Limited Impact of Intermittent Preventive Treatment-Sulfadoxine-Pyrimethamine (IPTp-SP) and long-lasting insecticidal bed nets (LLINs) on Plasmodium falciparum Genetic Diversity and Population Structure among Pregnant Women in Cameroon

Abstract Background Intermittent preventive treatment during pregnancy with Sulfadoxine-Pyrimethamine (IPTp-SP) together with long-lasting insecticidal bed nets (LLINs) are the recommended preventive interventions against malaria in pregnancy. However, transmission intensity and drug resistance in the parasite threatens the efficacy of IPTp-SP and may compromise naturally acquired pregnancy-specific immunity. This study determined the impact of IPTp-SP and LLIN use on the genetic diversity, infection complexity and population structure of Plasmodium falciparum in pregnant women across five geo-ecological zones of Cameroon. Method Pregnant women were enrolled through a cross-sectional survey conducted at antenatal clinics in selected health facilities across nine (9) regions of Cameroon between October 2019 and October 2022. Malaria was diagnosed with rapid diagnostic test (RDT) and quantitative real-time polymerase chain reaction (qPCR). The P. falciparum parasite was genotyped using neutral microsatellite and merozoite surface protein 2 markers. Genetic diversity, multiplicity of infection, and population structure were analysed using Geneious Prime (version 2019) and R (version 4.4.0) software, comparing infections across IPTp-SP and LLIN interventions and geo-ecological zones. Results Of 3,313 pregnant women enrolled, 58.8% (1947/3,313), were infected with P. falciparum while P. malariae and P. ovale were detected in 5.0% (165/3,313) and 3.4% (112/3,313) of the participants respectively. Overall, 36% (1191/3313) of participants received at least one dose of IPTp-SP and 30.2% (918/3044) reported concurrent use of IPTp-SP and LLINs. The overall prevalence of malaria in pregnancy was 26.9%, 35.7%, and 35.8 by mRDT, microscopy, qPCR respectively. IPTp-SP and bed net usage were associated with a significant reduction in polyclonal infections and heterozygosity (He), although the overall infection complexity and genetic diversity remain high. The genetic fingerprint of infections did not differ by use or type of interventions; however, low but significant genetic differentiation was observed between parasite infections from different geo-ecological regions. Conclusions Overall, these findings suggest sub-optimal protection from malaria infections by IPTp-SP and LLIN and limited influence on the overall genetic diversity and population structure of P. falciparum in pregnant women. Continuous molecular surveillance, SP efficacy studies and new approaches may be needed to strengthen malaria prevention in pregnant women across endemic settings.