Endemic Mycoses Flashcards
Endemic fungal infections
- These occur in immunologically normal and impaired hosts
- May have generally defined geographic endemic zones
- All are dimorphic
- Include
- Histoplasmosis
- Blastomycosis
- Sporotrichosis
- Paracoccidioidomycosis
- Penicilliosis (Talaromycosis)
- Coccidioidomycosis
Histoplasmosis
- Most common endemic mycosis in the United States
- Described by Samuel Darling in Panama in 1906
-originally thought to be Leishmania
• One species associated with human disease
- Histoplasma capsulatum
- var capsulatum
- var duboisii
Histoplasmosis - Mycology
Histoplasmosis - Ecology and epidemiology
Histoplasmosis - Clinical Disease
• Asymptomatic infection
- 50-85% of all cases
• Acute pulmonary
- Pneumonia
- Pericarditis
- Bob Dylan in 1997
- Chronic pulmonary
- Disseminated
- Fibrosing mediastinitis
Acute Pulmonary Histoplasmosis
- Often associated with a specific exposure
- Dry cough, fever, fatigue
- 5% erythema nodosum, myalgias, arthralgias
- Patchy alveolar infiltrates on chest radiograph
- Usually self-limited over several weeks
Chronic pulmonary histoplasmosis
Disseminated histoplasmosis
• Frequently associated with depressed cellular immune function
- AIDS
- Chronic course in older men
• Hepatosplenomegaly, lymphadenopathy, weight loss
- mucous membrane ulcers
- skin lesions
- adrenal insufficiency
Histoplasmosis - Fibrosing mediastinitis
- Excessive fibrosis enveloping mediastinal structures
- Obstruction of vena cava & other structures
- hemoptysis, dyspnea
- may mimic nodular sclerosis Hodgkins disease
Histoplasmosis - Diagnosis
• Culture
- growth as mold at 30°C
- may take 6 weeks
- DNA probe
- Histological identification
- budding yeasts 2-4 µm inside macrophages
• Antigen detection
- enzyme immunoassay (EIA) for H. capsulatum polysaccharide
- blood, urine, bronchoalveolar fluid, CSF
- in >75% of diffuse pneumonia and disseminated disease
- less likely positive in less severe infection
- cross-reacts with Blastomyces, Penicillium, Paracoccidioides, Coccidioides
- Serologic tests
- complement fixing (CF) and immunodiffusion (ID)
- yeast & mycelial antigens
- persist for years
- most useful for persistent and chronic pneumonia
Histoplasmosis Therapy
• Many cases do not require antifungal therapy
- self-limited pulmonary
- mediastinal fibrosis
- pericarditis
- Symptomatic pulmonary & disseminated diseas - liposomal amphotericin B
- severe disease
- itraconazole
• mild to moderate disease
Blastomycosis
Blastomycosis - Mycology
Blastomycosis - Clinical Presentation
Blastomycosis - Diagnosis
• Histopathology
- broad-based budding yeast in tissue
• Culture
- takes several weeks
- mold difficult to identify by appearance difficult
- exoantigen
- Antibody
- not useful
- many cross-reactions
- Antigen test now available
Blastomycosis - Treatment
• Pulmonary disease
- mild to moderate: itraconazole
- severe disease: amphotericin B
• Disseminated disease
- CNS: amphotericin B
- Other
- Severe: amphotericin
- Mild to moderate: itraconazole
Sporotrichosis
Sporotrichosis - Clinical Presentation
• Chronic subcutaneous suppurating infection
- pustules
- ulcers
- lymphangitic spread
• Pneumonia and osteoarticular infection increasingly reported
- older male, smoker and alcohol use
Sporotrichosis - Diagnosis
- mold usually grows 3-5 days at 30°C
• “daisy” clusters on microscopic examination - histopathology reveals 3-5 µm budding, oval yeasts
- but rarely seen in human cases;
- “asteroid bodies” radiating eosinophilic rays
Sporotrichosis - Treatment
• Lymphocutaneous sporotrichosis
- itraconazole
• 200 mg oral daily -
saturated solution potassium hydroxide (SSKI)
- was standard treatment
- 5 drops TID oral with increasing weekly
- terbinafine
• 500 mg oral twice daily
- limited experience
- hyperthermia
- may be effective because of thermal intolerance of S. schenckii
- Pneumonia and osteoarticular disease
- amphotericin B intravenously
- itraconazole 200 mg oral twice daily
Paracoccidioidomycosis
- Endemic to Brazil
- Name derived because of initial confusion with coccidioidomycosis
- also called South American blastomycosis
- Most cases in older men with heavy tobacco and alcohol use
- Ulcerated lesions of the nares, oral cavity
- Due to Paracoccidioides brasiliensis
- dimorphic
- yeast-form seen in tissue
- “steering wheel”
- Itraconazole primary therapy
Penicilliosis (Talaromycosis)
• Penicillium marneffei (now called Talaromyces marneffei)
- isolated from a bamboo rat in Vietnam in 1956
- named after Hubert Marneffe, director of the Institut Pasteur in Indochina
- dimorphic
• First non-iatrogenic human case reported in 1973
- missionary with Hodgkins disease
• With the AIDS epidemic, now a common opportunistic infection in Southeast Asia
- Thuy Le, M.D., Ph.D, Associate Professor, Duke University
- M.D. 2002 from University of Arizona
- Fever, weight loss, papular skin lesions hepatosplenomegaly, lymphadenopathy
Penicilliosis (Talaromycosis) - Diagnosis
- On culture, produces a red, diffusable pigment
- Septate yeast seen on biopsy
Penicilliosis (Talaromycosis) - Therapy
- amphotericin B followed by itraconazole has been most commonly used
Coccidioidomycosis
• Coccidioides is now recognized as two genetically distinct species
- C. immitis
• mostly confined to the San Joaquin Valley of California
- C. posadasii
• geographically diverse
- No clear morphological, biochemical or clinical differences between these two species
Life cycle of Coccidioides
Common presenting symptoms of pulmonary coccidioidomycosis
- Cough
- Pleuritic chest pain
- Fever
- Usually acute (over days)
- May be difficult to distinguish from community-acquired pneumonia (“CAP”) that is due to bacterial etiology
Symptoms suggestive of pulmonary coccidioidomycosis
- Night sweats
- Fatigue
- Rash
- Headache
- Weight loss
- Symptoms persisting for weeks
Rashes associated with primary pulmonary coccidioidomycosis
Coccidioidomycosis - Distinctive radiographic features
- Dense infiltrate
- Upper lobe
- Associated hilar or mediastinal adenopathy
Diffuse or “miliary” pulmonary coccidioidomycosis
• Occurs in highly immunocompromised patients
- presentation of AIDS in coccidioidal endemic region
- manifestation of fungemia
• May also occur from high inoculum exposure
- archeology
Clinically disseminated coccidioidomycosis
- Occurs in ≤1% of instances
- Most common sites
- Skin & soft tissue
- Bone & joint
- Meninges
- Diffuse pulmonary disease
• Generally associated with a lack of specific cellular immune response
Cutaneous Coccidioidomycosis
Vertebral Coccidioidomycosis
Coccidioidomycosis - Meningitis
• Presentation of subacute decreasing mental status, headache
- One-half present without preexisting pneumonia
• Lymphocytic pleocytosis with hypoglycorrhachia
- confused with tuberculous meningitis
- coccidioidal meningitis > tuberculous meningitis in endemic region
- Universally fatal if untreated
- Course can be complicated by hydrocephalus
- despite appropriate antifungal therapy
Coccidioidomycosis - Diagnosis Culture
Coccidioidomycosis - Diagnosis Histology
Coccidioidomycosis - Diagnosis Direct Examination
Coccidioidomycosis - Diagnosis Serology
•Serology is very commonly used in the diagnosis. While very specific, its sensitivity is not known and it may be negative early in the course of illness. There are a variety of serological tests and interpretation of results is different for each. In patients with disseminated disease, high titers of anti-coccidioidal IgG occur. These decline as the patient improves with therapy.
Issues with coccidioidal serology
• TP (IgM)
- False positive results
• latex agglutination (LPA), EIA
- Titer not prognostically useful
- Insensitive for diagnosis of meningitis
• CF
- Elevated titers reflect worsening clinical disease
- EIA IgG optical density ≠ titer
• Discrepancies between EIA IgG & other methods
- Concentrating serum may increase diagnostic yield
Coccidioidomycosis Treatment
- Most patients will not require any therapy
- Once started, prolonged therapy (≥12 months) is the rule
- Relapse occurs in 15 - 30%
- Meningitis appears to be rarely if ever cured
- Potential for teratogenicity in women with high-dose azoles
Indications for treatment of primary coccidioidal pneumonia
- Weight loss >10%
- Night sweats for > 3 weeks
- Extensive pneumonia
- Greater than 50% of one lung
- Both lungs
- Coccidioidal CF > 1:16
- Inability to work
- Persistence of symptoms for > 2 months
Treatment of non-meningeal disseminated infection
- Amphotericin B ± triazole for initial therapy in severly ill patients
- Amphotericin B can then be tapered and patient left on long-term triazole
- Length of therapy unclear
- low or undetectable CF titer
- evidence of cellular immunity
Treatment of meningeal disease
- Fluconazole or itraconazole
- Follow for development of hydrocephalus
- Failure
- newer triazoles
- intrathecal amphotericin B
• Treatment should be life-long
