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Respiratory/Musculoskeletal > M- Endemic fungal pathogens > Flashcards

M- Endemic fungal pathogens Flashcards

1
Q

What type of fungi are all endemic pathogens?

What is the primary portal of entry for endemic fungi?

A

Dimorphic-
Yeast at 37 (human body)
Mould at 25 (soil)

Primary portal of entry = the lungs by inhalation of conidia that have been aerolized from the soil

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2
Q

What are the 5 major endemic pathogens?

A
  1. histoplasma capsulatum
  2. blastomyces dermatitidis
  3. coccidioides immitis
  4. paracoccidioides brasiliensis
  5. penicillium marneffei
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3
Q

Describe the yeast form of histo.
What are its 2 types of conidia?
Which is the in vitro diagnostic form?
Which if inhaled transmits infection?

A

As a yeast it is a smaller, thin-walled oval (2-5 microns).
1. tuberculate macroconidia- thick fingerlike projections. In vitro diagnostic

  1. microconidia- thin-walled, smooth spores. If inhaled it causes infection
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4
Q

Most patients with histoplasmosis are asymptomatic. If they do present,

  1. what was the incubation period
  2. what are the symptoms
  3. CXR
A
  1. 10 days
  2. flu-like illness (malaise, fever, chest pain, dry cough, headache, hoarseness, muscle aches)
  3. CXR shows:
    - diffuse infiltrate OR nodular
    - solitary pulmonary nodule OR multiple nodules
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5
Q

What does an initial histoplasma infection progress to in immunocompromised (cancer chemo, high dose steroids, HIV) people?

A
  1. Chronic lung disease that resembles TB and can be reversed by antifungals
  2. Extrapulmonary dissemination- liver, spleen, CNS
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6
Q

People with a CD4 count below _____ are likely to have disseminated vs localized histo.

A

100

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7
Q

In endemic areas, as much as ______ test positive on skin test for histo, but only _____ have disseminated disease.
___ to _____ % of HIV infected people have diseminated disease.

A

90% + skin test
5% disseminated disease
10-25% of HIV

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8
Q

What strain is African histoplasmosis? How is the disease it causes different from capsulatum?
How is the structure different?

A

African form is H. duboisii.

Yeast form is 2x as big as capsulatum and it affects bone and skin more than lung

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9
Q

What is the endemic area of histoplasma capsulatum?

In what type of soil does it grow best?

A

Southern, central, eastern states
Ohio, Mississippi, St. Lawrence rivers and Rio Grande

It grows best in soil with a high nitrogen content

  1. bird manure- esp. blackbirds
  2. bat guano
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10
Q

What is the mode of transmission for histoplasma?

What factors determine whether a person will become ill?

A

Inhalation of microconidia from airborne spores from contaminated material.
CANNOT be spread person-to-person

How sick a person gets depends on:

  1. # of spores inhaled
  2. age of person
  3. immune status
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11
Q

A man was trekking through caves. What 2 infections are you worried about?

A
  1. histoplasma

2. rabies

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12
Q

What 2 pathogens should you associate with old buildings?

A
  1. histoplasma

2. aspergillus

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13
Q

Describe the pathogenesis of histoplasma. What is the most important part of the immune system to contain it?

A
  1. inhaled conidia/spores
  2. converts to yeast (thin-walled, small)
  3. grows inside alveolar macrophages preferentially, but can be extracellular as well
  4. Acute tissue response: mixed PMNs and granulomatous inflammation
  5. granulomas can undergo necrosis and hyalinization or calcification

Containing the infection relies on CMI to be able to make the granulomas.
IFNg is crucial (just like for TB)

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14
Q

What are the most frequently involved sites of dissemination for histoplasma in immunocompromised patients?

A

Reticuloendothelial system:

  1. liver
  2. spleen
  3. bone marrow
  4. lymph nodes
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15
Q

What are the 4 main laboratory tests for histoplasma?

How are MOST cases diagnosed?

A
  1. direct smear with PAS, Giemsa Wright, Silver
  2. culture at 37 with conversion to yeast and at 25 degrees with tuberculated macroconidia (takes wks)
  3. Urine Antigen Test (or serum, or CSF)
  4. Serology*****
    - Immunodiffusion tests
    - rise in complement fixation (CF) titer
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16
Q

When would you want to do urine antigen testing for histoplasma?

A

when you suspect disseminated disease or severe progressive acute pulmonary disease.

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17
Q

When doing serology for histoplasma, what 2 things do you want to look for?
What is more specific? sensitive?

A

Sensitive
- increased complement fixation titer

Specific
- immunodiffusion test which measures precipitating antibodies(M and H precipitin lines) to concentrated histoplasmin which is an extract from fungus

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18
Q

For endemic fungal infections, what are skin tests useful for?>

A

epidemiology only

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19
Q

When is the H band of immunodiffusion present?

What does the M band represent?

A

H- present 4 to 6 wks after exposure and indicates active infection
M band is observed more frequently, appears sooner after infection, and persists for 3 years

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20
Q

What is treatment for histoplasma in immunocompetent people? compromised?

A
  1. Oral itroconazole for less severe cases

2. IV amphotericin for immunocompromised with severe symptoms/dissemination

21
Q

How do azole drugs work?

A

They inhibit 14a-lanostrol demethylase which inhibits ergosterol biosynthesis

22
Q

Describe the yeast structure of blastomyces dermitidis.

What is its structure at 25-50 degrees?

A

Yeast: Broad base (10-12 microns) with bud attached

25-30 degrees:
septate hyphae with pear-shaped conidia at the apex of the conidiophore (lollipop appearance)

23
Q

What are the two major disease manifestations of blastomyces?

A
  1. pulmonary- inhalation of spores

2. cutaneous - direct implantation or dissemination from lungs

24
Q

Is primary blastomycosis acute or chronic?
What are symptoms? When does it resolve typically?
What % progresses to dissemination?

A

It can be either and it presents with a flu-like illness (fever, chills, productive cough, myalgia, arthralgia, pleuritic chest pain)
Acute resolves in 1-3 wks, but 20% can progress to disseminated disease

25
Q

Between histo and blaso, which has symptoms more commonly? Which is more severe?

A

Blasto more commonly has symptoms but histo is more severe

26
Q

Describe blasto skin infections, How are they acquired? How do they present?

A

Most are from direct implantation into the skin but some are from disseminated spread from the lungs.

Presents with:
erethymatous papules–> verucose, crusted–> ulcerated

27
Q

What is the distribution of blastomycoses in the US?

People who do what are most exposed?

A

Exact distribution of histoplasma- more prevalence in the Carolinas and southern eastern states.
Wisconsin, Minnesota

People who work are recreationally exposed to wooded areas (hunters, fisherman, campers, forestry)
Dogs are commonly affected and can serve as reservoir in outbreaks

28
Q

What is the pathogenesis of blastomycoses?

A

It is inhaled as conidia after disturbance of contaminated soil.
Acute response is suppurative and granulomatous inflammation
Skin may show pseudoepitheliomatous hyperplasia with focal abscess in papillary dermis

29
Q

What 4 tests are done to confirm diagnosis of blastomycoses?

A
  1. direct smear from sputum or ulcerated skin lesion. look for broad based buds
  2. culture (gold standard) - micro and macroconidia in LPCB stain (lactophenol blue)
  3. Serology- rise in complement factor (CF)
  4. UAT
30
Q

In histopathology/direct smear of biopsy, what is the size, shape, and distinguishing features of blastomycoses?

A

Round/ovoid 8-15microns

  • broad base to parent cell
  • thick cell wall that is doubly refractile
31
Q

What is treatment for mild to moderate blastomycosis?

What is treatment for life threatening pulmonary, CNS, or blastomycoses during pregnancy?

A

Mild- itroconazole

Severe/preg/CNS- amphotericin B

32
Q

Describe the structure of coccidioides as a mold and as a yeast.

A

Mold- arthroconidia (squares that easily break off hyphae)–> low infectious dose

Yeast- spherule containing yeast like forms

33
Q

Most patients infected by coccidioides have mild infection with fever, cough rash, myalgia that resolves on its own.
If it DOES progress, however, what are the 2 things that generally occur?

A
  1. Tuberculous like cavitations

2 .dissemination to meninges (and bone and skin)

34
Q

A patients comes in to see you with fever, myalgia, rash. On physical exam, you note erythema nodosum (tender palpable nodules on the shin). What is the likely cause?

A

Coccidioides immitis causing a hypersensitivity to fungal antigens (NOT the fungi itself causing the erythema nodosum)

35
Q

What is the endemic area of Coccidioides immitis?

What is the reservoir for the organism?

A

Desert southwest - NM, AZ, “lower sonoran Life Zone” which due to low rainfall and short winter provides the arid and semiarid soil cocci needs as its reservoir

36
Q

What is the mode of transmission of coccidioides?
What environmentally can increase the incidence of infection?
How many spores are necessary to infect?

A

Inhalation of 1-5 airborne arthroconidia released from the soil when it is disturbed (dust storms, earthquakes).
Incidence increases in years following seasons of rainfall.

37
Q

People with what occupations, sex, and race are more likely to get coccidioides infections?

A

Occupations:
contsruction, agriculture, archaeologist

Race:
Filipino, AA, Asians

Sex:
No difference before menses or after menopause but in adulthood men 20x more likely than women

38
Q

Describe the pathogenesis of coccidioides.

  1. portal of entry
  2. yeast form
  3. spread of infection
  4. host defenses
A
  1. Inhaled arthrospores
  2. conversion to spherules containing endospores
  3. Ruptured spherule releases endospores
  4. macrophage takes up endospore and transmits to lymph node

Immunity depends on host immune capability and IFNg ability to make granulomas (CMI)

39
Q

How do you make a laboratory diagnosis of coccidioides?

A
  1. direct microscopy- spherules with endospores
  2. culture of sputum, pus, urine, CSF, biopsy (REQUIRES BIOSAFETY LEVEL 3)
  3. Immunodiffusion test (m and h) and CF titer
    CF>1:32 suggests disseminated disease
  4. UAT- helpful but cross-reacts with histo/blasto
40
Q

What is treatment for mild/moderate coccidioides?
Coccidioidal meningitis?
Severe disease?
Severe disease WITH meningitis?

A

Mild to moderate : Itraconazole/fluconazole
Meningitis: fluconazole
Severe infection: Ampho B
Severe WITH meningitis: intrathecal Ampho B

41
Q

Where is paracoccidioides brasiliensis endemic?
What is the environmental niche?
Who does it occur in?

A

It is in South America (mexico to Argentina) and it occurs in immigrants/travelers to this area.
It is associated with perennial or seasonal rain forests or jungles

42
Q

What is the mode of transmission of paracoccidioides and what is the clinical presentation?

A

It is inhaled and the person will be asymptomatic OR present with:

  1. pneumonia.
  2. chronic cutaneous/mucocutaneous ulcers
43
Q

How do you diagnose paracoccidioides?

A
  1. direct microscopy of sputum, biopsy, crust of ulcer, draining lymph node —> captain’s wheel
44
Q

What is the diagnostic finding of paracoccidioides on histopathology?

A

Captains wheel

45
Q

What is treatment for paracoccidiodes?

A

itroconazole = mild
amphotericin = severe
Bactrim (trimethoprim-sulfamethoxazole)

46
Q

What is the structure of penicilliosis and what are the characteristic features in culture?

A

Mould- finger-like projections with infectious spores
Yeast- elongated oval with tranverse septum. often intracellular

In culture, penicilliosis produces a red pigment allowing for presumptive diagnosis

47
Q

What is the endemic region of penicilliosis?
What is the likely niche/reservoir?
Who is the typical person to be infected?

A

Southeast asia/China
It is thought to be in soil and in bamboo rats.

Penicilliosis affects ONLY people with HIV

48
Q

What is the clinical presentation of someone with penicilliosis?

A
  1. Tuberculosis-like pulmonary syndrome
  2. Dissemination to cause lymphadenopathy, hepatosplenomegaly, and pancytopenia
  3. umbilicated lesions in skin rash

Respiratory/Musculoskeletal (36 decks)

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