Select Committee on Science and Technology Minutes of Evidence

Additional information from Professor Paul Little

  Regarding the response to Lord Turnberg's question: How the HPA would help me with my work?

  In my reply I will draw the distinction between the following terms:

    —  Passive microbiological surveillance; surveillance of samples sent according to clinical indication.

    —  Enhanced passive clinical surveillance; using existing sources of routine data (eg NHS direct, GPs' computerised data).

    —  Systematic microbiological surveillance; routine microbiological sampling from all patients presenting with clinical syndromes (and possibly from asymptomatic individuals).

  1.   The HPA should detect outbreaks (new symptom patterns, or severe illness with high morbidity/mortality) using enhanced passive clinical surveillance

  The HPA should make better use of using existing routine data sources is likely to be the most effective way to spot new outbreaks. NHS direct is a rich source of such information. Another option could also be better use of clinical data from GP systems, which could be downloaded anonymously each day.

  Wherever the data originates from, once a severe local problem is identified the data could be fed back quickly ie within 24-36 hours to the local CCDC who could then initiate targeted microbiological sampling if appropriate (eg to confirm that an outbreak of chest infection with high morbidity in a nursing home was influenza rather than Legionella, or to confirm an outbreak of food poisoning). The sampling could either use infection control nurses visiting sites and patients, or if appropriate selected local GP surgeries (eg asked to send stool sample for anyone presenting with diarrhoea for a 24 hour period).

  A few principles apply:

    (a)  Preferably use staff to collect samples that are not involved in routine clinical care (ie with their own dedicated resources, such as infection control nurses) given the stretched resources and low morale in primary care.

    (b)  If staff performing routine clinical care are involved (eg GPs practice nurses), then setting the threshold for action appropriately is very important; ie only feed back to GPs or practice nurses that they need to do something when a suitably high threshold is reached.

    (c)  Pilot the system before introducing it nationally so that lessons can be learnt.

    (d)  Provide adequate training if usual samples are required (eg nasopharyngeal swabs).

    (e)  Explain clearly the rationale for data collection (otherwise the system will fall into disrepute).

  2.  The HPA should use the cascade system, and enhance training, to increase clinical index of suspicion for exotic infections.

  GPs have a low index of suspicion for unusual infections. Where there is a real danger of a new illness for which GPs have a low clinical index of suspicion, the Health Protection Agency will need to liaise with GP tutors and CCDCs to ensure that training about these illnesses is provided for all GPs and practice nurses. This should be complemented by the cascade system: where there is information that a new infection is likely (eg intelligence about bio-terrorism, or outbreak of new disease in common travel destination) the cascade system needs to be activated with a succinct clinical description and advice about management and sampling (if appropriate).

  3.   The HPA should monitor antibiotic resistance use occasional systematic microbiological surveillance from selected practices (eg spotter practices)

  Antibiotic resistance is a major threat and there clearly needs to be a robust monitoring. The problem for clinicians is that if routine microbiological surveillance was increased greatly ie widespread systematic microbiological surveillance this would (a) incur greatly increased time costs of sampling in an already over-stretched service, and (b) would also create the perception to the public that they need to see the doctor to have sampling performed. This would medicalise acute self limiting illness, probably drawing more people into the system who would otherwise have happily managed their own acute illness, and arguably increase antibiotic prescribing overall. The information from routine microbiological surveillance may also not be terribly useful clinically. This is in part because the documentation of laboratory resistance does not mean there is a clinical problem (since most illnesses are self limiting). Also, even where there is an apparent clinical problem (eg slowly resolving infection) laboratory resistance does not mean that in practice the organism is resistant due to two factors (a) the accuracy of the test and (b) in vivo antibiotics may still reach concentrations, that mean that low/intermediate level of in vitro resistance is not relevant (eg high concentrations in the urine of trimethoprim may overcome low levels of resistance).

  Thus greatly increased routine systematic microbiological sampling to monitor antibiotic resistance would result in an expensive data collection exercise, creating the wrong message to the public, and would have limited utility for clinical practice. The vital public health information about trends in antibiotic resistance could much more efficiently be achieved using intermittent systematic microbiological sampling in "spotter" practices (eg in patients with suspected UTI sending all samples of urine for an MSU for three days twice each year). The only question is how many spotter practices and how often should routine sampling be performed. This should be determined by calculations of the precision of estimates required. If the spotter practice scheme is enhanced the system will need to be properly funded.

  4.   The Health Protection Agency needs to identify a dedicated stream of funding for research into the targeting of antibiotics

  Nobody doubts that antibiotic resistance is one of the major threats to public health. To tackle the issue and contain resistance we need to be able to selectively use antibiotics for those that will benefit, and avoid antibiotics for those that will not. It is a much greater and urgent priority to tackle this issue than to spend much more money on surveillance.

  Unfortunately, we do not know who benefits for any of the common acute infections: this evidence base is simply not there (I can provide more detail on this point if required). We have shown that currently GPs manage their uncertainty by using variable and ad hoc clinical and socio-demographic features to target prescribing. We need several pieces of evidence to rationalise prescribing and improve care to patients:

    (a)  Evidence of the validity of clinical scoring methods and of near patient tests

    (b)  Evidence that clinical scoring methods and near patient tests predict benefit from treatment (otherwise why use them)

    (c)  Evidence about who is at risk of severe complications or severe/prolonged symptoms

    (d)  Evidence about whether those at risk of severe complications or severe/prolonged symptoms benefit from antibiotics.

  Paragraphs (a) and (b) above require validation studies nested in large randomised trials, (c) and (d) require case control studies, cohort studies, and trials. This work is not expensive since it requires large studies with associated microbiology. Nevertheless, it would easily repay the taxpayer if it were performed, given the huge costs to the Nation of managing acute infections.

  The problem for gaining funding for this kind of straightforward applied clinical epidemiology is that in open competition with other priorities (eg cancer, heart disease, back pain, mental health etc) and other methodologies (eg laboratory science) it is difficult to persuade existing funders that this is a priority (acute infections are common, debilitating, and incur considerable costs to society, but for most people do not cause major morbidity or mortality). This is exacerbated by the fact that NHS regional R+D funding stream has been abolished, and the MRC is currently suffering cash flow problems.

  Thus the Health Protection Agency has an opportunity to provide a major service to clinical practice, to provide the key information, which will enable GPs to rationalise prescribing and contain antibiotic resistance. It will do so by providing a stream of funding to answer basic questions about the targeting of antibiotics.

  I hope these points are reasonably clear and I would be happy to provide clarification or amplification if required.

Paul Little

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