Candidiasis: Opportunistic Mycosis

• Opportunistic mycoses are fungal infections that primarily affect immunocompromised individuals since causative agents are common with low virulence.
• These infections are not self-limiting and require intervention.

Candidiasis

• Candidiasis is the most frequently encountered opportunistic mycosis.
• It can be endogenous or nosocomial, leading to fungemia and disseminated infection.
• Candida species are part of normal microbiota in various body sites.
• In healthy individuals, infections usually stem from impaired epithelial barriers.
• Systemic candidiasis is typically observed in patients with cell-mediated immune deficiencies.
• Predisposing factors include altered skin and mucous membrane barriers, prolonged antibiotic use, immunosuppressive drugs, and immune system diseases.
• The most common etiologic agent is Candida albicans, but Candida parapsilosis, tropicalis, and glabrata are also significant.
• Candida species have two serotypes (A and B) and produce proteases, enolase, and heat shock proteins.

Clinical Manifestations of Candida spp.

• Oropharyngeal candidiasis is common in newborns, the elderly, and immunocompromised patients, presenting as oral thrush, glossitis, or stomatitis.
• A milky-like curd can be on the buccal mucosa, tongue, and gums, potentially causing burning, dryness, taste loss, and swallowing difficulties.
• Cutaneous candidiasis, or intertrigo, occurs in skin folds due to constant exposure to heat and friction.
• Chronic Candida onychomycosis affects nails, causing weakening, debris, disfigurement, and thickening, often seen in individuals with diabetes, hypothyroidism, or malnutrition.
• Paronychia is an infection around the cuticle area of the fingernails, common in individuals with constant exposure to water or flour.

Laboratory Diagnosis of Candidiasis

• Specimens include skin and nail scrapings, urine, sputum, CSF, pleural fluid, blood, and tissue samples for cutaneous types.
• Direct microscopic examination uses 10% KOH, Parker ink, or calcofluor white to identify budding yeast cells (blastoconidia) and pseudohyphae, which stain Gram-positive.
• Macroscopic observation reveals rapid-growing, raised, cream-colored, opaque colonies within 24-48 hours.
• ChromAgar Candida is useful to differentiate Candida species based on color production: C. albicans (green), C. tropicalis (blue), C. glabrata (purple), and C. krusei (pink).
• Cornmeal Agar with Tween 80 (CMA-T80) aids in identifying Candida species and other yeasts by observing pseudohyphae, chlamydospores, and blasto- and arthroconidia.
• Tween 80 reduces surface tension, stimulating conidiation.
• The Dalmau plate technique, using rice or cornmeal agar, allows conidiation and reveals chlamydospore and blastoconidia arrangement in C. albicans.

Germ Tube Test

• The germ tube test identifies Candida albicans via a hypha-like extension without constriction at the point of origin.
• It forms upon incubation with serum at 37°C for 1-3 hours and resembles pseudohyphae.

Cryptococcosis

• Cryptococcosis is a fungal infection with varied manifestations.
• Infections can be mild or asymptomatic, often not requiring treatment in immunocompetent individuals.
• In disseminated cases, meningitis is common that leads to life-threatening lesions on the brain.
• Etiologic agents include Cryptococcus neoformans, found in soil contaminated with bird droppings, and C. gattii, present in soil around trees.
• Transmission occurs through inhalation, leading to disseminated infections, including meningitis, endocarditis, hepatitis, and renal infection, primarily affecting immunocompromised individuals.
• Diagnosis involves direct microscopy of specimens, revealing thick-walled yeast cells with a wide polysaccharide capsule, visualized using India ink, mucicarmine, or Masson-Fontana staining.
• Latex test is used for cryptococcal capsular antigen detection.
• Treatment includes fluconazole for localized pulmonary disease and amphotericin B (with or without flucytosine) for meningitis or severe infections.

Aspergillosis

• Aspergillosis is commonly caused by the Aspergillus spp, often found in the lungs.
• While immunocompetent individuals might be asymptomatic, immunocompromised individuals can develop invasive infections.
• Transmission occurs through inhalation.

Manifestations of Aspergillosis

• Invasive lung infection is common, presenting as a pulmonary or sinus fungus ball which develops in open spaces in the body and gradually enlarges, destroying lung tissues.
• Allergic bronchopulmonary aspergillosis affects individuals with asthma or cystic fibrosis, causing allergic reactions with coughing, wheezing, and fever.
• Disseminated types, such as keratitis, otomycosis, onychomycosis, sinusitis, endocarditis, and CNS infection, occur.
• Aspergillus fumigatus is the most common agent, followed by A. flavus and niger.

Pathogenesis of Aspergillosis

• Binds to fibrinogen and laminin in the alveolar basement membrane.
• Produces gliotoxin and Neutrophils adhere and kill the hyphae.

Laboratory Diagnosis of Aspergillosis

• Septate hyphae with dichotomous branching at 45 degrees C and dome-shaped vesicles with bottle-shaped phialides.

Zygomycosis/Mucormycosis

• Zygomycosis/Mucormycosis is caused by a diverse fungi group, particularly the Mucorales order (Rhizopus, Rhizomucor, Mucor, Absidia, Cunninghamella).
• Symptoms may include necrotic lesions in the nose and palate, pain, fever, orbital cellulitis, purulent nasal discharge, and CNS symptoms.
• Pulmonary symptoms are severe and include productive coughing, high fever, and dyspnea.
• The site of infection can be related to inhalation, such as in the sinuses, lungs and gastrointestinal tract.
• Decaying vegetable matter, old bread, or soil are the common sources of Zygomycetes.
• Individuals with diabetes or those undergoing immunosuppressive treatments are at a high risk of acquiring the infection.
• Zygomycetes generally include Rhizopus, Mucor, Absidia, and Cunninghamella species.

Laboratory Diagnosis of Zygomycetes

• Characterized by "lollipop-like" fruiting bodies and large, ribbon-like branching, non-septate hyphae with zygospores in tissue specimens or exudates.
• The sacs (sporangia) are attached to sporangiophores.
• Hyphal structure that acts like roots are referred to as Rhizoids whereas stolons are hyphal structure that act like connectors.
• Colonies are typically fluffy, white to gray to brown, appearing within 24-95 hours, with the hyphae exhibiting brownish or black sporangia.

Hyalohyphomycosis

• Fusarium is within the common flora and its manifestations include Mycotic keratitis and wound infections along with sinusitis.
• The lab diagnosis includes hyaline and septate hyphae and brush-like Condiophores.

Talaromyces

• Talaromyces Infections can result in cutaneous ulcers of the extremities and bronchopulmonary and endocarditis as well.

Pneumocystosis

• A lung infection almost exclusively seen in individuals whose immune systems has been compromised by HIV or undergoing chemotherapy
• Etiologic Agent: Pneumocystis jiroveci (P. carinii) causing pneumonia in immunocompromised hosts
• Contains cholesterol in it's cell wall and exists as cystic and trophozoite forms.
• Specimen used includes BAL fluid or lung biopsy which does not artificially grow.
• Treatment is similar to TB patients with Trimethoprim-sulfamethoxazole.