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Paracoccidioidomycosis: an update
E Brummer1, E Castaneda, A Restrepo
1Department of Medicine, California Institute for Medical Research, Santa Clara Valley Medical Center, San Jose 95128.
Abstract:
This review summarizes knowledge on various aspects of paracoccidioidomycosis. Mycelial propagules, chlamydospores, and arthroconidia exhibit thermal dimorphism; arthroconidia are infectious in animals and, by electron microscopy, appear well provided for survival. The mycelial-to-yeast-phase transformation requires a strict control of glucan synthesis probably mediated by membrane enzymes. Hormonal influences on the transformation of the fungus (mycelium or conidium to yeast phase) have been demonstrated. Estrogen-binding proteins have been detected in the fungal cytosol, and during the transformation novel proteins are produced as a result of estradiol incorporation. Clinical forms have been better defined on the basis of better experimental models. Emphasis has been placed on the lungs as the portal of entry and on the existence of silent pulmonary infections. A specific Paracoccidioides brasiliensis antigen, the 43-kDa glycoprotein (Gp43), has been identified, characterized, and cloned. This has led to improved reproducibility and specificity of serologic tests. The depression of cell-mediated immune responses has been associated with severe disease in humans and in the experimental host. T-cell subsets in patients' tissues were characterized by means of monoclonal antibodies, and a reduced CD4/CD8 ratio was demonstrated. This has been related to alterations in lymphokine and tumor necrosis factor production, production of antigen-antibody complexes, etc. Amphotericin B has provided effective therapy. Azole derivatives have also improved prognosis and facilitated therapy. Itraconazole is presently the drug of choice, yet incapacitating sequelae (mainly pulmonary fibrosis) still constitute major problems.
Insights
This review details paracoccidioidomycosis, focusing on fungal dimorphism, host immune responses, and diagnostic advancements. It highlights challenges in treating this serious fungal infection, particularly pulmonary fibrosis.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Paracoccidioidomycosis is a systemic fungal infection caused by Paracoccidioides brasiliensis.
- The fungus exhibits thermal dimorphism, transitioning between mycelial and yeast phases, with yeast forms being infectious.
Purpose of the Study:
- To review current knowledge on paracoccidioidomycosis, encompassing fungal biology, host-pathogen interactions, diagnostics, and therapeutics.
- To highlight advancements in understanding the disease, including the identification of key antigens and immune response alterations.
Main Methods:
- Review of existing literature on paracoccidioidomycosis.
- Analysis of fungal dimorphism, hormonal influences, and immune responses.
- Evaluation of diagnostic tools and therapeutic strategies.
Main Results:
- The 43-kDa glycoprotein (Gp43) antigen has been identified, aiding serologic test development.
- Severe disease is linked to depressed cell-mediated immunity and a reduced CD4/CD8 ratio.
- Itraconazole is the current drug of choice, though pulmonary fibrosis remains a significant sequela.
Conclusions:
- Understanding fungal dimorphism and host immunity is crucial for managing paracoccidioidomycosis.
- Diagnostic and therapeutic strategies have improved, but long-term complications persist.
- Further research is needed to address treatment challenges and sequelae like pulmonary fibrosis.