Pulmonary Talaromycosis: A Window into the Immunopathogenesis of an Endemic Mycosis.

Narayanasamy, Shanti

Dougherty, John

van Doorn, H Rogier

Le, Thuy

2021-08-18T18:10:25Z

2021-08-18T18:10:25Z

2021-07-06

2021-08-18T18:10:23Z

Talaromycosis is an invasive mycosis caused by the thermally dimorphic saprophytic fungus Talaromyces marneffei (Tm) endemic in Asia. Like other endemic mycoses, talaromycosis occurs predominantly in immunocompromised and, to a lesser extent, immunocompetent hosts. The lungs are the primary portal of entry, and pulmonary manifestations provide a window into the immunopathogenesis of talaromycosis. Failure of alveolar macrophages to destroy Tm results in reticuloendothelial system dissemination and multi-organ disease. Primary or secondary immune defects that reduce CD4⁺ T cells, INF-γ, IL-12, and IL-17 functions, such as HIV infection, anti-interferon-γ autoantibodies, STAT-1 and STAT-3 mutations, and CD40 ligand deficiency, highlight the central roles of Th1 and Th17 effector cells in the control of Tm infection. Both upper and lower respiratory infections can manifest as localised or disseminated disease. Upper respiratory disease appears unique to talaromycosis, presenting with oropharyngeal lesions and obstructive tracheobronchial masses. Lower respiratory disease is protean, including alveolar consolidation, solitary or multiple nodules, mediastinal lymphadenopathy, cavitary disease, and pleural effusion. Structural lung disease such as chronic obstructive pulmonary disease is an emerging risk factor in immunocompetent hosts. Mortality, up to 55%, is driven by delayed or missed diagnosis. Rapid, non-culture-based diagnostics including antigen and PCR assays are shown to be superior to blood culture for diagnosis, but still require rigorous clinical validation and commercialisation. Our current understanding of acute pulmonary infections is limited by the lack of an antibody test. Such a tool is expected to unveil a larger disease burden and wider clinical spectrum of talaromycosis.

10.1007/s11046-021-00570-0

0301-486X

1573-0832

https://hdl.handle.net/10161/23595

eng

Springer Science and Business Media LLC

Mycopathologia

10.1007/s11046-021-00570-0

Cavitation

Effusion

Nodule

Respiratory tract

Talaromyces marneffei

Talaromycosis

Pulmonary Talaromycosis: A Window into the Immunopathogenesis of an Endemic Mycosis.

Journal article

Narayanasamy, Shanti|0000-0002-6667-2868

Le, Thuy|0000-0002-3393-6580

School of Medicine

Molecular Genetics and Microbiology

Duke Global Health Institute

Medicine, Infectious Diseases

Duke

Basic Science Departments

University Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Clinical Science Departments

Staff

Published