Jovel, Irina T; Björkman, Anders; Roper, Cally; Mårtensson, Andreas; Ursing, Johan; (2017) Unexpected selections of Plasmodium falciparum polymorphisms in previously treatment-naïve areas after monthly presumptive administration of three different anti-malarial drugs in Liberia 1976-78. Malaria journal, 16 (1). 113-. ISSN 1475-2875 DOI: https://doi.org/10.1186/s12936-017-1747-6
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Abstract
BACKGROUND: To assess the effect on malaria prevalence, village specific monthly administrations of pyrimethamine, chlorproguanil, chloroquine or placebo were given to children in four previously treatment-naïve Liberian villages, 1976-78. Plasmodium falciparum in vivo resistance developed to pyrimethamine only. Selection of molecular markers of P. falciparum resistance after 2 years of treatment are reported. METHODS: Blood samples were collected from 191 study children in a survey in 1978. Polymorphisms in pfcrt, pfmdr1, pfdhfr, pfdhps, pfmrp1 and pfnhe1 genes were determined using PCR-based methods. RESULTS: Pfcrt 72-76 CVIET was found in one chloroquine village sample, all remaining samples had pfcrt CVMNK. Pfmdr1 N86 prevalence was 100%. A pfmdr1 T1069ACT→ACG synonymous polymorphism was found in 30% of chloroquine village samples and 3% of other samples (P = 0.008). Variations in pfnhe1 block I were found in all except the chloroquine treated village (P < 0.001). Resistance associated pfdhfr 108N prevalence was 2% in the pyrimethamine village compared to 45-65% elsewhere, including the placebo village (P = 0.001). CONCLUSIONS: Chloroquine treatment possibly resulted in the development of pfcrt 72-76 CVIET. Selection of pfmdr1 T1069ACG and a pfnhe1 block 1 genotypes indicates that chloroquine treatment exerted a selective pressure on P. falciparum. Pyrimethamine resistance associated pfdhfr 108N was present prior to the introduction of any drug. Decreased pfdhfr 108N frequency concurrent with development of pyrimethamine resistance suggests a non-pfdhfr polymorphisms mediated resistance mechanism.
Item Type | Article |
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Faculty and Department | Faculty of Infectious and Tropical Diseases > Department of Infection Biology |
Research Centre |
Antimicrobial Resistance Centre (AMR) Malaria Centre |
PubMed ID | 28288632 |
ISI | 396300100001 |
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Filename: Unexpected selections of Plasmodium falciparum_GOLD VoR.pdf
Licence: Creative Commons: Attribution 3.0
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