{"doi":"10.1128/aac.42.7.1811","title":"Molecular Basis of In Vivo Resistance to Sulfadoxine-Pyrimethamine in African Adult Patients Infected with\n            <i>Plasmodium falciparum</i>\n            Malaria Parasites","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            In vitro sulfadoxine and pyrimethamine resistance has been associated with point mutations in the dihydropteroate synthase and dihydrofolate reductase domains, respectively, but the in vivo relevance of these point mutations has not been well established. To analyze the correlation between genotype and phenotype, 10 Cameroonian adult patients were treated with sulfadoxine-pyrimethamine and followed up for 28 days. After losses to follow-up (\n            <jats:italic>n</jats:italic>\n            = 1) or elimination of DNA samples due to mixed parasite populations with pyrimethamine-sensitive and pyrimethamine-resistant profiles (\n            <jats:italic>n</jats:italic>\n            = 3), parasite genomic DNA from day 0 blood samples of six patients were analyzed by DNA sequencing. Three patients who were cured had isolates characterized by a wild-type or mutant dihydrofolate reductase gene (with one or two mutations) and a wild-type dihydropteroate synthase gene. Three other patients who failed to respond to sulfadoxine-pyrimethamine treatment carried isolates with triple dihydrofolate reductase gene mutations and either a wild-type or a mutant dihydropteroate synthase gene. Three dihydrofolate reductase gene codons (51, 59, and 108) may be reliable genetic markers that can accurately predict the clinical outcome of sulfadoxine-pyrimethamine treatment in Africa.\n          </jats:p>","journal":"Antimicrobial Agents and Chemotherapy","year":1998,"id":677598,"datarank":0.6646225198264971,"base_score":4.430816798843313,"endowment":4.430816798843313,"self_citation_contribution":0.6646225198264971,"citation_network_contribution":0.0,"self_endowment_contribution":0.6646225198264971,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":83,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":4,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":772860,"name":"Rachida Tahar","orcid":"0000-0003-1799-231X","position":1,"is_corresponding":false},{"id":107757,"name":"Pascal Ringwald","orcid":null,"position":2,"is_corresponding":false},{"id":1770468,"name":"Leonardo K. Basco","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Molecular Basis of In Vivo Resistance to Sulfadoxine-Pyrimethamine in African Adult Patients Infected with\n            <i>Plasmodium falciparum</i>\n            Malaria Parasites","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            In vitro sulfadoxine and pyrimethamine resistance has been associated with point mutations in the dihydropteroate synthase and dihydrofolate reductase domains, respectively, but the in vivo relevance of these point mutations has not been well established. To analyze the correlation between genotype and phenotype, 10 Cameroonian adult patients were treated with sulfadoxine-pyrimethamine and followed up for 28 days. After losses to follow-up (\n            <jats:italic>n</jats:italic>\n            = 1) or elimination of DNA samples due to mixed parasite populations with pyrimethamine-sensitive and pyrimethamine-resistant profiles (\n            <jats:italic>n</jats:italic>\n            = 3), parasite genomic DNA from day 0 blood samples of six patients were analyzed by DNA sequencing. Three patients who were cured had isolates characterized by a wild-type or mutant dihydrofolate reductase gene (with one or two mutations) and a wild-type dihydropteroate synthase gene. Three other patients who failed to respond to sulfadoxine-pyrimethamine treatment carried isolates with triple dihydrofolate reductase gene mutations and either a wild-type or a mutant dihydropteroate synthase gene. Three dihydrofolate reductase gene codons (51, 59, and 108) may be reliable genetic markers that can accurately predict the clinical outcome of sulfadoxine-pyrimethamine treatment in Africa.\n          </jats:p>","is_dataset_classified":null,"base_score":4.430816798843313,"endowment":4.430816798843313,"datacite_reuse_total":4,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"9661026","pmcid":"PMC105688","openalex_id":"https://openalex.org/W2076702075","authors":[],"funders":[],"total_grants":0,"fwci":3.4638,"citation_percentile":0.9182112,"influential_citations":0,"citation_trend":[{"year":2012,"count":6},{"year":2013,"count":4},{"year":2014,"count":3},{"year":2015,"count":3},{"year":2016,"count":1},{"year":2019,"count":1},{"year":2020,"count":3},{"year":2021,"count":5},{"year":2024,"count":3},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://aac.asm.org/content/aac/42/7/1811.full.pdf","host_type":"journal"},{"url":"https://aac.asm.org/content/aac/42/7/1811.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/AAC.42.7.1811","host_type":"publisher"},{"url":"https://doi.org/10.1128/aac.42.7.1811","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/9661026","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/105688","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC105688","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC105688/pdf/ac001811.pdf","host_type":"repository"}],"fields_of_study":["Malaria Research and Control","Trypanosoma species research and implications","Drug-Induced Hepatotoxicity and Protection","Adolescent","Adult","Animals","Antimalarials","Drug Combinations","Drug Resistance","Female","Humans","Malaria, Falciparum","Male","Multienzyme Complexes","Plasmodium falciparum","Pyrimethamine","Sulfadoxine","Tetrahydrofolate Dehydrogenase","Thymidylate Synthase"],"mesh_terms":["Adolescent","Adult","Animals","Antimalarials","Drug Combinations","Drug Resistance","Female","Humans","Male","Multienzyme Complexes","Plasmodium falciparum","Pyrimethamine","Sulfadoxine","Tetrahydrofolate Dehydrogenase","Thymidylate Synthase","Malaria, Falciparum"],"keywords":["Dihydropteroate synthase","Dihydrofolate reductase","Sulfadoxine/pyrimethamine","Pyrimethamine","DHPS","Biology","Sulfadoxine","Plasmodium falciparum","Point mutation","Virology","Antifolate","Genotype","Genetics","Mutant","Malaria","Gene","Immunology","Antimetabolite"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.13550628.v1","title":"Additional file 6 of Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis (1998–2020)","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.13550628","title":"Additional file 6 of Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis (1998–2020)","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.13550631.v1","title":"Additional file 7 of Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis (1998–2020)","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.13550631","title":"Additional file 7 of Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis (1998–2020)","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T04:19:45.522257Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}