Therapeutic efficacy trial of artemisinin-based combination therapy for the treatment of uncomplicated malaria and investigation of mutations in k13 propeller domain in Togo, 2012–2013
Tóm tắt
Since 2005, the Togo National Malaria Control Programme has recommended two different formulations of artemisinin-based combination therapy (ACT), artesunate–amodiaquine (ASAQ) and artemether-lumefantrine (AL), for the treatment of uncomplicated malaria. Regular efficacy monitoring of these two combinations is conducted every 2 or 3 years. This paper reports the latest efficacy assessment results and the investigation of mutations in the k13 propeller domain. The study was conducted in 2012–2013 on three sentinel sites of Togo (Lomé, Sokodé and Niamtougou). Children aged 6–59 months, who were symptomatically infected with Plasmodium falciparum, were treated with either AL (Coartem®, Novartis Pharma, Switzerland) or ASAQ (Co-Arsucam®, Sanofi Aventis, France). The WHO standard protocol for anti-malarial treatment evaluation was used. The primary end-point was 28-day adequate clinical and parasitological response (ACPR), corrected to exclude reinfection using polymerase-chain reaction (PCR) genotyping. A total of 523 children were included in the study. PCR-corrected ACPR was 96.3–100 % for ASAQ and 97–100 % for AL across the three study sites. Adverse events were negligible: 0–4.8 % across all sites, for both artemisinin-based combinations. Upon investigation of mutations in the k13 propeller domain, only 9 (1.8 %) mutations were reported, three in each site. All mutant parasites were cleared before day 3. All day 3 positive patients were infected with k13 wild type parasites. The efficacy of AL and ASAQ remains high in Togo, and both drugs are well tolerated. ASAQ and AL would be recommended for the treatment of uncomplicated malaria in Togo.
Tài liệu tham khảo
O’Meara WP, Mangeni JN, Steketee R, Greenwood B. Changes in the burden of malaria in sub-Saharan Africa. Lancet Infect Dis. 2010;10:545–55.
WHO. World Malaria Report 2015. Geneva: World Health Organization; 2015.
Dorkenoo MA, Barrette A, Agbo YM, Bogreau H, Kutoati S, Sodahlon YK, et al. Surveillance of the efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum among children under five in Togo, 2005–2009. Malar J. 2012;11:338.
Vestergaard LS, Ringwald P. Responding to the challenge of antimalarial drug resistance by routine monitoring to update national malaria treatment policies. Am J Trop Med Hyg. 2007;77(6 Suppl):153–9.
Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014;371:411–23.
Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM. Evidence of artemisinin-resistant malaria in Western Cambodia. N Engl J Med. 2008;359:2619–20.
Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009;361:455–67.
Saralamba S, Pan-Ngum W, Maude RJ, Lee SJ, Tarning J, Lindegårdh N, et al. Intrahost modeling of artemisinin resistance in Plasmodium falciparum. Proc Natl Acad Sci USA. 2011;108:397–402.
Witkowski B, Khim N, Chim P, Kim S, Ke S, Kloeung N, et al. Reduced artemisinin susceptibility of Plasmodium falciparum ring stages in western Cambodia. Antimicrob Agents Chemother. 2013;57:914–23.
Mok S, Imwong M, Mackinnon MJ, Sim J, Ramadoss R, Yi P, et al. Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription. BMC Genom. 2011;12:391.
Witkowski B, Amaratunga C, Khim N, Sreng S, Chim P, Kim S, et al. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in vitro and ex vivo drug-response studies. Lancet Infect Dis. 2013;13:1043–9.
Chotivanich K, Tripura R, Das D, Yi P, Day NPJ, Pukrittayakamee S, et al. Laboratory detection of artemisinin-resistant Plasmodium falciparum. Antimicrob Agents Chemother. 2014;58:3157–61.
Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois A-C, Khim N, et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2013;505:50–5.
WHO. Methods for surveillance of antimalarial drug efficacy. Geneva: World Health Organization; 2009.
WHO. Methods and techniques for clinical trials on antimalarial drug efficacy: genotyping to identify parasite populations. Geneva: World Health Organization; 2008.
Stepniewska K, White NJ. Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria. Malar J. 2006;5:127.
WHO. Data entry form for antimalarial therapeutic efficacy studies. Geneva: World Health Organization. http://www.who.int/malaria/publications/atoz/9789241597531/en/. Accessed 15 Dec 2010.
Abuaku B, Duah N, Quaye L, Quashie N, Koram K. Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under five years of age in three ecological zones in Ghana. Malar J. 2012;11:388.
Abuaku B, Duah N, Quaye L, Quashie N, Malm K, Bart-Plange C, et al. Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine combinations in the treatment of uncomplicated malaria in two ecological zones in Ghana. Malar J. 2016;15:6.
Ogouyèmi-Hounto A, Azandossessi C, Lawani S, Damien G, Tove YSS, Remoue F, et al. Therapeutic efficacy of artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in northwest Benin. Malar J. 2016;15:37.
Mekonnen SK, Medhin G, Berhe N, Clouse RM, Aseffa A. Efficacy of artemether–lumefantrine therapy for the treatment of uncomplicated Plasmodium falciparum malaria in Southwestern Ethiopia. Malar J. 2015;14:317.
Oguche S, Okafor HU, Watila I, Meremikwu M, Agomo P, Ogala W, et al. Efficacy of artemisinin-based combination treatments of uncomplicated falciparum malaria in under-five-year-old Nigerian children. Am J Trop Med Hyg. 2014;91:925–35.
Ojurongbe O, Lawal OA, Abiodun OO, Okeniyi JA, Oyeniyi AJ, Oyelami OA. Efficacy of artemisinin combination therapy for the treatment of uncomplicated falciparum malaria in Nigerian children. J Infect Dev Ctries. 2013;7:975–82.
Shayo A, Buza J, Ishengoma DS. Monitoring of efficacy and safety of artemisinin-based anti-malarials for treatment of uncomplicated malaria: a review of evidence of implementation of anti-malarial therapeutic efficacy trials in Tanzania. Malar J. 2015;14:135.
Rasmussen C, Ringwald P, Tulloch J. Emergency response to artemisinin resistance in the Greater Mekong subregion: regional framework for action 2013–2015. Geneva: World Health Organization; 2013.
WHO. Status report on artemisinin and ACT resistance Geneva. Geneva: World Health Organization; 2015.