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Streptococcus

MBChB
First Year

Lusaka Apex Medical University


Wednesday, April 17, 2019

Genus
Streptococcus

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General Characteristics
• The genus Streptococcus is a diverse collection of
Gram-positive cocci
• Typically arranged in pairs or chains.

• Most species are facultative anaerobes,


• Some grow only in an atmosphere enhanced with carbon
dioxide (capnophilic growth).

• Complex nutritional requirements


• Necessitates the use of blood- or serum-enriched media
for isolation.

• Ferments Carbohydrates
• Resulting in the production of lactic acid

General Characteristics
• Gram positive cocci, nonmotile, non-spore forming
in chains, pairs

• Catalase negative differentiates from staph


species.

• Oxidase negative

• Often categorized based on Lancefield


classification
• Divided into serotypes based on bacteria’s antigens

• Lancefield Groups A and B include the significant


human pathogens

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Streptococcus

Streptococcus
• Rebecca Lancefield
• Developed a useful serogrouping system based on cell
wall Ag – 14 groups (A,B,C,….)
• As of 1992, serogroups A to H and K to V

• Another classification system is based on


haemolysis reactions

• β-haemolysis – A,B,C,G & some D strains


• Groups A, B, C, D and G are most associated with human
disease

• Viridans streptococci and Streptococcus


pneumoniae have no group-specific antigens

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Streptococcus & Related Genera

Gram-positive diplococci Gram-positive cocci in chains


e.g Streptococcus pyogenes

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α, β & γ Haemolysis on Blood Agar


• α-Haemolysis
• Colonies on blood agar are surrounded by a green zone
(Partial haemolysis).
• This "greening” is caused by H2O2, which converts haemoglobin
into methaemoglobin.

• β-Haemolysis
• Colonies on blood agar are surrounded by a large,
yellowish haemolytic zone in which no more intact
erythrocytes are present and the haemoglobin is
decomposed (Complete haemolysis).

• γ-Haemolysis
• This (illogical) term indicates the absence of
macroscopically visible haemolytic zones (no
haemolysis).

β, α & γ Haemolysis on Blood Agar

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Alpha-hemolysis –greenish discoloration of blood agar

Beta-hemolysis – clearing around colonies

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Medically Important Streptococcus


Species
• Streptococcus pyogenes
• Lancefield grp A

• Most impressive human pathogen

• Numerous virulence factors allow wide array of serious


infections

• Streptococcus agalactiae
• Lancefield grp B

• Serious neonatal infection

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Medically Important Streptococcus


species
• Streptococcus pneumoniae

• ‘pneumococcus’

• Common cause of community-acquired pneumonia

• Viridans group streptococci

• Streptococcus bovis

Natural Habitats
• Some Streptococcus function as opportunistic
pathogens

• Some live as avirulent commensals

• Normal flora of alimentary, respiratory, genital


tracts

• Viridans streptococci resident of oral cavity

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Group A Streptococci (GAS)


• Also known as S. pyogenes
• Causes a variety of suppurative and nonsuppurative dxs

• Gram Positive cocci


• Are spherical cocci, 1 to 2μm in diameter
• Short chains in clinical specimens and longer chains when
grown in liquid media,

• Typically appear in purulent lesions

• After 24 hours of incubation


• 1- to 2-mm white colonies with large zones of β-hemolysis
are observed

Virulence Factors of β-Haemolytic


S. pyogenes
Lancefield Group A
Produces surface antigens:
• C-carbohydrates – Protect against lysozyme

• Fimbriae – Adherence

• M-protein – contributes to resistance to


phagocytosis

• Hyaluronic acid capsule – provokes no immune


response

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Antigenic Structure
• M protein

• Major virulence factor of S. pyogenes (Grp A


streptococci)

• Resist phagocytosis by polymorphonuclear leucocytes

• >80 types of M protein; antibodies produced are type


specific.

• May cross react with cardiac tissue – important role in


rheumatic fever

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Antigenic Structures

Virulence Factors of β-
Haemolytic S. pyogenes (Group A)
Extracellular Toxins
• Streptolysin O, streptolysin S
• Destroy the membranes of erythrocytes and other
cells. Cause cell and tissue injury.
• Streptolysin O acts as an antigen.
• Past infections can be detected by measuring the antibodies to
this toxin (antistreptolysin titer)

• Pyrogenic streptococcal exotoxins (PSE) A, B, C.


• Responsible for fever, scarlet fever exanthem and
enanthem, sepsis, and septic shock.

• The pyrogenic exotoxins are superantigens and therefore induce


production of large amounts of cytokines

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Virulence Factors of β-Haemolytic S.


pyogenes (Group A
• Erythrogenic toxin
• 3 types: A, B, C

• Type A – mainly associated with


streptococcal toxic shock syndrome &
scarlet fever

• Type C – streptococcal toxic shock syndrome

• Type B - unknown

Virulence Factors of β-Haemolytic


S. pyogenes (Group A)
Extracellular Enzymes
• Streptokinase – Dissolves fibrin; facilitates
spread of streptococci in tissues.

• Hyaluronidase – Breaks down a substance that


cements tissues together (hyaluronic acid of
connective).

• Dnases – Breakdown of DNA, producing runny pus.

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Virulence Determinants of S.
pyogenes

Group A Streptococcal
Infections

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Group A Streptococcus

• Carrier 5%

• Nasal, throat, anal

• Nasal carrier more infective than throat carrier

• Transmission by direct contact with mucosa or


by droplets (cough, sneezing, conversation)

Streptococcus pyogenes
• Humans – Natural reservoir

Clinical Syndromes
• Pharyngitis
• Strains that elaborate pyrogenic exotoxins may cause
scarlet fever

• Suppurative complications
• Retropharyngeal abscess, peritonsillar abscess, otitis
media

• Non-suppurative complications
• Rheumatic fever, glomerulonephritis, Pyoderma and
erysipelas, Necrotizing fasciitis

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Pharyngitis
• Red and swollen pharynx, sometimes with
exudate

• Enlarged and painful cervical lymph nodes

• May be confused with viral pharyngitis

• Self-limiting fever subside by 3-5 days

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Pharyngitis

Left – red, swollem pharynx; Right – enlarged cervical lymphnodes

Pharyngitis
• Complications
• Spread beyond pharynx
• peritonsillar abscess

• Acute sinusitis

• Otitis media

• Pneumonia

• Bacteraemia, meningitis

• Acute rheumatic fever

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Impetigo
• Impetigo
• Localised skin infection

• Resulting from trauma to skin - skin abrasions, insect


bites

• 2-5 yr olds, poor hygiene, exposed skin areas

• Clinical characteristics

• start with small vesicle ( up to 1 cm) surrounded by area of


redness

• vesicles may enlarge, become pustular, yellow crust

• Complications Kidney disease - acute glomerulonephritis

Impetigo on the face

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Erysipelas
• Infection of the skin and subcutaneous tissues,
especially the dermis

• Usually occurs on the face

• Clinical characteristics
• Rapidly spreading erythema and edema

• Pain, fever, lymphadenopathy

• A serious infection require immediate antibiotic


treatment

Erysipelas

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Erysipelas of the leg

Necrotizing Fasciitis

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Diseases Associated with


Streptococcal Pyrogenic Exotoxins
• Scarlet fever
• infection with strains that elaborate any of the
pyrogenic exotoxins

• is a streptoccal pharyngitis with a characteristic rash

• clinical characteristics
• Buccal mucosa, cheeks, temples are deep red

• Pale area around mouth and nose

• Tongue covered with yellow white exudate (strawberry


tongue)

• Exudate stripped off later (red strawberry tongue)

Scarlet fever rash

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White strawberry tongue

Acute Rheumatic Fever-Pathogenic


Mechanism
• An autoimmune mechanism

• Related to antigenic similarities between


streptococci & human tissue

• Antistreptococcal antibodies react with both


heart tissues and streptococcal antigen

• Genetic predisposition to hyperreactivity to


streptococcal products

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Acute Glomerulonephritis
• Primarily a childhood disease

• Characterised by
• Edema
• Hypertension
• Hematuria
• Proteinuria

• Glomerulonephritis follows respiratory (after 10


days) or skin lesions (after 3 weeks)

• Involve only certain ‘nephrotoxigenic’ strains

Acute Glomerulonephritis
• Autoimmune mechanism

• Immunoglobulins, complement components react


with antibodies against group A streptococci

• Antigen-antibody complexes deposited at the


glomerulus and cause inflammation

• Usually benign with spontaneous healing (weeks to


months)

• Complications – renal failure & death

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Long-Term Complications of
Group A Infections
• Rheumatic fever
• follows overt or
subclinical pharyngitis in
children; carditis with
extensive valve damage
possible, arthritis, chorea,
fever

• Acute glomerulonephritis
• nephritis, increased blood
pressure, occasionally
heart failure; can become
chronic leading to kidney
failure

Streptococcus Pyogenes
• Streptococcal toxic shock

• Usually begins with Streptococcal soft tissue


infection

• Elaborates pyrogenic exotoxins

• Others cellulitis, myositis, necrotising


fasciitis, pneumonia, meningitis

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Laboratory Diagnosis
• Samples
• In pharyngitis - Swab of posterior pharynx &
tonsils

• Impetigo, erysipelas – culture of exudate

S. Pyogenes Identification
• Primary culture by pour or streak plate

• Domed, grayish/opalescent colonies

• Encapsulated cells produce mucoid colonies

• β-haemolytic
• Zone several times greater than diameter of
colony

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Streptococcus Identification

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Treatment & Prevention


• Grp A Streptococcus highly susceptible to Penicillin G
• Other antibiotics
• tetracycline ( resistance 5-10%)
• erythromycin
• chloramphenicol
• Cephalosporins

• Treatment of pharyngitis with 10 days prevent acute


rheumatic fever

• Treatment may not prevent acute glomerulonephritis

• Prophylaxis to patients with rheumatic heart disease


undergoing procedures that cause transient bacteremia
e.g. dental extraction

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S. Agalactiae (Group B
Streptococcus)
• Major cause of neonatal/perinatal disease
• 5-35% of pregnant women colonized (vagina/rectum)
• Newborns infected via vertical transmission during
birth
• Clinical syndromes
• Early onset – in utero/perinatal organism acquisition
• Presents in first 7days of life
• Bacteraemia, meningitis, pneumonia
• Late onset – 50% from birth canal, 50% post natal
• Presents 1 wk – 3months of life
• 10-15% mortality, 50% permanent neurological sequelae
• Bacteraemia, meningitis
• Prevention of infection by identifying moms with
colonization (vaginal/rectal culture) and give antepartum
antibiotics

S. Agalactiae
• Clinical syndromes
• Post partum infections

• Older children/non pregnant adults


• Pneumonia

• Meningitis

• Skin/soft tissue infection

• Endocarditis

• UTI

• Toxic shock like syndrome

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Group C, F and G Streptococcus


• Group C and G have been recovered from
patients with pharyngitis (and carriers)

• Normal flora of GI, vagina, oropharynx and


skin

• Cause numerous infections


• Bacteraemia, meningitis, skin/soft tissue
infections, septic arthritis

• Group F patients usually have significant


underlying diseases

Group D Strep & Viridans


Streptococcus
• Group D (S. bovis)
• Bacteraemia and endocarditis associated with colon
cancer
Viridans streptococci
• Normal URT and genital urinary tract flora
• Includes S. salivarius and S. imitis

• Causes 30-40% of cases of SBE (Subacute


Bacterial Endocarditis)
• Pre-existing native valve disease
• Prosthetic valves
• Poor oral hygiene

• Significant role in initiation and pathogenesis of


dental carries

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Streptococcus Pneumoniae
(Pneumococci)
Characteristics
• Gram positive, oval to lancet shaped cocci
usually occur in pairs or occur in pairs or short
chains

• Cells are surrounded by a thick capsule

• When cultured on blood agar, S. pneumoniae


develop α-haemolytic colonies with a mucoid
(smooth, shiny) appearance (hence “S” form).
• Mutants without capsules produce colonies with
a rough surface (“R” form).

Streptococcus pneumoniae

Figure 19.9

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Streptococcus Pneumoniae
• Virulence Factors
• Polysaccharide capsule, pneumolysin
• Clinical syndromes
• Pneumonia: Major cause of Community Acquired
Pnuemonia (CAP)
• Meningitis
• Most frequent cause of in infants/adults
• Most common cause after skull fracture/head injury
• Spontaneous bacterial peritonitis – cirrhosis
• Others: Septic arthritis, facial skin and soft tissue
infections
• Most serious infections in infants (˂2yrs) and
elderly

Pathogenesis and Clinical Pictures


• The capsule protects the pathogens from
phagocytosis and is the most important determinant
of pneumococcal virulence.

• Unencapsulated variants are not capable of causing


disease.

• Other potential virulence factors include pneumolysin


with its effects on membranes and an IgA1 protease.

• About 40–70% of healthy adults are carriers.


• Pneumococcal infections usually arise from this normal
flora (endogenous infections).

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Pathogenesis and Clinical Pictures


• Predisposing factors
• primary cardiopulmonary diseases, previous infections
(e.g., influenza).

• The most important pneumococcal infections are


lobar pneumonia and bronchopneumonia.

• Other infections
• Acute exacerbation of chronic bronchitis, otitis media,
sinusitis, meningitis, and corneal ulcer. Severe
pneumococcal

• Infections frequently involve sepsis.

Pneumococcal Pneumonia
• Aspiration of respiratory secretions containing
pneumococci

• 10-30% normal people carry in throat

• Aspirated material rapidly cleared by defense


mechanisms in lower respiratory tract

• Impaired defense mechanism


• Damaged bronchial epithelium – smoking, air pollution
• Trauma
• Alcoholic intoxication
• Diabetes mellitus

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S. pneumoniae and Pneumonia – The


Course of Bacterial Pneumonia

Pneumococcal Pneumonia

• Clinical manifestations

• Sudden onset

• Chill & high fever

• Cough – pink to rusty sputum (blood)

• Pleuritic chest pain

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Pneumococcal Meningitis

• One of leading cause of bacterial meningitis

• Signs & symptoms same as other bacterial


meningitis

• Complication of pneumonia; infection of other


sites; trauma; no evidence

• All age affected

S. Pneumoniae & Otitis Media

Chronic Inflammation

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Specimens
• Properly collected sputum

• Lung biopsy

• Blood

• Pleural aspirate

Identification of Pneumococci
• Gram stain
• May occur singly, in pairs, or chains
• S. pneumoniae-lancet shaped diplococcic

• Haemolysis on blood agar


• α-partial lysis of RBC = greenish/brownish
discolouration

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Treatment & Prevention


• Susceptible to penicillin & other ß-lactams.

• Resistance to above antibiotics have emerged –


vary from countries.
• Malaysia 30%

• Resistance to erythromycin in Malaysia 30%

• Resistance to chloramphenicol & tetracycline


uncommon

• Multiresistant strains – treat with vancomycin

Pneumococcal Pneumonia
• Vaccine prepared from capsular polysaccharide
(23 types)

• 5 yrs protection

• Recommended for patients at high risk – old age,


underlying disease, asplenic, poor immune status

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Identification of Pneumococci:
Presumptive ID
• Optochin susceptibility – differentiates S.
pneumoniae (S) from viridans streptococcus

• Bile solubility – differentiates S. pneumoniae


(soluble=colony disappears) from viridans
streptococci (colony stays)

Enterococcaceae
• Previously classified with group D streptococci

• Reclassified as a separate genus

• Normally found in the intestines of humans and


other animals

• Nonmotile, catalase-negative

• They are able to proliferate:


• at 45 8C, in the presence of 6.5% NaCl and at pH 9,
qualities that differentiate them from Streptococci.
• 90% of the isolates are identified as E. faecalis,
5–10% as E. faecium.

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Enterococcus faecalis in lung tissue

Figure 19.10

Enterococcus
• Clinical syndromes
• UTI
• Bacteraemia
• Endocarditis
• Abdominal/pelvic infections
• Soft tissue infections
• Resistance Issues
• Low level aminoglycoside
• High MICs for penicillin (use ampicillin)
• Vancomycin reistance

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End!!

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