Muia, Anne Ndanu (2009) Effect of Insecticide-Treated Bed Nets (ITNS) on the Genetic Diversity of P. Falciparum Circumsporozoite Protein (CSP) in a Malaria Holoendemic Area of Western Kenya. Masters thesis, Kenyatta University.
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Abstract
Malaria continues to place a major burden on health and economic development in the poorest and most marginalized areas of the world. Widespread parasite resistance to antimalarial drugs and vector resistance to insecticides led to renewed global efforts to explore alternative, cost-effective and efficacious malaria control tools. Use of insecticide-treated bed nets (ITNs) has emerged as one of the most cost-effective malaria control strategy prompting initiation of large-scale IlN programmes in many endemic areas. The use of ITNs has been associated with 70- 90% reduction in malaria transmission and significant reductions in morbidity and mortality in vulnerable populations. However, the intensity of malaria transmission determines parasitemia levels, rates of acquisition of immunity in human populations and parasite recombination rates in mosquito vectors. Therefore, we hypothesized that the significant reduction in parasitemia associated with ITN use could have an impact on genetic diversity of polymorphic parasite genes that are under selective pressure, therefore affecting the frequency of circulating haplotypes. To test the hypothesis, we designed the current study to assess the effect of on the genetic diversity of the polymorphic immune epitopes of Plasmodium falciparum circum sporozoite protein (CSP), a leading malaria vaccine candidate antigen. Parasite-positive blood samples collected from children enrolled in a series of cross-sectional surveys conducted at baseline, 14, 30 and 46-months post ITN intervention in a malaria holoendemic area were used to isolate DNA. Standard PCR and cycle sequencing were used to determine point mutations in the C-terminal domain of the CSP gene encoding helper T-cell epitopes, Th2R and Th3R. The nature and extent of CSP gene diversity was compared between parasites from children in intervention and control areas, and in the four cross-sectional surveys using haplotype diversity and the n statistic. Differences in the proportion of haplotypes between bed net and control areas and between the different surveys were determined by Chi-square and permutation tests. There were 77 Th2R and 33 Th3R haplotypes detected in this study signifying the high polymorphism of the CSP immune epitopes in natural parasite populations. The most prevalent Th2R and Th3R haplotypes were PSDQHIEKYLKTIQNSLS and NKPKDQLDYEND, 13% and 33.1% respectively. Most of the circulating haplotypes had a very low frequency « 5 copies). The 3D7-type haplotype had a very low frequency. Although there was no consistency in the prevalence of the haplotypes in ITN and control areas and overtime, there was a trend towards decreased genetic diversity after the first 30 months of ITN use. After 48 months of ITN use the genetic diversity had increased. This has implications on the ongoing field testing of CSP-based malaria vaccines including the RTS,S multi-site trials.
| Item Type: | Thesis (Masters) |
|---|---|
| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine |
| Divisions: | Africana |
| Depositing User: | Tim Khabala |
| Date Deposited: | 13 Sep 2017 08:51 |
| Last Modified: | 13 Sep 2017 08:51 |
| URI: | http://thesisbank.jhia.ac.ke/id/eprint/2088 |
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