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当前对治疗人类非洲锥虫病的化疗策略的分析。

A current analysis of chemotherapy strategies for the treatment of human African trypanosomiasis.

机构信息

University of Massachusetts, Boston, MA, USA.

出版信息

Pathog Glob Health. 2013 Jul;107(5):242-52. doi: 10.1179/2047773213Y.0000000105.

Abstract

Despite the recent advances in drug research, finding a safe, effective, and easy to use chemotherapy for human African trypanosomiasis (HAT) remains a challenging task. The four current anti-trypanosomiasis drugs have major disadvantages that limit more widespread use of these drugs in the endemic regions of sub-Saharan Africa. Pentamidine and suramin are limited by their effectiveness against the only first stage of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, respectively. In addition, melarsoprol and eflornithine (two second stage drugs) each have disadvantages of their own. The former is toxic and has increasing treatment failures while the latter is expensive, laborious to administer, and lacks efficacy against T. b. rhodesiense. Furthermore, melarsoprol's toxicity and decreasing efficacy are glaring problems and phasing out the drug as a frontline treatment against T. b. gambiense is now possible with the emergence of competent, safe combination chemotherapies such as nifurtimox-eflornithine combination treatment (NECT). The future of eflornithine, on the other hand, is more promising. The drug is useful in the context of combination chemotherapy and potential orally administered analogues. Due to the limits of monotherapies, greater emphasis should be placed on the research and development of combination chemotherapies, based on the successful clinical tests with NECT and its current use as a frontline anti-trypanosomiasis treatment. This review discussed the current and future chemotherapy strategies for the treatment of HAT.

摘要

尽管近年来在药物研究方面取得了进展,但寻找一种安全、有效且易于使用的化疗药物来治疗人类非洲锥虫病(HAT)仍然是一项具有挑战性的任务。目前有四种抗锥虫病药物,但都存在严重的缺点,限制了这些药物在撒哈拉以南非洲流行地区的更广泛使用。戊烷脒和苏拉明分别对布氏冈比亚锥虫和布氏罗得西亚锥虫的第一阶段有效,但效果有限。此外,美拉胂醇和依氟鸟氨酸(两种第二阶段药物)也各有其缺点。前者有毒,且治疗失败率不断上升,而后者昂贵、给药繁琐,且对布氏罗得西亚锥虫无效。此外,美拉胂醇的毒性和疗效下降是突出的问题,随着能够有效治疗布氏冈比亚锥虫的安全联合化疗药物(NECT)的出现,该药已逐渐被淘汰,不再作为布氏冈比亚锥虫的一线治疗药物。另一方面,依氟鸟氨酸的前景更加光明。该药在联合化疗和潜在的口服类似物方面具有应用价值。鉴于单药治疗的局限性,应更加重视联合化疗的研究和开发,基于 NECT 的成功临床测试及其作为一线抗锥虫病治疗方法的当前应用。本文综述了目前和未来治疗 HAT 的化疗策略。

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