The world barely escaped the outbreak in 1997 of a deadly form of influenza that might have rivalled the 1918 epidemic for its ability to kill. Dick Ahlstrom reports on a new study of the 1997 virus.
A deadly and entirely new form of influenza virus arose in Hong Kong in 1997. With it the world came perilously close to an outbreak that might have matched the infamous Spanish Flu epidemic that in 1918 killed 30 million worldwide.
There were only 18 cases of this lethal 1997 infection in humans, but it killed six, a third of those who contracted it. Now scientists have established what made it so dangerous.
Prof Robert Webster of St June's research Hospital, Tennessee, and colleagues write about the virus, H5N1, this week in the journal, Nature Medicine. The virus contains a gene that manages to disarm the body's key antiviral defences leaving the person open to unchecked infection and probable death.
Come winter, everyone will be talking about catching the flu and friends coming down with the flu, even though actual influenza is seldom involved. The common cold virus causes most of these upper respiratory tract infections. Although uncomfortable and annoying, they are not generally life-threatening and have little impact on public health.
Actual influenza is a different matter. Common influenza forms lead to 20,000 deaths annually in the US, and 100,000 hospitalisations. The virus is a particular threat to the very young and the very old, making it something much more dangerous.
Various flu forms emerge every year in the southern hemisphere during its winter months. Humans, birds and pigs all suffer from 'flu, but when these three species live close together the viruses can combine and mix to create new forms.
These infections are carried outwards by human contact. They typically begin reaching Europe by December and outbreaks are seen by late December or January, if an outbreak is to occur.
This long dispersal period gives scientists a chance to see just what form of virus is emerging each year. With this knowledge, they can alert health authorities what type of flu vaccine to have available for the coming season.
The virus is described on the basis of two key proteins located on its surface. Haemagglutinin (H) is a spike-shaped surface protein with 13 types, and neuraminidase (N) is a box-shaped protein with nine main forms. Researchers identify the forms and then use initials and numbers to describe the virus; for example, H1N1 is a common human form.
The impact of a given flu combination depends on how recently and how many times it has emerged before. If it is a common type then many people will have encountered it and will have natural resistance to it.
The 1997 flu, H5N1, was an entirely new variety against which there would have been virtually no immunity. It had only ever previously been seen in birds and seemed to jump directly into humans. It also carried a genetic change that made it particularly dangerous to humans, Prof Webster reports.
It contained a gene that produced a substance able to block the effects of two of the body's powerful antiviral defences, the interferons and TNF-alpha. Both are cytokines, essential chemical signals that initiate the immune response. "Our results show that H5N1 influenza viruses transmitted to humans in 1997 escape the antiviral activity exerted by the interferons and TNF-alpha. These cytokines are induced in the early phase of infection and serve as the first line of antiviral defence," the authors write.
The team described H5N1 as "highly pathogenic" because of the genetic mutation that disarmed the two cytokines, something borne out in the earlier clinical findings in Hong Kong, which had six deaths in 18 cases.
Scientists there moved quickly to identify the virus type recovered from these patients, which connected it to avian flu forms. Once this became clear health officials moved quickly, deciding to slaughter the city's three million chickens. This decisive action stopped H5N1 and prevented its escape from the city.