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

Mouhamadou Ndiaye,Baba Dieye,Ibrahima Diallo,Aida Sadikh Badiane,Mamadou Samb Yade,Yaye Die Ndiaye,Mamadou Alpha Diallo,Awa Bineta Dème,Saidou Abdoul Sy,Daouda Ndiaye,Jules François Gomis,Djiby Sow,Khadim Diongue,Mame Cheikh Seck,Mouhamad Sy

doi:10.1038/s41598-020-65553-5

Mouhamadou Ndiaye, Baba Dieye + Show 13 more

Open Access

https://doi.org/10.1038/s41598-020-65553-5

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Abstract

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.

Highlights

In 2006, Senegal adopted artemisinin-based combination therapy (ACT) as first-line treatment in the management of uncomplicated malaria
Since the abandoning of chloroquine, due to high rate of resistance, the Senegal national malaria control program (NMCP) adjusted its national guidelines for the treatment of uncomplicated malaria by introducing sulphadoxine-pyrimethamine (SP) in 2003, and artemisinin-based combination therapy (ACT) in 2006, complying with the World Health Organization (WHO) recommendations[1]. This policy review was adopted as ACTs were proven to be the most effective treatment in the context of resistance to chloroquine and other antimalarial drugs[2]
This situation is not yet reported in Africa, it is likely that this resistance could potentially spread in Africa as history showed for chloroquine[8]

Summary

Introduction

In 2006, Senegal adopted artemisinin-based combination therapy (ACT) as first-line treatment in the management of uncomplicated malaria. Since the abandoning of chloroquine, due to high rate of resistance, the Senegal national malaria control program (NMCP) adjusted its national guidelines for the treatment of uncomplicated malaria by introducing sulphadoxine-pyrimethamine (SP) in 2003, and artemisinin-based combination therapy (ACT) in 2006, complying with the World Health Organization (WHO) recommendations[1]. This policy review was adopted as ACTs were proven to be the most effective treatment in the context of resistance to chloroquine and other antimalarial drugs[2]. In accordance with WHO recommendations, the efficacy of first and second-line antimalarial drugs should be evaluated at least once every two years at all sentinel sites[10]

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