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Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
Published on: February 14, 2011
A complementary tool for management of disseminated Histoplasma capsulatum var. capsulatum infections in AIDS
Xavier Iriart1, Denis Blanchet2, Sandie Menard3
1Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, France; INSERM UMR1043/CNRS UMR5282/Université de Toulouse UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse F-31300, France.
Abstract:
In South America, disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum (H. capsulatum), is a severe and frequent opportunistic infection in AIDS patients. In areas outside the USA where specific-Histoplasma antigen detection is not available, the diagnosis is difficult. With the galactomannan antigen (GM) detection, a test commonly used for invasive aspergillosis diagnosis, there is a cross-reactivity with H. capsulatum that can be helpful for the diagnosis of histoplasmosis. The aim of this study was to evaluate the GM detection for the diagnosis of disseminated histoplasmosis in AIDS patients. The performance of the GM detection was evaluated with serum collected in French Guiana where H. capsulatum is highly endemic. Sera from AIDS patients with disseminated histoplasmosis occurring from 2002 to 2009 and from control HIV-positive patients without histoplasmosis were tested with the GM detection and Histoplasma-specific antibody detection (IEP). In 39 AIDS patients with proven disseminated histoplasmosis, the sensitivity of the Histoplasma IEP was only 35.9% and was linked to the TCD4+ lymphocyte level. For the GM detection, the sensitivity (Se) was 76.9% and specificity (Sp) was 100% with the recommended threshold for aspergillosis diagnosis (0.5). The test was more efficient with a threshold of 0.4 (Se: 0.82 [95% CI: 0.66-0.92], Sp: 1.00 [95% CI: 0.86-1.00], LR+: >10, LR-: 0.18). This study confirms that the GM detection can be a surrogate marker for the diagnosis of disseminated histoplasmosis in AIDS patients in endemic areas where Histoplasma EIA is not available.
Insights
Galactomannan (GM) antigen detection, a test for invasive aspergillosis, shows high sensitivity and specificity for diagnosing disseminated histoplasmosis in AIDS patients. This offers a valuable diagnostic tool in endemic areas lacking specific Histoplasma antigen tests.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Immunology
Background:
- Disseminated histoplasmosis caused by Histoplasma capsulatum is a severe opportunistic infection in AIDS patients, particularly in South America.
- Diagnosis is challenging in regions lacking specific Histoplasma antigen detection methods.
- Galactomannan (GM) antigen detection, typically used for invasive aspergillosis, exhibits cross-reactivity with Histoplasma capsulatum.
Purpose of the Study:
- To evaluate the utility of galactomannan (GM) antigen detection as a diagnostic marker for disseminated histoplasmosis in AIDS patients.
- To assess the performance of GM detection in serum samples from an endemic region (French Guiana).
Main Methods:
- Serum samples from 39 AIDS patients with confirmed disseminated histoplasmosis and HIV-positive controls without histoplasmosis were tested.
- Galactomannan (GM) antigen detection and Histoplasma-specific antibody detection (Immuno-electrophoresis, IEP) were performed.
- Performance metrics (sensitivity, specificity, likelihood ratios) were calculated for GM detection at different thresholds.
Main Results:
- Histoplasma-specific antibody detection (IEP) showed low sensitivity (35.9%) in proven disseminated histoplasmosis cases.
- GM detection achieved 76.9% sensitivity and 100% specificity at the standard 0.5 threshold for aspergillosis.
- Optimized at a 0.4 threshold, GM detection demonstrated improved sensitivity (82%) with 100% specificity.
Conclusions:
- Galactomannan (GM) antigen detection serves as a reliable surrogate marker for diagnosing disseminated histoplasmosis in AIDS patients.
- This diagnostic approach is particularly valuable in endemic areas where specific Histoplasma antigen enzyme immunoassays (EIA) are unavailable.
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