Diphtheria and Diphtheria Vaccination

Authored by , Reviewed by Dr Helen Huins | Last edited | Meets Patient’s editorial guidelines

This article is for Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the 6-in-1 Vaccine (Including DTaP, Polio, Hib and Hep B Immunisations) article more useful, or one of our other health articles.

Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.

This disease is notifiable in the UK - see NOIDs article for more detail.

This is an acute upper respiratory tract infection, but sometimes it infects the skin. Hippocrates first described the disease in the 4th century BC and major epidemics swept through Europe in the 17th century. It was known as 'the strangling angel of children'.

  • The organism is pathogenic only in humans.
  • Corynebacterium diphtheriae is a Gram-positive, aerobic, non-motile, rod-shaped bacterium.
  • The bacterium is classified as gravis, mitis or intermedius.
  • Pharyngeal or cutaneous diphtheria is caused by toxigenic strains of C. diphtheriae and occasionally by Corynebacterium ulcerans. The latter is usually an infection of cattle.
  • A fibrinous pseudomembrane is produced, usually on the respiratory mucosa.
  • An exotoxin affects a number of tissues, including the heart, peripheral nerves, and kidneys.
  • Diphtheria mainly occurs in epidemics.
  • A vaccine was introduced to the UK in 1941, after which the number of cases fell from 46,281 (2,480 deaths) in 1940, to 37 cases (six deaths) in 1957.
  • There was only one case of diphtheria in the UK in 2013[1].
  • The last disease outbreak was in Afghanistan in 2003 in which there were 50 cases and three deaths.
  • In 2013 there were 4,671 cases of diphtheria reported to the World Health Organization (WHO)[2].
  • Diphtheria cases are mainly from Southeast Asia, South America, Africa and India.
  • Although there has been a reduction in diphtheria incidence over a period of 10 years, maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and re-emergence of C. diphtheriae[3].
  • More recently, C. ulcerans has been increasingly isolated as an emerging zoonotic agent of diphtheria from pets such as cats or dogs, indicating the enduring threat of this thought-to-be controlled disease[4].

Risk factors

  • In countries where hygiene is poor, cutaneous diphtheria is the predominant clinical manifestation and source of infection.
  • Poor living conditions and lack of immunisation, especially where there is not an immunisation programme, increase risk.
  • Spread is via respiratory droplets or contact with exudate from skin lesions.
  • Adults are at risk as they lose protection from childhood vaccines unless they have boosters.
  • Very early symptoms may be similar to the common cold.
  • Often diphtheria presents with a nasal discharge that is initially watery and becomes purulent and blood-stained. The nostril can be sore or crusted with the pseudomembrane sometimes visible within the nostril.
  • Incubation period is usually 2-5 days, but may be up to 10 days.
  • In diphtheria of the upper respiratory tract, there is a membranous pharyngitis (often referred to as a pseudomembrane) with fever, enlarged anterior cervical lymph nodes and oedema of soft tissues giving a 'bull neck' appearance.
  • The pseudomembrane may cause respiratory obstruction.
  • Swallowing may be made difficult by unilateral or bilateral paralysis of the muscles of the palate.
  • The exotoxin also affects other parts of the body, including the heart and nervous systems. It may cause paralysis and cardiac failure.
  • Milder infections resemble streptococcal pharyngitis and the pseudomembrane may not develop, particularly where there has been previous vaccination.
  • Carriers do not usually have any symptoms.

Cutaneous infection is usually mild, but chronic:

  • Typical findings are vesicles or pustules that quickly rupture to form a 'punched-out' ulcer up to several centimetres in diameter.
  • It often appears on the lower legs, feet and hands.
  • It may be painful in the first week or two and covered with a dark pseudomembrane which separates to show a haemorrhagic base which may have exudate.
  • The surrounding tissue is pink or purple and oedematous.
  • It usually heals in 2-3 months to leave a depressed scar.
  • Infections at other mucocutaneous sites include otitis media, conjunctivitis and vulvovaginitis.

Effects of toxin

  • Cardiomyopathy and myocarditis are usually evident by the 10th to 14th day. There may be arrhythmias early or late in the illness. Myocardial involvement accounts for around half of all deaths.
  • Neuritis affects motor nerves, firstly with paralysis of the soft palate, causing dysphagia and nasal regurgitation, then ocular nerves, peripheral nerves and diaphragm with resulting infection and respiratory failure.
  • Nephritis and proteinuria may occur.
  • Thrombocytopenia may be present.
  • Definitive diagnosis of diphtheria requires a positive culture from respiratory tract secretions or cutaneous lesions, and a positive toxin assay.
  • Routine laboratory results are usually nonspecific and may include a moderately elevated white blood cell count and proteinuria.
  • Toxigenicity tests are usually undertaken by specialist laboratories.


  • Antibiotics are often given. The antibiotics of choice are usually erythromycin, azithromycin, clarithromycin or penicillin.
  • Patients should be immunised in the convalescent stage because clinical infection does not always induce adequate levels of antitoxin. They should receive a complete course or a reinforcing dose according to their age and immunisation history.
  • Completely immunised individuals should receive a single reinforcing dose of a diphtheria-containing vaccine according to their age.

Management of contacts

  • All contacts of either a person with diphtheria or a carrier should be given antibiotic prophylaxis. This is usually with erythromycin or penicillin.
  • Contacts of cases with C. ulcerans also need to be given antibiotic prophylaxis.
  • Contacts need treatment to eliminate both incubating disease and to prevent carriage to others.
  • Partially immunised or unimmunised individuals should complete immunisation according to the UK schedule. Completely immunised individuals should receive a single reinforcing dose of a diphtheria-containing vaccine according to their age.
  • Paralysis. This often involves the muscles of the palate and the hypopharynx is seen in 10-20% of patients, beginning as early as the first 10 days of illness.
  • Difficulty swallowing and nasal speech. These are often the first signs of neurological involvement.
  • Involvement of other cranial nerves. This may be delayed until as late as seven weeks after infection and produce oculomotor paralysis and blurred vision. Diffuse, usually bilateral, motor function deficits resulting from involvement of the anterior horn cells of the spinal cord may be seen as late as three months after initial disease, with progression of weakness either from proximal-to-distal regions or, more commonly, from distal-to-proximal regions.
  • Diaphragmatic paralysis. This will result if the phrenic nerve is involved. This may occur at any time between the 1st and 7th weeks of illness.
  • Cardiac complications. These may arise during the first 10 days of the illness or they may be delayed for 2-3 weeks by which time pharyngeal disease is subsiding:
    • The first sign of cardiac involvement is tachycardia disproportionate to the degree of fever. Fever is rarely above 39°C.
    • Heart block of first, second or third degree may be seen.
    • Atrioventricular dissociation and ventricular tachycardia can develop and congestive heart failure may result.
    • Echocardiogram may demonstrate dilated or hypertrophic cardiomyopathy.
    • In patients who survive, cardiac muscle regeneration and interstitial fibrosis lead to recovery of normal cardiac function, unless toxic damage has led to a permanent arrhythmia.
  • Airway obstruction. This is caused by the diphtheritic membrane and peripharyngeal oedema causing the 'strangling', and emergency tracheostomy may be required.
  • Overall there is a 5-10% mortality rate, but it is up to 20% in those younger than 5 years and older than 40 years[5].
  • Recovery is slow and particular caution should be advised after myocarditis.
  • Complete recovery from neurological damage is usual in those who survive.

Vaccination confers protection against disease by production of antibodies to the diphtheria toxin. When treated with formaldehyde and heat, diphtheria toxin loses its ability to bind to cells and its enzymatic activity, but retains its immunogenicity. This treatment converts diphtheria toxin to a toxoid. The vaccine is produced from purified inactivated toxin from a strain of C. diphtheriae.

Available vaccines[6]

Diphtheria vaccines are available in two strengths according to dose of toxoid:

  • High-dose - vaccines contain ≥30 IU of diphtheria toxoid and are used to achieve satisfactory primary immunisation of children - as in diphtheria/tetanus/acellular pertussis (DTaP) vaccine (capital D = high-dose).
  • Low-dose - vaccines contain approximately 2 IU of toxoid and are used for primary immunisation of those aged over 10 years and for subsequent boosters (lower case d signifies low-dose as in dTaP).

Monovalent diphtheria vaccine is not available. Vaccination should only given as a component of the following combination products:

  • Diphtheria/tetanus/acellular pertussis/inactivated polio/Haemophilus influenzae type b vaccines (DTaP/IPV/ Hib).
  • Diphtheria/tetanus/acellular pertussis/inactivated polio vaccines (DTaP/IPV or dTaP/IPV).
  • Tetanus/diphtheria/inactivated polio (Td/IPV).


  • Five doses of a diphtheria-containing vaccine are given intramuscularly.
  • Upper arm or anterolateral thigh sites are recommended to minimise risks of local reactions.
  • Other vaccinations such as measles, mumps and rubella (MMR), meningitis C or hepatitis B can be given at the same time but should be injected at an alternative site and preferably in a different limb.


Primary immunisation

  • All infants should receive the primary immunisation course involving three doses of diphtheria-containing vaccine.
  • It is recommended that DTaP/IPV/Hib be given at 2, 3 and 4 months of age as levels of passively acquired maternal antitoxin decline.
  • However, if necessary, the same dosing schedule can be used in children up to 10 years of age.
  • Older individuals (aged >10 years) should receive three doses of a d-containing preparation (usually Td/IPV) at monthly intervals.


  • The first booster dose is given to children between the ages of 3½ and 5 years.
  • Either DTaP/IPV or dTaP/IPV will elicit an adequate immune response.
  • If primary immunisation has been delayed, the first booster dose must be given at least one year after completion of the initial course.
  • All individuals aged over 10 years who require a first booster should be given a dose of Td/IPV.

The second booster dose is offered to those aged 13-18 by the school health service:

  • The Td/IPV preparation should always be used.
  • If previous doses have been delayed, the second booster should be given at least five years after the first booster.
  • Note that patients may have inadvertently already received a diphtheria booster associated with tetanus toxoid.

Other recipients

Children from developing countries may not be fully immunised against diseases such as diphtheria. If the history is unclear, children are considered unimmunised and should complete the full UK schedule.

Travellers to endemic areas should be fully immunised according to the UK schedule before travel. Travellers to developing countries for over one month's duration, who had their last diphtheria booster dose more than 10 years previously, should be offered a further booster of Td/IPV.

Laboratory and healthcare workers
Individuals who may be exposed to diphtheria at work must be fully immunised and should be offered a booster dose. Further boosters should be given every 10 years if risks persist. Workers who are unimmunised should undergo the complete vaccination schedule with subsequent antibody testing as proof of immunity.

The diphtheria vaccination should not be administered to patients with:

  • Confirmed anaphylactic reaction to diphtheria toxoid-containing vaccine.
  • Confirmed anaphylactic reaction to any of the components of the vaccine.

The following situations do not prohibit diphtheria vaccination:

  • History of a stable neurological condition, seizures or febrile convulsions (without neurological deterioration).
  • If there is evidence of current neurological deterioration, including poorly controlled epilepsy, immunisation should be deferred and the child should be referred to a child specialist for investigation to see if an underlying cause can be identified. If a cause is not identified, immunisation should be deferred until the condition has stabilised. If a cause is identified, immunisation should proceed as normal.
  • Fever, persistent screaming or crying (even for more than three hours), severe local reactions or hypotonic-hyporesponsive episodes following previous diphtheria vaccinations.
  • Immunosuppression including HIV infection (but individuals may not achieve an adequate immunological response).

This vaccine can be given to women who are pregnant or who are breast-feeding.

  • Pain, swelling, redness or a transient nodule at the injection site may occur.
  • Fever, convulsions, screaming, pallor, cyanosis and hypotonic-hyporesponsive episodes.
  • Allergic reactions and (very rarely) anaphylactic episodes.

Further reading and references

  1. UK and Northern Ireland diphtheria incidence time series: WHO vaccine-preventable diseases; World Health Organization, 2014

  2. Immunization, surveillance, assessment and monitoring; World Health Organization

  3. Wagner KS, White JM, Lucenko I, et al; Diphtheria in the postepidemic period, Europe, 2000-2009. Emerg Infect Dis. 2012 Feb18(2):217-25. doi: 10.3201/eid1802.110987.

  4. Zakikhany K, Efstratiou A; Diphtheria in Europe: current problems and new challenges. Future Microbiol. 2012 May7(5):595-607. doi: 10.2217/fmb.12.24.

  5. Wagner KS, White JM, Neal S, et al; Screening for Corynebacterium diphtheriae and Corynebacterium ulcerans in patients with upper respiratory tract infections 2007-2008: a multicentre European study. Clin Microbiol Infect. 2011 Apr17(4):519-25. doi: 10.1111/j.1469-0691.2010.03269.x.

  6. Immunisation against infectious disease - the Green Book (latest edition); Public Health England