Revival of Leishmanization and Leishmanin.

Revival of Leishmanization and Leishmanin.
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DOI:
10.3389/fcimb.2021.639801
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发表时间:
2021
影响因子:
5.7
通讯作者:
Nakhasi HL
Nakhasi HL
中科院分区:
医学2区
文献类型:
--
作者:
Pacheco-Fernandez T;Volpedo G;Gannavaram S;Bhattacharya P;Dey R;Satoskar A;Matlashewski G;Nakhasi HL

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利什曼病包括一系列疾病,从使人虚弱的皮肤感染到致命的内脏感染。这种疾病是由利什曼原虫属的寄生原虫引起的,利什曼原虫由受感染的沙蝇传播。在近100个国家的热带和亚热带地区,有10多亿人面临利什曼病的风险,每年的发病率超过200万例。利什曼病是唯一一种通过一种被称为利什曼化的程序接种成功的人类寄生虫病,这种程序在中东地区已经广泛使用了几十年。利什曼病包括皮内接种活的利什曼原虫主要寄生虫,导致皮肤损伤,自然愈合后提供对再次感染的保护性免疫力。然而,由于安全和伦理方面的考虑,利什曼化不再进行,因为接种部位的损害可能会在一些人身上持续几个月。涉及CRISPR的新基因组编辑技术现在已经有可能设计出更安全的减毒利什曼原虫菌株,这种菌株可以诱导保护性免疫,为进入人体试验的第二代利什曼病毒让路。一个主要的考虑因素将是如何在内脏利什曼病消除计划中测试疫苗的有效性。一种解决方案是使用利什曼宁皮试(LST),这种测试也使用了几十年来确定利什曼原虫的暴露和免疫力。LST包括将利什曼原虫的抗原注射到皮肤真皮,导致与Th1免疫反应相关的迟发性超敏反应(DTH)免疫反应,并防止内脏利什曼病。重新引入利什曼病的新方法和利什曼宁皮肤试验可以在消除利什曼病方面发挥重要作用。
Leishmaniasis includes a spectrum of diseases ranging from debilitating cutaneous to fatal visceral infections. This disease is caused by the parasitic protozoa of the genus Leishmania that is transmitted by infected sandflies. Over 1 billion people are at risk of leishmaniasis with an annual incidence of over 2 million cases throughout tropical and subtropical regions in close to 100 countries. Leishmaniasis is the only human parasitic disease where vaccination has been successful through a procedure known as leishmanization that has been widely used for decades in the Middle East. Leishmanization involved intradermal inoculation of live Leishmania major parasites resulting in a skin lesion that following natural healing provided protective immunity to re-infection. Leishmanization is however no longer practiced due to safety and ethical concerns that the lesions at the site of inoculation that can last for months in some people. New genome editing technologies involving CRISPR has now made it possible to engineer safer attenuated strains of Leishmania, which induce protective immunity making way for a second generation leishmanization that can enter into human trials. A major consideration will be how the test the efficacy of a vaccine in the midst of the visceral leishmaniasis elimination program. One solution will be to use the leishmanin skin test (LST) that was also used for decades to determine exposure and immunity to Leishmania. The LST involves injection of antigen from Leishmania in the skin dermis resulting in a delayed type hypersensitivity (DTH) immune reaction associated with a Th1 immune response and protection against visceral leishmaniasis. Reintroduction of novel approaches for leishmanization and the leishmanin skin test can play a major role in eliminating leishmaniasis.
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