Efficacy and safety of artemisinin-based combination therapy and the implications of Pfkelch13 and Pfcoronin molecular markers in treatment failure in Senegal

In 2006, Senegal adopted artemisinin-based combination therapy (ACT) as first-line treatment in the management of uncomplicated malaria. This study aimed to update the status of antimalarial efficacy more than ten years after their first introduction. This was a randomized, three-arm, open-label stu...

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Bibliographic Details
Published in:	Scientific reports Vol. 10; no. 1; p. 8907
Main Authors:	Diallo, Mamadou Alpha, Yade, Mamadou Samb, Ndiaye, Yaye Die, Diallo, Ibrahima, Diongue, Khadim, Sy, Saidou Abdoul, Sy, Mouhamad, Seck, Mame Cheikh, Ndiaye, Mouhamadou, Dieye, Baba, Gomis, Jules François, Sow, Djiby, Dème, Awa Bineta, Badiane, Aida Sadikh, Ndiaye, Daouda
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-06-2020 Nature Publishing Group
Subjects:	631/326/417 692/699/255/1629 Adolescent Amodiaquine Amodiaquine - administration & dosage Amodiaquine - adverse effects Amodiaquine - pharmacology Antimalarials - administration & dosage Antimalarials - adverse effects Antimalarials - pharmacology Artemether Artemether, Lumefantrine Drug Combination - administration & dosage Artemether, Lumefantrine Drug Combination - adverse effects Artemether, Lumefantrine Drug Combination - pharmacology Artemisinin Artemisinins - administration & dosage Artemisinins - adverse effects Artemisinins - pharmacology Artesunate Child Child, Preschool Combination therapy Dihydroartemisinin Drug Combinations Female Genotyping Humanities and Social Sciences Humans Infant Infant, Newborn Malaria Malaria, Falciparum - drug therapy Malaria, Falciparum - parasitology Male Microfilament Proteins - genetics multidisciplinary Mutation Patients Plasmodium falciparum - classification Plasmodium falciparum - drug effects Plasmodium falciparum - genetics Protozoan Proteins - genetics Quinolines - administration & dosage Quinolines - adverse effects Quinolines - pharmacology Science Science (multidisciplinary) Senegal Sequence Analysis, DNA Single-nucleotide polymorphism Treatment Failure Vector-borne diseases Senegal
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Summary:	In 2006, Senegal adopted artemisinin-based combination therapy (ACT) as first-line treatment in the management of uncomplicated malaria. This study aimed to update the status of antimalarial efficacy more than ten years after their first introduction. This was a randomized, three-arm, open-label study to evaluate the efficacy and safety of artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ) and dihydroartemisinin-piperaquine (DP) in Senegal. Malaria suspected patients were screened, enrolled, treated, and followed for 28 days for AL and ASAQ arms or 42 days for DP arm. Clinical and parasitological responses were assessed following antimalarial treatment. Genotyping ( msp1 , msp2 and 24 SNP-based barcode) were done to differentiate recrudescence from re-infection; in case of PCR-confirmed treatment failure, Pfk13 propeller and Pfcoronin genes were sequenced. Data was entered and analyzed using the WHO Excel-based application. A total of 496 patients were enrolled. In Diourbel, PCR non-corrected/corrected adequate clinical and parasitological responses (ACPR) was 100.0% in both the AL and ASAQ arms. In Kedougou, PCR corrected ACPR values were 98.8%, 100% and 97.6% in AL, ASAQ and DP arms respectively. No Pfk13 or Pfcoronin mutations associated with artemisinin resistance were found. This study showed that AL, ASAQ and DP remain efficacious and well-tolerated in the treatment of uncomplicated P. falciparum malaria in Senegal.
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-020-65553-5