Makindo Medical Notes.com

Immunisation is to the toxin rather than the bacterium. It is produced by a phage infecting the bacterium rather than encoded on bacterial DNA

About

• Corynebacterium diphtheria and occasionally C. ulcerans.
• Fatality rates between 5% and 10%
• Releases an exotoxin that blocks protein synthesis
• Toxin gene is encoded by a bacteriophage
• Mild cases can go undiagnosed

Microbiology

• Gram positive, club-shaped, non-motile rods
• They grow at angles forming V,L,W shapes "Chinese letter shapes"
• Grows best with oxygen at 37 degrees
• Exotoxin only produced by those with the relevant phage
• Exotoxin has two components A and B as described below
• Toxin acts as an RNA translational inhibitor
• 535 residues, 58 kDa exotoxin whose active form consists of two polypeptide chains linked by a disulphide bond
• Causes local tissue necrosis
• Toxaemia and paralysis due to demyelinating peripheral neuritis
• Cardiac failure due to myocarditis.

Virulence

• Those bacteria infected with the corynephage beta produces an A-B toxin
• The A component is an ADP ribosyl transferase that binds to eukaryotic elongation factor 2 blocking protein synthesis
• The B component directs the toxin to the oropharynx, heart and nerve cells

Spread

• Spread by direct physical contact
• Breathing aerosolized secretion from an infected person

Clinical (IP is 2-4 days)

• Pharyngitis - grey dirty pseudomembrane is visibly composed of fibrin and dead cells and there is associated lymphadenopathy producing a "bull neck"
• Nasal, laryngeal and pharyngeal mucosa affected
• Can lead to airway obstruction and stridor
• Sore throat, fever, malaise
• Heart failure, heart block and arrhythmias
• Cranial nerve palsies: diplopia, dysarthria, dysphagia
• Myocarditis and cardiac dysfunction - bradycardia, chest pain
• Laryngeal nerve palsy - hoarseness

Investigations

• Grows on Hoyle's media (Blood tellurite) producing black colonies reducing tellurite to tellurium. An alternative is the Tinsdales medium with added horse serum.
• There are 3 types - gravis (worst), intermedius, mitis (best) which suggest the severity of disease caused and can be separated by haemolysis and appearance
• Biochemical testing for catalase, urease, nitrate, pyranzinamidase, cystinase
• Test for toxin production using Elek test using antitoxin
• Serotyping and bacteriophage typing
• Culture of swabs from larynx/pharynx
• ECG/Monitor - heart block and arrhythmias
• Echocardiogram to assess LV function

Diphtheria was eradicated from much of the developed world by mass vaccination in the mid-20th century

Management

• ABCs. Bed rest. Telemetry. Isolation and treatment of the index case
• Diphtheria antitoxin produced from hyperimmune horse serum: neutralises any toxin not fixed to tissue but can cause anaphylaxis
• Give Amoxicillin or Erythromycin for two weeks and treat contacts
• Remove membrane by laryngoscopy or bronchoscopy to prevent airways obstruction.
• All contacts should also be immunised or given a booster dose of toxoid. Booster doses are required every 10 yrs to maintain immunity