Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania

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.

High Resistance of Plasmodium falciparum to Sulphadoxine/Pyrimethamine in Northern Tanzania and the Emergence of dhps Resistance Mutation at Codon 581

“…Our study in Hale found 581G in 54% of isolates (n = 84). In Ifakara[31] in 1997, 27.8% of isolates (n = 18) were found to carry the mutant while Mlimba[32] and Mbeya[33] had low prevalence of 1.6% (n = 128) and 1.2% (n = 81) respectively. Surveys in Butimba (n = 57), Mlimba (n = 59), Kyela (n = 67), Masasi (n = 73), Mkuzi (n = 127), reported no 581G mutations [8], and similarly a survey in Muheza (n = 28) [34].…”

Effect of IPTp on Plasmodium falciparum antibody levels among pregnant women and their babies in a sub-urban coastal area in Ghana

“…The presence of IgM suggests that the women were still infected despite the IPTp they were receiving during pregnancy or that the parasites were possibly resistant to SP to some degree [66]. However, SP-IPTp has recently been shown to clear parasitaemia in asymptomatic women [67].…”

Unpacking the Pathogen Box—An Open Source Tool for Fighting Neglected Tropical Disease

“…Malaria‐causing Plasmodium species account for more than 200 million new infections each year, resulting in roughly 500 000 annual deaths, with the burden disproportionally skewed toward children under five years of age . Emergence of resistance to first‐line treatments, including artemisinin combination therapies, continues to undermine the considerable progress made in eradicating infection, and puts into sharp focus the critical need to drug new targets with novel scaffolds . The Pathogen Box contains 125 compounds which possess antiplasmodial activity, many of which were identified from phenotypic screening of the GSK Tres Cantos Anti‐Malarial Set (TCAMS) …”