Health: Reason to be fearful?

Bird flu may have jumped to humans, but is it a real danger that threatens millions or just another scare story? Jeremy Laurance assesses the risks

On 2 September last year, an 11-year-old girl was taken by her aunt to a clinic in the village in Thailand where she lived. She had a fever, cough and sore throat. Five days later she was worse, suffering breathlessness, and was admitted to hospital.

The girl's mother, who lived in a distant city, came to be with her daughter and nursed her for at least 16 hours over 7 and 8 September. By now the girl was critically ill and she was transferred to a provincial hospital where she was placed on a ventilator. She died three hours later.

Blood tests showed the girl was a victim of avian flu - a virus that has decimated poultry flocks in South East Asia in the worst epidemic in living memory. Chickens kept by her aunt had fallen sick and died a few days before she became ill; she had played where they lived, under the house.

But what made her case unique was that, three days after her death, the mother fell ill with the same symptoms, went rapidly downhill, and died on 20 September. Crucially, she had had no contact with poultry, but the cause of her death was confirmed as avian flu. Sequencing of the virus showed it was the same strain. The girl's aunt also contracted it, but recovered.

Scientists who examined the family cluster say it provides the clearest evidence so far of what doctors have long feared - that the lethal avian- flu virus can be passed between people.

In a report on the case published in the online version of the New England Journal of Medicine last week, scientists from Thailand, the USA and the World Health Organisation in Geneva say the world has been given "unprecedented warning" of a pandemic, adding: "We need to put up safeguards while the storm is gathering."

There have been probable cases of human-to-human transmission before but this is the first in which the person infected - the mother - contracted severe illness and died. It proves that the virus can be passed from person to person without losing its lethality.

The strain of avian flu circulating in South East Asia is twice as lethal to humans as smallpox, but has not yet acquired the capacity to spread with the ease and rapidity of human flu. The fear now is that it is only a matter of time before avian flu "reassorts" with human flu to create a pandemic strain.

Should that happen it would become the 21st century's plague. The virus poses the greatest potential threat to the world - greater by far than the threat from bio-terrorism, natural disaster or nuclear accident. Three times in the last century - in 1918, 1957 and 1968 - avian flu jumped to humans, mutated and spread round the globe claiming millions of lives.

The world has been on high alert for the next pandemic of avian flu since 1997, when an outbreak of the H5N1 strain amongst poultry in Hong Kong caused panic in the city and led to the slaughter of more than a million chickens. There have been several outbreaks among humans since as avian flu has spread, devastating poultry flocks in South East Asia and infecting ducks, pigs, wild birds and even a snow leopard in a zoo.

Avian flu causes the same symptoms as ordinary flu in its early stages. But it can rapidly lead to secondary symptoms, such as pneumonia, resulting in death. With avian flu spreading unchecked through the bird population in South East Asia, the number of people exposed to it grows and the chances increase of a lethal mutant form developing.

The H5N1 virus that emerged in 1997 has already gone through many reassortment events and several genotypes have emerged. The currently circulating one, Z, appears to be more lethal to humans - the death rate has risen from 30 per cent to 70 per cent - and researchers say in the New England Journal of Medicine that the evidence points towards its becoming more efficient in transmitting to humans. "It has been shown that a single amino acid substitution... could change the receptor preference from avian-specific... to human-specific," they say.

The virus is transmitted through the air, as infected people breathe, and by touch, especially from hand to mouth. It would take only one infected person on an aircraft to put all other passengers at risk. A disturbing aspect is that children are the most infectious, because they shed the greatest amount of virus.

Last year avian flu infected 44 humans and caused 32 deaths in Vietnam and Thailand, a death rate of 72 per cent. More than 200 million birds were slaughtered across the region. The WHO warned, in a report to its executive board on 20 January, that the world was closer to an influenza pandemic now than at any time since 1968. The present situation resembled that which led to the 1918 pandemic that probably caused more than 40 million deaths, it said.

Two more cases were confirmed by the WHO in Vietnam last week, bringing the total since mid-December to 10. A second family cluster, involving three brothers in their forties, two of whom caught the virus, is under intense investigation because of suspicions that there may have been human-to-human transmission. One of the brothers died.

Some countries are preparing for the worst. Last August the US government announced measures to protect the population in the event of a pandemic, including the closure of schools, a ban on travel and the quarantining of international visitors. Americans would be advised to work from home, stop shaking hands and wear masks in public.

The UK health department has drawn up a similar plan, though reports last week that it would involve the evacuation of cities were wide of the mark. The worst thing, in the event of a flu epidemic, would be to encourage people to gather at railway stations, where they could pass the virus on.

A vaccine is not included in either country's plans. Although flu vaccines exist, they would be useless against an H5N1 strain. The vaccine, which is grown in hen's eggs, must be matched precisely to the virus to be effective. It would take at least six months from the moment a pandemic strain was identified to produce one. By then it would be too late.

The alternative to a vaccine is anti-viral drugs. Unlike vaccines, these can be used against any strain of flu. Although they have limited effect against the illness, shortening its course by a day or two, they help prevent secondary complications such as pneumonia, and reduce infectivity, cutting the rate of spread.

Some countries have begun stockpiling the anti-viral drug, Tamiflu (made by Roche). A spokeswoman for Roche UK said Denmark, France, Korea, the Netherlands, Norway and the US had placed orders for Tamiflu but negotiations were still ongoing with the UK. The retail cost of the drug is pounds 18 for a pack of 10 doses, enough for one person, and millions of packs would be required.

Some experts believe that the time for dithering is over and action is needed now. Sir John Skehel, the director of the National Institute for Medical Research, and Britain's leading authority on flu, said last week that the situation in Thailand and Vietnam was alarming.

"We are looking at a 70 per cent death rate for this virus. Once you have got a drug that is effective against influenza, it changes completely how you respond to a potential epidemic.

"I know the health department has a plan but what bothers me is: even if they had a stockpile, what size would it be? If this virus came in the human population we would need a lot. They should be doing something. The drug should be on people's minds."

THE OTHER POTENTIAL PLAGUES

SARS

What is the threat?

Severe acute respiratory syndrome sparked a global panic in 2003. It is making a slow comeback.

How lethal is it?

The 2003 outbreak spread to 27 countries in a little over a month, causing 774 deaths.

How great is the risk?

Efforts to track down the source of the infection have failed. The virus has been found in several animals, including the civet cat.

WEST NILE VIRUS

What is the threat?

The disease caused panic when it appeared in New York in 1999 and 2000, apparently carried by ships bringing exotic birds. Spraying was carried out to kill the mosquitoes that carry the virus.

How lethal is it?

More than 50 people were hospitalised in New York, and at least 10 died. In 2002, more than 3,700 cases were recorded across the US.

How great is the risk?

The disease originated in Uganda in 1937. Outbreaks have been recorded in recent years in Israel, Romania, France, Portugal, Italy, Russia and the US.

HANTAVIRUS

What is the threat?

The first recognised case occurred in 1993 in New Mexico. The disease, marked by fever and breathing problems, is spread by mice and rats.

How lethal is it?

As well as the pulmonary illness, which kills four out of five people infected, hantavirus also causes internal bleeding. There is no treatment.

How great is the risk?

Any big increase in mouse numbers increases the likelihood of their coming into contact with humans.