Lwin Khin Maung, Imwong Mallika, Suangkanarat Preyanan, Jeeyapant Atthanee, Vihokhern Benchawan, Wongsaen Klanarong, Snounou Georges, Keereecharoen Lilly, White Nicholas J, Nosten Francois
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Malar J. 2015 Aug 16;14:319. doi: 10.1186/s12936-015-0838-5.
Resistance to the artemisinin derivatives in Plasmodium falciparum has emerged in Cambodia and is now spreading throughout South-East Asia. The rapid elimination of P. falciparum seems to be the only viable option to avoid a public health disaster but this is difficult because even in low transmission settings many residents have asymptomatic parasitaemias.
In response to a large number of malaria cases reported in three remote villages on the Thai-Myanmar border where malaria is endemic and the disease is seasonal, surveys were conducted using an ultra-sensitive qPCR assay (LOD 22 parasites per mL). In one of the villages where it was feasible, mass anti-malarial drug administration was proposed to the population as a potential solution, and this was adopted.
In the three villages 204/356 (57.3 %), 212/385 (55.1 %) and 195/286 (68.2 %) of the resident populations were positive by qPCR (approximately one-third P. falciparum and two-thirds P. vivax). Of those positive for P. falciparum 62 % carried single point mutations in the P. falciparum kelch protein (a marker of artemisinin resistance). In one of the villages 217 of 674 inhabitants received at least one dose of dihydroartemisinin-piperaquine chemoprevention in June 2012, 155 (71.4 %) received two consecutive months, and 98 (45.2 %) received three treatment doses. The chemoprevention was generally well tolerated. The sub-microscopic reservoir of P. falciparum malaria was eliminated during the six-month follow-up period (prevalence fell from 7 to 0 %); P. vivax malaria persisted (prevalence fell from 35 to 8 %). From June to October 2012 (rainy season) the number of clinical episodes of P. falciparum was six times lower (46), than during the same period in the previous year (290).
Mass drug administration with dihydroartemisinin-piperaquine may be an effective strategy to eliminate P. falciparum rapidly where multi-drug resistance is present.
恶性疟原虫对青蒿素衍生物的耐药性已在柬埔寨出现,目前正在东南亚地区蔓延。迅速消除恶性疟原虫似乎是避免公共卫生灾难的唯一可行选择,但这很困难,因为即使在低传播环境中,许多居民也有无症状寄生虫血症。
针对泰国 - 缅甸边境三个疟疾流行且疾病呈季节性的偏远村庄报告的大量疟疾病例,使用超灵敏定量聚合酶链反应检测法(检测限为每毫升22个寄生虫)进行调查。在其中一个可行的村庄,向居民提议进行大规模抗疟药物给药作为一种潜在解决方案,并被采纳。
在这三个村庄中,通过定量聚合酶链反应检测,常住居民的阳性率分别为204/356(57.3%)、212/385(55.1%)和195/286(68.2%)(约三分之一为恶性疟原虫,三分之二为间日疟原虫)。在恶性疟原虫阳性者中,62%携带恶性疟原虫 Kelch 蛋白单点突变(青蒿素耐药性标志物)。在其中一个村庄,674名居民中有217人在2012年6月接受了至少一剂双氢青蒿素 - 哌喹化学预防,155人(71.4%)连续两个月接受预防,98人(45.2%)接受了三剂治疗。化学预防总体耐受性良好。在六个月的随访期内,恶性疟原虫疟疾的亚显微储存库被消除(患病率从7%降至0%);间日疟原虫疟疾仍然存在(患病率从35%降至8%)。2012年6月至10月(雨季),恶性疟原虫的临床发作次数比上一年同期(290次)低六倍(46次)。
在存在多重耐药性的地区,使用双氢青蒿素 - 哌喹进行大规模药物给药可能是迅速消除恶性疟原虫的有效策略。