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Continued Low Efficacy of Artemether-Lumefantrine in Angola in 2019
Pedro Rafael Dimbu1, Roberta Horth2, Ana Luísa M Cândido3
1National Malaria Control Program, Ministry of Health, Luanda, Angola.
Insights
This study monitored artemisinin-based combination therapy efficacy in Angolan children. Artemether-lumefantrine (AL) showed reduced efficacy in Lunda Sul, while artesunate-amodiaquine (ASAQ) maintained high effectiveness.
Area of Science:
- Malariology
- Infectious Diseases
- Pharmacology
Background:
- Artemisinin-based combination therapy (ACT) is vital for malaria control.
- Monitoring ACT efficacy is crucial due to potential drug resistance.
- Plasmodium falciparum malaria remains a significant public health issue in Angola.
Purpose of the Study:
- To assess the biennial therapeutic efficacy of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) for uncomplicated Plasmodium falciparum malaria in Angola.
- To identify potential molecular markers associated with treatment failures.
Main Methods:
- A 28-day clinical and parasitological efficacy study was conducted in sentinel sites across Benguela, Zaire, and Lunda Sul provinces.
- Children with acute uncomplicated Plasmodium falciparum infection received either AL or ASAQ.
- Molecular genotyping of treatment failure samples was performed for pfk13, pfcrt, and pfmdr1 genes.
Main Results:
- Day 3 parasite clearance rates were high (≥95%) for both AL and ASAQ.
- Day 28 corrected efficacy estimates for AL ranged from 87.6% to 98.4%, and for ASAQ from 95.6% to 100%.
- The 76T pfcrt allele was more prevalent in ASAQ failures, while the N86 pfmdr1 allele was common in overall treatment failures. AL efficacy in Lunda Sul fell below the WHO 90% threshold.
Conclusions:
- Artesunate-amodiaquine (ASAQ) demonstrated sustained high efficacy (≥95%) across all study sites in Angola.
- Artemether-lumefantrine (AL) efficacy in Lunda Sul dropped below the WHO threshold, indicating a need for vigilance.
- The pfcrt and pfmdr1 genes may play a role in treatment outcomes, warranting further investigation.
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.
