Angwe Martin Kamilo, Mwebaza Norah, Nsobya Sam Lubwama, Kiguba Ronald, Vudriko Patrick, Dralabu Savior, Omali Denis, Tumwebaze Maria Agnes, Ocan Moses
Department of Pharmacology and Therapeutics, College of Health Science, Makerere University.
Reseacrh Center for Tropical Diseases and Vector Control, School of Veterinary Medicine and Animal Resources, College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University.
medRxiv. 2025 Jun 14:2025.06.13.25329585. doi: 10.1101/2025.06.13.25329585.
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 allele may impact artemisinin exposure, potentially contributing to differences in treatment outcomes This study assessed the prevalence of the genotype among patients with uncomplicated malaria treated with artemether-lumefantrine at Adjumani District Hospital in the West Nile region, Uganda. A total of 100 randomly selected patients with microscopically confirmed uncomplicated 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 genotype of the participants. positivity was determined by microscopy and qPCR. For qPCR, parasite clearance was determined using comparative CT value. Data analysis was done using STATA 17.0 at a 95% significance level. Among the malaria patients genotyped, 65% were female, and 35% were male, with a mean age of 17±10 years. The variant allele frequency was 0.37, and the genotype frequency was 43% GG, 17% TT and 40% GT. 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 (=323.0; =-2.3442; =0.019). Malaria patients in Adjumani district had a high frequency of the variant allele. Interindividual variability in clearance exists, with heterozygous patients demonstrating slow artemether-lumefantrine parasite clearance. There is a need to consider incorporating host genomic factors, such as metabolising enzyme genotype into routine Therapeutic Efficacy Studies (TES).
细胞色素P450 2B6（CYP2B6）是多态性最高的酶之一，在青蒿素及其衍生物的代谢中起主要作用。最常见但功能缺陷的等位基因频率的变化可能会影响青蒿素的暴露量，这可能是导致治疗结果差异的原因之一。本研究评估了乌干达西尼罗河地区阿朱马尼区医院接受蒿甲醚-本芴醇治疗的非复杂性疟疾患者中该基因型的流行情况。该研究共纳入了100例经显微镜确诊为非复杂性疟疾且正在接受蒿甲醚-本芴醇（AL）治疗的随机选择患者。在给予AL后的第0天和第3天，使用乙二胺四乙酸（EDTA）管采集每份2 - 3毫升的血样。使用Qiagen DNA Mini试剂盒提取DNA。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法来确定参与者的基因型。通过显微镜检查和定量聚合酶链反应（qPCR）确定阳性情况。对于qPCR，使用比较CT值来确定寄生虫清除情况。使用STATA 17.0在9５%的显著性水平下进行数据分析。在进行基因分型的疟疾患者中，65%为女性，35%为男性，平均年龄为17±10岁。变异等位基因频率为0.37，基因型频率为GG型43%、TT型１7%和GT型40%。在第3天，GG型患者中显微镜检查阳性率为14%（6/43），GT型患者中为37.5%（15/40），TT型患者中为17.64%（3/17）。GG型患者的PCR阳性率为58.1%（25/43），GT型患者中为72.5%（29/40），TT型患者中为52.9%（9/17）。与纯合子（GG、TT）个体相比，杂合子个体（GT）的寄生虫清除速度慢10倍（=323.0；=-2.3442；=0.019）。阿朱马尼区的疟疾患者中变异等位基因频率较高。青蒿素-本芴醇的寄生虫清除存在个体间差异，杂合子患者的蒿甲醚-本芴醇寄生虫清除速度较慢。有必要考虑将宿主基因组因素，如代谢酶基因型纳入常规治疗效果研究（TES）中。
