Pulmonary Fungal Infection 2: Opportunistic Mycoses Flashcards
What is the most important predisposition for opportunistic mycoses?
prolonged neutrpenia (infections, aplastic anemia, arsenic poisoning, cancer, chemo- or radiation therapy, medications, hereditary disorders, vitamin deficiency, autoimmunity, hemodialysis, splenic sequestration)
Cryptococcosis
How many serotypes?
Where is it found?
What does it look like?
Cryptococcus neoformans and C. gattii form 5 serotypes
Cryptococcosis, esp cryptococcal meningitis
C. neoformans is environmental, found worldwide in soil contaminated w/ bird droppings, esp pigeon
C. gattii is found in litter under eucalyptus trees, causes less severe disease but prefers immunocompetent hosts (West Coast)
Oval yeasts w/ narrow-based buds and wide polysaccharide capsule
Cryptococcosis: organisms
Thermally dimorphic?
Human-to-human transmission?
Has the caseload increased?
Pathogenic strains grow at 37C
Not thermally dimorphic; does have a moldlike sexually reproducing form in environment called Filobasidiella neoformans
No human-to-human transmission except organ transplantation or needle sticks (causes localized cutaneous disease)
Cryptococcal meningitis was extremely rare prior to 1946. Use of steroids, survival w/ malignancy, and AIDS have dramatically increased caseload.
Disseminated disease was inevitably fatal prior to Amphotericin B (1968)
Cryptococcosis: pathogenesis
How is it transmitted?
How does an immunocompetent host respond?
What predisposing to dissemination?
Does C. neoformans raise an inflammatory response?
What are the virulence factors?
Transmitted by inhalation: pigeon droppings may be contagious for years
Lung infection may be asymptomatic or lead to pneumonia
Can be intracellular infection in alveolar macrophages
Immunocompetent hosts restrict infection to lungs
Successful host raises Helper Ts, skin test conversion, antibodies to capsule
Deficient CMI, esp AIDS, is predisposing but not required for dissemination
Dissemination leads to cryptococcal meningitis w/ skin nodules
C. neoformans raises very little inflammatory response or granuloma formation – organ damage is by tissue distortion from growing yeast
Virulence factors: capsule, melanin in cell wall (antiphagocytic), Phospholipase B for invading tissue
Cryptococcosis: Diagnosis: Exam
What would the Hx look like?
What would the meningitis look like?
History: steroid use, malignant disease, transplantation, HIV infection
Skin: Take biopsies of nodules
Pulmonary: range from asymptomatic to ARDS, cough and chest pain common
Cryptococcus + HIV: fever, cough, headache, weight loss, positive cultures from blood, CSF, and urine
CNS: subacute meningitis or meningoencephalitis, antifungal therapy required for survival. Perform CT and/or MRI
Meningitis: Headache, altered mental status, nausea and vomiting.
Fever and stiff neck are less common (arise from inflammation). May also be sensory issues w/ eyes or ears. If not acute pyogenic, may wait for CT/MRI results before lumbar puncture
Cryptococcomas: focal neurologic defects
May also be symptoms in prostate, eyes, medullary cavity of bones.
Blunted inflammatory response complicates diagnosis and means that presentation is late in disease
Cryptococcosis Diagnosis Lab
How do you stain?
CSF: stain w/ India ink to observe yeast w/ wide capsule
Biopsies: Stain w/ methenamine silver, periodic acid-Schiff, mucicarmine
Culture at 37C from CSF, blood, urine, sputum for mucoid colonies on Sabouraud agar, will produce melanin in culture on special media
Serology: “crag” for cryptococcal antigen in blood and CSF
Routine bloodwork may be normal (no inflammation)
Cryptococcosis tx
Meningitis or cryptococcoma: Amphotericin B (liposomal if kidney issues) plus flucytosine for 2 weeks followed by 10 more weeks of fluconazole
In AIDS patients, use fluconazole for long-term suppression: clearance may not be an option.
Prostate: Fluconazole
Pulmonary cryptococcosis in immunocompetent patients may not need treatment; can use 6-12mo fluconazole or itraconazole
Skin, bones, other: Amphotericin B
Examine CSF weekly to determine progress; glucose and cell count will return to normal but protein anomalies may persist for years. Do not discontinue therapy until cultures consistently fail.
Aspergillosis
Dimorphic?
What does it look like?
Where is it found?
What is infectious?
Where does it colonize?
What is a normal macrophage response? What can the Aspergillus do?
Ubiquitous environmental molds
Only mold, not dimorphic
Septate hyphae w/ V-shaped branches
Walls are nearly parallel
Conidia form radiating chains
Widespread on decaying vegetation worldwide
Infectious conidia are airborne
Conidia colonize abraded skin, burns, cornea, ear, sinuses, lung
Healthy macrophage and neutrophil response eradicates fungus, but some Aspergillus produce toxic metabolites that inhibit it, so do corticosteroids
Syndromes associated with aspergillosis
ABPA
Diagnostic characteristics
hypersensitivity reaction to infection of bronchi by aspergillus. Found in 1-10% of asthmatics, 7% of CF patients : exacerbates
▪ Positive skin test for Aspergillus allergy with asthma or CF
▪ Coughing up brownish bronchial plugs containing hyphae
▪ Fever, wheezing & pulmonary infiltrates unresponsive to antibiotics
▪ Hemoptysis
▪ Uncontrolled asthma
▪ Purulent sinus drainage
▪ Xray or CT may show “grape cluster” or “hand in mitten” clusters of mucus-clogged bronchi
Syndromes associated with aspergillosis
Aspergilloma
Fungus ball forms when aspergillus invades cavitary pulmonary lesions of TB, CF. Associated hemoptysis may be life-threatening.
▪ Fungus ball is visible on X-ray or CT (a mass in a cavity), changes position when patient sits up / lies down
▪ Does not invade tissue but may cause dangerous hemoptysis
▪ Cough, fever
▪ May appear as a complication of chronic necrotizing pulmonary aspergillosis or invasive aspergillosis
Syndromes associated with aspergillosis
Chronic necrotizing pulmonary aspergillosis (CNPA)
Diagnosis
In immunocompromised, can invade lungs, causing pneumonia w/ hemoptysis and granulomas (chronic necrotizing pulmonary aspergillosis). May find hyphae in granulomas. Rare, hard to diagnose, often found at autopsy. 10-100% mortality.
▪ Subacute pneumonia unresponsive to antibiotics
▪ Underlying disease of alcoholism, collagen-vascular disease, chronic granulomatous disease or COPD (chronic obstructive pulmonary disease) with long-term corticosteroid therapy
▪ Fever, cough, night sweats, weight loss
▪ History of ineffective empiric treatment for TB
▪ Needle biopsy, aspirate fluid if present, for histo and culture
Syndromes associated with aspergillosis
Invasive aspergillosis
Diagnosis
Rapidly progressive invasion of blood vessels in severely immunosuppressed patients, involves infarction, hemorrhage, necrosis, often fatal (30-95%). Relatively common in severely immunosuppressed patients (5-20%).
History of profound immunosuppression or COPD with long-term corticosteroid therapy
▪ Fever, cough, dyspnea, pleuritic chest pain, neutropenia, sometimes hemoptysis, worsening hypoxemia.
▪ Chest Xray is abnormal but variable.
▪ CT scan may show characteristic halo sign: ground-glass infiltrate surrounding a nodular density. Represents a hemorrhage; invasive aspergilliosis is most common cause.
▪ Bronchoscopy, needle biopsy, or open lung biopsy for culture and histology
Aspergillosis Virulence fators
Gliotoxin: immunosuppressive
Toxic metabolites interfere with phagocytosis and opsonization
Proteases may be involved in tissue invasion
Aspergillosis: Diagnosis Lab
Cultures from sputum, needle biopsy, or bronchoalveolar lavage fluid:
Visualize w/ silver stains
Colonies w/ radiating chains of conidia
Invasive: Septate hyphae branching at acute angles invading tissue Acute inflammatory infiltrate Tissue necrosis Blood vessel invasion High serum levels of glactomannan antigen
ABPA:
High levels of aspergillus-specific IgE, eosinophilia
Mucus with degenerating eosinophils and hyphae
Aspergillosis Treatment
ABPA
▪ Oral corticosteroids and itraconazole
▪ Consider sinus surgery and/or omalizumab (Xolair)
Aspergilloma
▪ Remove surgically if hemoptysis
▪ Oral itraconazole
Invasive or CNPA
▪ Voriconazole and/or amphotericin B, liposomal if kidney issues, alt capsofungin, but may not work.
▪ Decrease immunosuppression if possible.
▪ Surgical resection of diseased area may be considered
