Memorandum by the Academy of Medical Sciences
This submission was prepared in consultation with
Academy Fellows drawn from across the Fellowship, from laboratory
to clinic. We have also drawn upon the report of the Academy's
meeting with the Chief Medical Officer, Sir Liam Donaldson FMedSci,
which took place on 20 September 2005. We are much indebted to
Sir Liam for sharing his thoughts and concerns with us and much
of the discussion is reproduced here.
The evidence presented here is endorsed by the
How is the risk of pandemic influenza emerging
in south east Asia, and reaching the UK, being assessed; and how
can this assessment be improved?
How great are the risks, and what confidence can
be placed in these figures?
How is the UK working with international bodies
to: monitor the development of the virus; and reduce the risk
of pandemic influenza emerging and spreading?
1. Evidence shows that H5 bird flu is spreading
ever wider and it is now acknowledged that it is not a matter
of whether a pandemic will occur, but more a matter of when. It
seems most likely that a pandemic will originate in south east
Asia. There are significant concerns about the lack of surveillance
in likely pandemic influenza source countries. Following the SARS
episode, China took advice from the UK Health Protection Agency
(HPA), World Health Organisation (WHO) and others on improving
surveillance mechanisms, but progress appears to have been slow.
The Government, in conjunction with WHO, must work for greater
openness and improved surveillance in the relevant countries.
Ultimately, it is unrealistic to suppose that an emerging infection
will be contained in south east Asia.
2. It should be noted that an outbreak may
not necessarily occur in the Far East. Influenza can spread via
wild migrating birds, as well as poultry and people. The American
experience with West Nile Virus demonstrated that migratory birds
can rapidly spread infectious disease from east to west, as well
as north to south. It is therefore crucial that disease in bird
populations is monitored across Europe and the UK, in addition
to south east Asia. Similarly, in the event of an outbreak, measures
must be taken to protect British bird flocks. Current surveillance
work by the Department for Environment, Food and Rural Affairs
(Defra) in this area should be strengthened and communication
between the human and animal health sectors encouraged.
What is the current assessment of the likely impact
of pandemic influenza on the UK (both in terms of health and on
wider society, including the economy)?
3. The current H5N1 strain of avian influenza
circulating in south east Asia is extremely virulent, killing
approximately half of those people infected. Although this information
is based on only small number of human infections (~120) it is
reinforced by the viruses' very aggressive behaviour in vitro.
If virulence does not diminish when the virus achieves human-to-human
transmission, mortality will be significantly greater than the
1968 pandemic. The Academy therefore considers that the Government
should plan for more than the currently estimated 50,000 pandemic
4. Pandemic flu, unlike seasonal strains,
does not disproportionately affect older people, but will impact
on all age groups. However, morbidity and mortality are likely
to be particularly high in already vulnerable populations such
as those with diabetes, cardiovascular disease and those taking
immunosuppressants. Babies under one year old are also especially
How well co-ordinated are health, emergency and
other essential services for responding to a pandemic?
5. As mentioned previously, the Academy
is concerned that an under-estimate of the likely number of UK
pandemic flu cases will prevent effective co-ordination of health
and other services. A significant concern is the assumption that
local healthcare managers have robust local plans for coping with
a flu pandemic. The Government should consider potential difficulties
in switching largely devolved health administrations to a centralised
system of command and control" for the duration of
6. The Academy is particularly concerned
about the lack of planning for management of critical care services
in the event of a flu pandemic. Modelling work carried out by
the Professor David Menon et al has shown that an eight-week pandemic
with 25 per cent attack rate could create a demand for critical
care beds at 208 per cent of current capacity. An optimistic estimation
of impact factors (50 per cent reduction in critical care demand
with neuraminidase inhibitors and upgrading of some beds to critical
care levels), results in critical care bed occupancy at 75 per
It should be noted that staff illness rates of 25 per cent will
severely undermine normal, let alone enhanced, critical care services.
7. However, critical care capacity can be
expanded, for instance by co-opting surgical recovery areas and/or
operating theatres. There is a further problem that current critical
care bed density does not reflect population density and may not
reflect the geography of an outbreak. The need to transfer both
patients and staff must therefore be examined.
8. Planning for the management of critical
care services during a pandemic should include:
- Creation of libraries of equipment to
be mobilised if an expansion of critical care services is needed;
- Details of how critical care departments
could expand into theatre recovery areas and some operating theatres;
- Provisions to transfer patients and staff
between critical care facilities;
- Careful logging of non-NHS critical care
- Clear recognition of triggers to signal
the cancellation of elective surgery (and planning for the period
of catch up in the months following a pandemic);
- The impact of how the critical care focus
on influenza will negatively affect facilities available for other
- Expansion of mortuary facilities.
What is being done to ensure that the general
public are aware of the risks and likely effects of a pandemic,
and of how they should react?
9. The Academy considers public understanding
of the risks and effects of a pandemic to be crucial. There appears
to be a general lack of understanding about the nature of pandemic
flu and its relationship/differences with bird flu and normal"
seasonal flu. There also appears to be a lack of appreciation
amongst the public that some harm will result from a pandemic,
whatever measures are put in place. The Government must be explicit
in communicating that a pandemic cannot be entirely prevented,
but work can be done to limit the damage. Public health measures
such as school closures and patient isolations will operate more
effectively if there is full public understanding of the issues
involved. Effective communication will be crucial in potential
instances where measures appear counter-intuitive to journalists
and the wider public. For instance, preventing incoming flights
from affected countries might provide public reassurance, but
there is little evidence that such social controls of movement
are effective in preventing the spread of infection.
10. Care should be taken to ensure that
public messages regarding a pandemic are accurate. For instance,
the public should be aware of the true number of antiviral doses
available and who will receive them. Issues relating to essential
workers" are relevant to this and are discussed below.
Is the UK's stockpile of antiviral treatments
adequate, and how will it be distributed? What steps are being
taken to ensure that the UK has access to sufficient antiviral
treatment and vaccine in the event of a flu pandemic?
11. Current Government information indicates
that the target stockpile of 14 million antiviral doses will be
reached in approximately one year (covering 25 per cent of total
UK population). The Academy is concerned by the lack of detailed
plans on who should receive antiviral treatments and when. A key
element is defining an essential worker", upon which
Government policy is unclear. Essential workers are not necessarily
restricted to the public sector, for instance supermarket lorry
drivers would provide a key service in delivering food during
a pandemic. The size of the essential worker" population
must be known in order to assess the impact on the antiviral stockpile.
The identification of key workers within health care institutions
and those who should hold a limited antiviral supply is particularly
12. It is also unclear how the Government
intends to use antivirals in a pandemic situation. Relatively
little is known about the impact of antivirals on disease outbreaks,
with the only available data originating from Japan. Therapeutic
and prophylactic treatment would require a supply of one week
and up to six weeks per individual respectively. Current Government
policy does not appear to favour prophylactic antiviral use, which
would deplete the stockpile very rapidly. Rather, antivirals would
be given to people displaying early flu symptoms, in order to
reduce severity, infectivity and mortality. However, it might
be considered unreasonable to ask essential workers to expose
themselves to infection without prophylaxis. If essential workers
are to be given prophylactic antivirals, the longer duration of
treatment will significantly impact on the number of doses available.
13. A programme of research on the effects
of antivirals is therefore very important. While the mechanism
of antiviral action allows viral replication, it is unknown whether
this elicits immunity to re-infection. It is also unknown how
long any such immunity would last. Viruses that become resistant
to antiviral treatment show a considerable drop in neuraminidase
activity. However, more research is needed into the transmissibility
of resistant strains. It would also be useful to know if antiviral
treatment reduces transmissibility within households.
14. Effective distribution of, and access
to, antivirals must be ensured. Similarly, essential workers who
may be required to self-diagnose" and commence antiviral
treatment will require clear and robust guidance. Pressure on
those holding small antiviral supplies may become intense in a
pandemic situation. It is essential that such people receive effective
guidance and support.
15. The Government should review the licensing
arrangements for antivirals. For instance, neuraminidase inhibitors
are not licensed in babies, who would be particularly vulnerable
in a pandemic situation.
What will be the role of vaccine development,
manufacture and distribution in responding to a pandemic?
16. Government policy on vaccination accepts
the inherent difficulty that the particular strain of a pandemic
can never be known in advance. Policy is therefore focused on
early identification of the strain and shortening the time for
vaccine production. However, it appears that this position has
evolved and the Government has now tendered for one to two million
doses of vaccine active against the current H5N1 bird flu strain.
17. There is a question of whether, in mutating
to a human transmissible form, vaccines against current bird flu
virus would be rendered ineffective. Alternatively, the mutation
may be small enough to allow some vaccine protection. The Academy
therefore welcomes the Government's initiative and recommends
that expansion of vaccination with current bird flu vaccines should
be considered. We understand that the Government has considered
adding the bird flu vaccine to the seasonal flu jab, but manufacturing
difficulties have prevented taking this further.
18. However, further R&D must be undertaken
to establish an optimal vaccination strategy. The Academy is concerned
that the Department of Health (DH) is not sufficiently active
in the field of vaccine R&D to confront an emerging threat.
The UK has previously been at the forefront of work on the development
and assessment of candidate pandemic flu vaccines. Research on
an avian H5 Duck Singapore virus vaccine, as well as on an H9
vaccine highlighted several challenges. Current H5 flu vaccines
are poorly immunogenic when given in conventional subunit form
(ie as currently manufactured), with 80-90µg protein required
to elicit an immune response. This significantly reduces the number
of available doses.
19. It cannot be assumed that a new vaccine
is safe, especially if it is very different from existing vaccines.
It is likely that immunising a large proportion of the population
would give rise to side effects. It is therefore essential that
safety and efficacy trials on potential H5 vaccines be performed
in advance of an epidemic.
20. The Academy urges the DH to initiate
- Investigate different vaccine formulations
(adjuvanted and non-adjuvanted, subunit and whole virion);
- Investigate different vaccine doses;
- Evaluate priming to a future antigenic
- Evaluate safety and antigenicity in different
populations (children, adults, older people).
21. When planning R&D strategies it
is important to consider that pharmaceutical companies are committed
to making conventional vaccines for both northern and southern
hemisphere countries and only have a short period available each
year to research experimental" avian flu vaccines.
Researchers also stress that generic difficulties with the regulatory
framework for clinical research may prevent studies being approved
and undertaken quickly.
What is the long-term strategy for reducing the
threat of pandemic influenza?
22. Long term strategies for reducing the
threat of pandemic influenza must be multi-faceted. Research needs
and opportunities are the focus of this response. It is crucial
that research agencies and funders consider in advance what research
questions should be carried out during a pandemic, as it will
be extremely difficult to conduct research in an emergency situation.
Current work in this area by the DH and Medical Research Council
should be strengthened. It may be the case that researchers working
in other areas would be keen to switch to flu-related research
in a pandemic situation. The DH should compile a list of such
23. In the event of a pandemic, the Government
should consider the collection and fractionation of serum from
convalescent patients (as soon as they exist), perhaps to provide
a bank of immune immunoglobulin for future prophylaxis. Similarly,
it will be important to know whether there are any genetic associations
with mortality, morbidity or survival with pandemic influenza.
Preparations should be made to collect and store DNA samples for
future association studies.
The Academy is extremely grateful to Sir John
Skehel FRS FMedSci for assistance in preparing this response.
We also thank Professor David Menon FMedSci and Professor Karl
Nicholson for their contributions.
1 Menon DK et al Modelling the impact of an
influenza pandemic on critical care services in England Anaesthesia
2005; 60: 952-4. Back