STREPTOCOCCUSSTREPTOCOCCUS

UN AGENTE PATOGENO PER OGNI MALATTIA CRONICA

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LANCEFIELD GROUPS

Based on carbohydrate in cell wallBeta hemolytic (clear hemolysis)

streptococci- Group A – S. pyogenes – humans – oropharynx

- GroupB – S. agalactiae – human newborns, animals

Group C – animals & humansGroup D – Enterococcus faecalis et al. – humans &

animals – normal GI flora

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NO LANCEFIELD GROUPING

•Viridans streptococci – S. sanguis, S. salivarius, etc. – Normal oral flora of humans•Streptococcus pneumoniae –pneumococcus normal oropharyngeal flora of humans•Peptostreptococcus spp. – human GI tract

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STREPTOCOCCUS PYOGENES(Group A)

•Gram +•Cocci in chains•Colonies – small, gray-white on blood agar•Aerotolerant•Extracellular•Non-motile•Capsule - Hyaluronic acid

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EXOTOXINS

•Hemolysins - disrupt red blood cells•Streptolysin O - Beta hemolysis; inactivated by oxygen; immunogenic - host produces antibody (ASO); used for lab diagnosis•Streptolysin S - Beta hemolysis; resists inactivation by oxygen; Non-immunogenic, but may have leukocidin activity

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Erythrogenic Toxin

•Produces an erythematous reaction•Causes the rash of Scarlet Fever•Coded on viral DNA which gets integrated into the bacteria by lysogeny (temperate bacteriophage)

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CLINICAL

•Skin Infections•Impetigo (Streptococcal pyoderma) -purulent with crusting

•Cellulitis (causative agent) – infects wounds such as burns, trauma, and drug abuser injection sites•Erysipelas - mostly of face, “Slapped Cheek” rash

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CLINICAL cont.

•Necrotizing Fasciitis - “Flesh-Eating Streptococcal Disease”•Rapidly spreading gangrene of skin and fascia•Starts as trivial skin infection but is rapidly fatal

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CLINICAL cont.

•Pharyngitis - exudate on tonsils, mostly in children 5-15 yrs old•Scarlet Fever (Scarlatina)•Red, maculopapular “sandpaper rash on trunk, intense at skin folds•White and red “strawberry tongue”•Follows pharyngeal or other infections by strains which elaborate erythrogenic toxin

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CLINICAL cont.

SEQUELAE:•Post-Streptococcal Acute GlomerularNephritis (AGN)•Non-suppurative – no Group A streptococcus present•Post-pharyngitis or post-skin infection (after infection resolves)•Symptoms – facial edema, blood in urine

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CLINICAL cont.

SEQUELAE:•Post-Streptococcal Acute Rheumatic Fever (ARF)•Non-suppurative – no Group A streptococcus present•Post-pharyngitis only (after infection resolves)•Symptoms – migratory arthritis, subcutaneous nodules, carditis, & erythema marginatum•May proceed to Rheumatic Heart Disease•PANDAS

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SOURCE & TRANSMISSION

Normal flora of skin and oropharynx

Causes infections upon penetration of tissues

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VIRULENCE FACTORS

•Exotoxins -•M- protein of cell wall – provides antigenic variation; blocks opsonization by complement alternate pathway, thus evading phagocytosis•Capsule – resists phagocytosis•Hyaluronidase – degrades hyaluronic acid in connective tissue

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Virulence Factors cont.

•Peptidase – destroys C5a complement as a chemotactic signal to PMNs•Streptokinase – catalyzes activation of plasmin to lyse red blood clots•Streptodornase (Dnase) – provides antigenic variation•Pili, lipoteichoic acid, & F-protein – mediate attachment to epithelium

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VACCINE & TOXOID

•None•Host Defense & Immunity: IgA, IgM, IgG antibodies to M protein offer resistance and type specific immunity•PMNs•Autoimmunity develops via cross reaction in Rheumatic Fever

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HOST DEFENSE & IMMUNITY cont.

•Immune complexes C3 from complement alternate pathway deposited at glomerularbasement membrane in Glomerulonephritis•Elevated ASO titers in both rheumatic fever and glomerulonephritis

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DISEASES GROUP A

•Impetigo•Erysipelas•Tonsillitis•Scarlet Fever•Toxic Shock

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VIRULENCE FACTORS

•Exotoxins•M-protein (of cell wall) - provides antigenic variation; blocks opsonization by complement alternate pathway, thus evading phagocytosis•Capsule - resists phagocytosis•Hyaluronidase - spreading factor

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VIRULENCE FACTORS cont.

•Peptidase - destroys C5a complement as a chemotactic signal to PMNs•Streptokinase - catalyzes activation of plasmin to lyse blood clots•Streptodornase(Dnase) - degrades DNA & provides antigenic variation•Pili, Lipoteichoic acid, F-protein - mediate attachment to epithelium

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•HOST DEFENSE & IMMUNITY

•IgA, IgM, IgG antibodies to M protein offer resistance and type specific immunity•PMNs•Autoimmunity develops via cross-reaction in Acute Rheumatic Fever (ARF)•Immune complexes C3 from complement alternate pathway deposited at glomerular basement membrane acute glomerulonephritis (AGN)•Elevated ASO titers in AGN and ARF

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STREPTOCOCCUS AGALACTIAE(GROUP B)

•Gram stain - Positive•Aerotolerant•Extracellular•Cocci in pairs or short chains•Colonies - gray-white on blood agar•Non-motile, no exotoxins•Capsule - polysaccharide

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CLINICAL

•Neonate Meningitis•Symptoms: fever, lethargy, poor feeding•Seizures = poor prognosis•Invades via mucous membranes, respiratory tract and sepsis•Often fatal•Meningitis must be diagnosed via lumbar puncture•CSF - High PMNs, low glucose, cloudy, culture = group B strep

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CLINICAL cont.

•Early onset (age 0-5 days) - vertical transmission in utero; ascending, due to ruptured amniotic sac•Late onset (age 5-90 days) - vertical transmission at time of delivery; or can be nosocomial

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CLINICAL cont.

•Neonate Pneumonia•Symptoms - cyanosis (bluish color), tachypnea (rapid respiration), and respiratory distress - can be fatal•Early onset only; via ascending vertical transmission•Post-Partum Endometritis

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SOURCE & TRANSMISSION

•Normal flora of vagina

•Vertical transmission either at birth or via ascension in utero

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VIRULENCE FACTORS

•Capsule - type-specific polysaccharide, resists phagocytosis•Sialic Acid - capsular component, inhibits alternate pathway of complement especially type III strain

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HOST DEFENSE & IMMUNITY

•IgG antibodies to capsule, followed by phagocytosis by PMNs•Alternate path complement C1 activated by capsule, antibody-independent opsonization•Classical path complement is involved in antibody-dependent opsonization•NOTE: Neonate host defense is quickly defeated

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CAMP TEST

•Group B streptococci produce a diffusible, heat-stable protein (CAMP factor) that enhances beta-hemolysis of S. aureus.•S. aureus produces sphingomyelinase C, which can bind to RBC membranes•When exposed to CAMP factor, the cells undergo hemolysis

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STREPTOCOCCUS BOVIS and others - Group D

•Gram stain = positive•Aerotolerant•Extracellular•Cocci in pairs and/or chains•Colonies - gray-white, variable on blood agar•Non-motile• Capsule & glycocalyx - unknown•Exotoxins - NONE

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CLINICAL

•Bacteremia - enters blood via GI route•Sub-acute Endocarditis arises from bacteremia - can be fatal if untreated•Colon cancer - strong association between S. bovis bacteremia and colon cancer; it is unknown which is cause or effect

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SOURCE & TRANSMISSION

•Normal flora of GI tract•Causes infection upon entering •Blood stream via GI tract

HOST DEFENSE & IMMUNITY•Ig A and IgG antibodies•PMNs

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ENTEROCOCCUS FAECALIS (and others) – GROUP D

•Gram stain - Positive•Aerotolerant•Extracellular•Cocci singly, in pairs, or chains•Colonies - gray-white, variable on blood agar•Motility - NONE

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CLINICAL

•Urinary Tract Infection - upper (pyelonephritis); lower (cystitis); most often nosocomial•Bacteremia - via urinary tract infection, intra-abdominal infection, or nosocomial from various in-dwelling lines such as IV lines or during hemodialysis; may be pre-disposed by chronic illness or diabetes; often fatalSub-acute endocarditis - results from

bacteremia; enterococcus infects only abnormal valves or prosthetic valves•Fatal if untreated

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SOURCE & TRANSMISSION

•Normal flora of GI tract•Causes infection upon entering into blood•Nosocomial - exogenous acquisition of Enterococcus occurs often in hospitals

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VIRULENCE FACTORS

•Resistant to antibiotics - Synercidnow used•Adheres to heart valves and urinary tract epithelial cells•Mechanisms of virulence are unknown

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STREPTOCOCCUS VIRIDANS GROUP (STREPTOCOCCUS MUTANS and others)

•Gram stain - Positive•Aerotolerant•Extracellular•Cocci in pairs and/or chains•Colonies - gray-white, variable on blood•Non-motile•Capsule & glycocalyx - glycocalyx only -dextran

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CLINICAL

•Sub-acute Endocarditis (#1 causative agent)•Results from bacteremia, which follows recent dental work•Infects only abnormal valves or prosthetic valves•Can be fatal if untreated•DENTAL CARIES

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SOURCE & TRANSMISSION

•Normal flora of oropharynx•Causes infections when they enter the blood after dental work or due to poor oral hygiene

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VIRULENCE FACTORS

•Dextran exopolysaccharide glycocalyx - provides a means of adherence to defective heart valves; may block the action of antibiotics•Lipoteichoic Acid - mediates adhesion of fibronectin in clots on defective heart valves•Glucans are polysaccharides made by S. mutansfrom sucrose in the mouth, they provide a means of attachment to the tooth enamel•Acids made by S. mutans from sugar ferment.

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STREPTOCOCCUS PNEUMONIAE

•Gram Stain - Positive•Aerotolerant•Extracellular•Cocci in pairs•Colonies - gray-white, variable on blood•Non-motile•Capsule & Glycocalyx – polysaccharide capsule; over 80 serological types

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CLINICAL

•Lobar pneumonia - causative agent in adults•Symptoms - fever, cough with sputum, dull chest percussion, X-ray shows segmental consolidation -Can be fatal - Abscess rare

•Diagnosis - based on presence of S. pneumoniae and PMNs in sputum•Often predisposed by viral infection, alcoholism, smoking, or any condition which suppresses the cough reflex or disrupts the cilia

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CLINICAL cont.

•Meningitis - causative agent in adult meningitis•Symptoms – fever, neck pain, headache - can be fatal•Diagnosis - lumbar puncture prior to antibiotic treatment; CSF - increase in PMNs, decrease in glucose, cloudy, culture•Often follows sinusitis, otitis media, or bacteremia

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CLINICAL cont.

•Sinusitis - causative organism•Often follows allergy or viral induced edema which prevents sinus drainage•Otitis Media - causative organism•Often follows allergy or viral induced edema which prevents eustachian tube drainage

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SOURCE & TRANSMISSION

•Normal flora of upper respiratory tract•Pulmonary infections occur when mucocilliary action fails - alveoli get filled with bacteria which extend to the entire lobe•Meningitis occurs from extension of sinusitis or otitis media, or from choroid seeding due to bacteremia

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VIRULENCE FACTORS

•Capsule - enables S. pneumoniae to resist phagocytosis•IgA protease - prevents opsonizationby IgA at mucous membranes•Adhesins - mediate attachment of S. pneumoniae to epithelial cells

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VACCINE & TOXOID

•Vaccine made up of 23 capsular antigens•Recommended for anyone 65 years or older•Vaccine confers immunity for a few years

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HOST DEFENSE & IMMUNITY

•IgG antibody to capsule offers resistance and type-specific immunity•Alternate pathway complement C1 activated by capsule, antibody-independent opsonization•Classical path complement is involved in antibody-dependent opsonization•C5a complement attracts PMNs