Since the introduction of a vaccine in 1942, diphtheria has become very uncommon in the UK. Today, all children born in the UK are offered the vaccine as part of their primary childhood immunisations (it is the “D” of the DTP+Hib vaccine). The few cases seen in the UK now are in non-immunised patients who usually acquire their infection in Eastern Europe and the former Soviet Union as vaccination there is no longer routine practice.
Diphtheria most commonly affects the upper respiratory tract but it can affect any mucous membrane including the conjunctivae, vagina or ear. Diphtheria can also cause skin infections. Asymptomatic colonisation is more common than infection.
The respiratory features of the classical presentation of diphtheria are:
- Severe sore throat
- Painful cervical lymphadenopathy
- Swelling of the neck leading to a “bull neck” appearance
- Asymmetrical adherent greyish white membranes (pharyngeal membranes), with surrounding inflammation, which may extend into the trachea and cause airway obstruction (diphtheria looks more like opaque Clingfilm or plastic food wrap whereas in tonsillitis there is pus on the tonsils and no membrane, see image below)
- Cutaneous diphtheria – erythematous and yellow crusted lesions on the skin, indistinguishable clinically from impetigo (an acute skin infection usually caused by the Group A beta-haemolytic Streptococcus). Laboratory tests can differentiate the diagnoses
- Nasal diphtheria – a chronic mild infection with unilateral serosanguinous discharge from the nose
- Myocarditis – progressive heart block and congestive cardiac failure, usually occurring about 1 week after the original diphtheria illness and caused by absorption of the diphtheria exotoxin into the bloodstream
- Neurological complications – a polyneuropathy which usually occurs about 2 weeks after the original illness and can mimic Guillain-Barre syndrome
Corynebacterium diphtheriae – a Gram-positive bacillus of which there are four biotypes: gravis, mitis, intermedius and diphtheriae e.g. Corynebacterium diphtheriae var. gravis. Occasionally cases of diphtheria are caused by Corynebacterium ulcerans, a similar bacterium to C. diphtheriae.
In order to cause the disease diphtheria, the C. diphtheriae has to be able to produce the exotoxin; this occurs when the bacterium itself is “infected” by a bacteriophage containing the toxin gene (a “virus” that infects bacteria...I’ll blog about this in the future!) The exotoxin acts locally e.g. in the throat but sometimes it is also absorbed into the bloodstream leading to myocarditis.
The vast majority of C. diphtheriae isolated in UK laboratories does not produce exotoxin. This non-toxigenic form does not cause diphtheria, although the patient may present with a mild sore throat but without the pharyngeal membranes. The only way to tell if the patient has a toxigenic C. diphtheriae is to test the bacterium in the laboratory for the prescence of the toxin gene.
Throat swab for culture and sensitivity (it can take 24-48 to confirm the presence of a toxigenic bacterium)
Treatment with antitoxin and antibiotics should be started as soon as diphtheria is suspected clinically rather than waiting for laboratory confirmation.
Diphtheria antitoxin contains antibodies against the exotoxin. In order to make antitoxin horses are injected with the exotoxin; antibodies against the exotoxin contained in the horse serum are then extracted. It should only be used in the hospital setting, for confirmed or probable cases of diphtheria. Diphtheria antitoxin should be given to classic respiratory cases without waiting for laboratory confirmation as absorption into the bloodstream can occur. In most cutaneous diphtheria infections, exotoxin absorption into the bloodstream is unlikely and therefore the risk of giving antitoxin is usually considered to be substantially greater than the benefit, although large lesions may still warrant antitoxin e.g. >2cm diameter.
If considering using antitoxin in the UK then the patient should be discussed with the duty doctor at Public Health England’s Immunisation, Hepatitis, and Blood Safety Department (IHBSD) at Colindale.
In addition to antitoxin, patients should be treated with antibiotics.
2nd line (if 1st line contraindicated)
IV Benzylpenicillin or PO Phenoxymethylpenicillin
IV or PO Erythromycin (other macrolides e.g. Clarithromycin, Azithromycin)
If throat swabs are still positive at 14 days then a further 10 days of antibiotics should be given
Diphtheria is highly contagious. The main route of transmission is from person-to-person by droplet spread; therefore hand hygiene is the most important aspect of infection control. The incubation period is between 2-5 days. Patients with suspected diphtheria who are sick enough to be admitted to hospital should be isolated in a side room and universal precautions commenced. Patients should be kept isolated until discharge or until they have 2 negative throat swabs (taken 24 hours apart) after finishing treatment. If the patient does not need admitting they should remain at home and limit their contact with other people until symptoms have resolved.
Prognosis and Complications
Non-immunised diphtheria has a mortality of 5-10% even with appropriate treatment. Children are most at risk of death.
Prophylaxis and Prevention
Immunisation is with the DTP+Hib vaccine. The vaccine is highly effective at preventing diphtheria. Diphtheria patients should be immunised once they are stable in order to prevent future infections as the infection is not immunogenic enough to give long-term immunity.
Diphtheria is a notifiable disease. Public Health England have recently produced an excellent guideline on the public health control and management of diphtheria in England and Wales. It is not clear if this was in response to the BBC’s scriptwriter’s requests for information but I like to think it was!
Outcome (warning spoiler alert!)
So Demelza slowly got better but poor little Julia sadly died. In the 18th Century this was a common outcome, not everyone lived happily ever after, but at least the story was an accurate reflection of how diphtheria behaved in the past…
P.S. I loved Poldark and can’t wait for series 2!