Memorandum by the Centre for Applied Microbiology
and Research (CAMR) Porton Down, SALISBURY, UK
1. What are the main problems facing the
surveillance, treatment and prevention of human infectious disease
in the UK?
Although the PHLS surveillance system (through
CDSC) is widely considered to be a paradigm for infectious (and
non-infectious disease) surveillance systems across the world,
it is often seen as flawed and under-resourced. The surveillance
network currently in place covers England and Wales but data from
Scotland and Northern Ireland are gathered from separate systems
and collated by DH for the national picture.
Other than through DH, there is little unified
responsibility in Government for surveillance, treatment and prevention
of infectious diseases. Infectious disease commonly crosses Government
Departmental boundaries. This is particularly true for zoonotic
illness, which may be dealt with by several departments or agencies,
including DH itself, PHLS, NHS, FSA, LA, EA, NERC, VLA and their
regional counterparts. Indeed, the same suspected organism may
be dealt with by several different or collaborating agencies,
usually according to the route of dissemination; for example,
different aspects of food-borne Salmonella enteritidis phage-type
four disease may be dealt with by the DH and PHLS, VLA and DEFRA,
Local Authorities and also the FSA.
Primary diagnosis of infectious disease is based
on clinical judgement and diagnostic algorithms, rather than widespread
use of presumptive tests. This leads to risks of delayed diagnosis,
or empirical (and consequentially inappropriate) treatment. Widespread
application of (rapid) diagnostic testing may not be viewed as
cost-effective, particularly for illness with neither specific
therapy nor preventative strategies (eg vaccine). Similarly, the
widespread application of diagnostic assays for arenavirus and
filovirus infection in febrile patients returning from or domiciled
in Africa would seem largely academic and hardly cost-effective
when the presenting condition is usually malaria (ie common diseases
happen commonly). In the UK, the use of near-patient tests for
rapid diagnosis in the primary health-care setting (eg latex agglutination
tests for Streptococcus pyogenes in throat swabs) has not had
much impact and the reliability and cost-effectiveness of such
tests has been questioned. Although syndromic tests based on a
"pregnancy test" format would seem to afford an attractive
advantage in determining initial prescribing practice.
The number of vaccines available for control
of infectious disease in man is quite limited, and vaccine coverage
is largely determined by the paediatric and school age vaccination
schedule. Furthermore, the maintenance of vaccination status with
boosters once education is complete is very poor, except in the
armed services, and uptake of "adult" vaccines is poor
or patchy at best, eg seasonal 'flu vaccine in adults and 23-valent
pneumococcal vaccine in the elderly. Naturally, the costs of implementation
and surveillance of new vaccines, such as pneumococcal conjugate
vaccine, hepatitis vaccines and VZV vaccine is considerable and
must necessarily impact on policy.
There have been several instances of adverse
public perception of the value of vaccines, made more acute by
imprecise public perception of relative risk of disease morbidity
and mortality and adverse reactions. Notable recent examples include
pertussis and MMR vaccines. This can lead to impaired public health
control programmes reliant on high vaccine coverage rate. As vaccine-preventable
diseases become ever more rare in the public perception, for example
measles, the severity of tenuously associated adverse events and
syndromes arising from vaccine outweighs the spectre of the disease.
2. Will these problems be adequately addressed
by the government's recent infectious disease strategy Getting
Ahead of the Curve?
Yes, because if implemented as described, it
promises a more integrated strategy than that which exists at
present, with opportunity for this to be fully integrated across
A clear single point of accountability and responsibility
is promised, with opportunity for good inter-agency working and
fuller integration of services.
The Inspector of Microbiology concept is a commitment
to the implementation and continued review of common high quality
standard working practices across the HPA and allied service providers,
through effective introduction of standard operating procedures
and appropriate quality systems, including CPA.
The greater emphasis on surveillance builds
on the very considerable success of the PHLS Communicable Disease
Surveillance Centre and its regional surveillance networks. This
will drive improved diagnosis, treatment and service provision
across the HPA and NHS network.
As technological developments allow, there is
a clear intention to transfer rapid and sensitive microbiological
testing closer to the patient, with obvious advantage in timely
management of infectious disease (or indeed its exclusion). We
envisage the new diagnostic approaches being "rolled out"
from the reference and specialist laboratories and/or collaborating
centres, but always held under review by the HPA reference laboratories.
Getting Ahead of the Curve has a commitment
to vaccines, but it is less clear how new vaccines will be researched
and developed. We strongly support the development of a national
research & development strategy for health protection, as
proposed by the Chief Medical Officer. The proposed Health Protection
Agency will be well placed to assist the Department of Health
develop and implement such a strategy.
Furthermore, funding will be needed to:
improve surveillance of vaccine use;
raise public awareness of vaccine
efficacy and safety;
assess new vaccines for incorporation
into the UK immunisation schedule;
develop and assess new vaccines eg
for HIV disease, tuberculosis and Group B meningococcal disease;
develop and assess niche vaccines
for specific at-risk populations, eg travel-related infections,
cystic fibrosis patients;
develop and assess new vaccines eg
for HIV disease, tuberculosis and Group B meningococcal disease;
establish a core capability that
will ensure continued capability to respond to national emergency,
through the rapid development, manufacture and assessment of new
vaccines, including in response to bioterrorist threat.
3. Is the UK benefiting from advances in
surveillance and diagnostic technologies; if not, what are the
obstacles to doing so?
The HPA would facilitate a "national"
view of appropriate technologies and their implementation. While
this would minimise duplication of effort, we recognise that parallel
development is not in itself a bad thing and may assure faster
development and innovative approaches.
This would also allow "roll out" of
technologies nationwide from HPA reference and specialist laboratories
and collaborating centres through the regional network and further,
4. Should the UK make greater use of vaccines
to combat infection and what problems exist for developing new,
more effective or safer vaccines?
History has demonstrated that vaccination is
very effective in reducing the burden of infectious diseases.
There are however numerous challenges facing the introduction
of new vaccines:
An increasing trend towards the rights
of individuals (over a population benefit) means that an incidence
of side effects acceptable in the past is no longer acceptable,
and a higher level of safety has to be proven. This also leads
to a high (perceived) risk of litigation, which reduces the attractiveness
of vaccines as a business to industry.
The above, combined with increasing
costs of R&D and higher regulatory standards, means that the
costs of developing new vaccines are high, which inevitably leads
to high costs for the consumer (or health services).
To be cost-effective as a public health measure,
some vaccines need to effect "herd immunity" in which
transmission of infection is interrupted within the immunised
population and thus spares the un-vaccinated or ineffectively
vaccinated individuals. This requires continued surveillance to
ensure adequate immune coverage.
There is increasing recognition in the UK that
communication of risk-benefit of vaccines to both public and media
is critical to the continued success of public health policy.
The undoubted benefit of vaccination is being questioned increasingly
often in the UK (and in some other parts of the developed world)
and the spectrum of vaccine-related illness unsupported by objective
studies is growing. This parallels the recognition of similar
difficulties in communicating risk to the general public on food-related
illness, genetically-modified foods and nutrition, and the Food
Standards Agency is undertaking research in this area; there is
an opportunity to pool experience in this important area.
The historical high costs of vaccine R&D
and low returns are related to the low opportunity costs and the
considerable regulatory hurdles to the introduction of novel or
new formulations of vaccines. In contrast to medicines such as
antibiotics, vaccine safety is paramount as they are used on a
very large scale in an otherwise healthy general population and
often in paediatric populations. Proof of efficacy (Phase III
studies) for rare disease such as pertussis and meningococcal
disease require huge study populations for prolonged periods in
order to be adequately powered; for evaluation of competing candidate
vaccines this has very considerable logistic and cost implications
for the manufacturer and government.
New vaccine technologies, including the use
of DNA vaccines, live vectors, novel adjuvants, and novel routes
of vaccination, suffer from similar regulatory and cost hurdles,
in addition to the poor public perception of technologies such
as genetic manipulation of biologicals and medicines.
Thus vaccine R&D affords relatively low
incentive for industry (cost, liability, return) and argues for
more public sector investment. This has been particularly effective
in several European countries, notably the Netherlands and Finland.
Such Government funded operations must be seen to be separate
and distinct from Government regulatory assessment facilities,
such as NIBSC.
The DH has recognised that the UK population
is at risk from microbial hazards arising from the importation
of non-endemic infectious agents as a consequence of increasing
international leisure or business travel, via animal or other
natural vectors or through deliberate release by acts of bioterrorism.
Identified threat disease agents include: novel virulent influenza,
anthrax, plague, tularaemia, viral haemorrhagic fevers, pox viruses
(including smallpox), rickettsial diseases and multiple drug resistant
micro-organisms. Future threats, following successful global eradication,
will include polio and measles.
The rapid development and manufacture of vaccines
will form an important component of the Government's capability
to respond effectively to the threat posed by such infectious
diseases. This was recognised by the Parliamentary Under-Secretary
of State for Health, Yvette Cooper, in the House of Commons debate
on Vaccination Policy on 16 May 2002. The Minister said "Where
there is a military need, which is usually a low volume need,
or a requirement for capacity to respond rapidly, there remains
a need for the Government to fund research and development for
vaccines. We may need to respond, as we have in the past with
anthrax, to demand for vaccines".
In 1998, an outbreak of avian influenza (H5N1)
in Hong Kong presented a real threat of an influenza pandemic.
In response the DH funded a collaborative programme within which
CAMR successfully produced a bulk experimental vaccine for use
in a clinical trial to assess the immune response to the new,
virulent strain. This response was possible because of the fortunate
concomitant availability of high containment laboratory facilities,
rapid repair of key equipment, rapid development of key documentation
and the reassignment and training of skilled research and production
teams. This incident highlighted the need for the UK to have the
ability to respond rapidly to emergency microbiological threats
to the public health and CAMR's suitability to be the focus of
such effort. Whilst CAMR retains some of the skills necessary
for such an emergency response, the UK currently has no dedicated
and readily available capability to develop and supply experimental
vaccines for use in combating emergency microbial threats. This
national capability gap would be met by with a custom designed
Rapid Response Vaccine Facility (RRVF) sited at CAMR together
with focussed vaccine Research and Development programmes agreed
with the DH.
UK public sector science funding in vaccines
is focussed on research but much less supportive of vaccine development
and early Clinical Trial; this is often the block to the effective
evaluation of new vaccines in man. This "funding gap"
would argue for the establishment of a public sector vaccine development
fund to facilitate manufacture of GMP vaccines for Phase I and
II trials of promising vaccine candidates, determined by their
value to the UK public health, rather than as a pharmaceutical
5. Which infectious diseases pose the biggest
threats in the foreseeable future?
The major risk is from infectious diseases that
are transmissible from human to human. Particular examples of
such diseases are smallpox, measles and influenza, of which influenza
and measles present continuing threats. Although deemed by the
WHO as being eradicated, smallpox is currently seen as a major
potential bio-terrorism or biological warfare threat. Societal
changes, altered food processing and industrial practices may
also impact, TSE's and E.coli O157 are examples. In particular,
large scale industrialisation of food production and distribution
mean that introduction of a pathogen into the food supply chain
at an early point has the potential to affect a substantial number
Infectious disease threats may also result from
breakdown in living standards with deterioration of public and
environmental health and other controls; TSE's, tuberculosis,
HIV, MRSA and E.coli O157 are examples of the resulting microbial
Some diseases considered eradicated or controlled
may re-emerge if accompanied by a cessation or abuse of control
measures. Examples are tuberculosis, measles, poliomyelitis and
congenital rubella syndrome. An imminent challenge to health policy
is the eradication of poliomyelitis virus, and the decision on
whether to maintain routine immunisation. The impact of the spread
of resistance to anti-microbial drugs is exemplified by the real
threat posed in hospitals by MRSA.
Threats are also presented by zoonoses such
as pandemic influenza, bovine tuberculosis, paratuberculosis and
the spread of Salmonella enteritidis and E.coli O157 into the
Bio-terrorism is seen as presenting a real threat
to public health although the threat may be greater than the actual
likelihood or health impact. The actual extent of disease caused
by the anthrax letters in the USA was relatively low whereas the
societal and political impact was considerable. The range of potential
threat agents is extensive but the bio-warfare agents, anthrax,
botulism, smallpox and plague are on everyone's list. Vaccines
against these threat agents are either available or under development.
Many of the diseases mentioned above could have significant impact
if deliberately introduced into the community, particularly those
that would put the NHS services under pressure (influenza, diarrhoeal
6. What policy interventions would have greatest
impact on preventing outbreaks of and damage caused by infectious
disease in the UK?
By creating the framework for effective management
of the activities of the several bodies that have responsibility
for protecting the health of the public, the HPA represents a
significant policy development in the UK. A major challenge will
be to ensure effective liaison between the HPA and those responsible
bodies of close geographical neighbours, including the EC, since
infectious diseases are not likely to respect man made boundaries
(as witness the spread of FMDV).
Policies will need to be in place that encourage
and facilitate close co-operation with other national and international
bodies. In particular there will need to be compatibility of surveillance
systems, data collection and public health policies. Immunisation
and surveillance policies should be forward looking and progressive
across all agencies.
There should be a policy of active surveillance
for "exotic" diseases (such as Ebola and other viral
haemorrhagic fevers) and zoonotic disease agents (such as Dengue,
West Nile Fever etc). In particular policies need to consider
the impact on the spread of such diseases of human activity (business
and leisure travel, trade, societal and environmental change).
There should be policies for Public Sector research
and development vaccines, treatments and diagnostics reagents
and methods. In particular, there needs to be a recognition that
the risks in vaccine development render this unattractive to industry,
and public sector funding needs to be applied beyond the stages
of basic research and early development.
There should be a policy of proactive provision
of public information and communication of risk. The public trust
in science and government has been severely dented by issues such
as TSE's, E.coli O157 and FMDV. Without public confidence in the
information provided the reaction to a disease threat could exceed
the reality of the risk posed by that threat.
Above all, there should be a clear commitment
by government to investing in the nation's capability to respond
effectively to emergency microbial threats to public health. This
should include the provision of an adequate research and development
base for vaccines, risk assessment, detection and surveillance.
We strongly support the development of a national research and
development strategy for health protection, as proposed by the
Chief Medical Officer. The proposed Health Protection Agency will
be well placed to assist the Department of Health develop and
implement such a strategy.