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Performance of Diagnostic Tests for Histoplasmosis Across Clinical Syndromes and Immune Statuses

Nicolas Barros1,2, Mitch McClean1, Elisa Sarmiento1

  • 1Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Open Forum Infectious Diseases
|November 24, 2025
PubMed
Abstract

Insights

Histoplasma antigen testing is the most sensitive diagnostic method for histoplasmosis. Antibody testing offers complementary value, especially in immunocompetent individuals, while cultures remain less sensitive.

Area of Science:

  • Medical Mycology
  • Infectious Diseases
  • Diagnostic Microbiology

Background:

  • Histoplasmosis, caused by *Histoplasma capsulatum*, exhibits a wide clinical spectrum, ranging from asymptomatic infection to disseminated disease.
  • Current diagnostic methods, including culture, histopathology, antigen detection, and serologic testing, possess variable performance characteristics.
  • Evaluation of diagnostic test performance across diverse clinical presentations and patient immune statuses is crucial for effective management.

Purpose of the Study:

  • To evaluate the sensitivity and specificity of various diagnostic modalities for histoplasmosis.
  • To compare the performance of antigen detection and antibody testing in different patient populations.
  • To determine the optimal diagnostic strategy for histoplasmosis.

Main Methods:

  • Retrospective diagnostic study involving adults tested for *Histoplasma* antigen.
  • Classification of patients as histoplasmosis (proven/probable) or controls based on EORTC/MSG criteria.
  • Assessment of antigen enzyme immunoassay (EIA), antibody EIA (IgG/IgM), immunodiffusion (ID), complement fixation (CF), and fungal cultures.

Main Results:

  • *Histoplasma* antigen EIA demonstrated high sensitivity (97.6%) and specificity (93.7%).
  • Antibody EIA sensitivity was 80.2%, with reduced performance in immunocompromised patients (75.0% vs. 93.3%).
  • Combined antigen and antibody testing achieved 99.1% sensitivity; antigen testing alone was highly effective.

Conclusions:

  • *Histoplasma* antigen testing is the most sensitive diagnostic method.
  • Antibody testing serves as a valuable adjunct, particularly in immunocompetent patients with pulmonary disease.
  • Fungal culture remains a complementary diagnostic tool but is less sensitive than antigen detection.
Keywords:
antibodyantigendiagnosishistoplasmahistoplasmosis

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