Mi090717 F 3. Opportunisticmycoses

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Opportunistic fungi: ü Fungi fail to induce disease in most immunocompetent persons but can do so in those with impaired host defenses ü or by using antibiotics which suppresses the normal flora lead to the overgrowth of opportunistic fungi

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Candida   Candida albicans, the most important species of Candida. Diseases: Thrush, Vaginitis, and chronic mucocutaneous candidiasis Characteristics: ü oval yeast with a single bud when part of the normal flora of mucous membranes ü forms pseudohyphae when it invades tissue. ü yeast form produces germ tubes when incubated in serum at 37 0C

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Candida albicans methenamine silver stain. Pseudohyphae 5and budding yeast . ASCP 

Oval budding yeast cells of Candida albicans. Fluorescent 6 antibody stain.CDC

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Candida albicans showing germ tubes . Calcofluor white 8 stain in peptone medium .

Candida 

Transmission: Part of the normal flora of skin, mucous membranes, and gastrointestinal tract. No person-to-person transmission.

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Pathogenesis: ü Predisposing factors include depressed immune system, altered skin and mucous membrane, suppression of normal flora, and presence of foreign bodies. ü Skin lesions occur frequently on moisture-damaged skin. ü Disseminated infection occurs in immunosuppressed patients and intravenous drug users. ü Chronic mucocutaneous candidiasis occurs in children with a T cell defect in immunity to Candida. ü Vaginitis due to decreases in the vagina normal flora ‘Lactobacillus species’ by using antibiotics lead to overgrowth of Candidia albicans. 

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Oral thrush. CDC

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Candida 

Laboratory Diagnosis: ü yeasts and pseudohyphae. ü colonies of yeasts on Sabouraud’s agar. ü The yeast form produces germ tubes when incubated in serum at 37 0C: distinguish C albicans from other candida species. Treatment:  1- Skin and mucous membrane disease can be treated with oral or topical antifungal agents such as miconazole.  2- Disseminated disease requires amphotericin B.  3- Chronic mucocutaneous candidiasis: ketoconazole.  4- The drug of choice for oropharyngeal or esophageal thrush is fluconazole  Prevention: Predisposing factors should be reduced. Oral thrush can be prevented by using clotrimazole. 12

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Sputum smear from patient with pulmonary candidiasis. 14 Gram stain. CDC 

Cryptococcus neoformans   Disease: Cryptococcosis, especially cryptococcal meningitis. Characteristics: Oval, budding yeast surrounded by a wide polysaccharide capsule. Not dimorphic.

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Cryptococcus neoformans    

Habitat: is soil, especially where enriched by pigeon droppings.

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Transmission: Inhalation of airborne yeast cells.

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Pathogenesis: ü influenzalike syndrome or pneumonia. ü spread via the bloodstream to the meninges. ü Reduced cell-mediated immunity predisposes to severe disease, but some cases of cryptococcal meningitis occur in 16 immunocompetent people. 

Cryptococcus neoformans Laboratory Diagnosis: ü Visualization of the yeast cell surrounded by a wide unstained capsule in India ink preparations of spinal fluid. ü Culture of sputum or spinal fluid on Sabouraud’s agar produces colonies of yeasts. ü Latex agglutination test detects polysaccharide capsular antigen in spinal fluid Treatment: Amphotericin B plus flucytosine for meningitis. Prevention:Cryptococcal meningitis can be prevented in AIDS patients by using fluconazole. 

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Histopathology of lung shows widened alveolar septum containing a few inflammatory cells and numerous yeasts of Cryptococcus neoformans. The inner layer of the yeast 19 capsule stains red

Histopathology of lung shows numerous extracellular yeasts of Cryptococcus neoformans within analveolar space. Yeasts 20 show narrow-base budding and characteristic variation in size.

Aspergillus fumigatus  Diseases: ü infections of the skin, eyes, ears and other organs; ü “fungus ball” in the lung and allergic bronchopulmonary aspergillosis. ü Exist only as mold with septate hyphae that branch at a V-shaped angle. Habitat: is the soil. Transmission: Inhalation of airborne condidia.

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23 ) Lung: Aspergillus hyphae ( V shape angle in fungal pneumonia 

Aspergillus fumigatus  

Pathogenesis: ü In immunocompromised patients, invasive disease occurs. ü invades blood vessels, causing thrombosis and infarction. ü In a person with a lung cavity (TB cavity), a “fungus ball” (aspergilloma) can develop. An allergic person can develop allergic bronchopulmonary aspergillosis (ABPA). Laboratory Diagnosis: ü Septate hyphae invading tissue are visible microscopically. ü Forms colonies with characteristic radiating chains of conidia when cultured on Sabouraud’s agar. ü Serologic tests detect IgG precipitins in patients with aspergillomas and IgE antibodies in patients with allergic bronchopulmonary aspergillosis (ABPA). Treatment: Amphotericin B for invasive aspergillosis. Some lesions can be surgically removed. Steroid therapy is recommended for allergic bronchopulmonary aspergillosis. 24

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Aspergillus spores form in radiating

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of deer 

27 Aspergillus pneumonia in lung

Mucor & Rhizopus species Disease: Mucormycosis. Characteristics: hyphae with right dimorphic.

Molds with nonseptate angle branching. Not

Habitat: is the soil. Transmission: Inhalation of airborne sporangiospores.

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Mucor & Rhizopus species Pathogenesis: ü ketoacidotic diabetic and leukemic patients. ü nose and sinuses are typically involved. ü Hyphae invade the mucosa and progress into underlying tissue and vessels, leading to necrosis and infarction. ü erode into the bones of the cranium, causing a life threatening meningitis and or encephalitis that it is very difficult to treat.  Laboratory Diagnosis: ü Microscopic examination of tissue for the presence of invasive hyphae. ü Forms colonies with spores contained within a sporangium when cultured on Sabouraud’s agar 30 

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Pneumocystis carinii (jirovecii ) Disease: Pneumonia. Reclassified in 1988 as a yeast. Life cycle: uncertain Transmission: inhalation. Humans are reservoir. Occurs worldwide. Most infections asymptomatic. Pathogenesis: Organisms Bilaterally in Interstitial space and alveoli cause inflammation. Immunosuppression predisposes to disease. Laboratory Diagnosis: Organisms visible in silver stain of lung 32 tissue 32

Pneumocystis carinii (jirovecii ) Treatment: Trimethoprim-sulfamethoxazole (TMPSMX), pentamidine.

Prevention: Trimethoprim-sulfamethoxazole or aerosolized pentamidine in immunosuppressed individuals. 33

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Mucor & Rhizopus species

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Treatment: Amphotericin B and surgical removal of necrotic infected tissue.

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Prevention: ü No vaccine or prophylactic drug is available. ü Control of underlying disease, eg, diabetes, tends to prevent mucormycosis. 

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1. A 39 year old HIV positive woman is in severe respiratory distress with fever and chills. A lung biopsy was performed and a fungus was seen which has septate hyphae which branches acutely (45 angle). What is the fungus responsible for this patient’s symptoms? A. Cryptococcus neoformans B. Aspergillus fumigatus C. Histoplasma capsulatum D. Blastomyces dermatitidis E. Coccidioides immitis. 35

2. Which of the following fungi is associated with skin lesions occurring frequently on moisture-damaged skin? Disseminated infection also occurs in immunosuppressed patients and intravenous drug users. A. Cryptococcus neoformans B. Histoplasma capsulatum C. Candida albicans D. Blastomyces dermatitidis E. Coccidioides immitis 36

20. A 27 years old intravenous drug user presents with difficulty swallowing. Examination of the oropharynx reveals white plaques (thrush). Which of the following is BEST description of the microscopic appearance of the microorganism responsible for this patients iliness? (A) Sepherules (B) Mold with nonseptate hyphae (C) Mold with septate hyphae (D) Encapsulated yeast (E) Budding yeasts and pseudohyphae 37

15. Your patient is a 45-year-old woman. This morning, she awoke with a pain near her right eye. On physical examination, her temperature is 38 C and the skin near her eye is necrotic. A biopsy specimen of the lesion contains nonseptate hyphae invading the blood vessels. Of the following, which one is the MOST likely cause? (A) Histoplasma capsulatum (B) Aspergillus fumigatus (C) Cryptococcus neoformans (D) Mucor species 38

91. A 48 year old immunocompromised man is seen in the emergency. A lumbar puncture was performed which showed an encapsulated spherical fungal cell when isolated using an India Ink stain. Which of the following fungus is responsible for this patient’s symptoms? A. Cryptococcus neoformans B. Candida albicans C. Histoplasma capsulatum D. Blastomyces dermatitidis E. Coccidioides immitis 39