Prevalence of molecular markers of Plasmodium falciparum resistance to sulfadoxine–pyrimethamine during the intermittent preventive treatment in infants coupled with the expanded program immunization in Senegal

Abstract

Several studies have shown the efficacy of the intermittent preventive treatment (IPT) using sulfadoxine-pyrimethamine (SP) coupled with the expanded program of immunization (EPI) in infants. However, its adoption as a strategy is conditioned by the long-term efficacy of SP. The impact of IPT-SP coupled with the EPI on the prevalence of markers of resistance to SP was evaluated during this study conducted in Southern Senegal. Three cross-sectional surveys in two health districts (IPT+) were conducted prior to the implementation, 1 year, and 2 years after. A third district located between the two districts served as a test zone (IPT-). PCR tests were carried out from filter papers collected in children under five for the two first measures and from positive rapid diagnostic tests in the same population for the third measure. Mutations in codons 51, 59, and 108 of the DHFR gene and in codons 437 and 540 of the DHPS were analyzed. The results showed that the prevalence of DHFR triple mutation was more frequent after 2 years in IPT+ areas. Regarding quadruple mutation, DHFR (51, 59, and 108) and DHPS (437), no difference was noted between the two areas. The quintuple mutation was not observed after 2 years of implementation in both areas. However, an individual analysis showed significant differences in the individual mutation points 51, 59, 108, and 437. This study reveals that despite an increase in the prevalence of individual mutations, the IPT-SP coupled with the EPI has no major impact on DHFR and DHPS combined mutations.

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

“…Finally, a combined, high prevalence of quadruple mutant (triple mutant Pfdhfr + 437G mutations) haplotype was noted in both areas in 2009 but as well seemed to decrease in 2010. Compared with the baseline study conducted by Faye and others 29 in the same study area, a general increase in all mutant haplotypes was noted. However, comparing the two groups in 2009 and 2010, it appears that, although changes are observed as a trend for an increase of triple Pfdhfr haplotypes and a trend for a decrease in Pfdhps 437G this is not only seen in the IPTi/c group and thus, IPTi/c is not driving the selection of SP resistance in the study area.…”

Surveillance of Molecular Markers of Plasmodium falciparum Resistance to Sulphadoxine-Pyrimethamine 5 Years after the Change of Malaria Treatment Policy in Ghana

“…The authors therefore concluded that IPTi using SP did not impact the frequency of the combined dhfr and dhps mutations. 7 Another study in Mali observed no increase in the prevalence of the dhfr and dhps mutations after a year of IPTi. 24 In countries where SP is now being used in combination with artemisinin derivatives, a rapid increase in the prevalence of quintuple mutations have been reported.…”

“…6 With the increased use of SP in the country, there is the possibility of parasite resistance to the drug as observed in some malaria-endemic countries such as Mozambique and Senegal. 7,8 The SP mainly targets the inhibition of folate synthesis in the parasite, in particular the activity of dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps). The magnitude of SP susceptibility in the parasite depends on the frequency of mutations identified in the genes that encode for these enzymes.…”

“…A recent study in Senegal where SP is being used as an intermittent preventive treatment in infants (IPTi) has shown an increase in the prevalence of SP mutations after 2 years of IPTi. 7 The investigation involved the frequency of dhfr and dhps mutations in two study areas, one with ITPi and one without. The authors reported an increase in the dhfr triple mutant frequency in the area with IPTi after 2 years but not at the other site.…”

Application of loop analysis for evaluation of malaria control interventions

“…For example, it was shown that IPT targeting preschool children (age < six years) during the malaria transmission season markedly reduced clinical malaria cases, which occurred even in areas with high ITN use [81]. Despite its effectiveness, several studies suggested that IPT could accelerate the spread of resistance [85-87]. For example, IPT targeting infants is thought to accelerate the spread of resistant parasites in areas of low or unstable transmission and is more likely to accelerate the spread of resistance in high transmission areas than is IPT in adults [80].…”