Systemic Flashcards
Also known as San Joaquin Valley fever, Valley fever, or Desert Rheumatism,
Coccidioidomycosis
coccidioidomycosis is a fungal infection caused by (2)
Coccidioides immitis and Coccidioides posadasii.
It primarily affects the lungs and can cause systemic disease in immunocompromised individuals.
COCCIDIOIDOMYCOSIS
COCCIDIOIDOMYCOSIS
Causative Agents
• – Endemic in Central and Southern California, Northern Mexico.
• – Found in Arizona, Texas, Mexico, and parts of South America.
• Both species are ***phenotypically indistinguishable*** but can be differentiated by genotyping.
Coccidioides immitis
Coccidioides posadasii
COCCIDIOIDOMYCOSIS
History & Discovery
• 1891: (a medical student) first observed Coccidioides in a soldier with a verrucous facial lesion.
• 1892: described it as a coccidia-like parasite.
• 20 years later: The fungal dimorphism and endemicity in California were confirmed.
Alejandro Posadas
Posadas and Wernicke
COCCIDIOIDOMYCOSIS
Pathogenesis & Clinical Features
Transmission & Infection
• Mode of entry:_______
Inhalation of airborne arthroconidia from disturbed soil.
• Primary pulmonary infection – Spores enter the lungs, where they enlarge and form spherules filled with endospores.
• Rupture of spherules releases endospores, which mature into new spherules, continuing the infection cycle.
COCCIDIOIDOMYCOSIS
Asymptomatic infection (60%)
• No symptoms, but a positive skin test (delayed hypersensitivity) within 2-4 weeks.
• Recovery often leads to lifelong immunity.
COCCIDIOIDOMYCOSIS
Self-limiting respiratory illness (40%)
• Flu-like symptoms: fever, malaise, cough, headache, and arthralgia.
• “Valley Fever” - a term for this acute form.
• Lasts for weeks to months.
COCCIDIOIDOMYCOSIS
COCCIDIOIDOMYCOSIS
Hypersensitivity reactions (15%)
• _______ (“desert bumps”) – Red, tender nodules on the shins.
• _______– Target-like skin lesions.
• _______(desert rheumatism) – Joint pain and swelling.
Erythema nodosum
Erythema multiforme
Arthritis
COCCIDIOIDOMYCOSIS
Disseminated coccidioidomycosis (<3%)
• Spreads beyond lungs to (4)
• Skin: Ulcerated nodules or plaques. • Meningitis: Headache, stiff neck, confusion, seizures. • Risk factors: Filipinos, African Americans, men, pregnant women, AIDS, immunosuppression.
skin, bones, joints, meninges.
COCCIDIOIDOMYCOSIS
• Cavitary lung lesions that may rupture, leading to hemoptysis (coughing up blood). • Can mimic tuberculosis on chest X-ray.
Chronic pulmonary coccidioidomycosis (5%)
Highest risk: Filipinos and Blacks, favor males
Remissions and relapses occur
COCCIDIOIDOMYCOSIS
Pathogenesis & Clinical Findings
• Radiographic exam: hilar adenopathy, pulmonary infiltrates, pneumonia, pleural effusions, or nodules; pulmonary residua (solitary nodule or thin-walled cavity) in about 5%
• Risk factors:
heredity, sex, age, and compromised immune response, pregnant women,
AIDS, other conditions of cellular immunosuppression
COCCIDIOIDOMYCOSIS
Epidemiology & Control
• Endemic in low rainfall, semiarid regions (Lower Sonoran life zone)
• Highly endemic - Southwest, San Joaquin Valley of California, and southern Arizona; Mexico, parts of Central and South America;
It can be isolated from the soil and indigenous rodents.
COCCIDIOIDOMYCOSIS
More males at risk: digging, excavation, construction, archaeology, agriculture, firefighting, mining, gas or oil extraction
COCCIDIOIDOMYCOSIS
COCCIDIOIDOMYCOSIS
Diagnostic Laboratory Tests
• Specimens for culture: (6)
• Examined fresh (after centrifuging, if necessary) for typical spherules
sputum, exudate from cutaneous lesions, spinal fluid, blood, urine, tissue biopsies
COCCIDIOIDOMYCOSIS
Diagnostic Laboratory Tests
• _______ or _______; H&E, GMS, or PAS
• Cultures: ____ or _____ w/ or w/o antibiotics & cycloheximide, 30C or 37C, examine only in level____ biosafety cabinet.
20% KOH or calcofluor white stain
Level 3 biosafety cabinet
COCCIDIOIDOMYCOSIS
Diagnostic Laboratory Tests
• Confirm by detection of a________ or by animal inoculation or use of a specific DNA probe
C. immitis-specific antigen
Morphology & Identification
• Culture:22C, a rapid grower, within a week; white to gray/tan/brown cottony colony in circular bloom;
hyaline septate hyphae form chains of arthroconidia,
chains fragment into individual arthroconidia (airborne, highly resistant to adverse environmental conditions);
small arthroconidia (ave. 3 x 6 um) remain viable for years, highly infectious
COCCIDIOIDOMYCOSIS
COCCIDIOIDOMYCOSIS
Morphology & Identification
Following inhalation of arthroconidia - become_______
spherical, enlarged - SPHERULES
Morphology & Identification
• Mature: thick, doubly refractile walls, a size of 30-80 um in diameter, packed with endospores (2-5 um);
• Rupture releases endospores, develop into new spherules
• Young spherules: have a clear center with peripheral cytoplasm & a prominent thick wall.
COCCIDIOIDOMYCOSIS
COCCIDIOIDOMYCOSIS
Morphology & Identification
• Use_____ medium to produce spherules in the laboratory, 40°C at 20% carbon dioxide
• On wet mount/histologic sections of tissue, sputum, other specimens: Spherules are diagnostic of (2)
Converse
C immitis/ C posadasii.
COCCIDIOIDOMYCOSIS
Antigenic Structures
• 2 clinically useful antigens:
________
• An antigen preparation extracted from the filtrate of a liquid mycelial culture of C immitis
_______
• Produced from a filtrate of a broth culture of spherules
• Coccidioidin skin test: (≥5 mm in diameter) maximum induration between 24 and 48 hours after cutaneous injection of 0.1 ml standardized dilution; spherulin is more sensitive
Coccidioidin
Spherulin
COCCIDIOIDOMYCOSIS
Antigenic Structures
________
: (_____in diameter) maximum induration between 24 and 48 hours after cutaneous injection of 0.1 ml standardized dilution;
spherulin is more sensitive
Coccidioidin skin test
≥5 mm
COCCIDIOIDOMYCOSIS
Diagnostic Laboratory Tests
• ________– Rapid screening test.
• Immunodiffusion (ID) test:
• Positive exoantigen F precipitin line confirms diagnosis.
• – Indicates acute infection.
• – Suggests chronic or past infection.
EIA (IgM & IgG)
IgM
IgG
COCCIDIOIDOMYCOSIS
Diagnostic Laboratory Tests
Antigen Detection Tests
• – Useful in early stages, but cross-reactivity with other fungi.
• – Low specificity, not used for definitive diagnosis.
Urine & Serum Antigen Test
(1→3)-β-D-Glucan Test
COCCIDIOIDOMYCOSIS
Diagnostic Laboratory Tests
Complement Fixation (CF) Test:
• Rising titers (_____) = progressive disease.
• Declining titers = resolution.
• Cross-reactions with other fungi possible.
≥1:32
COCCIDIOIDOMYCOSIS
Diagnostic Laboratory Tests
• Detects Coccidioides DNA– Rapid (~4 hours), but requires specialized facilities. • More reliable than serology in AIDS patients, where antibody tests often fail
Molecular Diagnosis (PCR-based tests)
COCCIDIOIDOMYCOSIS
TREATMENT
• Symptomatic primary infection, self limiting: only supportive treatment,_____ may reduce symptoms
•_____: most commonly prescribed
• Severe cases:______(nephrotoxic), intravenous administration, followed by several months of oral therapy with itraconazole (higher efficacy)
• Coccidioidal meningitis: oral fluconazole, long-term therapy
• Surgical resection of pulmonary cavities sometimes necessary and often curative.
itraconazole
Fluconazole
amphotericin B
• The most prevalent pulmonary intracellular mycosis worldwide,
endemic in the Ohio - Mississippi River valleys of North America
HISTOPLASMOSIS
is the most common endemic mycosis in AIDS patients.
HISTOPLASMOSIS
HISTOPLASMOSIS
• Causative agent:_______ (Hc) (Dr. Samuel Darling, 1906)
• a dimorphic soil saprophyte, a mold in soil and avian habitats enriched by alkaline nitrogenous substrates in guano.
• Initiated by inhalation of the conidia.
Histoplasma capsulatum
HISTOPLASMOSIS
• In humans: Two distinct varieties
• Histoplasma capsulatum var. capsulatum
• Histoplasma capsulatum var. duboisii
HISTOPLASMOSIS
• In humans: Two distinct varieties
•________
• Found globally (mainly North, South, Central America,
Southeast Asia, and Africa)
• Pulmonary (resembles TB) & systemic histoplasmosis
• Darling’s disease, cave or
spelunker’s disease
Histoplasma capsulatum var. capsulatum
HISTOPLASMOSIS
• In humans: Two distinct varieties
•________
• Predominant in Western and Central Africa
• Causes skin and bone lesions
• African histoplasmosis
Histoplasma capsulatum var. duboisii
HISTOPLASMOSIS
• In horses: Hc var.________, lymphangitis
farciminosum
HISTOPLASMOSIS
Morphology and Identification
•_______ (gold standard):
CULTURE
Morphology and Identification
CULTURE
• Mold: white suede surface & pale yellow brown reverse colonies, varying appearance, 4-12 weeks (slow)
HISTOPLASMOSIS
Morphology and Identification
• Morphology: hyaline, septate hyphae produce microconidia (2-5 um) & large,
spherical thick-walled macroconidia with peripheral projections of cell wall material (8-16 um);
“tuberculate macroconidia”
HISTOPLASMOSIS
Morphology and Identification
• Tissue culture/ in vitro-rich medium, 37°C: convert to small, oval yeast cells (2 x 4 um)
• In tissue biopsy: yeasts typically seen within macrophages
• Its teleomorph:
BHIA, 5% sheep blood, 37C: Yeast colonies
Ajellomyces capsulatus, produce ascospores
HISTOPLASMOSIS
Facultative intracellular
Histoplasmosis
HISTOPLASMOSIS
Antigenic Structure
•________
• crude but standardized mycelial broth culture filtrate antigen
• In skin test: positive soon after infection, remains positive for years
• 95% asymptomatic - positive delayed hypersensitivity type skin test
• In progressive disseminated histoplasmosis - may become negative
Histoplasmin
HISTOPLASMOSIS
Antigenic Structure
• A positive “________” indicates past or present infection, but does not differentiate active and past infections.
• Rarely used today, replaced by blood and urine tests.
• Antibodies to yeast and mycelial antigens measurable
histoplasmin skin test
HISTOPLASMOSIS
Pathogenesis & Clinical Findings
Initial inflammatory reaction becomes granulomatous (over 95% CMI response, cytokines activate macrophages, inhibit intracellular growth)
HISTOPLASMOSIS
Pathogenesis & Clinical Findings
• With heavy inoculum: Acute pulmonary histoplasmosis, resolves without therapy, lung nodules heal with calcification
• Chronic pulmonary: mostly men, reactivation of a dormant lesion (lung damage like emphysema)
HISTOPLASMOSIS
Pathogenesis & Clinical Findings
Severe disseminated: infants, elderly, immunosuppressed (AIDS)
• RES - lymphadenopathy, enlarged spleen, liver, anemia, high mortality without antifungal therapy (Reticuloendothelial cytomycosis
• Mucocutaneous ulcers of nose, mouth, tongue, intestine
HISTOPLASMOSIS
Diagnostic Laboratory Tests
A. Specimens & Microscopic
Examination
• Specimens for culture - (5)
• Stain (GMS, PAS, Giemsa) blood films, bone marrow slides, biopsy specimens
• Disseminated histoplasmosis - bone marrow often positive
sputum, urine, scrapings from lesions, bone marrow aspirates, buffy coat blood cells.
HISTOPLASMOSIS
Diagnostic Laboratory Tests
B. Culture
•________ at 37C
• ______at 25-30C
• Alert lab if histoplasmosis is suspected to perform special blood culture methods such as lysis centrifugation or fungal broth medium to enhance recovery
• Confirm by in-vitro conversion to the yeast form
• Detection of a species-specific antigen, or PCR testing for specific DNA sequences
Glucose-cysteine-blood agar
SDA or IMA
Diagnostic Laboratory Tests
C. Serology
• CF tests - positive within 2-5 weeks after infection;
• titers rise during progressive disease (≥1:32), declines when inactive
• Cross reactions occur
• ID tests
antigens detecteins to two H-specific Astopdiests H antigen - active
• Antibodies to M antigen - repeated skin testing or past exposure
HISTOPLASMOSIS
HISTOPLASMOSIS
Diagnostic Laboratory Tests
_____ and______: most sensitive tests
• Circulating polysaccharide antigen of Hc
• Nearly all with disseminated form - positive test for antigen in the serum or urine
• Antigen level drops after successful treatment and recurs during relapse
• More sensitive than conventional antibody tests in AIDS patients with histoplasmosis
RA or EIA
Epidemiology and Control
• Acute outbreaks - highest in the US, Ohio-Mississippi River valleys o Disturbed soil mixed with bird feces (starling roosts, chicken houses, or bat guano in caves)
• Birds not infected, their increment provides superb culture conditions
• Conidia spread by wind and dust
• 80-90% residents have positive skin test.
• Not communicable from person-to-person.
• Spraying formaldehyde on infected soil may destroy Hc.
HISTOPLASMOSIS
