Endemic Mycoses Flashcards
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
Clinical Syndrome of Blasto
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%)
Strain Virulence of Blasto
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
Does blasto undergo latency and reactivation?
Rarely
Challenges presented by Blasto
Differential diagnosis from pneumonia, TB, lung cancer
Differentiating primary from metastatic cut. lesions
Ecology of cocci
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
Epidemiology of cocci
20,000 cases/yr
Infection is solely in endemic regions
Morphology of cocci
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
Primary infection of cocci
Infection via respiratory route
Can develop to a granulomatous respiratory infection
Caseation without calcification may occur
Immune response to cocci
Humoral: IgM Ab to IgG Ab
Cell mediated response is ncessary for recovery
Clinical syndromes of cocci
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
Special populations of cocci
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
Strain virulence of cocci
Most virulent fungal pathogen
Drug therapy of cocci
95% of acute episodes resolve without therapy
Special challenges of cocci
Ethnic biases
Pregnancy
Awareness of disease outside of endemic areas, clinicians outside of endemic areas are relatively quick to biopsy
Antifungal Drug Therapy Summary for Mild Pulmonary Endemic Fungi:
Histo: None or itraconazole
Blasto: Itraconazole
Cocci: None
Antifungal Drug Therapy Summary for Severe Disseminated Endemic Fungi:
Amphotericin B + Itraconazole for all
