Opportunistic Mycoses

Recall that "opportunistic" pathogens are micro-organisms that are commonly found in the environment, even our own microbiomes, that cause infection when the "opportunity" arises – for example, in immunosuppressed individuals or when trauma permits access to a novel niche within the body.

• The fungi responsible for opportunistic mycoses cause disease when normal host defenses are impaired.
• Thus, populations with increased risk of infection include the following:

– Patients with immunosuppression, especially due to: Underlying disease, such as HIV infection, hematological malignancies, or diabetes mellitus; Immune suppressing treatments, such as chemotherapy, organ transplants, antibiotics and corticosteroids; Additionally, the very young and elderly are more vulnerable. – Then, denote that some patients are at risk due to increased exposure to the fungi: For example, hospital settings, surgery, and medical devices or implants increase risk of infection.

• Be aware that, as the number of people living with immunosuppressive disorders and therapies has increased, so, too, has the frequency of opportunistic mycoses.
• Recent research indicates a possible link between host genetics and susceptibility to opportunistic infections.

Caused by species of Candida, especially Candida albicans* – Other important species include C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei. Candida are thermally dimorphic:* – They exist as budding yeast and pseudohyphae at 20 degrees Celsius, and form germ tubes at 37 degrees Celsius. – In the third image in the diagram, we can see a Candida albicans colony that comprises yeast-like cells with filamentous cells on top. Candida are commonly found in our gastrointestinal and urogenital tracts, and on the skin*. – Thus, most infections are endogenous. – Exogenous infections are less common, but are more likely in health care settings. Candidiasis can manifest in several forms throughout the body; we'll organize in terms of superficial and invasive infections. Superficial candidiasis is the result of localized overgrowth.

• On mucosal surfaces, overgrowth is visible as whitish plaques and pseudomembranes;
• On the skin, overgrowth produces erythematous and/or vesiculopustular lesions.
• Mucosal and cutaneous forms are typically easy to treat.
• Chronic muco-cutaneous candidiasis is rare, but difficult to treat.

– It is the result of T-lymphocyte defects. Examples of common mucosal and cutaneous candidiasis. Oropharyngeal overgrowth can produce thrush,* which manifests as whitish plaques or pseudomembranes over the palate, buccal surfaces, and tongue. – These lesions are generally painless, though they can cause a "cottony" feeling in the mouth and loss of taste. – Oropharyngeal candidiasis can also produce angular cheilitis, which are painful fissures at the corners of the mouth. – Adults who wear dentures can develop a form of oral candidiasis, called denture stomatitis, which is characterized by uncomfortable erythema without plaques.

• Esophageal candidiasis produces plaques or pseudomembranes in the esophagus, and produces pain upon swallowing (odynophagia); this is most common in HIV patients with low CD4+ T-cell counts (thus, it is an AIDS-defining illness).
• Intra-abdominal overgrowth is associated with hospitalized patients, especially those who have had abdominal surgery.

– Infection can involve the peritoneum and/or any of the abdominal viscera.

• Cutaneous candidiasis tends to occur in the body folds, where conditions are warm and moist, such as the armpits, under the breasts, and groin area.

– The red rash is often itchy, and can become painful. Diaper rash can also be caused by Candida* overgrowth; the red, itchy rash tends to appear in the folds of the groin, buttocks, and external genitalia.

• Vulvovaginal candidiasis (aka, vaginal yeast infections) is characterized by whitish plaques, itching, and a foul-smelling discharge.

• Invasive candidiasis

Occurs as the result of hematological dissemination or trauma that introduces fungi to a novel site.

• Infection can be focal, for example, localized within the heart, lungs, brain, bones, or other organ system, or, can be systemic.
• Candidemia and dissemination to the viscera is more likely in neutropenic and hospitalized patients.

Candida* species are major causes of central-line associated bloodstream infections. Infections of the CNS and pulmonary system caused by Cryptococcus neoformans and Cryptococcus gattii.

• These fungi are found in bird droppings, and, by association, soil and trees.
• They are encapsulated, spherical yeast

– Outer "halo" is the polysaccharide capsule – Inner yeast cell has melanin in its cell wall. Cryptococcus* is inhaled into the respiratory system, followed by dissemination to and localization within the CNS. Cryptococcus neoformans is a major opportunistic pathogen in AIDS patients.*

• Cryptococcosis typically manifests as CNS infections:

– Meningitis and encephalitis – In the image, we can see the characteristic "soap bubble" lesions of Cryptococcal encephalitis. Cryptococcus neoformans* CNS infection is associated with immunosuppressed patients

• Cryptococcus gattii tend to produce infection in relatively immunocompetent individuals

– These patients tend to have more granuloma formation – Some authors suggest that so-called immunocompetent patients actually have complicating illnesses or histories of immunosuppression.

• Cryptococcosis can also manifest as pulmonary infection, sometimes following CNS involvement.

– In the lungs, severity ranges from asymptomatic to pneumonia with pulmonary infiltrates. – Cryptococcus gattii tends to produce larger pulmonary lesions than Cryptococcus neoformans. Caused by species of Aspergillus, especially Aspergillus fumigatus – Additional important species include A. flavus, A. niger, and A. terreus. Aspergillus* forms hyaline molds with abundant conidia production. – Conidia are the asexual spores that are ubiquitous in our environment, both outside and inside, including hospitals. – We are constantly inhaling these spores, which, in the immunocompetent, are typically harmless.

• Spores can colonize and/or invade individuals who have immune abnormalities.

• Hypersensitivity, i.e., allergic reactions to Aspergillus:*

Allergic Aspergillus sinusitis* is a form of chronic rhinosinusitis that can obstruct the sinuses and produce asymmetrical swelling around the orbit and/or nasal sinuses.

• Allergic bronchopulmonary aspergillosis occurs in patients with asthma and cystic fibrosis.

– In these individuals, the fungi colonize the bronchopulmonary tissue. – This can lead to obstruction or, upon damage to the vasculature, hemoptysis (coughing up blood).

• Because allergic sinusitis and bronchopulmonary aspergillosis are the result of hypersensitivity reactions, corticosteroids are often recommended.

Underlying chronic pulmonary illnesses and/or immunosuppression Aspergillosis can take a variety of forms:

• Aspergillomas, aka, fungus balls (or mycetomas), can form within pre-existing cavities within the lungs or sinuses.

– For example, in a patient with a history of tuberculosis, fungal balls can form within cavities produced by TB infection. – These masses comprise fungal hyphae as well as tissue debris and inflammatory cells.

• Chronic pulmonary aspergillosis occurs in patients with chronic lung disease.

– In these individuals, localized lung tissue invasion occurs, which can lead to cavitation with or without formation of fungal balls, or even fibrosis.

• Invasive aspergillosis occurs in patients with severe immunodeficiency, and, because of the invasive nature, has a high mortality rate.

– In addition to pulmonary tissue invasion and destruction, the fungus may disseminate to other organs and cause invasive damage.

• Aspergillosis can also be a cutaneous mycosis, typically following a wound.

Learn about Mucormycoses