Day 3 parasitemia and Plasmodium falciparum Kelch 13 mutations among uncomplicated malaria patients treated with artemether-lumefantrine in Adjumani district, Uganda

被引:2
|
作者
Angwe, Martin Kamilo [1 ,2 ,3 ]
Mwebaza, Norah [1 ]
Nsobya, Sam Lubwama [4 ]
Vudriko, Patrick [2 ]
Dralabu, Saviour [2 ]
Omali, Denis [1 ,5 ]
Tumwebaze, Maria Agnes [2 ]
Ocan, Moses [1 ]
机构
[1] Makerere Univ, Coll Hlth Sci, Dept Pharmacol & Therapeut, Kampala, Uganda
[2] Makerere Univ, Sch Vet Med & Anim Resources, Res Ctr Trop Dis & Vector Control, Coll Vet Med Anim Resources & Biosecur,Dept Pharm, Kampala, Uganda
[3] Makerere Univ, Sch Biosecur Biotech & Lab Sci, Coll Vet Med Anim Resources & Biosecur, Dept Biomol Resources & Biolab Sci, Kampala, Uganda
[4] Makerere Univ, Infect Dis Res Collaborat, Kampala, Uganda
[5] Makerere Univ, Infect Dis Inst, Kampala, Uganda
来源
PLOS ONE | 2024年 / 19卷 / 06期
关键词
PLASMODIUM-FALCIPARUM; EMERGING RESISTANCE; ARTEMISININ; K13-PROPELLER; TRANSMISSION; POLYMORPHISM; CHILDREN;
D O I
10.1371/journal.pone.0305064
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Artemisinin resistance threatens malaria control and elimination efforts globally. Recent studies have reported the emergence of Plasmodium falciparum parasites tolerant to artemisinin agents in sub-Saharan Africa, including Uganda. The current study assessed the day 3 parasite clearance and its correlation with P. falciparum K13 propeller gene (pfkelch13) mutations in P. falciparum parasites isolated from patients with uncomplicated malaria under artemether-lumefantrine (AL) treatment. This study enrolled 100 P. falciparum-positive patients to whom AL was prescribed between 09/September/2022 and 06/November/2022. Blood samples were collected in EDTA tubes before treatment initiation (day 0) and on day 3. Parasitemia was assessed by microscopy from blood smears and quantitative polymerase chain reaction (qPCR) from the DNA extracted. The day 0 parasite K13 gene was sequenced using Sanger sequencing. Sequence data were analysed using MEGA version 11 software. The data were analysed using STATA version 15, and the Mann-Whitney U test was used to compare PCR parasite clearance on day 3 using the comparative CT value method and pfkelch13 mutations. The prevalence of day 3 parasitaemia was 24% (24/100) by microscopy and 63% (63/100) by qPCR from the AL-treated patients. P. falciparum K13-propeller gene polymorphism was detected in 18.8% (15/80) of the day 0 DNA samples. The K13 mutations found were C469Y, 12.5% (10/80); A675V, 2.5% (2/80); A569S, 1.25%, (1/80), A578S, 1.25%, (1/80) and; F491S, 1.25%, (1/80) a new allele not reported anywhere. The C469Y mutation, compared to the wild-type, was associated with delayed parasite clearance p = 0.0278, Hodges-Lehmann estimation 3.2108 on the log scale, (95%CI 1.7076, 4.4730). There was a high prevalence of day 3 P. falciparum among malaria patients treated using artemether-lumefantrine. We conclude the presence of the K13 mutation associated with artemisinin resistance by P. falciparum in Adjumani district, Uganda, necessitates regular surveillance of the effectiveness and efficacy of artemether-lumefantrine in the country.
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页数:13
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