Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine and prevalence of molecular markers of anti-malarial drug resistance in children in Togo in 2021.

Autor: Dorkenoo AM; Faculté des Sciences de la Santé, Université de Lomé, Lomé, Togo. monicadork@yahoo.fr., Warsame M; School of Public Health and Community Medicine, University of Gothenburg, Gothenburg, Sweden., Ataba E; Programme National de Lutte Contre le Paludisme, Lomé, Togo., Hemou M; Service de Pédiatrie, Centre Hospitalier Universitaire Campus, Lomé, Togo., Yakpa K; Programme National de Lutte Contre le Paludisme, Lomé, Togo., Sossou E; Service des Laboratoires, Centre Hospitalier Universitaire Sylvanus Olympio Lomé, Lomé, Togo., Mitigmsagou M; Faculté des Sciences de la Santé, Université de Lomé, Lomé, Togo., Teou CD; Faculté des Sciences de la Santé, Université de Lomé, Lomé, Togo., Caspar E; Institute of Parasitology and Tropical Diseases, Université de Strasbourg, UR7292 Dynamics of Host-Pathogen Interactions, 67000, Strasbourg, France., Ma L; Biomics Platform, C2RT, Institut Pasteur, 75015, Paris, France., Djadou KE; Faculté des Sciences de la Santé, Université de Lomé, Lomé, Togo., Atcha-Oubou T; Programme National de Lutte Contre le Paludisme, Lomé, Togo., Rasmussen C; Global Malaria Programme, World Health Organization, Geneva, Switzerland., Menard D; Institute of Parasitology and Tropical Diseases, Université de Strasbourg, UR7292 Dynamics of Host-Pathogen Interactions, 67000, Strasbourg, France.; Malaria Genetics and Resistance Unit, Institut Pasteur, Université Paris Cité, INSERM U1201, 75015, Paris, France.; Malaria Parasite Biology and Vaccines, Institut Pasteur, Université Paris Cité, 75015, Paris, France.; Laboratory of Parasitology and Medical Mycology, CHU Strasbourg, 67000, Strasbourg, France.
Jazyk: angličtina
Zdroj: Malaria journal [Malar J] 2024 Apr 03; Vol. 23 (1), pp. 92. Date of Electronic Publication: 2024 Apr 03.
DOI: 10.1186/s12936-024-04922-1
Abstrakt: Background: Artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are the currently recommended first- and second-line therapies for uncomplicated Plasmodium falciparum infections in Togo. This study assessed the efficacy of these combinations, the proportion of Day3-positive patients (D3 +), the proportion of molecular markers associated with P. falciparum resistance to anti-malarial drugs, and the variable performance of HRP2-based malaria rapid diagnostic tests (RDTs).
Methods: A single arm prospective study evaluating the efficacy of AL and DP was conducted at two sites (Kouvé and Anié) from September 2021 to January 2022. Eligible children were enrolled, randomly assigned to treatment at each site and followed up for 42 days after treatment initiation. The primary endpoint was polymerase chain reaction (PCR) adjusted adequate clinical and parasitological response (ACPR). At day 0, samples were analysed for mutations in the Pfkelch13, Pfcrt, Pfmdr-1, dhfr, dhps, and deletions in the hrp2/hrp3 genes.
Results: A total of 179 and 178 children were included in the AL and DP groups, respectively. After PCR correction, cure rates of patients treated with AL were 97.5% (91.4-99.7) at day 28 in Kouvé and 98.6% (92.4-100) in Anié, whereas 96.4% (CI 95%: 89.1-98.8) and 97.3% (CI 95%: 89.5-99.3) were observed at day 42 in Kouvé and Anié, respectively. The cure rates of patients treated with DP at day 42 were 98.9% (CI 95%: 92.1-99.8) in Kouvé and 100% in Anié. The proportion of patients with parasites on day 3 (D3 +) was 8.5% in AL and 2.6% in DP groups in Anié and 4.3% in AL and 2.1% DP groups in Kouvé. Of the 357 day 0 samples, 99.2% carried the Pfkelch13 wild-type allele. Two isolates carried nonsynonymous mutations not known to be associated with artemisinin partial resistance (ART-R) (A578S and A557S). Most samples carried the Pfcrt wild-type allele (97.2%). The most common Pfmdr-1 allele was the single mutant 184F (75.6%). Among dhfr/dhps mutations, the quintuple mutant haplotype N51I/C59R/S108N + 437G/540E, which is responsible for SP treatment failure in adults and children, was not detected. Single deletions in hrp2 and hrp3 genes were detected in 1/357 (0.3%) and 1/357 (0.3%), respectively. Dual hrp2/hrp3 deletions, which could affect the performances of HRP2-based RDTs, were not observed.
Conclusion: The results of this study confirm that the AL and DP treatments are highly effective. The absence of the validated Pfkelch13 mutants in the study areas suggests the absence of ART -R, although a significant proportion of D3 + cases were found. The absence of dhfr/dhps quintuple or sextuple mutants (quintuple + 581G) supports the continued use of SP for IPTp during pregnancy and in combination with amodiaquine for seasonal malaria chemoprevention.
Trial Registration: ACTRN12623000344695.
(© 2024. The Author(s).)
Databáze: MEDLINE
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