Strep Throat - Case Study 1

Location in body

- Enters the body via oropharyngeal route - it is very good at adhering to epithelial cells by adhesin molecules (particularly because of M protein). - Only causes pathogenesis when it penetrates the epithelial surface or localizes in deeper subcutaneous tissues. Asymptomatic carriage can be up to 20%. - Found as normal flora in throat

Manifestation of systemic/invasive infection

- Erysipelas is an acute skin infection accompanied by lymphadenopathy, fever, chills and leukocytosis. Painful inflamed skin that is raised and clearly demarcated from the surrounding healthy skin. This can occur anywhere, but the legs are a frequent site of infection. - Cellulitis is similar to erysipelas but involves connective tissue as well as the skin. - Necrotising fasciitis can also occur - this is a deep infection of connective tissue that destroys muscle and fat. The bacteria enter through a break in the skin. Over a matter of hours there is swelling and the appearance of a spreading red or dusky blue skin discoloration, often with fluid-filled bullae.

Host response - First Stage

- First stage of defence is epithelial cell - They act as a barrier against GAS - In the cytosol, GAS are combated by being enveloped by autophagosomes - killed when autophagosomes fuse with lysosomes

Organism Structure

- Gram positive - Catalase negative (distinguishes between strep. and staph.) - Grows in chain structures

Host response - Second Stage

- Host produces an acute inflammatory response - Host uses phagocytic cells to envelop GAS - Streptococci are opsonized by activation of the alternative and lectin innate complement pathways (and the classical pathway in the presence of anti-M protein antibodies in the plasma and tissue fluid). Neutrophils kill the pathogens by phagocytosis (helped by opsonisation).

Virulence Factors

- M protein (the most important virulence factor) binds factor H (inhibits complement pathways by degrading C3-convertase.). It also blocks deposition of C3b by binding fibrinogen - Produces C5a peptidase, which inactivates C5a (powerful chemoattractant for neutrophils, macrophages) - Many adhesins on surface help binding to epithelial cells - GAS has a hyaluronic acid capsule - anti-phagocytic

Diagnosis

- Microscopy - infected tissues can be observed under microscope with gram stain - Culture - swabs from the posterior pharynx/tissue/pus/blood can be grown on blood agar (24-48 hours on blood agar at 37 degrees and 5% CO2) to show the colonies with large zones of beta haemolysis. - Antigen detection - rapid tests detecting the A carbohydrate antigen on throat swabs. - Antibody testing can be used - serum testing

Treatment

- Penicillin first line treatment - If patients are allergic to penicillin, erythromycin or a cephalosporin can be used. - In cases of NF, surgery and clindamycin Antibiotic treatment prevents RF In patients who have had RF, prophylactic antibiotics are required for several years

Manifestation of local infection

- Pharyngitis (inflammation of pharynges) occurs 24-48hrs after infection - Sudden onset of sore throat, fever, malaise, headache - The pharynx and tonsils may be erythematous with creamy/yellow exudates

Mechanism of tissue damage

- Production of streptolysin S/O - responsible for beta-haemolysis. They also lyse host cells/WBCs - Bacterial enzymes destroy host cells and disrupt tissue integrity. - Components released from damaged cells and bacterial cell wall components (PAMPs) cause an acute inflammatory response.

Complications

- Scarlet fever - strawberry tongue, fever, red blanching rash across face, chest, back - Acute rheumatic fever (ARF) - an autoimmune disease in which antibodies induced against streptococcal antigens (M protein) cross-react with human tissues, particularly the heart, joints, subcutaneous tissue and the CNS. This occurs because M protein has a coiled-coil nature and this is similar to tropomysin, myosin, keratin and other coiled-coil proteins. - Acute glomerulonepthritis (AGN) is another autoimmune disease that can follow GAS infection with some M protein types. (ARF and AGN occur after infection with streptococcus.)

Transmission

- Spread from person to person through respiratory droplets - In case of skin infection, spread by contact or fomites - It can can seed lymphatics and the bloodstream.

Classification

Classified based on the type of haemolysis shown - Strep. Pyogenes shows beta-haemolysis, meaning complete haemolysis of RBCs, causing the agar to go transparent/yellow. (Beta haemolytic streptococci can be further sub-divided based on their carbohydrate antigens (groups A-T; S. pyogenes is group A).)

Prevention

Handwashing, good hygeine

Causative Organism

Streptococcus Pyogenes (Strep. A)