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Background: Sulphadoxine-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.
Methods: The 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.
Results: Children 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.
Conclusion: In 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 firstline
drug against malaria in Tanzania and other malaria-endemic countries. |
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