Efficacy of artemether\u2013lumefantrine, artesunate\u2013amodiaquine, and dihydroartemisinin\u2013piperaquine for treatment of uncomplicated Plasmodium falciparum malaria in Angola, 2015

Mateusz M Plucinski,Denise O Garrett,Eldin Talundzic,Joltim Quivinja,Richard Kiniffo,Dhruviben S Patel,Venkatachalam Udhayakumar,Filomeno Fortes,Eric S Halsey,Yun He,Marília Afonso,Aleixo Panzo Macaia,Pascal Ringwald,Pedro Rafael Dimbu,Claudete Samutondo,Eliane Mbounga,Carolina Miguel Ferreira,Julia S Kelley

doi:10.1186/s12936-017-1712-4

Abstract

BackgroundRecent anti-malarial resistance monitoring in Angola has shown efficacy of artemether–lumefantrine (AL) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy. In addition, a controversial case of malaria unresponsive to artemisinins was reported in a patient infected in Lunda Sul Province in 2013.MethodsDuring January–June 2015, investigators monitored the clinical and parasitological response of children with uncomplicated Plasmodium falciparum infection treated with AL, artesunate–amodiaquine (ASAQ), or dihydroartemisinin–piperaquine (DP). The study comprised two treatment arms in each of three provinces: Benguela (AL, ASAQ), Zaire (AL, DP), and Lunda Sul (ASAQ, DP). Samples from treatment failures were analysed for molecular markers of resistance for artemisinin (K13) and lumefantrine (pfmdr1).ResultsA total of 467 children reached a study endpoint. Fifty-four treatment failures were observed: four early treatment failures, 40 re-infections and ten recrudescences. Excluding re-infections, the 28-day microsatellite-corrected efficacy was 96.3% (95% CI 91–100) for AL in Benguela, 99.9% (95–100) for ASAQ in Benguela, 88.1% (81–95) for AL in Zaire, and 100% for ASAQ in Lunda Sul. For DP, the 42-day corrected efficacy was 98.8% (96–100) in Zaire and 100% in Lunda Sul. All treatment failures were wild type for K13, but all AL treatment failures had pfmdr1 haplotypes associated with decreased lumefantrine susceptibility.ConclusionsNo evidence was found to corroborate the specific allegation of artemisinin resistance in Lunda Sul. The efficacy below 90% of AL in Zaire matches findings from 2013 from the same site. Further monitoring, particularly including measurement of lumefantrine blood levels, is recommended.

Highlights

Recent anti-malarial resistance monitoring in Angola has shown efficacy of artemether–lumefantrine (AL) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy
Monitoring and tracking these parasites has been facilitated by identification of mutations in the K13 propeller gene that serve as molecular markers for artemisinin resistance [4]
Five of the six arms reached the 100 participant target; enrolment in the ASAQ arm in Lunda Sul was stopped at 78 children due to a diminishing rate of patient eligibility following the start of the dry season

Summary

Introduction

Recent anti-malarial resistance monitoring in Angola has shown efficacy of artemether–lumefantrine (AL) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy. Strong evidence has accumulated that malaria parasites resistant to artemisinins have emerged and are spreading in certain parts of Southeast Asia [2, 3]. Monitoring and tracking these parasites has been facilitated by identification of mutations in the K13 propeller gene that serve as molecular markers for artemisinin resistance [4]. Past experience with the spread of chloroquine and sulfadoxine-pyrimethamine resistance stresses the importance of continued vigilance [11]

Methods

Results

Conclusion