Diphtheria

Diphtheria has been practically absent from Austria for decades – and it is still in the syringe that every pregnant woman receives between weeks 27 and 36. The small “d” in the abbreviation dTpa stands for it. This page explains why an illness nobody sees any more is still vaccinated against, and what happened in the 1990s when a population lost its protection.

What diphtheria is

Diphtheria is caused by the bacterium Corynebacterium diphtheriae. The bacterium itself does comparatively little harm – what makes it dangerous is the poison it produces. This diphtheria toxin blocks protein production inside cells and thereby damages the heart muscle, the nerves and the kidneys.

Remarkably, not every bacterium of this species is able to form the toxin. That ability is conferred on it by a virus which in turn infects the bacterium. Without this virus, colonisation runs a harmless course.

The organism is transmitted by droplets while speaking, coughing and sneezing, less often via contaminated objects. Two to five days lie between infection and illness.

How the illness runs

The commonest form is pharyngeal diphtheria. It begins insidiously with a sore throat, difficulty swallowing and moderate fever – at first no different from an ordinary throat infection.

Then grey to greyish-white membranes form on the tonsils, palate and pharynx, and they adhere firmly. Any attempt to peel them off makes the mucous membrane beneath them bleed. These membranes are the defining feature, and they are also what constitutes the immediate danger: if they spread to the larynx they obstruct the airway. The barking cough and the wheezing breath that result gave the illness its old name – “true croup”.

Also characteristic are a sweetish, putrid smell from the mouth and a massive swelling of the cervical lymph nodes, which gives the neck a bloated appearance.

The second danger arises later and elsewhere. The toxin enters the bloodstream and damages the heart muscle – myocarditis appears in the second week of the illness and is the commonest cause of death in diphtheria. Nerve palsies, beginning at the palate, follow later still and mostly resolve.

Untreated, about five to ten per cent of those who fall ill die, considerably more among small children and older people. Even with optimal treatment, mortality remains around five per cent.

Treatment: why antibiotics are not enough

When diphtheria is suspected, nobody waits for laboratory confirmation. Two things happen at the same time:

Antitoxin – antibodies against the poison, obtained from horse serum – is given to bind the toxin still circulating freely in the blood. What has already been taken up into cells is beyond its reach. That is why timing decides the course, and why it is given without delay.

Antibiotics – penicillin or erythromycin – kill the bacteria and thereby end both the further production of the toxin and infectiousness. Against toxin already formed they achieve nothing.

This division explains why diphtheria has remained a life-threatening illness despite the availability of antibiotics. Antitoxin is scarce as well: it is produced by only a few manufacturers and managed in Europe through national stockpiles.

What happened in the 1990s

Anyone who wants to know why an illness that has vanished is still vaccinated against will find the answer in this section.

In the early 1990s a diphtheria epidemic broke out in the successor states of the Soviet Union. More than 150,000 people fell ill and several thousand died. The illness had been absent there for just as long as it had been in western Europe.

Two circumstances came together. Childhood immunisation programmes had been interrupted in the course of political and economic upheaval. And – this is the point that matters for this page – a large part of the adult population no longer had reliable protection, because boosters had not been given. Two thirds of those who fell ill were adults.

The epidemic ended only when adults, too, were vaccinated on a large scale. It is the reason why the diphtheria vaccination is expressly listed in European immunisation schedules as a lifelong booster – every ten years, and from the age of 60 every five.

Individual cases still occur in Europe, mostly imported. In recent years cutaneous diphtheria has also been observed more frequently, above all among people without settled accommodation and among travellers – a form that runs a less dramatic course but is infectious.

Diphtheria and pregnancy

The vaccination is a component of the dTpa vaccine, which in Austria is recommended to every pregnant woman between weeks 27 and 36. The actual reason for it is the whooping cough component – diphtheria and tetanus are, so to speak, along for the ride, because there is no whooping cough vaccine on its own.

That is not a drawback but a bonus. First, it deals with a booster that is due anyway in many women. Second, the diphtheria antibodies also cross the placenta to the child and contribute to its protection in the first months of life.

It is an inactivated vaccine containing a detoxified toxin. It contains no organisms capable of multiplying and is expressly licensed and recommended in pregnancy. More on the timing and the reasoning behind it is on the page whooping cough.

Even when the last booster was given only recently, the vaccination is still given in pregnancy. The minimum interval of five or ten years recommended in the past does not apply in this situation; studies covering many thousands of pregnancies found no accumulation of side effects at short intervals.

The immunisation schedule in Austria

For children, the diphtheria vaccination is part of the six-in-one vaccination in the first year of life, with doses in the third and fifth month of life and between the twelfth and the fourteenth. A booster follows at primary school age and another in adolescence.

For adults the rule is: every ten years, and from the age of 60 every five. The vaccine used contains a reduced amount of antigen – hence the small “d” in dTpa as against the capital “D” of the childhood vaccines. In people with basic immunity the smaller amount is enough for a booster and is better tolerated.

If a booster has been missed, the series is not begun again but continued – regardless of how many years have passed. Only someone who has never had a basic course needs the full series of three doses.

Tetanus and diphtheria after an injury

After an injury a combination vaccine is usually used, because an isolated tetanus vaccination rarely makes sense. Anyone given a booster in the emergency department because of a cut will as a rule receive diphtheria with it, and often whooping cough as well.

For pregnant women this is worth knowing: such a booster does not replace the intended dTpa vaccination in weeks 27 to 36 if it was given beforehand – but it can replace it if it happens to fall within that window and contains the whooping cough component. Check this against the actual preparation used; the details are on the entry in the vaccination record.

How diphtheria is diagnosed

Diagnosis begins with the clinical picture – grey, firmly adherent membranes in the throat that bleed when removed, together with the characteristic smell and the swollen cervical lymph nodes. That is enough to start treatment.

It is confirmed by a swab, which has to be taken from beneath the membrane – a superficial swab is not enough. In the laboratory the bacterium is cultured and then tested for its ability to form the toxin; without that ability the finding is of no significance. Both steps take time, and that is precisely why nobody waits for them.

Diphtheria is notifiable in Austria, on suspicion alone. The notification leads to an investigation of the surroundings in which contacts are swabbed.

What applies to contacts

Close contacts – members of the household and people with direct contact with secretions – are given a preventive antibiotic regardless of their vaccination status, usually over seven to ten days. In addition they are vaccinated if the last vaccination was more than five years ago.

Suitable antibiotics are available for pregnant women; erythromycin and related preparations can be used in pregnancy. The decision is taken by the public health authority together with the treating services.

Until diphtheria has been excluded or effectively treated, there is a ban on working in communal facilities. Here, too, the rule holds: someone who is vaccinated is as a rule not affected by the more far-reaching measures.

Cutaneous diphtheria

Besides the pharyngeal form there is cutaneous diphtheria. It shows itself as a poorly healing wound with a dirty coating, usually on the legs or arms, often on the basis of a pre-existing skin injury or eczema.

The course is less dramatic – uptake of the toxin through the skin is lower, and damage to the heart muscle or the nerves is rare. It is infectious nonetheless, and in recent years it has been commoner in Europe than the pharyngeal form. Those affected are above all people without settled accommodation, travellers from regions where diphtheria is widespread and people with chronic wounds.

In practical terms this means: a poorly healing wound after a journey deserves to be looked at. And for everyone else what applies anyway still holds – protection that is up to date makes the question moot.

Where the antitoxin comes from

A historical section, which explains why this illness occupies a special place in the history of medicine.

Until the end of the nineteenth century diphtheria was one of the commonest causes of death in childhood; in some years one child in twenty died of it in European cities. In 1890 Emil von Behring and Shibasaburo Kitasato showed that the blood serum of immunised animals can be transferred and cures animals that have fallen ill. A few years later diphtheria antitoxin was used in humans – the first effective treatment of an infectious disease at all.

For this Behring received the first Nobel Prize in Medicine in 1901. The method developed at that time is in principle the same one still used today: antibodies from the serum of immunised horses.

That this principle – giving ready-made antibodies from outside – still occurs in gynaecology today is no coincidence. Anti-D prophylaxis in rhesus-negative pregnant women, the administration of immunoglobulin after contact with measles and the passive immunisation of the newborn of an HBsAg-positive mother all follow the same idea. They work immediately, but only temporarily – the lasting answer has to be produced by the body itself.

Tolerability

The commonest reactions are local: pain, redness and swelling at the injection site for one to two days. General reactions such as fatigue, headache or slight fever occur and subside quickly.

With frequent boosters at short intervals, more pronounced local reactions can occur – one reason why the intended intervals are kept to wherever there are no pressing reasons against it. In pregnancy the benefit outweighs this consideration, see above.

Serious reactions are rare. The vaccination is not given where there has been a documented severe allergic reaction to one of its components; an acute febrile illness leads to postponement, not to abandonment.

A note on how to read local reactions: an upper arm that is red, swollen and painful for one to two days is not an allergy and not a sign that something has gone wrong. It shows that the immune system has noticed the vaccine – which is exactly the purpose of the adjuvant it contains. Cooling the arm and moving it help more than resting it.

What the vaccination does – and what it does not

A point that is rarely spelled out and that explains how it works: the diphtheria vaccination is not directed against the bacterium but against its toxin. What is given is a detoxified toxin which has lost its damaging effect but kept its recognisability for the immune system.

From this follows a limitation worth knowing about. A vaccinated person can be colonised with the bacterium and pass it on without falling ill themselves – they are protected against the consequences of the toxin, not against the presence of the organism. This is why vaccination does not make diphtheria disappear entirely from a population, but takes away its dangerousness.

And from it follows, conversely, the reason why having had the illness leaves no reliable protection: the amount of toxin produced in the body during it is often not enough for a lasting immune response. Anyone who has survived diphtheria is therefore vaccinated afterwards – one of the few illnesses where that applies.

The practical consequence for pregnant women: the protection of the child in the first weeks of life rests on the antibodies against the toxin passed on by the mother. How many of them cross depends on how high her level is in the third trimester – and that is precisely why the vaccination is given afresh in every pregnancy, regardless of when the last booster was.

Travel

Before travelling to regions where diphtheria continues to circulate – parts of southern and south-east Asia, Africa, South America and individual eastern European states – protection should be checked. If the last booster was more than ten years ago, it is renewed.

In pregnancy, long-distance travel calls for advice of its own that goes beyond vaccinations: the timing of the journey, medical care at the destination, the risk of thrombosis on long flights, malaria prophylaxis. Anyone planning such a journey is best advised to discuss it early.

The second trimester is regarded as the most favourable time to travel – the nausea is over, the burden of late pregnancy is not yet there, and the risk of miscarriage is lower than before. Airlines set their own limits for carriage, usually from week 36 and earlier with multiples; a medical certificate is often required from week 28. Ask the airline before you book – these rules differ considerably.

What happens next

In this practice the dTpa vaccination is discussed and given as part of antenatal care. Please bring your vaccination record. Arranging an appointment. Which vaccinations have to be completed before a pregnancy is set out under rubella; what the six-in-one vaccination for the child contains is on the page Hexyon.