The continuing problem of human African trypanosomiasis (Sleeping sickness)
The continuing problem of human African trypanosomiasis (Sleeping sickness)
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DOI：
10.1002/ana.21429
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发表时间：
2008-08-01
影响因子：
11.2
通讯作者：
Kennedy, Peter G. E.
中科院分区：
文献类型：
--
作者：
Kennedy, Peter G. E.
非洲锥虫病又称昏睡病，是一种被忽视的疾病，它继续对撒哈拉以南非洲36个国家的6 000万人构成重大威胁。该疾病由采采蝇叮咬传播，由锥虫属的原生动物寄生虫引起，并分为两种类型：由布氏锥虫罗得西亚引起的东非人类非洲锥虫和由布氏锥虫冈比亚引起的西非形式。有一个早期或血淋巴阶段和一个晚期或脑炎阶段，当寄生虫穿过血脑屏障侵入中枢神经系统时。目前的两个关键问题是疾病分期和药物治疗，特别是对于晚期疾病。腰椎穿刺分析脑脊液仍将是疾病分期的唯一方法，直到可靠的非侵入性方法被开发出来，但对于中枢神经系统疾病的确切生物学定义或哪些特定的脑脊液检查结果应证明晚期受累的药物治疗是合理的，还没有广泛的共识。用于治疗非洲锥虫病的四种主要药物都是有毒的，而美拉胂醇是唯一一种对两种中枢神经系统疾病都有效的药物，毒性很大，以至于5%的患者死亡。依氟鸟氨酸单独使用或与硝呋替莫合用，正越来越多地被用作冈比亚病的一线治疗。目前迫切需要所有有效、安全的口服药物来治疗这两个阶段的疾病，但这将需要西方政府和制药行业大幅增加对新药研发的投资。
Human African trypanosomiasis, also known as sleeping sickness, is a neglected disease, and it continues to pose a major threat to 60 million people in 36 countries in sub-Saharan Africa. Transmitted by the bite of the tsetse fly, the disease is caused by protozoan parasites of the genus Trypanosoma and comes in two types: East African human African trypanosomiasis caused by Trypanosoma brucei rhodesiense and the West African form caused by Trypanosoma brucei gambiense. There is an early or hemolymphatic stage and a late or encephalitic stage, when the parasites cross the blood-brain barrier to invade the central nervous system. Two critical current issues are disease staging and drug therapy, especially for late-stage disease. Lumbar Puncture to analyze cerebrospinal fluid will remain the only method of disease staging until reliable noninvasive methods are developed, but there is no widespread consensus as to what exactly defines biologically central nervous system disease or what specific cerebrospinal fluid Findings Should justify drug therapy for late-stage involvement. All four main drugs used for human African trypanosomiasis are toxic, and melarsoprol, the only drug that is effective for both types of central nervous system disease, is so toxic that it kills 5% of patients who receive it. Eflornithine, alone or combined with nifurtimox, is being used increasingly as first-line therapy for gambiense disease. There is a pressing need for all effective, safe oral drug for both stages of the disease, but this will require a significant increase in investment for new drug discovery from Western governments and the pharmaceutical industry.