Effectiveness and safety of 3 and 5 day courses of artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in an area of emerging artemisinin resistance in Myanmar

<strong>Background</strong> Artemisinin resistance in Plasmodium falciparum has emerged and spread in Southeast Asia. In areas where resistance is established longer courses of artemisinin-based combination therapy have improved cure rates. <strong>Methods</strong> The stand...

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Main Authors: Tun, KM, Jeeyapant, A, Myint, AH, Kyaw, ZT, Dhorda, M, Mukaka, M, Cheah, PY, Imwong, M, Hlaing, T, Kyaw, TH, Ashley, EA, Dondorp, A, White, NJ, Day, NPJ, Smithuis, F
Formato: Journal article
Idioma:English
Publicado em: BioMed Central 2018
Descrição
Resumo:<strong>Background</strong> Artemisinin resistance in Plasmodium falciparum has emerged and spread in Southeast Asia. In areas where resistance is established longer courses of artemisinin-based combination therapy have improved cure rates. <strong>Methods</strong> The standard 3-day course of artemether–lumefantrine (AL) was compared with an extended 5-day regimen for the treatment of uncomplicated falciparum malaria in Kayin state in South-East Myanmar, an area of emerging artemisinin resistance. Late parasite clearance dynamics were described by microscopy and quantitative ultra-sensitive PCR. Patients were followed up for 42 days. <strong>Results</strong> Of 154 patients recruited (105 adults and 49 children &lt; 14 years) 78 were randomized to 3 days and 76 to 5 days AL. Mutations in the P. falciparum kelch13 propeller gene (k13) were found in 46% (70/152) of infections, with F446I the most prevalent propeller mutation (29%; 20/70). Both regimens were well-tolerated. Parasite clearance profiles were biphasic with a slower submicroscopic phase which was similar in k13 wild-type and mutant infections. The cure rates were 100% (70/70) and 97% (68/70) in the 3- and 5-day arms respectively. Genotyping of the two recurrences was unsuccessful. <strong>Conclusion</strong> Despite a high prevalence of k13 mutations, the current first-line treatment, AL, was still highly effective in this area of South-East Myanmar. The extended 5 day regimen was very well tolerated, and would be an option to prolong the useful therapeutic life of AL.