Sokoine University of Agriculture

Dhfr and dhps mutations in plasmodium falciparum isolates in Mlandizi, Kibaha, Tanzania: association with clinical outcome

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dc.contributor.author Kidima, W
dc.contributor.author Nkwengulila, G.
dc.contributor.author Premji, Z.
dc.contributor.author Malisa, A.
dc.contributor.author Mshinda, H
dc.date.accessioned 2016-11-30T10:32:13Z
dc.date.available 2016-11-30T10:32:13Z
dc.date.issued 2006-05
dc.identifier.uri http://hdl.handle.net/123456789/1030
dc.description Tanzania Health Research Bulletin en_US
dc.description.abstract Sulfadoxine-pyrimethamine (SP), the current first line antimalarial drug in Tanzania, is compromised by evolution and spread of mutations in the parasite's dhfr and dhps genes. In the present study we established the baseline frequencies of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) mutant genotypes and their potential for predicting the in vivo efficacy of SP in Mlandizi, Tanzania. The efficacy of SP treatment was by following 116 children with uncomplicated falciparum malaria for 14 days after treatment. Infected blood samples were collected on filter paper at days 0, 3, 7 and 14. Parasite genomic DNA was extracted and point mutations at positions 51, 59, 108 and 164 of the dhfr gene and at 581, 540 and 437 of the dhps gene were analysed by nested Polymerase Chain Reaction/ Restriction Fragment Length Polymorphism. Out of 116 children enrolled, 98 (86%) of eligible children demonstrated an adequate clinical response by day 14. There were 7.3 % early and 6.7% late therapeutic failures. At day 0, only 8.0% (4/50) the parasites showed no mutation at the dhfr locus; for dhps this was 73%. Triple mutant dhfr alleles (Ile 51, Arg 59, Asn 108) occurred in 47%, double mutant dhps (Gly 437, Glu 540) alleles in 7.9%. No mutation was detected at codon 164 of the dhfr gene. The presence of triple dhfr mutant alleles was related to clinical failure, but did not show significant association (Fisher exact test, P=0.166, OR 2.15 0.77<OR>6.20). The higher rates of mutation on the dhfr do not spell a bright future for SP treatment in Tanzania. It is rational to think of an alternative first line antimalarial drug, while retaining SP for malaria intermittent treatment in pregnancy. en_US
dc.language.iso en en_US
dc.publisher Tanzania Health Research Bulletin en_US
dc.subject Plasmodium falciparum en_US
dc.subject Sulfadoxine-pyrimethamine en_US
dc.subject dhfr, dhps en_US
dc.subject Mlandizi en_US
dc.subject Kibaha en_US
dc.subject Tanzania en_US
dc.title Dhfr and dhps mutations in plasmodium falciparum isolates in Mlandizi, Kibaha, Tanzania: association with clinical outcome en_US
dc.type Article en_US


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