Mycology - True Pathogens (Systemic Infections) Flashcards
What common characteristics do the fungi that cause systemic infections share?
- They are all caused by endemic, dimorphic fungi
- Most are restricted to a particular geographical area (endemic)
- Grow in a filamentous, saprobic form in nature
- Mode of infection is through inhalation
- Diseased person is not infectious: spores that are inhaled are converted into yeast in the body, they do not form filaments and cannot germinate and form new spores.
- The disease depends upon the dose and the immune status of the infected individual
- Chronic cases develop granulomatous lesions; can primarily form in the lungs, or at a disseminated site
BHPC
What types of systemic fungal infections are their based on their causative pathogen? [4]
- Blastomycosis- Blastomyces dermatitidis
- Histoplasmosis- Histoplasma capsulatum
- Coccidioiomycosis- Coccidioides immitis
- Paracoccidioidomycosis- Paracoccidioides brasiliensis
Outline the habitat and mode of infection of Blastomyces dermatitidis.
- Habitat: soil and organic debris, endemic in South-eastern USA Ohio-Mississippi River valley, and Africa.
- Mode of Infection: inhalation of conidia (99%), inoculation of conidia (1%), no patient to patient transmission, not common (1 or 2/100K people per year)
- Sprobic phase (25ºC) has septate mycelium and conidium, and parasitic phase (37ºC) yeast form seen in tissue (large, broad-based budding yeast, thick double-contoured wall. Pictured)
Outline the pathogenesis and virulence factors of Blastomyces dermatitidis.
- Pathogenesis: inhaled conidia convert to yeast, invasion of the host initiates inflammation, yeast escapes recognition of macrophages and may disseminate through the blood stream. Chronic, suppurative (pus forming) and granulomatous inflammation in chronic cases.
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Putative (widely recognised) virulence factors:
- Growth at 37ºC
- Dimorphic
- Adhesin (BAD-1) promotes the binding of yeasts to macrophages
- BAD-1 expression by yeasts also suppresses TNF-alpha pro-inflammatory cytokine expression
- High levels of alpha-(1, 3)-glucan on cell walls is associates with virulence (not recognised by innte immune system)
What diseases are caused by Blastomyces dermatitidis (blastomycoses)?[4]
Severity and course of disease depends on the immune status and the level of exposure to B. dermatitidis. Less than half of infected persons show symptoms.
- Primary pulmonary blastomycosis: mild and difficult to diagnose, flu-like symptoms
- Advanced pulmonary disease: occasionally develops, frequently resembles tuberculosis (high fever, cough, lobar infiltrates), ARDS may occur.
- Primary skin lesion: uncommon
- Disseminated blastomycosis: chronic cutaneous- result of haematogenous dissemination from the lung (bone, prostate, liver, GI tract)
Outline the symptoms, diagnosis, and treatment of Blastomyces dermatitidis infection.
- Symptoms of chronic disease: anorexia, weight loss, cough, haemoptysis, night sweats, cutaneous ulcerations, osteomyelitis of long bones
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Diagnosis:
- Specimen collection: sputum, bronchoalveolar lavage, pus, biopsy, urine
- Microscopy: thick walled, double contour single bud yeast
- Culture: 4 weeks, 25ºC observe hyphae and conidia, 37ºC double contour budding yeast
- Serological test: complement fixation test (not sensitive), immunodiffusion (specific).
- Treatment: itraconazole (mild pulmonary), AmB (advanced disseminated), variconazole (effective, less side effects).
What pathogen causes histoplasmosis?
Histoplasma capsulatum
What pathogen causes blastomycosis?
Blastomyces dermititidis
Outline Histoplasma capsulatum infection. (including habitat, mode of transmission, and pathogenesis)
Hisoplasmosis is a self-limiting pulmonary infection, primary histoplasmosis occasionally developing into chronic pulmonary disease and disseminated infection. It infects and resides inside phagocytic cells.
- Habitat: Eastern USA, most of Latin America, parts of Asia, Europe. Found in soil enriched with bird and bat droppings (blackbird and bat habitats, and chicken houses)
- Either inhaled (most cases) or inoculated conidia
- Pathogenesis: inhaled conidia from excreta contaminated soil, conidia convert into yeasts in the lung. The conidia are ingested by phagocytes, some survive and convert to yeast and proliferate in the phagosomes, while others remain dormant.
- Establishes a focal lesion in the lung, which elicits a granulomatous response
- Yeast resides in phagocytes and disseminates lymphohaematogenously to liver, spleen, bone marrow, and occasionally the kidney, adrenal glands and intestine.
Outline the virulence factors Histoplasma capsulatum.
- Growth at 37ºC
- Thermal dimorphism
- Survival in macrophages
- Modulation of pH of phagosome between 6-6.5
- Iron and calcium uptake through channels
- Cell wall composition- high levels of alpha-(1 ,3)-glucan that isnt recognised by the innate immune system
(Granuloma in picture)
Outline the clinical manifestations of Histoplasma capsulatum.
- Asymptomatic: 90% cases, low exposure
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Symptomatic:
- Acute pulmonary histoplasmosis: flu-like symptoms lasting weeks
- Chronic pulmonary disease: productive cough, shortness of breath, anorexia, weight loss, x-ray shows ‘snowstorm’ appearance
- Disseminated disease: liver, spleen, bone marrow, and occasionally kidneys and adrenal glands.
Acute disseminated histoplasmosis is fatal if left untreated.
Outline the diagnosis and treatment of histoplasmosis.
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Diagnosis:
- Specimen: sputum, BAL, bone marrow, peripheral blood, gastric wash, biopsy
- Culture: 25ºC, 4 weeks (mycelial phase, ‘morning stars’), at 37ºC yeast form.
- Serological tests: complement fixation tests (antigen from mycelium or yeast, titre >1:1332), immunodiffusion test (H band: acute infection, M band: past or present infection)
- Urine ELISA for histoplasmin antigen
- Treatment: itraconazole (mild), AmB followed by itraconazole (severe)
Pictured: morning stars
Outline coccidioidomycosis.
- Occurs as either an acute, benign, self-limiting disease of the lung, or a chronic disseminated disease involving the skin, bone, and viscera.
- Caused by Coccidioides immitis/C. posasasii
- Dimorphic fungi found in soil, growth enhanced on bird and bat droppings
- The filamentous form produces athroconidia (saprobic phase) that can be inhaled. In the body these conidia enlarge and form spherules
- Epidemiology: SW USA, Mexico, Central America, south America, up to 90% in endemic area have positive skin test
Outline the lifecycle of Coccidioides immitis.
Outline the pathogenesis and virulence factors of Coccidioides immitis.
- Pathogenesis: inhaled conidia reach alveoli and produce a proteinase to break down collagen and elastin, IgG and IgA. Converts to a spherule (20-40μm) giving rise to endospores that are phagocytised, but survive. Large spherules can escape phagocytosis. Generating an alkaline environment allows survival in the phagosome.
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Virulence factors:
- Growth at 37ºC
- Conidia resistant to phagocytic degradation
- Stimulation of ineffective Th2 response
- Extracellular protease production
List the manifestations of Coccidioides immitis infections. [2]
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Primary coccidioidomycosis
- Over half of cases are asymptomatic
- Few cases develop fever, cough, malaise, arthralgias (joint pain), erythema multiformis (skin condition)
- Chest X-rays usually negative, but may show hilar adenopathy (enlarged lung lymph nodes)
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Secondary coccidioidomycosis (>6 weeks)
- Nodules, cavitary disease, progressive pulmonary disease
- Disseminated cases: skin, bone, brain (meningitis)
Outline the diagnosis and treatment of Coccidioidomycosis.
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Diagnosis:
- Specimen collection: sputum, pus, gastric wash, bronchial wash, biopsy.
- Parasitic phase: spherules and endospores in biopsy and clinical specimen. No true yeast form in lesion.
- Culture: white compact colony, septate hyphae and athroconidia
- Athroconidia: barrel shaped, alternate pattern.
- Treatment: fluconizol/itraconazol (mild), AmB (severe)
What is the causative pathogen for coccidioidomycosis?
Coccidioides immitis and C. posadasii
What is the causative pathogen for paracoccidioidomycosis?
Paracoccidioides brasiliensis
Outline paracoccidioidomycosis.
- Caused by Paracoccidioides brasiliensis
- Saprobic phase: septate hyphae, conidia; parasitic phase: yeast with multiple buds
- Habitat: soil and vegetation, Central and South America
- Infection through inhalation of conidia, inoculation is rare.
Outline the pathogenesis of Paracoccidioides brasiliensis.
Conidia are inhaled and convert to large, multi-polar budding yeast, which are then ingested by macrophages (but not cleared). Can lie dormant for up to 40 years in latent infection, and can disseminate to oral and nasopharyngeal mucosa.
Can lead to granulomas. Air bubble appearance.
What are the clinical manifestations of paracoccidioidomycosis infections?
- Prolonged latent infection
- Primary lesion in lung
- Mucocutaneous and cutaneous ulcers are the prominents features
- Regional lymph nodes and reticuloendothelial organs may be involved
- Single or multiple organs involved.
Outline the diagnosis, virulence factors, and treatment of paracoccidioidomycosis infections.
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Virulence factors:
- growth at 37ºC
- Thermal dimorphism
- Intracellular survival
- Alteration of cell wall
- Ineffective Th2 response
- Diagnosis: history, immunodiffusion test, microscopic examination, biopsy, culture of specimens.
- Treatment: AmB, sulphonamide-trimethorpin, itraconazole.
