INVESTIGATION OF STRAIN DIVERSITY IN PLASMODIUM FALCIPARUM POPULATIONS FROM PAPUA NEW GUINEA
Abstract (Summary)Genetic polymorphism in Plasmodium falciparum populations is important as standing genetic variability may provide the potential for populations to adapt quickly when faced with environmental changes such as introduction of new antimalarial drugs. To characterize genetic diversity in this human malaria parasite, presumably neutral microsatellite (MS) and single nucleotide polymorphism (SNP) markers were identified and compared to historic methods of antigenic marker genotyping. In P. falciparum infected samples from Papua New Guinea (PNG), the three methods were shown to be equally viable for identifying diversity, (all heterozygosities > 0.930). To examine the effect of selection pressure by chloroquine (CQ, previously successful antimalarial), on presumably neutral markers in close proximity to a SNP located in the P. falciparum CQ-resistance transporter gene that is responsible for in vitro CQ-resistance, intronic MS were examined. Maximum heterozygosity for these intronic MS in sensitive parasites was 0.879, while in resistant parasites the maximum heterozygosity was 0.232 suggesting that loss of MS heterozygosity results from hitchhiking along with the pfcrt SNP. The data suggests that these markers are not representative of whole genome diversity and should be avoided for overall population studies. For a different perspective of population diversity, 7 bi-allelic SNP markers were genotyped in PNG parasite populations. While heterozygosity was high (range: 0.956-0.980), a defined population structure was found with 80 of 128 possible multi-locus genotypes (MLG) observed. Thirteen predominant MLGs accounted for 50.5% of the samples, suggesting that recrudescence rates in PNG may be overestimated as there is a high probability of pre- and post-treatment strains being similar by chance. The remaining 49.5% of the samples contained 67 MLGs (each at frequencies Currently, new antimalarial combination therapies are being introduced in PNG. To monitor the efficacy, antigenic genotyping is usually employed. The SNP-assay described here was found to be a viable alternative, though increasing SNP-numbers may be necessary for better strain differentiation. SNP-based analyses provide powerful approaches for monitoring antimalarial drug and vaccine efficacy, as well as the effect of additional control measures such as bed nets on parasite strain diversity.
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:malaria strain diversity plasmodium
Date of Publication:05/05/2009