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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Malaria Journal 1/2017

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

Zeitschrift:
Malaria Journal > Ausgabe 1/2017
Autoren:
Irina T. Jovel, Anders Björkman, Cally Roper, Andreas Mårtensson, Johan Ursing
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12936-017-1747-6) contains supplementary material, which is available to authorized users.

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.
Zusatzmaterial
Additional file 1: Table S1. Alignment of pfnhe1 ms4760variants found in Liberia in 1978 (Jovel et al. [ 40]).
Literatur
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