Heidelberg Institute of Global Health, Medical School, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
Medical College of Yangzhou University, Yangzhou University, Yangzhou, China.
J Travel Med. 2019 Jun 1;26(4). doi: 10.1093/jtm/taz030.
Artemisinin-based combination therapy (ACT) is the global standard of care for uncomplicated falciparum malaria. First reports of ACT resistance came from western Cambodia and the Thailand-Cambodia border in 2002-2004. The subsequent emergence and expansion of Plasmodium falciparum strains resistant to the artemisinin component and ACT are now threatening the efficacy of falciparum malaria treatment.
We performed a literature review on the history and the current degree of geographic expansion of artemisinin and ACT resistance. Resistance against artemisinins is defined as >5% of patients carrying PfKelch13 (K13) mutations, all of whom have been found to have persistent parasitaemia by microscopy on Day 3 after treatment.
Several studies including the multi-centre Tracking Resistance to Artemisinin Collaboration study investigated artemisinin resistance in Southeast Asia and beyond and demonstrated increasing prevalence of P. falciparum infections with slow parasite clearance rates in the Greater Mekong Subregion (GMS). K13 mutations were strongly associated with delayed P. falciparum parasite clearance, and the prevalence of the mutation PfKelch13 C580Y is increasing in the GMS. Resistance to ACT regimens is now well established in western Cambodia and in eastern Thailand, southern Laos and southern Vietnam. Moreover, the prevalence of slow P. falciparum parasite clearance has continuously increased over the past 10-15 years at the Thailand-Myanmar border, in nearly all regions of Myanmar, and at the Myanmar-China border.
Multidrug resistant malaria is a rapidly increasing problem, but fortunately still limited to Southeast Asia, in particular to the GMS. In the long-term it may threaten global progress in malaria control but is not yet of concern with regards to malaria prophylaxis, as ACTs are not used for prevention in travellers, current ACT regimens are still effective in most malaria endemic areas outside the GMS and the preferred travellers' prophylaxis atovaquone-proguanil and doxycycline remain protective. However, artemsinin resistance in the GMS is of real concern to travellers as it will affect the choice of malaria treatment including standby-emergence treatment.
青蒿素类复方疗法（ACT）是治疗无并发症恶性疟原虫感染的全球标准疗法。2002-2004 年，首次在柬埔寨西部和泰柬边境报告了 ACT 耐药病例。随后，对青蒿素类药物和 ACT 敏感的恶性疟原虫株的出现和传播，现在正威胁着恶性疟原虫病治疗的疗效。
我们对青蒿素和 ACT 耐药的历史和当前地理扩展程度进行了文献回顾。对青蒿素的耐药性定义为>5%的患者携带 PfKelch13（K13）突变，所有这些患者在治疗后第 3 天通过显微镜检查均发现持续存在寄生虫血症。
包括多中心追踪抗青蒿素耐药合作研究在内的几项研究调查了东南亚及其他地区的青蒿素耐药性，并表明大湄公河次区域（GMS）的恶性疟原虫感染清除率较慢，感染率不断上升。K13 突变与恶性疟原虫清除延迟密切相关，GMS 中 PfKelch13 C580Y 突变的流行率正在上升。ACT 方案的耐药性现在在柬埔寨西部和泰国东部、老挝南部和越南南部已经得到证实。此外，过去 10-15 年，在泰缅边境、缅甸几乎所有地区以及缅中边境，恶性疟原虫清除率缓慢的情况一直在持续增加。
多药耐药性疟疾是一个迅速增加的问题，但幸运的是，它仍然局限于东南亚，特别是 GMS。从长期来看，它可能会威胁到全球疟疾控制的进展，但目前还不会对疟疾预防产生影响，因为 ACT 并不用于旅行者预防，目前的 ACT 方案在 GMS 以外的大多数疟疾流行地区仍然有效，旅行者首选的预防药物阿托伐醌-磺胺多辛和多西环素仍然具有保护作用。然而，GMS 中的青蒿素耐药性确实让旅行者感到担忧，因为它将影响疟疾治疗的选择，包括备用出现治疗。
