Abstract
BackgroundSulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries. Nevertheless, the response of parasites to SP treatment has shown significant variation between individuals.MethodsThe genes for dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) were used as markers, to investigate parasite resistance to SP in 141 children aged less than 5 years. Parasite DNA was extracted by Chelex method from blood samples collected and preserved on filter papers. Subsequently, polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP) were applied to detect the SP resistance-associated point mutations on dhfr and dhps. Commonly reported point mutations at codons 51, 59, 108 and 164 in the dhfr and codons 437, 540 and 581 in the dhps domains were examined.ResultsChildren infected with parasites harbouring a range of single to quintuple dhfr/dhps mutations were erratically cured with SP. However, the quintuple dhfr/dhps mutant genotypes were mostly associated with treatment failures. High proportion of SP resistance-associated point mutations was detected in this study but the adequate clinical response (89.4%) observed clinically at day 14 of follow up reflects the role of semi-immunity protection and parasite clearance in the population.ConclusionIn monitoring drug resistance to SP, concurrent studies on possible confounding factors pertaining to development of resistance in falciparum malaria should be considered. The SP resistance potential detected in this study, cautions on its useful therapeutic life as an interim first-line drug against malaria in Tanzania and other malaria-endemic countries.
Highlights
Sulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries
Treatment outcomes From clinical evaluation, a total of 172 children with acute uncomplicated malaria were recruited into the study and treated with SP
The impact of other drugs with similar mechanisms of action used as antibiotics in selecting mutations responsible for SP resistance need be studied especially for co-trimoxazole, which is currently used as a prophylaxis against opportunistic infections in HIV-infected individuals
Summary
Sulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries. P. falciparum has been found to be the most lethal of all human malaria parasites This parasite causes epidemics in malaria-endemic countries, resulting in large numbers of deaths. The parasite has been observed to develop resistance to this drug combination associated with point mutations in the genes for the enzymes involved in the obligatory parasite-folate biosynthesis pathway. Studies [6] have shown that multiple mutations in the genes for both enzymes result in exceedingly high SP treatment failure. Detection of these mutations in field isolates has been proposed as an alternative strategy for rapid screening of antifolate drug resistance [7,8,9,10,11,12]
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