Substantial increase in mutations in the genes pfdhfr and pfdhps puts sulphadoxine–pyrimethamine‐based intermittent preventive treatment for malaria at risk in Burkina Faso
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E-Article
Title:
Substantial increase in mutations in the genes pfdhfr and pfdhps puts sulphadoxine–pyrimethamine‐based intermittent preventive treatment for malaria at risk in Burkina Faso
Description:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Sulphadoxine–pyrimethamine (<jats:styled-content style="fixed-case">SP</jats:styled-content>) is widely used as intermittent preventive treatment (<jats:styled-content style="fixed-case">IPT</jats:styled-content>) for malaria in pregnant women in Sub‐<jats:styled-content style="fixed-case">S</jats:styled-content>aharan <jats:styled-content style="fixed-case">A</jats:styled-content>frica. There are reports of wide‐spread <jats:styled-content style="fixed-case">SP</jats:styled-content> resistance in countries where <jats:styled-content style="fixed-case">SP</jats:styled-content> had once been used as a first‐line treatment. It is unclear whether the development of <jats:styled-content style="fixed-case">SP</jats:styled-content> resistance also affects countries where <jats:styled-content style="fixed-case">SP</jats:styled-content> is mainly used in the context of <jats:styled-content style="fixed-case">IPT</jats:styled-content>, as is the case in <jats:styled-content style="fixed-case">B</jats:styled-content>urkina <jats:styled-content style="fixed-case">F</jats:styled-content>aso. To assess the efficacy of <jats:styled-content style="fixed-case">SP</jats:styled-content>‐based <jats:styled-content style="fixed-case">IPT</jats:styled-content>, we monitored the prevalence of <jats:styled-content style="fixed-case">SP</jats:styled-content> conferring genetic mutations in the genes <jats:italic>dhfr</jats:italic> and <jats:italic>dhps</jats:italic> in <jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content>lasmodium falciparum</jats:italic> populations in a rural area of <jats:styled-content style="fixed-case">B</jats:styled-content>urkina <jats:styled-content style="fixed-case">F</jats:styled-content>aso over a period of 13 years.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Molecular epidemiological study consisted of six consecutive cross‐sectional surveys of rainy and dry seasons (2009–2012). Data from the rainy season in 2000 served as a baseline. Mutations in <jats:italic>dhfr</jats:italic> and <jats:italic>dhps</jats:italic> associated with <jats:styled-content style="fixed-case">SP</jats:styled-content> resistance were analysed by pyrosequencing in 861 parasite‐positive samples.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The prevalence of the <jats:styled-content style="fixed-case">SP</jats:styled-content> resistance conferring triple <jats:italic>dhfr</jats:italic> mutation 51I, 59R, 108N increased from 1.3% in the rainy season of 2000 to 35.3% in 2009, and 54.3% in 2011 (<jats:italic>P </jats:italic>≤ 0.001). Comparing rainy and dry seasons, we observed an increasing step‐like pattern with higher prevalence of the <jats:italic>dhfr</jats:italic> triple mutant in the respective dry season compared with the preceding rainy season. The proportion of the <jats:italic>dhps</jats:italic> 437Gly mutation in the rainy season of 2000 was 53.2% and subsequently increased to 77.6% in 2009 (<jats:italic>P </jats:italic>≤ 0.001).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The increase in molecular markers linked with <jats:styled-content style="fixed-case">SP</jats:styled-content> resistance jeopardises the efficacy of <jats:styled-content style="fixed-case">IPT</jats:styled-content>p and the planned <jats:styled-content style="fixed-case">IPT</jats:styled-content>i interventions in <jats:styled-content style="fixed-case">B</jats:styled-content>urkina <jats:styled-content style="fixed-case">F</jats:styled-content>aso, calling for careful monitoring of genotypic resistance markers and <jats:italic>in vivo</jats:italic> validation of <jats:styled-content style="fixed-case">IPT</jats:styled-content> efficacy.</jats:p></jats:sec>