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Food Standards Agency
Open Board – 15 November 2011
THE SECOND STUDY OF INFECTIOUS INTESTINAL DISEASE IN
THE COMMUNITY (IID2 STUDY)
Report by: Alison Gleadle, Director of Food Safety Group
Andrew Wadge, Chief Scientist
1
SUMMARY
1.1 This information paper provides an update to the Board on the findings of the
second study of infectious intestinal disease in the community (IID2 study).
This study was undertaken to estimate the incidence of IID in the UK, to
identify the main microorganisms which cause IID and to determine whether
the burden of IID has changed since a similar study was carried out in the mid1990s.
1.2 The findings indicate that the burden of IID in the UK is substantial with an
estimated 17 million cases per year resulting in 11 million days lost due to
illness. Enteric viruses (norovirus, sapovirus and rotavirus) were the main
causes of IID illness in the UK. Campylobacter was found to be the most
common bacterial cause of IID in the UK. The FSA has funded new research
which will use the IID2 findings, as well as outbreak and surveillance data, to
estimate the burden of foodborne disease in the UK. This work will be
completed in 2012.
1.3 The Board is asked to:
note the key findings of the IID2 study, and
note that further work is being undertaken, as part of an extension to the
IID2 study, to establish the burden of foodborne disease in the UK. This
work will be completed in 2012.
2
INTRODUCTION
2.1 Infectious intestinal disease (IID) is a subset of gastroenteritis and is caused
by a range of infectious microorganisms such as bacteria (e.g. Campylobacter
and Salmonella), viruses (e.g. norovirus and rotavirus) and parasites (e.g.
Cryptosporidium). Symptoms of IID in otherwise healthy individuals are
diarrhoea or vomiting or a combination of the two. There are a range of other
conditions which may present with symptoms of diarrhoea and vomiting but do
not involve an infectious cause and therefore are not IID. This would include
Irritable Bowel Syndrome, food intolerance, pregnancy and alcohol. There
may be additional symptoms associated with IID, such as fever, but usually
the illness is short lived (typically one or two weeks) and usually resolves
completely, although in some circumstances it can lead to long term chronic
illness such as reactive arthritis and Guillain-Barré syndrome. A large
proportion of IID is preventable by employing good personal hygiene and food
hygiene measures.
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2.2 The public health impact of IID was underlined by the publication of the
Department of Health (DH) funded IID study in England in the mid 90‟s which
was published by the Food Standards Agency (FSA) in 2000. At the time the
study estimated that 20% of the population of England suffered from IID in a
year, which is equivalent to 9.5 million cases. Not all cases of IID in the
community are captured by national surveillance for a variety of reason such
as people with IID not visiting their GPs, stool samples not being taken and
when they are not being able to identify a microbiological cause. The IID1
study estimated the contribution that each of these stages makes to underreporting to national surveillance so that a “true” level of IID in the community
could be calculated (i.e. to estimate cases that are truly in the community for
every case reported). The IID1 findings were also used, in part, to estimate
the burden of foodborne disease which has been key to FSA work in this area.
2.3 Since that study, a number of changes have occurred in national surveillance
systems which may have altered the relationship between the burden of IID in
the community and that reported in official statistics. To address this issue, in
2006 the FSA commissioned a second study of infectious intestinal disease in
the community (IID2 study).
2.4 The purpose of the IID2 study was to provide up-to-date data on the incidence
of IID in the UK, identify the microorganisms causing illness and whether the
incidence has changed since IID1 study was carried out in the mid-1990s.
The IID2 study also compared the incidence of IID reported in IID2 with that
reported to national surveillance systems to get a “true” picture of the level of
IID experienced by people in the UK, as it is widely accepted that there is
significant under-reporting of IID cases in the UK. The study was carried out
by a group of organisations, led by the University of Manchester, and was
funded by the FSA with contributions from DH and NHS.
2.5 This study reports on all IID, not just that transmitted by food. Only a
proportion of IID is transmitted by food, with other significant transmission
routes including person-to-person, direct animal-to-person contact, water and
environment contact. The IID2 study was not designed to determine the
proportion of IID which is foodborne.
3
STRATEGIC AIMS
3.1 The IID2 findings will be used together with other data, to provide estimates of
the foodborne disease burden in the UK which are necessary for monitoring
progress against our strategic objective of reducing foodborne disease in the
UK. The results are also useful in prioritising future work (i.e. microorganisms)
for improving microbiological food safety along the food chain. The findings
will also inform the continuing development, implementation and evaluation of
the Foodborne Disease Strategy (FDS) for 2010-15. It is clear from the
findings of the study that the high priority given to Campylobacter and
norovirus in the FDS 2010-15 is justified.
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4
DISCUSSION ON THE FINDINGS OF THE IID2 STUDY
4.1 The IID2 study was a complex study, which was carried out between April
2006 and July 2010. It involved seven separate but related studies which
included:
a Prospective Population-Based Cohort study, involving 6,836 people
recruited from 88 General Practices across the UK;
a General Practice (GP) Presentation study, which involved obtaining
samples for laboratory testing from everyone who consulted their
healthcare team with symptoms of diarrhoea and/or vomiting in 37
practices across the UK;
a GP Validation study, auditing the recruitment of the 37 practices in the
GP Presentation study;
a GP Enumeration Study, involving 40 practices in which Study Nurses
searched practice records for patients presenting with an episode of IID.
a Microbiology Study whereby stool samples from the Cohort and GP
Presentation Studies were examined using state-of-the-art diagnostic
methods;
a National Reporting Study to compare the incidence estimates from the
other studies with those generated from national surveillance, and
a retrospective Telephone Survey of self-reported illness, involving 14,726
people across the UK.
4.2 The findings of the IID2 study indicate that the burden of IID in the community
is significant with up to 17 million cases annually in the UK leading to 11
million working days lost. For every case of IID in the UK reported to national
surveillance there are around 147 cases in the community.
The
microorganisms most often associated with illness were norovirus, sapovirus,
Campylobacter spp. and rotavirus1.
4.3 Since IID1 was only carried out in England comparison with IID2 can only be
made using the IID2 data from England. The rate of IID in the community in
England was 43% higher in 2008-2009 (IID2) than in 1993-1996 (IID1), whilst
the number of people visiting their GP about IID was 50% lower. The survey
was not designed to determine the reasons for this but it was noted that the
study coincided with the emergence of a new strain of sapovirus in the UK
which might explain at least part of the increase in IID incidence seen in the
IID2 study when compared to the first study. The data also indicates that the
introduction of NHS Direct/NHS24 does not account for why less people with
IID are visiting their GPs. A list of the key findings and FSA news story on the
IID2 study has been provided in Annex 2 and 3. A copy of the paper
published in „Gut‟ is provided in Annex 4.
4.4 The data from the telephone survey, which was powered to determine
difference in IID rates by country, indicated that there was variation in the
estimates by country but these differences were not significantly different.
1
Sapovirus and rotavirus are primarily transmitted via person-to-person. These microorganisms
are not considered to be major causes of foodborne disease.
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5
IMPACT
5.1 IID results in a substantial burden on public health in the UK and has
implications for both the Agency and others working in the wider public health
field. The burden of IID is also likely to have significant economic impact both
in terms of cost to healthcare and potential loss of working days (over 11
million working days lost due to IID).
6
CONSULTATION
6.1 The IID2 final report has been peer-reviewed by external independent experts
in accordance with the FSA‟s good practice and science guidelines. The IID2
findings have also been presented to the Advisory Committee on the
Microbiological Safety of Food (ACMSF).
7
SUSTAINABILITY ISSUES
7.1 The findings will enable the FSA to monitor foodborne disease in the UK, to
identify the microorganisms of greatest significance to public health and target
our foodborne disease strategy on reducing these microorganisms in the
foodchain. This may indirectly lead to a reduction in foodborne disease in the
UK and a subsequent reduction in costs to the economy through a decrease in
number of working days lost and in hospital admissions. This will allow the
FSA to effectively and more efficiently focus resources on our foodborne
disease strategy with the aim of reducing pathogenic microorganisms in the
foodchain.
8.
CONCLUSION AND RECOMENDATIONS
8.1 This paper is provided for information only. An update paper will be provided
in 2012.
For further information, please contact:
Paul Cook (Tel: 0207 276 8950; Email: [email protected])
Bobby Kainth (Tel: 0207 276 8958; Email: [email protected]).
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ANNEXE 1
GLOSSARY
Community is a group of individuals organised into a unit, or manifesting some
unifying trait or common interest; loosely, the locality or catchment area population,
for which a service is provided, or more broadly, the state, nation or body politic.
For the purpose of the IID2 study the community is discussed in terms of the UK
population and excludes hospital-acquired infections.
Disease burden is the impact of a health problem in an area measured by financial
cost, mortality, morbidity, or other indicators.
Enteric viruses are a class of viruses that are acquired by ingestion and replicate
in the intestinal tract causing local rather than generalised infection.
Guillain-Barré syndrome is a disorder affecting the peripheral nervous system.
Ascending paralysis, weakness beginning in the feet and hands and migrating
towards the trunk, is the most typical symptom. It can cause life-threatening
complications, particularly if the breathing muscles are affected or if there is
dysfunction of the autonomic nervous system. The disease is usually triggered by
an acute infection. Guillain-Barré syndrome is a form of peripheral neuropathy.
Reactive arthritis (commonly known as Reiter's syndrome) is classified as an
autoimmune condition that develops in response to an infection in another part of
the body. Coming into contact with bacteria and developing an infection can trigger
the disease. Reiter's syndrome has symptoms similar to various other conditions
collectively known as “arthritis”. By the time the patient presents with symptoms,
often time the "trigger" infection has been cured or is in remission in chronic cases,
thus making determination of the initial cause difficult.
Under-reporting occurs because all cases of IID in the community are not officially
recorded/captured by national surveillance. The reasons for under-reporting are
complex, but can be due to a number of reasons:
The person has IID but symptoms are mild and therefore they do not consult
their GPs or seek advice from health professionals
The person has IID symptoms and consults NHS Direct/NHS24 rather than
contacting their GP
The person has IID symptoms and goes to see their GP, but does not have a
stool sample taken to test
The person has IID symptoms, goes to see their GP, has a sample taken to
be tested, but the sample is negative i.e. no organism is identified
The person has IID symptoms, goes to see their GP, has a sample taken to
be tested, but the sample is positive (i.e. a organism is identified) but he
result is not reported to official statistics
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ANNEXE 2
KEY FINDINGS OF THE SECOND STUDY OF INFECTIOUS
INTESTINAL DISEASE IN THE COMMUNITY (IID2 STUDY)
The key findings of the IID2 study are provided below:
UK situation
The incidence of IID in the community in the UK was substantial, with around 1
in 4 of the population suffering from an episode of IID in a year – up to 17
million cases annually. Around 2% of the population visit their GP with
symptoms of IID each year – an estimated 1 million consultations annually.
Approximately 50% of people with IID reported absence from school or work
because of their symptoms. The University of Manchester has calculated that
this represents in nearly 19 million days lost (over 11 million days lost in people
of working age).
The most commonly identified microorganisms found in stool samples from
those with IID in the community were norovirus (16.5%), sapovirus (9.2%),
Campylobacter spp. (4.6%) and rotavirus (4.1%).
The most commonly identified microorganisms found in stool samples from
those with IID presenting to GPs were norovirus (12.4%), Campylobacter spp.
(13%), sapovirus (8.8%) and rotavirus (7.3%).
For every case of IID in the UK reported to national surveillance there were
around 10 GP consultations and 147 cases in the community.
Only 1 specimen tested positive for Clostridium difficile (<1%), suggesting that
this microorganism, which is usually associated with healthcare settings, is not
found very often in the community at large.
Situation in England in 2008-09 compared with the mid-1990s
The rate of IID in the community in England was 43% higher in 2008-2009
(IID2) than in 1993-1996 (IID1), whilst the number of people visiting their GP
about IID was 50% lower2.
Reporting of IID to national statistics had improved for those presenting to their
GP with symptoms, suggesting that GPs are more likely to take a stool sample
and/or there have been improvements in recording episodes of IID for those
using primary healthcare services. However, fewer people are visiting their GP
when they have an episode of IID. Therefore more cases in the community now
go unrecognised and, therefore, unreported.
A very small proportion of people with IID (~2%) contacted NHS Direct. Contact
with NHS Direct was insufficient to account for the observed drop in rates of
consultation to general practice.
The rates of IID estimated from a telephone survey of self-reported illness were
between 2 and 5 times higher than the rates in the Cohort Study depending on
2
The reasons for the increase in incidence rate of IID in England and why people suffering from IID
are not consulting their GPs cannot be determined from the IID2 study as it was beyond the scope
of the work. This may be an area that warrants further investigation.
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the length of recall (28-days or 7-days respectively). Data from the other
studies in the project and from external sources3 suggest the Cohort Study
provided more reliable estimates and so this was used to determine IID rates in
the community.
3
Royal College of General Practitioners (RCGP) Weekly Returns Service
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ANNEXE 3
FSA NEWS STORY ON THE SECOND STUDY OF INFECTIOUS
INTESTINAL DISEASE IN THE COMMUNITY (IID2 STUDY)
Provided below is a copy of the FSA news story which was published on the Food
Standards Agency website (www.food.gov.uk) on Tuesday 6th September 2011.
Upset stomachs cost UK 11 million working days
Tuesday 6 September 2011
Nearly 17 million people suffer from stomach upsets in the UK every year, leading to about 11 million lost
working days, new research published today by the Food Standards Agency (FSA) has found.
„We are also funding research on norovirus, which was identified as one of the most common causes of
illness.‟
The study, which is the biggest of its kind for more than 10 years, looked at the impact of all cases of infectious
intestinal disease (IID), not just those linked to food, on the UK population. IID is typically vomiting or diarrhoea,
or a combination of the two. The research was carried out by a group of organisations led by the University of
Manchester.
Key findings
The research found:
There are up to 17 million cases of IID annually, which is the equivalent of one in four people becoming ill
during the year.
Approximately 50% of people with IID took time off from work or school because of their symptoms. The
University of Manchester has calculated that this represents nearly 19 million days lost – more than 11
million of these were in people of working age.
For every case of IID recorded in national surveillance there are 147 that are unreported.
Viruses, particularly norovirus, and the bacteria campylobacter are the most common causes of IID.
Norovirus was identified as the largest cause of IID in the UK. Although many norovirus infections are spread by
person-to-person transmission, it does have the potential to cause foodborne disease and is included in the
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Agency‟s Foodborne Disease Strategy 2010–2015.
The study also shows that campylobacter was the main cause of bacterial IID in the UK, which emphasises the
need to reduce the high levels found on raw poultry in the UK. Campylobacter is estimated to cause about
500,000 cases of illness in the UK every year. It is mainly found on raw poultry, and a recent survey by the FSA
found that two thirds of chicken samples on sale within the UK were contaminated with the bacteria.
In comparison with a similar study carried out in England in the mid 1990s, the findings show the rate of IID in
England is now 43% higher, although fewer people are now visiting their GPs. Based on other studies, it is likely
that the majority of IID is not foodborne.
Andrew Wadge, Chief Scientist at the FSA, said: „This new study is very important as it gives us a more
accurate picture of the impact of IID on the UK population.
„The study shows the FSA is correct to make campylobacter a key priority in its strategic plan. We know that
levels of campylobacter on chicken are far too high in the UK, which is why we are working closely with the food
industry to bring these levels down. We are also funding research on norovirus, which was identified as one of
the most common causes of illness.
„This study has confirmed that the burden of IID is substantial in the UK. However, a large proportion of the
illnesses reported can be prevented by adopting good basic hygiene. The FSA‟s advice on preparation and
handling of food will help to minimise the risk from bacteria and viruses linked to food.‟
Professor Sarah O‟Brien, the study‟s lead researcher from the University of Manchester, said: „It‟s easy to
dismiss diarrhoea and vomiting as a trivial illness, but this study reinforces just how many people‟s lives are
affected, and shows the impact it can have on health services and the wider economy. Our research confirms
that public health policy should continue to be directed at preventing diarrhoea and vomiting by promoting good
personal and food hygiene.‟
More about the research
Official statistics only record a fraction of IID cases reported to healthcare services and many cases also go
unreported as people recover without seeking medical help. This new study recruited individuals from general
practices throughout the UK to participate in study. The data, generated from symptom questionnaires,
interviews and clinical analysis, was used alongside official statistics to estimate the true incidence of IID in the
UK.
The findings will help the FSA and other government departments with their work to reduce levels of IID in the
UK. They will also be used to monitor the patterns of IID in the population, identify the microorganisms of
greatest significance to public health, and target interventions for reducing these germs in the food chain.
A copy of the full report can be found at the link below.
Related links
B18021: The second study of infectious intestinal disease in the community (IID2)
Read about the Agency's study
See also
A UK survey of campylobacter and salmonella contamination of fresh chicken at retail
sale
Foodborne disease strategy More about the strategy to reduce foodborne disease
Infectious Intestinal Disease study
NHS Choices: Preparing food safely NHS Choices website
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ANNEXE 4
IID2 STUDY PAPER PUBLISHED IN ‘GUT’
10
Downloaded from gut.bmj.com on July 12, 2011 - Published by group.bmj.com
Gut Online First, published on July 5, 2011 as 10.1136/gut.2011.238386
Paper
Longitudinal study of infectious intestinal disease in
the UK (IID2 study): incidence in the community and
presenting to general practice
Clarence C Tam,1 Laura C Rodrigues,1 Laura Viviani,1 Julie P Dodds,2
Meirion R Evans,3 Paul R Hunter,4 Jim J Gray,5 Louise H Letley,2 Greta Rait,2
David S Tompkins,6 Sarah J O’Brien,7 On behalf of the IID2 Study Executive
Committee*
< An additional appendix is
published online only. To view
this file please visit the journal
online (http://gut.bmj.com).
For numbered affiliations see
end of article.
Correspondence to
Dr Clarence C Tam, Department
of Infectious Disease
Epidemiology, Faculty of
Epidemiology and Population
Health, London School of
Hygiene & Tropical Medicine,
London WC1E 7HT, UK;
[email protected]
Data from the IID2 study will be
archived and made available
publicly in due course.
*Members are: Bob Adak, Eric
Bolton, Paul Cook (Chair), John
Cowden, Meirion Evans, Jim
Gray, Paul Hunter, Louise Letley,
Jim McLauchlin, Keith Neal,
Sarah O’Brien, Greta Rait, Laura
Rodrigues, Gillian Smith, Brian
Smyth and David Tompkins.
Revised 23 May 2011
Accepted 25 May 2011
ABSTRACT
Objectives To estimate, overall and by organism, the
incidence of infectious intestinal disease (IID) in the
community, presenting to general practice (GP) and
reported to national surveillance.
Design Prospective, community cohort study and
prospective study of GP presentation conducted
between April 2008 and August 2009.
Setting Eighty-eight GPs across the UK recruited from
the Medical Research Council General Practice Research
Framework and the Primary Care Research Networks.
Participants 6836 participants registered with the 88
participating practices in the community study; 991
patients with UK-acquired IID presenting to one of 37
practices taking part in the GP presentation study.
Main outcome measures IID rates in the community,
presenting to GP and reported to national surveillance,
overall and by organism; annual IID cases and GP
consultations by organism.
Results The overall rate of IID in the community was
274 cases per 1000 person-years (95% CI 254 to 296);
the rate of GP consultations was 17.7 per 1000 personyears (95% CI 14.4 to 21.8). There were 147 community
cases and 10 GP consultations for every case reported to
national surveillance. Norovirus was the most common
organism, with incidence rates of 47 community cases
per 1000 person-years and 2.1 GP consultations per
1000 person-years. Campylobacter was the most
common bacterial pathogen, with a rate of 9.3 cases per
1000 person-years in the community, and 1.3 GP
consultations per 1000 person-years. We estimate that
there are up to 17 million sporadic, community cases of
IID and 1 million GP consultations annually in the UK.
Of these, norovirus accounts for 3 million cases and
130 000 GP consultations, and Campylobacter is
responsible for 500 000 cases and 80 000 GP
consultations.
Conclusions IID poses a substantial community and
healthcare burden in the UK. Control efforts must focus
particularly on reducing the burden due to Campylobacter
and enteric viruses.
BACKGROUND
This paper is freely available
online under the BMJ Journals
unlocked scheme, see http://
gut.bmj.com/site/about/
unlocked.xhtml
The Health Protection Agency recorded 49 880
laboratory-confirmed cases of infectious intestinal
disease (IID) due to Campylobacter and 9885 cases of
non-typhoidal salmonellosis in England and Wales
Significance of this study
What is already known about this subject?
< Infectious intestinal disease (IID) is a common
cause of illness in the community and results in
a high burden of consultations to general
practice (GP).
< Most cases of IID are not reported to national
surveillance systems, making it difficult to
determine the true burden in the population.
< Recent interventions and changes in healthcare
delivery may have resulted in changes in
disease burden in the community and presenting
to primary care; population-based studies are
needed to monitor such changes.
What are the new findings?
< In the UK, there are up to 17 million cases and 1
million GP consultations due to IID every year.
IID incidence in the community
appears to have increased since the 1990s,
consultations to GP have halved.
< Norovirus is the most common recognised
cause of IID, accounting for 3 million cases
and 130 000 GP consultations annually, while
Clostridium difficile, an important pathogen in
healthcare settings, is a rare cause of diarrhoea
in the community.
< Although
How might it impact on clinical practice in the
foreseeable future?
< Use of recently introduced telephone advice
services such as NHS Direct is relatively low
and has little impact on the burden of GP
consultations for IID. Instead, changes in healthcare use are likely to be behind the decreasing
trend in IID-related GP consultations.
in 20081 2; rotavirus and norovirus accounted for
13 935 and 6828 reports, respectively.3 4 Most IID is
self-limiting, requiring no clinical intervention, but
commonly causes high levels of healthcare usage
and absenteeism.5 Organisms such as verocytotoxin-producing Escherichia coli (VTEC) and
Campylobacter are also associated with long-term,
potentially fatal sequelae, including haemolytic
uraemic syndrome6 and GuillaineBarré syndrome.7
Tam CC, Rodrigues
LC, Viviani
L, et (or
al. Gut
(2011).employer)
doi:10.1136/gut.2011.238386
1 of 9
Copyright
Article
author
their
2011. Produced by BMJ Publishing Group Ltd (& BSG) under licence.
Downloaded from gut.bmj.com on July 12, 2011 - Published by group.bmj.com
Paper
National statistics underestimate the incidence, because only
a fraction of IID presents to health services, and many
presenting cases are not investigated further. Reported cases are
not a random subset of all cases, as seeking healthcare is related
to greater disease severity, recent foreign travel and lower
socioeconomic status.8 National statistics can be useful for
monitoring trends, but difficult to interpret if there are secular
changes in healthcare-seeking behaviour, faecal sampling,
diagnostic procedures or surveillance methods. Evaluating
control strategies requires accurately estimating population
burden and understanding the relationship between national
statistics and disease incidence.
In its first 5 years of operation the UK, Food Standards Agency
was tasked with reducing food-borne illness by 20%.9 The
Second Study of IID in the UK (IID2 Study) was commissioned
to assess progress towards this target and determine whether
changes in healthcare provision might influence the
interpretation of national statistics.
We present results from the IID2 Study, a multicentre longitudinal study to estimate the current incidence of IID in the
community, presenting to general practice (GP) and reported to
national surveillance.
computerised practice records monthly, using a predefined list of
diagnostic Read codes,11 to identify all IID-related consultations.
National surveillance study
We obtained records of IID cases reported in each UK country
over the study period, by organism, from the UK national
surveillance centres. Data on sapovirus and non-O157 VTEC
were not available, because they are not routinely reported. We
excluded national C difficile reports because these are mostly
from healthcare settings rather than the community.
NHS direct usage
We obtained the number of telephone consultations to NHS
Direct (England only) for diarrhoea and vomiting during the
study period from the Health Protection Agency Birmingham
Regional Surveillance Unit.
Ethics approval
All participants gave signed, informed consent. The North West
Research Ethics Committee granted a favourable ethics opinion
(07/MRE08/5), and 37 NHS Research Management and Governance organisations for the 88 practices approved the study.
METHODS
Case definitions
The IID2 Study methods are detailed elsewhere.10 Briefly, we
conducted the study between 28 April 2008 and 31 August
2009 in a population of 800 000 people served by 88 UK GPs.
We recruited practices from the Medical Research Council
General Practice Research Framework and Primary Care
Research Networks in England, Northern Ireland and Scotland.
The number of practices in the four UK countries was
proportional to population size. The study comprised a population cohort, a GP presentation study and a national surveillance study.
Definite IID was defined as loose stools or clinically significant
vomiting lasting less than 2 weeks, in the absence of a known
non-infectious cause, preceded by a symptom-free period of
3 weeks. Vomiting was clinically significant if it occurred more
than once in a 24 h period and if it incapacitated the patient or
was accompanied by other symptoms such as cramps or
fever.10 12 Symptomatic people not meeting the case definition
because they did not provide a questionnaire or because
symptom information was missing were considered possible
IID cases. Cases in which the patient reported travel outside
the UK in the 10 days before illness onset were excluded.
Population cohort study
We followed up participants from 88 practices weekly for
symptoms of diarrhoea and/or vomiting for up to 52 weeks,
recruiting throughout the study period. From each practice list,
we invited randomly selected individuals to a recruitment
interview with the practice study nurse. People were eligible if
they did not have: a terminal illness or severe mental incapacity;
a recognised, non-infectious cause of diarrhoea or vomiting
(precluding determination of onset date and infectious
aetiology), such as Crohn’s disease, ulcerative colitis, cystic
fibrosis or coeliac disease; or a surgical obstruction. Non-English
speakers were also excluded.
We asked participants to report weekly, by email or prepaid
postcard, whether or not they had experienced diarrhoea and/or
vomiting. We asked those reporting symptoms to complete
a case questionnaire, enquiring about type and duration of
symptoms, healthcare usage and recent travel, and to submit
a stool specimen for microbiological examination. We asked
them not to report symptoms related to excess alcohol, morning
sickness or, among infants, regurgitation.
GP presentation study
In 37 of the 88 participating practices, we asked GPs to refer to
the study nurse all patients presenting with IID. The nurse
administered a case questionnaire and requested a stool
specimen. To assess the degree of under-ascertainment of IID
cases in this study (ie, the proportion of all IID cases actually
referred and recruited to the study), study nurses searched the
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Microbiological analysis
First, all stool samples were cultured for Campylobacter jejuni/coli,
E coli O157, Listeria monocytogenes, Salmonella spp., Shigella spp.
and Yersinia spp. They were also examined by ELISA for Clostridium perfringens enterotoxin, C difficile cytotoxins A and B,
Cryptosporidium and Giardia, by a commercial PCR test
(Cepheid) for C difficile, and by light microscopic examination of
a stained smear for Cyclospora and Cryptosporidium. Samples that
were immunoassay positive for C difficile toxin or PCR-positive
were cultured using National Standard Method BSOP 10, and all
isolates were ribotyped.13 Samples from children under 5 years
were examined for rotavirus and adenovirus 40/41 by
immunoassay.
Next, two nucleic acid extracts were prepared from each stool
sample.14e16 Each extract was examined by real-time PCR for C
jejuni, C coli, L monocytogenes, Salmonella spp., rotavirus, norovirus, sapovirus, adenovirus, astrovirus, Cryptosporidium, Giardia
and E coli (enteroaggregative and VTEC (genes encoding VT1
and VT2)).
Further information on microbiological methods has been
published elsewhere.10 For quantitative PCR assays, a cycle
threshold value <40 was considered positive for most organisms,
with two exceptions: a cycle threshold cut-off value <30 was
used to define clinically significant norovirus and rotavirus
infection.17 18
In this study, C difficile-associated diarrhoea (CDAD) was
defined as symptoms of diarrhoea not attributable to another
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cause (ie, in the absence of other enteropathogens), but with
a positive C difficile toxin assay, in a patient aged >2 years.19
Data analysis
We calculated incidence rates of IID with 95% CIs, overall and
by organism. In the cohort study, the denominator was the total
person-years at risk among cohort participants. Individuals
could contribute multiple episodes of illness. We omitted the
first 3 weeks of follow-up to exclude prevalent cases. Participants
were followed-up until the 52nd week, or 31 August 2009, or
until they dropped out or withdrew for other reasons, whichever
occurred earliest. People were ‘dropped out’ after four consecutive non-response weeks.
In the GP presentation study, the denominator in each practice was the practice population on 31 December 2008
multiplied by the time the practice was in the study. For the
national surveillance component, the denominator was the UK
midyear population at the 2001 census. For the NHS Direct
component, the mid-2001 England population was used.
obtained from the model as under-ascertainment factors in the
incidence calculations.
CIs accounted for clustering of observations within individuals (cohort study) and within practices (GP presentation
study).
Imputation of specimen data
We used multiple imputation by chained equations20 to account
for missing organism data in participants who did not submit
a specimen. We developed separate imputation models for cases
in the cohort and GP presentation studies. For each organism,
the imputation model included age group, sex and presence or
absence of five symptoms (diarrhoea, bloody diarrhoea,
vomiting, abdominal pain and fever) as covariates. Overall, we
imputed values for 35% of records in the cohort study and 11%
of records in the GP presentation study. We combined results
from analysis of 20 imputed datasets to produce a point
estimate for the rate and 95% CI, accounting for uncertainty in
the observed rate and the imputation process.
Reporting ratios
Statistical adjustments
We standardised rates in the cohort study to the UK census age
and sex population structure. We adjusted rates in the GP
presentation study by an under-ascertainment factor representing the ratio of all cases identified in the practice records to
actual cases recruited. We obtained the under-ascertainment
factors from a two-level logistic regression model using age
group, sex, Read code category, and a random intercept for GP
practice to predict the probability of a case being recruited. We
grouped the Read codes assigned to each consultation into seven
categories: diarrhoea; vomiting; diarrhoea and vomiting;
gastroenteritis; organism-specific codes; codes indicating that
a stool sample was sent for analysis; and codes for symptoms
compatible with IID, for example, ‘gastrointestinal symptoms’.
We used the inverse of the predicted ascertainment probabilities
We calculated rate ratios comparing rates in the community,
presenting to the GP and reported to national surveillance. We
assumed that the rates came from a log-normal distribution
with the observed mean and SD. The rate ratios were estimated
by simulating 100 000 random draws from each pair of rate
distributions. We took the median, 2.5th and 97.5th centiles of
the resulting RR distribution as the point estimate and lower
and upper 95% confidence limits.
Finally, we applied the estimated rates to the mid-2009 UK
population estimate to calculate the annual number of cases and
GP consultations associated with each organism.
Multiple imputation was conducted in R 2.11. Analysis of
under-ascertainment and analysis of imputed data were
performed using the glamm21 and mi22 modules in Stata V.11,
respectively.
Figure 1 Recruitment in the cohort
study, Infectious Intestinal Disease 2
Study, UK 2008e9.
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RESULTS
Participation
Of 77 995 people invited in the cohort study, 8336 (10.5%)
responded positively and 7033 were recruited (9.0%) (figure 1).
Some people recruited near the study end date had no eligible
follow-up time (n¼184), and two people withdrew consent. We
analysed data from 6836 participants. Compared with the 2001
census population, cohort participants were more likely to be
older, female, employed in managerial and professional occupations, less deprived and in rural areas (online appendix 1). The
median follow-up duration was 39 weeks (IQR 27e45 weeks);
overall, 86% of the maximum achievable follow-up time to 31
August 2009 was completed. Six hundred and ten (9.5%)
participants dropped out, accounting for 219 (4.5%) lost personyears of follow-up.
In the GP presentation study, 2233 eligible symptomatic
patients were referred and 2203 invited to participate. A total of
1392 people (63.2%) responded positively, and 1254 (56.9%)
were recruited (figure 2). We excluded 140 people reporting
recent foreign travel, 77 with illness lasting over 2 weeks, and 46
because of missing or inconsistent information on symptoms
and/or travel. Ultimately, we analysed data from 991 cases.
Rate of overall IID
There were 4658 person-years of follow-up and 1201 definite IID
cases in the cohort. The crude IID incidence rate was 258 cases
per 1000 person-years. The age- and sex-standardised rate was
274 cases per 1000 person-years (95% CI 254 to 296). When both
definite and possible cases were considered, this rose to 523 cases
per 1000 person-years (95% CI 497 to 551). There was little
evidence that rates varied by socioeconomic characteristics or
between urban and rural areas (data not shown).
In the under-ascertainment analysis, approximately one case
was recruited into the GP presentation study for every six
identified in the medical records, although this varied by age
group, Read code category and practice. After adjustment for
under-ascertainment, there were 5546 IID cases and 312 232
person-years of follow-up, yielding a consultation rate of 17.7
per 1000 person-years (95% CI 14.4 to 21.8). This was lower
than that estimated from definite cases in the cohort who
reported consulting their GP for their illness (25.3 cases per 1000
person-years, 95% CI 20.7 to 31.3). The age-specific rates of GP
consultation in the two studies were similar except for young
children and older adults (figure 3). Among children <5 years,
the rate was 133 consultations per 1000 person-years in the
cohort study (95% CI 92 to 199) and 85 consultations per 1000
person-years in the GP presentation study (95% CI 59 to 122),
while among those aged 65 and over, the corresponding rates
were 30 consultations per 1000 person-years (95% CI 22 to 42)
and 20 consultations per 1000 person-years (95% CI 15 to 27),
respectively.
Call rates to NHS Direct in England for diarrhoea and
vomiting were 6.1 per 1000 person-years, similar to that estimated from cohort study patients in England who reported
contacting NHS Direct for their illness (5.5 per 1000 personyears, 95% CI 3.4 to 9.5).
Rates of IID by organism
Rates of IID by organism in the community, presenting to the
GP and reported to national surveillance are shown in table 1.
For organisms tested by more than one method, rate estimates
are presented separately for routine diagnostic methods and for
routine and PCR methods combined.
Rates in the community
Viruses predominated among IID cases in the community: the
estimated rates (cases per 1000 person-years) were 47 for norovirus, 26 for sapovirus, 13 for rotavirus and 10 for adenovirus.
The most common bacteria were Campylobacter (11 cases per
1000 person-years) and enteroaggregative E coli (six cases per
1000 person-years). The Salmonella rate was less than one case
per 1000 person-years. Based on ELISA, Cryptosporidium and
Giardia rates were around one case per 1000 person-years,
although PCR-based estimates were slightly higher.
E coli O157 was present in only one sample, and there were no
cases of CDAD or L monocytogenes IID in the community cohort.
GP presentation rates
Norovirus was the most common organism among cases
presenting to the GP (two consultations per 1000 person-years
(table 1)); approximately one in every 23 people with norovirus
IID consulted a GP. Rotavirus and sapovirus were also common
(w1.5 consultations per 1000 person-years). One in seven
patients with campylobacteriosis consulted their GP, resulting in
approximately one consultation per 1000 person-years based on
culture diagnostics. Other organisms occurred at rates of less
than one consultation per 1000 person-years. Salmonellosis was
uncommon (<0.2 consultations per 1000 person-years),
although one in three patients consulted their GP.
Only one case of CDAD occurred in the GP presentation
study, and no cases of L monocytogenes IID were identified.
Ratios to national surveillance
Figure 2 Recruitment in the general practice presentation study,
Infectious Intestinal Disease (IID) 2 Study, UK 2008e9.
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Table 2 presents, by organism, the rates of IID in the community
and presenting to GP, and the ratios of these rates to those
estimated from national surveillance data. Figures 4 and 5
illustrate reporting patterns for all IID and for the four major
pathogens, Campylobacter, Salmonella, norovirus and rotavirus. In
each diagram, the rates in the community, presenting to GP and
reported to national surveillance are represented as ellipses, with
the area of each ellipse proportional to the rate.
The ratios of community and GP presentation rates to
national surveillance rates were much higher for viruses than for
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Figure 3 Age-specific rates of
infectious intestinal disease general
practice (GP) consultationsdestimates
from the cohort and general practice
presentation studies, Infectious
Intestinal Disease 2 Study, UK 2008e9.
corresponding figures for giardiasis were somewhat higher,
although there was considerable uncertainty in the estimates.
bacteria and protozoa. For every national surveillance case of
norovirus IID, there were 12.7 GP consultations (95% CI 8.8 to
18.3) and 288 community cases (95% CI 239 to 346). The
corresponding ratios for rotavirus were one in five (95% CI
3 to 7) and one in 43 (95% CI 30 to 62). By contrast, for every
national surveillance case of campylobacteriosis, there were
1.3 GP consultations (95% CI 0.9 to 1.8) and 9.3 community
cases (95% CI 6.0 to 14.4). For Salmonella, the corresponding
ratios were 1.4 GP consultations (95% CI 0.6 to 3.3) and
approximately five community cases (95% CI 1.2 to 18.2).
Among the protozoa, 2.3 GP consultations (95% CI 1.0 to 5.6)
and 8.2 (95% CI 2.1 to 31.7) community cases occurred for every
case of cryptosporidiosis reported to national surveillance. The
Estimated annual cases and GP presentations
In 2009, there were approximately 16.9 million cases of IID and
over 1 million IID-related GP consultations. Campylobacter
accounted for over 500 000 cases and approximately 80 000 GP
consultations (table 3). Norovirus caused nearly three million
sporadic (non-outbreak-related) IID cases and approximately
130 000 GP consultations. The burden from sapovirus was also
considerable, with an estimated 1.6 million sporadic cases and
nearly 100 000 GP consultations, while rotavirus caused more
than 750 000 cases and 80 000 GP consultations.
Table 1 Incidence rates of infectious intestinal disease in the community and presenting to general practice by organism, Infectious Intestinal
Disease 2 Study, UK 2008e9
Community
Organism
Bacteria
C perfringens
Campylobacter spp.
E coli O157 (VTEC)
Enteroaggregative E coli
Salmonella spp.
Protozoa
Cryptosporidium
Giardia
Viruses
Adenovirusx
Astrovirus
Norovirus
Rotavirusx
Sapovirus
Test methods
Cases*
Presenting to GP
PYy
Ratez (95% CI)
Cases*
PYy
Ratez (95% CI)
Ratio community/GP
RR (95% CI)
78
400
693
4
66
57
56
312 232
312 232
312 232
312 232
312 232
312 232
312 232
0.24
1.28
2.22
0.01
0.21
0.18
0.18
(0.11
(0.90
(1.65
(0.00
(0.11
(0.08
(0.07
to
to
to
to
to
to
to
0.52)
1.82)
2.97)
0.09)
0.41)
0.44)
0.44)
6.0 (1.7 to 20.9)
7.2 (4.1 to 12.7)
4.9 (3 to 7.9)
22.8 (0.9 to 610)
28.4 (11.8 to 68.2)
3.4 (0.7 to 17.4)
3.5 (0.7 to 17.9)
65
80
29
35
312 232
312 232
312 232
312 232
0.20
0.25
0.09
0.11
(0.08
(0.11
(0.03
(0.05
to
to
to
to
0.48)
0.58)
0.27)
0.26)
3.5 (0.7 to 17.6)
4.9 (1.2 to 20.6)
9.3 (1.8 to 49.2)
18.2 (4.8 to 69.6)
265
127
648
424
491
312 232
312 232
312 232
312 232
312 232
0.84
0.40
2.07
1.36
1.57
(0.49
(0.20
(1.44
(0.89
(1.08
to
to
to
to
to
1.45)
0.82)
2.99)
2.07)
2.29)
12.1 (6.1 to 23.9)
13.1 (5.2 to 32.7)
22.7 (15.1 to 34.2)
9.4 (5.3 to 16.5)
16.6 (10.5 to 26.2)
A
A
E
A
D
A
E
7
43
51
1
28
3
3
4658.6
4658.6
4658.6
4658.6
4658.6
4658.6
4658.6
1.5 (0.5 to 3.9)
9.3 (6 to 14.3)
10.9 (7.4 to 15.9)
0.3 (0 to 4.3)
5.9 (3.4 to 10.2)
0.6 (0.2 to 2.4)
0.6 (0.2 to 2.4)
B
C
B
C
3
6
4
9
4658.6
4658.6
4658.6
4658.6
0.7
1.2
0.8
2.0
C
D
D
C
D
48
25
219
59
121
4658.6
4658.6
4658.6
4658.6
4658.6
10.2 (6.8 to 15.4)
5.3 (3 to 9.4)
47.0 (39.1 to 56.5)
12.7 (8.7 to 18.4)
26.1 (20.1 to 33.8)
(0.2
(0.4
(0.2
(0.7
to
to
to
to
2.7)
3.9)
3)
5.6)
*Mean number of cases from 20 imputations.
yPerson-years.
zCases per 1000 person-years.
xELISA for adenovirus and rotavirus was conducted in specimens from patients aged <5 years.
A, culture; B, enzyme immunoassay; C, ELISA and/or PCR; D, PCR; E, culture and/or PCR; GP, general practice; VTEC, verotoxin-producing E coli.
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Table 2 Incidence rates of infectious intestinal disease (IID) in the community and presenting to general practice by organism, and ratios to national
surveillance, IID2 Study, UK 2008e2009
Organism
Bacteria
C perfringens
Reporting ratioy
Campylobacter
Reporting ratioy
E coli O157 VTEC
Reporting ratioy
Salmonella
Reporting ratioy
Protozoa
Cryptosporidium
Reporting ratioy
Giardia
Reporting ratioy
Viruses
Adenovirus
Reporting ratioy
Astrovirus
Reporting ratioy
Norovirus
Reporting ratioy
Rotavirus
Reporting ratioy
A
A
A
A
B
B
C
D
D
C
Community
Rate* (95% CI)
Presenting to general practice
Rate* (95% CI)
Reported to national surveillance
Rate* (95% CI)
1.5 (0.5 to 3.9)
2518.7 (890.7 to 7179.4)
9.3 (6 to 14.3)
9.3 (6 to 14.4)
0.3 (0 to 4.3)
7.4 (0.5 to 104.4)
0.6 (0.2 to 2.4)
4.7 (1.2 to 18.2)
0.2 (0.1 to 0.5)
419.1 (181.9 to 962.8)
1.3 (0.9 to 1.8)
1.3 (0.9 to 1.8)
0.0 (0 to 0.1)
e
0.2 (0.1 to 0.4)
1.4 (0.6 to 3.3)
0.001
1.0
0.997
1.0
0.042
1.0
0.133
1.0
0.7 (0.2 to 2.7)
8.2 (2.1 to 31.7)
0.8 (0.2 to 3)
14.0 (4 to 49)
0.2
2.3
0.1
1.5
0.086 (0.084 to 0.089)
1.0
0.061 (0.059 to 0.063)
1.0
10.2 (6.8 to 15.4)
184.5 (122 to 279.3)
5.3 (3 to 9.4)
1763.5 (970.1 to 3218.1)
47.0 (39.1 to 56.5)
287.6 (239.1 to 346)
12.7 (8.7 to 18.4)
42.9 (29.5 to 62.4)
0.8 (0.5 to 1.5)
15.3 (8.8 to 26.3)
0.4 (0.2 to 0.8)
135.1 (65.5 to 278.9)
2.1 (1.4 to 3)
12.7 (8.8 to 18.3)
1.4 (0.9 to 2.1)
4.6 (3 to 7)
(0.1 to 0.5)
(1 to 5.6)
(0 to 0.3)
(0.5 to 4.5)
0.055
1.0
0.003
1.0
0.164
1.0
0.296
1.0
(0 to 0.001)
(0.989 to 1.005)
(0.04 to 0.043)
(0.13 to 0.136)
(0.053 to 0.057)
(0.003 to 0.003)
(0.011 to 0.02)
(0.232 to 0.268)
*Cases per 1000 person-years.
yThe reporting ratios represent the ratio of rates in the community and presenting to general practice relative to the rate of reports to national surveillance. Enteroaggregative E coli and
sapovirus are omitted from this table, as data on these organisms are not routinely collected at national level in all UK countries.
A, culture; B, enzyme immunoassay; C, ELISA and/or PCR; D, PCR; VTEC, verocytotoxin-producing E coli.
DISCUSSION
Summary of main findings
This is one of the largest population-based studies of IID to date,
comprising over 4500 person-years of community follow-up and
over 300 000 person-years of GP follow-up. Few researchers12 23
have investigated the aetiology of IID in the general population
so comprehensively. We included a broad panel of organisms
using conventional and novel quantitative PCR diagnostics. The
greater sensitivity of PCR methods for viral diagnostics allows
much more reliable incidence estimates, particularly for norovirus and sapovirus. The results show Campylobacter is the major
bacterial IID agent, causing over half a million cases and 80 000
GP consultations annually. Norovirus, commonly thought to
Figure 4 Patterns of reporting to national surveillance for all infectious
intestinal disease (IID), UK 2008e9. Black numbers represent the rates
(with 95% CIs) in the community, presenting to general practice and
reported to national surveillance. Red numbers represent the ratios of
incidence in the community and presenting to general practice
respective to the incidence of infectious intestinal disease reported to
national surveillance (with 95% CIs).
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cause mild illness in institutional outbreaks, nevertheless
accounts for nearly 3 million sporadic cases annually and
130 000 GP consultations.
To our knowledge, this is the first study to report the high
population burden of sapovirus, which may partly be due to
emergence of a novel sapovirus strain during the study.24 Low
population immunity levels may have facilitated its rapid
spread. Our estimates also provide a useful baseline for rotavirus
burden before the introduction of routine vaccination in the UK,
and indicate that C difficile is a very uncommon cause of
diarrhoea in the community.
Comparison with other studies
In a previous study,12 limited to England in the mid-1990s, using
the same case definition and similar methods, the reported IID
rates were 194 community cases and 33.1 GP consultations per
1000 person-years. In our study, the community incidence is
w40% higher, but GP consultation rates for all the major
pathogens have almost halved. This is consistent with data from
the Royal College of General Practitioners Weekly Returns
Service indicating a threefold decrease in IID-related consultations to its GP network between 1996 and 2008.25 A major
change to primary care since the 1990s is the introduction of
telephone information and advice services. However, use of
services such as NHS Direct in England was low in our study
and cannot account for the decline in GP consultations. Instead,
increased self-management and perhaps a decrease in the
severity of illness from certain pathogens may be responsible.
Our case definition was more sensitive than those used in
other studies and may have resulted in milder illness being
captured. The effect of varying case definitions will be the
subject of more detailed investigation. The Dutch SENSOR
Study, which used a definition for IID of three or more loose
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Figure 5 Patterns of reporting to national surveillance for Campylobacter, Salmonella, norovirus and rotavirus, UK 2008e9. Black numbers represent
the rates per 1000 person-years (with 95% CIs) in the community, presenting to general practice and reported to national surveillance. Red numbers
represent the ratios of the incidence rates in the community and presenting to general practice compared with infectious intestinal disease reports to
national surveillance (with 95% CIs).
stools in a 24 h period,23 produced a similar estimate (283 per
1000 person-years) to ours. Approximately 20% of patients in
our cohort experienced fewer than three loose stools in a 24 h
period, implying that, using comparable definitions, our study
would produce somewhat lower estimates of all-cause IID in the
community. Nevertheless, using comparable diagnostic
methods, rates in the community for Campylobacter, norovirus
and rotavirus were similar to those in both the previous IID
Study12 26 and the Dutch SENSOR Study.23 By contrast, the
incidence of salmonellosis in our study was considerably lower
than in those two studies. This reflects a decrease in contami-
nation of poultry products, particularly from Salmonella
Enteritidis phage type 4, following the introduction of vaccination of breeder and layer flocks in the mid-1990s.27
We estimate that there are up to 17 million cases of sporadic
IID in the UK every year. Studies of IID burden in similar
settings using telephone survey methods generally produce
incidence estimates two to three times higher.28 The reasons are
unclear, but may include differences in case definitions, telescoping of symptoms among telephone survey respondents, and
reporting fatigue among cohort participants followed-up for
long periods.28 In the IID2 Study, we conducted a parallel
Table 3 Estimated annual numbers of infectious intestinal disease (IID) cases in the community and presenting to general practices by organism, IID2
Study, UK 2008e2009
Community
Organism
Bacteria
C perfringens
Campylobacter spp.
E coli O157 VTEC
Enteroaggregative E coli
Salmonella spp.
Protozoa
Cryptosporidium
Giardia
Viruses
Adenovirus
Astrovirus
Norovirus
Rotavirus
Sapovirus
All IID
Cases
Presenting to GP
95% CI
Cases
95% CI
A
A
A
D
A
89 847
571 949
18 916
365 297
38 606
33 565 to 240 508
369 936 to 884 276
1339 to 267 201
211 351 to 631 374
9968 to 149 529
14 983
78 973
824
12 893
11 291
6981 to 32 157
55 486 to 112 401
120 to 5664
6501 to 25 567
4649 to 27 418
B
B
43 834
52 434
11 393 to 168 655
15 022 to 183 020
12 488
5617
5232 to 29 805
1875 to 16 822
C
D
D
C
D
630 251
325 642
2 905 278
783 737
1 610 041
16 935 420
417 285 to 951 906
1 82 466 to 581 165
2 418 208 to 3 490 451
539 535 to 1 138 466
1 239 580 to 2 091 219
15 680 690 to 18 277 944
52 106
24 982
128 022
83 850
97 024
1 096 190
30 219 to 89 845
12 260 to 50 905
88 784 to 184 600
54 868 to 128 141
66 661 to 141 217
891 659 to 1 348 301
A, culture; B, enzyme immunoassay; C, ELISA and/or PCR; D, PCR; VTEC, verocytotoxin-producing E coli.
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telephone survey to study these differences in detail (to be
reported elsewhere).
IID-related GP consultation rates vary considerably by study:
the SENSOR study rate was half that estimated by us,29 while
the rate recently reported in Germany was double.30 These
differences are difficult to interpret, but variations in primary
care provision and usage between countries may explain them.
Study limitations
Adherence to weekly follow-up in the cohort study was high.
Drop-outs accounted for losing <5% of total follow-up time.
Nevertheless, w10% of those invited were recruited into the
study. This is lower than previous studies in England (35%)12
and the Netherlands (42%),23 but similar to recent prospective,
population-based UK studies.31 32 Study participants may differ
from the general population in terms of IID risk or propensity to
report symptoms. We standardised all rates to account for
differences in the age and sex structure between the cohort and
census populations, and we did not find important differences in
IID rates by ethnicity, socioeconomic group, urbanerural residence or area-level deprivation (data not shown).
We based our estimates of community incidence on definite
IID cases. These could be conservative, since some cohort
participants reporting illness were classified as possible cases
because of missing symptom information. If definite and
possible cases were considered, the community rate nearly
doubled. We used definite cases only because information from
them on health service usage agrees with estimates from the GP
presentation study and NHS Direct, suggesting that these estimates are more reliable than those based on all definite and
possible cases. In addition, our results show a marked decline in
community Salmonella incidence, but for Campylobacter, norovirus and rotavirus, for which control measures have not been
implemented, our estimates are similar to those reported
previously in England12 26 and the Netherlands.23
One in six patients presenting to GP with IID-compatible
symptoms was recruited into the GP presentation study, with
considerable variation by practice. Although we publicised the
study widely in participating practices, some GPs may not have
referred patients if they were too busy. To satisfy ethics
requirements, invited patients were given a 24 h cooling-off
period before providing consent. Some patients were unable or
unwilling to return for an interview on another day, and others
were no longer interested because their condition had improved.
We corrected for under-ascertainment using adjustment factors
to account for differences in ascertainment by age group, sex,
diagnostic category and practice.
In the cohort study, a third of cases did not provide a stool
specimen for microbiological examination, so we used multiple
imputation methods to infer missing organism information. Our
imputation models included variables most likely to predict the
likelihood of infection with different organisms, namely age
group and symptom profile, but may not have dealt adequately
with missing data if other important factors related to positivity
with specific organisms had been omitted.
We used both conventional and quantitative PCR methods for
microbial diagnosis. PCR-based methods have greater sensitivity
for enteric viruses. For norovirus and rotavirus, however,
a substantial fraction of asymptomatic people have evidence of
infection using PCR.33 We used previously validated PCR cut-off
values to distinguish clinically significant from coincidental
infection with norovirus and rotavirus. Similar data do not exist
for other organisms, and we opted for a more sensitive
threshold. We may have overestimated incidence, particularly
8 of 9
for sapovirus, adenovirus and astrovirus, since, in some people,
infection may have been coincidental rather than causative.
Conversely, we may have underestimated Cryptosporidium and
Giardia rates; these organisms often cause illness lasting over
2 weeks, so cases of longer duration may have been excluded.
Despite extensive microbiological testing, w50% and 60% of
specimens tested in the GP presentation and cohort studies,
respectively, were negative for all the organisms investigated.
This is similar to previous studies23 34 and may reflect the role of
other organisms for which we did not test, or hitherto unknown
pathogens. We excluded patients with known non-infectious
causes of IID, and required cases to be symptom-free for the
preceding 3 weeks and have illness lasting less than 2 weeks.
However, it is possible that a fraction of these stool-negative
cases had non-infectious causes such as transient irritable bowel
syndrome, either pre-existing or resulting from a prior episode of
IID.
The reporting ratios should be interpreted in their epidemiological context. Norovirus cases in national statistics arise
primarily from institutional outbreaks, which were not included
in our study. We may therefore have overestimated the proportion of sporadic cases in the community captured by national
surveillance. For organisms such as Campylobacter, which is
uncommonly associated with large outbreaks, the reporting
ratio reflects more accurately the ratio of community incidence
to national statistics.
Conclusions
The UK burden of IID is substantial, resulting in up to 17 million
sporadic cases annually. Despite this, IID-related GP consultations have declined substantially since the 1990s. Changes in
healthcare usage, rather than increased use of telephone information and advice services, probably explain this. Tackling
Campylobacter is central to the Food Standards Agency’s strategy
and crucial for reducing food-borne illness burden.35 This involves
reducing contamination in poultry, a major source of human
infection,36 and promoting safe food preparation to avoid crosscontamination. By contrast, salmonellosis has declined dramatically. C difficile, very important in healthcare settings, appears to
be a rare cause of community IID, while enteric viruses account
for a large burden of healthcare use and disease in the community.
New rotavirus vaccines, if deemed cost-effective for routine
immunisation in the UK, show great promise for reducing burden
of rotavirus disease in children.37 38 Our study provides
contemporaneous baseline estimates of rotavirus burden before
introduction of routine immunisation. For norovirus and sapovirus, organisms commonly regarded as mainly causing institutional outbreaks, the large pool of community infection raises
important questions about control. Mitigating the impact of
these viruses includes scrupulous personal hygiene to avoid
person-to-person spread, and protecting shellfish beds against
human sewage contamination to reduce food-related norovirus
infection. Understanding better the burden of disease that is
food-borne, and the relationship between virus circulation in the
community and transmission in institutional and healthcare
settings, is crucial for developing appropriate control strategies.
Author affiliations
1
Department of Infectious Disease Epidemiology, Faculty of Epidemiology and
Population Health, London School of Hygiene & Tropical Medicine, London, UK
2
Medical Research Council General Practice Research Framework and University
College London, London, UK
3
Department of Primary Care and Public Health, Cardiff University, Cardiff, UK
4
School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, UK
5
Department of Gastrointestinal, Emerging & Zoonotic Infections, Health Protection
Agency Centre for Infections, London, UK
Tam CC, Rodrigues LC, Viviani L, et al. Gut (2011). doi:10.1136/gut.2011.238386
Downloaded from gut.bmj.com on July 12, 2011 - Published by group.bmj.com
Paper
6
Regional Microbiology Network, Health Protection Agency Yorkshire and the Humber,
Leeds Laboratory, Leeds, UK
7
School of Translational Medicine, University of Manchester and Manchester
Academic Health Science Centre, Manchester, UK
Acknowledgements We thank all the participants, study nurses, general
practitioners, practice staff, laboratory, research and administrative staff who took
part in the IID2 Study. We are grateful to the Medical Research Council General
Practice Research Framework, the Primary Care Research Networks in England and
Northern Ireland and the Scottish Primary Care Research Network for assistance
with the recruitment of general practices. We thank the UK Food Standards Agency
and the Department of Health for funding the research component of the IID2 Study
(Project B18021). We also thank the Department of Health, the Scottish Primary
Care Research Network, NHS Greater Glasgow and Clyde, NHS Grampian, NHS
Tayside, the Welsh Assembly government (Wales Office of Research and
Development) and, in Northern Ireland, the Health and Social Care Public Health
Agency (HSC Research and Development) for providing service support costs. We
thank Julian Gardiner for help with aspects of the analysis.
Funding This study was funded by the Food Standards Agency and sponsored by
University of Manchester. Neither the funder nor the sponsor were involved in the
analysis, interpretation or decision to submit for publication.
Correction notice This article has been corrected since it was published Online First.
In the results section of the abstract, the following sentence has been corrected as
follows: “Campylobacter was the most common bacterial pathogen, with a rate of
9.3 cases per 1000 person-years in the community, and 1.3 GP consultations per
1000 person-years.”
Competing interests All authors have completed the Unified Competing Interest
form at http://www.icmje.org/coi_disclosure.pdf (available on request from the
corresponding author).
Patient consent Obtained.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
Ethics approval This study was conducted with the approval of the North West
MREC, Stockport PCT, Gateway House, Piccadilly South, Manchester M60 7LP, UK.
Contributors SJOB, GR, JJG, PRH, DST, CCT and LCR conceived the ideas for the
study. All authors participated in its design and coordination. SJOB, GR, JD and LHL
led the prospective studies. JJG and DST led the laboratory studies. MRE participated
in the national surveillance studies. CCT, LCR and LV led and conducted the analysis.
CCT, LCR and SJOB drafted the manuscript. All authors have read and approved the
final manuscript. All authors had full access to all of the data (including statistical
reports and tables) in the study and can take responsibility for the integrity of the data
and the accuracy of the data analysis. SJOB is the guarantor of the study.
24.
25.
26.
27.
Provenance and peer review Not commissioned; externally peer reviewed.
28.
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Longitudinal study of infectious intestinal
disease in the UK (IID2 study): incidence in
the community and presenting to general
practice
Clarence C Tam, Laura C Rodrigues, Laura Viviani, et al.
Gut published online June 27, 2011
doi: 10.1136/gut.2011.238386
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