Haemophilus influenzae type b

Until the 1990s Haemophilus influenzae type b was the commonest cause of bacterial meningitis in small children. Today even paediatricians with long experience hardly ever see a case. This change is one of the clearest successes a single vaccination has ever achieved – and it explains why the “Hib” is in the six-in-one vaccination.

What the organism is

Haemophilus influenzae is a bacterium that colonises the nose and throat of many healthy people without causing symptoms. Its name is a historical error: during the influenza pandemic of 1892 it was taken to be the cause of the flu. It has nothing to do with influenza, which is caused by viruses.

One distinction is decisive. Most strains have no capsule and do little harm – they cause infections of the middle ear and the sinuses. Type b, by contrast, carries a sugar capsule that protects it from the immune defences. This allows it to enter the bloodstream and from there to cause serious illness.

It is transmitted by droplets. Colonisation was common, illness never was – but when it occurred, it was severe.

What Hib used to cause

Before vaccination, Hib was responsible in Europe for the greater part of bacterial meningitis in children under five. About one affected child in twenty died, and in up to thirty per cent of survivors damage remained – most commonly hearing loss, together with seizure disorders and developmental delay.

The second commonest form was epiglottitis, an inflammation of the epiglottis. It develops within a few hours: the child has a high fever, can no longer swallow, sits leaning forward with the mouth open and lets saliva run out of the mouth, because swallowing hurts too much. The swollen epiglottis can block the airway completely. It is one of the few situations in paediatric medicine where minutes count.

Besides this, Hib caused blood poisoning, pneumonia, inflammation of joints and bones and deep soft-tissue infections of the face.

Those affected were almost exclusively children under five, with the peak between the sixth and the eighteenth month of life. After that the risk falls steeply, because the immune system matures and most people in time form antibodies against the capsule themselves – through repeated, unnoticed colonisations of the throat, which act like a natural series of vaccinations.

Why age is so decisive here

Here lies the key to understanding this vaccination, and it explains at the same time why protection carried over from the mother helps less here than with other illnesses.

The capsule of the bacterium consists of sugar. The immune system of an infant can form practically no antibodies against pure sugar structures – that ability develops only in the second year of life. A small child is therefore particularly at the mercy of this organism, and a conventional vaccine made of capsular sugar would not have worked in it.

That is exactly where the first Hib vaccines of the 1980s failed. They protected children from eighteen months onwards – that is, from the age at which the illness was becoming rare anyway.

The solution was the conjugate vaccine: the capsular sugar is chemically coupled to a protein. This brings it into a different recognition pathway of the immune system – one that works in infants too and leaves a memory behind. The principle was later transferred to pneumococci and meningococci and is among the most consequential developments in vaccine research.

The success in figures

After the introduction of conjugate vaccination in the early 1990s, the frequency of invasive Hib disease in Europe fell by more than 95 per cent. In Austria today there are individual cases per year, mostly in unvaccinated or incompletely vaccinated children.

A second effect is remarkable. Vaccinated children carry the organism in the throat less often and pass it on less often. As a result the frequency of illness falls among the unvaccinated as well – with Hib there is thus, unlike with tetanus, a genuine herd effect.

For parents today this success has an unwelcome side effect: nobody knows the illness any more. A decision about vaccination is thus taken between a visible small drawback and an invisible large benefit – and psychologically that is an unfavourable starting position. Anyone who still talks to doctors who worked in children's hospitals before 1990 will get very clear answers on this, however: epiglottitis was among the situations that generation remembers without being asked.

The gap before the first vaccination

The gynaecological part of this subject is an honest account of a limit.

With whooping cough, the time until the child's first vaccination can be bridged by vaccinating the mother in pregnancy: her antibodies cross the placenta. With Hib that hardly works.

The reason is the same as above. Antibodies against capsular sugar are usually low in adults who have not been vaccinated, and what is transferred does not go far. A Hib vaccine for pregnant women does not exist and would not be the obvious route either.

What does protect is something else: the peak of the illness lies between the sixth and the eighteenth month of life – that is, after the point at which the basic course takes effect. The most vulnerable period is thus covered, provided the appointments in the third and fifth month of life are kept.

From this follows a practical recommendation that is regularly made in this practice: the vaccination appointments of the first year of life should not be postponed where that can be avoided. Every postponement lengthens the time during which a child grows unprotected into the age at which the illness becomes dangerous.

The immunisation schedule

In Austria the Hib component is part of the six-in-one vaccination. It is given in the third and fifth month of life and between the twelfth and the fourteenth – the same three appointments as for the other five components.

Here too the third dose is the decisive one for the duration of protection. After it, immunisation is complete; no further boosters are provided for, because the illness practically no longer occurs beyond early childhood.

If the series is started later, the number of doses needed falls with increasing age – a child over twelve months needs only one. From the fifth birthday, healthy children are as a rule no longer vaccinated at all. That is unusual and follows a simple consideration: where there is no longer any danger, no vaccination is needed either.

Exceptions apply to people without a spleen or with certain immune deficiencies: they remain at risk lifelong and are vaccinated in adulthood as well. More on this in the section after next.

Conjugate vaccines: why this development changed so much

The Hib vaccine was the first conjugate vaccine of all, and the principle behind it is worth explaining – it now underlies several vaccinations given in the first year of life.

The immune system processes sugars and proteins by different routes. To pure sugar structures it responds immediately, but without memory: it forms antibodies which disappear after a while, and at the next contact everything starts again from the beginning. In infants this route hardly works at all – it matures only in the second year of life.

To proteins it responds differently. Here helper cells are brought in, the response is stronger, it leaves a memory behind, and it works from birth. This is exactly what the classic vaccines against tetanus and diphtheria rest on, which contain detoxified proteins.

The idea of the conjugate vaccine consists in binding the sugar chemically to a protein and thereby smuggling it, so to speak, into the better route. The immune system processes the protein, learns the sugar along with it and forms a memory for it.

After Hib this principle was transferred to pneumococci and meningococci – both organisms with sugar capsules, both causes of severe illness in infancy. Without this development the corresponding vaccinations in the first year of life would not be possible.

A side effect that explains the herd effect: conjugate vaccines prevent not only the illness but also colonisation of the throat. In this way they interrupt transmission – which pure sugar vaccines do not do.

When the spleen is missing

The spleen filters encapsulated bacteria out of the blood. Anyone without a spleen – after removal because of an injury, because of a blood disorder, or because it has lost its function through sickle cell disease – is at risk from precisely the three organisms against which conjugate vaccines exist: pneumococci, meningococci and Hib.

Separate recommendations therefore apply to these people, lifelong and regardless of age: vaccination against all three, annual influenza vaccination, and immediate medical assessment in the event of fever, because blood poisoning can develop there within hours. Many of those affected carry an emergency antibiotic with them.

For gynaecology this is relevant at two points. First, these vaccinations should be checked before a planned pregnancy and boosted where necessary – they are inactivated vaccines which would also be possible in pregnancy, but are more straightforward beforehand. Second, such a circumstance belongs in the parent-child pass and should be known to the maternity unit: fever after the birth is assessed differently where the spleen is missing.

What is worth asking at a vaccination appointment

Parents are given information before every vaccination, and the consent sheets are complete. Complete, however, does not mean comprehensible. In practice four questions yield most:

• What exactly is being vaccinated against today? With a combination vaccine this is not self-evident – six illnesses in one injection are often listed on the sheet under a single brand name.
• When is the next appointment, and what happens if we postpone it? With some vaccinations a postponement has no consequences; with rotavirus it ends the opportunity completely.
• What is normal over the next few days, and what is not? Knowing this boundary saves a restless night – and makes sure that the rare genuine reaction is not dismissed as normal.
• Is everything in the vaccination record? With date, preparation and batch number. A photograph of it after every appointment later replaces any amount of searching.

What is left of Hib today

Invasive disease due to type b has disappeared. Two things have remained.

The strains without capsules. They are not covered by the vaccine and continue to cause infections of the middle ear and sinuses as well as bronchitis. That is not a failure of the vaccination but its intention: it is directed against the capsule of type b and against nothing else.

Adults. Invasive disease due to Haemophilus influenzae now occurs more often in older people and in people with weakened defences than in children – predominantly through strains without capsules. That too is a shift brought about by the vaccination, without being an argument against it.

What is done when a case occurs

Invasive Hib disease is notifiable in Austria. For close contacts – members of the household and childcare groups with unvaccinated small children – a preventive antibiotic is provided for, usually rifampicin.

For pregnant women rifampicin is not the agent of choice; another preparation is used instead. The decision is taken by the public health authority together with the treating services.

The illness itself is treated with intravenous antibiotics, and with epiglottitis while the airway is secured. Both belong in hospital, and neither tolerates any delay.

What parents should keep in mind

Even though Hib has become rare, the warning signs remain the same – they apply to any severe bacterial infection in early childhood:

• high fever with striking listlessness or restlessness
• neck stiffness, shrill crying, a bulging fontanelle
• refusal to feed in infants
• sudden difficulty swallowing with drooling and a forward-leaning posture
• pinpoint bleeding into the skin that does not blanch under pressure
• rapid deterioration within hours

With these signs the rule is: hospital, do not wait. More on this on the page meningitis.

One point that helps parents in the first months and goes beyond Hib: in an infant, behaviour counts for more than the height of the fever. A child with a temperature of 39 degrees that feeds, makes eye contact and can be settled is in a different situation from one with 38 degrees that seems listless and no longer feeds. In infants under three months, however, any temperature above 38 degrees is a reason for medical assessment – regardless of how the child otherwise seems.

How Hib disease used to be diagnosed

Because the illness has become rare, it is now easily overlooked – a circumstance that arises with every illness that has disappeared and the reason why the duty to notify remains in place.

The diagnosis is confirmed by detecting the bacterium in a normally sterile material: in the blood, in the cerebrospinal fluid or in joint fluid. Detection in a throat swab, by contrast, says nothing, because colonisation without illness is common there. It is then determined whether it is the encapsulated type b – only then is it Hib disease in the narrower sense.

One detail concerning epiglottitis that is passed on in paediatric medicine: where it is suspected, a child's throat is not examined with a spatula and the child is not made to lie down. Both can block the swollen epiglottis completely. The child stays sitting as it wants to sit, and is taken to hospital that way.

Tolerability

The Hib component is well tolerated. Because in Austria it is given exclusively as part of combination vaccines, the pattern of reactions corresponds to that of the six-in-one vaccination: redness and swelling on the thigh, occasionally fever and restlessness for one to two days.

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 – with this vaccination, however, with the reservation stated above that a postponement costs time, which counts particularly here.

What happens next

The child's vaccinations are given by the paediatrician. What belongs to this practice is the preparation: the dTpa vaccination in pregnancy, clarifying your own vaccination status and the question of which appointments are due in the first year of life – so that they do not get lost between the postnatal period and everyday life. Arranging an appointment.