Lawrence J. Wheat

Diagnosis of Disseminated Histoplasmosis by Detection of Histoplasma capsulatum Antigen in Serum and Urine Specimens

The diagnosis of Histoplasma capsulatum infection by serologic testing for the presence of antibodies is limited by a high rate of false positive and false negative results and by the requirement that the patient have a normal immune response. We have developed a radioimmunoassay for the detection of H. capsulatum antigen in urine and serum specimens. Antigenuria was noted in 20 of 22 episodes of disseminated histoplasmosis that occurred in 16 patients, in 6 of 32 patients with self-limited infection, in 2 of 32 patients with cavitary histoplasmosis, and in 4 of 8 patients with a sarcoid-like illness caused by H. capsulatum. The detection of antigen in urine was reproducible in 38 of 41 (93 percent) retests of specimens. H. capsulatum antigen was also detected in the serum during 11 of the 22 episodes of disseminated histoplasmosis, in none of the 12 episodes of other types of histoplasmosis in patients with antigenuria, in 1 of the 33 patients with histoplasmosis who lacked the urinary antigen, and in none of the 50 controls. Antigenemia and antigenuria decreased after initiation of antifungal therapy and recurred in patients who had a relapse. We conclude that this radioimmunoassay for H. capsulatum antigen represents a useful new method for the rapid diagnosis of disseminated histoplasmosis.

A large urban outbreak of histoplasmosis: clinical features.

An outbreak of histoplasmosis estimated to involve more than 100,000 residents in Indianapolis, Indiana, occurred between September 1978 and August 1979. In the 435 cases evaluated, 52% of the patients were between 15 and 34 years old, and 63% were black. Fifteen patients died, and 46 progressive disseminated infection. Twenty-four patients had pericarditis, and 26 had rheumatologic syndromes. Unusual manifestations that occurred in 18 patients included esophageal and vocal cord ulcers, parotitis, adrenal insufficiency, uveitis, fibrosing mediastinitis, interstitial nephritis, intestinal lymphangiectasia, and epididymitis. The highest attack rate was in the central part of the city, which is a densely populated, disproportionately black section. The source of the outbreak has not been proved by positive culture results; two sites, however, were suspected on an epidemiologic basis.

Histoplasma capsulatum infections of the central nervous system. A clinical review.

Central nervous system manifestations occur in 10 to 20% of patients with disseminated histoplasmosis. Additionally, histoplasmosis may be the cause of cases of chronic meningitis in patients with no other evidence for dissemination. Histoplasmosis may also cause cerebral or spinal cord mass lesions resembling neoplasms or abscesses, and encephalitis. Diagnosis of chronic meningitis or mass lesions caused by H. capsulatum may be difficult and involves careful analysis of serologic tests for antibodies, cultures and tests for HPA in body fluids. Amphotericin B remains the treatment of choice, but relapses occur in half of cases despite total courses of at least 35 mg/kg. Accordingly, careful long-term follow-up is required to identify patients with relapsing infection. Newer antifungal agents which cross the blood brain barrier are needed. A trial of amphotericin B treatment without surgical excision can be justified in patients with cerebral or spinal cord histoplasmomas, in view of the apparent success of such treatment in a few cases. Progression of clinical abnormalities or persistence of the lesion following completion of treatment would support the need for surgical excision.

Risk Factors for Disseminated or Fatal Histoplasmosis: Analysis of a Large Urban Outbreak

An outbreak of histoplasmosis in Indianapolis involving 488 clinically recognized cases including 60 patients with disseminated or fatal infection permitted statistical analysis of risk factors. Being male, white, under 5 years of age, having chronic obstructive lung disease, and living near the presumed source of the outbreak were not risk factors for fatal or disseminated histoplasmosis. Age greater than 54 years and immunosuppression were the only risk factors for disseminated or fatal infection. Dissemination should be excluded in patients with histoplasmosis who are immunosuppressed or older than 54 years. Specific antifungal treatment is more likely to be required in those two groups rather than in patients without risk factors.

Performance Characteristics of the Platelia Aspergillus Enzyme Immunoassay for Detection of Aspergillus Galactomannan Antigen in Bronchoalveolar Lavage Fluid

ABSTRACT We have evaluated the Platelia Aspergillus enzyme immunoassay for detection of galactomannan in bronchoalveolar lavage (BAL) specimens in solid organ transplant patients with aspergillosis. The precision and reproducibility in serum or BAL to which galactomannan was added were similar. Sensitivity was 81.8% in patients with aspergillosis, and specificity was 95.8% in lung transplant patients who underwent BAL for surveillance for infection or rejection. Among transplant controls, positive results were more common in patients (i) who underwent diagnostic BAL performed for evaluation of symptoms or chest computed tomographic abnormalities, (ii) who had undergone lung transplantation, or (iii) who were colonized with Aspergillus. Galactomannan testing in BAL is useful for diagnosis of aspergillosis in transplant patients. The significance of positive results in patients without confirmed aspergillosis requires further evaluation.

Detection of Coccidioides antigenemia following dissociation of immune complexes.

ABSTRACT Having reported that pretreatment of serum samples with EDTA at 100°C improved the sensitivity for the detection of Histoplasma antigenemia, we have evaluated this method for the detection of Coccidioides antigenemia. Urine and serum samples from patients with coccidioidomycosis were tested using the MVista Coccidioides enzyme immunoassay, and serum samples with and without EDTA-heat treatment were tested. Antigenemia was detected in 28.6% of patients whose samples were not EDTA-heat treated and in 73.1% of those whose samples were treated. Antigenuria was detected in 50% of patients. Specificity of 100% was obtained in healthy subjects, but cross-reactions were seen in 22.2% of patients with histoplasmosis or blastomycosis. EDTA-heat treatment improves the sensitivity for the detection of Coccidioides antigenemia.

Pericarditis as a manifestation of histoplasmosis during two large urban outbreaks.

During two histoplasmosis outbreaks in Indianapolis 45 patients presented with pericarditis. The pericarditis occurred as a late complication in individual patients and during the outbreak. Risk factors for this complication included young age, immunocompetence, and male sex in persons between 20 and 39 years old. Intrathoracic adenopathy was present in 66% of cases. Since cultures were uniformly negative, including pericardial fluid or tissue from nine patients, serologic studies provided the basis for diagnosis. Although the course was usually benign, nine patients presented with tamponade and another with constrictive pericarditis. Prompt response to antiinflammatory medications and failure to identify H. capsulatum in the pericardial fluid or tissue support a noninfectious, inflammatory mechanism for this complication. Of 20 patients reexamined 1 year later, none had evidence of constriction but three had pericardial thickening by echocardiography. Histoplasmosis should be considered in patients with pericarditis from endemic areas, particularly when associated with intrathoracic adenopathy.

Improved Detection of Histoplasma Antigenemia following Dissociation of Immune Complexes

ABSTRACT The sensitivity for detection of Histoplasma antigen is lower in serum than in urine. In other antigen assays, treatment of serum at 104°C in the presence of EDTA was required for detection of antigenemia. Sensitivity and specificity for detection of Histoplasma antigenemia were examined with or without EDTA heat treatment of the serum using the MVista Histoplasma antigen enzyme immunoassay. A total of 94.6% of serum specimens from patients with AIDS and histoplasmosis that were negative untreated were positive after EDTA-heat treatment. Two-thirds of the negative serum specimens from patients with probable histoplasmosis, based upon clinical suspicion and Histoplasma antigenuria, were positive after heat treatment. Specificity was 99.0% in controls, including healthy subjects and patients in whom histoplasmosis or blastomycosis, were excluded. Precision and reproducibility were good and excellent, respectively. These findings demonstrate improvement in sensitivity without reduction in specificity, precision, or reproducibility after heat-EDTA treatment.

Endemic mycoses: Overlooked causes of community acquired pneumonia

The endemic mycoses are important but often overlooked causes for community acquired pneumonia. Delays in recognition, diagnosis and proper treatment often lead to disastrous outcomes. This topic is not usually discussed in reviews and guidelines addressing the subject of community acquired pneumonia. In this review we discuss the three major endemic mycoses in North America that present as community acquired pneumonias; Coccidioidomycosis, Histoplasmosis and Blastomycosis. We discuss their epidemiology, clinical presentations, methods of diagnosis and current treatment strategies.

Antigen detection in bronchoalveolar lavage fluid for diagnosis of fungal pneumonia.

Purpose of review The purpose of this review is to describe important findings published during the past 18 months using bronchoalveolar lavage (BAL) for diagnosis of pulmonary mycoses. Recent findings Clinical studies and meta-analysis have established a high sensitivity and specificity for Aspergillus galactomannan testing of BAL specimens for diagnosis of invasive aspergillosis, superior to that observed with other diagnostic methods. Similar findings have been reported in histoplasmosis and blastomycosis. Summary Fungal antigen testing of BAL specimens is recommended if bronchoscopy is performed for diagnosis of pulmonary infiltrates in patient groups at risk for aspergillosis or the endemic mycoses if the diagnosis cannot be established by evaluation of sputum specimens or detection of antigen in the urine or serum.