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

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 As a result of the increasing prevalence of SP resistance markers, IPTp-SP was withdrawn from Rwanda in 2008.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 rece...

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Published inThe American journal of tropical medicine and hygiene Vol. 109; no. 5; pp. 1057 - 1062
Main Authors Alruwaili, Muharib, Uwimana, Aline, Sethi, Reena, Murindahabi, Monique, Piercefield, Emily, Umulisa, Noella, Abram, Andrew, Eckert, Erin, Munguti, Kaendi, Mbituyumuremyi, Aimable, Gutman, Julie R, Sullivan, David J
Format Journal Article
LanguageEnglish
Published United States Institute of Tropical Medicine 01.11.2023
The American Society of Tropical Medicine and Hygiene
Subjects
Antimalarials - pharmacology
Antimalarials - therapeutic use
Antiparasitic agents
Birth Weight
Dihydrofolate reductase
Drug Combinations
Drug Resistance - genetics
Female
Humans
Malaria
Malaria - drug therapy
Malaria, Falciparum - drug therapy
Malaria, Falciparum - epidemiology
Malaria, Falciparum - parasitology
Placenta
Plasmodium falciparum - genetics
Polymorphism, Single Nucleotide
Pregnancy
Pregnant Women
Prevalence
Pyrimethamine - pharmacology
Pyrimethamine - therapeutic use
Rwanda - epidemiology
Sulfadoxine - pharmacology
Sulfadoxine - therapeutic use
Rwanda
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Summary: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 As a result of the increasing prevalence of SP resistance markers, IPTp-SP was withdrawn from Rwanda in 2008.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.
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Financial support: This study was made possible by the generous support of the American people through the President’s Malaria Initiative and the United States Agency for International Development under the terms of Cooperative Agreement AID-OAA-A-14-00028. This study was also supported by the Johns Hopkins Malaria Research Institute at the Johns Hopkins Bloomberg School of Public Health. The facility was supported in part by Center for AIDS Research (CFAR) 5P30AI094189-04 (Chaisson).
Disclaimer: The findings and conclusions in this work are those of the authors and do not necessarily represent the official position of the US CDC and the US Agency for International Development.
Disclosure: D. J. S. is a founder and board member of AliquantumRx and has stock options. NIAID Safety monitoring Committee (SMC) as Independent safety monitor (ISM). He also received royalties for malaria test reagents from Binax Inc/Inverness Medical. The ethics committees at the Johns Hopkins Bloomberg School of Public Health and the Rwanda Biomedical Center approved the study. The CDC Human Research Protections Office reviewed and approved CDC participation as nonengaged. Written informed consent was obtained from all participants.
Authors’ addresses: Muharib Alruwaili, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia, Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, and Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, E-mail: mfalrwaili@ju.edu.sa. Aline Uwimana and Aimable Mbituyumuremyi, Malaria and Other Parasitic Diseases Division, Rwanda Biomedical Center, Kigali, Rwanda, E-mails: aline.uwimana@rbc.gov.rw and aimable.mbituyumuremyi@rbc.gov.rw. Reena Sethi, Maternal and Child Survival Program/Jhpiego, Washington, DC, E-mail: reena.sethi@gmail.com. Monique Murindahabi, Malaria and Other Parasitic Diseases Division, Rwanda Biomedical Center, Kigali, Rwanda, and Roll Back Malaria, Ouagadougou, Burkina Faso, E-mail: mmurindahabi@alma2030.org. Emily Piercefield, U.S. President’s Malaria Initiative, Malaria Branch, U.S. Centers for Disease Control and Prevention, Kigali, Rwanda, E-mail: emily.w.piercefield@uscg.mil. Noella Umulisa, Maternal and Child Survival Program/Jhpiego, Kigali, Rwanda, E-mail: noella.umulisa@jhpiego.org. Andrew Abram, US Peace Corps, Kigali, Rwanda, E-mail: abram6andrew@gmail.com. Erin Eckert, RTI International, Washington, DC, E-mail: eleckert@gmail.com. Kaendi Munguti, U.S. President's Malaria Initiative, U.S. Agency for International Development, Kigali, Rwanda, E-mail: kmunguti@usaid.gov. Julie R. Gutman, Malaria Branch, U.S. Centers for Disease Control and Prevention, Atlanta, GA, E-mail: fff2@cdc.gov. David J. Sullivan, Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, E-mail: dsulliv7@jhmi.edu.
ISSN:0002-9637
1476-1645
DOI:10.4269/ajtmh.23-0225