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恰加斯病的实验与临床治疗综述

Experimental and Clinical Treatment of Chagas Disease: A Review.

作者信息

Sales Junior Policarpo Ademar, Molina Israel, Fonseca Murta Silvane Maria, Sánchez-Montalvá Adrián, Salvador Fernando, Corrêa-Oliveira Rodrigo, Carneiro Cláudia Martins

机构信息

Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.

Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.

出版信息

Am J Trop Med Hyg. 2017 Nov;97(5):1289-1303. doi: 10.4269/ajtmh.16-0761. Epub 2017 Oct 10.

Abstract

Chagas disease (CD) is caused by the protozoan parasite that infects a broad range of triatomines and mammalian species, including man. It afflicts 8 million people in Latin America, and its incidence is increasing in nonendemic countries owing to rising international immigration and nonvectorial transmission routes such as blood donation. Since the 1960s, the only drugs available for the clinical treatment of this infection have been benznidazole (BZ) and nifurtimox (NFX). Treatment with these trypanocidal drugs is recommended in both the acute and chronic phases of CD. These drugs have low cure rates mainly during the chronic phase, in addition both drugs present side effects that may result in the interruption of the treatment. Thus, more efficient and better-tolerated new drugs or pharmaceutical formulations containing BZ or NFX are urgently needed. Here, we review the drugs currently used for CD chemotherapy, ongoing clinical assays, and most-promising new experimental drugs. In addition, the mechanism of action of the commercially available drugs, NFX and BZ, the biodistribution of the latter, and the potential for novel formulations of BZ based on nanotechnology are discussed. Taken together, the literature emphasizes the urgent need for new therapies for acute and chronic CD.

摘要

恰加斯病(CD)由原生动物寄生虫引起,该寄生虫可感染包括人类在内的多种锥蝽和哺乳动物。它在拉丁美洲折磨着800万人,并且由于国际移民增加以及诸如献血等非媒介传播途径,其在非流行国家的发病率正在上升。自20世纪60年代以来,临床治疗这种感染的唯一可用药物一直是苯硝唑(BZ)和硝呋替莫(NFX)。在恰加斯病的急性期和慢性期都推荐使用这些杀锥虫药物进行治疗。这些药物的治愈率较低,主要是在慢性期,此外这两种药物都有副作用,可能导致治疗中断。因此,迫切需要更有效且耐受性更好的新药或含有BZ或NFX的药物制剂。在这里,我们综述了目前用于恰加斯病化疗的药物、正在进行的临床试验以及最有前景的新实验药物。此外,还讨论了市售药物NFX和BZ的作用机制、后者的生物分布以及基于纳米技术的BZ新制剂的潜力。综上所述,文献强调了迫切需要针对急性和慢性恰加斯病的新疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a736/5817734/14a988bdca2d/tpmd160761f1.jpg

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