Aspergillosis

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Morphology & Species - Fungal ID Parade

  • Ubiquitous saprophytic molds.
  • Key Species:
    • Aspergillus fumigatus (most common)
    • A. flavus (aflatoxin)
    • A. niger (otomycosis, "salt & pepper")
    • A. terreus (amphotericin B resistant)
  • Microscopic Features:
    • Septate hyphae.
    • Acute angle (approx. 45°) dichotomous branching. 📌 A for Acute Angle.
    • Conidiophore structure: foot cell → vesicle → phialides → chains of conidia. Aspergillus morphology: hyphae, conidiophore, colony

Aspergillus fumigatus is the most common species causing human aspergillosis, known for its thermotolerance (can grow at >37°C).

Pathogenesis & Virulence - Spore Invasion Secrets

  • Entry: Inhalation of Aspergillus conidia.
  • Host Factors (↑ Susceptibility): Neutropenia (<500/μL), corticosteroid therapy, Chronic Granulomatous Disease (CGD), immunosuppression.
  • Virulence Factors:
    • Adhesion: Hydrophobins on conidia aid attachment.
    • Survival: Thermotolerance (growth at 37°C); Catalase (resists oxidative stress); Melanin (protects from host defenses, ROS).
    • Damage & Spread: Gliotoxin (immunosuppressive, pro-apoptotic); Proteases (elastase, collagenase for tissue invasion).
    • Toxin: Aflatoxins (produced by A. flavus, carcinogenic).

Aspergillus conidia inhalation and immune response

⭐ Angioinvasion is a hallmark of Invasive Aspergillosis, leading to tissue infarction and necrosis.

Clinical Syndromes - Aspergillus' Disease Faces

SyndromeHostKey FeaturesDiagnostic Clues
ABPAAsthma, Cystic FibrosisType I & III hypersensitivity, eosinophilia, fleeting pulmonary infiltrates↑ Total IgE (>1000 IU/mL), Aspergillus specific IgE/IgG, central bronchiectasis (CT)
AspergillomaPre-existing lung cavity (e.g., TB, sarcoid)Fungus ball (colonization), often asymptomatic; hemoptysisMobile intracavitary mass on imaging ("Monod sign")
Invasive (IA)Severely Immunocompromised (neutropenia)Angioinvasion, thrombosis, infarction, necrosis; fever, pneumonia, disseminatedHalo sign, air-crescent sign (CT chest); +ve galactomannan, β-D-glucan; biopsy for definitive diagnosis
  • Cutaneous Aspergillosis: Primary (direct inoculation at trauma sites) or secondary (hematogenous spread in IA) skin lesions (e.g., necrotic ulcers).

Aspergilloma on chest X-ray and CT scan

⭐ The 'halo sign' (ground-glass opacity surrounding a nodule) on CT chest is an early, albeit non-specific, sign of Invasive Aspergillosis in neutropenic patients.

Diagnosis - Unmasking the Culprit

  • Microscopy: Direct (KOH, Calcofluor); Histopathology (GMS, PAS) shows septate hyphae, acute-angle branching.

  • Culture: Sabouraud Dextrose Agar (SDA) - rapid growth, species-specific colonies.
  • Antigen Detection:
    • Galactomannan (GM) assay (Serum/BAL): Crucial for Invasive Aspergillosis (IA). Index >0.5 often positive.
    • (1→3)-β-D-Glucan (BDG): Panfungal.
  • Antibody Detection: IgG/IgE (ABPA, CPA).
  • Molecular: PCR for Aspergillus DNA.
  • Imaging: CXR; CT (halo/air-crescent signs in IA; aspergilloma).

⭐ Detection of Galactomannan antigen in serum or bronchoalveolar lavage (BAL) fluid is a cornerstone in the early diagnosis of Invasive Aspergillosis.

Treatment - Mold Combat Plan

Voriconazole is the primary drug of choice for the treatment of Invasive Aspergillosis, demonstrating superior efficacy over Amphotericin B in pivotal trials.

High‑Yield Points - ⚡ Biggest Takeaways

  • Aspergillus fumigatus is the most frequent species.
  • Key morphology: Septate hyphae with acute angle (45°) dichotomous branching.
  • Allergic Bronchopulmonary Aspergillosis (ABPA): Associated with asthma/CF, ↑IgE, eosinophilia.
  • Aspergilloma: Fungus ball in pre-existing lung cavities (often post-TB).
  • Invasive Aspergillosis: Seen in immunocompromised (especially neutropenia); characterized by angioinvasion.
  • Diagnosis: Galactomannan antigen (serum/BAL) and β-D-glucan are important markers.
  • Voriconazole is the first-line treatment for invasive aspergillosis.

Practice Questions: Aspergillosis

Test your understanding with these related questions

On CT chest, the 'halo sign' is particularly associated with which condition in immunocompromised patients?

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Flashcards: Aspergillosis

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A _____ stain or culture gives physicians a definitive diagnosis in histoplasmosis, blastomycosis, coccidioidomycosis (fungal infections)

TAP TO REVEAL ANSWER

A _____ stain or culture gives physicians a definitive diagnosis in histoplasmosis, blastomycosis, coccidioidomycosis (fungal infections)

KOH

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