Molecular monitoring of resistant dhfr and dhps allelic haplotypes in Morogoro and Mvomero districts in south eastern Tanzania.

BACKGROUND: Resistance to the antimalarial drug sulfadoxine-pyrimethamine (SP) emerged in Plasmodium falciparum from Asia in the 1960s and subsequently spread to Africa. In Tanzania, SP use as a national policy began in 1983 as a second line to chloroquine (CQ) for the treatment of uncomplicated malaria, until August 2001 when it was approved to replace CQ as a national first line. OBJECTIVE: The present study assesses the frequency of resistant dhfr and dhps alleles in Morogoro-Mvomero district in south eastern Tanzania and contrast their rate of change during 17 years of SP second line use against five years of SP first line use. METHODOLOGY: Cross sectional surveys of asymptomatic infections were carried out at the end of rainy season during July-September of 2000, when SP was the national second line (CQ was the first line) and 2006 when SP was the national first line antimalarial treatment. Genetic analysis of SP resistance genes was carried out on 1,044 asymptomatic infections and the effect of the two policies on SP evolution compared. RESULTS: The frequency of the most resistant allele, the double dhps-triple dhfr mutant genotype, increased by only 1% during 17 years of SP second line use, but there was a dramatic increase by 45% during five years of SP first line use. CONCLUSION: We conclude that National policy change from second line to first line SP, brought about an immediate shift in treatment practice and this in turn had a highly significant impact on drug pressure. The use of SP in specific programs only such as intermittent preventive treatment of infants (IPTi) and intermittent preventive treatment of pregnant women (IPTp) will most likely reduce substantially SP selection pressure and the SP resistance alleles alike.

Knowledge and practices on malaria and its control among pastoralists in Simanjiro District, northern Tanzania.

Community knowledge and practice related to malaria is important for the implementation of appropriate, effective and sustainable interventions. This study was carried out to assess knowledge and practices on malaria and identify factors contributing to the low mosquito net coverage in Simanjiro District in northern Tanzania. A combination of direct observation, focus group discussion (FGD) and questionnaire were employed in data collection. A sample of 200 respondents was selected randomly from 5542 people from the study village. The findings show that, although most (75%) of the respondents were informed that mosquitoes transmit malaria, the remaining quarter of respondents reserved a considerable doubt on the link between mosquitoes and malaria. Sixty five percent of the respondents were aware of the use of insecticide treated nets (ITNs). However, the coverage of any mosquito net and ITN was 12.5% and 5%, respectively. Affordability, unavailability and gender inequality were identified to be major factors associated with the low ITN coverage. The study recommends that, an advocated pluralistic approach of ITN delivery which encourages a coordinated public private alliance is required to ensure equitable and large scale distribution of ITNs in the village.

Dhfr and dhps mutations in Plasmodium falciparum isolates in Mlandizi; Kibaha; Tanzania: association with clinical outcome

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 7.3early and 6.7late 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 0.77OR6.20). 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