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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

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 comp...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042398/
https://www.ncbi.nlm.nih.gov/pubmed/29996844
http://dx.doi.org/10.1186/s12936-018-2404-4
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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
author_facet 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
author_sort Tun, Kyaw Myo
collection PubMed
description 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 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-018-2404-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-60423982018-07-13 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 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 Malar J Research 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 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-018-2404-4) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-11 /pmc/articles/PMC6042398/ /pubmed/29996844 http://dx.doi.org/10.1186/s12936-018-2404-4 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
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
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042398/
https://www.ncbi.nlm.nih.gov/pubmed/29996844
http://dx.doi.org/10.1186/s12936-018-2404-4
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