Opportunisic Mycoses Flashcards
• Infections which occur almost exclusively in debilitated patients whose normal defense mechanisms are impaired
• Caused by cosmopolitan fungi which have a very low inherent virulence.
Opportunistic mycoses
• Increased incidence paralleled:
• the emergence of AIDS, more aggressive cancer, post transplantation chemotherapy, the use of antibiotics, cytotoxins, immunosuppressives, corticosteroids, and other macro disruptive procedures that result in lowered resistance of the host
Opportunistic mycoses
Opportunistic Invasive Mycoses
• Endogenous yeasts, normal mammalian microbiota, i.e._____
• Exogenous fungi, in soil, water, and air, i.e. (MCAPP)
Candida species
Mucor, Cryptococcus, Aspergillus, Penicillium, Pneumocystis, etc.
• Incidence and the roster of fungal species continue to increase
• Every year there are reports of novel infections caused by those previously thought to be nonpathogenic.
• Medical advances prolong the lives of patients with impaired host defenses.
Opportunistic Invasive Mycoses
Members of the normal flora of skin, mucous membranes, and gastrointestinal tract
Candida
- the most notorious yeast infection
Candidiasis
Candidiasis
Most common agents:
______(major cause of yeast infection in the world)
______(5) (non albicans Candida, NAC)
C albicans
C. parapsilosis,
C glabrata,
C. tropicalis,
C. guilliermondii,
C. dubliniensis
Widespread use of fluconazole — azole resistant species: (4)
most alarming, not part of microbiota, healthcare-associated infections)
C. glabrata,
C. krusei,
C. lusitaniae,
C auris
Widespread administration of broad-spectrum antibiotics promotes large increases in the endogenous population of Candida in the (3)
GIT, oral, & vaginal mucosa.
• Increase population of Candida leads to phenotypic switching (_____ to ______) damaging the______.
Local invasion occurs characterized initially by pyogenic abscesses then to chronic granulomas -
yeasts to pseudohyphae
epithelium
Cutaneous or mucosal candidiasis
Crossing intestinal mucosa, Candida enters the bloodstream & when innate phagocytic host defenses (neutrophils) are inadequate to contain the growth, dissemination of the yeasts ensues -
Systemic candidiasis
: From contaminated indwelling intravenous catheters to infecting kidneys, prosthetic heart valves, almost any sites
• Nosocomial cases
-produce a family of ALS (agglutinin-like sequence)
surface glycoproteins (adhesins)
• Innate host defense: pattern recognition reception (lectins, Toll-like receptors, macrophage mannose receptor)
• Examples: Host cell lectin (dectin-1) binds to B-1,3-glucan of Candida → robust inflammatory response → release of cytokines (TNFa, IFN-y, G-CSF) → activation of neutrophils &monocytes (leukocytes and macrophages)
C. albicans and other Candida
• The binding of B-glucan to dectin-1 on dendritic cells induces______ to secrete interleukin-17.
Th17 lymphocytes
CANDIDIASIS
virulence factors
Mannans, glucans, ALS surface glycoproteins,
Enolase, secreted aspartyl proteinases, & heat-shock proteins
Phospholipase (PLB1)
Phenotypic switching
Biofilms with extracellular matrix
, - facilitate attachment to host cells
Mannans, glucans, ALS surface glycoproteins
- facilitate invasion of host cells, degrade host cell membranes & destroy immunoglobulins
• Enolase, secreted aspartyl proteinases, & heat-shock proteins
- hydrolyze phospholipids
Phospholipase (PLB1)
morphology - yeasts to pseudohyphae - making them difficult to phagocytize
Phenotypic switching
- allow them to resist penetration by host immune responses & antifungal drugs
• Biofilms with extracellular matrix
CANDIDIASIS -
Risk Factors: AIDS, pregnancy, diabetes, young or old age, birth control pills, trauma (burns, maceration of the skin), treatment with corticosteroids or antibiotics, diabetes, cellular immunodeficiency
Mucocutaneous Candidiasis
CANDIDIASIS - Mucocutaneous Candidiasis
• Occur on the tongue, lips, gums, or palate
• Patchy confluent, whitish pseudomembranous lesions, form intractable biofilm
Thrush (oropharyngeal candidiasis)
CANDIDIASIS - Mucocutaneous Candidiasis
Predisposed by diabetes, pregnancy, antibacterial drugs, oral contraceptives, local acidity, or secretions
Vulvovaginitis/Monilial vaginitis/ Vaginal yeast infection
CANDIDIASIS - Mucocutaneous Candidiasis
• Yeast invasion of the vaginal mucosa
• Irritation, pruritus, vaginal “curdy” discharge (lumps of cottage cheese); odor unpleasant but not foul; pale to red labia, burning on urination
Vulvovaginitis/Monilial vaginitis/ Vaginal yeast infection
(- former genus of Candida)
Monilia
CANDIDIASIS - Mucocutaneous Candidiasis
Between fingers:
repeated prolonged immersion in water (homemakers, bartenders, cooks, vegetable & fish handlers)
Intertriginous infections
CANDIDIASIS - Mucocutaneous Candidiasis
• Occurs in moist, warm parts of the body: axillae, groin, intergluteal or inframammary folds (common in obese & diabetics)
Newborns: diaper rash, skin infections - red moist, develop vesicles
Intertriginous infections
CANDIDIASIS - Mucocutaneous Candidiasis
• Invasion of the nails, around the nail plates
• Painful, erythematous swelling of the nail fold resembling pyogenic paronychia (proximal/lateral nail, eventually destroy the nail
Onychomycosis
Patients develop chronic, raised, and crusty highly disfiguring keratitic lesions on the skin, oral mucosa, and scalp.
Many of them are unable to mount effective Th17 response to Candida.
Candidiasis - Chronic Mucocutaneous Candidiasis (CMC)
An immune disorder of T cells.
Rare but distinctive clinical manifestation characterized by the formation of granulomatous candidal lesions on any or all cutaneous & mucosal surfaces.
Classification based on early childhood, associated with autoimmunity and hypoparathyroidism
Candidiasis - Chronic Mucocutaneous Candidiasis (CMC)
Most often associated with chronic administration of corticosteroids or other immunosuppressive agents; hematologic diseases (leukemia, lymphoma, aplastic anemia), chronic granulomatous disease
CANDIDIASIS - Systemic Candidiasis
CANDIDIASIS - Systemic Candidiasis (4)
Candidemia
Candidal Endocarditis
Kidney infections
Urinary tract infections
- caused by indwelling catheters, surgery, intravenous drug abuse,
aspiration, or damage to the skin or gastrointestinal tract;
develop occult lesions anywhere - kidney, skin, eye, heart, meninges
Candidemia
- deposition & growth of the yeasts, pseudohyphae or vegetations & the formation of recalcitrant biofilms on prosthetic heart valves
Candidal Endocarditis
- C. glabrata comes 2nd to C. albicans.
Often associated with
Foley catheters, diabetes, pregnancy, and use of antibacterial antibiotics
Urinary tract infections
Urinary tract infections (2 Candida)
Often associated with
Foley catheters, diabetes, pregnancy, and use of antibacterial antibiotics
C. glabrata comes 2nd to C. albicans.
Skin or nail scrapings are first placed in a drop of (2)
KOH and calcofluor white.
- positive to germ tubes (serum, 90 minutes, 37°C); “true hyphae or germ tubes”
C. albicans
• On nutritionally deficient media: produce large, spherical chlamydospores.
• Confirmatory test & speciation: sugar fermentation and assimilation tests
Candidiasis
is dimorphic (?) (unlike other species of Candida) - produce true hyphae
• C. albicans
• Culture or tissue:
grow as oval, budding yeast cells (3-6 um),
form pseudohyphae (when buds continue to grow but fail to detach - chains of elongated cells, pinched or constricted at septations between cells);
submerged below agar surface
• Within 24h, 37°C or RT: soft, cream-colored colonies with a yeasty odor
Candida
*(based on enzymatic action on chromogenic substrates in the medium, 1-4 days)
- Easier identification by MALDI-TOF directly from a colony
CHROMagar Candida Plus
Candida
Interpretation of positive cultures varies with the specimen.
•_____ cultures have no value because
Candida species are part of the oral microbiota.
Sputum
Candida
Interpretation of positive cultures varies with the specimen.
• Positive____ cultures may reflect systemic candidiasis or transient candidemia due to contaminated intravenous line.
blood
Candida
Interpretation of positive cultures varies with the specimen.
• Positive culture from normally______ is significant.
• Diagnostic value of a quantitative_____ culture.
Contaminated Foley catheters lead to “false-______” urine cultures.
sterile body sites
urine
positive
C. Carbohydrate Assimilation Tests
________ - assimilated glucose and trehalose;
________ - assimilated glucose only.
Lactose is assimilated only by______.
Candida glabrata
C. krusei
Candida kefyr
C. Carbohydrate Assimilation Tests
Cellobiose assimilation is positive for______which differentiates it from______ and ______
________is not assimilated by these Candida species.
C. tropicalis
C. albicans and C. parapsilosis.
Dulcitol
Molecular Methods
•______ cultures for Candida augmented by real-time PCR with species-specific primers (ribosomal DNA genes)
• Crucial is extraction of_____ from yeast cells. Adequate cells needed. Early detection of infection.
•_______ - species identification takes several days; MALDI-TOF-MS has become a rapid method of identifying species of Candida, other pathogenic fungi, and bacteria.
Blood
DNA
Non-C. albicans
Serology
• 2 serotypes of C. albicans:
______( latron Factor 6 antiserum. )
& ____(anti-C. albicans antiserum) by flow cytometry
• In______ candidiasis, antibody titers to candidal antigens may be elevated, but no clear criteria to establish diagnosis.
A
B
systemic
Serology
• ________ test or______ - more specific; detects Candida cell wall mannan,
lacks sensitivity as patients are only transiently positive & don’t develop significant antigen titers until late in the disease
Latex agglutination
enzyme immunoassay
Serology
•_______ test for circulating B-(1,3) d-glucan (not specific to Candida), normal levels
10-40 pg/ml; above 80 pg/ml invasive infections
Biochemical
CANDIDIASIS
Immune Response
_______- crucial for resistance to systemic candidiasis
_______-important for controlling mucosal candidiasis
Stimulation of specific_____ lymphocytes triggers a cascade of cytokines that activate macrophages, inflammation, and enhance phagocytic activity.
Circulating neutrophils
Cell mediated immune responses
Th17
CANDIDIASIS
Treatment
______: treated with topical nystatin or oral ketoconazole or fluconazole
______: treated with liposomal amphotericin B, sometimes in conjunction with oral flucytosine, fluconazole, caspofungin
______: oral ketoconazole, other azoles, often require lifelong treatment
Thrush, mucocutaneous forms
Systemic form
Chronic mucocutaneous
- not communicable, all persons harbor the organism
• Molecular epidemiological studies have documented outbreaks caused by the nosocomial transmission of particular strains to susceptible patients (leukemics, transplants neonates, ICU patients)
• Fourth most common blood culture isolate and the attributable mortality ranges from 30% to 40%
CANDIDIASIS
