The terror is infectious

Fear of new and deadly diseases has spawned a wave of lurid fiction. The reality may be even more frightening. Steve Connor reports

Vic Rail was a worried man. A dozen of the prize racehorses trained by him in Brisbane had already succumbed to a mysterious illness when he himself began to feel under the weather. By late September 1994, Vic's lungs had become a "hot zone" of actively replicating virus. His temperature had soared to over 40C with a fever that had knocked him for six. Already the infectious agent had made the cells lining his lungs clump together, causing watery liquid to leak into the tiny air sacs where oxygen enters the blood. Vic was drowning in his own body fluids.

After nearly a week in intensive care, Vic died of pneumonia at the age of 49. By this time, some of Australia's leading virus-hunters were already on the trail of the mystery infectious agent. They had isolated something from the dead horses and a post-mortem revealed the telltale signs of virus lurking in Vic's kidneys - his lungs were too ravaged for analysis.

Under a high-powered electron microscope - the sort that can make the inside of a human cell look like the Albert Hall - the virus bore the characteristic shape of a group familar to expert virologists. Further tests to determine its genetic structure confirmed that it was a morbillivirus, a type that includes the infectious agents responsible for canine distemper, cattle rinderpest and human measles.

The scientists studying the mystery outbreak at Vic's stables were now in little doubt of the gravity of their find. No living scientist had reported a new human morbillivirus. In fact, what took place in Vic's lungs had not happened since the 10th century, when measles was reported for the first time to have entered the human population.

An outbreak of a totally new infectious agent, an Andromeda Strain, is the stuff of nightmares and Michael Crichton novels. Australian health authorites took no risks. They imposed a "category III" alert, the highest there is to deal with an outbreak of an exotic infectious disease. Government vets could only enter Vic's stables - now a designated "hot zone", the term used by the US military to identify any area occupied by deadly infectious organisms - wearing bright orange "spacesuits" and breathing helmets that could protect them from the agent.

Finding the virus soon enabled the scientists to develop a blood test to survey 1,600 horses and 90 humans in the immediate vicinity, to see how far the outbreak had travelled. To their immense relief, the virus seemed to have burnt itself out in Vic's stables, after killing 14 of his 21 infected horses and nearly killing the only other human to become infected, a 40-year-old stablehand, who recovered completely after a severe flu-like illness.

For the time being, the world's second human morbillivirus had disappeared, retreating to its natural "reservoir", probably a wild animal, where it can hide undetected until the next time it jumps the species barrier into humans or horses. As Frederick Murphy of the University of California, an international authority on the emergence of new viruses, says: "We have no idea where it came from, or where it's going to ... but the odds are it will reappear."

The story of Vic Rail's virus is not unique. Over the past 20 years, there have been a number of instances where an apparently new infectious agent has arisen as if from nowhere. Aids and HIV, which were unknown before the early Eighties, are the most dramatic example of the terror that infectious agents can still provoke at the end of the same century that brought us mass vaccinations, antibiotics and a revolution in health care.

Control of infectious disease has been one of the greatest achievements of modern science and with it came the inevitable complacency towards nature's biggest killers. Thanks to vaccines, many viral infections have been all but conquered. Smallpox is now eliminated from the wild and polio is largely eradicated, particularly in the developed world. Bacterial infections such as syphillis, tuberculosis and cholera, which caused massive suffering and carnage in previous centuries, were also thought to be largely a scourge of the past.

Now, with the emergence of new viral diseases and drug-resistant microbes, the illusion of safety has been shattered. John La Montagne, a scientist at the US National Institute of Allergy and Infectious Diseases, says the events of the past 15 years have clearly demonstrated that human diseases are not static ``but dynamic problems that will continue to pose public health threats and constantly challenge the scientific community''.

Laurie Garrett, the American science writer whose scholarly book The Coming Plague will be published in the UK later this year, describes how even she, a medical scientist by training, was taken in by the post-war "era of confident, curative medicine and minimal concern for infectious diseases". The list of new viruses that has changed her mind is long: the Aids virus, HIV; the T-cell leukaemia viruses, which cause blood cancers; several types of hepatitis viruses, and the deadly haemorrhagic viruses, such as Ebola and Marburg, that have jumped from monkeys to humans on several recent occasions with frightening results.

It is the Ebola virus that has stirred some of the greatest passions regarding infectious disease. Richard Preston's book The Hot Zone and the film Outbreak centre on the story of how in 1989 a new strain of Ebola emerged in a colony of monkeys kept at the US army's Reston Primate Quarantine Unit in Virginia, a few miles from Washington. The outbreak eventually fizzled out, but not until the US authorities had done their damnedest to cover things up.

Preston's graphic descriptions of people who succumb to the agony of haemorrhage-induced death at the hands of Ebola, and its close relative Marburg, leave little to the imagination. "The only sound is a choking in his throat as he continues to vomit while unconscious. Then comes a sound like a bedsheet being torn in half, which is the sound of his bowels opening at the sphincter and venting blood. The blood is mixed with intestinal lining. He has sloughed off his gut. The lining of his intestines have come off and are being expelled along with huge amounts of blood."

Despite the horrors of dying from Ebola virus, or even morbillivirus, the reality is that such viruses as they are do not pose the threat to human survival that some authors and Hollywood directors would lead us to suppose. What makes a virus a real problem is its mode of transmission. Neither Ebola nor morbillivirus has proven to be as infectious as, say, influenza and it must be remembered that Vic Rail's solitary death and the several hundred that died of the first known outbreak of Ebola in Zaire and Sudan in the Seventies pale beside the estimated 20 million people who died of Spanish 'flu in the winter of 1918-1919. Last November, a Swiss scientist in the Ivory Coast became infected with Ebola while dissecting a chimpanzee, probably the first human case since the Seventies; she survived and is said by the Institut Pasteur in Paris to be recovering well.

What makes HIV such a disturbing infectious agent is that it can be passed unwittingly during the most intimate acts between people who can appear perfectly healthy for several years. The virus itself is not particularly infectious, but its delayed action combined with its transmission during the most compulsive human activity can cause the complacency and denial that makes it such a great threat.

The problem with HIV and any other new virus is that the world at the end of the 20th century is a much more inviting place for infectious agents than it was 50, even 25 years ago. Infections thrive on a large number of humans living in close proximity. In 1900, a mere 15 per cent of the world's population lived in cities. By 2010, it is expected that more than half of humanity will live in huge urban centres, notably the megacities of the developing world. In 1980, there were 10 cities with a population exceeding 10 million. By the year 2000 there will be 24, of which the majority will be in the poorest countries that can ill afford the sanitation and civic infrastructure that can stem the spread of disease.

There will be more pressure to develop pristine environments for human habitation, such as the rainforests, from which new viruses are most likely to emerge in their natural reservoirs of host animals, so increasing the risk of the agents jumping the species barrier into humans. The global village, the rise of sex tourism and the continued use of unsterilised needles in the poorest nations will undoubtedly offer more opportunities for a new virus to spread.

As Jonathan Mann, a Harvard professor who once ran the World Health Organisation's global Aids programme, says in his preface to Laurie Garrett's book: "A person harbouring a life-threatening microbe can easily board a jet plane and be on another continent when the symptoms of illness strike. The jet plane itself, and its cargo, can carry insects bringing infectious agents into new ecologic settings. Few habitats on the globe remain truly isolated or untouched, as tourists and other travellers penetrate into the most remote and previously inaccessible areas in their search for new vistas, business or recreation."

Mann, like many other scientists studying infectious disease, has called for a global early warning system capable of detecting and responding to new viruses wherever they may emerge. Those of us who sleep peacefully unaware of the danger from new diseases and the re-emergence of past plagues need to be awakened to the risks, he says. "There is no clearer warning than Aids."

What is a virus?

A virus is the simplest lifeform possible, consisting almost entirely of the chemical blueprint for its own replication. Viruses have no life- support systems of their own. They live as parasites within the cells of higher organisms, including humans.

Imagine that the human body is the size and complexity of America. A ship such as the QE2 coming into dock at New York can be likened in size and comparative complexity to a bacterium or human cell.

On board that ship are simple circular lifebelts, bearing the message ``replicate me''. These are the viruses that enter human cells and subvert the cellular machinery to make more copies of the lifeform until the cell bursts under the pressure of its viral brood.

Viruses evolve over thousands of years in close association with their host animal - which acts as a natural reservoir - but can on occasion jump the ``species barrier'' to another host. When this happens, the virus can become more lethal in the new body which it invades.

The most dangerous viruses, which are given level 4 status by scientists, are those that combine lethality with a certain degree of infectiousness. Flu and measles are highly infectious but not particularly lethal and so are not level 4 viruses. The haemorrhagic viruses, such as Ebola, Marburg and Lassa fever, can only be handled by level 4 containment laboratories because, although not highly infectious, they are extremely deadly.

In addition to the sudden appearance of new viruses within the human population, such as HIV, scientists are worried that old viruses may mutate enough for them to pose more insidious risks, perhaps by becoming more infectious or lethal. One concern is that Ebola virus, or something equally deadly, may mutate enough for its route of transmission to change, rendering it as infectious as flu.