Abstract

Histoplasmosis is a worldwide-distributed systemic mycosis caused by the dimorphic fungus Histoplasma capsulatum. Its clinical manifestations range from subclinical or mild respiratory illness to progressive disseminated histoplasmosis (PDH), a life-threatening disease, whose accurate diagnosis is still challenging and limited in many countries, where this disease is highly endemic. In this regard, Histoplasma antigen testing is now included in the WHO Essential Diagnostics List. The final diagnosis of histoplasmosis is established by culture and/or visualization of the yeast cells by cytology or histopathology using specific stains. However, both procedures have limited sensitivity to detect the disease and cultures are time-consuming. Antibody detection assays are effective for the subacute and chronic clinical forms of histoplasmosis. However, their sensitivity is low in the immunocompromised host. Several molecular “in-house” tests were also developed and showed promising results, but none of these tests are commercially available and their standardization and validation are still pending. Antigen detection assays have high sensitivity in PDH cases and are of great value for the follow-up of patients with histoplasmosis; however, cross-reactivity with other related fungi are common. In addition, this assay is expensive and only performed in few laboratories. Novel protein antigen candidates have been recently identified and produced by DNA-recombinant techniques in order to obtain standardized and specific reagents for the diagnosis of histoplasmosis, as opposed to the unspecific antigens or crude extracts currently used. This review describes the currently available assays, highlighting their strengths and limitations and reports the latest approaches to achieve reliable and rapid diagnostic tests for histoplasmosis.

Key points

• PDH causes thousands of deaths per year globally.

• Rapid accurate diagnosis of PDH is unfeasible in many regions.

• Fast, accurate, and low-cost diagnostic alternatives are currently under development.

中文翻译：

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组织胞浆菌病的诊断：现状和观点

摘要

组织胞浆菌病是一种由二形性真菌荚膜组织胞浆菌引起的全身性真菌病。它的临床表现从亚临床或轻度呼吸道疾病到进行性弥漫性组织胞浆菌病（PDH），这是一种威胁生命的疾病，在许多该病是高度流行的国家，其准确诊断仍然具有挑战性且受到限制。在这方面，组织胞浆抗原检测现已包括在WHO基本诊断清单中。组织胞浆菌病的最终诊断是通过使用特定染色剂通过细胞学或组织病理学对酵母细胞进行培养和/或可视化来建立的。但是，这两种方法检测疾病的敏感性均有限，培养费时。抗体检测测定法对亚急性和慢性组织胞浆菌病有效。但是，它们在免疫受损宿主中的敏感性较低。还开发了几种分子“内部”测试，并显示出令人鼓舞的结果，但是这些测试都没有市售，其标准化和验证仍在进行中。抗原检测法在PDH病例中具有很高的敏感性，对组织胞浆菌病患者的随访具有重要价值。然而，与其他相关真菌的交叉反应很常见。另外，该测定是昂贵的，并且仅在很少的实验室中进行。与目前使用的非特异性抗原或粗提物相反，最近已经通过DNA重组技术鉴定并生产了新型蛋白质抗原候选物，以便获得用于诊断组织胞浆菌病的标准化和特异性试剂。这篇综述描述了当前可用的测定法，着重介绍了它们的优势和局限性，并报告了实现针对组织胞浆病的可靠，快速诊断测试的最新方法。与目前使用的非特异性抗原或粗提物相反，最近已经通过DNA重组技术鉴定并生产了新型蛋白质抗原候选物，以便获得用于诊断组织胞浆菌病的标准化和特异性试剂。这篇综述描述了当前可用的检测方法，着重介绍了它们的优势和局限性，并报告了实现可靠而快速的组织胞浆病诊断检测的最新方法。与目前使用的非特异性抗原或粗提物相反，最近已经通过DNA重组技术鉴定并生产了新型蛋白质抗原候选物，以便获得用于诊断组织胞浆菌病的标准化和特异性试剂。这篇综述描述了当前可用的测定法，着重介绍了它们的优势和局限性，并报告了实现针对组织胞浆病的可靠，快速诊断测试的最新方法。

关键点

•PDH在全球每年导致数千人死亡。

•在许多地区，无法快速准确地诊断PDH。

•目前正在开发快速，准确和低成本的诊断替代方案。