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Reviews of "Day 3 Parasitemia and Plasmodium Falciparum Kelch 13 Mutations among Uncomplicated Malaria Patients Treated with Artemether-lumefantrine in Adjumani District, Uganda"

Reviewers: M C Lee (Sanger Institute) | 📘📘📘📘📘 • N Lucchi (CDC) | 📗📗📗📗◻️ • J Raman (University of Witwatersrand) | 📒📒📒◻️◻️ • M Oboh (London School of Hygiene & Tropical Medicine) | 📘📘📘📘📘

Published onMay 28, 2024
Reviews of "Day 3 Parasitemia and Plasmodium Falciparum Kelch 13 Mutations among Uncomplicated Malaria Patients Treated with Artemether-lumefantrine in Adjumani District, Uganda"
key-enterThis Pub is a Review of
Day 3 parasitemia and Plasmodium falciparum Kelch 13 mutations among uncomplicated malaria patients treated with artemether-lumefantrine in Adjumani district, Uganda
Day 3 parasitemia and Plasmodium falciparum Kelch 13 mutations among uncomplicated malaria patients treated with artemether-lumefantrine in Adjumani district, Uganda
Description

Abstract 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 that the K13 mutation associated with artemisinin resistance by P. falciparum is present in Adjumani district, Uganda. This necessitates regular surveillance of the effectiveness and efficacy of artemether-lumefantrine in the country.

To read the original manuscript, click the link above.

Summary of Reviews: This study evaluated the day 3 clearance of Plasmodium falciparum parasites in people with malaria treated with artemether-lumefantrine and its correlation with K13propeller gene (pfkelch13) mutations present in the parasites (which are associated with artemether resistance). P. falciparum K13-propeller gene polymorphism was detected in 18.8% of the day 0 DNA samples and it was associated with delayed parasite clearance. The reviewers overall state that the manuscript is potentially informative, suggesting a need to continuously evaluate the effectiveness of artemether in this context. However, they pointed out that it is unclear if parasitemia at day 3 corresponds to delayed clearance, reinfection or recrudescence, which could weaken the study conclusions.

Reviewer 1 (Marcus C L…) | 📘📘📘📘📘

Reviewer 2 (Naomi L…) | 📗📗📗📗◻️

Reviewer 3 (Jaishree R…) | 📒📒📒 ◻️◻️

Reviewer 4 (Mary O…) | 📘📘📘📘📘

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

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