Systematic Review of Prevalence of Histoplasma Antigenuria in Persons with HIV in Latin America and Africa.

Histoplasmosis is a fungal disease associated with substantial mortality rates among persons with advanced HIV disease. Our systematic review synthesized data on the global prevalence of Histoplasma--caused antigenuria in persons with HIV. We searched PubMed/Medline, Embase, and Scopus databases on January 3, 2023, to identify cross-sectional and cohort studies evaluating Histoplasma antigenuria prevalence among adults with HIV infection. We calculated point estimates and 95% CIs to summarize prevalence. Of 1,294 studies screened, we included 15. We found Histoplasma antigenuria among 581/5,096 (11%; 95% CI 11%-12%) persons with HIV and 483/3,789 persons with advanced HIV disease (13%; 95% CI 12%-14%). Among persons with HIV and symptoms consistent with histoplasmosis, Histoplasma antigenuria prevalence was 14% (95% CI 13%-15%; 502/3,631 participants). We determined that persons with advanced HIV disease, inpatients, and symptomatic persons might benefit from a systematic approach to early detection of histoplasmosis using urine antigen testing.

Diagnostic accuracy of a novel lateral flow assay for histoplasmosis.

Antigen testing is an important diagnostic tool for histoplasmosis but has limited availability globally. We evaluated the OIDx urine lateral flow antigen assay among 204 persons suspected to have histoplasmosis. Among patients with proven histoplasmosis, sensitivity was 33.3% (3/9, 95% CI 7.5%-70.1%) and specificity 80.5% (157/195, 95% CI 74.3%-85.8%). The MiraVista urine antigen test had better specificity (96.9%) and equal sensitivity. The OIDx test demonstrated 33.3% (3/9) positive agreement and 84.0% (163/194) negative agreement with the MiraVista test. These results should be considered in the context of our low HIV prevalence population with a mixture of pulmonary and disseminated disease.

We evaluated a new lateral flow antigen test for the diagnosis of histoplasmosis. Proven/probable cases were mostly pulmonary disease making antigen tests likely to be less sensitive in this population. The test had similar sensitivity to the established antigen test but was less specific.

Cross-reactivity of a Histoplasma capsulatum antigen enzyme immunoassay in urine specimens from persons with emergomycosis in South Africa.

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. LAY SUMMARY: 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.

Histoplasma capsulatum 100-kilodalton antigen: recombinant production, characterization, and evaluation of its possible application in the diagnosis of histoplasmosis.

The goal of the present work was to develop a novel reagent with potential for histoplasmosis diagnosis. For this purpose, the genetic sequence of the 100 kDa protein of Histoplasma capsulatum (Hcp100) was cloned and expressed as a secretory protein in Pichia pastoris. After optimizing the culture conditions and purifying by immobilized metal ion affinity chromatography, the highest yield of Hcp100 reached approximately 1.3 mg/l with > 90% purity in shake flasks using basal salt medium supplemented with casamino acids after 72 h of methanol induction. To investigate its potential for diagnosis, its detection in urine samples using specific polyclonal antibodies as reagent was evaluated by dot blot in 6 patients with progressive disseminated histoplasmosis (PDH), of whom all had AIDS. Antigen was detected in urine from all 6 (100%) PDH patients. Urine samples from a pool of 20 healthy individuals did not react with the anti-Hcp100 antibodies. The dot blot assay performed in this study provides preliminary data of a simple technology that can be performed in medical institutions with limited resources to facilitate the rapid diagnosis of histoplasmosis, particularly the disseminated forms. Hence, use of these assays may provide a rapid diagnostic tool of PDH in endemic areas for histoplasmosis where PDH-related mortality is high, hastening treatment and improving patient survival. Finally, this novel antigen and its specific antibodies may provide an alternative diagnostic reagent to the largely unknown and poorly characterized polysaccharide antigens (HPA, galactomannan, histoplasmin) frequently used in the diagnostic tests. KEY POINTS: Few antigens are used as laboratory tools for the immunodiagnosis of histoplasmosis. P. pastoris was an excellent system for recombinant Hcp100 expression. Maximum expression levels of rHcp100 were achieved in BSM with 1% casamino acids. Dot blot assays with anti-rHcp100 antisera can be successfully used for diagnosing PHD.

Multicenter Validation of Commercial Antigenuria Reagents To Diagnose Progressive Disseminated Histoplasmosis in People Living with HIV/AIDS in Two Latin American Countries.

Histoplasmosis is an important cause of mortality in patients with AIDS, especially in countries with limited access to antiretroviral therapies and diagnostic tests. However, many disseminated infections in Latin America go undiagnosed. A simple, rapid method to detect Histoplasma capsulatum infection in regions where histoplasmosis is endemic would dramatically decrease the time to diagnosis and treatment, reducing morbidity and mortality. The aim of this study was to validate a commercial monoclonal Histoplasma galactomannan (HGM) enzyme-linked immunosorbent assay (Immuno-Mycologics [IMMY], Norman, OK, USA) in two cohorts of people living with HIV/AIDS (PLHIV). We analyzed urine samples from 589 people (466 from Guatemala and 123 from Colombia), including 546 from PLHIV and 43 from non-PLHIV controls. Sixty-three of these people (35 from Guatemala and 28 from Colombia) had confirmed histoplasmosis by isolation of H. capsulatum Using the standard curve provided by the quantitative commercial test, the sensitivity was 98% (95% confidence interval [CI], 95 to 100%) and the specificity was 97% (95% CI, 96 to 99%) (cutoff = 0.5 ng/ml). Semiquantitative results, using a calibrator of 12.5 ng/ml of Histoplasma galactomannan to calculate an enzyme immunoassay index value (EIV) for the samples, showed a sensitivity of 95% (95% CI, 89 to 100%) and a specificity of 98% (95% CI, 96 to 99%) (cutoff ≥ 2.6 EIV). This relatively simple-to-perform commercial antigenuria test showed a high performance with reproducible results in both countries, suggesting that it can be used to detect progressive disseminated histoplasmosis in PLHIV in a wide range of clinical laboratories in countries where histoplasmosis is endemic.

Histoplasma capsulatum urinary antigen detection in a kidney transplant recipient with acute paracoccidioidomycosis: Case study and literature review.

BACKGROUND: Paracoccidioidomycosis (PCM) and histoplasmosis are endemic fungal diseases in South America. Both can lead to lung involvement with fungal dissemination progressing to systemic and severe clinical manifestations, especially in immunosuppressed hosts. As the population of immunosuppressed individuals has been rising, a higher occurrence of fungal infections is predicted in this setting. This poses challenges regarding the differential diagnosis due to overlapping clinical and laboratorial findings, hampering the management of cases. OBJECTIVES: In this study, the authors discuss the occurrence of a false-positive Histoplasma urinary antigen detection in a kidney transplant recipient with acute PCM. Given the scarce information about this subject, a review on literature data is provided. METHODS: A comprehensive literature search was conducted to investigate previous studies that found cross-reactivity between Histoplasma urinary antigen assays in human patients with confirmed diagnosis of PCM. Additionally, an update of PCM in transplant recipients is provided. FINDINGS: The included studies reported 120 samples from patients with PCM tested for Histoplasma antigen, presenting an overall cross-reactivity of 51.67% and 17 cases of PCM in transplant recipients. CONCLUSIONS: The galactomannan urinary antigen developed to diagnose histoplasmosis can cross react with PCM, which may represent a concern in countries where both mycoses overlap.

Evaluation of the Histoplasma capsulatum 100-kilodalton antigen dot blot for the rapid diagnosis of progressive histoplasmosis in HIV/AIDS patients.

Among people living with HIV (PLHIV), progressive disseminated histoplasmosis (PDH) represents an important cause of mortality. Since antigen detection allows a rapid diagnosis and the instauration of a specific treatment this study aimed to evaluate the analytical performance of the Hcp100 dot blot, an in-house assay that detects the Histoplasma capsulatum 100-kilodalton antigen in urine and compare it with 2 commercially available assays the Histoplasma Urine Antigen Lateral Flow Assay (MVD-LFA) (MiraVista® Diagnostics) and the Clarus Histoplasma Galactomannan EIA (Clarus HGM) (IMMY). Urine specimens from 23 PLHIV with PDH, 13 patients with other infectious diseases, and 20 healthy individuals were tested. The Hcp100 dot blot showed higher sensitivity (87.0%), specificity (97.0%) and accuracy (92.9%) than the MVD-LFA (73.9%, 78.8%, and 76.8%, respectively) and the Clarus HGM (78.3%, 90.9%, and 85.7%, respectively). The Hcp100 dot blot had high analytical performance and would be a valuable screening tool for diagnosing PDH among PLHIV.

Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico.

BACKGROUND: The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283220SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. METHODOLOGY/PRINCIPAL FINDINGS: We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78-30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4-76.2) / 96.2% (95% CI, 93.2-98.0) for IAHE, 91.3% (95% CI, 84.2-96.0) / 90.9% (95% CI, 87.0-94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0-95.3) / 92.3% (95% CI, 88.6-95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3-72.5)/ 89.5% (95%CI, 86.0-93.0), 65.9% (95%CI, 56.0-75.8)/ 89.0% (95%CI, 85.2-92.9), 62.1% (95%CI, 44.4-79.7)/ 82.6% (95%CI, 71.7-93.6) and 34.9% (95%CI, 24.8-46.2)/ 67.3% (95%CI, 60.6-73.5) respectively; and 1281-1283220SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9-74.7)/ 58.8% (95%CI, 53.2-64.5), 70.8% (95%CI, 61.3-80.2)/ 52.9% (95%CI, 46.8-59.1), 71.4% (95%CI, 54.7-88.2)/ 40.4% (95%CI, 26.4-54.5) and 18.1% (95%CI, 10.5-28.1)/ 90.4% (95%CI, 85.5-94.0), respectively. CONCLUSIONS/SIGNIFICANCE: The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.

Histoplasma capsulatum recovery from the urine and a short review of genitourinary histoplasmosis.

Although virtually any organ can be involved in disseminated histoplasmosis, the recovery of Histoplasma capsulatum from the urine is a rare finding. Here we describe that a renal transplant recipient had H. capsulatum recovered from urinary sediment. The organism was also recovered from urine cultures. The potential implications of this finding are discussed, and the literature on genitourinary histoplasmosis is reviewed.

A monoclonal antibody-based urine Histoplasma antigen enzyme immunoassay (IMMY®) for the diagnosis of histoplasmosis in cats.

BACKGROUND: An in-house Histoplasma urine antigen test for cats might be desirable in certain situations. OBJECTIVE: To validate and compare the diagnostic performance of a monoclonal antibody-based IMMY urine Histoplasma antigen enzyme immunoassay (IMMY EIA) to the commercially available urine Histoplasma antigen enzyme immunoassay (MiraVista Diagnostics, MV EIA). ANIMALS: One hundred ninety-three urine samples from 105 client-owned and purpose-bred research cats. METHODS: Cats were classified as Histoplasma positive or negative based on diagnostic investigation. The IMMY EIA and MV EIA were performed on all urine samples. Correlation and agreement between the assays were determined. Diagnostic performance was determined and compared between assays. RESULTS: The IMMY EIA, with a 0.25 ng/mL diagnostic cutoff, provided a diagnostic sensitivity (DSe), diagnostic specificity (DSp), and diagnostic accuracy (DAc) of 89% (95% confidence interval [CI]; 73%-97%), 80% (67%-89%), and 83% (74%-90%), respectively. The IMMY EIA, with a 1.1 ng/mL diagnostic cutoff, provided a DSe, DSp, and DAc of 77% (95% CI 60%-90%), 97% (88%-100%), and 89% (81%-95%), respectively. The MV EIA provided a DSe, DSp, and DAc of 94% (95% CI 81%-99%), 97% (89%-100%), and 96% (90%-99%), respectively. Moderate overall agreement was found between MV EIA and IMMY EIA using the 0.25 ng/mL cut-off (к = 0.44; 95% CI 0.31-0.57) and the 1.1 ng/mL cut-off (к = 0.43, 95% CI, 0.31-0.56). CONCLUSIONS AND CLINICAL IMPORTANCE: The IMMY EIA might be useful as a diagnostic test for histoplasmosis in cats. Further modifications of the IMMY EIA are required to achieve the diagnostic performance of the MV EIA.

Comparison of Urine Antigen Assays for the Diagnosis of Histoplasma capsulatum Infection.

BACKGROUND: Urine antigen testing is a rapid sensitive method for detecting active infection with the endemic fungi Histoplasma capsulatum and Blastomyces dermatitidis. Herein, we compared the performance of the MiraVista Diagnostics (MVista) Histoplasma urine antigen assay with the Niche Diagnostics (ND) Histoplasma urine antigen assay for the detection of histoplasmosis and blastomycosis. METHODS: Two hundred fifty urine samples from 234 patients previously tested by the MVista Histoplasma urine antigen assay as part of routine care were tested by the ND Histoplasma and Blastomyces urine antigen assays. The electronic medical records of all patients whose samples were tested were retrospectively reviewed to identify patients with a clinical diagnosis of and/or treatment for histoplasmosis or blastomycosis, and the diagnostic workup undertaken to support these diagnoses. RESULTS: The MVista and ND Histoplasma urine antigen assays were highly concordant, showing 99% overall agreement (90.5% positive agreement and 99.6% negative agreement). Three specimens collected after antifungal therapy returned discrepant results, with the MVista assay positive in 2 of these and the ND assay positive in 1; in each case, the antigen concentration was near the lower quantification limit. Both Histoplasma assays were positive in all patients with culture-proven blastomycosis (n = 3). CONCLUSIONS: The MVista and ND Histoplasma urine antigen assays performed similarly in identifying histoplasmosis cases encountered in routine clinical practice, with discrepancies affecting posttreatment specimens. Given the paucity of Blastomyces-positive samples, further studies are needed to better compare the utility of the MVista and ND Histoplasma urine antigen assays in diagnosing blastomycosis.

Pretreatment Histoplasma capsulatum urine enzymatic immunoassay concentrations do not correlate with outcome but may be influenced by renal function in cats with histoplasmosis.

OBJECTIVES: The objective of this study was to determine if urine Histoplasma antigen (HAg) enzyme immunoassay (EIA) concentrations at the time of diagnosis and prior to the administration of antifungal agents are predictive of outcome for cats infected with Histoplasma capsulatum and to determine if compromised renal function affects urine HAg EIA measurements. METHODS: Medical records at four institutions were searched to identify cats diagnosed with histoplasmosis between April 2012 and December 2015. Pretreatment urine Histoplasma EIA values were recorded, along with patient signalment, serum creatinine concentration, urine specific gravity, site(s) of infection and survival data. RESULTS: Pretreatment urine HAg EIA measurements were available for 50 cats, and ranged from 0-19.1 ng/ml (median 6.3 ng/ml). Thirty-five cats were alive at day 180, 12 had died or were euthanized (median survival time 24 days; range 2-124 days) and three were lost to follow-up. The median urine HAg EIA at the time of diagnosis for cats alive at 6 months was 5 ng/ml (range 0-19.1); this was similar to findings for the non-survivors (median 7.29 ng/ml; range 0.78-19.1; P = 0.54). Surviving cats were significantly younger (mean age 6.9 years) than non-survivors (mean age 9.9 years; P = 0.03) but median body weights (3.8 kg vs 3.6 kg) and rates of pulmonary involvement (22/35 vs 9/12) were similar for the two groups. Median urine HAg EIA concentration was lower in cats with evidence of renal compromise than cats with acceptable renal function (0.54 ng/ml vs 7.2 ng/ml; P <0.013). CONCLUSIONS AND RELEVANCE: Urine HAg EIA concentrations at the time of diagnosis are not predictive of outcome in cats with histoplasmosis and should not be used as a prognostic indicator in this species. Renal function may influence urine HAg EIA concentrations in cats; further investigation is needed to see if concurrent kidney disease impacts test sensitivity.

Histoplasma Urinary Antigen Testing Obviates the Need for Coincident Serum Antigen Testing.

OBJECTIVES: Serum and urine antigen (SAg, UAg) detection are common tests for Histoplasma capsulatum. UAg detection is more widely used and reportedly has a higher sensitivity. We investigated whether SAg detection contributes meaningfully to the initial evaluation of patients with suspected histoplasmosis. METHODS: We reviewed 20,285 UAg and 1,426 SAg tests ordered from 1997 to 2016 and analyzed paired UAg and SAg tests completed on the same patient within 1 week. We determined the positivity rate for each test. RESULTS: Of 601 paired specimens, 542 were concurrent negatives and 48 were concurrent positives (98% agreement). Medical records were available for eight of 11 pairs with discrepant results. UAg was falsely positive in six instances, truly positive once, and falsely negative once. CONCLUSIONS: These findings support using a single antigen detection test, rather than both UAg and SAg, as an initial screen for suspected histoplasmosis. This aligns with the current practice of most physicians.

Sensitivity and Specificity of Histoplasma Antigen Detection by Enzyme Immunoassay.

The objective of this study was to evaluate the sensitivity and specificity of an antigen enzyme immunoassay (EIA) on urine samples for the diagnosis of histoplasmosis in dogs. This retrospective medical records review included canine cases with urine samples submitted for Histoplasma EIA antigen assay between 2007 and 2011 from three veterinary institutions. Cases for which urine samples were submitted for Histoplasma antigen testing were reviewed and compared to the gold standard of finding Histoplasma organisms or an alternative diagnosis on cytology or histopathology. Sensitivity, specificity, negative predictive value, positive predictive value, and the kappa coefficient and associated confidence interval were calculated for the EIA-based Histoplasma antigen assay. Sixty cases met the inclusion criteria. Seventeen cases were considered true positives based on identification of the organism, and 41 cases were considered true negatives with an alternative definitive diagnosis. Two cases were considered false negatives, and there were no false positives. Sensitivity was 89.47% and the negative predictive value was 95.35%. Specificity and the positive predictive value were both 100%. The kappa coefficient was 0.9207 (95% confidence interval, 0.8131-1). The Histoplasma antigen EIA test demonstrated high specificity and sensitivity for the diagnosis of histoplasmosis in dogs.

The Histoplasma capsulatum antigen assay in disseminated histoplasmosis in children.

Progressive disseminated histoplasmosis is often fatal without treatment and requires rapid and accurate laboratory diagnosis. Radioimmunoassay for Histoplasma capsulatum var. capsulatum antigen has been established as a sensitive and accurate diagnostic technique for disseminated histoplasmosis in adults; this study examines the radioimmunoassay in children. The clinical and laboratory records of 26 patients 18 years old or younger in whom H. capsulatum antigen was detected in urine by radioimmunoassay and at least one other positive corroborative standard test were evaluated. Twenty-two (85%) had disseminated disease, and 4 (15%) had self-limited pulmonary disease. Positive corroborative tests included serologic tests in 17 of 22 (77%) patients tested, tissue stains in 5 of 9 (56%) and fungal cultures in 16 of 24 (67%). Patients with disseminated histoplasmosis had a greater degree of antigenuria than those with self-limited infection. In 20 patients with progressive disease treated with amphotericin B, antigen levels declined, and the decrease in antigenuria correlated with clinical improvement. The radioimmunoassay for H. capsulatum antigen in urine is an important test in the diagnosis of disseminated histoplasmosis and is useful for assessing the efficacy of treatment. The presence of urinary antigen is strong evidence for progressive disease that requires treatment.

Diagnosis of histoplasmosis by antigen detection based upon experience at the histoplasmosis reference laboratory.

Histoplasmosis is a common infection in endemic regions of North and Latin America, causing a broad spectrum of clinical findings. The diagnosis may be missed or delayed because histoplasmosis is not considered in the differential. A battery of serologic and mycologic tests may be used for the diagnosis, but each has advantages and limitations. Antigen detection may be particularly helpful for making a rapid diagnosis in patients with more extensive infection. The purpose of this review is to provide a comprehensive discussion of the role of antigen detection in the diagnosis of histoplasmosis, to provide the clinician and laboratory worker with a fuller understanding of the benefits and limitations of this useful laboratory method. This report is based soley upon the experience at the Histoplasmosis Reference Laboratory, and can not be used in interpretation of results of Histoplasma antigen testing done at other laboratories.

Diagnosis of histoplasmosis in urine cytology: reactive urothelial changes, a diagnostic pitfall. Case report and literature review of urinary tract infections.

Histoplasmosis not uncommonly causes systemic infection, particularly in immunocompromised patients. In systemic infection, the urinary tract is often involved, although the diagnosis of histoplasmosis in urine cytologic specimens has never been reported. Urinary tract histoplasmosis may present with gross hematuria, raising clinical suspicion for malignancy. The index case presented with intermittent gross hematuria, suprapubic pain, significant weight loss, hoarse voice, and a painful tongue ulcer. Examination of the patient revealed an ulcerated tongue lesion, an anal ulcer, a polypoid lesion on the vocal cord, and cystoscopic examination of the urinary bladder revealed erythematous patchy areas. Surgical biopsy sections from the vocal cord and tongue lesion were diagnostic of histoplasma infection. Urine cytologic examination showed atypical urothelial cells suspicious for malignancy. However, fungal stains performed on the urine specimen showed histoplasma organisms. We conclude that with a high index of suspicion, and the use of special stains, histoplasma organisms can be identified in urine.