Microbe of the Month: Protecting children from the killer 'b': A new vaccine has greatly reduced deaths caused by 'Hib' infection, says Bernard Dixon

IS THIS 'the beginning of the end?' the editor asks in the current issue of the Journal of the American Medical Association. He is referring to three remarkable papers in the journal which signal defeat for a relatively unknown but extremely dangerous microbe, Haemophilus influenzae type b.

Each paper describes spectacular successes achieved in the United States recently in immunising children against this life-threatening organism.

'Hib' is responsible for several types of infection, but has become particularly feared as an agent of meningitis. This disease has caused death or permanent brain damage in tens of thousands of children throughout the world. Now, as demonstrated by the three latest reports, a vaccine introduced in the US in 1987 has proved a formidable weapon in thwarting this bacterium.

The first paper documents a 71 per cent decline between 1989 and 1991 in disease caused by Hib in children under five, and an 82 per cent drop between 1985 and 1991 in Hib meningitis. A second, independent study shows an 85 per cent decrease in Hib disease in children in Minnesota, and a 92 per cent fall in Dallas, between 1983 and 1991. A third survey, among young children of American soldiers, demonstrates similarly massive reductions, not only in meningitis but also in pneumonia and other conditions caused by Hib.

One could scarcely wish for more striking evidence of the value of the Hib vaccine, which became available for the first time in Britain last October. As the British Medical Journal has commented, we can look forward to a rapid and dramatic reduction in Hib disease here, too.

There are about 1,500 cases of Hib infection each year in the UK, of which more than half are meningitis. Although antibiotics can treat this disease, 65 children die from Hib meningitis each year, and another 150 suffer permanent brain damage.

Why has it taken so long to introduce a vaccine to protect children against this vicious microbe? The principal reason rests on the fact that by far the most virulent strains of H. influenzae are those in which the bacterial cells are surrounded by a thick capsule of polysaccharide.

When a person becomes infected, the polysaccharide stimulates the body to produce antibodies. However, the immunity is both short-lived and much less substantial than that which occurs after many other infections. These drawbacks have long thwarted efforts to develop a vaccine. That problem has now been solved by coupling the polysaccharide to a protein, producing a vaccine that does induce solid and long-lasting immunity.

But why has so little been heard about Hib until comparatively recently? The question is all the more pointed because the great German bacteriologist Richard Pfeiffer first described the organism as long ago as 1892. Finding it in the throats of victims of the influenza pandemic that raged around the world in 1889-90, he believed it was the cause of that disease.

The organism certainly appeared widely in victims of influenza, and was not associated with other conditions. Variously known as Pfeiffer's bacillus, the influenza bacillus or Haemophilus influenzae, its role as the agent of flu was generally accepted.

Then, gradually, doubts crept in, as other investigators failed to find Pfeiffer's bacillus in some flu patients and began to suspect that it was a secondary invader rather than the primary agent of the disease. By the late Twenties most microbiologists had come to believe that H. influenzae was indeed an opportunist, attacking respiratory tissues already invaded by the real culprit. Maybe a virus, a type of microbe much smaller than a bacterium, was the actual cause of influenza?

So it proved - thanks to a fortuitous accident 60 years ago. In 1933, scientists at the Wellcome Laboratories in London were using ferrets for research into canine distemper. One day, in the midst of an epidemic of human influenza, some of the ferrets developed symptoms suggesting that they had caught flu. The Wellcome researchers knew that Christopher Andrewes, Wilson Smith and Patrick Laidlaw, working at the National Institute for Medical Research in north London, were trying to infect various laboratory animals with flu so that they could study the disease more closely and perhaps develop a vaccine or cure.

Ironically, as the news reached Andrewes, he himself was rapidly becoming a victim of the epidemic. 'I began to feel ill. My temperature shot up. I was getting flu,' he later recalled. 'Wilson Smith made me gargle to get some washings and I went home to bed.'

While Andrewes was sweating it out, his colleague inoculated a portion of the washings into some healthy ferrets.

The rest is history. 'The day I came back to work, about 10 days later,' Andrewes wrote, 'Wilson Smith was able to report that the first ferret was looking ill, with a stuffy nose and sneezing.'

Following their piece of luck, Andrewes and his colleagues were soon able to demonstrate that that the microbe was indeed a virus, because it could pass through filters much too fine to permit bacteria through. In turn, this led within a few years to the realisation that there were three different types of influenza virus: A, B and C.

Although our defences against flu still leave something to be desired, these discoveries have been of far-reaching importance in facilitating the introduction of vaccines and laboratory techniques for charting epidemics.

But there was a downside, too. Once the flu virus(es) had been discovered, H. influenzae was relegated to the footnotes of medical textbooks, dismissed as the microbe that did not cause flu. It took the much later, dedicated efforts of virologists such as David Turk, working in Newcastle upon Tyne and Oxford, to convince the world that this microbe, and particularly type b, is indeed a killer. Thanks to the companies that have introduced the Hib vaccines (each using a different carrier protein to induce immunity), it need be a killer no more.