Immunity

Second infections with diphtheria are reported but they are rare. Immunisation protects against systemic disease but does not give protection against the carriage of organisms. The cutaneous disease does protect against the more serious pharyngeal version of the illness.

Treatment

Patients with the pharyngeal form should be isolated to prevent further spread of the disease. Infection can also be transmitted from skin lesions.

Aetiology

This disease is caused by a bacterial disease known as Corynebacterium diphtheriae which is a non-motile, non-spore bearing gram positive organism. It is club-shaped and produces an exotoxin.

Geographical Distribution

The disease is found throughout the world but is more common in regions where immunisation programmes have been limited or withdrawn due to economic reasons or from civil strife. More recently we have witnessed the major epidemic of diphtheria which has affected Russia and some of the newer CIS states. In these regions there have been many thousands of cases and hundreds of deaths. During 1980 in the European region there were 623 cases. This rose to 3170 cases in 1990 and 19,046 cases during 1993. 80% of these cases had been exposed in the Russian Republic and 16% from the Ukraine. In the Ukraine 111 fatal cases occurred in 1994 with 80% of these from Kiev, Odessa and Lvov. No cases have been reported in Ireland from 1974 until 2000.

In some of the warmer tropical regions the overall incidence has significantly increased and this may be partially due to improving standards of personal hygiene which has resulted in a lessening in the incidence of cutaneous diphtheria.

Transmission

Man is the only known host and transmission is most commonly by droplet or dust contamination. The bacteria can withstand drying and also be transmitted through fomites from carriers and cases. It is estimated that asymptomatic carrier rates between 3% to 7% can occur during epidemics. A throat carrier rate in asymptomatic health children was found in 7% of Ugandan children in 1970. The organism has also caused human infection from contaminated unpasturised milk.

Clinical Features

Most infections are asymptomatic. The disease can gain access to the body through the throat (pharyngeal diphtheria) or through skin lesions (cutaneous diphtheria). Spontaneous healing can occur but other patients will go on to develop invasive disease with heart block and paralysis (both cranial and peripheral). The incubation period is typically between 1 to 7 days.

• * Pharyngeal diphtheria
  The symptoms show locally and also distally from the effects of the exotoxin. Patients may complain of a sore throat which becomes inflamed. A membrane forms to cover the tonsils, pharynx and the palate. It tends to be adherent and gives the appearance of a greyish green sheet across the back of the patients throat. If this membrane is removed a distinct haemorrhagic area is exposed. Lymph glands become swollen and the patient becomes obviously toxic. Nausea and vomiting are frequently seen at this stage and the patient may also complain of a painful dysphagia. The infection may spread down into the laryngeal region and cause cough, stridor and respiratory obstruction. (It should be noted that the laryngeal element of the disease can present by itself without the more obvious pharyngeal disease leading to great difficulty in the diagnosis).
  Patients may die at this early stage of the disease from respiratory obstruction. Others may develop some of the later symptoms related to the effects of the diphtheria exotoxin. In these patients cardiac arrhythmias and conduction defects are common. Complete heart block can lead to sudden death. Myocarditis may be seen with a rapid weak pulse, dyspnoea and a raised jugular venous pressure. Neurological may be seen some weeks after the onset of the illness with palatal paralysis being common. Other cranial nerves may also be affected (3rd, 6th, 7th, 9th, 10th) and a peripheral neuropathy (mainly motor) may appear many months after infection. In general this neuropathy will respond well to adequate treatment.
• * Cutaneous diphtheria
  This is also known as Veld Sore. Infection may be from an infected patients throat or skin and occurs through a scratch or abrasion on the recipients skin. The resultant sore is usually single but may be multiple and is very painful. There is usually a vesicle filled with a straw coloured fluid. On bursting this leaves a deep ulcer with punched out edges and covered with a membrane which comes off easily. The lesions are most often seen on hands, arms and legs. Infection of the nasopharynx is found in 20% of patients with cutaneous diphtheria. Patients may develop neurological symptoms with blurring of the eyes being a common early symptom. Numbness and coldness of the extremities is also noted. Wrist and / or ankle drop may be seen with evidence of ataxia. General pareses may be seen in the second week. Death from cardiac involvement may occur as in patients with pharyngeal diphtheria.

Diagnosis

Initially the diagnosis of both pharyngeal and cutaneous diphtheria is based on clinical suspicion. Confirmation may be obtained by isolation of the organism perhaps following culture on Loeffler’s medium. The patient may also show signs o The symptoms of the disease are due to the local multiplication of the organism (throat or skin) and also the effects of the exotoxin. An equine antitoxin is available but should only be used in confirmed (or strongly suspected severe) cases because immediate serious hypersensitivity reactions occur in 5% – 7% of cases.

Both Erythromycin and Penicillin are usually effective in eradicating the disease but they do not affect the acute phase of the disease due to the exotoxin. Treatment should be continued for 10 days. Patients shown to have a carrier state should also be treated. Resistance to erythromycin is reported.

Immunisation

Some years ago the Schick test was used to determine the susceptibility of individuals to infection with diphtheria. A small (0.1ml) injection of the diphtheria toxin was injected intradermally and assessed 48 hours later. A positive reaction related to the individual not having protection (the opposite to the situation with the mantoux/heaf tests for tuberculosis). Unfortunately the Schick test has been unavailable in Ireland for many years though it is likely that the recent epidemics in Russia will encourage some of the manufacturers to reconsider it revival.

The vaccine is a killed toxoid and is one of the recommended vaccines for childhood. In many countries it is combined with pertussis and tetanus and given on three occasions during the first six months of life. This gives very adequate protection against diphtheria in most cases and a booster dose is then given (against all three diseases) at about 5 years of age. The recent UK recommendations now include a further booster for all children at 15 years of age against both diphtheria and tetanus. This vaccine is now available in Ireland (Diftavax – Aventis Pasteur MSD) and it contains the lower dosage of the diphtheria vaccine which is recommended for adult usage. It needs to be remembered that the higher dosage childhood vaccine may produce very toxic symptoms (even death) in an adult.

Who should be offered vaccination?

As mentioned above it is important that all children are adequately covered against diphtheria during their childhood years. One of the biggest concerns over the past years has related to the numbers of Irish travellers to Eastern Europe who are not adequately vaccinated. This would be particularly true for the business population who travel on a regular basis to regions like Moscow, Leningrad and the Ukraine. For these individuals it is essential that they are offered protection through vaccination with the low dose adult vaccine. For those under 45 years of age they will probably just require a single injection to boost they immunity as they will have had previous childhood vaccination against the disease. Those over this age who may never previously have had vaccination against diphtheria should be offered the low dose injection given of three occasions over the standard six month period. [A quicker 2 month schedule may be used if the risk is thought to be significant]

All expatriates moving to live in developing countries should be offered vaccination cover.

General Protection

If travellers find themselves in the midst of a diphtheria epidemic they should stay clear of public transport, cinemas, local market places and other regions where close contact with the local population is unavoidable. This is especially true during the colder times of the year.