6B: Rheumatic Fever

Question 1

How do pathogens cause illness?

Answer 1

1. Direct damage to tissues/cells
2. Immune response
   - Inflammation
   - Acute (pyogenic) inflammation e.g. pneumonia, cellulitis
   - Chronic inflammation e.g. tuberculosis
   - Immune mediated e.g. HIV infection leading to low platelets
3. Toxin e.g. food poisoning, cholera
4. Carcinogenesis e.g. human papilloma virus (HPV)

Question 2

Rheumatic fever

Answer 2

• An “immune mediated” illness characterised by inflammation in joints
• Rebecca Lancefield (1895 – 1981) discovered that Streptococcus pyrogenes was the cause of rheumatic fever

Question 3

Streptococcus pyrogenes

Answer 3

1. Colonises pharynx in 15 – 40% of children
2. Common cause of pharyngitis & skin infection
3. RARELY some children develop rheumatic fever or glomerulonephritis (inflammation of kidney) following infection

• M proteins differ between strains
• There are 250+ types of M proteins
• Some M types are associated with rheumatic fever
• In the 1960s vaccination with M protein caused some cases of rheumatic fever

Question 4

Development of rheumatic fever or glomerulonephritis

Answer 4

1. Innate immune system activation & S. pyrogenes toxins damage cells in pharynx
2. Inflammation of pharynx
3. Pain, erythema, swelling, purulent exudate
4. S. pyrogenes has surface proteins that it uses to bind to cells in the pharynx
5. Antibodies that form against these bacterial proteins sometimes also bind to human tissues
6. If antibodies bind to human tissues (heart, joints, kidneys etc) local inflammation occurs, unrelated to initial site of infection
7. Symptoms of Rheumatic fever OR glomerulonephritis after an interval

• T cells tell B cells to make antibody against S. pyrogenes surface proteins (M proteins?)
• In some people these antibodies recognise and bind to shapes of proteins on human cells
• White blood cells will react to antibodies bound to a protein & initiate inflammation

Question 5

Antibiotics to prevent rheumatic fever

Answer 5

• The proportion of people who still have a sore throat after 7 days: 40% reduction
• The proportion of people who get rheumatic fever in 2 months: 70% reduction
• If 98% of the population (100% - 1.6%) is not susceptible to developing RF, then ~2:10,000 benefit
• Thus, although this is an oversimplification – treatment targeted to “high risk” groups

Question 6

Cure of S. pyrogenes pharyngitis or carriage:

Answer 6

Oral phenoxy-methyl PENICILLIN for 10 days