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PubMedDate not supplied

Histoplasmosis in solid organ transplant recipients at a large Midwestern university transplant center.

Histoplasma capsulatum sporadically causes severe infections in solid organ transplant (SOT) patients in the Midwest, but it has been an unusual infection among those patients followed at the University of Nebraska Medical Center (UNMC), located at the western edge of the 'histo belt.' Nine SOT patients with histoplasmosis are described (6 renal or renal-pancreas and 3 liver recipients) who developed severe histoplasmosis over a recent 2.5-year period at UNMC. Symptoms started a median of 11 months (range, 1.2-90 months) after organ transplant and consisted primarily of fever, cough, shortness of breath, and malaise or fatigue present for approximately 30 days prior to medical evaluation. All patients had an abnormal chest radiograph and/or computed tomographic scan. Tacrolimus was the main immunosuppressant in all 9 patients, along with prednisone or mycophenolate. Dacluzimab or thymoglobulin had been given around the time of transplant in 6 of 9. None was treated for an episode of acute rejection within 2 months before onset of histoplasmosis, although 2 were on high-dose immunosuppression after recent transplants. Diagnosis was made by culture in 8 of the 9 patients, with positive serum and urine histoplasma antigen tests in all 9 cases. From 1997 to 2001, during a period of relative quiescence of the disease in the general population, the rate of clinical histoplasmosis among SOT patients at UNMC was estimated at 0.11%, whereas during 2002 through the first half of 2004, the rate rose 17-fold to 1.9%. Histoplasmosis can present as a prolonged febrile illness with subacute pulmonary symptoms in a cohort of SOT patients, despite the absence of a regional outbreak.

Academic Medical Centers↗

PubMed2005

Gastrointestinal histoplasmosis.

Gastrointestinal histoplasmosis (GIH) is an uncommon disease with protean manifestations. It may occur as a result of mediastinal histoplasmosis or in the setting of progressive dissemination. GIH may be misdiagnosed as inflammatory bowel disease, malignancy, or other intestinal diseases leading to inappropriate therapies and unnecessary surgical interventions. Patients with bowel obstruction, perforation, or bleeding, and systemic findings suggestive of histoplasmosis should be evaluated for GIH. This is especially true for immunosuppressed patients, especially those with AIDS. Diagnosis first requires consideration of histoplasmosis in the differential in patients with the above types of gastrointestinal abnormalities, and second, familiarity with a battery of mycologic and serologic tests. Progressive disseminated histoplasmosis (PDH) is lethal if left untreated, and treatment is highly effective. This review will focus on the clinical and histopathologic features of GIH, the approach to diagnosis, and recommendations for treatment.

Gastrointestinal Diseases↗

PubMed1999

Bat-associated histoplasmosis in returning travelers: case presentation and description of a cluster.

Histoplasma capsulatum is a dimorphic fungus with the mycelial form producing spores that are readily airborne and able to reach small bronchi and alveoli. Isolation of the mycelial form of H. capsulatum in nature shows a striking correlation with moist, acidic soils, frequently contaminated with bird or bat excreta. Bats, but not birds, may be infected by H. capsulatum and may excrete the fungus in their feces. Skin test surveys show that the infectious agent is present worldwide in the areas between 45 degrees north and 30 degrees south of the equator. Clusters of cases may occur because of the disturbance of soil contaminated with H. capsulatum, or by visiting bat caves. Cave-associated histoplasmosis has been reported from the Americas, Africa, Oceania, and Africa. Recently, cave-associated histoplasmosis has been reported in travelers returning from Costa Rica and Peru. We report a cluster of cave-associated acute histoplasmosis that occurred in college students returning from Ecuador. Advice regarding histoplasmosis prevention should be given to travelers planning to visit bat-infested caves, and histoplasmosis should be considered in the differential diagnosis of febrile illness in returning travelers with a history of epidemiologic or geographic exposure.

Acute Disease↗

PubMed1995

[An outbreak of acute pulmonary histoplasmosis among travelers to a bat-inhabited cave in Brazil].

Histoplasmosis is known to be endemic in various parts of the world, especially in North and Latin America. In Japan, Histoplasma capsulatum has rarely been isolated from the natural environment. To date, only seven cases of histoplasmosis have been reported in Japan including some that were contracted in foreign countries. Herein, we report the occurrence of acute histoplasmosis among Japanese travelers who were exposed to bat guano in a cave near Manaus, Brazil. A group of 8 Japanese travelers entered a cave for a total of 2 hours in March, 1993. All the visitors had been healthy and had no history of abnormal chest roentgenograms. From 10 to 20 days after the exposure, 7 (87.5%) of the 8 individuals developed abnormal symptoms including fever, malaise, loss of appetite, myalgia, arthralgia, chest pain and dry cough. Five (62.5%) had nodular infiltrative shadows with or without hilar lymphadenopathy in the chest roentgenograms. Eight (100%) of the individuals showed serologic evidence of histoplasmosis. Despite the small number of subjects, this high rate of infection may be related to the fact that the subjects stayed in an enclosed area where air exchange was minimal, at the end of a deep cave infested with numerous bats. The cave involved has never been documented as being endemic for histoplasmosis. The threat of H. capsulatum infection in bat-inhabited caves should be emphasized to travelers and also to physicians.

Adult↗

PubMed2007

Histoplasmosis: a clinical and laboratory update.

Infection with Histoplasma capsulatum occurs commonly in areas in the Midwestern United States and Central America, but symptomatic disease requiring medical care is manifest in very few patients. The extent of disease depends on the number of conidia inhaled and the function of the host's cellular immune system. Pulmonary infection is the primary manifestation of histoplasmosis, varying from mild pneumonitis to severe acute respiratory distress syndrome. In those with emphysema, a chronic progressive form of histoplasmosis can ensue. Dissemination of H. capsulatum within macrophages is common and becomes symptomatic primarily in patients with defects in cellular immunity. The spectrum of disseminated infection includes acute, severe, life-threatening sepsis and chronic, slowly progressive infection. Diagnostic accuracy has improved greatly with the use of an assay for Histoplasma antigen in the urine; serology remains useful for certain forms of histoplasmosis, and culture is the ultimate confirming diagnostic test. Classically, histoplasmosis has been treated with long courses of amphotericin B. Today, amphotericin B is rarely used except for severe infection and then only for a few weeks, followed by azole therapy. Itraconazole is the azole of choice following initial amphotericin B treatment and for primary treatment of mild to moderate histoplasmosis.

Amphotericin B↗

PubMed1999

Relatedness analyses of Histoplasma capsulatum isolates from Mexican patients with AIDS-associated histoplasmosis by using histoplasmin electrophoretic profiles and randomly amplified polymorphic DNA patterns.

The present paper analyzes the histoplasmin electrophoretic profiles and the randomly amplified polymorphic DNA (RAPD) patterns of the fungus Histoplasma capsulatum isolated from Mexican patients with AIDS-associated histoplasmosis. Clinical isolates from Guatemala, Colombia, and Panama, as well as H. capsulatum isolates from different sources in nature, were also processed. All histoplasmin samples shared four antigenic fractions of 200, 49, 10.5, and 8.5 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). According to their percentage of relatedness, based on SDS-PAGE histoplasmin electrophoretic image analysis, H. capsulatum isolates were divided in two groups: group A contained all AIDS-associated isolates studied and two human reference strains from Mexican histoplasmosis patients without AIDS; group B included bat guano, infected bat, and cock excreta isolates from the State of Guerrero, Mexico, plus three human histoplasmosis strains from Guatemala, Panama, and Colombia. Polymorphic DNA patterns evaluated by RAPD-PCR showed three major bands of 4.4, 3.2, and 2.3 kb in most H. capsulatum isolates studied. Four groups were related by DNA polymorphisms: group I was formed by most of the AIDS-associated H. capsulatum isolates studied, one human histoplasmosis strain from Colombia, two human reference strains from Mexican patients without AIDS, and one human histoplasmosis strain from Guatemala. Group II consisted of only a single strain from Panama. Group III included three strains: one from a Mexican patient with AIDS and two isolated from nature in Guerrero (cock excreta and bat guano). The last, group IV, consisted of only one strain isolated from an infected bat, captured in Guerrero. A tight relationship between phenotypic and genotypic characterization was observed, and both analyses could be useful tools for typing H. capsulatum from different sources and geographic origins.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Experimental pulmonary histoplasmosis and emphysema.

Chronic pulmonary histoplasmosis often occurs in the setting of emphysema. However, it is unknown whether emphysema directly predisposes to the development of the necrotizing lesions of chronic pulmonary histoplasmosis. We evaluated this possibility using a murine model of pulmonary histoplasmosis. Using intratracheal inoculation of elastase, we induced pulmonary emphysema in Balb/c mice. When mice with emphysema were challenged intranasally with H. capsulatum (HC) yeast cells, the course of their disease was not significantly different from that of normal mice. Mice were also exposed to HC antigens by sublethal intranasal challenge with viable or heat-killed HC, or immunized with histoplasmin. Prior sublethal challenge with viable HC did not cause prolonged illness or increased mortality in the setting of emphysema. In contrast, such mice were protected against a severe rechallenge. Additional studies showed that intranasal administration of heat-killed HC or subcutaneous immunization with histoplasmal antigens had neither protective nor deleterious effects on the course of histoplasmosis. Therefore, in this murine model, we could not substantiate an interaction of underlying emphysema with acute primary or rechallenge pulmonary histoplasmosis.

Animals↗

PubMed1992

Diagnosis of histoplasmosis in patients with the acquired immunodeficiency syndrome by detection of Histoplasma capsulatum polysaccharide antigen in bronchoalveolar lavage fluid.

Diagnosis of histoplasmosis in patients with Acquired Immunodeficiency Syndrome (AIDS) may be established by detection of the organism in lung tissue or bronchoalveolar lavage fluid. In this report we have evaluated the utility of Histoplasma capsulatum polysaccharide antigen (HPA) detection in bronchoalveolar lavage fluid for diagnosis of histoplasmosis. HPA was detected in bronchoalveolar lavage fluid of 19 of 27 cases (70.3%). Of 122 controls with a variety of underlying diseases, HPA was detected in none. Eight of the negative specimens from patients with histoplasmosis were retested after fivefold concentration, and HPA was detected in five. Fivefold concentration of 10 control samples had no effect on HPA level. H. capsulatum was seen by methenamine silver or Giemsa stain in 19 of the 27 (70.3%) and isolated by culture in 24 of 27 (88.9%) cases. Twenty-four of 26 (92.3%) cases had positive cultures from extrapulmonary sites as well. HPA was detected in the urine of 25 (92.6%) and the serum of 23 (88.5%) of the 26 cases. We conclude that HPA detection offers a rapid method for identification of pulmonary histoplasmosis in patients with AIDS and could be a helpful addition to the battery of tests performed on bronchoalveolar lavage fluids in areas where histoplasmosis is endemic.

Acquired Immunodeficiency Syndrome↗

PubMed1984

Tissue morphology of Histoplasma capsulatum in acute histoplasmosis.

Reports of histopathology in acute histoplasmosis are rare. A case of fulminating acute histoplasmosis with hematogenous dissemination is described in which Histoplasma capsulatum was identified in transbronchial biopsy. This report represents the first morphologic description of H. capsulatum within human pulmonary tissue in the early phase of acute histoplasmosis. The yeast forms observed were of typical size, but they were present within the alveoli and were budding. No tissue granulomata were noted. This unusual morphology is in sharp contrast to the classic description of the organism in tissues and presented diagnostic difficulties, which are discussed in this report. Hematogenous dissemination is considered to be an important part of the pathogenesis of the disease, but it is rarely documented during the symptomatic phase of acute histoplasmosis. Cultural documentation of hematogenous dissemination was obtained in this patient. These observations stress the importance of obtaining culture material from extrapulmonary sites early in the course of acute histoplasmosis when a specific diagnosis is necessary.

Acute Disease↗

PubMed2006

Spinal intramedullary histoplasmosis as the initial presentation of human immunodeficiency virus infection: case report.

OBJECTIVE: Spinal intramedullary histoplasmosis is an extremely rare condition. We report a case of isolated intramedullary histoplasmosis as the initial manifestation of human immunodeficiency virus (HIV) infection. CLINICAL PRESENTATION: A 27-year-old man presented with a rapidly progressive paraparesis. Magnetic resonance imaging scans revealed an enhancing lesion at C7-T1 with edema extending as far as the cervicomedullary junction. He improved with steroid medications. INTERVENTION: The patient underwent laminectomy and biopsy of the lesion. The diagnosis of histoplasmosis was made by histology, culture, and polymerase chain reaction identification of fungal deoxyribonucleic acid. The patient did not have disseminated histoplasmosis. Subsequent to the biopsy, the patient was discovered to have HIV infection. CONCLUSION: The isolated spinal histoplasmosis lesion thus represented the initial presentation of HIV infection. Management of the case and diagnostic issues are discussed.

Adult↗

PubMed1989

Bronchoscopy in the diagnosis of pulmonary histoplasmosis.

Although histoplasmosis is the most common fungal infection of the lungs in the United States, there are no reports evaluating the efficacy of fiberoptic bronchoscopy in the diagnosis of this disease. We reviewed all cases of histoplasmosis diagnosed at our institution from 1972 to 1987. Of 469 patients, 71 underwent fiberoptic bronchoscopy and had culture/histologic proof of histoplasmosis established by fiberoptic bronchoscopy or other means. A diagnosis of pulmonary histoplasmosis could be made without thoracotomy in only 27. Among those not requiring thoracotomy, diagnosis of pulmonary histoplasmosis was confirmed by fiberoptic bronchoscopy and cultures of sputum, gastric washings, blood, bone marrow, and urine. In this subgroup, fiberoptic bronchoscopy was the only positive diagnostic method in eight of 27 patients. We conclude that fiberoptic bronchoscopy is a useful adjunct to other noninvasive measures yielding diagnostic material in most cases, except for solitary pulmonary nodule where it is rarely helpful.

Adolescent↗

PubMed2006

Improvements in diagnosis of histoplasmosis.

Understanding the uses and limitations of a battery of laboratory methods is essential to diagnose histoplasmosis. Antigen detection and serology are valuable adjuncts to histopathology and culture. Improvements incorporated into the second-generation Histoplasma antigen assay have increased its sensitivity and specificity for diagnosis of histoplasmosis. More recently, the antigen assay has been modified to provide quantitation, which improves reproducibility and facilitates monitoring antigen clearance during treatment. Furthermore, detection of antigen in bronchoalveolar lavage fluid increases the sensitivity for diagnosis of pulmonary histoplasmosis. Serological tests for antibodies are also useful, but may be falsely negative in immunosuppressed patients. In addition, elevated antibody titres persist for several years following initial infection, complicating their interpretation. Although histopathology may provide for rapid diagnosis, its sensitivity is < 50% in patients with disseminated disease and even lower in pulmonary histoplasmosis. Polymerase chain reaction has been described, but sensitivity is less than that of histopathology. Culture, although highly specific, has notable limitations, including insensitivity, a need for invasive procedures and delayed growth. This review provides the background for understanding the role of a battery of diagnostic methods in histoplasmosis. Tests facilitating a rapid diagnosis are expected to improve the outcome in patients with severe disease.

Animals↗

PubMed1989

Long-term amphotericin B therapy for disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome (AIDS).

STUDY OBJECTIVE: To assess the efficacy and toxicity of long-term maintenance amphotericin B therapy in preventing relapses after treatment in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. DESIGN: Open, nonrandomized pilot study. SETTING: Three private, university-affiliated community hospitals. PATIENTS: We studied 22 consecutive patients with disseminated histoplasmosis and human immunodeficiency virus (HIV) infection. Sixteen patients completed the study, 5 patients died before completing the initial intensive phase of treatment, and 1 patient received a different treatment regimen. INTERVENTIONS: Seven patients were treated with an initial intensive course of 1000 mg of amphotericin B, followed by weekly infusions of 50 to 80 mg until a cumulative dose of 2000 mg was attained; biweekly infusions of 50 to 80 mg were then continued indefinitely. Nine patients received an initial amphotericin B course of 2000 mg followed by weekly infusions of 80 mg. MEASUREMENTS AND MAIN RESULTS: Of the 7 patients in the 1000-mg intensive regimen group, 6 patients have survived without clinical or laboratory evidence of a histoplasmosis relapse, and 1 died of unrelated causes. Of the 9 patients in the 2000-mg intensive regimen group, 7 patients have survived, 1 patient died of a histoplasmosis relapse, and 1 patient died of other causes. Thus, 13 of 14 patients (93%) who did not die of other causes remained relapse-free. The median follow-up period was 14 months (range, 2 to 23 months). No apparent differences in outcome were observed between patients treated with weekly maintenance regimens and those treated with biweekly maintenance regimens. Sixty-three percent of patients developed intravascular device-related complications. CONCLUSIONS: Long-term, intermittent maintenance amphotericin B therapy in HIV-infected patients with disseminated histoplasmosis is well tolerated and is highly effective in suppressing relapses after treatment.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To assess the efficacy and safety of itraconazole in preventing relapse of histoplasmosis after induction therapy with amphotericin B in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. DESIGN: A prospective, multicenter, open-label clinical trial, with follow-up for at least 52 weeks. SETTING: Tertiary care hospitals participating in a clinical investigation sponsored by the National Institutes of Allergy and Infectious Diseases (AIDS Clinical Trial Group and Mycoses Study Group). PATIENTS: Forty-two patients with AIDS who had successfully completed induction therapy for disseminated histoplasmosis amphotericin B, at least 15 mg/kg body weight given over 4 to 12 weeks. INTERVENTIONS: Itraconazole, 200 mg given orally twice daily. MAIN OUTCOME MEASURES: Response to therapy, specifically prevention of histoplasmosis relapse, was the main outcome measure. Secondary end points were survival and the effect of therapy on Histoplasma capsulatum variety capsulatum antigen levels in urine and serum. Plasma itraconazole concentrations were measured to document drug absorption and compliance with therapy. RESULTS: The median follow-up was 109 weeks, and median survival was 98 weeks. Two relapses occurred (5%; 95% CI, 0.5% to 16%), one in a patient withdrawn from the study 18 weeks earlier and one in a patient who did not comply with the study therapy. Patients with elevated antigen levels at study entry showed clearance of antigen from urine and serum; urine specimens became negative in 43% of patients (CI, 26% to 59%), and serum specimens became negative in 75% of patients (CI, 56% to 94%). Only one patient discontinued treatment because of itraconazole toxicity (hypokalemia). CONCLUSIONS: Itraconazole, 200 mg twice daily, is safe and effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. Antigen clearance from blood and urine correlates with clinical efficacy.

AIDS-Related Opportunistic Infections↗

PubMed2000

Disseminated cutaneous histoplasmosis and AIDS: case report.

Histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum. It manifests by the presence of fever as the only symptom in most individuals. The disease may present as self-limited pneumonia, or as an hematogenous widespread fungal infection with a potentially fatal outcome in elderly individuals and people with compromised T-cell mediated immunity. Here, we report a case of disseminated cutaneous histoplasmosis in a patient with AIDS. The patient was a 33 year old male homosexual, intravenous drug user, who had been diagnosed with HIV infection 5 years earlier. He was in good health, but had erythematous papules and pustules in the skin of the scalp, face, back, thighs, abdomen, palms, and soles. He was placed on anti-retroviral therapy, fluconazole for mucosal candidiasis, trimethoprim/sulfamethoxazole for pneumocystis prophylaxis, and antibiotics for the skin pustules. The skin lesions improved remarkably within 14 days. He was discharged and soon lost to follow-up. After his discharge, skin biopsy and fungal culture results revealed H. capsulatum. He was seen again 1 year later. The interim history revealed that he had taken fluconazole 100 mg/day for 1 month and fluconazole 150 mg/week for 7 months. He had not continued anti-retroviral therapy, nor taken other antifungal drugs. The clinical evolution of the disease was exceptional in that there was disappearance of all the skin lesions attributed to histoplasmosis with fluconazole. Although itraconazole remains the drug of choice for histoplasmosis. Cutaneous histoplasmosis should be considered in the differential diagnosis of atypical cutaneous lesions in individuals infected with HIV.

AIDS-Related Opportunistic Infections↗

PubMed2001

Histoplasmosis as an isolated liver lesion: review and surgical therapy.

Histoplasmosis is the most common cause of fungal infection in the Ohio River Valley of the United States. Ninety-nine per cent of patients exposed to histoplasmosis develop only subclinical infections. Liver involvement is common in disseminated histoplasmosis, which usually originates in the lungs. There has been only one prior case described in the literature of histoplasmosis presenting as an isolated liver mass. We report a rare case that presented as a solitary right-sided liver lesion invading the diaphragm, with review of the literature for therapy of histoplasmosis of the liver.

Adult↗

PubMedDate not supplied

Histoplasmosis in Africa: a review.

Classical histoplasmosis caused by Histoplasma capsulatum var. capsulatum, and African histoplasmosis caused by H. capsulatum var. duboisii are both endemic in Africa. In South Africa, only classical histoplasmosis caused by Histoplasma capsulatum var. capsulatum is known to occur and cases are seen frequently. It occurs sporadically in several other African countries. Histoplasma capsulatum var. capsulatum is known to occur naturally in caves inhabited by bats in some parts of South Africa, namely, Transvaal and Cape province, Zimbabwe and Tanzania. Outbreaks of histoplasmosis have been reported in cave explorers. Surveys of histoplasmin skin sensitivity carried out in Africa have shown the rate of positive reactors to be from 0.0% to 28%. African histoplasmosis caused by H. capsulatum var. duboisii is prevalent in Western and Central Africa, and in the island of Madagascar between the Kalahari and Sahara deserts, that is between latitudes 20 degrees North and 20 degrees South of the Equator. A natural reservoir of this fungus in soil admixed with bat guano has been found in a bat cave in a rural area, viz. Ogbunike in Anambra State of Nigeria. The clinical features and epidemiology of the two forms of the disease in Africa are reviewed.

Africa↗

PubMed2004

Oral histoplasmosis presenting as oral ulcer in a non-HIV patient.

A 40-year-old man presented with chronic mouth ulcer for the last six months. Histopathological examination of the biopsy from the lesion confirmed a diagnosis of histoplasmosis. Although histoplasmosis commonly manifests in immunocompromized patients, like HIV, the present case was negative for HIV. Histoplasmosis is endemic in certain parts of the world and it is comparatively rare in the South Asian region, particularly Malaysia. Thirty-seven cases of histoplasmosis were reported from Malaysia (Ng and Siar, 1996), between July 1967 and October 1997. Despite the apparent rarity of the disease, clinicians and pathologists should be aware of the possibility of histoplasmosis when cases of oral ulcer are encountered.

Adult↗