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Background  Sulphadoxine-pyrimethamine (SP) has been in use for the treatment of uncomplicated falciparum malaria in Malaysia since the 1970s and is still widely employed in spite of widespread clinical resistance. Resistance to SP is known to be mediated by mutations in the  pfdhfr  and  pfdhps  genes. The aim of the present study was to investigate the distribution of  pfdhfr  and  pfdhps  gene polymorphism in  Plasmodium falciparum  field isolates from Kalabakan, Sabah, in northern Borneo.    Methods  A total number of 619 individuals were screened from 23 study sites of which 31 were positive for  P. falciparum.  Analysis of restriction fragment length polymorphisms (RFLP) was used to identify polymorphism in the  pfdhfr  and  pfdhps  genes at positions 16, 51, 59, 108, 164 and 437, 540, 581, respectively.    Results  All samples had at least one mutation in each of the genes associated with drug resistance. The prevalence of  pfdhfr  59arg, 164leu and 108asn were 100%, 80.65% and 58.06%, respectively.  Pfdhps  mutants 437gly and 581gly accounted for 100% and 74.19% respectively. In  pfdhfr , the most common mutant genotypes were combination 59arg + 164leu (22.58%) and 59arg + 108asn + 164leu (51.61%). In  pfdhps  the most common genotype was 437gly + 581gly (74.19%). One individual (3.22%) harboured parasites with four  pfdhfr  (16 val + 59arg + 108asn + 164leu) and two  pfdhps  (437gly + 581gly) mutations. The highest quintuple  pfdhfr/pfdhps  (41.94%) was three  pfdhfr  (59arg + 108asn + 164gly) and two  pfdhps  (437gly + 581gly).    Conclusion  The data suggest a high prevalence of genetic variations conferring resistance to SP which can predict treatment failure before becoming clinically evident. In areas like this, the use of SP may no longer be indicated.

High prevalence of mutation in the Plasmodium falciparum dhfr and dhps genes in field isolates from Sabah, Northern Borneo