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

OPPORTUNISTIC MYCOSES

Faculty: Samuel Aguazim M.D.

Lange Chapter 50

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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 0C 3

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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

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

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

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CandidaTransmission: 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.

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12 Oral thrush. CDC

Vaginal candidiasis 

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Cutaneous candidiasis

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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).

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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 0C: 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 mouthwash5. Caspofungin or micafungin can also be used for

esophageal candidiasis Prevention: Predisposing factors should be reduced.

Oral thrush can be prevented by using clotrimazole.

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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

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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

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Cryptococcus neoformans: note the thick capsule and unequal budding.

Cryptococcus neoformans growing on Sabouraud’s agar.

Cryptococcosis, lung, GMS stain. Credit: Ed Uthman, MD.

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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.  

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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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In cryptococcal meningitis, "soap bubble" lesions, fungus-filled cysts, may be present in gray matter.

Cryptococcosis, lung, mucicarmine stain. Credit- Ed Uthman, MD.

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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 capsule stains red

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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.

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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

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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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36Aspergillus spores form in radiating

37 Aspergillus pneumonia in lung of deer

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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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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

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Periorbital mucormycosis; the patient was immunocompromised.

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Mucormycosis infection of the nose.

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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.

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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 tissue

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

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Diagnostic silver stain of sputum culture demonstrating Pneumocystis carinii cysts.

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

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Pneumocystis carinii (jirovecii )

Treatment: Trimethoprim-sulfamethoxazole (TMP-SMX), pentamidine. 

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