L7 Opportunistic Mycoses

• Opportunistic Invasive Mycoses

  • Candidiasis
  • Cryptococcosis
  • Aspergillosis
  • Mucormycosis
  • Pneumocystis pneumonia
• Opportunistic Invasive Mycoses


  • Infections that occur almost exclusively in debilitated patients whose normal defense mechanisms are impaired
  • Caused by cosmopolitan fungi with very low inherent virulence
• Increased incidence of opportunistic invasive mycoses

  Paralleled the emergence of AIDS, more aggressive cancer and post-transplantation chemotherapy, and the use of antibiotics, cytotoxins, corticosteroids, immunosuppressives, and other macro disruptive procedures resulted in lowered resistance of host
• Endogenous yeasts, normal mammalian microbiota

  • Candida species
• Candida albicans


  Initially was a true yeast, now classified as dimorphic - can produce a true hyphae, can produce longer hyphae septated hyphae after germ tubes even at 37°C
• Exogenous fungi, in soil, water, and air

  • Cryptococcus
  • Aspergillus
  • Mucor
  • Penicillium
  • Pneumocystis
• Incidence and roster of fungal species continue to increase
• Medical advances prolong the lives of patients with impaired host defenses
• Every year, reports of novel infections caused by those previously thought to be nonpathogenic
• Candidiasis


  Members of the normal flora of skin, mucous membranes, and gastrointestinal tract, the most prevalent systemic mycosis
• Most common Candida agents

  • C. albicans
  • C. parapsilosis
  • C. glabrata
  • C. tropicalis
  • C. guilliermondii
  • C. dubliniensis
• Germ Tube Test


  Demonstrates the production of germ tube by C. albicans, positive: appendage half the width, 3x-4x length of yeast, no point of constriction at origin
• Cornmeal Tween 80 Agar


  Showcases the chlamydospores
• Azole resistant Candida species

  • C. glabrata
  • C. krusei
  • C. lusitaniae
  • C. auris
• Candida


  • Cause both cutaneous and systemic infections, clinical manifestations have different mechanisms of pathogenesis
• Morphology & Identification of Candida

  Grow as oval, budding yeast cells (3-6 μm), form pseudohyphae, chains of elongated cells, pinched or constricted at septations between cells, submerged below agar surface, soft, cream-colored colonies with a yeasty odor within 24h at 37°C or RT
• Candida albicans


  Dimorphic, produces true hyphae or germ tubes, positive to germ tube test, other Candida spp. are only yeasts and do not produce pseudohyphae
• Nutritionally Deficient Media


  Produce large, spherical chlamydospores
• Candida species without pseudohyphae

  • C. tropicalis
  • C. parapsilosis
  • C. guilliermondii
  • C. kefyr
  • C. krusei
  • C. lusitaniae
• Antigenic Structure of Candida albicans

  Two serotypes: A (includes C. tropicalis) and B
• Cell Wall Components of Candida

  • Mannans
  • Glucans
  • Other polysaccharides
  • Glycoproteins
  • Enzymes
• Cell Wall Components


  Released during infection, facilitate attachment and invasion of host cells, elicit innate defenses and Th1, Th17, Th2 immune responses, sera of patients with systemic candidiasis contain detectable antibodies to enolase, secretory proteases, and heat-shock proteins
• Pathogenesis of Candidiasis


  Prolonged use of antibiotics reduces good bacteria, increased population of Candida spp. damages the epithelium leading to local invasion by yeasts/pseudohyphae, can cause pyogenic abscesses to chronic granulomas
• 2 Types of Candidiasis

  • Systemic
  • Nosocomial
• Systemic Candidiasis


  Enters by crossing intestinal mucosa, occurs when Candida spp. enters the bloodstream and innate phagocytic host defenses are inadequate to contain the growth and dissemination of the yeasts
• Nosocomial Candidiasis


  From contaminated indwelling IV catheters, can infect kidneys, prosthetic heart valves, almost anywhere
• Critical Host Defense against Candidiasis

  Adequate number of functional neutrophils capable of ingesting and killing the yeast cells
• Virulence Factors of Candida

  Produce a family of ALS (agglutinin-like sequence) surface glycoproteins (some adhesins), secrete 10 Secreted Aspartyl Proteinases (SAP) to degrade host cell membranes and destroy immunoglobulins, produce Phospholipase (PLB1) to hydrolyze phospholipids, evade host defenses through morphology/pseudohyphae and form biofilms
• Innate Host Defense against Candida

  • Pattern recognition reception (lectins, Toll-like receptors, macrophage mannose receptor), binding of β-1,3-glucan to dectin-1 on host cells induces robust inflammatory response and Th17 lymphocytes to secrete IL-17
• Risk Factors for Cutaneous and Mucosal Candidiasis

  • AIDS
  • Pregnancy
  • Diabetes
  • Young or old age
  • Birth control pills
  • Trauma (burns, maceration of the skin)
• Thrush


  Common among AIDS patients accompanied by an extremely low CD4 count, occurs on the tongue, lips, gums, or palate, patchy confluent, whitish pseudomembranous lesions, form intractable biofilm
• Vulvovaginitis/Monilial vaginitis/Vaginal yeast infection

  Yeast invasion of the vaginal mucosa, irritation, pruritus, vaginal "curdy" discharge, pale to red labia, burning on urination, predisposed by diabetes, pregnancy, antibacterial drugs, oral contraceptives, local acidity, or secretions
• Intertriginous Infection


  Occurs in moist, warm parts of the body (axillae, groin, intergluteal or inframammary folds), common in obese and the diabetic, newborns: diaper rash, skin infections - red moist, develop vesicles
• Onychomycosis


  Invasion of the nails, around the nail plates, painful, erythematous swelling of the nail fold resembling pyogenic paronychia, eventually destroy the nail

  
• Systemic Candidiasis


  Causes: Chronic administration of corticosteroids or other immunosuppressive agents, hematologic diseases (leukemia, lymphoma, aplastic anemia), chronic granulomatous disease (CGD)
• Candidemia


  Causes: Indwelling catheters, surgery, intravenous drug abuse, aspiration, or damage to the skin or gastrointestinal tract, can cause occult lesions anywhere (kidney, skin, eye, heart, meninges)
• Candidal Endocarditis


  Frequently preceded by deposition and growth of the yeasts/pseudohyphae on prosthetic heart valves, or vegetations and the formation of recalcitrant biofilms
• Kidney Infections and Urinary Tract Infections

  Usually systemic manifestation of candidiasis, often associated with Foley catheters, diabetes, pregnancy, and antibacterial antibiotics
• Chronic Mucocutaneous Candidiasis (CMC)

  Immune disorder of T cells, many of them are unable to mount effective Th17 response to Candida, characterized by the formation of granulomatous candidal lesions on any or all cutaneous/mucosal surfaces
• Diagnostic Laboratory Tests for Candidiasis

  Microscopic examination of swabs, scrapings, biopsies, fluids for pseudohyphae and budding cells, culture on SDA, CHROMagar Candida, biochemical tests for species identification, molecular methods like PCR, serology