opportunistic mycoses

Opportunistic Mycoses

• Opportunistic fungi usually don't cause disease in immunocompetent individuals.
• Those with impaired host defenses are susceptible.
• Summaries of key features of opportunistic fungal diseases are available in table format.
• Eight fungi include Candida, Cryptococcus, Aspergillus, Mucor & Rhizopus, Pneumocystis, Penicillium marneffei, Pseudallescheria boydii, and Fusarium solani.

Medically Important Fungi Genera

• Five genera are considered medically important: Candida, Cryptococcus, Aspergillus, Mucor, and Rhizopus.

Candida

• Approximately 90% of Candida infections are caused by Candida albicans.
• Pathogenic non-albicans Candida (NCAC) species include, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida krusei Candida auris and Candida guilliermondii.

Candida Diseases

• Candida albicans is the most important species.
• It can cause diseases such as thrush, vaginitis, and esophagitis.
• Can also cause diaper rash and chronic mucocutaneous candidiasis.
• It can also cause disseminated infections like right-sided endocarditis, bloodstream infections (candidemia), and endophthalmitis.
• Other important infections are related to indwelling intravenous and urinary catheters.

Candida Properties

• C. albicans is an oval yeast with a single bud.
• C. albicans is part of the normal flora of mucous membranes, found in the upper respiratory, gastrointestinal, and female genital tracts.
• In tissues, Candida may appear as yeasts or pseudohyphae.
• Pseudohyphae are elongated yeasts that resemble hyphae but are not true hyphae.
• True hyphae are created when C. albicans invades tissues.
• Carbohydrate fermentation reactions effectively differentiate Candida from other species like Candida tropicalis, Candida parapsilosis, Candida krusei, and Candida glabrata.

Candida Transmission

• C. albicans is already present as part of the normal flora on skin and mucous membranes.
• The presence of C. albicans on the skin predisposes individuals to infections when skin is penetrated by instruments like needles (especially in intravenous drug use) and indwelling catheters.

Candida Pathogenesis & Clinical Findings

• Disease occurs when local or systemic host defenses are impaired. Mouth: Overgrowth of C albicans in the mouth produces a pseudomembrane
• This presents as white, creamy patches on the oral mucosa that can be scraped off, revealing inflamed tissue underneath and is called oral thrush.
• Vaginitis presents with itching and discharge, favored by high pH, diabetes, and antibiotics.
• Antibiotics suppress Lactobacillus, which keeps pH low, causing pH to rise and favoring Candida growth.
• Skin invasion occurs in warm and moist areas, leading to red and weeping lesions.

Oral Candidiasis

• Characterized by lacy, white patches on top of reddened areas on the tongue, throat, and mouth.
• May include fever and a burning sensation in the mouth.
• On the tongue and soft palate, also called oral candidiasis, mycotic stomatitis, or white mouth.
• Characterized by raised white patches on the tongue, which, when gently scraped, reveal inflamed tissue that bleeds easily.
• Begins on the tongue and can spread to the gums, palate, tonsils, throat, and elsewhere.

Vaginal Candidiasis

• Thick white discharge is present without cervical inflammation in vaginal candidiasis.
• A wet mount will show pseudohyphae.

Cutaneous Candidiasis

• Cutaneous Candidiasis (Candida Skin Infection).
• Candidal Intertrigo occurs in moist, overlapping skin folds, like under the breasts, in the inner thighs, and armpits.
• Characterized by red, raw skin surrounded by scaling and lesions that itch, ooze, or hurt.
• Hands and feet become involved when repeatedly immersed in water
• Fingers and nails can become involved, leading to thickening or loss of the nail.

Candidal Intertrigo

• Superficial skin-fold infection caused by candida.
• Triggered by a combination of a hot and damp environment in skin folds, conducive to candida albicans growth, and increased skin friction.
• Risk factors include occlusive clothing, excessive sweating, obesity, diabetes mellitus, incontinence, and immune deficiency conditions.

Candida Diaper Rash

• Occurs in infants when wet diapers are not changed promptly.

Candida Nail Infections

• Candida nail infections (paronychia) start near the nail fold or cuticle presenting redness and swelling at the base of the nail.
• White, yellow, green, or black marks develop on the nail, which may lift off its bed and be tender.

Chronic Mucocutaneous Candidiasis

• May disseminate to many organs or cause chronic mucocutaneous candidiasis in immunosuppressed individuals.
• Prolonged infection of the skin, oral and genital mucosa, and nails which occurs in individuals deficient in T-cell immunity.
• Patients with mutations in the gene encoding interleukin-17 (IL-17) and its receptor are predisposed to chronic mucocutaneous candidiasis.
• After organ transplantation, patients receiving immunosuppressive drugs are predisposed to invasive candida infections.

Candida Esophagitis

• Candida esophagitis, often accompanied by involvement of the stomach and small intestine, is seen in patients with leukemia and lymphoma.
• Subcutaneous nodules are often seen in neutropenic patients with disseminated disease.
• C. albicans is the most common species causing disseminated disease in these patients.
• C. tropicalis and C. parapsilosis are also important pathogens.

Laboratory Diagnosis

• In exudates or tissues, budding yeasts and pseudohyphae appear gram-positive.
• Can be visualized using calcofluor-white staining.
• Typical yeast colonies are formed in culture, resembling large staphylococcal colonies.
• The germ tube test (GTT) is performed in serum at 37°C and distinguishes C. albicans from most other Candida species.
• Chlamydospores are typically formed by C. albicans but not by other Candida species.
• Serologic testing is rarely helpful.

Candida Macroscopic morphology

• Colonies on Sabouraud dextrose agar are white to cream, soft, and smooth to wrinkled.

Candida Microscopic morphology

• On culture media following 72 hours incubation at 25°C, abundant branched pseudohyphae and true hyphae with blastoconidia are present.
• Grape-like clusters of blastoconidia form along the length of hyphae. Terminal chlamydoconidia can form with extended incubation.

Skin Tests

• Skin tests with Candida antigens are uniformly positive in immunocompetent adults.
• Skin tests are also used as indicators of a person's ability to mount a cellular immune response.
• A person who does not respond to Candida antigens in the skin test is presumed to have deficient cell-mediated immunity.
• Such a person is anergic; therefore, other skin tests cannot be interpreted reliably.
• A negative Candida skin test means a negative purified protein derivative (PPD) skin test for tuberculosis could be false-negative.

Candida Treatment & Prevention

• Fluconazole is the drug of choice for oropharyngeal or esophageal thrush.
• Itraconazole and Voriconazole are also effective.
• Caspofungin or Micafungin are used for esophageal candidiasis.
• Skin infections are treated with topical antifungal drugs like clotrimazole or nystatin.
• Candida vaginitis is treated with topical (intravaginal) azole drugs, such as clotrimazole or miconazole, or with oral fluconazole.
• Ketoconazole is appropriate for management of mucocutaneous candidiasis.
• Amphotericin B or Fluconazole is suitable choices for treatment of disseminated candidiasis.
• Liposomal Amphotericin B is used in patients with pre-existing kidney damage.
• Flucytosine can be used with or without either of these two drugs.
• Treatment of candidal infections with antifungal drugs should be supplemented by reduction of predisposing factors.
• Strains of C. albicans have emerged that are now resistant to azole drugs emerged, especially in AIDS patients on long-term fluconazole prophylaxis.
• Certain Candidal Infections (e.g., Thrush) are preventable with Oral Clotrimazole Troches, Buccal Miconazole Tablets, or Nystatin "swish & swallow".
• Fluconazole is helpful in preventing candidal infections in high-risk patients, such as those undergoing bone marrow transplantation and premature infants.
• Micafungin can also be useful.
• There is no available vaccine.

Cryptococcus

• Two species are called Cryptococcus neoformans & Cryptococcus gattii.

Cryptococcus Disease

• Cryptococcus neoformans causes cryptococcosis.
• Can cause Cryptococcal Meningitis
• Cryptococcosis is considered the most common life-threatening invasive fungal disease worldwide, especially in AIDS patients.
• Cryptococcus gattii, another species, less frequently causes human disease .

Cryptococcus Properties

• C. neoformans is an oval, budding yeast surrounded by a wide polysaccharide capsule.
• The yeast is not dimorphic.
• It forms a narrow-based bud.
• C. neoformans is india ink preparation with budding yeasts with wide capsules.
• India ink stains the background, not the yeast itself.

Cryptococcus Transmission

• C. neoformans occurs widely in nature, growing abundantly in soil containing bird droppings, especially pigeon droppings.
• Birds, however, are not infected.
• Human infection results from the inhalation of the organism.
• No human to human transmission.
• C. gattii is associated with eucalyptus trees but also found in subtropical and tropical areas of many countries.

Cryptococcus Pathogenesis and Clinical Findings

• Lung infections are often asymptomatic but have the potential to produce pneumonia.
• Disease caused by C. neoformans occurs mainly in patients with reduced cell-mediated immunity, especially AIDS patients.
• The organism disseminates to the CNS (meningitis) and other organs in AIDS patients.
• Subcutaneous nodules are often seen in disseminated disease.
• Roughly half the patients with cryptococcal meningitis do not show evidence of immunosuppression,.
• In some patients with AIDS infected with Cryptococcus, Highly Active Antiretroviral Therapy (HAART) can cause exacerbation of symptoms.
• This is called Immune Reconstitution Inflammatory Syndrome. Increasing the # of CD4 cells, this increases inflammatory response.
• Cryptococcal IRIS has been shown to be, sometimes, fatal.
• To avoid these, underlying infection should be dealt with pre-HAART.
• C. gattii , although it is less prevalent, is more likely to cause infection in immunocompetent person
• C. gattii more likely to cause Cryptococcomas (Granulomas).

Cryptococcus Laboratory Diagnosis:

• In CSF mixed with India ink, yeasts are surrounded a wide, unstained capsules.
• Appearance in Gram stain is unreliable & Stains such as Methenamine Silver, Periodic Acid-Schiff & Mucicarmine all allow the organism to be visualized.
• Can be cultured from spinal fluid & other specimens.
• Colonies are Highly Mucoid due to a large amount of capsular polysaccharide.
• Capsular antigen occurs in High Titer is found in infected spinal fluid & can be detected by Latex Particle Agglutination Test and is named Cryptococcal Antigen Test "crag".
• Distinguishing between C. neoformans & C. gattii in laboratory requires specialized media, many C. gattii infections may go undiagnosed
• SDA without cycloheximide
• Colony morphology creamy & shiny, smooth, mucoid colony

Cryptococcus Treatment & Prevention

• Combined treatment with Amphotericin B & Flucytosine is indicated for meningitis and other disseminated diseases..
• Liposomal Amphotericin B would be used in patients with Preexisting Kidney Damage.
• There are no known prevention methods.
• Fluconazole is used in AIDS patients to suppress cryptococcal meningitis in the long term.
• C. gattii is less responsive to antifungal drugs than is C. neoformans.

Aspergillus

• Can cause Aspergillosis

Aspergillus Name

• The name Aspergillus comes from the Latin word Aspergillum, meaning holy water sprinkler, which refers to the fungus's sprinkler-like appearance when viewed under a microscope.
• Aspergillus includes 132 species.
• The most common version is Black Mould.
• Few species of Aspergillus, A. Flavus, A. Niger and A. Fumigatus, make up human and animal pathogens and cause Aspergillosis- a group of lung diseases.

Aspergillus Properties

• Aspergillus species exist only as molds not dimorphic.
• Aspergillus has Septate Hyphae that make V-shaped (Dichotomous) Branches.
• Walls are more mostly Parallel.
• Conidia of Aspergillus form Radiating Chains.
• Galactomannan antigen exists a polysaccharide found in the cell walls of fungi like Aspergillus & Penicillium.
• To diagnose invasive aspergillosis test blood & bronchoalveolar lavage.

Aspergillus Transmission

• Molds are Widely Distributed in Nature.
• Aspergillus mostly saprophytes and develop in Decaying Vegetation, Fruits, and Vegetables- generating Chains of Conidia.
• Some versions of Aspergillus are grown in soil.
• The virus trasmits by Airborne.

Aspergillus Disease

• Aspergillus fumigatus causes Infections of the Skin, Eyes, & Ears.
• Can cause Fungus Balls in Lungs along with Allergic Bronchopulmonary Aspergillosis.

Aspergillus Pathogenesis & Clinical Findings

• A. fumigatus invade Abraded Skin, Wounds, Burns, Cornea, External Ear, or Paranasal Sinuses and causes colonization.
• The common cause for this infection is Fungal Sinusitis.
• Immunocompromised Persons A. fumigatus produce Hemoptysis and Granulomas. especially those are with Neutropenia- A form of disease that targets Lungs & other Organs.
• The organism is transmitted by the Airborne.
• The organism also grows on soil.
• Infections mostly originate with people with damaged or susceptible systems; and can target most humans & animals

Aspergillus Well known for what:

• Growth ability in cavities within lungs (especially those that cause TB.)- causing Aspergillomas in the lungs.
• When moved to patients from supine position to erect, physicians look for radiopaque indications that change position on Chest X-Ray
• Patients with ABPA indicate those indications & symptoms.
• Allergic Bronchopulmonary Aspergillosis is a hypersensitivity reaction to the presence of Aspergillus in the bronchi. Patients indicate Asthmatic Sympt and high 1gE.
• Inhalation is airborne & frequent.

Aspergillus Laboratory Diagnosis

• Biopsy specimens show Septate, Branching Hyphae.
• While colonies provide Radiating Chains of Conidia.
• If culture indicates present, disease may not be confirmed due to the commonality.
• Invasive Aspergillosis has High Titers of Galactomannan antigen.
• Allergic Bronchopulmonary Aspergillus have Levels of IgE specific and prominent Eosinophilia.

Aspergillus Treatment & Prevention

• For patients with Aspergillosis administer voriconazole & Amphotericin B.
• Patients undergoing Liposomal Amphotericin B that have kidney damage.
• Caspofungin for patients with Invasive Aspergillosis that do not respond to Amphotericin B.
• Surgically Removed fungus in sinus/pulmonary.
• Patients may want to incorporate Corticosteroid & Antifungal Agents like Itraconazole. With no definite means of prevention.

Mucor & Rhizopus

• Disease mucormycosis which comes from a disease with saprophytic species.
• Non-Dimorphic
• Transmits by Airborne
• Proliferates in walls leading to Paranasal Synuses.
• Patients that undergo these issues may include patients with:
  • Ketoacidosis
  • Undergo Bone Marrow transplants
  • Leukemia

Pathogenesis & Clinical Findings

• Susceptibility to Rhinocereberal - a diabetic state which causes sinuses and germinates into blood supply of the brain.
• Rhizopus orzae one species about 60 percent cases Mucormycosis death is complication and prognosis increases

Laboratory Diagnosis

• Biopsy Specimens in bodies found microscopic Non-Septate Hyphae, walls and branches
• difficulty with cultures and ability to limit part it from growing.

Treatment & Preventions

• early with treatment in underlying disorder.
• administer B with removal Necrotic Tissue.
• if patients Kidney Damage, Liposomal can take Kidney Damage.
• can involve Pasaconazole

Fungi of Minor Importance ###Pneumocystis

• yeast type & analyzed in molecular studies while protozoan based thinking also includes as an unclassified organism. In 2002 Pneumocystis reclassified. carinnji used by at species only.

  • Pnenicillium marneffei is is one that is tuberculosis affecting.

• Small Yeast and grows at temperature 37 Degrees and mirrors that of that form this is shown only by.

  • The rat carries same conditions & is known known to only hold this and can be made with fluorescent antibody staining or with stain body to analyze affected regions. For treatment with infection

  • administer body and treat oral for period weeks can be prevented by using oral long term.

  • Mold with affect which occurs more often and is usually has Aspergillus in studies or in analysis of Septate analysis microscope views closely to.

  • Color will appear of a differeent appearance versus the original Aspergillus. Which usually contains a brownish-gray hue and can cause drug based responses. The use of Ketoconazole & Itraconazole is important .

  • In this Debridemnt removes necrotic tissue.

  • Similarities can be drawn between this and other fungi that affect Skin & Lever.

  • This has been know to effect invassivly affect the septum.