PA-255 Genetic profiling of plasmodium falciparum antigenic biomarkers among asymptomatic pregnant women on intermittent preventive treatment with sulfadoxine-pyrimethamine from Southwest Nigeria

Abstract

<h3>Background</h3> The genetic complexity of Plasmodium falciparum is a contributory factor to the emergence of drug-resistant parasites. WHO recommends intermittent preventive treatment of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) to reduce the deleterious effects of maternal and neonatal malaria in high transmission settings. However, asymptomatic malaria still persists in areas of endemicity despite IPTp-SP regimen. The study evaluated the allelic profiles of Plasmodium falciparum merozoite surface proteins (Pfmsp-1, Pfmsp-2), glutamate-rich protein (Pfglurp) and multidrug resistance-1 gene (Pfmdr-1) in pregnant women on IPTp-SP regimen from southwest Nigeria. <h3>Methods</h3> 100 PCR-confirmed Plasmodium falciparum isolates, comprising visit 1 (V1) (n = 52), Delivery (n = 31) and Cord blood (n = 17) were randomly selected from EDCTP2 funded study (Trial no. 98867 IPTp-SP resistance in Nigeria TMA 2015 CDF – 973). Genomic DNA was genotyped using nested PCR. The Pfmdr-1 gene was further evaluated using restriction fragment length polymorphism (RLFP) at codon 86 with Apo1 restriction-digestion enzyme. Allelic frequencies, proportions and multiplicity of infection was calculated. Statistical significance was considered at p ≤ 0.05. <h3>Results</h3> Isolates from V1 confers 21.2% (Pfmsp-1), 32.7% (Pfmsp-2) and 9.6% (Pfglurp) distinct alleles, while delivery samples had 45.2% (Pfmsp-1), 32.3% (Pfmsp-2) and 6.5% (Pfglurp) allelic types. Cord isolates recorded the highest alleles; 70.6% (Pfmsp-1), 58.0% (Pfmsp-2) and 5.9% (Pfglurp). The MOI for V1 was 2.7, 2.1 and 1.1 for Pfmsp-1, Pfmsp-2 and Pfglurp. Delivery and cord isolates recorded 3.2, 1.9 and 2.7, 1.9 for Pfmsp-1 and Pfmsp-2 respectively; but had monoclonal Pfglurp alleles. The Pfmdr-1 wild/mutant allelic combination (N86Y) was present in 11.8% (V1), 61.3% (Delivery) and 58.8% (Cord blood) p ≤ 0.05. Single point mutation (86Y) was only present in 5.9% cord isolates. <h3>Conclusion</h3> Antigenic falciparum strains with N86Y Pfmdr-1 mutations may limit the efficacy of intermittent sulfadoxine-pyrimethamine prophylaxis of malaria during pregnancy in southwest Nigeria.