Infectious intestinal disease: do we know it all?
ABSTRACT Infectious intestinal disease (IID), with associated high morbidity and considerable mortality worldwide, causes a wide spectrum of illness. This ranges from mild discomfort to illness with severe complications. The economic burden from direct and indirect costs may be high. It is acquired by oral ingestion of micro-organisms which are transmitted from person to person; via food or water or through contact with animals or contaminated objects. Viruses are the commonest cause in developed countries. In Malta, medical practitioners and laboratories are the main source of data on IID. However, under-reporting is a problem. In order to fill in the lacunae in information on the disease burden, population-based-studies are required. Along with other countries, Malta has embarked on a number of studies to describe and quantify under-reporting of IID. This may assist in strengthening the surveillance system which, in combination with other measures, should result in an improvement of the control of IID.
- SourceAvailable from: medint.at[show abstract] [hide abstract]
ABSTRACT: Diarrhoea is a problem, not only of the developing world, but also of the Western world. However, the economic implications of diarrhoeal diseases are particularly evident in the poorer countries. The most common worldwide cause of diarrhoea is intestinal infection and infants, pre-school children, the elderly, and those with congenital or acquired immunodeficiency run a high risk of contracting such infections. Diarrhoeal disease can be classified into three major clinical syndromes: acute watery diarrhoea, bloody diarrhoea, and persistent diarrhoea. A number of different micro-organisms can cause infectious diarrhoea, depending on the clinical setting. The development of oral rehydration solution has provided a simple approach to rehydration and maintenance of hydration in patients with acute watery diarrhoea, and has been implemented worldwide under the auspices of the World Health Organization. However, rehydration does not treat the diarrhoea itself, which will persist until the infection resolves. Since the drugs currently used for the treatment of diarrhoea, such as the opiate agents and antibiotics, have limitations, the search continues for a drug that acts predominantly on secretory pathways without affecting gastrointestinal motility. Novel therapeutic approaches include 5-HT(2) and 5-HT(3) receptor antagonists, calcium-calmodulin antagonists, and sigma-receptor agonists. Another approach has concentrated on the antisecretory role of the neurotransmitter, enkephalin, and has resulted in the development of the enkephalinase inhibitor, racecadotril. This drug has true antisecretory activity, and has demonstrated good efficacy and tolerability in clinical trials.International Journal of Antimicrobial Agents 03/2000; 14(1):65-9. · 4.42 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: To determine the excess mortality associated with infections with Salmonella, Campylobacter, Yersinia enterocolitica, and Shigella and to examine the effect of pre-existing illness. Registry based, matched cohort study. Denmark. 48 857 people with gastrointestinal infections plus 487 138 controls from the general population. One year mortality among patients with gastrointestinal infections compared with controls after adjustment for comorbidity. 1071 (2.2%) people with gastrointestinal infections died within one year after infection compared with 3636 (0.7%) controls. The relative mortality within one year was 3.1 times higher in patients than in controls. The relative mortality within 30 days of infection was high in all four bacterial groups. Furthermore, there was excess mortality one to six months after infection with Yersinia enterocolitica (relative risk 2.53, 95% confidence interval 1.38 to 4.62) and from six months to one year after infection with Campylobacter (1.35, 1.02 to 1.80) and Salmonella (1.53, 1.31 to 1.79). Infections with all these bacteria were associated with an increased short term risk of death, even after pre-existing illnesses were taken into account. Salmonella, Campylobacter, and Yersinia enterocolitica infections were also associated with increased long term mortality.BMJ (Clinical research ed.). 03/2003; 326(7385):357.
- Emerging Infectious Diseases 12/1999; 5(6):841-2. · 6.79 Impact Factor
Malta Medical Journal Volume 18 Issue 04 December 2006 7
Charmaine Gauci, Herbert Gilles, Sarah O’Brien, Julian Mamo
Infectious intestinal disease:
do we know it all?
Charmaine Gauci* MD, PhD
Disease Surveillance Unit, Department of Public Health, Malta
Herbert Gilles DSc, FRCP
Emeritus Professor, University of Liverpool, UK
Sarah O’Brien MB BS, FFPH
University of Manchester, UK
Julian Mamo MD, PhD
Department of Public Health, University of Malta, Malta
Infectious intestinal disease, surveillance, under-reporting
Infectious intestinal disease (IID), with associated high
morbidity and considerable mortality worldwide, causes a
wide spectrum of illness. This ranges from mild discomfort
to illness with severe complications. The economic burden
from direct and indirect costs may be high. It is acquired by
oral ingestion of micro-organisms which are transmitted from
person to person; via food or water or through contact with
animals or contaminated objects. Viruses are the commonest
cause in developed countries. In Malta, medical practitioners
and laboratories are the main source of data on IID. However,
under-reporting is a problem. In order to fill in the lacunae in
information on the disease burden, population-based-studies
are required. Along with other countries, Malta has embarked
on a number of studies to describe and quantify under-reporting
of IID. This may assist in strengthening the surveillance system
which, in combination with other measures, should result in an
improvement of the control of IID.
* corresponding author
The term infectious intestinal disease (IID) is used to
describe gastrointestinal symptoms (diarrhoea, vomiting and
abdominal pain) due to micro-organisms or their toxins. It is one
of the leading causes of morbidity and mortality worldwide.1-3 In
less developed countries, the mortality rate from this category
of disease is slowly decreasing but the incidence remains very
high.4-5 In more developed countries, improvements in hygiene
and treatment of disease have radically reduced the number of
deaths while the clinical course is often self-limiting. However,
the morbidity remains high.6
IID causes a wide spectrum of diseases ranging from minor
discomfort to extreme dehydration which may result in death.
Most episodes are self limiting. However, some may lead to
complications. It has been estimated that 2-3% of IID cases
develop a variety of secondary long term illnesses.7 The most
recognised of these are irritable bowel syndrome,8-9 Guillain-
Barré syndrome,10-11 reactive arthritis and haemolytic uraemic
The economic burden of IID to society is high.14-16 There
are direct costs involved which include those relating to general
practitioner (GP) consultations, laboratory tests, hospital
admissions and medications. Indirect costs include losses in
income and productivity.17
Aetiology of infectious intestinal illness
IID is acquired predominantly by oral ingestion of micro
organisms or their toxins. They are transmitted by close
contact with other infected persons; by the consumption of
contaminated food or water; through contact with animals or by
contact with contaminated objects (fomites).18 Some pathogens
are associated with a specified mode of transmission such as
the rotavirus which is mainly non-foodborne. However, most
pathogens have multiple modes of transmission (Table 1).
Viral infections are the commonest cause of IID in the
community. Noroviruses are suspected to be the most common
cause in the United States.19 Other viruses include rotavirus,20
sapovirus, adenovirus and astrovirus. The commonest bacterial
agents responsible for IID are Campylobacter and Salmonella.
Other bacteria include Escherichia coli, Shigella, Staphylococcus
aureus, Bacillus cereus and Yersinia. The main protozoa causing
infectious intestinal disease are Cryptosporidium and Giardia
In Malta, Salmonella was the commonest identifiable
8 Malta Medical Journal Volume 18 Issue 04 December 2006
Micro-organism Common sources Symptoms of infection
Eating contaminated meat (especially
undercooked poultry); drinking contaminated lasting 1 day to a week or more
water or unpasteurised milk
Often bloody, sometimes watery diarrhoea
Eating contaminated food, contact with
reptiles (iguanas, snakes, turtles)
especially in day-care centres
Eating undercooked ground beef or drinking
unpasteurised milk or juice; swimming in
contaminated pools; person-to-person
contact; touching infected animals
and then putting
High fever, abdominal cramps, nausea, vomiting,
diarrhoea that may or may not be bloody.
Symptoms usually last 3 to 7 days
May be mild or severe. In mild cases, watery,
loose stools. In severe cases, high fever, severe
abdominal cramps, painful passage of stool
containing blood and mucus. Symptoms usually
last about a week without treatment
Sudden abdominal cramps, watery diarrhoea
that usually becomes bloody within 24 hours,
fingers in one’s mouth
Eating or drinking contaminated
food or water
Eating or drinking contaminated
food or water
Eating or drinking contaminated
food or water
Bloody diarrhoea, abdominal pain, weight loss
lasting 1 to 3 weeks. Can cause infection in liver
and other organs
Frequent watery diarrhoea.
Usually lasts 3 to 5 days
Painless, watery diarrhoea; vomiting.
Can lead to massive fluid loss, shock.
Watery, diarrhoea, often with little
nausea or vomiting
Eating food contaminated by toxins
produced by bacteria
Eating food contaminated by
toxins produced by bacteria
Epidemic and often seasonal
Severe nausea and vomiting beginning about
2 to 8 hours after eating contaminated food
Usually mild. When severe, abdominal
pain, abdominal expansion, severe diarrhoea,
dehydration, shock. Symptoms usually begin
8 to 16 hours after eating contaminated food
Frequent watery diarrhoea; vomiting and fever
(milder in astroviruses). Usually lasts 2 to 7 days
(10 days or more for enteric adenoviruses)
Drinking contaminated stream water;
person-to-person contact, particularly
in day-care centres
Drinking contaminated water;
person-to-person contact. People with AIDS
are particularly susceptible
Diarrhoea, nausea, loss of appetite.
More long-term illness (lasting several
days to several weeks) may occur, with grassy
stools, abdominal bloating, gas, and weight loss
Watery diarrhoea, crampy abdominal pain,
Table 1: Micro-organisms known to cause IID, their source and symptoms
Malta Medical Journal Volume 18 Issue 04 December 2006 9
Figure 1: Reported sporadic foodborne illness
in Malta 1992-2005 by aetiological agent
Number of reported cases
Figure 2: The reporting fraction of IID in Malta
Reported to Public Health/DSU
Lab tests for organism
Persons seeks care
Person becomes ill
Exposures in the general population
pathogen in cases of IID over recent years up to 2003. However,
as of 2004 the number of reported cases of Campylobacter is
higher than that for Salmonella.22 A substantial number of
notified cases in the same year are still defined as unspecified
where the aetiological agent has not been identified (Figure 1).23
In these cases, the pathogen may not identified. Alternatively
it may well be a pathogen not yet identified. These will become
apparent with time and investigation.
It may well be that the majority of the cases labelled as
unspecified in Malta are of viral origin, since tests for viruses
are not routinely used and particularly the laboratory test for
norovirus is not available locally to date.
Sources of information on infectious
intestinal illness in Malta
In Malta, a small island state with traditionally strict
infectious disease legislation, surveillance of infectious
diseases dates back over a century. During the 19th century, the
importance of improving the sanitary condition of the Island was
highlighted through a number of legal ordinances introduced
in 1875. The Sanitary Office was set up through these laws and
was responsible for, amongst other public health issues, the
investigation and control against infective diseases and for the
keeping of statistics.24 Today, the Disease Surveillance Unit,
within the Public Health Department, is responsible for the
surveillance of infectious intestinal disease. This unit receives
notifications from general practitioners, hospital physicians
and laboratories. The majority of notifications received include
cases, which required hospitalisation or referral for stool culture
analysis. Notifications from general practitioners are very few
even though these have a statutory obligation to notify. To be
included in the present surveillance system, an individual must
first present to the health care provider who should notify the
case. Of those that present to the health care provider, only a
small proportion of specimens are submitted for microbiological
testing. Naturally, only the severe cases would require
hospitalisation. Hence, the surveillance system captures only
a tiny fraction of the infectious intestinal disease that is actually
occurring in the community. This indicates that there must be
significant lacunae in information describing the magnitude of
infectious intestinal disease, especially at the population level.
Figure 2 represents the relatively unknown quantity of IID and
an undefined portion that is reported.
?0 Malta Medical Journal Volume 18 Issue 04 December 2006
The international situation
The problem of under-reporting is a recognised problem
internationally.25-30 In order to better estimate the burden
associated with IID, research is required to provide information
to base estimates. A number of international initiatives have
been designed to determine the burden of disease.
WHO Global Salm-Surv. This an international capacity-
building programme which strengthens national laboratory-
based surveillance and outbreak detection of diseases commonly
transmitted via food.31
WHO Sentinel Sites Project. This project defined
surveillance systems in four categories based on the ability
of the system to generate information on foodborne illness.32
Category 1 included countries where no formal surveillance
existed; Category 2 included countries with syndromic
surveillance; Category 3 included countries with laboratory-
based surveillance and Category 4 included those with integrated
food-chain surveillance. The countries with Category 3 and 4
surveillance systems were recommended for burden studies.
Jordan was chosen as the first sentinel site for this project.
International Collaboration on enteric diseases:
the Burden of Illness Studies. This was set up to bring
epidemiologists conducting population studies together to
share information and collaborate on international studies.33
This network includes researchers from more than 30 countries
amongst which are the United States, Canada, Australia, Ireland,
Scotland, the United Kingdom, Japan, the Netherlands and
Malta who are performing studies in an attempt to estimate
the actual burden from IID. The main aims of this network
• Foster communication between researchers via a list-
server, conference calls, and an annual face-to face-
• Create a forum for sharing information about the design,
implementation and analysis of studies on the burden of
• Provide advice to countries wishing to conduct burden of
• Contribute to global estimates.
A number of countries have undertaken national initiatives
in estimating the burden of infectious intestinal disease. The
first countries to embark on community studies to estimate the
burden of IID were England, The Netherlands and the United
States.25, 34-37 After this a number of other countries conducted
similar studies. Some researchers used a prospective cohort
study whilst others used a retrospective cross-sectional study.
England. A prospective population cohort study was
performed in England over the period 1993-1995.25, 38-39 Cohorts
from 70 general practices were recruited and stool samples were
obtained and tested for bacteria, viruses and parasites. It was
estimated that 19.4% (CI ± 2.7) of the population of England
suffered from IID in a year and 3.3% of the population presented
to their GP with IID. The most common aetiologic agents were
norovirus, Campylobacter species, rotavirus, and non-typhoidal
The Netherlands. A similar study was carried out in the
Netherlands during the period 1998-1999 where 60 practitioners
reported the number of consultations for acute gastroenteritis
that occurred each week. An age-stratified random sample of
patients identified from the same registers was selected for a
community-based cohort. This provided an estimate of 28.3%
(CI ± 6.3) of the population suffered from gastroenteritis36 and
1.4% consulted their GP.35 This study also investigated a broad
range of pathogens causing gastroenteritis.9 The most common
pathogen at community level was norovirus (11%).21
United States. The FoodNet population survey,
established in 1996 out as part of CDC’s Emerging Infectious
Programme is based on retrospective self-reported symptoms.37
During 1996-1997, this survey reported 11.0% (CI ± 0.8) of the
people suffering from diarrhoeal illness in the 4 weeks before
Ireland. A retrospective telephone study of self-reported
symptoms of gastroenteritis that was performed during the
period 2000 to 2001 in Ireland estimated that 4.5% (CI ± 0.8)
of the population reported suffering from acute gastroenteritis
in the 4 weeks prior to the interview with a rate of 0.60 episodes
per person per year.40-41
Australia. A retrospective study conducted in Queensland
in 2001 via OzFoodNet, estimated that 13.6% (CI ± 2.4) of the
adult cases (18 years or older) and 13.9% (CI ± 8.1) of children
(7 months to 4 years) reported diarrhoea in the preceding
Canada. The National Studies on acute gastrointestinal
Illness conducted a retrospective population based study
which estimated a monthly prevalence of 10% and an adjusted
incidence rate of 1.3 episodes per person per year.43
Norway. A retrospective population-based study was
carried out in 1999-2000 using a self-administered postal
questionnaire. The prevalence of acute gastroenteritis was
14.4% (CI ± 2.6) of which 17% consulted a physician.44
Situation in Malta
Information on the burden of IID illness is lacking in
Malta. Various issues were considered in the choice of the
methodology for a possible exploratory study.45 A cohort study
is not applicable in a country like Malta where no general
practitioner based patient lists exist, with patients referring to
any doctor they wish and hence, a doctor would not be able to
follow up patients prospectively. Hence, a cross sectional study
was chosen as the method to estimate the prevalence of IID
in Malta. The advantages of the cross-sectional methodology
include the fact that it is less expensive and can be performed
more quickly, enabling a larger sample size, hence, decreasing
Type II error*. Attrition of participants is not a concern and
there is no difficulty and cost in maintaining contact with the
* Type II error: the error of rejecting a true null hypothesis i.e.
declaring that a difference exists when it does not.
Malta Medical Journal Volume 18 Issue 04 December 2006 ??
subjects since they are not followed up. Another factor is that
this type of study can capture community cases, since it does
not rely on persons presenting to their GP. There are a number
of disadvantages to this approach which includes difficulty
in separating the chronology of cause and effect because of
the short time studied and the inherent biases (selection,
confounding and information bias).
Four studies have been launched in Malta in order to
estimate the incidence of infectious intestinal disease at various
levels and to identify where and how cases are lost along the
surveillance chain. These include:
1. A Community based survey interviewing an age-
stratified random sample of the population to estimate
the baseline incidence of self-reported infectious
intestinal disease in the community and to estimate the
proportion of cases which do not present to the health
care system and are notified, thereby quantifying under-
reporting of infectious intestinal disease.
2. A Sentinel Surveillance study consisting of
intensified surveillance by a number of GPs for a defined
period of time in order to estimate the true number of
cases presenting to GPs with IID and to test the feasibility
of carrying out sentinel surveillance in Malta.
3. A Knowledge, Attitude and Practice survey of
physicians consisting of a focus study and a postal
survey of a sample of local physicians to assess their
attitudes and awareness of the notification system in
order to identify the reasons behind under-notification
or delayed notification, with a view to developing
recommendations aimed at reducing this problem.
4. A Laboratory Study consisting of interviews at local
laboratories to identify practices in laboratories that
impact on the sensitivity of finding an aetiologic agent in
submitted stool specimens and their attitudes towards
In a small island state such as Malta, the epidemiology of
infectious disease ought to be more practical and complete.
Describing and quantifying under-reporting may assist in
strengthening the surveillance system of IID by:
a) identifying where and how cases are lost along the
b) finding ways to reduce loss of data and
c) developing correction factors to compensate for a known
magnitude of under reporting.
Strengthening the national surveillance system in
combination with other measures should result in a marked
improvement in the ability to detect, investigate and control
food and water-borne enteric pathogens.
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