INFLUENZA

INFLUENZA

Professor K.F. Shortridge

Department of Microbiology

H5N1 virus electron micrograph

BACKGROUND

Throughout history, influenza pandemics have appeared suddenly often with an Asian connection

Hong Kong (H3N2) pandemic influenza virus of 1968 retrospectively found to be antigenically related to an influenza virus previously isolated from a duck

This suggested that pandemic influenza viruses are partly or wholly of non-human origin

Ecological studies in the 1970 's fostered by WHO showed that influenza viruses occur naturally in a limited number of animals worldwide with aquatic birds as the prime reservoir in which they live harmlessly in the intestine

Southern China

Ecological studies conducted in the region from 1975-88 to explore the range of animals harbouring influenza viruses and their interelationship with the influenza viruses of humans. This will enable us to understand where and how a future pandemic virus might emerge.

Hypothetical interrelationship amongst influenza viruses and their hosts in southern China

Cardinal points to arise -

Southern China is a hypothetical epicentre for the emergence of pandemic influenza viruses.
The domestic duck is the principal reservoir of influenza viruses in southern China, geese are infrequently infected and chicken rarely.
The domestic pig is a hypothetical 'mixing vessel' for avian and human influenza viruses to reassort their genes to give rise to a putative pandemic influenza virus capable of human-to-human transmission.

These points provided the culture or understanding about influenza within this region.

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Aspiration after 1968 pandemic -

1.	To recognize a possible pandemic influenza virus in humans as an early warning sign and so blunt the effect of the pandemic.
2.	A higher aspiration was to recognize untoward influenza activity in animals as an even earlier warning sign of a possible pandemic virus.

Always worried that a pandemic virus with the force of the 1918-19 virus which killed 20-40 million worldwide could arise again.

1997 Influenza H5N1 virus

It had been 29 years since the Hong Kong pandemic virus appeared. Influenza authorities worldwide were concerned about the possible emergence of a pandemic influenza virus.
Hong Kong recognized a new virus, H5N1, the so-called 'bird flu' virus, in chicken and humans. The situation suggested an incipient pandemic. A global alert of the possibility of an influenza pandemic was issued by WHO - reagents prepared, steps to make vaccine, preventive measures prepared in many countries.
About 20% of market chicken carried the H5N1 virus, also 2.5% ducks and geese. Enormous virus 'load' upon the Hong Kong population favouring interspecies transmission to humans.
H5N1 virus genetically avian but genes evolving rapidly some giving rise to virus proteins with short amino acid sequences characteristically found in human influenza viruses. This could account for high case fatality rate (33%) but low human-to-human transmission.
Slaughter of poultry prevented further adaptation of the virus to humans or genetic reassortment with a prevailing human influenza virus in a human or pig.
Pandemic averted.
Poultry markets subsequently segregated so that aquatic birds (ducks and geese) cannot be a source of H5N1 virus for chicken.

1998/99 Influenza H9N2 virus

During the H5N1 incident, about 5% of the chicken and a small number of ducks, geese, pigeon and quail were found to be infected with H9N2 virus.
Genetic studies on the H9N2 virus showed an almost identical relationship with the replicating genes of H5N1 virus. Phylogenetic studies indicated that the H5N1 virus is in effect H9N2 virus surrounded by an H5N1 coat (Guan et al).
This makes H9N2 virus a particularly dangerous virus.
H9N2 virus has spread in chicken in Asia, is now in the middle East and has recently been reported in Europe occurring in three distinct lineages.
H9N2 virus isolated in Hong Kong from two pigs in 1998. WHO advised WHO Influenza Collaborating Laboratories and provisional diagnostic reagents prepared.
H9N2 virus isolated from two human cases of mild influenza-like illness in 1999 - increased concern by WHO.
Could H9N2 virus be a future pandemic virus in its own right or after reassortment in another HxNy guise?
Given the spread of the H9N2 virus, it is possible that it could arise in humans anywhere in the Eruoasian landmass or beyond.
While the H5N1 incident is a stepforward in understanding the origin of pandemic influenza viruses through recognizing an incipient pandemic, the emerging information on the H9N2 virus stands potentially to move that understanding further forward.

ACKNOWLEDGEMENTS

The work during and after the H5N1 incident was financially supported by the World Health Organization, Geneva; National Institutes of Health, Bethesda; Department of Health, Government of the HKSAR and The University of Hong Kong.

Follow-up studies on the epidemiology of influenza viruses are now supported by the National Institutes of Health, Bethesda in a seven-year contract 'Influenza pandemic preparedness in Asia' and The Wellcome Trust, London in an initial two-year Phase I award 'International Partnership Research Awards in Veterinary Epidemiology' This will help facilitate Hong Kong being an international centre for influenza studies. Principal co-investigators: K.F. Shortridge, J.S.M. Peiris and R.G. Webster.