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
Paracoccidioides brasiliensis Characteristics
* 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
Paracoccidiodes brasiliensis Epidemiology
* 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
Paracoccidioides brasiliensis Transmission
**Inhalation or traumatic inoculation of conidia.** Most have contact with soil.
28
Paracoccidioides Clinical Presentation
* **Primary disease** * Usually asymptomatic or self-limiting * **Adults** ⇒ _primary 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
Paracoccidioides Diagnosis
* **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
Paracoccidioides Treatment
**Itraconazole for 6 months.** Severe infections may require Amphotericin B.
31
Opportunistic Fungi Overview
* 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
Zygomycetes Characteristics
"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
Zygomycetes Transmission & Epidemiology
* 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
Zygomycosis Risk Factors
* Organ or BM transplant recipient * Diabetic ketoacidosis * Renal failure * Hematologic malignancy * Neutropenia
35
Zygomycetes Clinical Presentation
* **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
Zygomycetes Pathogenesis
* **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
Zygomycosis Diagnosis
* 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
Zygomycosis Treatment
* **Amphotericin B** * **Surgical debridement** * Correct underlying condition * Mortality high (50%)
39
Aspergillus Overview
* ***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
Aspergillus Morphology
* Exist as **molds** * Composed of **septate hyphae** * Branches @ **45° angles** ⇒ _dichotomous branching_ * Characteristic of Aspergillus * Reproduce **asexually** by **conidiaphore formation**
41
Aspergillus Transmission
**Spread by inhalation of conidiaspores** No person to person transmission
42
Allergic Aspergillosis
* **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
Aspergilloma
* **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
Systemic or Invasive Aspergillosis
* **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
Aspergillus Diagnosis
* **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
Aspergillus Immunology
* Conidia (inhaled) ⇒ **MΦ** * 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
Aspergillus Treatment
**Amphotericin B** for invasive aspergilliosis Surgical removal of aspergilloma