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Molecular Monitoring of Plasmodium falciparum Super-resistance to Sulfadoxine-pyrimethamine in Tanzania.

Kavishe, R. A., Kaaya, R. D., Nag, S., Krogsgaard, C., Notland, J. G., Kavishe, A. A., Ishengoma, D., Roper, C. and Alifrangis, M. (2016) Molecular Monitoring of Plasmodium falciparum Super-resistance to Sulfadoxine-pyrimethamine in Tanzania. Malaria journal, 15. p. 335. ISSN 1475-2875

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Abstract

Sulfadoxine-pyrimethamine (SP) is recommended for prophylactic treatment of malaria in pregnancy while artemisinin combination therapy is the recommended first-line anti-malarial treatment. Selection of SP resistance is ongoing since SP is readily available in health facilities and in private drug shops in sub-Saharan Africa. This study reports on the prevalence and distribution of Pfdhps mutations A540E and A581G in Tanzania. When found together, these mutations confer high-level SP resistance (sometimes referred to as 'super-resistance'), which is associated with loss in protective efficacy of SP-IPTp. DNA samples were extracted from malaria-positive blood samples on filter paper, used malaria rapid diagnostic test strips and whole blood collected from eight sites in seven administrative regions of Tanzania. PCR-RFLP and SSOP-ELISA techniques were used to genotype the A540E and A581G Pfdhps. Data were analysed using SPSS version 18 while Chi square and/or Fischer Exact tests were used to compare prevalence between regions. A high inter-regional variation of Pfdhps-540E was observed (χ(2) = 76.8, p < 0.001). High inter-regional variation of 581G was observed (FE = 85.3, p < 0.001). Both Tanga and Kagera were found to have the highest levels of SP resistance. A high prevalence of Pfdhps-581G was observed in Tanga (56.6 %) in northeastern Tanzania and in Kagera (20.4 %) in northwestern Tanzania and the 540-581 EG haplotype was found at 54.5 and 19.4 %, respectively. Pfdhps-581G was not detected in Pwani and Lindi regions located south of Tanga region. Selection of SP super-resistant Pfdhps A581G is highest in northern Tanzania. Variation in distribution of SP resistance is observed across the country: northeastern Tanga region and northwestern Kagera region have highest prevalence of SP super-resistance markers, while in Pwani and Lindi in the southeast the prevalence of super-resistance was zero. More studies should be conducted to understand the factors underlying the remarkable heterogeneity in SP resistance in the country.

Item Type: Article
Keywords: Anti-malarial drugs, Drug resistance, Malaria, Mutations, Parasites, Plasmodium falciparum, Polymorphisms, SP-resistance, SP-super resistance, Sulfadoxine-pyrimethamine, Tanzania
Subjects: Malaria > Diagnosis & treatment
Divisions: Kilimanjaro Christian Medical Centre
Depositing User: Mr Joseph Madata
Date Deposited: 27 Jul 2016 08:46
Last Modified: 27 Jul 2016 08:46
URI: http://ihi.eprints.org/id/eprint/3863

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