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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  T1069 ACT→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  T1069 ACG  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.    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.

malaria journal

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