Sickness and death from ‘H5N1’ pale into insignificance when compared to many other infectious diseases that plague the world. But the dangers from new flu strains go well beyond those posed by this virus.

The bird flu known as ‘H5N1,' which the world had largely forgotten about, suddenly sprang back into the news when recently the Food and Agriculture Organisation of the United Nations (FAO) issued a release warning of a ‘mutant strain' of the virus that was spreading in Asia and beyond “with unpredictable risks to human health.”

Immediately afterwards, the World Health Organisation (WHO) issued a release of its own: “Based on available information, this evolution of the H5N1 virus poses no increased risk to public health. It is not considered unusual because influenza viruses are constantly evolving, especially in areas where they circulate regularly in poultry.”

The principal risk from the new mutant strain, designated H5N1-2.3.21, appears to be to poultry. The new virus is able to evade existing poultry vaccines against H5N1, and could therefore spread to other countries from China and Vietnam where it has been found.

As was the case with human flu vaccines whose composition needed to be reviewed annually, avian flu vaccines also needed to be regularly checked for their efficacy against viruses circulating in the field, the World Organisation for Animal Health (OIE) pointed out.

The OIE Reference Laboratory in Harbin, China, had developed a vaccine seed strain that experimentally protected poultry from the new virus. Registration and manufacture of a poultry vaccine with the new seed strain was in progress, it added in a press release.

Influenza virus are grouped into three types (A, B and C). Human pandemics have been caused by the type A viruses, which infect a wide range of birds and animals. The type A flu viruses are further categorised into subtypes based on two proteins they carry. The ‘H' in the virus designation indicates the sort of haemagglutinin it possesses and the ‘N' its neuraminidase subtype. While many subtypes are found in wild aquatic birds, only a few are able to infect humans.

When the highly pathogenic form of the H5N1 virus was first detected in dead geese in China's Guangdong province in 1996, it didn't attract much notice. But that changed the following year when it swept through Hong Kong's live poultry markets and infected 18 people, a third of whom died. The administration in Hong Kong responded by culling all the poultry, which ended the outbreak.

The virus, however, continued to circulate in southern China. In the following years, it spread to other countries in the neighbourhood. But even in 2005, the virus was largely confined to South-East Asia. In May that year, the virus infected and killed a large number of migrating water birds that had gathered at the Qinghai Lake in western China.

“The deaths of swans and geese marked H5N1's spread into Europe, India, and Africa,” remarked Robert G. Webster and Elena A. Govorkova of the Department of Infectious Diseases at the St. Jude Children's Research Hospital in Memphis, U.S., in a paper published in the New England Journal of Medicine.

According to the FAO, “ since 2003, H5N1 has killed or forced the culling of more than 400 million domestic poultry and caused an estimated $20 billion of economic damage across the globe before it was eliminated from most of the 63 countries infected at its peak in 2006.” The virus was still firmly entrenched in six countries — Bangladesh, China, Egypt, India, Indonesia and Vietnam.

With outbreaks in poultry, the virus has from time to time jumped to humans too. Since 2003, it has infected 565 people, according to data maintained by the WHO. More worrying is the fact that the resulting disease killed half of them.

However, an analysis published in Eurosurveillance recently by scientists at Germany's Robert Koch Institute found that the human case-fatality rate from H5N1 infection varied from 28 per cent in Egypt to 87 per cent in Indonesia. Even when adjusted for age, sex and time to hospitalisation, Egypt still had the lowest odds of people dying from the virus. Differences in the viral strains found in Egypt and Asia could not be ruled out as a factor, they said.

The scientists also noted that longer delay, from the onset of symptoms to hospitalisation and belonging to older age groups were associated with higher mortality.

Human sickness and death from H5N1 pale into insignificance when compared to many other infectious diseases that plague the world (malaria, for instance, is responsible for nearly a million deaths a year). But the worry has long been that this bird flu virus might take on a pandemic form and then sweep swiftly across the globe.

At present, the virus is not able to easily infect humans or pass from one individual to another. Could the virus become better adapted to humans through mutation and exchanging genes with other flu viruses (a process known as reassortment)? If that does happen, would the H5N1's lethality be reduced in the process?

The rationale for particular concern about a H5N1 pandemic was not its inevitability but its possible severe impact on human health, wrote J.S. Malik Peiris, a well-known virologist at the University of Hong Kong, and others in a paper published in 2007.

Such a pandemic, especially if it arose by the bird flu virus directly adapting to humans, rather than through genetic reassortment with a pre-existing human virus, could well be unusually virulent in humans. “Thus, an H5N1 pandemic is an event of low probability but one of high human health impact,” they concluded.

When the flu pandemic of 2009 broke out, it was produced not by H5N1 but by a strain that made the leap from pigs to humans bearing a mix of human, swine and bird flu virus genes.

Pandemics have been caused by flu viruses that came over from animals, remarked Dr. Peiris when this correspondent met him last year. It was flu viruses from domestic livestock that were most likely to make the jump to humans.

Surveillance to monitor the viruses circulating in poultry and pigs was therefore essential. It was necessary to keep watch on whether such viruses were actively undergoing reassortment and if they possessed certain molecular markers, such as those for easily infecting humans, he added.

Pigs are of particular concern because they can become infected with both bird and human flu viruses, creating opportunities for gene swapping between viruses. The last three pandemics — and quite possibly the severe pandemic of 1918 too — were produced by flu strains that arose through such genetic reassortment.

Genes from the 2009 pandemic strain have been found in various reassortant viruses. A paper in the journal Science last year spoke of a novel virus that had been isolated from pigs in an abattoir in Hong Kong, which combined genes from the 2009 pandemic strain with those of a H1N2 virus.

Just recently, the U.S. Centers for Disease Control and Prevention reported a new H3N2 swine virus that had been able to infect children. The virus possessed a gene that had come from the 2009 pandemic strain.

In a paper earlier this year in the Proceedings of the National Academy of Sciences, a team of Chinese scientists showed in the laboratory that a mix of genes from the 2009 pandemic strain with those of the H9N2 bird flu virus could result in viruses that were more virulent than the parental forms. The H9N2 bird flu is found in poultry in many countries across Asia and so such reassortment could potentially occur naturally too.

The threat to human health from new flu viruses therefore go well beyond those posed by the H5N1 bird flu virus.

Flu viruses can evolve rapidly and scientists would like to find universal vaccines that can protect humans against all strains or at least a wide range of them. Current flu vaccines are able to target only closely related forms of a virus. As a result, the seasonal flu vaccine has to be modified annually depending on what viruses are circulating. As for pandemic strains, which are able to spread rapidly because few people have immunity to them, a vaccine can be mass manufactured only after the outbreak begins.

Recent research publications show that scientists are exploring a number of approaches for developing a universal flu vaccine. Francis S. Collins, director of the U.S. National Institutes of Health, was recently quoted as saying that he was “guardedly optimistic” that such a vaccine could be created within five years.

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