Evidence of artemisinin partial resistance in North-western Tanzania: clinical and drug resistance markers study.

Autor:	Ishengoma DS; National Institute for Medical Research, Dar es Salaam, Tanzania.; Harvard T.H Chan School of Public Health, Boston, MA, USA.; Faculty of Pharmaceutical Sciences, Monash University, VIC, Australia.; Department of Biochemistry, Kampala International University in Tanzania, Dar es Salaam, Tanzania., Mandara CI; National Institute for Medical Research, Dar es Salaam, Tanzania., Bakari C; National Institute for Medical Research, Dar es Salaam, Tanzania., Fola AA; Department of Pathology and Laboratory Medicine and Center for Computational Molecular Biology, Brown University, Providence, RI, USA., Madebe RA; National Institute for Medical Research, Dar es Salaam, Tanzania., Seth MD; National Institute for Medical Research, Dar es Salaam, Tanzania., Francis F; National Institute for Medical Research, Dar es Salaam, Tanzania., Buguzi C; National Institute for Medical Research, Dar es Salaam, Tanzania., Moshi R; National Institute for Medical Research, Dar es Salaam, Tanzania., Garimo I; National Malaria Control Program (NMCP), Dodoma, Tanzania., Lazaro S; National Malaria Control Program (NMCP), Dodoma, Tanzania., Lusasi A; National Malaria Control Program (NMCP), Dodoma, Tanzania., Aaron S; National Malaria Control Program (NMCP), Dodoma, Tanzania., Chacky F; National Malaria Control Program (NMCP), Dodoma, Tanzania., Mohamed A; National Malaria Control Program (NMCP), Dodoma, Tanzania., Njau RJA; Malariologist and Public Health Specialist, Muhimbili University of Health and Allied Sciences, School of Public Health and Social Sciences Dar es Salaam, Tanzania., Kitau J; World Health Organization Country Office, Dar es Salaam, Tanzania., Rasmussen C; World Health Organization, Geneva, Switzerland., Bailey JA; Department of Pathology and Laboratory Medicine and Center for Computational Molecular Biology, Brown University, Providence, RI, USA., Juliano JJ; University of North Carolina, Chapel Hill, NC, USA., Warsame M; Gothenburg University, Gothenburg, Sweden.; Benadir University, Mogadishu, Somalia.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 Feb 01. Date of Electronic Publication: 2024 Feb 01.
DOI:	10.1101/2024.01.31.24301954
Abstrakt:	Background: Artemisinin-based combination therapies (ACTs) are the recommended antimalarial drugs for the treatment of uncomplicated malaria. The recent emergence of artemisinin partial resistance (ART-R) in Rwanda, Uganda and Eritrea is of great concern. In Tanzania, a nationwide molecular malaria surveillance in 2021 showed a high prevalence of the Kelch13 (K13) 561H mutation in Plasmodium falciparum from the north-western region, close to the border with Rwanda and Uganda. This study was conducted in 2022 to evaluate the efficacy of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) for the treatment of uncomplicated falciparum malaria and to confirm the presence of ART-R in Tanzania. Methods: This single-arm study evaluated the efficacy of AL and ASAQ in eligible children aged six months to 10 years at Bukangara Dispensary in Karagwe District, Kagera Region. Clinical and parasitological responses were monitored for 28 days according to standard WHO protocol. Mutations in K13 gene and extended haplotypes with these mutations were analysed using Sanger and whole genome sequencing data, respectively. Findings: 176 children (88 in each AL and ASAQ group) were enrolled and all achieved the defined outcomes. PCR-corrected adequate clinical and parasitological response (ACPR) was 98.3% (95% CI: 90.8-100) and 100.0% (95% CI: 95.8-100) for AL and ASAQ, respectively. Parasitaemia on day 3 was observed in 11/88 (12.5%) and 17/88 (19.3%) in the AL and ASAQ groups, respectively. The half-life of parasitaemia was significantly higher (>6.5 hrs) in patients with parasitaemia on day 3 and/or mutations in K13 gene at enrolment. Most patients with parasitaemia on day 3 (8/11 = 72.7% in the AL group and 10/17 = 58.8% in the ASAQ group) had 561H mutation at enrolment. The parasites with K13 mutations were not similar to those from south-east Asia and Rwanda, but had the same core haplotype of a new 561H haplotype reported in Kagera in 2021. Interpretation: These findings confirm the presence of ART-R in Tanzania. A context-specific strategy to respond to artemisinin partial resistance is urgently needed. Although both AL and ASAQ showed high efficacy, increased vigilance for reduced efficacy of these ACTs and detection of ART-R in other parts of the country is critical. Competing Interests: Declaration of conflict of interest All authors declare no conflict of interest
Databáze:	MEDLINE
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