WHAT THE RAT BROUGHT IN

There is no cure for a range of bleeding viruses.

Deep Inside a freezer in a high-security laboratory a few miles outside Salisbury lies a family of the world's most deadly viruses. For those infected with any of these viruses there is no cure, no vaccine, and for many people, no hope.

As many as nine out of 10 people attacked by viruses like those stored here in frosted phials will die. Victims bleed to death, the infection attacks vital organs, including the liver, and destroys the blood-clotting mechanism. Vomiting, anorexia, fever and bleeding from gums, nose, lungs, uterus and intestines are all symptoms.

Scientists hunting for a cure for the deadly infections of this family of viral haemorrhagics at the Centre for Applied Microbiology and Research (CAMR) at Porton Down handle them only via robotic arms in air-tight cabinets. Their maximum containment laboratory is one of only six labs around the world which can comply with Grade Four security - the most stringent of WHO conditions involving triple packing and high-security systems that limit movement to within the containment lab.

For millions of people, though, in a growing list of countries, there is no such protection from the mysterious and deadly bleeding viruses which in many cases are carried symbiotically by unknown host rodents. In dozens of countries, the viruses are at large and infecting increasing numbers of people, many of whom have died.

These viral haemorrhagic fevers (VHFs) are mostly named after the area where they claimed their first victims. Ebola, one of the two most potent strains and one of the most hazardous biological agents known to man, was first identified 20 years ago in the synonymous river in Zaire.

Despite knowing the genetic make up of the virus, scientists do not fully understand the various mechanisms by which the infection causes the disease, which can affect the liver or reduce the number of platelets in the blood- clotting system. VHFs can attack blood cells directly, causing vital plasma to escape, and can trick the immune system into delaying the vital production of antibodies needed to ward off the attack.

"VHFs are severe and life-threatening diseases caused by a range of viruses, their key characteristic is that they produce this bleeding ... which causes the severity of the disease and the resultant shock," says Dr Graham Lloyd, head of diagnostics at CAMR. "These viruses ooze mystery and danger and present a major challenge to man's scientific capabilities."

The emergence of many of the VHFs is thought to be linked to environmental changes and ecological disturbances and destruction. Host rodents have been disturbed by man's intrusion into forests or savannahs, or by changing agricultural practices in what were wilderness areas. In parts of South America, for example, clearing of forests has exposed human to viruses carried by animals with which they had not previously come into contact.

An outbreak of Guanarito virus in Venezuela began when a rural community began to clear woodland. It is suspected that the felling work disturbed dust which included dried urine from a species of rat which carries the virus. The virus got directly into the lungs of its victims when they breathed in the contaminated dust.

"This virus came out of nowhere," says Dr Lloyd. "Due to deforestation, man comes into contact with rodents that carry the virus. The rodents themselves are not affected, and the virus only starts causing disease when it jumps the species."

Dr Bernard Le Guenno, director of the Centre for Haemorrhagic Disease at the Pasteur Institute in Paris agrees: "The emergence of these viruses is due to new conditions. The growing population of the world changes the balance of the ecological system. It upsets stable ecosystems and puts man into contact with animals that carry these viruses."

Other kinds of environmental change also can trigger outbreaks. Five years ago in the American Midwest, a combination of exceptionally heavy rainfall and increased groundnut production drew in the deer-mouse which carries a virus that attacks the lung in humans. In Argentina, land cultivation has attracted a huge population of vester mice which carry the Junin virus. And the expansion of reservoirs affects the spread of mosquito-borne viruses.

In a number of cases, including Ebola and the equally deadly Marburg, the host of the virus has not been tracked down despite extensive research. But in other instances where humans have contracted the disease from monkeys, the monkey seems to be just as much a victim as man.

There is no cure in sight for VHFs and concern is growing in the West for the health of tourists. The incidence of VHFs in Africa, South America and the Far East has been growing and there are increasing fears that tourism to those areas will eventually bring the viruses to Europe. Scientists at CAMR and colleagues in the Public Health Laboratory Service now operate a 24-hour hotline for doctors in the UK to check the symptoms of patients who may have the diseases.

"We thought Ebola was confined to Zaire and Sudan where it was first discovered, but in the last few years we have had a bit of a shock because it was found in primates from the Philippines," says Dr Lloyd. "That taught us not to be complacent.

"People have to be on their guard. There is always the possibility that if you have a large tourist population moving around and going to places that have not traditionally been open to tourism, someone is going to bring the virus back. We have to be vigilant about spotting it."

The ideal would be to have a vaccine and to be able at least to advise travellers on what to avoid, but there is no immunisation available and in many cases the host of the virus is unknown. As Dr Lloyd says, "In the case of Ebola and a number of other viruses we don't know what carries it. We don't know why it suddenly disappears and then comes back. If you know the answers to these sorts of things you can do something about them. The fact is, we don't know, and that's frightening." !

EMERGING & RE-EMERGING VHFs

SIN NOMBRE: First reported in 1993 when two young people died of respiratory problems in New Mexico. Cases then found in Colorado and Nevada. Virus invades blood cells in the lungs.

BRAZILIAN SABIA: Fatality rate 15 to 30 per cent. Three incidents since 1990. Death is usually the result of haemorrhaging and jaundice.

GUANARITO: In 1990, an outbreak in Venezuela affected 104 people of whom 26 died. Cotton and cane rats are likely hosts.

MACHUPO CIRUS: Three years ago nine cases were reported in Bolivia. Seven died.

JUNIN: First found in corn harvested in Argentina. The host appears to be a rodent. Major research programme underway to find vaccine.

KYANANUR FOREST DISEASE AND OMSK FEVER: Affects central nervous system, causes bleeding from vital organs over days before death.

DENGUE: Mosquito-borne. Life-threatening, particularly among young children.

CRIMEAN-CONGO FEVER: Reported fatality rate of up to 50 per cent. Host carriers: hares, birds and a species of tic. No vaccine.

EBOLA: Cause of the most severe and lethal haemorrhagic illnesses known. First documented in 1976 when 280 died in Yambuku, Zaire. Last year 190 died in an outbreak in Kitwit, Zaire. In reported outbreaks since 1976, the death rate was 82 to 90 per cent. Total death toll to date estimated at around 800. Host unknown.

HANTAVIRUS: Carried by rodents. New lethal form found in south-western USA.

MARBURG: Similar to Ebola but with 25 per cent death rate. Host unknown.

RIFT VALLEY FEVER: Mosquito-borne. Cause of the most explosive epidemics seen in Africa.