An interferon gamma release assay specific for Histoplasma capsulatum to detect asymptomatic infected individuals: A proof of concept study

ABSTRACT : Histoplasmosis is the most common endemic mycosis in the Americas. Currently, there is no laboratory test capable to detect subclinical or latent infections by Histoplasma capsulatum (Hc), which might develop as severe infections in immunocompromised individuals. For the first time to our...

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Autores:
Rubio Carrasquilla, Marcela
Santa Escobar, Cristian David
Rondón Marín, Juan Pablo
Botero Garcés, Jorge Humberto
Guimaraes, Allan J.
Moreno Frias, Ernesto
Cano Restrepo, Luz Elena
Tipo de recurso:
Article of investigation
Fecha de publicación:
2018
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/26552
Acceso en línea:
http://hdl.handle.net/10495/26552
Palabra clave:
Antígenos Fúngicos
Antigens, Fungal
Histoplasmosis
Histoplasma
Histoplasmosis
Ensayos de Liberación de Interferón gamma
Interferon-gamma Release Tests
Valor Predictivo de las Pruebas
Predictive Value of Tests
Prueba de Estudio Conceptual
Proof of Concept Study
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc/2.5/co/
Description
Summary:ABSTRACT : Histoplasmosis is the most common endemic mycosis in the Americas. Currently, there is no laboratory test capable to detect subclinical or latent infections by Histoplasma capsulatum (Hc), which might develop as severe infections in immunocompromised individuals. For the first time to our knowledge, we explore the suitability of an interferon gamma release assay (IGRA) to detect latent Hc infection in asymptomatic individuals. A cohort of 126 volunteers was enrolled in the study, 13 of which underwent a Hc infection in the past, and 93 of them showing risk factors for this infection. The remaining 20 participants did not refer any risk factors of Hc infection, but eight of them showed evidences of infection with Mycobacterium tuberculosis. All participants were recruited in Medellin, Colombia, between January 2014 and December 2017. Whole blood samples were cultured with four different Hc crude antigens and phytohemaglutinin as positive control. The interferon (IFN)-γ released by T lymphocytes upon antigen stimulation was quantified by ELISA. A defined cutoff value of 20 pg/ml for the IFN-γ concentration allowed us to distinguish between the group with documented past infections and the group of noninfected individuals with high sensitivity (70– 92%) and specificity (85–95%), for the four tested antigens. Positive 82–95% and negative 77–92% predictive values were also very high, comparable to those reported for commercially available IGRAs. The new test constitutes a promising screening method to detect individuals with latent Hc infection, even decades after the primary infection, as evidenced in this study.