11 Dec 2015
DiphtheriaDiphtheria is a bacterial infection common in many resource poor countries
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Diphtheria is a bacterial infection usually caused by the toxin producing strains of Corynebacterium diphtheriae and Corynebacterium ulcerans.
Although rare in most of the developed world, diphtheria is still common in many resource poor countries.
Diphtheria is rare in UK travellers, but unvaccinated travellers visiting countries where diphtheria is common are at risk.
Diphtheria commonly affects the respiratory tract but may also affect the skin (cutaneous diphtheria).
Complications are caused by spread of the toxin and typically affect the heart and nervous system.
Vaccination is the most effective method of preventing diphtheria.
Diphtheria is a disease caused by the toxin producing strains of the bacteria Corynebacterium diphtheriae, Corynebacterium ulcerans, and, very rarely, Corynebacterium pseudotuberculosis . The term diphtheria is derived from the Greek for leather referring to the tough coating that typically occurs in the throat of infected individuals. In the early part of the twentieth century diphtheria was a major cause of disease worldwide with a high mortality . Diphtheria has now become rare in much of the developed world, due in part to the introduction of successful vaccination programs.
The toxin produced by the bacteria is responsible for much of the damage caused by the infection. The disease typically affects the upper-respiratory tract (commonly the throat and tonsils) or skin (cutaneous diphtheria). Spread of the toxin throughout the body can lead to complications affecting the heart and nervous system .
Since the early 1990s C. ulcerans has overtaken C. diphtheria as the most common laboratory confirmed toxin-producing strain of diphtheria in the UK . C. ulcerans is associated with consumption of unpasteurised dairy products and close contact with farm and possibly some domestic animals; it is usually acquired in the UK . C. diphtheriae is usually acquired by unvaccinated individuals in countries where diphtheria is more common although the risk to travellers remains very low . An effective vaccination is available to prevent all toxin-producing strains of diphtheria.
At the beginning of the 1980s, many countries in the industrialised world were progressing toward the elimination of diphtheria . Important factors that contributed to this decline include improved sanitation and the implementation of routine vaccination programmes. During the 1990s a resurgence of diphtheria was seen in countries of the former Soviet Union [2, 6]. By the mid 1990s the outbreak had affected all 15 states of the former Soviet Union and had spread to other countries in Eastern Europe [2, 5]. At its peak in 1995 the outbreak was responsible for more than fifty thousand cases of diphtheria and between 1990 and 1998 it accounted for over eighty percent of all diphtheria cases reported worldwide [7, 8]. The outbreak was due in part to a failure of diphtheria control measures following the break-up of the Soviet Union [2, 9]. As control measures improved after 2000 the outbreak largely abated .
In 2014 7,321 cases of diphtheria were reported to the World Health Organization (WHO) with the vast majority of these cases being reported from developing countries, where control systems may be sub-optimal . Between 2000 and 2014 countries reporting the highest number of cases to WHO included: India, Indonesia, Nepal, Iran, Pakistan, Sudan, Thailand, the Lao People’s Democratic Republic, the Philippines, Myanmar and Niger . Reported data on diphtheria however must be interpreted with caution due to variations in case definitions and reliability of surveillance systems.
Risk for travellers
Cases of diphtheria occasionally occur in unvaccinated or incompletely vaccinated travellers to endemic regions . Travel associated diphtheria is most commonly caused by C. diphtheriae which is usually transmitted by respiratory droplets or direct contact with an infected skin lesion. Travel associated C. ulcerans is rarely reported in the UK, but close contact with cattle or other farm animals and companion animals including cats and dogs, are potential risk factors for infection [4, 9].
Between 1986 and 2014, there were 68 isolates of toxigenic C. diphtheriae reported to Public Health England . The majority of cases were imported: 26 from the Indian sub-continent (ISC), 11 from South East Asia, eight from Africa, two from Pacific islands and one each from the Middle East, Russia, and western Europe. Ten isolates were presumed to have been acquired in the UK of which one, in 2003, was acquired in a laboratory, and nine did not have a country of infection stated. Twenty-four cases were cutaneous diphtheria.
Between 2000 and 2014, there were 33 isolates of toxigenic C. ulcerans reported in England and Wales; the vast majority were thought to have been acquired in the UK . The imported cases represent patterns of travel to areas where diphtheria is still endemic i.e. the ISC, South East Asia and Africa.
C. diphtheriae is usually spread between humans via respiratory droplets or direct contact with secretions from the respiratory tract or infected skin . Conditions of crowding and poor hygiene increase the risk of transmission. C. ulcerans is associated with consumption of unpasteurised dairy products and contact with infected animals .
Signs and symptoms
The incubation period is usually between two and five days, but is occasionally up to 10 days. The symptoms may be classified as local or systemic, depending upon whether or not the exotoxin has spread.
Respiratory tract diphtheria
There are several forms of respiratory tract diphtheria. The most common is pharyngeal diphtheria affecting the soft palate, tonsils, and pharynx (area at the back of the throat). In ‘classical’ respiratory diphtheria a tough, ‘leathery’ grey/yellow membrane is formed and is firmly attached to the underlying tissue, the lymph glands become swollen, prominent, and tender producing a ‘bull neck’ appearance. However, in non-endemic countries where vaccine coverage is high ‘classical’ respiratory diphtheria is now rare and most cases of respiratory diphtheria are mild and occur in people who have been partially vaccinated.
Infection may spread to the larynx (voice box) leading to laryngeal diphtheria. As a result there will be a husky voice, a brassy cough and if there is airway obstruction, difficulty in breathing. Nasal diphtheria may also occur.
This presents as a chronic non-healing ulcer of the skin and is usually co-infected with other bacteria. Cutaneous C. diphtheriae has typically been seen in the tropics, although cases have been described in western settings among homeless populations and in returning travellers . Cutaneous C. ulcerans has been associated with contact with infected farm and companion animals but is not usually associated with travel. Systemic complications and fatalities are rare with the cutaneous form of infection.
Spread of the toxin throughout the body can lead to effects on other organs and body systems. The systems most commonly affected are the cardiovascular (around ten percent of patients) and nervous systems (ten to 20 percent of patients). The overall mortality of diphtheria is around five to ten percent .
Diagnosis and treatment
Diphtheria should be suspected in the presence of typical symptoms particularly in individuals who are unvaccinated or have incomplete vaccination who have visited endemic countries. The diagnosis is confirmed using laboratory techniques to culture and identify the organism and to determine whether the diphtheria isolated is a toxin producing strain.
Treatment of diphtheria requires both antibiotics to eradicate the bacteria and in severe cases antitoxin to neutralise the effects of the toxin. Typical antibiotics include macrolides (e.g. erythromycin) or penicillins. Diphtheria antitoxin should only be used for confirmed or probable cases of diphtheria in a hospital setting . Diphtheria antitoxin should be given to classic respiratory cases without waiting for laboratory confirmation. Antitoxin should be administered early in the course of infection to prevent disease progression. As the antitoxin is an equine product (produced using horse’s blood), anaphylaxis and serum sickness can occur, and patients should be skin-tested before administration.
Vaccination is the most effective method of preventing diphtheria. Maintaining high vaccination coverage in a population will lead to herd immunity and decreased circulation of the bacteria. Public health measures leading to improved sanitation as well as decreased population crowding will also lessen conditions leading to transmission of the bacteria. Travellers should be advised to avoid close contact with cattle/other farm animals and the consumption of raw dairy products in order to minimise their risk of C. ulcerans infection. Contacts of cases should be traced, screened for infection by throat culture, and treated as necessary. They should also receive a booster dose of diphtheria vaccination.
Travellers should ensure they are up to date with their routine vaccinations according to the NHS vaccination schedule. The primary UK vaccination course consists of three doses of diphtheria-toxoid containing vaccine at two, three and four months of age. A first booster should be administered at around three years and four months and a second booster between 13 to 18 years of age.
Country specific diphtheria recommendations are not routinely provided on our country pages. As diphtheria tetanus and polio are combined in a single vaccine in the UK a traveller receiving a tetanus or polio booster will also be vaccinated against diphtheria. Should there be an outbreak of diphtheria in a country, diphtheria vaccination guidance will be provided.
There are six combined vaccines containing diphtheria toxoid that are licensed for use in the UK see table below. Click the individual vaccine to see the Summary of Product Characteristics (SPC) for each of these.
|Vaccine||Schedule and age range|
|Pediacel or Infanrix IPV Hib DTaP/IPV/Hib||3 doses given 1 month apart (offered at 2,3,4 months of age- primary course of 3 vaccines)|
|Infanrix-IPV DTaP/IPV or Repevax dTaP/IPV||Pre-school: single dose (offered at 3 years and 4 months or soon after as first booster dose)|
|Revaxis Td/IPV||Single dose booster (offered at 14 years of age as second booster dose. Also used for adults and children from 10 years of age requiring initial course of 3 doses 1 month apart or travellers requiring single dose boosters)|
|Boostrix-IPV dTaP/IPV||Single dose booster (for pregnant women 16 to 32 weeks gestation)*|
* Recommended for pregnant women between 16 to 32 weeks to protect unborn child against whooping cough (pertussis).
It is unnecessary to restart an interrupted series of a vaccine or toxoid or to add extra doses, because the immune system has been primed . Longer than recommended intervals between doses do not reduce antibody concentrations upon completion of the series, although protection may not be attained until the recommended number of doses has been administered . Information about vaccinating individuals with uncertain or incomplete immunisation status is available from Public Health England.
Contraindications to vaccines
There are very few individuals who cannot receive diphtheria-containing vaccines. When there is doubt, appropriate advice should be sought from a consultant paediatrician, immunisation co-ordinator or consultant in communicable disease control, rather than withholding the vaccine.
The vaccine should not be given to individuals with:
- A history of confirmed anaphylactic reaction to a previous dose of a diphtheria-containing vaccine, or a confirmed anaphylactic reaction to any of the components of the vaccine.
- Unstable neurological conditions of unknown cause.
- History of a neurological condition of unknown cause, occurring within seven days following previous vaccination and lasting longer than seven days .
Pain, swelling or redness at the injection site are common and may occur more frequently following subsequent doses. A small, painless nodule may form at the injection site that usually resolves without treatment. Fever, convulsions, high pitched screaming and episodes of pallor (paleness), cyanosis (bluish colour of skin and lips) and limpness occur rarely. Confirmed anaphylaxis occurs extremely rarely .
First Published : 11 Dec 2015
Last Updated :  12 Oct 2016
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