Mycology 2: Oportunistic Pathogens Flashcards
(41 cards)
What are the 4 main opportunistic fungi?
Cryptocococcus neoformans, Candida, Aspergillus, and Pneumocystis jiroveci.
Chronic Granulomatous Disease (CGD)
Mechanism and associated bugs
Mutations affecting NADPH oxidase, which normally causes oxidative burst in neutrophils and macrophages. Pxs have problems w/ Candida and Aspergillus.
Severe Combined Immunodeficiency
Lack of mature T and B cells. Often results in death early in life due to opportunistic infections
TNFa blockers
Use
2 examples
Monoclonal Abs against TNFa or receptors. Reduce fever, inflammation, and acute phase response. Used for autoimmune disorders and psoriasis. Examples include infliximab and etanercept.
Calcineurin Inhibitors
Mechanism
Use
2 examples
Suppress T cell activation. Used for transplant pxs. Examples include cyclosporine A and tacrolimus.
Mycophenolate Mofetil mechanism / use
Metabolic inhibitor that blocks T and B cell proliferation / function in transplant pxs.
What does HIV do? What does it not do?
Kills CD4 T cells. Damages CMI.
Does not damage innate immunity
Order of typical fungal infections in HIV pxs
1) Oral / esophageal candidiasis
2) Vaginal candidiasis
3) Oral candidiasis again
4) Pneumocystic pneumonia, Cryptococcal meningitis, Histo, Coccidiodomycosis
5) Aspergilliosis and resistant candidiasis
What are pxs w/ mono at risk of?
What viruses cause mono?
Epstein-Barr virus (EBV) suppresses immune function –> risk of oropharyngeal candidiasis.
How does diabetes increase risk of infection? (4 things)
- Hyperglycemia fosters microbial growth and hinders phagocyte function.
- Acidosis facilitates iron release from host transferrin → fungal use
- Poor vasculature reduces access of WBCs and AB’s to infections
- Peripheral neuropathy → undetected injuries / pathogen entry
3 varieties of Cryptococcus
Serotype
Location
- C grubii – serotype A. Most common. (Serotype based on capsule)
- C neoformans – serotype D. Common in Europe.
- C gattii – serotypes B and C. Associated w/ eucalyptus trees. Mainly found in tropical regions.
Cryptococcus neoformans
Environment
Morphology
- Ubiquitous in soil. Found in bird guano, especially pidgeons.
- Monomorphic budding yeast
- Natural environment – dry, low CO2, iron. Capsule is downregulated and yeast is easily aerosolized for inhalation.
- Host environment – moist, high CO2, low iron. Capsule is upregulated. Yeast more easily resists host defense.
Cryptococcus neoformans virulence factors (3)
Polysaccharide capsule made of glucuronoxylomannan (GXM)
Thermotolerance - grows at 37 degrees
Melanin
Functions of cryptococcus capsule (3 things)
What is it made of?
Made of glucoronoxylomannan.
Antiphagocytic, depletes complement, and down regulates immune functions
What organism makes melanin? What is it’s function?
How is it made?
Cryptococcus
Antioxidative effects of melanin combat oxidative burst to inhibit host defense. Tough melanin coat also aids in resistance to heat, pH, UV, phagocytes, and antifungals.
• Phenols (NTs such as L dopa, dopamine, epi, and NE) → quinones via phenoloxidases or laccases → autopolymerize to melanins
Cryptococcus neoformans infection What is infecting route and morphology? Population What is the main disease Pulmonary diseases (4) Hematogenous diseases (4) Diagnosis Treatment
- Infection occurs via inhalation of yeasts or sexual / asexual spores
- Typically only occurs in immunocompromised pxs, especially HIV/AIDS pxs
- Main disease is meningitis.
- Initial pulmonary infection is usually asymptomatic. May cause diffuse interstitial pneumonia, pleural effusion and acute respiratory distress syndrome.
- Spreads in blood → meningitis, encephalitis, skin, and prostate (reservoir site).
- Encephalitis = infection w/in brain parenchyma.
- Diagnosis - Cryptococcal antigen latex slide agglutination test (Ab against capsule) is most sensitive. India Ink has low sensitivity. Halo sign seen on imaging. Histology shows “soccer ball” appearance of encapsulated yeast.
- Liposomal amphotericin B + 5-flucytosine for severe infection. May switch to fluconazole after improvement. Fluconazole used for less severe infection, prophylaxis, or suppression (may not be necessary in HIV pxs if on ART).
What is the leading cause of meningitis in pxs w/ AIDS?
Cryptococcus
What virulence factor aids in CNS infection?
What bugs? (5)
CNS is common target for encapsulated pathogens.
Cryptococcus neoformans, Neisseria meningitides, Strep pneumoniae, Haemophilus influenzae type B, E coli K1
Candida albicans Location of normal microbiota Route / cause of infection Morphology (normal microbiota, mucocutaneous disease, and disseminated disease; what aids transition?) Virulence factors (4)
Normal microbiota in oropharynx, colon, vagina, and sometimes moist skin.
•Infection is usually endogenous, mainly in immunocompromised pxs or change in microbiota after AB’s.
•Morphology
• Normal microbiota – Budding yeast
• Localized mucocutaneous disease (skin, oropharynx, vagina) – germ tubes, pseudohyphae, and hyphae (all filamentous structures). Transition from yeast is aided by neutral pH, 37 degrees, and presence of serum. Occurs w/in minutes.
• Disseminated disease (rare), such as blood / kidneys – both yeast and filamentous forms
•Virulence factors – morphogenesis, adhesins, biofilm formation, hydrolytic enzymes
Cutaneous candidiasis
Sxs
Location of Balantis candidiasis
Sxs - erythema, pain, itching
Balantis = head of penis / foreskin
Oropharyngeal candidiasis (OPC, thrush)
Risk factors
Sxs
Diagnosis
- Risk factors – HIV, young / old, diabetes, cancer, chemo, corticosteroids, infectious mononucleosis (EBV, CMV), AB’s, xerostomia (dry mouth), dentures (biofilms)
- Sxs – white plaques w/ underlying erythema, pain, poor feeding, weight loss
- Diagnosis – clinical from history, sxs, and appearance. May use KOH prep.
What is the most common opportunistic infection in HIV pxs?
Oropharyngeal candidiasis. 90% of pxs have this at some point.
Candida esophagitis
Population
Sxs (4)
Occurs w/ severe immunocompromise.
Sxs - odynophagia (painful swallowing), dysphagia (difficulty swallowing), weight loss, and malnutrition.
Vulvovaginal candidiasis Lifetime incidence for women Risk factors Sxs (7) Diagnosis pH of vagina
- 75% lifetime incidence.
- Risk factors – AB’s, pregnancy, diabetes, corticosteroids, HIV
- Sxs (non-specific) – erythema, itching, pain, thick cheesy vaginal discharge, external dysuria (painful urination at labia), dyspareunia (painful sex)
- White plaques seen on speculum exam
- Diagnosis requires pelvic exam and pelvic sampling. KOH. Culture of vaginal fluid or plaque.
- Vaginal pH is normal (4.0).
