Assessing competition between drug resistant and drug sensitive parasites in natural populations of Plasmodium falciparum Open Access

Sekar, Gayatri (2012)

Permanent URL: https://etd.library.emory.edu/concern/etds/0z708w593?locale=en
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Abstract

ABSTRACT

Understanding the intra host dynamics of infections by multiple clones has been of great interest to studies of the dynamics of anti-malarial drug resistance in Plasmodium falciparum. The evolution and spread of drug resistance in high and low endemic regions of malaria is considered a public health calamity that requires immediate attention and resolution. In an attempt to broaden our understanding of the reasons for the patterns of drug resistance and efficient drug use, we characterized natural populations of Plasmodium falciparum in Tanzania and Kenya, both highly endemic regions, using quantitative Real Time PCR methods. In our attempt to assess within host dynamics in mixed infections, we also tested the hypothesis that drug resistant parasites suffer a lowered fitness in the absence of drug pressure. We optimized pre-existent techniques to suit our study conditions and analyzed our samples. Each of our study sites presented a different situation. While there is a trend towards competition and lowered fitness of resistant parasites in Tanzania, the analyzed Kenyan population lacks evidence for competition and lowered fitness of the resistant genotype. We describe our reasoning and methods; and report our results and speculate on reasons for these trends in our study.

Understanding the within-host dynamics of drug resistant parasites and the threshold for lowered resistance of resistant parasites can prove immensely valuable for the continued usage of antimalarial drugs, as well as effective drug policy making. This study is an exploratory attempt to understand these dynamics in natural populations.

Table of Contents

Table of Contents
Introduction...1
Background

Malaria...2
Antimalarial Drugs and Drug resistance...6
Selection, fitness and fixation of drug resistant alleles in natural populations...11
Influence of immunity in the evolution of drug resistance...12
Multiplicity and its relevance...13
Rationale for study: Competition between parasite clones& Evidence for loss of fitness in natural populations...14

Hypothesis...19

Study design...19
Study sites...20
qPCR and Quantification...21
Statistical Tests and Analysis...26

Results

Tanzania...27
Kenya...29

Discussion...32
Summary...37
Future Directions...37
Conclusion...38

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