Select Committee on Science and Technology Written Evidence

Memorandum by Dr Alan Hay, Director of the World Influenza Centre


  1.  The WHO Global Influenza Programme takes responsibility for co-ordinating international efforts to monitor the emergence and spread of potential pandemic influenza viruses, provides up-to-date information on recent developments and advises on strategic actions to mitigate the impact of an influenza pandemic. In this, the WHO works closely with other international organisations with responsibilities for animal health, OIE and FAO, and national authorities, to optimize information on the epidemiological and virological links between human and avian (and animal) infection.

  2.  The WHO Global Influenza Surveillance Network provides the international framework: for monitoring the incidence of human infection by novel (animal/avian) influenza viruses, such as the H5N1, H9N2 or H7N7 viruses, and the capacity of these viruses to spread from one person to another and more widely within the community; to assess the potential significance of changes in the viruses, including genetic reassortment with circulating human or animal viruses, which may be associated with adaptation to the human host; and for assisting early intervention which might reduce the chance of emergence or the spread of a pandemic virus.

  3.  Enhanced surveillance in south east asia in recent years, especially in response to the SARS outbreaks and more recently to H5N1, has enabled detection of human infection by avian H5N1 (and other avian/animal) viruses, the detailed genetic characterization of the viruses and provided an understanding of the interrelationships between the viruses responsible for human infections and those causing outbreaks in domestic poultry. However, there is still relatively little definite information on the true extent of human infections, especially subclinical or mild infections, particularly among rural communities (in Vietnam) and the role of domestic ducks, with asymptomatic infection, and other animals in spreading disease.

  4.  Intensive collaboration between many agencies, from diagnostic labs to national public health/veterinary authorities to international agencies (WHO, OIE, FAO) has been essential to facilitate the necessary scientific investigations in the context of both local and international interests. Future increased co-operation, supported by the provision of necessary financial resources, particularly in south east Asia, is essential to enhance our understanding of the epidemiology of these viruses and the links between animal disease and the risk of human infection, to allow a more objective assessment of the present pandemic threat posed by these viruses and to monitor their future significance. A role for migratory birds in spreading the H5N1 viruses to other regions is supported by the similarities between viruses isolated from wild and domestic birds in distant geographical locations and has led to calls for more intensive international surveillance.


  5.  Since 1997 there have been a number of ­outbreaks" of human infection by avian influenza viruses associated with outbreaks of disease in domestic poultry: by H5N1 subtype viruses in Hong Kong in 1997, in southern China in 2003 and during 2004 and 2005 in Vietnam, Thailand, Cambodia and more recently Indonesia; by H9N2 viruses in Hong Kong in 1999 and 2002; and by H7N7 viruses in the Netherlands in 2003. In contrast to the high fatality associated with H5N1 infection, infections by the H9N2 and H7N7 (which like H5N1 is highly pathogenic for chickens) viruses were, with one exception, relatively mild. Evidence indicates that most infections were contracted directly from infected birds. The H5N1 viruses have not spread readily from one person to another and evaluation of clusters of cases have provided only limited evidence of human-to-human transmission. Thus removal of the source of infection, by culling the birds in Hong Kong in 1997 or controlling the outbreak in the Netherlands in 2003, halted cases of human infection. Although greater efforts and resources to control the outbreaks in poultry would lesson the risk of human infection, the H5N1 viruses are now endemic in a number of countries in eastern Asia and the recent wider spread of the viruses in poultry in western Asia and their potential intercontinental spread by infected migratory birds (or other means) provide the bases for a more persistant pandemic threat, requiring maintained heightened surveillance.

  6.  To date all the human isolates have been exclusively avian in genetic makeup and there is no evidence for genetic reassortment with human viruses, as occurred to produce the H2N2 and H3N2 subtypes which caused the 1957 and 1968 pandemics, respectively. However, H5N1 human infections have occurred co-incidentally with outbreaks of normal human influenza. There is also little evidence to date that the H5N1 viruses adapt during human infection to acquire a greater capacity for human infection or human-to-human transmission. However, the virus isolated from the single fatal human case of H7N7 in the Netherlands in 2003 had undergone significant change during prolonged infection, indicative of adaptation which may have increased its pandemic potential. Thus, the greater the number of human infections and the longer they persist, together with an increase in the number of variants of H5N1 viruses responsible, will increase the risk that one will emerge with a greater capacity for human infection and transmission.

  7.  H5N1 infection of pigs, and other animals such as cats, provides the possibility that these animals might act as an intermediate hosts in the emergence of a human pandemic virus. The recent emergence in pigs in North America of reassortant viruses possessing genes of human, swine and avian virus orgin, together with the frequency of human infection associated with outbreaks of influenza in pigs, lends credence to this mechanism.


  8.  The World Influenza Centre (WIC) was established at the MRC National Institute for Medical Research in 1948, at the behest of the newly established WHO, and has a long history of international collaboration in influenza. Today it is one of five WHO Collaborating Centres for Reference and Research on human and animal influenza which together with some 112 WHO National Influenza Centres (NICs), including the HPA Centre for Infections, Colindale (HPA-CFI), in over 80 countries worldwide comprises the WHO Global Influenza Surveillance Network. The WIC receives viruses from many of these laboratories in different parts of the world, to monitor changes in influenza viruses circulating in the human population and advise WHO (biannually) on its recommendations for the compositions of influenza vaccines, and to detect (as early as possible) and characterise novel human influenza viruses, from animal or avian sources, which may have the potential to cause a pandemic.

  9.  The WIC is one of the WHO H5 Reference Laboratories and participates in the characterisation of the antigenic and genetic properties of the recent H5 (N1) viruses. Of particular interest are:

    (i)  the genetic relationships between the human isolates and avian (and animal) viruses and the significance of changes which might indicate adaptation of the avian virus to the human (or animal) host and increased potential for human-to-human transmission and to cause a pandemic;

    (ii)  changes/differences in the antigenic characteristics of recent human viruses in relation to suitability of prototype vaccine strains;

    (iii)  changes in drug susceptibility. Together with the National Institute for Biological Standards and the HPA-CFI, it has been involved in the selection and evaluation of potential pandemic vaccines.

  10.  The WIC works closely with many NICs and laboratories of the European Influenza Surveillance Scheme and provides advice on the characteristics of H5N1 and other potential pandemic influenza viruses and provision of reference reagents for their detection. Also, as members of the international Neuraminidase Inhibitor Susceptibility Network and a European antiviral drug resistance network (VIRGIL), the WIC and the HPA-CFI have international responsibilities for monitoring the emergence of drug resistance in relation to anti-influenza drug use.

  11.  The WIC and the Central Veterinary Laboratories Agency (VLA), Weybridge, the OIE European Reference Laboratory for avian influenza, collaborate with other members of the recently formed WHO Working Group on Influenza Research at the Human/Animal Interface which co-ordinates the surveillance and research interests of WHO, OIE and FAO laboratories in relation to the emergence of potential pandemic viruses. The VLA is also a member of OFFLU, a network co-ordinating the efforts of OIE and FAO laboratories on avian influenza. The WIC also has a specific, Wellcome Trust supported, collaboration with the University of Hong Kong and Massey University, New Zealand, on the epidemiology and zoonotic potential of avian influenza viruses in southeastern China.

26 September 2005

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