Diphtheria

Classical respiratory diphtheria

• membranous pharyngitis with fever (thick, fibrinous, firmly adherent grey membrane - not always)
• enlarged anterior cervical lymph nodes
• oedema of the surrounding soft tissue (‘bull neck’)
• atypical/ mild respiratory cases without classical pseudomembrane may occur in vaccinated cases 

Laryngeal diphtheria

• hoarseness and stridor
• usually an extension of pharyngeal involvement in children 

Nasal diphtheria

• mild and chronic
• unilateral or bilateral nasal discharge, initially clear and later becomes bloody

Cutaneous diphtheria

• appears on exposed limbs, particularly the legs
• initially vesicles, becoming small, clearly demarcated ulcers
• similar in appearance to impetigo
• becoming an eschar with a hard bluish-grey membrane that is slightly raised
• may be present with respiratory symptoms in the same individual 

• Suspected cases should always be discussed with ID Micro so that appropriate investigations and management can be instigated promptly.
• Laboratory confirmation is typically by a combination of culture, bacterial isolation and preliminary identification of C. diphtheriae, C. ulcerans or C. pseudotuberculosis in a clinical laboratory followed by confirmation and toxigenicity testing at a reference laboratory.
• Dacron, Viscose or flocked applicator swabs should be used to collect samples from each suspected case and placed in a routine semi-solid transport medium, such as Amies, immediately after collection and sent to the local diagnostic laboratory for bacterial culture. 

Includes C. diphtheriae, C. ulcerans, or C. pseudotuberculosis 

Cases needing admission should be managed in isolation:

• Isolate in a side room with use of gloves, apron and surgical mask
• Continue isolation until 2 cultures from the nose and throat (or skin lesions if cutaneous diphtheria) taken at least 24 hours apart and more than 24 hours after completing antibiotics are negative

For non-hospitalised cases

• Restricted contact with others for the first 6 days of an appropriate course of antibiotics
• Clearance swabs should be obtained 24- and 48-hours after completion of antibiotics to ensure elimination of carriage 

The mainstays of treatment are

• Supportive management, including airways management
• Thorough cleaning of the lesion
• Diphtheria antitoxin (DAT) 
• Antibiotic management

Diphtheria antitoxin (DAT)

• Early treatment with DAT is critical for successful management
• Should be used in a hospital setting for CONFIRMED or PROBABLE cases of diphtheria
• Should be given to classic respiratory cases without waiting for laboratory confirmation 
• For cutaneous diphtheria infection, the role of DAT is less clear, but where ulcers are sufficiently large (for example more than 2cm² ) and/or membranous, then DAT is justified

CAUTION: Diphtheria antitoxin is based on horse serum and therefore severe, immediate anaphylaxis occurs more commonly than with human immunoglobulin products. Tests to exclude hypersensitivity to horse serum should be carried out as described in the Summary of Product Characteristics (SPC). Local policies for the management of anaphylaxis should be followed. 

Antibiotic management

• Antibiotic treatment is advised to eliminate the organism and prevent spread in both cases and contacts
• Antibiotics are not a substitute for antitoxin treatment if indicated
• All specimens should be collected BEFORE antibiotic treatment is started if possible. If antibiotics have already been started then samples should still be taken.

Mild disease

Preferred: clarithromycin 500mg po bd for 14 days

Alternatives: erythromycin 500mg po qds for 14 days OR azithromycin 1g od po on day 1 then 500mg od po for 7-10 days

Severe disease/ hospital treatment

• benzylpenicillin 1.2g iv qds + clarithromycin 500mg iv bd
• Add vancomycin IV, for extremely severely ill cases
• oral conversion when possible

Close contacts of confirmed / probable cases / asymptomatic carriers

Preferred: clarithromycin 500mg po bd for 10 days

Alternative: azithromycin 1g od po on day 1 then 500mg od po for 5 days

Immunisation

• Infection does not always induce adequate levels of antitoxin.
• CONFIRMED or PROBABLE cases should receive a booster dose of a diphtheria-toxoid containing vaccine or immunisation appropriate to age and immunisation history.
• Cases should be immunised once they are clinically stable.
• Close contacts of confirmed or probable diphtheria cases and asymptomatic carriers should also be immunised
• No booster dose is required if the last dose was given within the last 12 months. 

If a dose of diphtheria-containing vaccine has NOT been given in the last 12 months:

immunised adults – one injection of adsorbed low-dose diphtheria-containing vaccine for adults

unimmunised adults - 3 injections of adsorbed low-dose diphtheria-containing vaccine at monthly intervals

a person with immunisation status unknown – where there is no reliable history of previous immunisation, it should be assumed that they are unimmunised and follow as above.

The incubation period for diphtheria is usually 2 to 5 days, but may be up to 10 days 

Contacts at risk are those with:

• prolonged close contact with a case or known carrier in a household-type setting
• transient close contact if directly exposed to large particle droplets or secretions
• direct contact with cutaneous lesions or articles soiled with the discharge of infected people or animals 

Transmission routes include:

• droplet spread from a person with respiratory diphtheria
• direct contact with cutaneous diphtheria lesions, infected secretions 
• contact with infected animals (C. ulcerans), or consumption of unpasteurised dairy products (C. ulcerans).  

Diphtheria is a notifiable disease under the Infectious Disease (Notification) Act of 1889 and the updated 2010 regulations. For further advice on how to notify, see Notifiable diseases