Select Committee on Science and Technology Written Evidence

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 the UK.

  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, as appropriate.

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 per se.

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 of people.

  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 threats.

  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 food chain.

  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 diseases).

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.

October 2002

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