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Selection of antimalarial drug resistance after Intermittent Preventive Treatment of infants and children (IPTi/c) in Senegal

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Introduction

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.

Methodology

P. falciparum positives samples (n=352) were collected from children under five 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 Southern part of Senegal.

Results

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) were 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).

Conclusion

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 2 groups, the IPTi/c strategy does only seem to have limited impact on resistance development with other factors impacting as well

Supervisors:

Yemou Dieng (UCAD) & Michael Alifrangis (UoC)

Advisors:

Babacar Faye (UCAD) & Rachel Hallett (LSHTM)

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