Study Of Infectious Intestinal Disease Research Articles

The journey of the germ: commentary on routes of infection and targeted hand hygiene.

The World Health Organization (WHO) estimates that there are 4 billion cases of diarrhoea causing 4% of deaths worldwide and killing 2.2 million people globally, mostly under 5 years old.1 Findings of the Second Study of Infectious Intestinal Disease (IID2) led to the estimate that in the United Kingdom, every year possibly 17 million people or 25% of the population suffer from an infectious intestinal disease (IID).2 In the IID2 study, microorganisms most commonly identified from people with an IID were norovirus, sapovirus, Campylobacter spp. and rotavirus. An estimated 3 million cases of norovirus were thought to occur.Campylobacter is considered to be responsible for 280,000 cases of illness every year in the United Kingdom. A Food Standards Agency study indicated that 73% of raw chickens may be contaminated with Campylobacter, and furthermore, it was identified on 7% of external packaging,3 posing a real risk of transmission directly via hands to mouth, via surfaces during shopping or while preparing chicken at home.Respiratory tract infections (RTIs) are another major cause of illness throughout the world; for example, the Communicable Diseases Center (CDC) in the United States estimates that adults have, on average, two to three colds per year and children have even more (3.5-5.5).These burdensome infectious diseases can transfer from sources via hands directly or indirectly to cause illness. Routes of infection can be simple, for example, from source to hand to mouth: in the case of Campylobacter, transferred from raw poultry to hands to mouth when someone preparing food bites their nails without washing their hands thoroughly first (Figure 1).However, many routes of infection can be far more complex, involving a number of vehicles along the way, from contaminated hands, utensils, surfaces, cloths and clothes. The source of infection may be also separated by time and distance from the person infected, and where incubation periods are extended, for example, with infections from Campylobacter, the actual source may never be identified in sporadic cases. Targeted control and intervention for prevention then become more complicated, and an explanation of the 'Journey of the Germ' may be meaningful to raise awareness.From Figures 2 and 3, it can be seen that hands play an important role in the transmission of disease. The WHO identifies hand washing as the single most important and cost-effective means of reducing illness. Studies have suggested that hand hygiene can contribute to the reduction in infectious diseases,4 with the risk of respiratory diseases being reduced by up to 21% or more by hand washing and intestinal illness reduced by 31%.5 In the United Kingdom, an internet-delivered hand washing intervention study providing information about the role of hand washing in prevention of influenza suggested a reduction in RTIs by 14% for participants; additionally, it had a positive effect on reducing gastrointestinal illness and antibiotic prescription.6This important control measure of hand washing can be unpopular in all walks of life, from health care to food preparation settings. A study of caterers carried out for the Food Standards Agency7 in 2002 found that only 61% said they would wash their hands after using the toilet. Furthermore, only 48% would wash their hands after handling raw meat, and surprisingly, only 21% of respondents said they would wash their hands when they are dirty. A survey carried out by Rentokil Initial found that around 27% of office workers did not wash their hands after using the toilet. …

The second study of infectious intestinal disease (IID2): increased rates of recurrent diarrhoea in individuals aged 65 years and above

BackgroundInfectious intestinal disease (IID) is a major health and economic burden in high-income countries. In the UK, there are an estimated 17 million IID cases annually, of which 6 million are caused by the 12 most common pathogens. Host factors that influence risk of IID are not well understood.MethodsWe analyzed data from the IID2 Study, a UK cohort that measured IID incidence, to investigate factors associated with recurrent IID. We calculated rates of IID by age group, sex, previous episodes experienced, and socioecomic indicators. We used Cox models to investigate factors associated with recurrent illness.ResultsThe rate of IID was five times higher among infants than those aged 65 years and above (hazard ratio, HR = 5.0, 95% CI: 3.1 – 8.0). However, the association between previous IID and a subsequent IID episode was stronger in the elderly. Among those aged 65 years and above, each additional IID episode increased the rate of subsequent IID three-fold (HR = 3.1, 95% CI: 2.5 – 3.7). Among infants, the corresponding increase was 1.7-fold (HR = 1.7, 95% CI: 1.3 – 2.3).ConclusionsElderly populations have a high propensity for recurrent IID. More detailed studies are needed to identify vulnerable subgroups and susceptibility factors, and inform adequate control policies among the elderly.

Universal extraction method for gastrointestinal pathogens

A universal stool extraction method for recovery of nucleic acids (NAs) from gastrointestinal pathogens was developed to support rapid diagnostics for the London 2012 Olympics. The method involved mechanical disruption (bead beating) of the stools, followed by automated extraction and detection using real-time PCR. This method had been used extensively in the Second Infectious Intestinal Disease Study (IID2) for the isolation of NA from bacteria and parasites (and was effective for the robust recovery of Cryptosporidium spp.) but had not been used for enteric viruses. To ensure this method was universally suitable, panels of samples known to contain target bacteria, viruses or parasites were processed in triplicate using the pre-treatment method routinely used for each target and the new extraction method (bead beating). The extracts were tested using real-time PCR and the cycle threshold values were compared. The results from this study showed that bead beating improved yields for the bacterial and parasitic targets and was suitable for the viral targets. The implementation of this universal method should confer cost- and time-saving benefits and streamline the processes required for the characterization of an array of pathogens from faecal samples.

Human Bocaviruses Are Not Significantly Associated with Gastroenteritis: Results of Retesting Archive DNA from a Case Control Study in the UK

Gastroenteritis is a common illness causing considerable morbidity and mortality worldwide. Despite improvements in detection methods, a significant diagnostic gap still remains. Human bocavirus (HBoV)s, which are associated with respiratory infections, have also frequently been detected in stool samples in cases of gastroenteritis, and a tentative association between HBoVs, and in particular type-2 HBoVs, and gastroenteritis has previously been made. The aim of this study was to determine the role of HBoVs in gastroenteritis, using archived DNA samples from the case-control Infectious Intestinal Disease Study (IID). DNA extracted from stool samples from 2,256 cases and 2,124 controls were tested for the presence of HBoV DNA. All samples were screened in a real time PCR pan-HBoV assay, and positive samples were then tested in genotype 1 to 3-specific assays. HBoV was detected in 7.4% but no significantly different prevalence was observed between cases and controls. In the genotype-specific assays 106 of the 324 HBoV-positive samples were genotyped, with HBoV-1 predominantly found in controls whilst HBoV-2 was more frequently associated with cases of gastroenteritis (p<0.01). A significant proportion of HBoV positives could not be typed using the type specific assays, 67% of the total positives, and this was most likely due to low viral loads being present in the samples. However, the distribution of the untyped HBoV strains was no different between cases and controls. In conclusion, HBoVs, including HBoV-2 do not appear to be a significant cause of gastroenteritis in the UK population.

Changes in Causes of Acute Gastroenteritis in the United Kingdom Over 15 Years: Microbiologic Findings From 2 Prospective, Population-Based Studies of Infectious Intestinal Disease

Large-scale, prospective studies of infectious intestinal disease (IID) in developed countries are uncommon. Two studies of IID incidence and etiology have been conducted in the United Kingdom: the Infectious Intestinal Disease Study in England (IID1) in 1993-1996 and the Second Study of Infectious Intestinal Disease in the Community (IID2) in 2008-2009. We examined changes in etiology and diagnostic yield of IID cases over 15 years. Fecal samples submitted by IID cases were examined for a range of bacterial, viral, and protozoal pathogens using traditional and molecular microbiological methods. We calculated the percentage of specimens positive for each organism based on traditional methods and on traditional and molecular methods combined. We compared the distributions of organisms in the 2 studies. For pathogens investigated in both studies, 40% of fecal samples submitted by cases in IID2 were positive compared with 28% in IID1. Viruses were most frequent among community cases in IID2. Campylobacter was the most common bacterial pathogen among cases presenting to healthcare. Major differences between the 2 studies were increases in the detection of norovirus and sapovirus and a decline Salmonella. Most fecal specimens were negative for the pathogens tested in both studies, so new strategies are needed to close the diagnostic gap. Among known pathogens, effective control of norovirus, rotavirus, and Campylobacter remain high priorities. The reduction in nontyphoidal salmonellosis demonstrates the success of Europe-wide control strategies, notably an industry-led Salmonella control program in poultry in the United Kingdom.

Longitudinal study of infectious intestinal disease in the UK (IID2 study): incidence in the community and presenting to general practice

ObjectivesTo 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.DesignProspective, community cohort study and...

Methods for determining disease burden and calibrating national surveillance data in the United Kingdom: the second study of infectious intestinal disease in the community (IID2 study)

BackgroundInfectious intestinal disease (IID), usually presenting as diarrhoea and vomiting, is frequently preventable. Though often mild and self-limiting, its commonness makes IID an important public health problem. In the mid 1990s around 1 in 5 people in England suffered from IID a year, costing around £0.75 billion. No routine information source describes the UK's current community burden of IID. We present here the methods for a study to determine rates and aetiology of IID in the community, presenting to primary care and recorded in national surveillance statistics. We will also outline methods to determine whether or not incidence has declined since the mid-1990s.Methods/designThe Second Study of Infectious Intestinal Disease in the Community (IID2 Study) comprises several separate but related studies. We use two methods to describe IID burden in the community - a retrospective telephone survey of self-reported illness and a prospective, all-age, population-based cohort study with weekly follow-up over a calendar year. Results from the two methods will be compared. To determine IID burden presenting to primary care we perform a prospective study of people presenting to their General Practitioner with symptoms of IID, in which we intervene in clinical and laboratory practice, and an audit of routine clinical and laboratory practice in primary care. We determine aetiology of IID using molecular methods for a wide range of gastrointestinal pathogens, in addition to conventional diagnostic microbiological techniques, and characterise isolates further through reference typing. Finally, we combine all our results to calibrate national surveillance data.DiscussionResearchers disagree about the best method(s) to ascertain disease burden. Our study will allow an evaluation of methods to determine the community burden of IID by comparing the different approaches to estimate IID incidence in its linked components.

Asymptomatic Rotavirus Infections in England: Prevalence, Characteristics, and Risk Factors

Rotavirus is a major cause of infectious intestinal disease in young children; a substantial prevalence of asymptomatic infection has been reported across all age groups. In this study, the authors determined characteristics of asymptomatic rotavirus infection and potential risk factors for infection. Healthy persons were recruited at random from the general population of England during the Study of Infectious Intestinal Disease in England (1993-1996). Rotavirus infection was identified using reverse-transcription polymerase chain reaction. Multivariable logistic regression was used to compare exposures reported by participants with rotavirus infection with those of participants who tested negative. Multiple imputation was used to account for missing responses in the data set. The age-adjusted prevalence of asymptomatic rotavirus infection was 11%; prevalence was highest in children under age 18 years. Attendance at day care was a risk factor for asymptomatic rotavirus infection in children under age 5 years; living in a household with a baby that was still in diapers was a risk factor in older adults. The results suggest that asymptomatic rotavirus infection is transmitted through the same route as rotavirus infectious intestinal disease: person-to-person contact. More work is needed to understand the role of asymptomatic infections in transmission leading to rotavirus disease.

Community Incidence of Norovirus-associated Infectious Intestinal Disease in England: Improved Estimates Using Viral Load for Norovirus Diagnosis

Existing estimates of the incidence of infectious intestinal disease (IID) caused by norovirus are based on electron microscopy or reverse transcription-polymerase chain reaction (RT-PCR). Neither method accurately represents norovirus disease burden: Electron microscopy has poor diagnostic sensitivity, and RT-PCR has poor diagnostic specificity. In this study, viral load measurements were used to identify cases of norovirus-associated IID and to produce new incidence estimates for England. IID cases were ascertained in the Study of Infectious Intestinal Disease in England (1993-1996), and stool specimens were tested by semiquantitative real-time RT-PCR for norovirus. The age-adjusted community incidence of norovirus-associated IID was 4.5/100 person-years (95% credibility interval: 3.8, 5.2), equating to 2 million episodes/year. Among children aged less than 5 years, the community incidence was 21.4/100 person-years (95% credibility interval: 15.9, 27.7), and the incidence of consultations to general practitioners for norovirus-associated IID was 3.2/100 person-years (95% credibility interval: 2.6, 3.8), with 100,000 children visiting their general practitioner for norovirus-associated IID each year. Norovirus is the most common cause of IID in the community in England and is responsible for a similar number of pediatric primary care consultations as rotavirus.

Prevalence and characteristics of asymptomatic norovirus infection in the community in England

Norovirus is a major cause of infectious intestinal disease, and a substantial prevalence of asymptomatic infection has been reported. We describe the prevalence, seasonality and characteristics of asymptomatic norovirus infection in England. Healthy individuals were recruited at random from the general population during the Study of Infectious Intestinal Disease (1993-1996). Norovirus was identified using real-time RT-PCR. The age-adjusted prevalence of asymptomatic norovirus infection was 12%; prevalence was highest in children aged <5 years and showed wintertime seasonality. More work is needed to understand whether asymptomatic infections are important for norovirus transmission leading to sporadic illness and outbreaks.

Detection by PCR of eight groups of enteric pathogens in 4,627 faecal samples: re-examination of the English case-control Infectious Intestinal Disease Study (1993–1996)

The English case-control Infectious Intestinal Disease Study (1993-1996) failed to detect an enteric pathogen or toxin in 49% of cases of gastroenteritis. In the present study, polymerase chain reaction (PCR) assays were applied to DNA and cDNA generated from 4,627 faecal samples from cases and controls archived during the original study for the detection of norovirus, rotavirus, sapovirus, Campylobacter spp., Salmonella spp., enteroaggregative Escherichia coli, Cryptosporidium spp., and Giardia spp. The percentage of archived samples from cases and from controls in which at least one agent (or toxin) was detected increased from 53% in the original study to 75% and from 19 to 42%, respectively, after the application of PCR assays. Among cases, the following percentages of enteric pathogens were detected: norovirus 36%, rotavirus A 31%, sapovirus 4%, Salmonella spp. 6%, Campylobacter jejuni 13%, Campylobacter coli 2%, other Campylobacter spp. 8%, enteroaggregative E. coli 6%, Giardia spp. 2%, and Cryptosporidium spp. 2%. The present study provides additional insight into the aetiology of infectious intestinal disease in England and highlights the occurrence of viral infections in cases as well as in asymptomatic individuals. Other notable findings include the frequent presence of Campylobacter spp. other than C. jejuni or C. coli, the high frequency of multiple agents in 41% of cases and in 13% of controls, and the variation in the aetiology and rate of infection found for different age groups. The results demonstrate the greater sensitivity of PCR-based methods compared to current conventional methods.

Detection of Viral, Bacterial, and Parasitological RNA or DNA of Nine Intestinal Pathogens in Fecal Samples Archived as Part of the English Infectious Intestinal Disease Study

Fecal samples were collected from cases and controls as part of the Infectious Intestinal Disease (IID) study in England and were stored as frozen suspensions for 8 to 12 years. The purpose of this study was to apply PCR-based procedures to assess the stability of pathogen-specific nucleic acid sequences present in this archive. Samples from which Cryptosporidium, Giardia, Salmonella, Campylobacter, enteroaggregative Escherichia coli (EAggEC), enterotoxigenic Clostridium perfringens, rotaviruses, noroviruses, or sapoviruses had been previously detected during the IID study using conventional methods were selected from the archive. A generic nucleic acid extraction method to recover RNA or DNA was used. Complementary DNA was generated from RNA by reverse transcription with random priming. Block-based and real-time PCR assays were used to amplify and detect gene fragments from each of these pathogens. The percentage reconfirmation of target was as follows: Giardia duodenalis 68%, Cryptosporidium 96%, Campylobacter 98%, Salmonella 98%, enterotoxigenic C perfringens 34%, EAggEC 93.3%, rotavirus 95%, norovirus 73%, and sapovirus 85%. This study has shown that nucleic acid can be extracted and specific sequences amplified and detected from archived fecal samples. The IID archive therefore represents a valuable resource for further studies, especially the investigation of the samples from which no pathogens had previously been detected.

Guillain-Barré syndrome associated with Campylobacter jejuni infection in England, 2000-2001.

Guillain-Barré syndrome (GBS) is a rare but serious complication of infectious intestinal disease due to Campylobacter jejuni. To date, estimates of the burden of C. jejuni-associated GBS have been based on limited data regarding the proportion of GBS attributable to this pathogen. In this paper, we combine data obtained from Sweden and a large study of infectious intestinal disease with routine and surveillance data from England to estimate the number and proportion of GBS cases attributable to C. jejuni. We estimate that, between 1 April 2000 and 31 March 2001, symptomatic C. jejuni infection was responsible for 157 cases of GBS, constituting approximately 15% of all GBS cases in England.

The infectious intestinal disease study of England: a prospective evaluation of symptoms and health care use after an acute episode.

The sequelae of Infectious Intestinal Disease (IID) in a population-based sample of cases and matched controls were investigated for a period of 3 months following the initial infection. Incident cases of IID presenting to GPs or occurring in the community and controls were studied at 3 weeks and over a 3-month follow-up period. Cases were six times more likely than controls to have gastrointestinal symptoms, particularly diarrhoea, at 3 weeks. Ten per cent of cases consulted their GP in the 3 months after episode and 2.3% were referred to hospital. GP presentation rates were twice as high in cases. Gastrointestinal symptoms persist after IID, leading to an increased likelihood of GP consultation and hospital referral. Diagnosis of irritable bowel syndrome may be more likely following IID. The burden of IID is likely to be considerable given its high incidence and the frequency of such sequelae.

The study of infectious intestinal disease in England: what risk factors for presentation to general practice tell us about potential for selection bias in case-control studies of reported cases of diarrhoea.

Cases reported to national surveillance systems commonly form the sampling frame for population-based case-control studies of infectious intestinal diseases (IID). However, reported cases represent a minority of all cases in the population, differ systematically from unreported cases, and their use in case-control studies could introduce biases. Case reporting is a selective process involving multiple stages, the first of which requires presentation by a symptomatic person to the health services. Factors affecting a person's likelihood of presentation will thus affect the characteristics of reported cases. Data from a large study of IID in England were used to investigate factors influencing presentation to a general practitioner (GP) following an episode of IID. Multivariable logistic regression was performed, comparing GP presenters with non-presenters. Explanatory variables used were illness severity, recent foreign travel and socioeconomic indicators. Severe illness (OR = 12.54, 95% CI: 7.58-20.74), recent foreign travel (OR = 2.4, 95% CI: 1.39-4.14), leaving full-time education at an earlier age (OR = 2.06, 95% CI: 1.22-3.50) and housing categories representing lower socioeconomic status (SES) were all independently associated with GP presentation. Case reporting to national surveillance is shaped by complex biological and social factors, of which illness severity appears to be the most important. Results from case-control studies comparing cases of IID identified by surveillance with population controls are likely to generalize mainly to cases severe enough to be reported. Controlling for educational and SES (mostly housing) is required.

The study of infectious intestinal disease in England: socio-economic impact.

To assess the socio-economic impact of infectious intestinal disease (IID) on the health care sector, cases and their families, cases of IID ascertained from a population cohort component and those presenting to general practices were sent a socio-economic questionnaire 3 weeks after the acute episode. The impact of the illness was measured and the resources used were identified and costed. The duration, severity and costs of illness linked to viruses were less than those linked to bacteria. The average cost per case of IID presenting to the GP was Pound Sterling253 and the costs of those not seeing a GP were Pound Sterling34. The average cost per case was Pound Sterling606 for a case with salmonella, Pound Sterling315 for campylobacter, Pound Sterling164 for rotavirus and Pound Sterling176 for SRSV. The estimated cost of IID in England was Pound Sterling743m expressed in 1994/5 prices. The costs of IID are considerable and the duration of the illness was found to be longer than previous reports have suggested.

Vero cytotoxin-producing Escherichia coli in a study of infectious intestinal disease in England

An investigation of infectious intestinal disease in England included examination of feces for Vero cytotoxin-producing Escherichia coli (VTEC). Using DNA probe hybridization 27 VTEC strains were identified, 12 were from cases, and of these three belonged to serogroup O157. The remaining 15 strains were isolated from controls. The strains were confirmed biochemically as E. coli, they were serotyped and characterized according to their toxin production, the presence of sequences encoding intimin (eae) and enterohemolysin was determined and resistance to antimicrobial agents was determined. Six of the nine cases with non-O157 VTEC were less than 16 years old, only two of the 15 controls were under 16. Infection with more than one micro-organism was also considered.

The study of infectious intestinal disease in England: risk factors for cases of infectious intestinal disease with Campylobacter jejuni infection.

This is a case-control study aimed at identifying risk factors for intestinal infection with Campylobacter jejuni. Cases were defined as subjects with diarrhoea occurring in community cohorts or presenting to General Practitioners (GPs) with Campylobacter jejuni in stools. Controls were selected from GP lists or cohorts, matched by age, sex, and GP practice. Travel abroad and consumption of chicken in a restaurant were statistically significantly associated with being a case. There was no statistically significant risk associated with consumption of chicken other than in restaurants nor with reported domestic kitchen hygiene practices. Consumption of some foods was associated with a lower risk of being a case. Most cases remained unexplained. We suggest that infection with low numbers of micro-organisms, and individual susceptibility may play a greater role in the causation of campylobacter infection than previously thought. It is possible that in mild, sporadic cases infection may result from cross contamination from kitchen hygiene practices usually regarded as acceptable. Chicken may be a less important vehicle of infection for sporadic cases than for outbreaks, although its role as a source of infection in both settings requires further clarification in particular in relation to the effect of domestic hygiene practices. The potential effect of diet in reducing the risk of campylobacteriosis requires exploration.

A study of infectious intestinal disease in England: risk factors associated with group A rotavirus in children.

To identify risk factors for infectious intestinal disease (IID) due to rotavirus group A in children aged under 16 years. Case-control study of cases of IID with rotavirus infection presenting to general practitioners (GPs) or occurring in community cohorts, and matched controls. There were 139 matched pairs. In children under 16 years the following risk factors were significantly associated with rotavirus IID: living in rented council housing (adjusted OR = 3.78, P = 0.022), accommodation with more than five rooms (OR = 0.72, P = 0.002), contact with someone ill with IID (OR = 3.45, P < 0.001). Some foods were associated with decreased risk. In infants, bottle feeding with or without breast feeding was associated with increased risk (OR = 9.06, P < 0.05). Contact with persons with IID, living in rented council housing and accommodation with fewer rooms, were significant risk factors for sporadic rotavirus IID in children whereas breast feeding is protective in infants.

Characterisation of strains of enteroaggregative Escherichia coli isolated during the infectious intestinal disease study in England.

Strains of Escherichia coli, hybridising with a DNA probe for enteroaggregative E. coli (EAggEC), were isolated from patients with infectious intestinal disease (IID) or gastro-enteritis, and healthy controls during the study of IID in England. Of 3506 cases presenting with an IID, 160 (4.6%) had faecal EAggEC as compared with 46 (1.7%) of 2772 healthy controls, 53% of EAggEC isolated from each of the 'case' and the 'control' groups adhered in a 'stacked-brick' formation. Strains from cases and controls belonged to over 39 and 14 different serogroups respectively, and approximately half of the strains isolated did not react with antisera in the current somatic antigen serotyping scheme. Forty-nine cases with EAggEC (31%) had a known history of foreign travel. Over 50% of strains isolated from cases and controls were resistant to one or more of eight antimicrobials, and antimicrobial resistance was not statistically significantly more common among cases with a known history of foreign travel (p = 0.57). These data form part of the largest investigation carried out on these organisms in the UK to date and provide the most comprehensive analysis of strains of EAggEC isolated from the general population of England.