Effectiveness and Safety of a Treatment Regimen Based on Isoniazid Plus Vaccination with Mycobacterium tuberculosis cells' Fragments: Field-Study with Naturally Mycobacterium caprae-Infected Goats
Effectiveness and Safety of a Treatment Regimen Based on Isoniazid Plus Vaccination with Mycobacterium tuberculosis cells' Fragments: Field-Study with Naturally Mycobacterium caprae-Infected Goats
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DOI：
10.1111/j.1365-3083.2009.02251.x
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发表时间：
2009-06-01
影响因子：
3.7
通讯作者：
Cardona, P. -J.
中科院分区：
文献类型：
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作者：
Domingo, M.;Gil, O.;Cardona, P. -J.
一群患有结核病的山羊的鉴定使我们能够测试针对潜伏性结核感染（LTBI）的新治疗方案。使用大型动物实验模型可以更好地了解人类结核病的免疫病理参数。基于显示ESAT-6特异性干扰素（IFN）-γ分泌与肺部病变严重程度之间相关性的初步研究，该参数与X射线检查联合使用，以筛选纳入疗效和安全性研究的动物。所有动物均被证明感染了山羊分枝杆菌。在根据治疗分为三个实验组的动物中进行功效研究：未治疗（CT）、用异烟肼（INH）治疗和用INH +鲁蒂（一种基于M.结核病细胞碎片）接种两次。在体外用ESAT-6、纯化蛋白衍生物和鲁蒂刺激外周血后，鲁蒂暂时增加IFN-γ的产生。INH化疗减少了肺和肺外病变，但没有减少肺淋巴结病变。加用鲁蒂可能进一步减少肺外疾病，但对肺或肺淋巴结本身没有益处。安全性研究表明，接种鲁蒂引起直肠温度暂时升高（1-2摄氏度）和局部肿胀，这两种不良反应均耐受良好。接种疫苗未诱导全身毒性或死亡。由INH化疗+鲁蒂组成的治疗方案对山羊感染的控制及其安全性，代表了在未来测试其在人类LTBI中的作用的进一步步骤。
The identification of a herd of goats with tuberculosis let us test a new treatment regimen against latent tuberculosis infection (LTBI). Using large animal experimental models allows a better approach to understanding human tuberculosis according to immunopathological parameters. Based on an initial study showing a correlation between the ESAT-6-specific interferon (IFN)-gamma secretion and the severity of pulmonary lesions, this parameter was used in combination with an X-ray examination to screen the animals to be included in the efficacy and safety studies. All the animals proved to be infected with Mycobacterium caprae. The efficacy study was run in animals distributed in three experimental groups according to treatment: untreated (CT), treated with isoniazid (INH), and treated with INH + RUTI (a vaccine based on M. tuberculosis cell fragments) inoculated twice. RUTI temporarily increased the IFN-gamma production after stimulating the peripheral blood with ESAT-6, purified protein derivative and RUTI in vitro. The INH chemotherapy reduced both pulmonary and extra pulmonary affectation, but not disease in pulmonary lymph nodes. The addition of RUTI may have decreased extrapulmonar disease further but had no benefit to lung or lung lymph-nodes itself. Safety studies showed that inoculation of RUTI caused a temporary increase of rectal temperature (1-2 degrees C) and local swelling, both adverse effects being well tolerated. Neither systemic toxicity nor mortality was induced by the vaccination. The control of goats' infection by the therapeutic regimen consisting in INH chemotherapy + RUTI as well as its safety, represented a further step towards testing its effects in human LTBI in a future.