Prevalence of molecular markers of resistance to sulfadoxine-pyrimethamine before and after community delivery of intermittent preventive treatment of malaria in pregnancy in sub-Saharan Africa: a multi-country evaluation

Abstract

Background: The effectiveness of community delivery of intermittent preventive treatment (C-IPT) of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine has been evaluated in selected areas of the Democratic Republic of the Congo, Madagascar, Mozambique, and Nigeria. We aimed to assess the effect of C-IPTp on the potential development of Plasmodium falciparum resistance to sulfadoxine-pyrimethamine, since it could threaten the effectiveness of this strategy.

Methods: Health facility-based cross-sectional surveys were conducted at baseline and 3 years after C-IPTp implementation in two neighbouring areas per country, one with C-IPTp intervention, and one without, in the four project countries. Dried blood spots from children under five years of age with clinical malaria were collected. Sulfadoxine-pyrimethamine resistance-associated mutations of the P falciparum dhfr (Asn51Ile/Cys59Arg/Ser108Asn/Ile164Leu) and dhps (Ile431Val/Ser436Ala/Ala437Gly/Lys540Glu/Ala581Gly/Ala613Ser) genes were analysed.

Findings: 2536 children were recruited between June 19 and Oct 10, 2018, during baseline surveys. Endline surveys were conducted among 2447 children between July 26 and Nov 30, 2021. In the Democratic Republic of the Congo, the dhfr/dhps IRNI/ISGEAA inferred haplotype remained lower than 10%, from 2% (5 of 296) at baseline to 8% (24 of 292) at endline, and from 3% (9 of 300) at baseline to 6% (18 of 309) at endline surveys in intervention and non-intervention areas respectively with no significant difference in the change between the areas. In Mozambique, the prevalence of this haplotype remained stable at over 60% (194 [64%] of 302 at baseline to 194 [64%] of 303 at endline, and 187 [61%] of 306 at baseline to 183 [61%] of 301 in endline surveys, in non-intervention and intervention areas respectively). No isolates harbouring the dhps ISGEAA genotype were found in Nigeria. In Madagascar, only five isolates with this haplotype were found in the non-intervention area (2 [>1%] of 300 at baseline and 3 [1%] of 300 at endline surveys). No isolates were found carrying the dhps ISGEGA genotype.

Interpretation: C-IPTp did not increase the prevalence of molecular markers associated with sulfadoxine-pyrimethamine resistance after three years of programme implementation. These findings reinforce C-IPTp as a strategy to optimise the control of malaria during pregnancy, and support the WHO guidelines for prevention of malaria in pregnancy.

Funding: UNITAID [2017-13-TIPTOP].