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Background  Anti-malarial drug resistance remains a key concern for the global fight against malaria. In Ghana sulfadoxine-pyrimethamine (SP) is used for intermittent preventive treatment of malaria in pregnancy and combined with amodiaquine for Seasonal Malaria Chemoprevention (SMC) during the high malaria season. Thus, surveillance of molecular markers of SP resistance is important to guide decision-making for these interventions in Ghana.    Methods  A total of 4469 samples from uncomplicated malaria patients collected from 2009 to 2018 was submitted to the Wellcome Trust Sanger Institute, UK for DNA sequencing using MiSeq. Genotypes were successfully translated into haplotypes in 2694 and 846 mono infections respectively for  pfdhfr  and  pfdhps genes  and the combined  pfhdfr/pfdhps  genes across all years.    Results  At the  pfdhfr  locus, a consistently high (> 60%) prevalence of parasites carrying triple mutants ( IRN I) were detected from 2009 to 2018. Two double mutant haplotypes (N RN I and  I C N I) were found, with haplotype N RN I having a much higher prevalence (average 13.8%) than  I C N I (average 3.2%) across all years. Six  pfdhps  haplotypes were detected. Of these, prevalence of five fluctuated in a downward trend over time from 2009 to 2018, except a  pfdhps  double mutant ( AG KAA), which increased consistently from 2.5% in 2009 to 78.2% in 2018. Across both genes,  pfdhfr/pfdhps  combined triple (N RN I +  A AKAA) mutants were only detected in 2009, 2014, 2015 and 2018, prevalence of which fluctuated between 3.5 and 5.5%. The combined quadruple ( IRN I +  A AKAA) genotype increased in prevalence from 19.3% in 2009 to 87.5% in 2011 before fluctuating downwards to 19.6% in 2018 with an average prevalence of 37.4% within the nine years. Prevalence of parasites carrying the quintuple ( IRN I +  AG KAA or S GE AA) mutant haplotypes, which are highly refractory to SP increased over time from 14.0% in 2009 to 89.0% in 2016 before decreasing to 78.9 and 76.6% in 2017 and 2018 respectively. Though quintuple mutants are rising in prevalence in both malaria seasons, together these combined genotypes vary significantly within season but not between seasons.    Conclusions  Despite high prevalence of  pfdhfr  triple mutants and combined  pfdhfr/pfdhps  quadruple and quintuple mutants in this setting SP may still be efficacious. These findings are significant as they highlight the need to continuously monitor SP resistance, particularly using deep targeted sequencing to ascertain changing resistance patterns.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12936-021-03693-3.

malaria journal

Temporal evolution of sulfadoxine-pyrimethamine resistance genotypes and genetic diversity in response to a decade of increased interventions against Plasmodium falciparum in northern Ghana