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

Erasto V Mbugi¹^,3^,5 , Benezeth M Mutayoba¹ , Allen L Malisa² , Sakurani T Balthazary¹ , Thomas B Nyambo³ and Hassan Mshinda⁴

¹Department of Veterinary Physiology, Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Sokoine University of Agriculture (SUA), P.O. Box 3017, Morogoro, Tanzania

²Department of Biological Sciences, Faculty of Science, Sokoine University of Agriculture, P.O. Box 3038, Morogoro, Tanzania

³Department of Biochemistry, School of Medicine, Muhimbili University College of Health Sciences (MUCHS), P.O. Box 65001, Dar es Salaam, Tanzania

⁴Ifakara Health Research and Development Centre (IHRDC), Off Mlabani Road, P.O. Box 53, Ifakara, Kilombero District, Morogoro, Tanzania

⁵Cell Biology and immunology group, Department of Animal Sciences, Wageningen University, P.O. Box 338, 6700 AH Wageningen, The Netherlands

author email corresponding author email

Malaria Journal 2006, 5:94doi:10.1186/1475-2875-5-94


Published:	31 October 2006

Abstract

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 first-line drug against malaria in Tanzania and other malaria-endemic countries.