Author:
Tun Kyaw Myo,Jeeyapant Atthanee,Myint Aung Hpone,Kyaw Zwe Thiha,Dhorda Mehul,Mukaka Mavuto,Cheah Phaik Yeong,Imwong Mallika,Hlaing Thaung,Kyaw Thar Htun,Ashley Elizabeth A.,Dondorp Arjen,White Nicholas J.,Day Nicholas P. J.,Smithuis Frank
Abstract
Abstract
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 ultra-sensitive 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.
Trial registration NCT02020330. Registered 24 December 2013, https://clinicaltrials.gov/NCT02020330
Funder
Three Millennium Development Goals Fund
Publisher
Springer Science and Business Media LLC
Subject
Infectious Diseases,Parasitology
Cited by
26 articles.
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