Endemic Mycoses Flashcards

1
Q

Three Endemic Fungal Pathogens and Diseases

A
Histoplasma capsulatum (Histo) - Histoplasmosis
Blastomyces dermatitidis (Blasto) - Blastomycosis
Coccidiodes immits (Cocci) - Coccidioidmycosis
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2
Q

Morphology of fungi

A

Fungi undergo “phenotype switching” and are dimorphic

Morphology is thermally regulated-

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3
Q

Form of fungi

A

In environment all three fungi are free-living molds
In host: Histo, blasto become a budding yeast
In host: Cocci become endosporulating spherule

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4
Q

Most often route of infection

A

Respiratory tract via small particles (2-5 micrometers)
Primary site of infection is lung
Can become localized and cause pneumonia or disseminate via the blood

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5
Q

Alternate route of infection

A

Cutaneous lesions as primary sites

Lesions can also be result of dissemination

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6
Q

Does a patient need to be immunocompromised to contract these fungi?

A

No, but usually infection is mild in immunocompetent patients.

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7
Q

Are these fungi considered contagious?

A

No, normally not transmitted between people or animals.

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8
Q

Method for definitive diagnosis

A

Microscopic examination of stains and histology plus any additional laboratory cultivation

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9
Q

Differences in endemic areas

A

Blasto: Across the central and southeastern parts of the country (Mississippi + Ohio rivers + Great Lakes)
Histo: Triangle from Illinois, Louisiana, West Virginia (Mississippi + Ohio rivers)
Cocci: Southwest

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10
Q

Differences between types

A

Most important: Antifungal drug therapy
Others: Morphology, clinical syndromes, anatomical targets of dissemination, danger to immunocompromised, virulence determinants, possibility of latency and reactivation

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11
Q

Ecology of histo

A

Moist, rich, acidic soil
Bird and bat guano
Bats can be naturally infected, birds are not

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12
Q

Geographic distribution of histo

A

Most common endemic mycosis in US and fungal respiratory infection in the world
Incidence of histoplasmin in some geographic regions exceeds 85%
Nearly all lifelong residents of endemic areas are exposed by 20 yo

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13
Q

Morphology of histo

A

In envrionment: Multinucleated branched hyphae with microconidia and macroconidia
In host: Oval budding yeast (2-4 micrometers) with narrow bud neck, found inside mononuclear phagocytes and extracellularly

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14
Q

Primary infection of histo

A

Microconidia become airborne and penetrate alveoli
Then are engulfed by macrophages and convert to yeast form, beginning to replicate
Cellular immunity develops within 2 weeks, CD4+ T-cells are vitally important
By 3-6 weeks, become hypersensitive to histo Ag, yielding positive response to skin Ag test
Most frequent result of infection (75-90% of the time) in immunocomptent is asymptomatic or non-specific flu-like syndrome, 3-17 days after exposure

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15
Q

Clinical symptoms of histo (in order of declining incidence)

A

Pulmonary - Resembles miliary TB on X-ray, lesions in lung
Acute pericardititis - 5% of symptomatic patients, result of immunologic response in the mediastinal lymph nodes
Dissemination: 1/2000 immunocompetent, 4-27% of immunocompromised, metastatic sites usually rich in mononuclear phagocytic cells
Occular histoplasmosis syndrome - Retinal scarring from host fibrosing inflammatory response
Fibrosing mediastinisis - Enlargement of multiple lymph nodes undergoing necrosis, causing Ag leakage into the mediastinum; abnormal inflammatory response leads to fibrosis

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16
Q

Strain virulence of histo

A

Microconidia have receptors for CD2/CD18 integirns on macrophage surface initiating phagocytosis
Survices oxidative burst and can neutralize peroxide
Modulates phagolysomal pH to be less acidic

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17
Q

Antifungal drug therapy of histo

A

Not all clinical manifestations require drug treatment

Anti-fungal drugs are considred a therapeutic adjunct to assist host immune response

18
Q

Can histo remain latent and then reactivate?

A

Probably yes, although incidence rates are unknown and is heavily based on anecdotal reports

19
Q

Important challenges histo presents

A

Hard to differential diagnosis (blastomycosis, pneumonia, TB, etc)
Skin test in endemic area only representative of exposure not active infection
Organisms can be seen in PAS and GMS-stained specimens but hard to directly detect otherwise

20
Q

Ecology of Blasto

A

Rich moist soil

21
Q

Blastomycosis in Wisconsin

A

100 cases per year
7-50 cases per outbreak
44% in 10 northern-most counties
20% in Milwaukee area3 deaths per year

22
Q

Morphology of Blasto

A

Environment: Uninucleate hyphae producing microconidia
Host: Large budding yeast (8 to 30 micrometers) with broad bud neck

23
Q

Primary Infection of Blasto

A

Inhalation of microconidia which transform at body temperature to yeast
Incubation time is 4-6 weeks (useful for differentiating from histo)
Primary pulmonary infections unapparent in 50% of patients
Infections indistinguishable from other lobar or segmented pneumonias
Trauma can lead to deep cut. infections (“Chicago (Carpenter) Disease”)

24
Q

Canine blasto

A

Common and serves as an indicator of human disease risk in shared environment
No evidence of animal to human transmission

25
Q

Clinical Syndrome of Blasto

A

Blasto can be benign and self-limiting or a chronic granulomatous
Can be coincident with bronchogenic carcinoma, histo, TB, or other severe pulmonary disease
Unlike TB, blasto lesions rarely caseate or calcify
Cutaneous disease develops slowly as a subcut nodule or papule
Skin is the most common site of dissemination in about 20-40% of cases with dissemination
Other dissemination sites: bone (10-25%), UG tract (5-15%), CNS (5%)

26
Q

Strain Virulence of Blasto

A

Binds to integrins on host macrophages
Does not necessarily lead to phagocytosis due to blasto’s size
WI-1 mediates the binding
Contains BAD1 to prevent complement deposition on yeast cell

27
Q

Does blasto undergo latency and reactivation?

A

Rarely

28
Q

Challenges presented by Blasto

A

Differential diagnosis from pneumonia, TB, lung cancer

Differentiating primary from metastatic cut. lesions

29
Q

Ecology of cocci

A

Soil rich in organic material, hot/semi-arid climates
Highest incidence is in late summer or fall, when dusty conditions exist leading to soil disruption that disperse the arthroconidia

30
Q

Epidemiology of cocci

A

20,000 cases/yr

Infection is solely in endemic regions

31
Q

Morphology of cocci

A

Environment: Septate multicellular hyphae with alternate cells developing into barrel-shaped arthroconidia (“joint” seperated coindia)
Host: Arthroconidia convert within 72 hours into large spherules, which contin numerous endospores. Spherule ruptures releasing endospores to reproduce

32
Q

Primary infection of cocci

A

Infection via respiratory route
Can develop to a granulomatous respiratory infection
Caseation without calcification may occur

33
Q

Immune response to cocci

A

Humoral: IgM Ab to IgG Ab

Cell mediated response is ncessary for recovery

34
Q

Clinical syndromes of cocci

A

60% of primary pulmonary infections are asymptomatic, with only effect being hypersensitivity in skin test to coccidiodin
Symptoms range from mild flu-like syndrome developing 7-21 days after exposure to acute severe pneumonia
Dissemination occurs in approximately 1% of cases: Severe problems due to meninges, bone and skin being targets. Meningitis can lead to permanent neurological damage or death

35
Q

Special populations of cocci

A

Construction workers, Agricultural workers, Cattle ranchers
Racial bias towards “dark-skinned” populations
Special risk for pregnancy, highest risk during 3rd trimester, azole antifungal agents can be teratogenic
Special risk to AIDS patients being 3rd most life-threatening opportunisitic infection in patients, 25% of AIDS patients in endemic areas

36
Q

Strain virulence of cocci

A

Most virulent fungal pathogen

37
Q

Drug therapy of cocci

A

95% of acute episodes resolve without therapy

38
Q

Special challenges of cocci

A

Ethnic biases
Pregnancy
Awareness of disease outside of endemic areas, clinicians outside of endemic areas are relatively quick to biopsy

39
Q

Antifungal Drug Therapy Summary for Mild Pulmonary Endemic Fungi:

A

Histo: None or itraconazole
Blasto: Itraconazole
Cocci: None

40
Q

Antifungal Drug Therapy Summary for Severe Disseminated Endemic Fungi:

A

Amphotericin B + Itraconazole for all