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PA-255 Genetic profiling of plasmodium falciparum antigenic biomarkers among asymptomatic pregnant women on intermittent preventive treatment with sulfadoxine-pyrimethamine from Southwest Nigeria
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  1. Roland Funwei1,2,
  2. Atinuke Olaleye2,3,
  3. Uyaiabasi Noblefather1,2,
  4. Wasiu Hammad2,
  5. Charles Elikwu2,4,
  6. Akinmade Adepoju2,5,
  7. Chika Okangba4,
  8. Akinwumi Akinyede6,
  9. Olusola Ojurongbe7,
  10. Catherine Falade8,
  11. Oladapo Walker1,2
  1. 1Department of Pharmacology, Babcock University, Nigeria
  2. 2Centre for Advanced Medical Research and Biotechnology, Babcock University, Nigeria
  3. 3Two Hills Medical Clinic, Canada
  4. 4Department of Medical Microbiology, Babcock University, Nigeria
  5. 5Centre for Research, Innovation and Development, Babcock University, Nigeria
  6. 6Department of Pharmacology, Therapeutics and Toxicology, University of Lagos, Nigeria
  7. 7Department of Medical Microbiology, Ladoke Akintola University of Technology, Nigeria
  8. 8Institute for Advanced Medical Research and Training, University of Ibadan, Nigeria

Abstract

Background 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.

Methods 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.

Results 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.

Conclusion Antigenic falciparum strains with N86Y Pfmdr-1 mutations may limit the efficacy of intermittent sulfadoxine-pyrimethamine prophylaxis of malaria during pregnancy in southwest Nigeria.

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