Thanh Ngo Viet, Thuy-Nhien Nguyen, Tuyen Nguyen Thi Kim, Tong Nguyen Thanh, Nha-Ca Nguyen Thuy, Dong Le Thanh, Quang Huynh Hong, Farrar Jeremy, Thwaites Guy, White Nicholas J, Wolbers Marcel, Hien Tran Tinh
Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, 764 Vo Van Kiet Street, Ward 1, District 5, Ho Chi Minh City, Vietnam.
Institute of Malariology, Parasitology, and Entomology, Ho Chi Minh City, Vietnam.
Malar J. 2017 Jan 13;16(1):27. doi: 10.1186/s12936-017-1680-8.
Artemisinin resistant Plasmodium falciparum has emerged in the countries of the Greater Mekong sub-region posing a serious threat to global malaria elimination efforts. The relationship of artemisinin resistance to treatment failure has been unclear.
In annual studies conducted in three malaria endemic provinces in the south of Vietnam (Binh Phuoc, Ninh Thuan and Gia Lai) between 2011 and 2015, 489 patients with uncomplicated P. falciparum malaria were enrolled in detailed clinical, parasitological and molecular therapeutic response assessments with 42 days follow up. Patients received the national recommended first-line treatment dihydroartemisinin-piperaquine for three days.
Over the 5 years the proportion of patients with detectable parasitaemia on day 3 rose steadily from 38 to 57% (P < 0.001). In Binh Phuoc province, the parasite clearance half-life increased from 3.75 h in 2011 to 6.60 h in 2015 (P < 0.001), while treatment failures rose from 0% in 2012 and 2013, to 7% in 2014 and 26% in 2015 (P < 0.001). Recrudescence was associated with in vitro evidence of artemisinin and piperaquine resistance. In the treatment failures cases of 2015, all 14 parasite isolates carried the C580Y Pfkelch 13 gene, marker of artemisinin resistance and 93% (13/14) of them carried exoE415G mutations, markers of piperaquine resistance.
In the south of Vietnam recent emergence of piperaquine resistant P. falciparum strains has accelerated the reduced response to artemisinin and has led to treatment failure rates of up to 26% to dihydroartemisinin-piperaquine, Vietnam's current first-line ACT. Alternative treatments are urgently needed.
青蒿素耐药性恶性疟原虫已在大湄公河次区域各国出现，对全球疟疾消除工作构成严重威胁。青蒿素耐药性与治疗失败之间的关系一直不明确。
在2011年至2015年期间于越南南部三个疟疾流行省份（平阳、宁顺和嘉莱）开展的年度研究中，纳入了489例非复杂性恶性疟原虫疟疾患者，进行详细的临床、寄生虫学和分子治疗反应评估，并随访42天。患者接受国家推荐的一线治疗药物双氢青蒿素 - 哌喹，疗程三天。
在这5年中，第3天可检测到寄生虫血症的患者比例从38%稳步上升至57%（P < 0.001）。在平阳省，寄生虫清除半衰期从2011年的3.75小时增加到2015年的6.60小时（P < 0.001），而治疗失败率从2012年和2013年的0%上升至2014年的7%和2015年的26%（P < 0.001）。复发与青蒿素和哌喹耐药的体外证据相关。在2015年的治疗失败病例中，所有14株寄生虫分离株均携带C580Y Pfkelch 13基因（青蒿素耐药标志物），其中93%（13/14）携带exoE415G突变（哌喹耐药标志物）。
在越南南部，近期出现的对哌喹耐药的恶性疟原虫菌株加速了对青蒿素反应的降低，并导致对越南目前的一线青蒿素联合疗法双氢青蒿素 - 哌喹的治疗失败率高达26%。迫切需要替代治疗方法。
