28 Systemic Mucoses

Question 1

What are Primary Fungal Systemic Pathogens?

What are Opportunistic Fungal Systemic Pathogens?

Answer 1

P: Capable of infecting a host who has a capable immune system
O: Infect hosts who have compromised immune systems

Question 2

Do Primary Fungal Systemic Pathogens have dimorphism?

Is it Classical Thermal Dimorphism?

Answer 2

Classical Thermal Dimorphism: Hyphae in environment. Yeast in body.

Question 3

Are Primary Fungal Systemic Pathogens contagious person to person?
How does a person become infected?

Answer 3

No.

Spoil saprophytes grow hyphae and release conidial spores. Spores are inhaled.

Question 4

Note: Systemic Fungal Pathogens are endemic

Answer 4

.

Question 5

What is the normal host immune response to systemic fungal pathogens?

Answer 5

Both innate and cell mediated immunity
Macrophages can wall off the fungus and produce granulomas
If a person becomes immunocompromised, the fungus can escape the granuloma
Therefore there are latent infections.

Question 6

What is Dx for LATENT systemic fungal pathogens

Answer 6

DTH skin test

Question 7

Are Systemic Fungal Pathogens cultured?

Answer 7

Laboratory cultures of the mold forms are dangerous because they can release spores into the air

Question 8

What pathogens cause Valley Fever aka Coccidioidomycosis?

Answer 8

Coccidioides immitis

Coccidioides posadasii

Question 9

What are the environmental stages and host-infected stages of Coccidioidomycosis aka Valley Fever?

Answer 9

Environmental mycelial phase contains barrel-shaped ARTHROCONIDIA which are easily fragmented and airborne.

Host-infected stage consistes of thick walled SPHERULES containing numerous ENDOSPORES

Question 10

What is a SPHERULE?

Answer 10

Once inhaled the fungus grows into a large sphere.
The sphere invaginates with many septa.
The sphere can form endospores which can be released into the host.
This structure is called a ______.

Question 11

Where is Coccidioidomycosis endemic?

How many U.S. citizens are infected annually?

Answer 11

North, Central, and South America
Texas
100,000!

Question 12

Coccidioidomycosis grows in “Lower Sonoran Life Zone.” What is that?

Answer 12

Arid climates
Hot summers
Low altitude
Alkaline soil
Sparse flora

Question 13

What demographics are most at risk for infection by Coccidioidomycosis?

Answer 13

Dark-skined races, particularly Filipinos

Third trimester pregnant women

Question 14

What is the pathogenesis of Coccidioidomycosis?

Answer 14

Inhaled athroconidia lodge in alveoli&raquo_space; form spherules in tissues&raquo_space; ruptures endospores&raquo_space; each endospore can form into a spherule

Question 15

What is the host response to Coccidioidomycosis…
Initial?
2-4 weeks later?

Answer 15

Initially: MACROPHAGES and NEUTROPHILS

2-4 weeks later: Cell-mediated immunity (can be detected by DTH)

Question 16

Can Coccidioimycosis aka Valley Fever be killed by Neutrophils?

Answer 16

No

Question 17

If infected, what does a positive DTH indicate in terms of prognosis?

What does a negative DTH indicate?

Answer 17

Positive DTH indicates a protective host response

Negative DTH indicates no protection and the endospores may gain entry into the blood stream and lodge systemically

Question 18

Cocidioimycosis…

How many are symptomatic vs assymptomatic?

Answer 18

60% ASYMPTOMATIC

40% SYMPTOMATIC

Question 19

Whart are the symptoms of Coccidioimycosis (4 sets listed)?

Answer 19

10% get Eyrthema Nodosum (do not contain organism and are not indicative of disseminated desease)

Lower respiratory infection and/or

Systemic illness with: Cough, Suptum, Chest Pain, Malaise, Fever, Chills, Night Sweats, Anorexia, Weakness, and Arthralgia

Chronic: Cavity formation

Question 20

What is Erythema Nodosum?

Answer 20

an inflammation of the fat cells under the skin (panniculitis) characterized by tender red nodules or lumps that are usually seen on both shins. EN is an immunologic response to a variety of different causes.

Question 21

How long does Valley Fever last?

Answer 21

VF: 2-6 WEEKS or may become CHRONIC with CAVITY FORMATION

Question 22

Is Coccidioimycosis a Primary or Opportunistic infection?

Answer 22

Primary infection, but immunocompromised people are more at risk for disseminated disease

Question 23

What is the Dx fo Coccidioimycosis (3 techniques and 1 concern)?

Answer 23

1) Spherules may be detected with KOH mounts or fungal stains in infected tissues
2) Can be cultured on SABOURAUD’S AGAR
3) Demonstration of DIMORPHISM and TISSUE FORM is required for identification
Concern: Environmental form produces air spores and is dangerous to lab techs

Question 24

How is the progression of the Coccidioimycosis disease monitored?

Answer 24

Serological tests

Question 25

Detail: In serological tests for Coccidioimycosis when do IgMs develop? When do IgGs develop? How long do the Igs last?

Answer 25

IgM develop in 2-4 weeks IgG later Antibodies disappear upon resolution and persist with infection

Question 26

What organisms causes Histoplasmosis?

Answer 26

Histoplasma capsulatum

Question 27

Describe the Envrionmental form and Tissue-Infected form of Histoplasma capsulatum.

Answer 27

Environmental consists of septate branching hyphae that produce micro- and macro- conidia (spores). Often found in bird poop. Yeast are oviod and are taken up by macrophages. The "capsular" appearance is an artifact of staining. NO CAPSULE.

Question 28

Where is Histoplasma capsulatum endemic?

Answer 28

Temperata, subtropical, and tropical zones | Ohio and Mississippi Valley

Question 29

How pervasive is Histoplasma capsulatum?

Answer 29

90% of people in endemic areas are skin test positive

Question 30

Describe the pathogenic steps of infection for Histoplasma capsulatum.

Answer 30

Inhaled spores germinate in 3 days >> yeast proliferate in macrophages (VIRULENCE FACTOR) >> migrate to mediastinal lymph nodes, spleen, and liver.

Question 31

When is cell-mediated immunity stimulated?

Answer 31

9-15 days after yeast proliferation

Question 32

Are Histoplasma INTRA or EXTRAcellular pathogens?

Answer 32

Mostly intracellular in Macrophages and Epithelial Cells | Extracellular state occurs in overwhelming infection

Question 33

Why can Histoplasma capsulatum survive inside macrophages?

Answer 33

Increases pH of phagolysosome by producing bicarbonate and ammonia Inactivates host degradative enzymes

Question 34

Describe the clinical features of Histoplasma capsulatum with regard to Symptomatic vs asymptomatic... Immunocompetent... Immunocompromised…

Answer 34

Most infections are asymptomatic. IMMUNOCOMPETENT: have Acute pulmonary histoplasmosis that has self-limited FLU-LIKE SYMPTOMS in which fungal infection goes unrecognized. IMMUNOCOPROMIZED: Chronic histoplasmosis is an OPPORTUNISTIC infection that is often mistaken for tuberculosis

Question 35

What is Dx for Histoplasma capsulatum... What is necessary for identification? Dx techniques for disseminated infection? Dx techniques for tissue infection?

Answer 35

Demonstration of DIMORPHISM is necessary for identification along with the presence of TUBERCULATE MACROCONIDIA in mold cultures For disseminated infection: WRIGHT STAINED SMEAR of blood has intracellular yeasts in macrophages. Also LAB CULTURE from blood samples. For infected tissue: FUNGAL STAIN and identification of LAB CULTURES

Question 36

Explain the usefulness of Antibody and Serological tests for Histoplasma capsulatum.

Answer 36

Histoplasma antigen in urine is helpful Sero tests monitor progression of disease. When disease resolves antibody titers decrease

Question 37

Why is skin testing NOT useful for Histoplasma capsulatum?

Answer 37

Cross reactivity with B. dermatitidis (explained next) | Also may interphere with serological testing

Question 38

What infection causes Blastomycosis aka North American Blastomycosis?

Answer 38

Blastomyces dermatitidis (B. dermatitidis)

Question 39

Describe the yeast form of Blastomycosis dermatitidis. Describe the environmental form of Blastomycosis dermatitidis.

Answer 39

Large yeasts with characteristic morphology 5 -30 microns in diameter with SINGLE BUDS having a characteristic BROAD BASE. Environmental mold forms produce small pear shaped conidia

Question 40

Where is Blastomycosis dermatitidis endemic? | Why are the endemic areas difficult to pinpoint?

Answer 40

Mississippi and Ohio river basins, especially wooded areas near the river Environmental distribution is difficult to define because of the lack of a specific and sensitive skin test. Blastomycosis dermatitidis cross-reacts with H. capsulatum.

Question 41

How are dogs affected by Blastomycosis dermatitidis? | How are tourists affected?

Answer 41

Dogs: severe or lethal | Tourists demonstrate a high frequency of clinical symptoms

Question 42

What are the pathogenic steps to infection with Blastomycosis dermatitidis?

Answer 42

Infection by inhaling spores from soil hyphae | Yeast phase multiply in lung and may disseminate via bloodstream and lympatics to visceral organs

Question 43

What is required for VIRULENCE of Blastomycosis dermatitidis?

Answer 43

Surface protein BAD1

Question 44

What is BAD1?

Answer 44

Has homology to INVASIN genes of gram negative bacteria | BAD1 promotes uptake by macrophages

Question 45

Describe pathogenic steps occuring after macrophage phagocytosis of Blastomycosis dermatitidis.

Answer 45

Yeast replicate in macrophage until activated by cytokines from T cells Macrophages may carry fungus to other organs Within several weeks, cell-mediated immunity leads to protection

Question 46

``` What are clinical features of Blastomycosis dermatitidis... Symptomatic vs asymptomatic Acute infection? Chronic infection? What organ tissues are targeted? ```

Answer 46

Acute pulmonary infection may be symptomatic or may produce flu-like symptoms Acute MAY RESOLVE or MAY PROGRESS Disease has tropism for SKIN and BONE

Question 47

What is Dx of Blastomycosis dermatitidis?

Answer 47

KOH mounts or stained biopsy specimens Observation of THICK-WALLED YEAST with SINGLE BROAD-BASED BUDS CULTURE to demonstrate THERMAL DIMORPHISM

Question 48

What serologic events occur with Blastomycosis dermatitidis?

Answer 48

Circulating antibodies DO occur

Question 49

What organism causes Paracoccidioidomycosis aka South American Paracoccidioidomycosis?

Answer 49

Paracoccidioidomycosis brasiliensis

Question 50

Describe the Yeast form of Paracoccidioidomycosis | Describe the environmental form

Answer 50

Yeast have characteristic morphology Yeast are THICK-WALLED and have MULTIPLE BUDS with a WAGON WHEEL appearance Environmental mold forms produce small pear shaped condidia

Question 51

In what natural medium (soil, plants, animals) does Paracoccidioidomycosis grow? Where is it endemic?

Answer 51

SOIL | SOUTH AMERICA

Question 52

What is Tx for ALL SYSTEMIC FUNGAL PATHOGENS?

Answer 52

Infections are often mild and self-limiting | Severe infections use: AMPHOTERICIN B or various FLUCONAZOLES