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Abstract：
Histoplasma antigen detection in urine is a rapid diagnostic method for disseminated histoplasmosis, although cross-reactivity has been reported in specimens from patients with other thermally dimorphic fungal infections. We tested urine specimens, from persons with suspected invasive fungal infections, using a commercial monoclonal antibody Histoplasma enzyme immunoassay (EIA) at a South African national mycology reference laboratory from August 2014 through December 2018. Corresponding fungal culture and histopathology results were obtained from an electronic laboratory information system. In some cases, cultured fungal isolates were sent with the urine specimen for species-level identification by phenotypic and molecular methods. Cross-reactivity was confirmed using culture filtrates of several fungal pathogens. Of 212 referred cases, 41 (19%) were excluded since they had no recorded clinical history (n = 1), alternative diagnoses were confirmed (n = 2), or no fungal culture or histopathology results (n = 38). Eighty-seven of 212 (41%) had laboratory evidence of an invasive fungal disease, while 84 (40%) did not. Of the 87 cases, 37 (43%) were culture-confirmed mycoses: emergomycosis (n = 18), histoplasmosis (n = 8), sporotrichosis (n = 6), cryptococcosis (n = 2), talaromycosis (n = 1), and other fungi isolated (n = 2). The sensitivity and specificity of the EIA were calculated for two groups: culture-confirmed (n = 37) and histology-confirmed invasive fungal disease (n = 50). The sensitivity and specificity of the EIA for diagnosis of histoplasmosis compared to culture were 88% (7/8, 95%CI 47-100%) and 72% (21/29, 95%CI 53-87%), respectively, and for diagnosis of emergomycosis/histoplasmosis compared to histology was 83% (29/35, 95%CI 66-93%) and 93% (14/15, 95%CI 68-100%), respectively. Cross-reactions occurred in urine specimens of patients with Emergomyces africanus infection and in culture filtrates of E. africanus, T. marneffei and Blastomyces species. A commercial Histoplasma EIA had satisfactory accuracy for diagnosis of culture-confirmed histoplasmosis, but cross-reacted in urine specimens from patients with invasive disease caused by the closely-related pathogen, E. africanus and in culture filtrates of E. africanus and other related fungi.
UNASSIGNED: Emergomyces africanus and Histoplasma capsulatum are fungi that cause a multi-system disease among HIV-seropositive persons with a low CD4 cell count. Handling live cultures of these fungi to confirm a diagnosis requires specialized laboratory equipment and infrastructure which is infrequently accessible in low-resource settings. The features of the two diseases (i.e., disseminated histoplasmosis and emergomycosis) may be indistinguishable when infected tissue is prepared, stained, and examined under a microscope. Enzyme immunoassays (EIA) have been developed as rapid diagnostic tools for the detection of a cell wall component of H. capsulatum in urine specimens, although cross-reactions have been reported in specimens from patients with other fungal infections. We evaluated the accuracy of a commercial Histoplasma EIA to diagnose histoplasmosis and to assess cross-reactions in urine specimens from persons with emergomycosis and in cultures of E. africanus and related fungi. We report a sensitivity and specificity of 88% (95%CI 47-100%) and 72% (95%CI 53-87%) for diagnosis of histoplasmosis compared to culture and 83% (95%CI 66-93%) and 93% (95%CI 68-100%) for diagnosis of either histoplasmosis/emergomycosis compared to a diagnosis made by microscopic examination of infected tissue. The assay cross-reacted in urine specimens from patients with emergomycosis and in culture filtrates of related fungi. Although the EIA cross-reacted with other related fungi, this test can decrease the time to diagnosis and facilitate early treatment of emergomycosis and histoplasmosis in South Africa.
UNASSIGNED: Emergomyces africanus and Histoplasma capsulatum are fungi that cause a multi-system disease among HIV-seropositive persons with a low CD4 cell count. Handling live cultures of these fungi to confirm a diagnosis requires specialized laboratory equipment and infrastructure which is infrequently accessible in low-resource settings. The features of the two diseases (i.e., disseminated histoplasmosis and emergomycosis) may be indistinguishable when infected tissue is prepared, stained, and examined under a microscope. Enzyme immunoassays (EIA) have been developed as rapid diagnostic tools for the detection of a cell wall component of H. capsulatum in urine specimens, although cross-reactions have been reported in specimens from patients with other fungal infections. We evaluated the accuracy of a commercial Histoplasma EIA to diagnose histoplasmosis and to assess cross-reactions in urine specimens from persons with emergomycosis and in cultures of E. africanus and related fungi. We report a sensitivity and specificity of 88% (95%CI 47-100%) and 72% (95%CI 53-87%) for diagnosis of histoplasmosis compared to culture and 83% (95%CI 66-93%) and 93% (95%CI 68-100%) for diagnosis of either histoplasmosis/emergomycosis compared to a diagnosis made by microscopic examination of infected tissue. The assay cross-reacted in urine specimens from patients with emergomycosis and in culture filtrates of related fungi. Although the EIA cross-reacted with other related fungi, this test can decrease the time to diagnosis and facilitate early treatment of emergomycosis and histoplasmosis in South Africa.
摘要：
尿液中的组织胞浆抗原检测是播散性组织胞浆菌病的快速诊断方法，尽管在其他热双态真菌感染患者的标本中已经报道了交叉反应性。我们测试了尿液样本,怀疑有侵袭性真菌感染的人，2014年8月至2018年12月在南非国家真菌学参考实验室使用商业单克隆抗体组织血浆酶免疫测定法(EIA).从电子实验室信息系统获得相应的真菌培养和组织病理学结果。在某些情况下,培养的真菌分离株与尿液标本一起发送，以通过表型和分子方法进行物种水平鉴定。使用几种真菌病原体的培养滤液确认交叉反应性。在212个移交案件中，41（19％）被排除，因为他们没有记录的临床病史（n=1），替代诊断得到证实（n=2），或无真菌培养或组织病理学结果（n=38）。212人中有87人（41%）有侵袭性真菌病的实验室证据，而84（40％）没有。在87个案例中，37（43％）是培养证实的真菌病：初生菌病（n=18），组织胞浆菌病（n=8），孢子丝菌病（n=6），隐球菌病（n=2），真菌病（n=1），和其他真菌分离（n=2）。计算了两组的EIA的敏感性和特异性：培养证实（n=37）和组织学证实的侵袭性真菌病（n=50）。与培养物相比，EIA诊断组织胞浆菌病的敏感性和特异性分别为88％（7/8，95CI47-100％）和72％（21/29，95CI53-87％），分别,与组织学相比，诊断为急性真菌病/组织胞浆菌病的比例为83％（29/35，95CI66-93％）和93％（14/15，95CI68-100％），分别。发生交叉反应的患者的尿液标本与非洲产卵菌的培养滤液，马内菲T.和Blastomyces物种。商业组织胞浆EIA对培养证实的组织胞浆菌病的诊断具有令人满意的准确性，但是在由密切相关的病原体引起的侵袭性疾病患者的尿液标本中发生交叉反应，非洲E.Africanus和其他相关真菌的培养滤液。
■在CD4细胞计数低的HIV-血清反应阳性的人中，非洲胚和荚膜组织胞浆是引起多系统疾病的真菌。处理这些真菌的活培养物以确认诊断需要专门的实验室设备和基础设施，这在低资源环境中很少使用。这两种疾病的特征(即，播散性组织胞浆菌病和胚真菌病）在制备受感染的组织时可能无法区分，染色,并在显微镜下检查。酶免疫测定（EIA）已被开发为快速诊断工具，用于检测尿液标本中荚膜H.尽管在其他真菌感染患者的标本中已经报道了交叉反应。我们评估了商业组织胞浆菌EIA诊断组织胞浆菌病的准确性，并评估了来自胚乳菌病患者的尿液标本以及非洲E.Africanus和相关真菌培养物中的交叉反应。我们报告了与培养物相比，组织胞浆菌病诊断的敏感性和特异性分别为88％（95CI47-100％）和72％（95CI53-87％），而与通过显微镜检查感染组织的诊断相比，用于诊断组织胞浆病/母菌病的敏感性和特异性分别为83％（95CI66-93％）和93％（95CI68-100％）。该测定法在来自白菌病患者的尿液标本和相关真菌的培养滤液中发生交叉反应。尽管EIA与其他相关真菌发生交叉反应，该试验可缩短诊断时间,并有助于南非的胚芽菌病和组织胞浆菌病的早期治疗.
■在CD4细胞计数低的HIV-血清反应阳性的人中，非洲胚和荚膜组织胞浆是引起多系统疾病的真菌。处理这些真菌的活培养物以确认诊断需要专门的实验室设备和基础设施，这在低资源环境中很少使用。这两种疾病的特征(即，播散性组织胞浆菌病和胚真菌病）在制备受感染的组织时可能无法区分，染色,并在显微镜下检查。酶免疫测定（EIA）已被开发为快速诊断工具，用于检测尿液标本中荚膜H.尽管在其他真菌感染患者的标本中已经报道了交叉反应。我们评估了商业组织胞浆菌EIA诊断组织胞浆菌病的准确性，并评估了来自胚乳菌病患者的尿液标本以及非洲E.Africanus和相关真菌培养物中的交叉反应。我们报告了与培养物相比，组织胞浆菌病诊断的敏感性和特异性分别为88％（95CI47-100％）和72％（95CI53-87％），而与通过显微镜检查感染组织的诊断相比，用于诊断组织胞浆病/母菌病的敏感性和特异性分别为83％（95CI66-93％）和93％（95CI68-100％）。该测定法在来自白菌病患者的尿液标本和相关真菌的培养滤液中发生交叉反应。尽管EIA与其他相关真菌发生交叉反应，该试验可缩短诊断时间,并有助于南非的胚芽菌病和组织胞浆菌病的早期治疗.
