and meso-endemic transmission, respectively. Plasma samples were further analyzed for their functional activity by testing their ability to inhibit the growth of P. falciparum in culture. Our results, determined by microscopy and verified by the LDH assay revealed that plasma from the three locations had similar inhibitory activity against the growth of P. falciparum in vitro.; The genetic variability of parasites from the three locations was further analyzed by genotyping parasite DNA at the MSP-1, MSP-2 and GLURP loci. Parasites from the three locations were genetically diverse showing different allele sizes and frequencies at MSP-1, MSP-2 and GLURP. Based on MSP-1 block2 which has three allelic families, K1, RO33 and Mad20, the only allelic type that was monomorphic was R033 and it was distributed equally among the three locations. The K1 allele was overrepresented in Kariba (p=0.02) while Mad20 alleles occurred at a high frequency in Bindura compared to Kariba. The two main allelic families of MSP-2, i.e IC/3D7 and FC-27 were differentially prevalent in the three locations with IC/3D7 being more common in Kariba and FC-27 being more frequent in Bindura and Chiredzi. From all the three areas, 6 and 11 different MSP-1 and MSP-2 alleles, respectively were detected and the frequency of individual allele sizes was similar among the three locations. (Abstract shortened by UMI.)...
Keywords/Search Tags:Three locations, Malaria endemicity, Altitudinal analysis, Areas, MSP-1, Different, Falciparum, Described
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