Respiratory Fungi Flashcards

1
Q

Systemic Mycoses

A

Histoplasma, Coccidiodes, Blastomyces, Paracoccidioides

  • Primary pathogens
  • Severe disease in immunocompromised hosts
  • Airborne/Environmental transmission
    • No person-to-person transmission
    • Starts in the lungs but frequently disseminates to viscera
  • Endemic to certain geographic areas
  • Dimorphic
    • Molds @ 25°C
    • Yeast or spherules @ 37°C
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2
Q

Histoplasma capsulatum

Characteristics

A
  • Causes Histoplasmosis
  • Dimorphic
    • Mold grows in soil w/ high N2 content
      • Bat and bird droppings promote growth
      • Filamentous septate hyphae
      • Produces spores ⇒ micro and macroconidia
        • Macroconidia = tuberculate chlamydospores
    • Yeast grows @ 37°C within Mφ
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3
Q

Histoplasma

Transmission

A

Inhalation of microconidia

(Asexual spores)

Causes histoplasmosis.

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4
Q

Histoplasmosis

Epidemiology

A

Ohio and Mississippi Valleys

&

Central and South America

Outbreaks associated with bird roosts, caves, urban renal projects involving excavation.

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5
Q

Histoplasmosis

Clinical Presentation

A
  1. Asymptomatic infection ⇒ 90%
  2. Flu-like sx ⇒ 5%
    • Fever, chills, malaise, HA, lymphadenopathy
  3. Some progress to pulmonary histoplasmosis ⇒ 1%
    • Cough, SOB
    • Resembles TB w/ caseating granulomas
  4. Progressive disseminated disease ⇒ 1%
    • Immunocompromised hosts
    • Found in 10-25% of AIDS pts living in endemic areas
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6
Q

Histoplasmosis

Pathogenesis

A

Disease manifestations depend on innoculum size & host immune status:

  • Microconidia enter lung
  • Converts to yeast form
  • Phagocytosis by alveolar MΦ
    • Replicate within MΦ
    • Facultative intracellular parasites
  • MΦ transport yeast to regional LN
  • Transient fungemia
    • Skin, liver, spleen common sites
    • Does not necessarily mean disseminated disease
    • Can be seen even with mild cases
  • T-cell sensitization ⇒ fungicidal activity of Tc & MΦ
    • Can take 6-8 weeks
  • Subsequent granuloma formation
    • Clinical picture frequently resembles TB
  • Resolution or progression
  • Possible reactivation when immunity wanes
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7
Q

Histoplasmosis

Diagnosis

A
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8
Q

Histoplasmosis

Treatment

A
  • Mild pulmonary disease
    • Self-limiting
    • No treatment
  • Severe acute pulmonary disease
    • Itraconazole
  • Systemic disease
    • Amphotericin B followed by oral itraconazole
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9
Q

Histoplasma vs Tuberculosis

A
  • Both histoplasmosis & TB
    • Primary pathogen w/ severe disease in immunocompromised
    • Facultative intracellular organisms
    • Infection by respiratory route
    • Pulmonary infection that can disseminate
    • Can detect infection by skin testing
    • Reactivation can occur
  • Mtb only ⇒ person to person transfer
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10
Q

Coccidioides immitis

Characteristics

A
  • Causes Coccidiomycosis
    • AKA Valley Fever or Desert Rheumatism
  • Most virulent of the mycoses
  • Dimorphic
    • Arthrospores grow in warm, alkaline soil
      • Barrel-shaped septate hyphae
      • Growth enhanced by bird droppings
    • Spherules containing endospores grow @ 37°C
      • Extracellular pathogens
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11
Q

Coccidioides

Epidemiology

A
  • Prefers soil of arid regions
    • San Joaquin Valley
    • Southwest US
    • Mexico and parts of Central and South America
  • Conditions that favor aerosols promote outbreaks
    • Cycles of heavy rain followed by draught
  • Warming trends leading to dispersal
  • 150k new infections/yr
  • 80% of longterm residents infected
  • Non-immune visitors/new residents at risk
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12
Q

Coccidioides

Transmission

A

Inhalation of arthrospores (arthroconidia)

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13
Q

Coccidioides

Risk Factors

A

High risk for chronic/disseminated disease:

  • > 65 y/o
  • HIV
  • 1st trimester of pregnancy
  • DM
  • Native Americans, Filipinos, African Americans, Hispanics
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14
Q

Coccidioides

Pathogenesis

A
  • Most virulent of systemic mycosis ⇒ only need a few for infection
  • Arthrospores (conidia) inhaled into mid-lung area
  • Temperature causes conversion into a large spherule w/ many small endospores
    • Extracellular pathogen
  • Spherule rupture releasing endospores ⇒ ± dissemination
  • Requires cell-mediated immunity to eradicate spherules
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15
Q

Coccidioides

Clinical Presentation

A
  • Asymptomatic ⇒ 50-60%
  • Flu-like illness ⇒ called Desert Rheumatism, Valley Fever, or Primary coccidiomycosis
    • Cough, CP, weight loss, arthralgia, skin rash
    • Can last for weeks to months
  • Severe/chronic pulmonary disease ⇒ 5-10%
    • Cavitary disease common
  • Disseminated disease ⇒ 1%
    • Also called chronic meningitis
    • Fatal if untreated
    • Requires lifelong treatment
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16
Q

Coccidioides

Diagnosis

A
  • Skin test ⇒ reactivity within 2 weeks
    • Anergy in disseminated disease
    • Indicates infection has occurred but not neccessarily responsible for present illness
  • Biopsy ⇒ spherule forms
  • Culture ⇒ mold forms
    • Sputum or tissue sample
    • Grown on Sabouraud’s agar
    • Takes 2-3 days
    • Lab acquired infections a problem
  • Serology
    • CSF ⊕ within 2-3 weeks
    • Rising titers after 2-3 months suggest dissemination
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17
Q

Coccidioides

Treatment

A
  • Most difficult of systemic mycoses to treat
  • Recurrent/relapse disease is common
    • Reinfection after successful treatment
  • 12-24 months of azole depending on severity
  • Amphotericin B for severe disease
  • Chronic meningitisamphotericin B then switch to azole for life
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18
Q

Blastomyces dermatitidis

Characteristics

A
  • Causes Blastomycosis
  • Morphology ⇒ dimorphic
    • Septate hyphae and asexual spores @ 25°C
    • Broad-based budding yeast cells @ 37°C
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19
Q

Blastomyces

Epidemiology

A
  • Endemic east of the Mississippi River
    • Esp. Arkansas, Kentucky, Louisiana, North Carolina, Tennessee, Mississippi
  • Spores grown in soil high in decaying organic matter
    • E.g. wooded areas
  • Outbreaks via occupational or recreational contact w/ soil
  • See disease commonly in 20-50 y/o males
20
Q

Blastomyces

Transmission

A

Inhalation of asexual spores

Natural disease in dogs and horses.

21
Q

Blastomyces

Pathogenesis

A
  • Inhaled conidia (asexual spores)
  • Yeast forms in lung within MΦ
  • See a mixed granulomatous & pyogenic response (abscess)
    • Similar to TB & bacterial PNA
  • Dissemination may involve skin and bone but is rare
    • Not a common opportunist in immunocompromised but causes severe disease when it occurs
  • Cell-mediated immunity critical but PMNs also play a role in clearing infection
  • Reactivation possible
22
Q

Blastomyces

Clinical Presentation

A
  • Asymptomatic to flu-like illness
  • Pulmonary form
    • Similar to bacterial PNA ⇒ infiltrates but no calcification
    • Cough and CP
  • Dissemination with or without pulmonary resolution
    • Skin, joints, bone, CNS
    • Ulcerative lesions of skin and bones
23
Q

Blastomyces

Diagnosis

A
  • ID organism in tissue
  • Culture - takes > 1 week
    • Mold form
    • Yeast form (broad-based budding yeast)
  • Ag based tests
24
Q

Blastomyces

Treatment

A

Treatment depends on severity of infection and host immune status.

Moderate disease ⇒ Azoles (Ketoconazole, itraconazole)

Disseminated disease ⇒ Amphotericin B

25
Q

Paracoccidioides brasiliensis

Characteristics

A
  • Causes South American Blastomycosis
  • Morphology ⇒ dimorphic
    • Septate hyphae @ 25°C
    • Yeast form grow in vivo @ 37°C
      • Multiple daughter cells off a single parent cell connected by a thin isthmus ⇒ blastoconidia
      • Seen in tissue and can be grown in culture
  • “Pilot wheel” morphology seen w/ GMS stain or H&E in tissue
26
Q

Paracoccidiodes brasiliensis

Epidemiology

A
  • Major systemic mycoses in Latin America > Central America
    • Highest incidence in Brazil
  • Mold form grows in areas of high humidity, rich vegetation, and acidic soil
    • Esp. along river banks in the Amazon
  • Common in rural areas
  • Children frequently infected but asymptomatic
  • Disease common in men 30-50 y/o
27
Q

Paracoccidioides brasiliensis

Transmission

A

Inhalation or traumatic inoculation of conidia.

Most have contact with soil.

28
Q

Paracoccidioides

Clinical Presentation

A
  • Primary disease
    • Usually asymptomatic or self-limiting
  • Adultsprimary or reactivation disease
    • Chronic pulmonary disease
      • Productive cough, weight loss, fever
    • Mucocutaneous forms
  • Juvenile form
    • Flu-like, lymphadenopathy, hepatosplenomegaly
  • Disseminated form
    • Young children and immunocompromised
29
Q

Paracoccidioides

Diagnosis

A
  • Demonstrate yeast form in tissue or sputum
    • “Pilot wheel” ⇒ yeast
    • Don’t confuse with tuberculate macroconidia of Histoplasma ⇒ spores
      • These won’t be found in tissue or sputum samples
  • Organisms grown in culture need biosafety cabinet
  • Serology ⇒ evaluate response to treatment
30
Q

Paracoccidioides

Treatment

A

Itraconazole for 6 months.

Severe infections may require Amphotericin B.

31
Q

Opportunistic Fungi

Overview

A
  • Class ⇒ Zygomycetes aka Mucormycetes
    • Order ⇒ Mucorales
      • Genera ⇒ Rhizopus, Mucor
  • Causes rare, sporadic disease worldwide
  • When they do occur ⇒ acute and rapidly progressive
    • Mortality rates of 70-100%
32
Q

Zygomycetes

Characteristics

A

“Mucormycetes”

  • Cause Mucormycosis
  • Molds that grow rapidly
  • Morphology
    • Broad hyphae w/ few or no septa
    • Asexual spores contained in sporangium ⇒ sporangiospores
    • Root-like structure called rhizoids
33
Q

Zygomycetes

Transmission & Epidemiology

A
  • Ubiquitous in soil and decaying matter worldwide
  • Transmission via spores
    • Inhalation, ingestion, or contamination of wounds
    • Nosocomial spread may occur through HVAC systems
      • Esp. near construction sites
  • Hospital outbreaks associated w/ contaminated dressings/tongue depressors
  • Causes invasive zygomycosis in immunocompromised pts and diabetics
34
Q

Zygomycosis

Risk Factors

A
  • Organ or BM transplant recipient
  • Diabetic ketoacidosis
  • Renal failure
  • Hematologic malignancy
  • Neutropenia
35
Q

Zygomycetes

Clinical Presentation

A
  • Pulmonary zygomycosis
    • Primary infection in neutropenic pts
    • Pulmonary invasion, infarcts in pulmonary vessels, and hemorrhage
  • Rhinocerebral zygomycosis
    • Invasive infection
    • Starts in nasal cavity, sinuses, or orbit
    • Extends into face and CNS
    • Most common in DKA and hematologic malignancy
  • Cutaneous zygomycosis
    • Primary or secondary
    • Nodular with ecchymotic center
36
Q

Zygomycetes

Pathogenesis

A
  • Angioinvasive
    • Similar to aspergillus infection
    • Tissue and vessel infarction
  • Dissemination
    • May cause disease in multiple organ systems
  • Cutaneous manifestations from invasive infection or following traumatic injury
37
Q

Zygomycosis

Diagnosis

A
  • Tissue biopsy for direct microscopy and culture
  • Stain with KOH w/ calcofluor white
  • See broad irregularly branched, twisted or folded hypae w/ few septa
  • Culture is frequently negative
38
Q

Zygomycosis

Treatment

A
  • Amphotericin B
  • Surgical debridement
  • Correct underlying condition
  • Mortality high (50%)
39
Q

Aspergillus

Overview

A
  • Aspergillus fumigatus and Aspergillus flavus
    • Most commonly associated with invasive disease
  • Opportunistic fungi
  • Disease usually associated with severe neutropenia
  • Found ubiquitously in the environment
  • Infection is acquired exogenously
40
Q

Aspergillus

Morphology

A
  • Exist as molds
  • Composed of septate hyphae
  • Branches @ 45° anglesdichotomous branching
    • Characteristic of Aspergillus
  • Reproduce asexually by conidiaphore formation
41
Q

Aspergillus

Transmission

A

Spread by inhalation of conidiaspores

No person to person transmission

42
Q

Allergic Aspergillosis

A
  • Seen in people with chronic asthma or CF
  • Symptoms
    • Episodic wheezing, fever, eosinophilia
    • Transient pulmonary infiltrates
  • May become severe with age
  • Can lead to fibrosis
43
Q

Aspergilloma

A
  • Usually seen in those with underlying lung diease
    • Particularly those with pre-existing cavities in the lung
  • Non-allergic colonization
  • Chronic process with development of pathological changes in the lung
    • Formation of Aspergillus containing granulomas
    • Causes “fungus ball” formations on CXR
  • Granulomas must be surgically removed + antifulgal medications
44
Q

Systemic or Invasive

Aspergillosis

A
  • Only in immunocompromised individuals
    • Risk factor ⇒ neutropenia
  • May involve pulmonary, sinus, cerebral, or cutaneous sites
  • Pathogenesis involves angioinvasion, thrombosis, and dissemination to other organs
  • Damage caused by tissue infarcts, hemorrhage, and necrosis
45
Q

Aspergillus

Diagnosis

A
  • Gomeri silver stain of tissue sections
    • ID by dichotomously branched (45° angle) septate hyphae
  • Isolation in culture on Sabouraud’s Dextrose Agar (SDA)
  • Allergic aspergillosis
    • Elevated specific IgE
    • Eosinophilia
    • Positive skin test (Type I) to Aspergillus Ag
46
Q

Aspergillus

Immunology

A
  • Conidia (inhaled) ⇒
    • Hyphae ⇒ PMNs
      • Line up along hyphal walls and secrete lysosomal enzymes
      • Patrol blood vessels
        • Aspergillus is an angioinvasive organism
  • Neutropenia is the #1 risk factor for invasive aspergillosis
47
Q

Aspergillus

Treatment

A

Amphotericin B for invasive aspergilliosis

Surgical removal of aspergilloma