{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:25:27Z","timestamp":1768350327723,"version":"3.49.0"},"reference-count":26,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"5","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,1]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>Intermittent preventive therapy during pregnancy (IPTp) with sulfadoxine\u2013pyrimethamine (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 As a result of the increasing prevalence of SP resistance markers, IPTp-SP was withdrawn from Rwanda in 2008.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 <jats:italic>Plasmodium falciparum<\/jats:italic> dihydropteroate synthase (<jats:italic>pfdhps<\/jats:italic>) and dihydrofolate reductase (<jats:italic>pfdhfr<\/jats:italic>) genes associated with SP resistance among 148 pregnant women from 2016 to 2018 within Rwanda\u2019s Southern Province (Huye and Kamonyi districts) was measured using a ligase detection reaction\u2013fluorescent microsphere assay. The frequency of <jats:italic>pfdhps<\/jats:italic> K540E, A581G, and the quintuple (<jats:italic>pfdhfr<\/jats:italic> N51I + C59R + S108N\/<jats:italic>pfdhps<\/jats:italic> A437G + K540E) and sextuple (<jats:italic>pfdhfr<\/jats:italic> N51I + C59R + S108N\/p<jats:italic>fdhps<\/jats:italic> 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\u2009km apart. Observed agreements for matched peripheral to placental blood were reported and found to be 207 of 208 (99%) for <jats:italic>pfdhfr<\/jats:italic> and 239 of 260 (92%) for <jats:italic>pfdhps<\/jats:italic>. The peripheral blood sample did not miss any <jats:italic>pfdhfr<\/jats:italic> drug-resistant mutants or <jats:italic>pfdhps<\/jats:italic> 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.<\/jats:p>","DOI":"10.4269\/ajtmh.23-0225","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T14:32:15Z","timestamp":1696257135000},"page":"1057-1062","source":"Crossref","is-referenced-by-count":4,"title":["Peripheral and Placental Prevalence of Sulfadoxine\u2013Pyrimethamine Resistance Markers in Plasmodium falciparum among Pregnant Women in Southern Province, Rwanda"],"prefix":"10.4269","volume":"109","author":[{"given":"Muharib","family":"Alruwaili","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia;"},{"name":"Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana;"},{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline","family":"Uwimana","sequence":"additional","affiliation":[{"name":"Malaria and Other Parasitic Diseases Division, Rwanda Biomedical Center, Kigali, Rwanda;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reena","family":"Sethi","sequence":"additional","affiliation":[{"name":"Maternal and Child Survival Program\/Jhpiego, Washington, District of Columbia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"Murindahabi","sequence":"additional","affiliation":[{"name":"Malaria and Other Parasitic Diseases Division, Rwanda Biomedical Center, Kigali, Rwanda;"},{"name":"Roll Back Malaria, Ouagadougou, Burkina Faso;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Piercefield","sequence":"additional","affiliation":[{"name":"U.S. President\u2019s Malaria Initiative, Malaria Branch, U.S. Centers for Disease Control and Prevention, Kigali, Rwanda;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noella","family":"Umulisa","sequence":"additional","affiliation":[{"name":"Maternal and Child Survival Program\/Jhpiego, Kigali, Rwanda;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Abram","sequence":"additional","affiliation":[{"name":"U.S. Peace Corps, Kigali, Rwanda;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Eckert","sequence":"additional","affiliation":[{"name":"RTI International, Washington, District of Columbia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaendi","family":"Munguti","sequence":"additional","affiliation":[{"name":"U.S. President\u2019s Malaria Initiative, U.S. Agency for International Development, Kigali, Rwanda;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aimable","family":"Mbituyumuremyi","sequence":"additional","affiliation":[{"name":"Malaria and Other Parasitic Diseases Division, Rwanda Biomedical Center, Kigali, Rwanda;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie R.","family":"Gutman","sequence":"additional","affiliation":[{"name":"Malaria Branch, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","reference":[{"key":"b1","series-title":"World Malaria Report 2022","year":"2022"},{"key":"b2","series-title":"Malar J","first-page":"237","article-title":"Malaria case clinical profiles and Plasmodium falciparum parasite genetic diversity: a cross sectional survey at two sites of different malaria transmission intensities in Rwanda","volume":"15","author":"Kateera","year":"2016"},{"key":"b3","series-title":"Proc Natl Acad Sci USA","first-page":"9109","article-title":"Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum.","volume":"85","author":"Cowman","year":"1988"},{"key":"b4","series-title":"Drug Resist Updat","first-page":"15","article-title":"The mechanism of resistance to sulfa drugs in Plasmodium falciparum.","volume":"2","author":"Triglia","year":"1999"},{"key":"b5","series-title":"N Engl J Med","first-page":"1959","article-title":"Return of chloroquine antimalarial efficacy in Malawi","volume":"355","author":"Laufer","year":"2006"},{"key":"b6","series-title":"PLOS Comput Biol","first-page":"e1010317","article-title":"Spatiotemporal spread of Plasmodium falciparum mutations for resistance to sulfadoxine\u2013pyrimethamine across Africa, 1990\u20132020","volume":"18","author":"Flegg","year":"2022"},{"key":"b7","series-title":"Trends Parasitol","first-page":"497","article-title":"Monitoring antifolate resistance in intermittent preventive therapy for malaria","volume":"29","author":"Venkatesan","year":"2013"},{"key":"b8","series-title":"Lancet Infect Dis","first-page":"546","article-title":"Effect of Plasmodium falciparum sulfadoxine\u2013pyrimethamine resistance on the effectiveness of intermittent preventive therapy for malaria in pregnancy in Africa: a systematic review and meta-analysis","volume":"19","author":"Van Eijk","year":"2019"},{"key":"b9","series-title":"Lancet Glob Health","first-page":"e942","article-title":"Overall, anti-malarial, and non-malarial effect of intermittent preventive treatment during pregnancy with sulfadoxine\u2013pyrimethamine on birthweight: a mediation analysis","volume":"8","author":"Roh","year":"2020"},{"key":"b10","series-title":"Lancet","first-page":"1020","article-title":"Effect of monthly intermittent preventive treatment with dihydroartemisinin\u2013piperaquine with and without azithromycin versus monthly sulfadoxine\u2013pyrimethamine on adverse pregnancy outcomes in Africa: a double-blind randomised, partly placebo-controlled trial","volume":"401","author":"Madanitsa","year":"2023"},{"key":"b11","author":"Gutman","year":"2022"},{"key":"b12"},{"key":"b13","series-title":"Clin Infect Dis","first-page":"127","article-title":"Effectiveness of intermittent screening and treatment of malaria in pregnancy on maternal and birth outcomes in selected districts in Rwanda: a cluster randomized controlled trial","volume":"77","author":"Uwimana","year":"2023"},{"key":"b14","series-title":"J Clin Microbiol","first-page":"2564","article-title":"Optimization of a ligase detection reaction\u2013fluorescent microsphere assay for 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