Peripheral and Placental Prevalence of Sulfadoxine–Pyrimethamine Resistance Markers in Plasmodium falciparum among Pregnant Women in Southern Province, Rwanda

Author:

Alruwaili Muharib123,Uwimana Aline4,Sethi Reena5,Murindahabi Monique46,Piercefield Emily7,Umulisa Noella8,Abram Andrew9,Eckert Erin10,Munguti Kaendi11,Mbituyumuremyi Aimable4,Gutman Julie R.12,Sullivan David J.3

Affiliation:

1. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia;

2. Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana;

3. Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;

4. Malaria and Other Parasitic Diseases Division, Rwanda Biomedical Center, Kigali, Rwanda;

5. Maternal and Child Survival Program/Jhpiego, Washington, District of Columbia;

6. Roll Back Malaria, Ouagadougou, Burkina Faso;

7. U.S. President’s Malaria Initiative, Malaria Branch, U.S. Centers for Disease Control and Prevention, Kigali, Rwanda;

8. Maternal and Child Survival Program/Jhpiego, Kigali, Rwanda;

9. U.S. Peace Corps, Kigali, Rwanda;

10. RTI International, Washington, District of Columbia;

11. U.S. President’s Malaria Initiative, U.S. Agency for International Development, Kigali, Rwanda;

12. Malaria Branch, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia

Abstract

ABSTRACT. Intermittent preventive therapy during pregnancy (IPTp) with sulfadoxine–pyrimethamine (SP) is recommended in areas of moderate to high malaria transmission intensity. As a result of the increasing prevalence of SP resistance markers, IPTp-SP was withdrawn from Rwanda in 2008. Nonetheless, more recent findings suggest that SP may improve birthweight even in the face of parasite resistance, through alternative mechanisms that are independent of antimalarial effects. The prevalence of single nucleotide polymorphisms in Plasmodium falciparum dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr) genes associated with SP resistance among 148 pregnant women from 2016 to 2018 within Rwanda’s Southern Province (Huye and Kamonyi districts) was measured using a ligase detection reaction–fluorescent microsphere assay. The frequency of pfdhps K540E, A581G, and the quintuple (pfdhfr N51I + C59R + S108N/pfdhps A437G + K540E) and sextuple (pfdhfr N51I + C59R + S108N/pfdhps A437G + K540E + A581G) mutant genotypes was 90%, 38%, 75%, and 28%, respectively. No significant genotype difference was seen between the two districts, which are approximately 50 km apart. Observed agreements for matched peripheral to placental blood were reported and found to be 207 of 208 (99%) for pfdhfr and 239 of 260 (92%) for pfdhps. The peripheral blood sample did not miss any pfdhfr drug-resistant mutants or pfdhps except at the S436 loci. At this level of the sextuple mutant, the antimalarial efficacy of SP for preventing low birthweight is reduced, although overall SP still exerts a nonmalarial benefit during pregnancy. This study further reveals the need to intensify preventive measures to sustain malaria control in Rwanda to keep the overall incidence of malaria during pregnancy low.

Publisher

American Society of Tropical Medicine and Hygiene

Subject

Virology,Infectious Diseases,Parasitology

Reference26 articles.

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3. Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum.;Cowman,1988

4. The mechanism of resistance to sulfa drugs in Plasmodium falciparum.;Triglia,1999

5. Return of chloroquine antimalarial efficacy in Malawi;Laufer,2006

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