Nosten F, van Vugt M, Price R, Luxemburger C, Thway K L, Brockman A, McGready R, ter Kuile F, Looareesuwan S, White N J
Shoklo Malaria Research Unit, Mae Sot, Thailand.
Lancet. 2000 Jul 22;356(9226):297-302. doi: 10.1016/s0140-6736(00)02505-8.
Worsening drug resistance in Plasmodium falciparum malaria is a major threat to health in tropical countries. We did a prospective study of malaria incidence and treatment in an area of highly multidrug-resistant P. falciparum malaria.
We assessed incidence of P. falciparum malaria and the in-vivo responses to mefloquine treatment over 13 years in two large camps for displaced Karen people on the northwest border of Thailand. During this time, the standard mefloquine dose was first increased, and then combined artesunate and mefloquine was introduced as first-line treatment for uncomplicated P. falciparum malaria.
Early detection and treatment controlled P. falciparum malaria initially while mefloquine was effective (cure rate with mefloquine [15 mg/kg] and sulphadoxine-pyrimethamine in 1985, 98% [95% CI 97-100]), but as mefloquine resistance developed, the cure rate fell (71% [67-77] in 1990). A similar pattern was seen for high-dose (25 mg/kg) mefloquine monotherapy from 1990-94. Since the general deployment of the artesunate-mefloquine combination in 1994, the cure rate increased again to almost 100% from 1998 onwards, and there has been a sustained decline in the incidence of P. falciparum malaria in the study area. In-vitro susceptibility of P. falciparum to mefloquine has improved significantly (p=0.003).
In this area of low malaria transmission, early diagnosis and treatment with combined artesunate and mefloquine has reduced the incidence of P. falciparum malaria and halted the progression of mefloquine resistance. We recommend that antimalarial drugs should be combined with artemisinin or a derivative to protect them against resistance.
恶性疟原虫疟疾耐药性的不断恶化对热带国家的健康构成了重大威胁。我们在一个恶性疟原虫高度多重耐药的疟疾流行地区对疟疾发病率和治疗情况进行了一项前瞻性研究。
我们在泰国西北边境的两个克伦族难民大型营地中评估了13年间恶性疟原虫疟疾的发病率以及对甲氟喹治疗的体内反应。在此期间，甲氟喹的标准剂量先是增加，随后青蒿琥酯-甲氟喹联合用药被引入作为非复杂性恶性疟原虫疟疾的一线治疗方案。
在甲氟喹有效时，早期检测和治疗最初控制住了恶性疟原虫疟疾（1985年甲氟喹[15毫克/千克]与磺胺多辛-乙胺嘧啶联合用药的治愈率为98%[95%可信区间97-100]），但随着甲氟喹耐药性的出现，治愈率下降（1990年为71%[67-77]）。1990 - 1994年期间高剂量（25毫克/千克）甲氟喹单药治疗也出现了类似情况。自1994年普遍采用青蒿琥酯-甲氟喹联合用药以来，治愈率从1998年起再次升至近100%，且研究地区恶性疟原虫疟疾的发病率持续下降。恶性疟原虫对甲氟喹的体外敏感性显著提高（p = 0.003）。
在这个疟疾传播率较低的地区，青蒿琥酯与甲氟喹联合进行早期诊断和治疗降低了恶性疟原虫疟疾的发病率，并阻止了甲氟喹耐药性的发展。我们建议抗疟药物应与青蒿素或其衍生物联合使用，以防止产生耐药性。
