28 Systemic Mucoses Flashcards
What are Primary Fungal Systemic Pathogens?
What are Opportunistic Fungal Systemic Pathogens?
P: Capable of infecting a host who has a capable immune system
O: Infect hosts who have compromised immune systems
Do Primary Fungal Systemic Pathogens have dimorphism?
Is it Classical Thermal Dimorphism?
Classical Thermal Dimorphism: Hyphae in environment. Yeast in body.
Are Primary Fungal Systemic Pathogens contagious person to person?
How does a person become infected?
No.
Spoil saprophytes grow hyphae and release conidial spores. Spores are inhaled.
Note: Systemic Fungal Pathogens are endemic
.
What is the normal host immune response to systemic fungal pathogens?
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.
What is Dx for LATENT systemic fungal pathogens
DTH skin test
Are Systemic Fungal Pathogens cultured?
Laboratory cultures of the mold forms are dangerous because they can release spores into the air
What pathogens cause Valley Fever aka Coccidioidomycosis?
Coccidioides immitis
Coccidioides posadasii
What are the environmental stages and host-infected stages of Coccidioidomycosis aka Valley Fever?
Environmental mycelial phase contains barrel-shaped ARTHROCONIDIA which are easily fragmented and airborne.
Host-infected stage consistes of thick walled SPHERULES containing numerous ENDOSPORES
What is a SPHERULE?
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 ______.
Where is Coccidioidomycosis endemic?
How many U.S. citizens are infected annually?
North, Central, and South America
Texas
100,000!
Coccidioidomycosis grows in “Lower Sonoran Life Zone.” What is that?
Arid climates Hot summers Low altitude Alkaline soil Sparse flora
What demographics are most at risk for infection by Coccidioidomycosis?
Dark-skined races, particularly Filipinos
Third trimester pregnant women
What is the pathogenesis of Coccidioidomycosis?
Inhaled athroconidia lodge in alveoli»_space; form spherules in tissues»_space; ruptures endospores»_space; each endospore can form into a spherule
What is the host response to Coccidioidomycosis…
Initial?
2-4 weeks later?
Initially: MACROPHAGES and NEUTROPHILS
2-4 weeks later: Cell-mediated immunity (can be detected by DTH)
Can Coccidioimycosis aka Valley Fever be killed by Neutrophils?
No
If infected, what does a positive DTH indicate in terms of prognosis?
What does a negative DTH indicate?
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
Cocidioimycosis…
How many are symptomatic vs assymptomatic?
60% ASYMPTOMATIC
40% SYMPTOMATIC
Whart are the symptoms of Coccidioimycosis (4 sets listed)?
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
What is Erythema Nodosum?
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.
How long does Valley Fever last?
VF: 2-6 WEEKS or may become CHRONIC with CAVITY FORMATION
Is Coccidioimycosis a Primary or Opportunistic infection?
Primary infection, but immunocompromised people are more at risk for disseminated disease
What is the Dx fo Coccidioimycosis (3 techniques and 1 concern)?
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
How is the progression of the Coccidioimycosis disease monitored?
Serological tests
Detail: In serological tests for Coccidioimycosis when do IgMs develop?
When do IgGs develop?
How long do the Igs last?
IgM develop in 2-4 weeks
IgG later
Antibodies disappear upon resolution and persist with infection
What organisms causes Histoplasmosis?
Histoplasma capsulatum
Describe the Envrionmental form and Tissue-Infected form of Histoplasma capsulatum.
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.
Where is Histoplasma capsulatum endemic?
Temperata, subtropical, and tropical zones
Ohio and Mississippi Valley
How pervasive is Histoplasma capsulatum?
90% of people in endemic areas are skin test positive
Describe the pathogenic steps of infection for Histoplasma capsulatum.
Inhaled spores germinate in 3 days»_space; yeast proliferate in macrophages (VIRULENCE FACTOR)»_space; migrate to mediastinal lymph nodes, spleen, and liver.
When is cell-mediated immunity stimulated?
9-15 days after yeast proliferation
Are Histoplasma INTRA or EXTRAcellular pathogens?
Mostly intracellular in Macrophages and Epithelial Cells
Extracellular state occurs in overwhelming infection
Why can Histoplasma capsulatum survive inside macrophages?
Increases pH of phagolysosome by producing bicarbonate and ammonia
Inactivates host degradative enzymes
Describe the clinical features of Histoplasma capsulatum with regard to
Symptomatic vs asymptomatic…
Immunocompetent…
Immunocompromised…
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
What is Dx for Histoplasma capsulatum…
What is necessary for identification?
Dx techniques for disseminated infection?
Dx techniques for tissue infection?
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
Explain the usefulness of Antibody and Serological tests for Histoplasma capsulatum.
Histoplasma antigen in urine is helpful
Sero tests monitor progression of disease. When disease resolves antibody titers decrease
Why is skin testing NOT useful for Histoplasma capsulatum?
Cross reactivity with B. dermatitidis (explained next)
Also may interphere with serological testing
What infection causes Blastomycosis aka North American Blastomycosis?
Blastomyces dermatitidis (B. dermatitidis)
Describe the yeast form of Blastomycosis dermatitidis.
Describe the environmental form of Blastomycosis dermatitidis.
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
Where is Blastomycosis dermatitidis endemic?
Why are the endemic areas difficult to pinpoint?
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.
How are dogs affected by Blastomycosis dermatitidis?
How are tourists affected?
Dogs: severe or lethal
Tourists demonstrate a high frequency of clinical symptoms
What are the pathogenic steps to infection with Blastomycosis dermatitidis?
Infection by inhaling spores from soil hyphae
Yeast phase multiply in lung and may disseminate via bloodstream and lympatics to visceral organs
What is required for VIRULENCE of Blastomycosis dermatitidis?
Surface protein BAD1
What is BAD1?
Has homology to INVASIN genes of gram negative bacteria
BAD1 promotes uptake by macrophages
Describe pathogenic steps occuring after macrophage phagocytosis of Blastomycosis dermatitidis.
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
What are clinical features of Blastomycosis dermatitidis... Symptomatic vs asymptomatic Acute infection? Chronic infection? What organ tissues are targeted?
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
What is Dx of Blastomycosis dermatitidis?
KOH mounts or stained biopsy specimens
Observation of THICK-WALLED YEAST with SINGLE BROAD-BASED BUDS
CULTURE to demonstrate THERMAL DIMORPHISM
What serologic events occur with Blastomycosis dermatitidis?
Circulating antibodies DO occur
What organism causes Paracoccidioidomycosis aka South American Paracoccidioidomycosis?
Paracoccidioidomycosis brasiliensis
Describe the Yeast form of Paracoccidioidomycosis
Describe the environmental form
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
In what natural medium (soil, plants, animals) does Paracoccidioidomycosis grow?
Where is it endemic?
SOIL
SOUTH AMERICA
What is Tx for ALL SYSTEMIC FUNGAL PATHOGENS?
Infections are often mild and self-limiting
Severe infections use: AMPHOTERICIN B or various FLUCONAZOLES
