The facts about...

Diphtheria

What is diphtheria?

Diphtheria is an acute infectious disease caused by the bacteria Corynebacterium diphtheriae and Corynebacterium ulcerans. This disease usually affects the throat, as well as occasionally the skin. The latter is mainly seen in persons who already have a skin disease.
Some strains of Corynebacterium diphtheriae produce a toxin, which can damage the heart muscles and nervous tissues, although non-toxigenic strains can cause a localised infection. A diphtheria-like illness is sometimes caused by toxin-producing Corynebacterium ulcerans, the latter is usually carried by livestock although pet animals have also been show to carry this organism.
Hippocrates provided the first clinical description of diphtheria in the 4th Century B.C. There are also references to the disease in ancient Syria and Egypt. In the 17th century, murderous epidemics of diphtheria swept Europe. From 1735-1740, a diphtheria epidemic in the New England colonies was said to have killed as much as 80% of the children under 10 years of age in some towns. Diphtheria was otherwise called the 'Strangling Angel of Children' as it caused death of many children by suffocation and was a dreaded common childhood illness. Diphtheria was also prevalent in the British Royal family during the late 19th Century. One famous case includes Queen Victoria's second daughter, Princess Alice of Hesse and her family. Princess Alice died of diphtheria after she contracted it from her children in December of 1878 while nursing them. One of Princess Alice's own daughters, Princess May, also died of diphtheria in November of 1878.
Immunisation against diphtheria was introduced on a national scale throughout the United Kingdom in the early 1940s and resulted in a dramatic drop in the number of cases and deaths from the disease. For example, in 1940 46,281 cases and 2,480 deaths were notified, compared with 37 cases and six deaths in 1957. Diphtheria is now rare in the United Kingdom, nearly all new cases are acquired abroad, and there are a few UK-acquired cases every year due to toxin producing strains of Corynebacterium ulcerans. There has been a rise in the identification of infections due to non-toxic Corynebacterium diphtheriae in the recent years; these cases have presented with a mild sore throat.

How does diphtheria spread?

Humans are the only known source of Corynebacterium diphtheriae and the disease is usually spread by close (face-to-face) contact via air-borne droplets or direct contact with secretions from the nose and throat of a recent case or someone who, without any symptoms, is carrying the bacterium in their nose or throat or skin ulcers. Transmission may rarely be with contaminated articles. Untreated patients are infectious for up to 4 weeks but cases receiving antibiotic treatment are no longer infectious after 3 days. Diphtheria is not highly infectious, although exposed skin lesions are more infectious than respiratory cases.

What symptoms does diphtheria cause?

After an incubation period of usually between two and five days the onset of the disease is gradual and the new case may become generally unwell with a mild fever, headache, rapid pulse and sore throat, as well as problems with swallowing. The toxin produced by the bacterium causes swelling of the soft tissues of the neck together with swollen glands due to the enlarged lymph nodes may cause the typical ‘bull neck’ appearance. Swelling of the throat may also occur leading to breathing difficulties. This swelling is due to inflammation of the lining of the throat also resulting in an exudate or 'membrane' which is typically pale grey or white in colour, thick and firmly stuck to the throat and therefore hard to remove. There may often be high pitched sound on breathing and hoarseness. Sometimes the infection is confined to the nose causing a foul smelling, bloodstained discharge. Progression of the illness then depends on whether or not the infecting strain of C. diphtheriae produces toxin and the amount of immunity already possessed by the patient from previous diphtheria immunisation. Milder cases caused by toxigenic isolates will usually have an uneventful recovery after about a week.

More serious infections are characterised by increasingly severe heart and nervous system complications, which develop after two to six weeks and can lead to collapse, paralysis, coma and death. About 5 to 10% of diphtheria cases die.
Chronic skin lesions due to diphtheria are unusual in developed countries except among alcoholic homeless individuals and in impoverished groups where this manifestation is on the rise. However, skin diphtheria is the commonest manifestation of diphtheria in the tropics. The lesions may be due to either toxigenic or non-toxigenic strains of C. diphtheriae. Typical findings for infections caused by toxigenic isolates are vesicles or pustules that quickly rupture to form a "punched-out" ulcer up to several centimetres in diameter. Spread of this infection is by direct contact with the infected lesions. The diagnosis and treatment of cases and the management of contacts is similar to toxigenic diphtheria of the respiratory tract.

How is diphtheria diagnosed?

Swabs are taken from the nose and throat of the patient suspected of having diphtheria, ideally before antibiotic treatment is started. Any wounds or skin lesions are also swabbed. These swabs are sent to a microbiology laboratory where the bacterium can be grown on special culture media. If Corynebacterium diphtheriae or Corynebacterium ulcerans is isolated then the bacterium will be tested to see whether or not it produces the toxin.

How are diphtheria cases treated?

Patients with diphtheria require urgent admission to a hospital where they will be nursed in isolation. If diphtheria is confirmed then they will remain isolated until their treatment has been completed and two negative cultures 24 hours apart have been obtained from nose and throat swabs. Treatment consists of an injection of antitoxin to counteract the effects of the toxin produced by Corynebacterium diphtheriae and Corynebacterium ulcerans and antibiotics by injection and then by mouth for a total of as many as fourteen days, to kill the bacteria. The effect of diphtheria toxin is irreversible, so early diagnosis and treatment with antitoxin is vital. The antitoxin and the antibiotics are therefore usually commenced before there is bacteriological confirmation of the infection. If necessary, action is taken to assist the patient's breathing and bed-rest, together with general nursing and medical care, are given as required. Patients should be immunised as soon as they recover usually before discharge from hospital because clinical infection does not always induce adequate level of immunity.

How are further cases prevented in those who are in close contact with a case of diphtheria?

Once diphtheria due to a toxigenic strain is either strongly suspected or confirmed, then a number of complex public health measures are urgently undertaken. These measures are coordinated by professionals from the local Health Protection Unit and microbiology department in consultation with the national HPA Centre for Infections Respiratory and Systemic Infection Laboratory and Immunisation Department.
In addition to the isolation of the case at a suitable hospital ward, contacts are traced and evaluated for risk of acquisition of the infection. In case of diphtheria a significant contact is defined as a person who has had close contact with the case in the previous seven days, such as other household members, regular visitors to the patient's house, kissing or sexual contacts of the case. Contacts in either a school classroom, workplace or hospital are at much lower risk.
The follow-up of significant contacts includes taking nose and throat swabs to see whether they have become carriers of the organism and daily assessment for signs and symptoms of diphtheria for seven days. In addition, all close contacts should be given a suitable antibiotic and booster dose of diphtheria vaccine where the last dose was given more than 12 months previously.

What are the recommendations for immunisation against diphtheria?

Diphtheria immunisation has been available in the United Kingdom for over 50 years. It is recommended for all infants from two months old. The primary course of immunisation consists of three doses starting at two months with an interval of one month between each dose and is given as part of a combined vaccine of diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b (Hib). A booster dose of vaccine (containing diphtheria, tetanus, pertussis and polio) is also recommended for children before school entry and final booster (containing diphtheria, tetanus and polio) before leaving school, between thirteen and eighteen years of age.

Diphtheria ‘hot spots’

Mass immunisation against diphtheria in Europe almost transformed the disease to one of the first infectious diseases to be 'conquered'. However, factors such as inadequate healthcare delivery systems, poverty and other social factors have led to diphtheria being an endemic/epidemic in many regions of the world e.g. the former USSR, the Indian subcontinent, South East Asia and South America. Diphtheria therefore, continues to be a serious health problem within these countries and presents potential health risks to other countries. An epidemic of diphtheria in the Russian Federation and the Ukraine began in 1990 and has now spread to the neighbouring newly independent states. During 1994, 47,853 cases were reported from these countries, representing 87% of diphtheria cases within the World Health Organisation European region. The outbreak peaked in 1995 when there were approximately 52,000 cases and 1,700 deaths recorded. This was so great an increase that diphtheria was cited in the Guinness Book of World Records as "the most resurgent disease".
In Europe, there were less than 1,000 cases by 2002, most in Russia, although a small number of cases still occur every year in the Baltic States. On a global scale, there were 8,229 cases reported to the WHO in 2005 and 3,978 in 2006 and an estimated 5,000 deaths in 2002. The disease is still endemic in many parts of the world in particular South East Asia, South America, Africa and in specific countries within the European Region.