{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T14:02:07Z","timestamp":1764770527355,"version":"3.46.0"},"reference-count":16,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,3]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>\n                    Drug resistance is a major obstacle for malaria control and elimination. Prophylactic antimalarial drug use may contribute to antimalarial drug resistance. We evaluated samples collected from a randomized, controlled clinical trial comparing chloroquine (CQ) with trimethoprim-sulfamethoxazole (TS) prophylaxis among adults with HIV on successful antiretroviral therapy in Malawi. We hypothesized that compared with no prophylaxis controls, participants receiving prophylaxis would have higher rates of polymorphisms associated with antifolate resistance in dihydrofolate reductase (\n                    <jats:italic>pfdhfr<\/jats:italic>\n                    ) and dihydropteroate synthase (\n                    <jats:italic>pfdhps<\/jats:italic>\n                    ) for the TS group and higher rates of the chloroquine resistance transporter (\n                    <jats:italic>pfcrt<\/jats:italic>\n                    ) for the CQ group. Pyrosequencing of these key molecular markers revealed no significant differences in resistance mutation prevalence across treatment arms. Compared with those infecting controls, parasites infecting those receiving TS or CQ prophylaxis did not have increased prevalence of resistance-associated polymorphisms in\n                    <jats:italic>pfdhfr<\/jats:italic>\n                    ,\n                    <jats:italic>pfdhps<\/jats:italic>\n                    , and\n                    <jats:italic>pfcrt<\/jats:italic>\n                    . Importantly, we did not detect a mutation indicating CQ resistance in any breakthrough infection.\n                  <\/jats:p>","DOI":"10.4269\/ajtmh.25-0136","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T19:38:51Z","timestamp":1761766731000},"page":"1289-1292","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Trimethoprim-Sulfamethoxazole and Chloroquine Prophylaxis on Drug-Resistant Plasmodium falciparum Mutations in Adults with HIV in Malawi"],"prefix":"10.4269","volume":"113","author":[{"given":"Kate J.","family":"Fairhurst","sequence":"first","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randy G.","family":"Mungwira","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Titus H.","family":"Divala","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osward M.","family":"Nyirenda","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhoda","family":"Masonga","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudhaunshu","family":"Joshi","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Fern","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joep J.","family":"van Oosterhout","sequence":"additional","affiliation":[{"name":"Dignitas International, Zomba, Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam K.","family":"Laufer","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew B.","family":"Laurens","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","reference":[{"year":"2014","key":"b1","article-title":"Guidelines on Post-Exposure Prophylaxis for HIV and the Use of Co-Trimoxazole Prophylaxis for HIV-Related Infections among Adults, Adolescents and Children: Recommendations for a Public Health Approach: December 2014 Supplement to the 2013 Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection."},{"key":"b2","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":"b3","series-title":"Clin Infect Dis","first-page":"1058","article-title":"Revisiting co-trimoxazole prophylaxis for African Adults in the era of antiretroviral therapy: A randomized controlled clinical trial","volume":"73","author":"Laurens","year":"2021"},{"year":"2021","key":"b4","article-title":"Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring: Recommendations for a Public Health Approach"},{"key":"b5","series-title":"Lancet Microbe","first-page":"100841","article-title":"Pathogen diversity and antimicrobial resistance transmission of Salmonella enterica serovars Typhi and Paratyphi A in Bangladesh, Nepal, and Malawi: A genomic epidemiological study","volume":"5","author":"Dyson","year":"2024"},{"key":"b6","series-title":"PLoS Negl Trop Dis","first-page":"e0007223","article-title":"The prevalence and antifolate drug resistance profiles of Plasmodium falciparum in study participants randomized to discontinue or continue cotrimoxazole prophylaxis","volume":"13","author":"Juma","year":"2019"},{"key":"b7","series-title":"Trials","first-page":"322","article-title":"TSCQ study: A randomized, controlled, open-label trial of daily trimethoprim-sulfamethoxazole or weekly chloroquine among adults on antiretroviral therapy in Malawi: Study protocol for a randomized controlled trial","volume":"17","author":"Laurens","year":"2016"},{"key":"b8","series-title":"J Clin Microbiol","first-page":"495","article-title":"Rapid and simple method for purification of nucleic acids","volume":"28","author":"Boom","year":"1990"},{"key":"b9","series-title":"J Clin Microbiol","first-page":"3900","article-title":"Pyrosequencing, a high-throughput method for detecting single nucleotide polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes of Plasmodium falciparum.","volume":"44","author":"Zhou","year":"2006"},{"key":"b10","series-title":"Malar J","first-page":"31","article-title":"A high-throughput method for quantifying alleles and haplotypes of the malaria vaccine candidate Plasmodium falciparum merozoite surface protein-1 19 kDa","volume":"5","author":"Takala","year":"2006"},{"key":"b11","series-title":"J Infect Dis","first-page":"380","article-title":"Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria","volume":"185","author":"Kublin","year":"2002"},{"key":"b12","series-title":"Malar J","first-page":"104","article-title":"Malaria chemoprevention and drug resistance: A review of the literature and policy implications","volume":"21","author":"Plowe","year":"2022"},{"key":"b13","series-title":"Mol Cell","first-page":"861","article-title":"Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance","volume":"6","author":"Fidock","year":"2000"},{"key":"b14","series-title":"Curr Epidemiol Rep","first-page":"46","article-title":"Antimalarial drug resistance and implications for the WHO global technical strategy","volume":"8","author":"Ippolito","year":"2021"},{"key":"b15","series-title":"J Infect Dis","first-page":"694","article-title":"Persistence of sulfadoxine-pyrimethamine resistance despite reduction of drug pressure in Malawi","volume":"212","author":"Artimovich","year":"2015"},{"key":"b16","series-title":"Lancet","first-page":"685","article-title":"HIV","volume":"392","author":"Ghosn","year":"2018"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/113\/6\/article-p1289.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/113\/6\/article-p1289.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/113\/6\/article-p1289.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T13:32:15Z","timestamp":1764768735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/113\/6\/article-p1289.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,3]]},"references-count":16,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.25-0136","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"type":"print","value":"0002-9637"},{"type":"electronic","value":"1476-1645"}],"subject":[],"published":{"date-parts":[[2025,12,3]]}}}