Endemic Mycoses Flashcards
(40 cards)
Three Endemic Fungal Pathogens and Diseases
Histoplasma capsulatum (Histo) - Histoplasmosis Blastomyces dermatitidis (Blasto) - Blastomycosis Coccidiodes immits (Cocci) - Coccidioidmycosis
Morphology of fungi
Fungi undergo “phenotype switching” and are dimorphic
Morphology is thermally regulated-
Form of fungi
In environment all three fungi are free-living molds
In host: Histo, blasto become a budding yeast
In host: Cocci become endosporulating spherule
Most often route of infection
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
Alternate route of infection
Cutaneous lesions as primary sites
Lesions can also be result of dissemination
Does a patient need to be immunocompromised to contract these fungi?
No, but usually infection is mild in immunocompetent patients.
Are these fungi considered contagious?
No, normally not transmitted between people or animals.
Method for definitive diagnosis
Microscopic examination of stains and histology plus any additional laboratory cultivation
Differences in endemic areas
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
Differences between types
Most important: Antifungal drug therapy
Others: Morphology, clinical syndromes, anatomical targets of dissemination, danger to immunocompromised, virulence determinants, possibility of latency and reactivation
Ecology of histo
Moist, rich, acidic soil
Bird and bat guano
Bats can be naturally infected, birds are not
Geographic distribution of histo
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
Morphology of histo
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
Primary infection of histo
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
Clinical symptoms of histo (in order of declining incidence)
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
Strain virulence of histo
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
Antifungal drug therapy of histo
Not all clinical manifestations require drug treatment
Anti-fungal drugs are considred a therapeutic adjunct to assist host immune response
Can histo remain latent and then reactivate?
Probably yes, although incidence rates are unknown and is heavily based on anecdotal reports
Important challenges histo presents
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
Ecology of Blasto
Rich moist soil
Blastomycosis in Wisconsin
100 cases per year
7-50 cases per outbreak
44% in 10 northern-most counties
20% in Milwaukee area3 deaths per year
Morphology of Blasto
Environment: Uninucleate hyphae producing microconidia
Host: Large budding yeast (8 to 30 micrometers) with broad bud neck
Primary Infection of Blasto
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”)
Canine blasto
Common and serves as an indicator of human disease risk in shared environment
No evidence of animal to human transmission
