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1

Infectious disease is due to...

agents/toxins, multiplication, and host responses

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Three principles one can contract infectious disease...

inoculum size, host defense, toxic agents.

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Bacterial classifications

Shape: cocci, curved, spiral, bacilli (rod)

Gram Stain: Positive and negative

colony morphology

spore formation

serotyping

biochemical and genetic characteristics

growth (atmosphere): obligate aerobe, microaerophile, obligate anaerobe, facultative anaerobe, capnophile

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obligate aerobe

requires oxygen

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microaerophile

reduced oxygen

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obligate anaerobe

no oxygen

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facultative anaerobe

anaerobic or aerobic

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capnophile

requires increased CO2

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Streptococci

Heterogeneous group of bacteria, form a significant portion of the indigenous microflora of the oropharynx

causing many diseases in humans: strep throat, meningitis, pneumonia, bacteremia, brain abscess, endocarditis, and gangrene

the genus is classified on the basis of colony morphology hemolysis, biochemical reactions, and serologic specificity

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General characteristics of streptococci

gram +

cocci arranged in pairs or chains

non motile

facultative anaerobic or capnophilic

Catalase negative

nutritional requirement: complex, need blood or serum enrich media for isolation.

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Streptococcal species classification

Serological: Lancefield classification: Antigenic characteristics of carbohydrate (A, B, C, D, E through S.)

Biochemical and genetic: Physiological properties

Hemolytic patterns alpha hemolytics, Beta hemolytic, and gamma hemolytic

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alpha hemolytic

partial hemolysis

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beta hemolytic

complete hemolysis

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gamma hemolytic

no hemolysis

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Group of streptococci

Group A or streptococcus pygoenes

Group B or streptococcus agalactia

Group C and G streptococci

Group D streptococci (enterococci)

Viridans streptococci

streptococcus pneumoniae

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Group A or streptococcal pyogenes

Gram + with cocci in chain

facultative anaerobe

capsule (hyaluronic acid)

beta hemolytic on blood agar

M proteins (80 Types)

F protein binds to fibronectin (helps establish infection)

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Capsule (GAS)

nonimmunogeneic and antiphagocytic

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M proteins (GAS)

Inhibits opsonization by interfering binding of C3b and degrades C3b via factor H; binding to Fc of antibodies; immunogenic

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C5a peptidase (GAS)

Antichemotactic and reduces inflammation mediated by C5a

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DNase (Gas)

Aids in bacterial spread

Four immunologically distinct forms (A, B, C, D)

AntiDNAS B important marker of cutaneous group A streptococcal infections, particularly useful for those who do not failed ASO test

Depolymerizes cell free DNA in pus (reduction of viscosity); contribute to spread from local site

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Streptolysin O and S (gas)

lyse blood cells and plates, stimulate release of lysosomal enzymes

O: lyses leukocytes platelets, and erythrocytes; antigenically related to oxygen labile toxins produced by other gram positive bacteria such as S. Pneumonia, clostridium tetani, bacillus cereus and listeria monocytogenes; immunogenic, indicating a recent GAS infection (ASO)

S: the s indicated serum stable. Lyses leukocytes, platelets, and erythrocytes; stimulates release of lysosomal enzymes; Beta hemolysis; nonimmunogenic

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Hyaluronidase (gas)

promotes tissue destruction and bacterial spread

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streptokinase (GAS)

promotes bacterial spread into tissue by breaking down blood clots

catalyzes activation of plasmin to lyse blood clots

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Pyrogenic/erythrogenic exotoxins (gas)

some act as super antigens

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Suppurative streptococcal disease (bacterial colonization)

pharyngitis

scarlet fever

skin infections: Impetigo (streptococcal pyoderma): purulent with crusting

cellulitis (#1 causative agent) GAS cellulitis infects wounds (burns, trauma, IV drug abuser injection site)

Erysipelas: acute infection of the skin. Mostly of the face "slapped cheek" rash

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Suppurative streptococcal disease

pharyngitis: "strep throat" exudates on tonsils (children 5-15 years)

scarlet fever: complication of strep pharyngitis that occurs when the infection strain is lysogenized by a bacteriophage that produces a pyrogenic exotoxin. Within 1-2 days, red maculopapular "sand paper" rash on trunk and then spreads to extremities. Intense at skin folds white and red "strawberry tongue". The rash disappears over 5-7 days and followed by desquamation of the superficial skin layer

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Impetigo (streptococcal pyoderma): purulent with crusting

colonization is due to direct contact with an infected person or fomites. Entry of organism follwed by pathology development. Regional lymph node enlarged, but lack systemic signs.

primarily seen in young children (2-5 yr.) or poor personal hygiene

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Erysipelas

localized pain, inflammation, lymph node enlargement, system sign (chills, fever and leukocytosis)

affect all age group fiery red, advancing erythema. Historically on face but now more common on the legs.

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Necrotizing faciitis (suppurative streptoccoccal disease)

"flesh eating" rapidly spreading gangrene of skin and fascia

stars with trivial skin infection but is rapidly fatal (due to multi-organ failure)

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Nonsuppurative streptococcal disease-AGN (GAS)

no group A streptoccus present (autoimmune)

AGN (acute glomerular nephritis)

acute inflammation of the renal glomeruli with edema, hypertension, hematuria and proteinura

post pharyngitis or post skin infection (after infection resolves)

symptoms: facial edema, blood in urine (smoky urine)

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AGN: acute inflammation of renal glomeruli (GAS)

occurs most commonly in children

nephritogenic strain

damage due to immune complex deposition on the glomerular basement membrane.

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Acute rheumatic fever (GAS)

pancarditis (endo, peri, and myocarditis)

no group A streptococcus present

post pharyngitis only

due to cross reactivty of anti M protein antibody with human cardiac tissue

symptoms: migratory arthritis, subcutaneous nodules, carditis and erythema marginatum

may proceed to rheumatic fever

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Source of transmission: GAS

normal flora of skin and oropharynx

cause infection upon penetration of tissue

transmission: person to person

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Diagnosis: GAS

microscopy

antigen detection: throat swabs

antibody detection: ASO test in rheumatic fever

culture: blood agar or specialized selective agar

TX: very sensitive to penicillin. Oxacillin or vancomycin (in mixed culture) Sensitive to bacitracin

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Group B streptococcus (GBS) S agalactiae

Gram positive

cocci in pair

capsule

CAMP test positive

Beta hemolytic (1-2% non hemolytic)

threat to infants infected perinatally

also responsible for post partum endometritis (especially following C section)

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Source and transmission: GBS

normal flora of GI tract and vagina

vertical transmission: either at birth or via ascension in utero

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Virulence factors: GBS

capsule: resist phagocytosis

Sialic acid: capsular component, inhibit alternate pathway of complement

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Group B streptococcal diseases

early onset neonatal disease begins with 7 days of birth

acquired in utero or at delivery. Most common in premature infants. High mortality rate. Symptoms: Bacteremia, pneumonia, meningitis.

Late onset neonatal disease begins 1 week to 3 months after birth.

Acquired postpartum. Low mortality rate (<20%) Symptoms: bacteremia, meningitis

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Postpartum sepsis (GBS)

usually acquired via wound inflected during parturition

SX: post partum endometriosis

fever, chills

wound infection

possible UTI

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CAMP test GBS

CAMP factor produced by GBS that enhances beta hemolysis of S. Aureus

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TX of GBS

penicillin G alone or in combination with an aminoglycosides

passive immunization in serious caes

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Streptococcus pneumoniae

gram positive

cocci in pair or short chain

capsule= Most important

CAMP test negative

bile solubility- positive

Alpha hemolytic (aerobically)

beta hemolytic (anaerobically)

genome diversity: 20% of DNA sequences different, still the same species

Catalase: negative: grow best in 5% CO2. Requires a source of catalase (blood) to grown on agar. Chronic granulomatous disease resistance to SP

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Virulence factors of streptococcus pneumoniae

capsules: resist phagocytosis; >90 serotypes identified, the major protective antigen

robust biofilm formation

IgA proteases cleaves IgA into FAB and Fc fragments

adhesins: mediates attachment of S. Pneumonia to epithelial cell lysis

pneumolysis: destroys the ciliated epithelial cell

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Streptococcus pneumoniae infections

lobar pneumonia (#1 causative organism in adults and in sickel cell disease)

meningitis (1# causative agent in adult meningitis)

Sinusitis (#1 causative organism)

Otitis media (1# causative organism)

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Diagnosis: Streptococcus Pneumoniae

Microscopic examination: Gram stain

Quellung reaction: Polyvalent anticapsular antibodies are mixed with the bacteria: increase in refractive mass around the bacteria

bile sensitive

optochin sensitive

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TX and prevetion of streptoccus pneumoniae

penicillin

vancomycin combined with ceftriaxone in penicillin allergy

two vaccines 13 and 23 valent polysaccharide vaccine