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- Penicilliosis Maneffei
General Characteristics of Systemic Mycoses:
1) Primarily causes _____
3) Endemic in locals, can be asymptomatic and self-limited
4) What types of immune response are required?
- 1) Pulmonary infections
- 2) Dimorpic (one form in environment, another in body). Temp. may be a causative agent.
- 3) Innate and cell-mediated immunity are important
What types of immune response are important in systemic mycoses?
Innate and cell-mediated
In systemic mycoses, the cellular response can be _____
Can systemic mycoses be tranmitted human-to-human?
Deep mycoses disseminate throughout the body and include infections of:
- Internal organs:
Superficial, cutaneous, and subcutaneous mycoses generally ________
Have very little or no immune response.
Hair, nails, skin
The cells of mycoses are _____.
Eukaryotic, like us!
Must be careful with drug interactions.
What is a major target for anti-mycotic drugs?
Ergosterol in the cell membrane
Name 4 categories of anti-mycoses.
- Polyenes (Amphotericin B) --> ergosterol in cell membrane --> cell death
- Azoles --> ergosterol synthesis --> cell death
- 5-Fluorocytosine --> inhibits DNA and protein synthesis --> cell death
- Candins --> D-glucan synthase --> inhibits glucan synthesis of the cell wall --> cell death
Polyenes attack _____ in the cell membrane and cause ____. Results in ______
- pore formation
- cell death
Azoles target ____ ____ leading to less in the membrane. Results in ____
- ergosterol synthesis
- cell death
Candins (echinocandin) inhibits _________ affects synthesis of _________ in the _____. Results in ______.
- Fungal glucan synthase
- Glucan, cell wall
- Cell death
What organism causes Blastomycosis?
What does Blastomyces dermatitidis cause? Where is it found?
- Found in North and Central America, endemic to MS and OH river basins
What organism is endemic to the MS and OH river basins?
Who does Blastomycosis most commonly present in ? How is it attained?
Males 40-60 who are rural/ farm workers (wooded areas)
Attained via respiratory inhalation, most patients present with secondary cutaneous infection
Disease prevalent in males 40-60 who are rural/farm workers
Common infection in dogs (endemic in areas) that is typically severe and often fatal.
How does Blastomycosis infection present?
- Pulmonary (acute or chronic)
- Skin lesions
What dimorphic organism is at Yeast Phase at 37 C?
What phase is it in at room temperature?
- Mycelial phase
Blastomycosis is dimorphic. Phase at:
1) Room temp?
2) 37 degrees
What other organisms have these same phases?
- 1) Mycelial phase (room temp)
- 2) Yeast phase (37)
H. capsulatum, P. brasiliensis
What particle is responsible for infection of Blastomycosis dermititidis?
Microconidia (< 5 micrometers in size)
Exudate from a skin abscess shows a thick-walled single budding yeast, 8-20 um w/ a wide junction between blastoconidium. What is the responsible organism?
Blastomycosis skin lesions:
1) Begin as _____ lesion w/ microabscesses at the edge
2) Evolve to __________
3) May not see lung involvement, but organism can be cultured from ______
- 1) papulopustular
- 2) ulcerated granuloma
- 3) sputum
On a skin lesion, blastomyces dermititidis (the causative agent) is found ______.
on the edge
What organism is found on the edge of the skin lesions that it causes?
Coccidioidomysis is caused by?
- Coccidiodes immitis
- Found in soil in arid regions (SW US, San Joaquin fever) and Latin America
Regions most common:
- B. dermititidis- MS and OH river basins (wooded areas); rural
- C. immitis- SW US and Latin America (soil)
- H. capsulatum- Eastern and central US, esp. MS and OH river valleys (bat, chicken, and bird droppings-esp. starlings); rural and urban
- P. brasiliensis: Latin America ONLY! (soil)- think Brazil= LA
5-10% of patients with C. immitis develop ______
Both B. dermititidis and C. immitis are commonly
- C. immitis (60%)
5-10% of patients with a _____ infection develop erthema nodosum
Erythema nodosum are red tender nodules found on _____ surfaces, such as ___
Not necessarily a sign of disseminated disease!
Where is the organism found?
B. dermititidis skin lesion-
C. immitis erythema nodosum-
- B = on edges
- C= no organisms in nodule
Erthema nodosum is a _______ response to fungal antigens and has a _____ prognosis
- Delayed Type Hypersensitivity Response
- Good prognosis
2 forms of C. immitis
- Mycelial phase (environment) - produces arthrospores or arthroconidia
- Spherules with endospores in the host
Which of the 4 fungi can be an AIDS-defining illness?
Leading mycotic infection in SW US?
How long does immunity last for C. immitus?
Infection can confer lifelong immunity.
What complication predicts the worse prognosis in dissemination of C. immitus?
CNS involvement worsens the outcome.
Organism that causes Histoplasmosis?
- Histoplasma capsulatum
- Endemic in eastern and central US (especially, MS and OH River valleys) -associated w/ bat, chicken, and bird droppings.
2 Phases of H. capsulatum
- 1) Mycelial phase (room temp)
- 2) Yeast phase (37)
What organism can be seen within pulmonary macrophages within days of infection of the respiratory tract?
Mononuclear phagocytes can be found (demonstrating systemic dissemination) throughout the RES containing H. capsulatum within
2 weeks of infection
Reactivation of old foci of infection can occur with what organism?
H. capsulatum, usually a result of immunosuppression
How does H. capsulatum evade macrophage killing?
Raises pH in phagolysosome from 5.5-6.5 (does NOT inhibit phagolysosome fusion)
Which organism evades macrophages killing by raising the phagolysosome pH?
What portion of H. capsulatum is inhaled and causes infection?
Does H. capsulatum have a capsule? Why does it have this name?
No, has clear space around yeast form
True/False: The histplasmin skin test is a good way to test for H. capsulatum infection? Why?
- 50-80% of individuals in endemic area are positive
- Can be positive for years after recovery
- Falsely negative in 20% of patients w/ Chronic Pulmonary Histoplasmosis
Causative agent of Paracoccidioidesmycosis?
- Paracoccidiodes brasiliensis
- Found in Latin America (soil), disease ONLY occurs in that region
Myceial phase has what physical characteristics?
What organism has a pilot-wheel/flower appearing yeast form under microscopic observation?
Causative agent of Penicilliosis Marneffei?
- Penicillium maneffei
- Found in immunocompromised individuals in SE Asia and China
- Pulmonary involvement, skin lesions
2 forms of Penicillium maneffei
- Mold at 25 C
- Yeast at 37 C
Which one doe NOT have a yeast form at 37 C?
Which ones have mycelial phase in environment? What do the other two have?
- Blastomycosis: Mycelial, yeast phase
- Coccidioidomycosis: Mycelial, Spherules w/ endospores in host
- Histoplasmosis: Mycelial, yeast
- Paracoccidioidmysis: Mycelial, yeast
- Penicilliosis Maneffei: Mold (25C), yeast