{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:30:57Z","timestamp":1768570257007,"version":"3.49.0"},"posted":{"date-parts":[[2025,6,14]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":55,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T00:00:00Z","timestamp":1749859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  CYP2B6, one of the most polymorphic enzymes, plays a major role in the metabolism of artemisinin and its derivatives. Variation in the frequency of the most common yet functionally deficient\n                  <jats:italic>CYP2B6*6<\/jats:italic>\n                  allele may impact artemisinin exposure, potentially contributing to differences in treatment outcomes. This study assessed the prevalence of the\n                  <jats:italic>CYP2B6*6<\/jats:italic>\n                  genotype among patients with uncomplicated malaria treated with artemether-lumefantrine at Adjumani District Hospital in the West Nile region, Uganda.\n                <\/jats:p>\n                <jats:p>\n                  A total of 100 randomly selected patients with microscopically confirmed uncomplicated\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  malaria receiving artemether-lumefantrine (AL) were included in the study. Blood samples, 2-3 mL each, were collected using EDTA tubes on days 0 and 3 after AL administration. DNA was extracted using Qiagen DNA Mini kit. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used to determine the\n                  <jats:italic>CYP2B6*6<\/jats:italic>\n                  genotype of the participants.\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  positivity was determined by microscopy and qPCR. For qPCR, parasite clearance was determined using comparative CT value. Data analysis was done using STATA\n                  <jats:italic>ver<\/jats:italic>\n                  17.0 at a 95% significance level.\n                <\/jats:p>\n                <jats:p>\n                  Among the malaria patients genotyped, 65% were female, and 35% were male, with a mean age of 17\u00b110 years. The\n                  <jats:italic>CYP2B6*6<\/jats:italic>\n                  variant allele frequency was 0.37, and the genotype frequency was 43% GG, 17% TT and 40% GT.\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  day 3 microscopy positivity was 14% (6\/43) among the GG, 37.5% (15\/40) among the GT, and 17.64% (3\/17) among the TT patients. PCR positivity rates were 58.1% (25\/43) in the GG, 72.5% (29\/40) in the GT, and 52.9% (9\/17) in the TT patients. Heterozygous individuals (GT) had slow parasite clearance by a 10-fold difference compared to the homozygous (GG, TT) individuals (\n                  <jats:italic>U<\/jats:italic>\n                  =323.0;\n                  <jats:italic>Z<\/jats:italic>\n                  =-2.3442;\n                  <jats:italic>p<\/jats:italic>\n                  =0.019).\n                <\/jats:p>\n                <jats:p>\n                  Malaria patients in Adjumani district had a high frequency of the\n                  <jats:italic>CYP2B6*6<\/jats:italic>\n                  variant allele. Interindividual variability in\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  clearance exists, with heterozygous patients demonstrating slow artemether-lumefantrine\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  parasite clearance. There is a need to consider incorporating host genomic factors, such as metabolising enzyme genotype into routine Therapeutic Efficacy Studies (TES).\n                <\/jats:p>","DOI":"10.1101\/2025.06.13.25329585","type":"posted-content","created":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T14:00:12Z","timestamp":1749909612000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>CYP2B6<\/i>\n                  *\n                  <i>6<\/i>\n                  single nucleotide polymorphism among patients with uncomplicated malaria in Adjumani district, Uganda: implications on efficacy of artemether-lumefantrine"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1211-7762","authenticated-orcid":false,"given":"Martin Kamilo","family":"Angwe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norah","family":"Mwebaza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sam Lubwama","family":"Nsobya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Kiguba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Vudriko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savior","family":"Dralabu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Omali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Agnes","family":"Tumwebaze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8852-820X","authenticated-orcid":false,"given":"Moses","family":"Ocan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025061703251091000_2025.06.13.25329585v1.1","unstructured":"World Health Organization. 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