MICROBIO 4.3 - OPPORTUNISTIC MYCOSES

Opportunistic Mycoses Overview

• Opportunistic mycoses are caused by fungi
• They cause life-threatening systemic disease
• Opportunistic Mycoses almost entirely occur in immunosuppressed patients
• Risk factors include hematological malignancies, organ/blood transplants, neutropenia, HIV, and corticosteroids
• Further risk factors include immunosuppressive drugs, major burn wounds, trauma and central venous catheters
• Broad-spectrum antibiotics, parenteral nutrition, diabetes, renal insufficiency requiring dialysis, prematurity and elderly increase the risk
• There is increased risk in hospital settings
• Possible genetic factors exist
• Opportunistic mycoses are not "true pathogens"

Types

• Three Most common genera are Candida, Cryptococcus and Aspergillus
• Candida causes Candidiasis and are yeasts found as part of the normal human flora
• Cryptococcus causes Cryptococcosis, they are yeasts that live in the environment
• Aspergillus causes Aspergillosis and are ubiquitous in the environment
• Less common types include Mucorales causing Mucormycosis
• Pneumocystis jiroveci causes Pneumocystis pneumonia

Candida

• Candida is the most common opportunistic infection
• It is found in the GI and urogenital tracts and on the skin; it is an endogenous infection
• Exogenous sources are common in healthcare settings like nosocomial infections
• Superficial candidiasis results from localized overgrowth
• Superficial candidiasis manifests in whitish plaques & pseudomembranes on mucosal surfaces
• Alternatively it manifests as erythematous and/or vesiculopustular lesions on skin
• Invasive candidiasis is the result of hematological dissemination or trauma that introduces fungi to a novel site
• Candida is caused by Candida albicans (frequent), C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei (Ascomycota)
• Budding yeast & pseudohyphae form at 68°F
• Germ tubes become true hyphae at 98.6°F

Superficial Candidiasis

• Oropharyngeal overgrowth presents as thrush with whitish plaques or pseudomembranes over the palate, buccal surfaces, & tongue
• Thrush is generally painless, causes a "cottony" feeling in the mouth, and loss of taste
• Angular cheilitis presents as painful fissures at the corners of the mouth
• Denture stomatitis presents as uncomfortable erythema without plaques and is common in denture-wearers
• Esophageal candidiasis causes plaques/pseudomembranes in the esophagus, and pain upon swallowing (odynophagia)
• Esophageal candidiasis is most common in patients living with HIV with low CD4+ T-cell counts (AIDS-defining illness)
• Intra-abdominal overgrowth is an infection of the peritoneum and/or abdominal viscera
• This is associated with hospitalized patients, especially abdominal surgery patients
• Cutaneous candidiasis presents as a red rash that is often itchy & can be painful
• Cutaneous candidiasis tends to occur in the body folds (warm & moist), i.e. armpits, under the breasts, & groin area
• Diaper rash presents as a red, itchy rash in folds of the groin, buttocks, & external genitalia but can have other causes other than candida
• Vulvovaginal candidiasis presents as whitish plaques, itching, & foul-smelling discharge

Invasive Candidiasis

• Invasive candidiasis occurs as the result of hematological dissemination or trauma that introduces fungi to a new site
• Focal invasive candidiasis is localized within the heart, lungs, brain, bones, or other organ systems
• Systemic invasive candidiasis is spread throughout the whole body
• Candidemia occurs with presence of Candida species in the bloodstream
• Candidemia is the 4th most common cause of nosocomial bloodstream infections
• Candidemia is associated with central-lines of the central venous catheter

Candida treatment

• Candida can be treated with Polyenes (Ampho B, Nystatin*)
• Candida can be treated with Imidazoles (ketoconazole, miconazole*, clotrimazole*)
• Candida can be treated with Triazoles (Fluconazole*, Itraconizole,Voriconazole*, Isavuconazole)
• Mucosal & cutaneous forms are typically easy to treat
• No invasion through the mucosa occurs
• Chronic mucocutaneous candidiasis is rare, but difficult to treat, and typically results from T-cell defects
• The main host defense that holds Candida in check on mucosal surfaces is T-cell–mediated immunity

Aspergillosis

• Aspergillus presents with hypersensitivity and underlying chronic pulmonary illnesses &/or immunosuppression
• This is caused by species of Aspergillus, especially Aspergillus fumigatus +others (Ascomycota)
• This forms hyaline molds with abundant conidia production
• Conidia spores are ubiquitous in the environment, both outside & inside, including hospitals
• Humans are constantly inhaling these spores
• Spores can colonize and/or invade immunocompromised individuals
• Aspergillosis can be treated with Polyenes (Ampho B, Nystatin) or Triazoles (Itraconizole, Vorizonazole)
• It can also be treated with Allylamines (Naftifine, Terbinafine)

Pathology

• Hypersensitivity occurs due to corticosteroid treatment
• The fungi colonize bronchopulmonary tissue, leading to obstruction, vasculature damage, hemoptysis
• Allergic Aspergillus sinusitis causes chronic rhinosinusitis and can obstruct sinuses & produce asymmetrical swelling around the orbit and/or nasal sinuses
• Allergic bronchopulmonary aspergillosis occurs in patients with asthma & cystic fibrosis
• Aspergillomas ("fungus balls" or mycetomas) form in pre-existing cavities in the lungs or sinuses, e.g. TB patients
• These are made up of fungal hyphae, tissue debris, & inflammatory cells
• Chronic pulmonary aspergillosis is localized lung invasion which can lead to cavitation, sometimes fungal balls or fibrosis, and is common in patients with chronic lung disease
• Invasive aspergillosis causes fungi to invade pulmonary tissue, causing destruction and even dissemination to other organs, occurs in patients with severe immunodeficiency, and has a high mortality rate
• Cutaneous aspergillosis can occur when fungi enter a wound

Cryptococcosis

• Presentation involves the CNS (meningitis & encephalitis, “soap-bubble” lesions) & pulmonary infections
• Severity ranges from asymptomatic to pneumonia with pulmonary infiltrates
• and Cryptococcus gattii (Basidiomycota) caused by: Cryptococcus neoformans
• It is found in bird droppings, soil, & trees
• It has an encapsulated, spherical yeast
• Outer "halo" is the polysaccharide capsule
• Inner yeast cell has melanin in its cell wall
• Occurs due to the opportunistic pathogen C. neoformans in AIDS, with CNS symptoms in immunosuppression
• C. gattii impacts relatively “immunocompetent” patients with More lesions & granuloma formation in respiratory infection
• Cryptococcosis is treated with Polyenes (Ampho B), Imidazoles (ketoconazole), and Triazoles (Fluconazole, Isavuconazole)

Mucormycosis

• Angioinvasive molds cause embolism & necrosis
• Primary infection occurs in immunosuppressed patients and people living with diabetes
• Rhinocerebral infection is infection of the sinuses that can spread to the brain, can involve headache, one-sided facial swelling, congestion, and black lesions, and is associated with uncontrolled diabetes mellitus
• Pulmonary infection involves fever, cough, chest pain, invades pulmonary vessels, hemoptysis, and associated with cancer patients
• Pulmonary infection can also occur in or transplant recipients
• Gastrointestinal infection- abdominal pain, nausea & vomiting, can lead to hemorrhaging/perforation, and is more common in children
• Cutaneous infection involves blisters or ulcers that may turn black, and is the most common form in immunocompetent individuals
• Disseminated infection spreads & commonly involves the brain
• The cause of Mucormycosis is Rhizopus and Mucor and is often found in decaying organic matter such as bread, fruit, veggies, soil, & compost
• Mucormycosis is treated with Polyenes (Ampho B),Triazoles (Isavuconazole), and Allylamines (Naftifine, Terbinafine)

Pneumocystis Pneumonia

• Pneumocystis Pneumonia is a presentation of asymptomatic infections, infantile pneumonia, pneumonia in immunocompromised hosts, and extrapulmonary infections
• It is caused by: Pneumocystis jiroveci (maybe others?) (Ascomycota)
• Originally believed to be a protozoa but morphologically similar to protozoa, does NOT have ergosterol in its cell membrane and can’t grow in routine lab media like the rest of the fungi
• Genetic analysis in 1988 revealed it’s closer to fungi
• It is a significant AIDS-associated illness
• Pneumocystis Pneumonia does not respond to antifungals, and should be treated with trimethoprim/sulfamethoxazole

Ana Traven, PhD

• Candida albicans is a microscopic fungus commonly found in the human body
• Candida albicans can turn into a dangerous infection in vulnerable hospital patients
• Life threatening infections affect an estimated 400,000 people worldwide annually with an alarming mortality rate of 40%
• Candida albicans is one of a handful of fungal species that collectively kill at least 1.5 million people per year The sugar glucose is important for macrophages to mount an effective attack on disease-causing microbes
• As macrophages respond to infection, macrophages undergo a metabolic shift increasing consumption of glucose
• The fungus competes with the macrophages, rapidly consuming the glucose and causing the macrophages to die
• Candida albicans switches to deadly hyphae or filamentous shape