Prevalence of molecular markers associated with chloroquine, sulphadoxine-pyrimethamine and lumefantrine resistance following the deployment of artemether-lumefantrine as first-line treatment for uncomplicated falciparum malaria in Gaza Province, Mozambique.
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Abstract
Antimalarial drug resistance is a major contributing factor to the sustained malaria burden in sub-Saharan Africa. Under extreme drug pressure, drug resistant parasites have a selective fitness advantage over wild-type parasites. However this selective advantage is negated once the drug pressure is removed. Over the past decade, malaria treatment policy in Mozambique has changed at least twice. In 2006 the monotherapy chloroquine (CQ) was replaced by artemisinin-based combination therapy artesunate plus sulphadoxine-pyrimethamine (SP) which in turn was replaced by artemether-lumefantrine in 2008. This study investigates the effect these changes in drug pressure had on the prevalence of molecular markers associated with CQ, SP and lumefantrine resistance in Gaza Province, Mozambique. Finger prick filter paper blood samples were collected from malaria rapid diagnostic test positive children at 20 sentinel sites during annual cross-sectional malaria prevalence surveys in 2010 and 2011. Chelex extracted parasite DNA confirmed as being P. falciparum positive using quantitative and nested PCR methods was subjected to mutational analysis using nested PCR and RFLP protocols to determine the prevalence of molecular markers associated with SP,CQ and lumefantrine resistance. Over the study period, the prevalence of SP resistance markers were nearing fixation, while all samples analysed had a single copy of the pfmdr1 gene. Despite the reduction of SP drug pressure since 2008, the prevalence of SP resistance markers were still high suggesting that SP pressure still exists in the region, raising concerns over the efficacy of intermittent preventative treatment using SP. This study supports the change from artesunate plus SP to artemether-lumefantrine in Gaza Province The prevalence of CQ resistance markers in the pfcrt gene increased over the study period whilst a decrease was observed in the pfmdr1 gene. These results suggest that CQ could still be in use in Gaza Province probably due to a lack of ACTs and availability of CQ. Whilst markers of artemisinin resistance have yet to be identified, the selection of the pfmdr1 86N allele, indicative of lumefantrine resistance, suggests that the pfmdr1 gene is under selection because of CQ withdrawal and raises concern for the continued use of the drug combination in the region. Further studies, using other markers of artemether-lumefantrine resistance are required. The pfmdr1 86Y marker was found to be associated with the pfcrt CVIET haplotype and the SP quintuple marker prevalence with residence influencing this association. This study contributes to the body of knowledge regarding drug resistance markers in Gaza Province which could be used to inform drug policy in the future.
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M. Sc. University of KwaZulu-Natal, Pietermaritzburg 2013.
Keywords
Plasmodium falciparum -- Mozambique., Malaria -- Treatment -- Mozambique., Artemisinin., Antimalarials., Theses -- Biochemistry.