Continued Low Efficacy of Artemether-Lumefantrine in Angola in 2019
| Autor: | Filomeno Fortes, Carolina Miguel Ferreira, Belmira José Bondo, Ana Luísa Micolo Cândido, Mateusz M. Plucinski, Kialanda André, Roberta Horth, García Nazaré Pembele, Naomi W. Lucchi, Sarah M Labuda, Samaly S. Svigel, Eldin Talundzic, Pedro Rafael Dimbu, Joana Morais, Domingos Jandondo, Julia Kelley, Luzala Elisabeth Armando Garcia, Gabriel Ponce de Leon, Benjamin Nieto Andrade, Felismina Caquece, José Franco Martins, Dhruviben Patel |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Artemether/lumefantrine molecular markers 030231 tropical medicine malaria Plasmodium falciparum infection World health Epidemiology and Surveillance resistance 03 medical and health sciences 0302 clinical medicine Internal medicine parasitic diseases medicine Pharmacology (medical) Artemisinin Pharmacology 0303 health sciences 030306 microbiology business.industry medicine.disease Confidence interval Infectious Diseases business Malaria medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.01949-20 |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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