Continued Low Efficacy of Artemether-Lumefantrine in Angola in 2019

Antimicrob Agents Chemother. 2021 Jan 20;65(2):e01949-20. doi: 10.1128/AAC.01949-20. Print 2021 Jan 20.

Abstract

Biennial therapeutic efficacy monitoring is a crucial activity for ensuring the efficacy of currently used artemisinin-based combination therapy in Angola. Children with acute uncomplicated Plasmodium falciparum infection in sentinel sites in the Benguela, Zaire, and Lunda Sul Provinces were treated with artemether-lumefantrine (AL) or artesunate-amodiaquine (ASAQ) and monitored for 28 days to assess clinical and parasitological responses. Molecular correction was performed using seven microsatellite markers. Samples from treatment failures were genotyped for the pfk13, pfcrt, and pfmdr1 genes. Day 3 clearance rates were ≥95% in all arms. Uncorrected day 28 Kaplan-Meier efficacy estimates ranged from 84.2 to 90.1% for the AL arms and 84.7 to 100% for the ASAQ arms. Corrected day 28 estimates were 87.6% (95% confidence interval [CI], 81 to 95%) for the AL arm in Lunda Sul, 92.2% (95% CI, 87 to 98%) for AL in Zaire, 95.6% (95% CI, 91 to 100%) for ASAQ in Zaire, 98.4% (95% CI, 96 to 100%) for AL in Benguela, and 100% for ASAQ in Benguela and Lunda Sul. All 103 analyzed samples had wild-type pfk13 sequences. The 76T pfcrt allele was found in most (92%; 11/12) ASAQ late-failure samples but in only 16% (4/25) of AL failure samples. The N86 pfmdr1 allele was found in 97% (34/35) of treatment failures. The AL efficacy in Lunda Sul was below the 90% World Health Organization threshold, the third time in four rounds that this threshold was crossed for an AL arm in Angola. In contrast, the observed ASAQ efficacy has not been below 95% to date in Angola, including this latest round.

Keywords: malaria; molecular markers; resistance.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amodiaquine / therapeutic use
  • Angola
  • Antimalarials* / therapeutic use
  • Artemether / therapeutic use
  • Artemether, Lumefantrine Drug Combination
  • Child
  • Democratic Republic of the Congo
  • Drug Combinations
  • Ethanolamines / therapeutic use
  • Humans
  • Infant
  • Malaria, Falciparum* / drug therapy
  • Plasmodium falciparum / genetics

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Drug Combinations
  • Ethanolamines
  • Amodiaquine
  • Artemether