Selection of Antimalarial Drug Resistance after Intermittent Preventive Treatment of Infants and Children (IPTi/c) in Senegal.


Ndiaye, M; Tine, R; Faye, B; Ndiaye, JL; Lo, AC; Sylla, K; Abiola, A; Dieng, Y; Ndiaye, D; Hallett, R; Gaye, O; Alifrangis, M; (2013) Selection of Antimalarial Drug Resistance after Intermittent Preventive Treatment of Infants and Children (IPTi/c) in Senegal. The American journal of tropical medicine and hygiene. ISSN 0002-9637 DOI: https://doi.org/10.4269/ajtmh.12-0739

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Abstract

Since 2003, Senegal has 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. Plasmodium falciparum-positive samples (N = 352) were collected from children < 5 years of age during two cross-sectional surveys in 2010 and 2011 living 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-enzyme-linked immunosorbent assay. The prevalence of the Pfdhfr double mutant haplotypes (CNRN and CICN) were stable between years at < 10% in the control group (P = 0.69), whereas 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, because 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 impacted as well. However, continuous monitoring will be needed because of the up scaling of the IPTi/c strategy in Senegal according to recommendations by the World Health Organization (WHO).

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Malaria Centre
PubMed ID: 23589534
Web of Science ID: 319957700018
URI: http://researchonline.lshtm.ac.uk/id/eprint/790316

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