OPPORTUNISTIC MYCOSES Faculty: Samuel Aguazim M.D. Lange Chapter 50 1

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

Candida Candida albicans, the most important species of Candida. Diseases: Thrush, Vaginitis, and chronic mucocutaneous candidiasis Characteristics: oval yeast with a single bud when part of the normal flora of mucous membranes forms pseudohyphae when it invades tissue. yeast form produces germ tubes when incubated in serum at 37 0 C 3

4 Gram stain of C. albicans in a "yeast infection" Potassium hydroxide examination. Candida. Pseudohyphae with budding spores (higher magnification). C. albicans germ tube

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

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

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

10 Candida Transmission:Part of the normal flora of skin, mucous membranes, and gastrointestinal tract. No person-to-person transmission. Pathogenesis: Predisposing factors include depressed immune system, altered skin and mucous membrane, suppression of normal flora, and presence of foreign bodies. Skin lesions occur frequently on moisture-damaged skin. Disseminated infection occurs in immunosuppressed patients and intravenous drug users. Chronic mucocutaneous candidiasis occurs in children with a T cell defect in immunity to Candida. Vaginitis due to decreases in the vagina normal flora ‘Lactobacillus species’ by using antibiotics lead to overgrowth of Candidia albicans.

Clinical findings C. albicans overgrowth can lead to: Oral thrush of the mouth that appears as a white exudate on mucous membranes. Vaginitis that presents with itching, copious secretion, and “cottage cheese” appearing clumps. Cutaneous candidiasis can present as a beefy red rash with satellite pustular lesions in moist intertriginous areas (where two skin areas touch) such as under the breasts, axilla of the arm, or anogenital region. 11

12 Oral thrush. CDC

Vaginal candidiasis 13

Cutaneous candidiasis 14

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In immunocompromised individuals In immunocompromised individuals, persistent infection can spread and lead to esophagitis and disseminated candidiasis, which may lead to infective endocarditis. Candida esophagitis presents as retrosternal pain upon swallowing is considered an AIDS-defining illness. Oral thrush is not considered AIDS-defining. T-cell deficient patients are more likely to get superficial Candida infections, whereas neutropenic patients are more likely to have disseminated candidiasis (hematogenous). 16

17 Candida Laboratory Diagnosis: yeasts and pseudohyphae. colonies of yeasts on Sabouraud’s agar. The yeast form produces germ tubes when incubated in serum at 37 0 C: distinguish C albicans from other candida species. Chlamydospores are typically formed by C. albicans but not by other species of cadida. Skin tests with candida antigens are uniformly positive in immunocompetent adults and are used as an indicator that the person can mount a cellular immune response.

Treatment and Prevention 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 or Fluconazole. 3- Chronic mucocutaneous candidiasis: ketoconazole. 4- The drug of choice for oropharyngeal or esophageal thrush is fluconazole and Nystatin mouthwash 5. Caspofungin or micafungin can also be used for esophageal candidiasis Prevention:Predisposing factors should be reduced. Oral thrush can be prevented by using clotrimazole. 18

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

Cryptococcus neoformans Disease: Cryptococcosis, especially cryptococcal meningitis. Cryptococcosis is the most common life- threatening fungal disease in AIDS patients 21

Properties Characteristics: Oval, budding yeast surrounded by a wide polysaccharide capsule. Not dimorphic. Note that this organism forms a narrow based bud, whereas the yeast form of Blastomyces dermatitidis forms a broad- based bud 22

23 Cryptococcus neoformans: note the thick capsule and unequal budding. Cryptococcus neoformans growing on Sabouraud’s agar. Cryptococcosis, lung, GMS stain. Credit: Ed Uthman, MD.

24 Cryptococcus neoformans Habitat: is soil, especially where enriched by pigeon droppings. Transmission: Inhalation of airborne yeast cells. Pathogenesis: influenzalike syndrome or pneumonia. spread via the bloodstream to the meninges. Reduced cell-mediated immunity predisposes to severe disease, but some cases of cryptococcal meningitis occur in immunocompetent people.

25 Cryptococcus neoformans Laboratory Diagnosis: Visualization of the yeast cell surrounded by a wide unstained capsule in India ink preparations of spinal fluid. Culture of sputum or spinal fluid on Sabouraud’s agar produces colonies of yeasts. Latex agglutination test detects polysaccharide capsular antigen in spinal fluid Mucicarmine stain is specific for Cryptococcus and highlights both the yeast form and the capsule. In cryptococcal meningoencephalitis, "soap bubble" lesions, fungus-filled cysts, may be present in gray matter.

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27 In cryptococcal meningitis, "soap bubble" lesions, fungus-filled cysts, may be present in gray matter. Cryptococcosis, lung, mucicarmine stain. Credit- Ed Uthman, MD.

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

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

Treatment and Prevention Treatment: intrathecal administration of amphotericin B and flucytosine combination therapy (fungicidal) for meningitis Prevention: Cryptococcal meningitis can be prevented in AIDS patients by using fluconazole. 30

31 Aspergillus fumigatus Diseases: infections of the skin, eyes, ears and other organs; “fungus ball” in the lung and allergic bronchopulmonary aspergillosis. 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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33 Lung: Aspergillus hyphae ( V shape angle) in fungal pneumonia

34 Aspergillus fumigatus Pathogenesis: In immunocompromised patients, invasive disease occurs. invades blood vessels, causing thrombosis and infarction. 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: Septate hyphae invading tissue are visible microscopically. Forms colonies with characteristic radiating chains of conidia when cultured on Sabouraud’s agar. 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.

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36 Aspergillus spores form in radiating

37 Aspergillus pneumonia in lung of deer

38 Mucor & Rhizopus species Disease: Mucormycosis. Characteristics:Molds with nonseptate hyphae with right angle branching. Not dimorphic. Habitat: is the soil. Transmission:Inhalation of airborne sporangiospores.

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

41 Periorbital mucormycosis; the patient was immunocompromised.

42 Mucormycosis infection of the nose.

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44 Mucor & Rhizopus species Treatment:Amphotericin B and surgical removal of necrotic infected tissue. Prevention: No vaccine or prophylactic drug is available. Control of underlying disease, eg, diabetes, tends to prevent mucormycosis.

45 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 tissue

46 Pneumocystis jirovecii at high magnification. Numerous trophozoites scattered throughout. Note the round cyst in the center with 8 haploid nuclei.

47 Diagnostic silver stain of sputum culture demonstrating Pneumocystis carinii cysts.

48 Chest x-ray may show diffuse, bilateral infiltrates extending from the perihilar region described as “ground-glass.”

49 Pneumocystis carinii (jirovecii ) Treatment: Trimethoprim-sulfamethoxazole (TMP- SMX), pentamidine. Prevention: Trimethoprim-sulfamethoxazole or aerosolized pentamidine in immunosuppressed individuals.