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PubMed1997

Development of a novel antigen detection test for histoplasmosis.

Histoplasmosis is an important systemic fungal infection, particularly among immunocompromised individuals living or travelling in areas of endemicity, who, without antifungal therapy, may develop a progressive disseminated fatal infection. For such patients, the detection of antibody responses by immunodiffusion or complement fixation test is of limited use. In contrast, the detection of Histoplasma capsulatum circulating antigens may provide a more practical approach to the rapid diagnosis of the disease. Accordingly, an inhibition enzyme-linked immunosorbent assay (ELISA) for the detection of a 69- to 70-kDa H. capsulatum-specific determinant and incorporating a species-specific murine monoclonal antibody was developed. With sera from patients with different forms of the disease (n = 35), the overall sensitivity of the test was found to be 71.4%, while the specificity was found to be 98% with normal human sera from areas of endemicity (n = 44) and 85.4% with sera from patients with other chronic fungal or bacterial infections (n = 48). This novel, highly specific ELISA provides a significant addition to the existing diagnostic tests for the detection of histoplasmosis.

Adolescent↗
PubMed2001

Diagnosis and monitoring of murine histoplasmosis by a nested PCR assay.

A newly developed nested PCR assay was applied to murine models of histoplasmosis. ICR and BALB/c mice were intravenously infected with Histoplasma capsulatum and sacrificed up to 29 days later. Samples of blood, spleen, and lung homogenates were cultured and examined by the PCR assay. In the ICR mouse model, 265 of 319 organ samples showed concordant results. With 7 samples, the culture was positive and the PCR assay was negative whereas a positive PCR but a negative culture were obtained with 47 samples (P < 0.0001 according to McNemar's test). Organ homogenates and blood samples of either spontaneously cured or treated BALB/c mice were PCR negative. The nested PCR assay performs excellently in the monitoring of spontaneously and treatment-cured murine histoplasmosis. It limits the infection risks of the laboratory staff and might be of diagnostic value for humans.

Animals↗
PubMed1997

Diffuse histoplasmosis in a patient with sarcoidosis.

A case is presented of a woman with a long history of sarcoidosis who developed diffuse histoplasmosis. Although association between these two entities has been described before, there are only a few case reports of histoplasmosis among sarcoid patients. Diagnosis was finally established by bone marrow biopsy which saved the patient's life.

Adult↗
PubMed2000

Histoplasmosis of the small bowel in patients with AIDS.

Two cases of jejunal strictures caused by Histoplasma capsulatum in AIDS patients are presented. Both patients were intravenous drug abusers. One patient, who was being treated for Pneumocystis carnii pneumonia, presented with jejunal perforation and the other presented with lower gastrointestinal bleeding and intestinal obstruction. On exploration, both patients were found to have jejunal strictures; one had intestinal perforation, and the other had intestinal obstruction with ulcers and strictures resulting in gastrointestinal bleeding. In areas where it is endemic, histoplasmosis is rarely disseminated. Dissemination is most commonly seen in immunosuppressed patients. Dissemination and extrapulmonary histoplasmosis is now included in the case definition of AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1991

Imaging of pediatric mediastinal histoplasmosis.

Histoplasmosis can present a diagnostic dilemma if unusually large masses of lymph nodes, invasive mediastinal fibrosis, or pericarditis result from the infection. These rare, late sequelae are often first suspected from findings on chest radiographs obtained for unrelated reasons. Organisms are not always evident at histologic analysis at this stage. Mediastinal granulomas consist of lobulated masses of enlarged lymph nodes with central caseation, a peripheral thin capsule, and, occasionally, calcification. The mass does not invade or compromise adjacent anatomic structures. Mediastinal fibrosis invades and can seriously compromise the function of the tracheobronchial tree, superior vena cava, pulmonary arteries and veins, and esophagus; its symptoms mimic those of many other disorders. Pericarditis is commonly accompanied by pericardial effusion, pneumonia, and adenopathy. Although the radiologic findings of these conditions are nonspecific, they can be used with the clinical findings to suggest a diagnosis. Complications of histoplasmosis should be included in the differential diagnosis for patients residing in areas endemic to Histoplasma capsulatum.

Adolescent↗
PubMed1984

Histoplasmosis of the adrenal glands studied by CT.

Computed tomography (CT) of the adrenal glands was performed on seven patients who had histologically proved disseminated histoplasmosis. All seven patients showed some degree of adrenal gland abnormality. The range of CT findings included minimal enlargement with faint flecks of calcium, moderate enlargement with focal low attenuation nodules, and massive enlargement with large areas of necrosis or dense calcification. The changes in each patient were bilateral and symmetrical. Adrenal gland shape was usually preserved. Findings of percutaneous adrenal biopsy, which was performed under CT guidance, made the diagnosis in one patient. Five of seven patients had adrenal insufficiency. We conclude that the diagnosis of disseminated histoplasmosis should be considered in any patient who has bilateral adrenal gland enlargement and who resides in an endemic area, especially if there is evidence of adrenal insufficiency, and that CT is superb for the assessment of adrenal gland morphology in this disease, and CT-directed biopsy is the recommended method of confirming the diagnosis in difficult cases.

Adrenal Gland Diseases↗
PubMed2005

[Disseminated histoplasmosis].

We describe two cases of disseminated histoplasmosis, which are of interest due to their severity and the infrequency of this infection in our environment. Both children were immunocompromised immigrants from Latin America who developed prolonged fever, weight loss, hepatosplenomegaly and pancytopenia. One patient had respiratory symptoms with associated alterations on x-ray, while no radiological alterations were found in the other patient. Despite administration of broad-spectrum antibiotics and extraction of samples for microbiological analysis, both patients had a rapid and fatal outcome and the diagnosis was made post mortem. Because of its severity, disseminated histoplasmosis should be considered in the differential diagnosis of fever, hepatosplenomegaly and pancytopenia, with or without alterations on chest x-ray, in immunosuppressed children who were born in or have visited endemic regions. In these patients, therapy should be started immediately without waiting for the results of diagnostic tests.

Child↗
PubMed1987

Expansion of a T lymphocyte subpopulation (CD3+,4-,8-) after immunodepression associated with disseminated histoplasmosis.

A major subpopulation of T lymphocytes bearing a high density of CD3 (T3/Leu 4) with no detectable CD4 (T4/Leu 3a) or CD8 (T8/Leu 2a) was found in a patient with cardiomyopathy. Previously the patient had developed disseminated histoplasmosis which had been associated with a profound anergic state. The proportion of CD3+ lymphocytes that bore the phenotype CD3+,4-,8- has been increasing in the absence of reactivation of the histoplasmosis. The CD3+,4-,8- lymphocytes bound anti-CD2 but did not bind WT31, a monoclonal antibody specific for the alpha beta heterodimer of the T cell antigen receptor.

Adult↗
PubMedDate not supplied

Cytology of gastrointestinal histoplasmosis. A report of two cases with differential diagnosis and diagnostic pitfalls.

BACKGROUND: Gastrointestinal (GI) histoplasmosis is a rare manifestation of Histoplasma capsulatum (HC) infection. There are no reports of its cytologic diagnosis in the literature. CASES: A search of the cytology and surgical pathology files of the Methodist Hospital uncovered two cases of GI histoplasmosis and histiocytes within cytologic specimens. Papanicolaou-stained endoscopic brushings of an obstructing, apple-core, right colonic mass in a 58-year-old, heterosexual male revealed numerous vacuolated single cells interpreted as suspicious for signet ring cell carcinoma. The resected colon showed granulomatous inflammation with numerous histiocytes containing pale, oval yeasts of HC. The patient was subsequently found to be human immunodeficiency (HIV) positive; this was his first manifestation of the acquired immunodeficiency syndrome. The second patient was a 69-year-old, HIV-negative male with a fungating anal mass suspicious for squamous cell carcinoma. Direct smears showed oval histiocytes with intracellular yeasts of HC. CONCLUSION: Accurate diagnosis is crucial to patient management and therapy. Careful attention to the nuclear and cytoplasmic details of histiocytes and histiocytelike cells is important to avoid interpretive errors. Diagnostic pitfalls include signet ring cell adenocarcinoma, lymphoma, melanoma, goblet cell carcinoid, malakoplakia and such infections as mycobacteria, Entamoeba histolytica and Calymmatobacterium granulomatis. Ancillary studies, such as microbiologic cultures and immunohistochemical and histochemical staining, can be performed in the appropriate clinical setting.

AIDS-Related Opportunistic Infections↗
PubMed1987

Evaluation of enzyme immunoassay as a rapid screening test for histoplasmosis and blastomycosis.

This study evaluates the usefulness of enzyme immunoassay (EIA) as a screening test for serum antibodies to Histoplasma capsulatum and Blastomycoses dermatitidis and compares the results using this assay with those using complement fixation (CF), immunodiffusion (ID), and radioimmunoassay (RIA), in 12 patients with active histoplasmosis, 12 with active blastomycosis, 28 with other acute or chronic lung diseases and 25 healthy blood donors from an endemic area; EIA was as sensitive as RIA and more sensitive than CF and ID in the 24 patients with active fungal infections. The specificity of EIA was equal to that of the other serologic tests. We conclude that EIA is a useful screening test for serum antibodies to H. capsulatum and B. dermatitidis that avoids some of the problems associated with other sensitive assays such as RIA. A negative EIA result is evidence against invasive histoplasmosis or blastomycosis and suggests an alternative diagnosis.

Antigens, Fungal↗
PubMed1990

Significance of false-positive serologic tests for histoplasmosis and blastomycosis in an endemic area.

False-positive serologic tests for histoplasmosis (H) and blastomycosis (B) are common in populations from endemic areas. In order to determine the significance of false-positive test results, we reviewed the final diagnoses of all patients whose sera were submitted to our laboratory for radioimmunoassay (RIA) and immunodiffusion (ID) during a 3-yr period. Of the 263 patients whose sera were examined, 29 (11%) had H or B; 41 (17.5%) of the remaining 234 patients had false-positive test results. Of these 41 patients, 31 were positive for H alone, and 10 had antibodies to both H and B. All three patients with false-positive ID tests for histoplasmosis also had positive titers (greater than or equal to 1:16) on RIA. No patient had a false-positive ID result for blastomycosis. The percentage of patients in each of five major diagnostic categories with and without false-positive serologic tests was similar (p greater than 0.05). The majority of patients had pulmonary infections, almost half of which were granulomatous infections other than H or B; this reflects the clinical indications for requesting fungal serologic tests. A positive fungal serology is not useful in suggesting the presence of a pulmonary disease other than H or B in patients from an endemic area suspected of having a pulmonary mycosis.

Blastomycosis↗
PubMed1991

Immunohistopathology of murine pulmonary histoplasmosis during normal and hypersensitive conditions.

Pulmonary histoplasmosis was induced in nonimmunized and immunized Balb-C nu/+ mice. The lung tissue burden of H. capsulatum, histopathology, the size of the inflammatory area, and the numbers of total T lymphocytes and subtypes in situ were evaluated serially after challenge. Over 3 days previously immunized mice developed a large lymphocyte/macrophage inflammatory response. This rapidly decreased in the next 2 wk. In contrast, the nonimmunized control mice developed a predominantly polymorphonuclear infiltrate that evolved more slowly over the first week of infection. This initial response was nonspecific but, after the first week, shifted to lymphocytes and granuloma formation. The lymphocyte infiltration in both immunized and nonimmunized mice was predominantly CD4. Previously immunized mice had a rapid decrease in tissue counts of H. capsulatum after Day 3, but nonimmunized mice continued to have increased counts through Day 7 after infection. These studies reproduce in the mouse model a host response similar to acute reinfection histoplasmosis in the human. In this condition an intense cell-mediated inflammatory response is thought to be elicited by fungal antigens and to represent host reaction rather than fungal replication. Our experimental model added new information relevant to the understanding of the pathogenesis of this process.

Alveolitis, Extrinsic Allergic↗
PubMed1985

Detection of histoplasmal antigens in mice undergoing experimental pulmonary histoplasmosis.

A micro-ELISA assay was developed for the quantitation of Histoplasma capsulatum antigen in lungs, bronchoalveolar lavage fluid (BALF), and serum of intranasally infected mice. As little as 0.2 ng of antigen/ml could be detected. During the course of experimental histoplasmosis, immunologically intact, thymus-containing mice (nu/+) had detectable histoplasmal antigens in their lungs, serum, and BALF within 1 day of challenge. Lung, BALF, and serum antigen concentration rose to a peak 2 wk after challenge; in nu/+ mice, antigen concentration then declined through the next 2 wk. In contrast, athymic nude mice have depressed cell-mediated immunity; their antigen concentration continued to rise throughout the course of progressive, ultimately lethal, illness. Antigen concentrations correlated with quantitative cultures of the lungs and BALF. There was little cross reactivity in mice challenged intranasally with Candida albicans or Blastomyces dermatitidis. The sensitivity of this test, and the apparently minimal cross reactivity, suggest that the micro-ELISA for histoplasmal antigen might have significant clinical application in diagnosing and monitoring the course of histoplasmosis.

Animals↗
PubMed1986

Treatment of murine histoplasmosis with UK 49,858 (fluconazole).

Fluconazole was compared with ketoconazole and with amphotericin B in treatment of pulmonary histoplasmosis in immunologically intact mice and in congenitally athymic nude mice. Both fluconazole and amphotericin B increased survival and reduced fungal burden in normal mice. All 3 drugs equally prolonged survival of nude mice challenged with Histoplasma capsulatum, and all effectively reduced the fungal burden. Fluconazole may be a useful antifungal drug in treatment of murine histoplasmosis.

Animals↗
PubMed2003

Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy.

Anti-tumor necrosis factor-alpha (TNF-alpha) antibodies are frequently used to treat inflammatory diseases. However, these drugs also have immunosuppressive effects. We report on three patients who developed disseminated histoplasmosis on therapy with TNF-alpha inhibitors. In vitro assays were used to characterize the role of these agents in host defense against Histoplasma capsulatum. Intracellular proliferation of H. capsulatum was measured in alveolar macrophages and peripheral monocytes of normal volunteers in the presence and absence of the TNF-alpha antibody, infliximab. Both infliximab and control antibody enhanced fungal growth in monocytes and alveolar macrophages, suggesting this was a nonspecific antibody response. Despite similar intracellular fungal loads in the presence of both antibodies, lymphocyte proliferation in response to blood monocytes and alveolar macrophages infected with H. capsulatum was inhibited by the addition of physiologic doses of infliximab, whereas control antibody had no effect. The production of H. capsulatum-induced interferon-gamma and TNF-alpha was assessed in 5-day cultures containing lymphocytes and alveolar macrophages or monocytes. Interferon-gamma secretion was significantly reduced in the presence of infliximab. In summary, patients receiving anti-TNF-alpha therapy are at risk for developing disseminated histoplasmosis. This may be due to a defect in the TH1 arm of cellular immunity.

Adolescent↗
PubMed1994

Chloroquine induces human macrophage killing of Histoplasma capsulatum by limiting the availability of intracellular iron and is therapeutic in a murine model of histoplasmosis.

We investigated the role of intracellular iron on the capacity of Histoplasma capsulatum (Hc) yeasts to multiply within human macrophages (Mphi). Coculture of Hc-infected Mphi with the iron chelator deferoxamine suppressed the growth of yeasts in a concentration-dependent manner. The effect of deferoxamine was reversed by iron-saturated transferrin (holotransferrin) but not by iron-free transferrin (apotransferrin). Chloroquine, which prevents release of iron from transferrin by raising endocytic and lysosomal pH, induced human Mphi to kill Hc. The effect of chloroquine was reversed by iron nitriloacetate, an iron compound that is soluble at neutral to alkaline pH, but not by holotransferrin, which releases iron only in an acidic environment. Chloroquine (40-120 mg/kg) given intraperitoneally for 6 d to Hc-infected C57BL/6 mice significantly reduced the growth of Hc in a dose-dependent manner. At 120 mg/kg there was a 17- and 15-fold reduction (P < 0.01) in CFU in spleens and livers, respectively. The therapeutic effect of chloroquine also correlated with the length of treatment. As little as 2 d of chloroquine therapy (120 mg/kg), when started at day 5 after infection, reduced CFU in the spleen by 50%. Treatment with chloroquine for 10 d after a lethal inoculum of Hc protected six of nine mice; all control mice were dead by day 11 (P = 0.009). This study demonstrates that: (a) iron is of critical importance to the survival and multiplication of Hc yeasts in human Mphi; (b) in vitro, chloroquine induces Mphi killing of Hc yeasts by restricting the availability of intracellular iron; and (c) in vivo, chloroquine significantly reduces the number of organisms in the spleens and livers of Hc-infected mice and can protect mice from a lethal inoculum of Hc yeasts. Thus, chloroquine may be effective in the treatment of active histoplasmosis and also may be useful in preventing relapse of histoplasmosis in patients with acquired immunodeficiency syndromes.

Animals↗
PubMed1993

Acute histoplasmosis in a hyperreactive individual.

Acute histoplasmosis usually is asymptomatic and most commonly occurs in children. Symptomatic acute pulmonary infections range from mild to severe. Extrapulmonary lesions are common and oftentimes most prominent. In this report, we describe a patient with acute histoplasmosis with pulmonary findings as well as striking lesions within the liver and spleen.

Acute Disease↗
PubMed1977

Low-dose amphotericin B therapy for acute pulmonary histoplasmosis.

A patient wtih acute epidemic pulmonary histoplasmosis was treated with 500 mg of amphotericin B. Traditionally, such patients have not been treated, since the illness is usually self-limited; however, fatalities have been reported, and some authorities have recommended therapy with small doses of amphotericin B. Patients with acute pulmonary histoplasmosis who are acutely ill should be considered for low-dose treatment with amphotericin B, inasmuch as they are likely candidates for early dissemination. Cures have been reported with as little as 105 mg of amphotericin B administered intravenously.

Acute Disease↗