Journal
MALARIA JOURNAL
Volume 17, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12936-018-2404-4
Keywords
Plasmodium falciparum; Artemether-lumefantrine; Artemisinin resistance; kelch13 mutation; Myanmar
Categories
Funding
- Three Millennium Development Goals Fund
- Medical Action Myanmar
- Wellcome Trust of Great Britain
- Li Ka Shing Foundation
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Background: 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. Methods: 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 ultrasensitive PCR. Patients were followed up for 42 days. Results: Of 154 patients recruited (105 adults and 49 children < 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. Conclusion: 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.
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