Selection of antimalarial drug resistance after intermittent preventive treatment of infants and children (IPTi/c) in Senegal

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• 作者：Magatte Ndiaye ; Roger Tine ; Babacar Faye ; Jean L. Ndiaye ; Ibrahima Diouf ; Aminata C. Lo ; Khadime Sylla ; Yemou Dieng ; Rachel Hallett ; Michael Alifrangis ; Oumar Gaye
• 关键词：P. falciparum ; Malaria ; Sulphadoxine-pyrimethamine ; Children ; Mutation ; Senegal
• 刊名：Comptes Rendus Biologies
• 出版年：2013
• 出版时间：May-June, 2013
• 年：2013
• 卷：336
• 期：5-6
• 页码：295-300
• 全文大小：348 K

文摘

Senegal has since 2003 used sulphadoxine-pyrimethamine (SP) for Intermittent Preventive Treatment (IPT) of malaria in risk groups. However, the large-scale IPT strategy may result in increasing drug resistance. Our study investigated the possible impact of SP-IPT given to infants and children on the prevalence of SP-resistant haplotypes in the Plasmodium falciparum genes Pfdhfr and Pfdhps, comparing sites with and without IPTi/c. P.?falciparum positives samples (n = 352) were collected from children under 5 years of age during two cross-sectional surveys in 2010 and 2011 in three health districts (two on IPTi/c and one without IPTi/c intervention) located in the southern part of Senegal. The prevalence of SP-resistance-related haplotypes in Pfdhfr and Pfdhps was determined by nested PCR followed by sequence-specific oligonucleotide probe (SSOP)-ELISA. The prevalence of the Pfdhfr double mutant haplotypes (CNRN and CICN) was stable between years at < 10 % in the control group (P = 0.69), while it rose significantly in the IPTi/c group from 2 % in 2010 to 20 % in 2011 (P = 0.008). The prevalence of the Pfdhfr triple mutant haplotype (CIRN) increased in both groups, but only significantly in the IPTi/c group from 41 % to 65 % in 2011 (P = 0.005). Conversely, the Pfdhps 437G mutation decreased in both groups from 44.6 % to 28.6 % (P = 0.07) and from 66.7 % to 47.5 % (P = 0.02) between 2010 and 2011 in the control and the IPTi/c groups, respectively. Combined with Pfdhfr, there was a weak trend for decreasing prevalence of quadruple mutants (triple Pfdhfr + Pfdhps 437G) in both groups (P = 0.15 and P = 0.34). During the two cross-sectional surveys, some significant changes were observed in the SP-resistance-related genes. However, since these changes were observed in the two groups, the IPTi/c strategy does only seem to have limited impact on resistance development and other factors as well. However, continuous monitoring will be needed, due to the up-scaling of the IPTi/c strategy in Senegal according to WHO recommendations.