2026-09-18T22:49:49Zhttps://publikationen.uni-tuebingen.de/oai/requestoai:publikationen.uni-tuebingen.de:10900/990232020-03-19T11:40:34Zcom_10900_42126col_10900_42130
Publikationssystem UB Tuebingen
advisor
Mordmüller, Benjamin (Prof. Dr.)
author
Nguyen, The Trong
2020-03-13T10:45:44Z
2020-03-13
1692981846
http://hdl.handle.net/10900/99023
Understanding the population structure of malaria parasites and the host-parasite
interaction is of fundamental interest and may help in the development of improved
anti-malarial interventions. This thesis contributes to the improvement of procedures
and methods for the characterization of the malaria parasite and reports current
epidemiological characteristics of Plasmodium falciparum populations in Lambaréné,
Gabon.
The result of this thesis encourages the use of rapid diagnostic tests (RDT) not only as a
diagnostic tool but also as a source of DNA that can be subsequently used for molecular
assays to assess parasite diversity, species distribution, and genetic polymorphisms
(e.g. mutations associated with drug resistance) as well as diagnostic performance of
RDTs on large scale. In addition, performance and resolution of a genotyping method
based on size polymorphisms of the msp1 gene, by using conventional polymerase
chain reaction (PCR) followed by automated capillary electrophoresis (CE) (QIAxcel
system, Qiagen) has been improved. Furthermore, in order to overcome the
comparatively low sensitivity of conventional PCR, a barcoding assay with 9 single
nucleotide polymorphisms (SNPs) for genotyping of low-density P. falciparum
infection by Taqman-probe-based end-point PCR was adapted from a published
method. The alternative use of these two approaches will help to improve the accuracy
of parasite genotyping, covering different types of samples, applications, and lab
settings.
The improved techniques were applied in two case scenarios: i) an epidemiological
survey and ii) to assess parasite population structure in different compartments of the
body.
It was observed that in Lambaréné and surroundings, the multiplicity of infection (MOI)
and prevalence of chloroquine-resistance-associated mutations remain high;
particularly, in the most rural areas and despite a change in malaria control
recommendations, including withdrawal of chloroquine from the market. Decreasing
MOIs in central areas of Lambaréné may be the result of urbanization and its effect on
transmission intensity and spread of drug resistance, which results in less diverse
malaria parasite populations.
55
Within its human host, malaria parasite population structure in both severely anemic
and control patients was shown to be similar between bone marrow and peripheral
blood. If the differences observed in some patients is of pathophysiological importance
remains to be further investigated.
My thesis highlights the crucial role of adequate genotyping approaches in the
development of malaria eradication tools, identifies a commonly available source of
DNA for retrospective studies and suggests an improvement in the guidelines for
sample collection and molecular analyses for studying malaria in endemic regions.
en
ubt-podok
Development and implementation of molecular methods to genotype Plasmodium falciparum in uncomplicated malaria and severe malarial anemia in Gabon
PhDThesis
URL
https://publikationen.uni-tuebingen.de/xmlui/bitstream/10900/99023/1/Dissertation_The%20Trong%20Nguyen.pdf
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