The phenomenon of treatment failures in Human African Trypanosomiasis
The phenomenon of treatment failures in Human African Trypanosomiasis
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DOI：
10.1046/j.1365-3156.2001.00775.x
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发表时间：
2001-11-01
影响因子：
3.3
通讯作者：
Burri, C
中科院分区：
文献类型：
--
作者：
Brun, R;Schumacher, R;Burri, C
非洲人类锥虫病（HAT 或昏睡病）的治疗依赖于一些陈旧、有毒且昂贵的药物。治疗第二阶段感染最重要的药物是美拉丙醇。在过去 50 年中，melarsoprol 治疗失败并不是布氏冈比亚锥虫患者的主要问题。据报道，结核病的复发率通常为 5-8%，但近年来，在一些重要的结核病灶中，复发率急剧上升。冈比亚昏睡病。 T.b. 的治疗失败。除了 1960 年至 1985 年间关于 T.b. 难治性的一些报道外，罗德西亚的问题要小得多。东非的罗得西亚患者。对这些分离株的分析表明，它们对美拉丙醇的体外敏感性是敏感分离株的十分之一，并且在急性小鼠模型中，美拉丙醇水平与人类患者的水平相当，完全无法治愈感染。 T.b 中几乎没有抵抗力的迹象。冈比亚分离自科特迪瓦和乌干达西北部。复发患者和可治愈患者的体外美拉丙醇敏感性处于相同范围。治疗后24小时患者血浆和脑脊液中Melarsoprol浓度在复发患者和可治愈患者之间没有显示出任何差异。最近结核病复发的原因。冈比亚的流行病尚不清楚。可能涉及其他与寄生虫相关的因素，例如对中枢神经系统以外的血管外部位的亲和力，这些部位药物不易接近。总之，多种因素的结合而不是单一因素可能导致 T.b. 中 melarsoprol 治疗失败的现象。冈比亚患者。
Treatment of Human African Trypanosomiasis (HAT or sleeping sickness) relies on a few drugs which are old, toxic and expensive. The most important drug for the treatment of second stage infection is melarsoprol. During the last 50 years treatment failures with melarsoprol were not a major problem in Trypanosoma brucei gambiense patients. Commonly a relapse rate of 5-8% was reported, but in recent years it has increased dramatically in some important foci of T.b. gambiense sleeping sickness. Treatment failures for T.b. rhodesiense are much less of a problem apart from some reports between 1960 and 1985 of refractoriness in T.b. rhodesiense patients in East Africa. Analysis of those isolates revealed that their in vitro sensitivity to melarsoprol was one-tenth that of sensitive isolates, and complete failure to cure the infection in the acute mouse model with melarsoprol levels comparable with those in human patients. There was very little indication of resistance in T.b. gambiense isolates from Cote d'lvoire and NW Uganda. The in vitro melarsoprol sensitivities for populations from relapsing and from curable patients were in the same range. Melarsoprol concentrations in the plasma and cerebrospinal fluid of patients 24 h after treatment did not show any difference between patients who relapsed and those who could be cured. The reason for relapses in the recent T.b. gambiense epidemics are not known. Other parasite-related factors might be involved, e.g. affinity to extravascular sites other than the CNS which are less accessible to the drug. In conclusion, a combination of factors rather than a single one may be responsible for the phenomenon of melarsoprol treatment failures in T.b. gambiense patients.