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Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
Published on: February 14, 2011
Development and evaluation of an enzyme-linked immunosorbent assay to detect Histoplasma capsulatum antigenuria in
Christina M Scheel1, Blanca Samayoa, Alejandro Herrera
1Division of Foodborne, Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Mailstop G-11, Atlanta, GA 30333, USA. cscheel@cdc.gov
Abstract:
Histoplasma capsulatum infection causes significant morbidity and mortality in human immunodeficiency virus-infected individuals, particularly those in countries with limited access to rapid diagnostics or antiretroviral therapies. The fungus easily disseminates in persons with AIDS, resulting in progressive disseminated histoplasmosis (PDH), which can progress rapidly to death if undiagnosed. The availability of a simple, rapid method to detect H. capsulatum infection in less developed countries where the infection is endemic would dramatically decrease the time to diagnosis and treatment of PDH. We have developed an antigen-capture enzyme-linked immunosorbent assay (ELISA) to detect PDH antigenuria in infected patients. The assay uses polyclonal antibodies against H. capsulatum as both capture and detection reagents, and a standard reference curve is included to quantify antigenuria and ensure reproducibility. We evaluated this assay using specimens collected from patients with AIDS and culture-proven histoplasmosis in a Guatemalan clinic (n = 48), from healthy persons (n = 83), and from patients with other, nonhistoplasmosis diseases (n = 114). The ELISA demonstrated a sensitivity of 81% and a specificity of 95% in detecting H. capsulatum antigen in urine. This assay relies on simple technology that can be performed in institutions with limited resources. Use of this test will facilitate rapid diagnosis of PDH in countries where mortality is high, expediting treatment and likely reducing PDH-related mortality.
Insights
A new enzyme-linked immunosorbent assay (ELISA) detects Histoplasma capsulatum antigen in urine, aiding rapid diagnosis of progressive disseminated histoplasmosis (PDH) in HIV-infected individuals, especially in resource-limited settings.
Area of Science:
- Mycology
- Infectious Diseases
- Immunology
Background:
- Histoplasma capsulatum infection causes severe illness and death in individuals with HIV/AIDS, particularly in regions with limited diagnostic and treatment access.
- Progressive disseminated histoplasmosis (PDH) can rapidly become fatal if not diagnosed and treated promptly.
- There is a critical need for simple, rapid diagnostic tools for H. capsulatum infection in resource-limited endemic areas.
Purpose of the Study:
- To develop and evaluate a rapid antigen-capture enzyme-linked immunosorbent assay (ELISA) for detecting H. capsulatum antigenuria.
- To provide a tool for early diagnosis of PDH in settings with limited resources.
Main Methods:
- Development of a polyclonal antibody-based antigen-capture ELISA to detect H. capsulatum antigen in urine.
- Inclusion of a standard reference curve for quantitative antigenuria measurement and assay reproducibility.
- Evaluation of the ELISA using urine samples from patients with AIDS and histoplasmosis (n=48), healthy individuals (n=83), and patients with other diseases (n=114) in Guatemala.
Main Results:
- The developed ELISA demonstrated a sensitivity of 81% and a specificity of 95% for detecting H. capsulatum antigen in urine.
- The assay utilizes simple technology suitable for resource-limited healthcare facilities.
Conclusions:
- The antigen-capture ELISA is a promising tool for the rapid diagnosis of PDH in HIV-infected individuals in endemic countries.
- This assay can expedite treatment initiation, potentially reducing PDH-related mortality in areas with high incidence and limited healthcare infrastructure.

