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Background: Campylobacteriosis is the leading cause of bacterial gastroenteritis in most developed countries. People are exposed to infection from contaminated food and environmental sources. However, the translation of these exposures into infection in the human population remains incompletely understood. This relationship is further complicated by differences in the presentation of cases, their investigation, identification, and reporting; thus, the actual differences in risk must be considered alongside the artefactual differences.Methods: Data on 33,967 confirmed Campylobacter infections in mainland Scotland between 2000 and 2006 (inclusive) that were spatially referenced to the postcode sector level were analysed. Risk factors including the Carstairs index of social deprivation, the easting and northing of the centroid of the postcode sector, measures of livestock density by species and population density were tested in univariate screening using a non-spatial generalised linear model. The NHS Health Board of the case was included as a random effect in this final model. Subsequently, a spatial generalised linear mixed model (GLMM) was constructed and age-stratified sensitivity analysis was conducted on this model.Results: The spatial GLMM included the protective effects of the Carstairs index (relative risk (RR) = 0.965, 95% Confidence intervals (CIs) = 0.959, 0.971) and population density (RR = 0.945, 95% CIs = 0.916, 0.974. Following stratification by age group, population density had a significant protective effect (RR = 0.745, 95% CIs = 0.700, 0.792) for those under 15 but not for those aged 15 and older (RR = 0.982, 95% CIs = 0.951, 1.014). Once these predictors have been taken into account three NHS Health Boards remain at significantly greater risk (Grampian, Highland and Tayside) and two at significantly lower risk (Argyll and Ayrshire and Arran).Conclusions: The less deprived and children living in rural areas are at the greatest risk of being reported as a case of Campylobacter infection. However, this analysis cannot differentiate between actual risk and heterogeneities in individual reporting behaviour; nevertheless this paper has demonstrated that it is possible to explain the pattern of reported Campylobacter infections using both social and environmental predictors. [ABSTRACT FROM AUTHOR]

Crosstalk between metabolic and survival pathways is critical for cellular homeostasis, but the connectivity between these processes remains poorly defined. We used loss-of-function CRISPR/Cas9 knockout screening to identify metabolic genes capable of influencing cellular commitment to apoptosis, using sensitization to the BCL-2 inhibitor ABT-199 in BCL-2-dependent acute myeloid leukemia (AML) cell lines as a proxy for apoptotic disposition. This analysis revealed metabolic pathways that specifically cooperate with BCL-2 to sustain survival. In particular, our analysis singled out heme biosynthesis as an unappreciated apoptosis-modifying pathway. Although heme is broadly incorporated into the proteome, reduction of heme biosynthesis potentiates apoptosis through the loss of ETC activity, resulting in baseline depolarization of the mitochondrial membrane and an increased propensity to undergo apoptosis. Collectively, our findings chart the first apoptotic map of metabolism, motivating the design of metabolically engaged combination chemotherapies and nominating heme biosynthesis as an apoptotic modulator in AML., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This report discloses the discovery and SAR of a series of 6-alkyl-2-aminopyrimidine derived histamine H4 antagonists that led to the development of JNJ 39758979, which has been studied in phase II clinical trials in asthma and atopic dermatitis. Building on our SAR studies of saturated derivatives from the indole carboxamide series, typified by JNJ 7777120, and incorporating knowledge from the tricyclic pyrimidines led us to the 6-alkyl-2,4-diaminopyrimidine series. A focused medicinal chemistry effort delivered several 6-alkyl-2,4-diaminopyrimidines that behaved as antagonists at both the human and rodent H4 receptor. Further optimization led to a panel of antagonists that were profiled in animal models of inflammatory disease. On the basis of the preclinical profile and efficacy in several animal models, JNJ 39758979 was selected as a clinical candidate; however, further development was halted during phase II because of the observation of drug-induced agranulocytosis (DIAG) in two subjects.

Objective: The histamine H4 receptor (H4R) has been shown to drive inflammatory responses in models of asthma, colitis and dermatitis, and in these models it appears to affect both innate and adaptive immune responses. In this study, we used both H4R-deficient mice and a specific H4R antagonist, JNJ 28307474, to investigate the involvement of the H4R in mouse arthritis models., Methods: H4R-deficient mice and wild-type mice administered the H4R antagonist were studied in models of collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA). The impact on Th17 cells was assessed by restimulation of inguinal lymphocytes in the disease or immunisation models and with in vitro stimulation of whole blood., Results: Both H4R-deficient mice and mice treated with the H4R antagonist exhibited reduced arthritis disease severity in both CAIA and CIA models. This was evident from the reduction in disease score and in joint histology. In the CIA model, treatment with the H4R antagonist reduced the number of interleukin (IL)-17 positive cells in the lymph node and the total production of IL-17. Th17 cell development in vivo was reduced in H4R-deficient mice or in mice treated with an H4R antagonist. Finally, treatment of both mouse and human blood with an H4R antagonist reduced the production of IL-17 when cells were stimulated in vitro., Conclusions: These results implicate the H4R in disease progression in arthritis and in the production of IL-17 from Th17 cells. This work supports future clinical exploration of H4R antagonists for the treatment of rheumatoid arthritis.

Objective: Antagonism of the histamine H4 receptor (H4R) has been shown to be anti-inflammatory in a number of preclinical disease models, however the exact mechanisms behind this are still being uncovered. In vitro, the receptor interacts with TLR and impacts inflammatory mediator production from a number of different cell types. Here it is shown that this interaction also occurs in vivo., Materials and Methods: Wild-type and H4R deficient BALB/c mice received an i.p. injection of LPS in PBS in conjunction with p.o. JNJ 7777120 or JNJ 28307474 (H4R antagonists). Two hours later blood was collected and TNF was measured., Results: Two different H4R antagonists inhibited LPS-induced TNF production in mice and this production was also reduced in H4R-deficient mice. The TNF mRNA analysis showed that the major source of the cytokine was the liver and not blood, and that the H4R antagonist only reduced the expression levels in the liver. Depletion or inactivation of macrophages reduced the TNF levels and eliminated the H4R sensitivity. Treatment with an H4R antagonist also reduced LPS-induced liver injury and blocked LPS-enhanced lung inflammation in mice., Conclusion: The data support an interaction between H4R and TLR activation in vivo that can drive inflammatory responses.

Background: Genetic typing data are a potentially powerful resource for determining how infection is acquired. In this paper MLST typing was used to distinguish the routes and risks of infection of humans with Campylobacter jejuni from poultry and ruminant sources, Methods: C. jejuni samples from animal and environmental sources and from reported human cases confirmed between June 2005 and September 2006 were typed using MLST. The STRUCTURE software was used to assign the specific sequence types of the sporadic human cases to a particular source. We then used mixed case-case logistic regression analysis to compare the risk factors for being infected with C. jejuni from different sources., Results: A total of 1,599 (46.3%) cases were assigned to poultry, 1,070 (31.0%) to ruminant and 67 (1.9%) to wild bird sources; the remaining 715 (20.7%) did not have a source that could be assigned with a probability of greater than 0.95. Compared to ruminant sources, cases attributed to poultry sources were typically among adults (odds ratio (OR) = 1.497, 95% confidence intervals (CIs) = 1.211, 1.852), not among males (OR = 0.834, 95% CIs = 0.712, 0.977), in areas with population density of greater than 500 people/km2 (OR = 1.213, 95% CIs = 1.030, 1.431), reported in the winter (OR = 1.272, 95% CIs = 1.067, 1.517) and had undertaken recent overseas travel (OR = 1.618, 95% CIs = 1.056, 2.481). The poultry assigned strains had a similar epidemiology to the unassigned strains, with the exception of a significantly higher likelihood of reporting overseas travel in unassigned strains., Conclusions: Rather than estimate relative risks for acquiring infection, our analyses show that individuals acquire C. jejuni infection from different sources have different associated risk factors. By enhancing our ability to identify at-risk groups and the times at which these groups are likely to be at risk, this work allows public health messages to be targeted more effectively. The rapidly increasing capacity to conduct genetic typing of pathogens makes such traced epidemiological analysis more accessible and has the potential to substantially enhance epidemiological risk factor studies.

An investigation is currently underway to explain an outbreak of food-borne botulism in Scotland. Three children in the same family were confirmed as having botulism following consumption of a meal made with a jar of korma sauce. Residual sauce from the jar, the jar lid and a remnant of the meal, all tested positive for Clostridium botulinum type A toxin. The children are recovering, although two remain ventilated and in intensive care unit.

To determine the proportion of Escherichia coli O157 cases in Scotland attributable to secondary spread, we analyzed data obtained through entire-population enhanced surveillance. We identified 11% of cases as secondary. Secondary cases in single households were younger than secondary cases in outbreaks affecting >1 household and had similar risk for hemolytic uremic syndrome.

Background: Airway remodeling and dysfunction are characteristic features of asthma thought to be caused by aberrant production of Th2 cytokines. Histamine H4 receptor (H4R) perturbation has previously been shown to modify acute inflammation and Th2 cytokine production in a murine model of asthma. We examined the ability of H4R antagonists to therapeutically modify the effects of Th2 cytokine production such as goblet cell hyperplasia (GCH), and collagen deposition in a sub-chronic model of asthma. In addition, effects on Th2 mediated lung dysfunction were also determined., Methods: Mice were sensitized to ovalbumin (OVA) followed by repeated airway challenge with OVA. After inflammation was established mice were dosed with the H4R antagonist, JNJ 7777120, or anti-IL-13 antibody for comparison. Airway hyperreactivity (AHR) was measured, lungs lavaged and tissues collected for analysis., Results: Therapeutic H4R antagonism inhibited T cell infiltration in to the lung and decreased Th2 cytokines IL-13 and IL-5. IL-13 dependent remodeling parameters such as GCH and lung collagen were reduced. Intervention with H4R antagonist also improved measures of central and peripheral airway dysfunction., Conclusions: These data demonstrate that therapeutic H4R antagonism can significantly ameliorate allergen induced, Th2 cytokine driven pathologies such as lung remodeling and airway dysfunction. The ability of H4R antagonists to affect these key manifestations of asthma suggests their potential as novel human therapeutics.

Background: Infectious 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 pound0.75 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/design: The 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., Discussion: Researchers 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.

The role of histamine H(4) receptor (H(4)R) was investigated in a T-helper type 2 (Th2)-cell-mediated mouse skin inflammation model that mimics several of the features of atopic dermatitis. Treatment with two specific H(4)R antagonists before challenge with FITC led to a significant reduction in ear edema, inflammation, mast cell, and eosinophil infiltration. This was accompanied by a reduction in the levels of several cytokines and chemokines in the ear tissue. Upon ex vivo antigen stimulation of lymph nodes, H(4)R antagonism reduced lymphocyte proliferation and IL-4, IL-5, and IL-17 levels. One explanation for this finding is that lymph nodes from animals dosed with the H(4)R antagonist, JNJ 7777120, contained a lower number of FITC-positive dendritic cells. The effect of H(4)R antagonism on dendritic cell migration in vivo may be an indirect result of the reduction in tissue cytokines and chemokines or a direct effect on chemotaxis. In addition to anti-inflammatory effects, JNJ 7777120 also significantly inhibited the pruritus shown in the model. Therefore, the dual effects of H(4)R antagonists on pruritus and Th2-cell-mediated inflammation point to their therapeutic potential for the treatment of Th2-mediated skin disorders, including atopic dermatitis.

In Europe, rotavirus gastroenteritis peaks in late winter or early spring suggesting a role for weather factors in transmission of the virus. In this study, multivariate regression models adapted for time-series data were used to investigate effects of temperature, humidity and rainfall on reported rotavirus infections and the infection-rate parameter, a derived measure of infection transmission that takes into account population immunity, in England, Wales, Scotland and The Netherlands. Delayed effects of weather were investigated by introducing lagged weather terms into the model. Meta-regression was used to pool together country-specific estimates. There was a 13 per cent (95% confidence interval (CI), 11-15%) decrease in reported infections per 1 degrees C increase in temperature above a threshold of 5 degrees C and a 4 per cent (95% CI, 3-5%) decrease in the infection-rate parameter per 1 degrees C increase in temperature across the whole temperature range. The effect of temperature was immediate for the infection-rate parameter but delayed by up to four weeks for reported infections. There was no overall effect of humidity or rainfall. There is a direct and simple relationship between cold weather and rotavirus transmission in Great Britain and The Netherlands. The more complex and delayed temperature effect on disease incidence is likely to be mediated through the effects of weather on transmission.

Background: This article presents information on all potential outbreaks of infectious intestinal disease (IID) identified by Health Protection Scotland (HPS) involving residents of Scotland. Unlike other systems, this alert system covers potential outbreaks of IID rather than apparently sporadic cases and covers all gastrointestinal pathogens, all visited countries, and all groups of travelers., Methods: HPS collects information on all potential outbreaks of IID in residents of Scotland where infection is believed to have been acquired abroad and disseminates this to all public health teams in Scotland so other linked cases can be identified. Where possible HPS also disseminates the details to the national surveillance center in the country where infection is believed to have been acquired, enabling them to facilitate any investigations or control measures they believe necessary. The rate of outbreaks associated with travel to particular countries was determined using the number of visits reported for residents of Scotland from Travel Trends data from the Office of National Statistics., Results: Between 2003 and 2007, 319 such potential outbreaks were identified. Spain was the most frequently identified country reflecting the fact that it was also the most frequently visited country; the rate per 100,000 visits to Spain was 1.4, very similar to the overall rate for all countries of 1.3, while the highest rate of 46.7 per 100,000 visitors was associated with travel to Egypt. Salmonella sp was the most frequently identified pathogen within which Salmonella enteritidis was the most frequently identified serotype., Conclusions: The system provides a rapid alert mechanism for potential outbreaks of IID outside Scotland, allowing their investigation and control as appropriate and demonstrates the risks of outbreaks associated with different countries and pathogens.

Background: The long-term clinical outcome for children affected by hemolytic uremic syndrome associated with verocytotoxin-producing Escherichia coli (VTEC-HUS) is well documented, but the parental experience is not., Objective: The authors investigated the effects of the critical-care hospitalization for this condition on well-being of patients' families., Method: A group of 30 parents completed a free-response format survey when their child presented to the hospital; 19 of this cohort completed a 1-year follow-up., Results: Content analysis demonstrated that this cohort of parents experienced long-term emotional distress and substantive disruption to family and daily life., Discussion: These results corroborate anecdotal clinical observations. The authors suggest future research initiatives and best practices to reduce parental distress.

An outbreak of campylobacteriosis affected approximately one-half of 165 people attending an annual farmers' dance in Montrose, Scotland, in November 2005. Epidemiological investigations, including a cohort study (n = 164), identified chicken liver paté as the most likely vehicle of infection. Paté preparation involved deliberate undercooking of chicken livers by flash-frying, followed by mechanical homogenization. Typing of 32 Campylobacter strains (isolated from submitted stools) by multilocus sequence typing identified four distinct clades of Campylobacter jejuni. There was good agreement when isolates were typed by Penner serotyping, pulsed-field gel electrophoresis, and flaA short variable region sequencing but poorer agreement with phage and antibiotic susceptibility testing. At least three attendees were coinfected with two Campylobacter strains each. The outbreak was probably due to several livers contributing Campylobacter strains that survived undercooking and were dispersed throughout the paté. The study highlights improper culinary procedures as a potential human health risk and provides a striking counterexample to the "dominant outbreak strain" view of point source outbreaks of food-borne infections. It also demonstrates that previous exposure to biologically plausible sources of Campylobacter may confer protection against subsequent infection.

Aims: To assess the effect of several measures of infant feeding on diarrhoeal disease, and whether these effects vary according to markers of social deprivation., Methods: Case-control study of diarrhoeal disease cases presenting to 34 general practices in England. Controls were stratified on age group, area deprivation index for the practice, and whether or not the practice was in London. Data were available on 304 infants (167 cases and 137 controls)., Results: After adjustment for confounders, breast feeding was associated with significantly less diarrhoeal disease. Associations were striking even in infants aged > or = 6 months. They did not vary by social class, but were greater in those living in rented council accommodation and in more crowded households. The effect of receiving no breast milk was stronger in more deprived areas than in less deprived areas. The effect of not receiving exclusive breast milk was stronger in more deprived areas than in less deprived areas. In formula fed infants, there was significantly more diarrhoeal disease in those not sterilising bottles/teats with steam or chemicals. The protective effect of breast feeding did not persist beyond two months after breast feeding had stopped., Conclusions: Breast feeding protects against diarrhoeal disease in infants in England although the degree of protection may vary across infants and wear off after breast feeding cessation. Education about the benefits of breast feeding and the risks of inadequate sterilisation should be targeted at carers in deprived areas or households.

Two serovars of salmonella which are currently of particular importance in both human and animal infections are Salmonella enterica serovars Enteritidis phage type 4 (PT4) and Typhimurium definitive type 104 (DT104). This paper describes the trends in the relationships between the levels of infection of people and a range of farm animal species with these two serovars and explores some of the reasons behind them. In 1996, there was a peak of 520 reports of S Typhimurium DT104 infection in people in Scotland, but the number has decreased every year since, to 96 in 2001. In cattle the incidence of S Typhimurium DT104 also peaked in 1996, with 138 incidents, and it has similarly decreased every year to 2001 when there were 10 reported incidents. Similar declines have been observed in its incidence in sheep and pigs. In people the number of reports of S Enteritidis PT4 peaked in 1997 at 1684 and then declined to 457 in 2001. In chickens, the number of reports of S Enteritidis PT4 peaked in 1998 at 34 incidents, but no incidents were reported in the following three years.

Objective: To describe the clinical, epidemiologic and microbiological features of a large outbreak of infection with a multiresistant Salmonella enterica serotype Typhimurium definitive type DT204b infection involving at least 392 people in five European countries., Methods: Icelandic public-health doctors responded to a report on an Internet news site of an outbreak of infection with a multiresistant strain of Typhimurium DT104 in England by contacting the Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC). An international alert was sent out through Enter-net. All strains from England & Wales, The Netherlands, Scotland and Germany, and 17 of the outbreak isolates from Iceland, were phage-typed, screened for antimicrobial resistance, and subjected to molecular typing. Hypothesis-generating interviews were conducted, followed by case-control studies performed in Iceland and England., Results: Isolates from cases in Iceland, England and Wales, The Netherlands, Scotland and Germany were identified as Typhimurium DT204b. The antimicrobial resistance pattern was ACGNeKSSuTTmNxCpL. All strains tested displayed an identical plasmid profile. Strains from five cases in England & Wales and five cases in Iceland possessed identical pulsed-field profiles. Although a common source was suspected, only Iceland implicated imported lettuce as a vehicle, with an analytic epidemiologic study (OR = 40.8; P = 0.005; 95% CI 2.7-3175)., Conclusion: The identification of international outbreaks, necessary for investigation and control, can be facilitated by standardized phage-typing techniques, the electronic transfer of molecular typing patterns, formal and informal links established through international surveillance networks, and the early reporting of national outbreaks to such networks.

Two outbreaks of infection with Salmonella enteritidis phage types 5c and 6a occurred in a number of Scottish health board areas between May 2000 and January 2001. A case-control study of food businesses was subsequently carried out to ascertain whether the scores derived from Environmental Health Officers' inspections prior to the outbreaks differed between food businesses where outbreak cases had eaten in the week before the onset of their illness (case food businesses) and neighbouring food businesses at which no outbreak case had eaten (control food businesses). The study showed no significant difference between the scores of case and control food businesses. The results suggest that the inspections were ineffective in identifying those food businesses that are more likely to cause incidents of food poisoning.

In 2000, the United Kingdom Government's Food Standards Agency published "A report of the study of infectious intestinal disease in England". This report was the result of over a decade's endeavour and cost well in excess of 2 million pound sterling (approximately 3.3 million euros). The study originated in 1989. In response to national epidemics of foodborne infection with Salmonella enteritidis phage type 4 and Listeria monocytogenes, the Government set up the Committee on the Microbiological Safety of Food (the Richmond Committee). This committee wished to know the actual level of clinical disease in the population giving rise to the laboratory reports of gastro-intestinal pathogens in national surveillance data and recommended studies to achieve this objective. In addition, successors to the to Richmond Committee decided that it would be of value to collect information from both cases and controls, including documenting exposure to biologically plausible risk factors so that differences between the ill and the well could be identified. Enquiries were also made about the clinical course of disease, so that long term sequelae and socio-economic costs could be estimated. A full description of this enormous study is beyond the scope of this paper, which defends the personal view that resources might have been better spent on a less ambitious enquiry.

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.

On Friday, 22 November 1996, the microbiologist at a hospital in Lanarkshire, Scotland, identified presumptive Escherichia coli O157 in faecal specimens submitted by three patients with bloody diarrhoea, and confirmed its presence in one. Over the next 6 h, 12 more potential cases were identified. Investigations first indicated then confirmed a single food premises as the source of infection. Effective control measures were applied promptly. The outbreak was declared over on 20 January 1997, by which time 512 cases had been identified, and infection with the outbreak strain confirmed in 279. Twenty deaths occurred in cases during the outbreak and there were two more in cases during 1997. Seventeen of these deaths resulted from the outbreak. This paper describes the outbreak's epidemiological investigation, referring to other investigations, and control measures, where appropriate.

Objective: To identify risk factors for infectious intestinal disease (IID) due to rotavirus group A in children aged under 16 years., Methods: Case-control study of cases of IID with rotavirus infection presenting to general practitioners (GPs) or occurring in community cohorts, and matched controls., Results: 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)., Conclusions: 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.

Recognition of the potential of Escherichia coli O157 and other Vero cytotoxin producing E. coli (VTEC) organisms to cause serious disease led to the recommendation that all diarrhoeal stool specimens be examined for E. coli O157. National guidelines exist for the testing and exclusion of cases and contacts of VTEC infection. A survey was conducted to discover the extent to which these recommendations are followed in Scotland by asking about current practices for public health management of identified cases and laboratory investigation of E. coli infection. About two thirds of Scottish health boards followed national guidelines for testing and exclusion of cases and contacts of VTEC O157 infection. Most laboratories tested all diarrhoeal stools for E. coli O157 but detection methods varied and a minority tested selected stools for non-O157 E. coli serogroups. Standardisation of policies for laboratory testing of VTEC infection would improve national surveillance. Adherence to evidence based guidelines would standardise public health management of VTEC infections in Scotland.

The notification of food poisoning is a statutory obligation of medical practitioners in the United Kingdom. Its objectives and methods are vague and ill documented, and the value of its output doubtful. Statutory notification of food poisoning is poor at identifying outbreaks, or single cases of severe disease, or as a measure of longer term trends. It should be fundamentally reformed.

The Committee on the Microbiological Safety of Food, set up in 1989 by the Department of Health in response to national epidemics of foodborne infection, considered the available evidence and commissioned a study of infectious intestinal disease (IID) in England. Seventy practices (with 489,500) patients overall) recruited from the Medical Research Council's General Practice Research Framework between August 1993 and January 1995 collected data for one year. The practice populations were representative of practices in England by area and urban/rural location, but with fewer small and affluent practices. There were five main components. i) A population cohort of 9776 (40% of those eligible) were enrolled to estimate the incidence and aetiology of IID in the community, and a large proportion were followed up. A median of 10% of patients on practice age-sex registers had moved away or died. ii) A nested case control component based on cases ascertained in the cohort was used to identify risk factors for IID in the community. iii) In a case control component used to identify risk factors and to estimate the incidence and aetiology of IID presenting in 34 general practices 70% of the 4026 cases returned risk factor questionnaires, 75% submitted stools, and matched controls were found for 75% of cases. iv) An enumeration component was used to estimate the incidence of IID presenting to general practitioners (GPs) in 36 practices and the proportion of specimens sent routinely for microbiological examination. v) In a socioeconomic costs component used to estimate the burden of illness of IID in the community and presenting to GPs 63% of those who returned a risk factor questionnaire also returned a socioeconomic questionnaire and were representative by age, sex, and social class. Despite variable enrolment and compliance the study sample had sufficient power for the multivariable analysis. The characteristics associated with low enrollment and compliance must be considered in the interpretation of the main study results.

Objective: To establish the incidence and aetiology of infectious intestinal disease in the community and presenting to general practitioners. Comparison with incidence and aetiology of cases reaching national laboratory based surveillance., Design: Population based community cohort incidence study, general practice based incidence studies, and case linkage to national laboratory surveillance., Setting: 70 general practices throughout England., Participants: 459 975 patients served by the practices. Community surveillance of 9776 randomly selected patients., Main Outcome Measures: Incidence of infectious intestinal disease in community and reported to general practice., Results: 781 cases were identified in the community cohort, giving an incidence of 19.4/100 person years (95% confidence interval 18.1 to 20.8). 8770 cases presented to general practice (3.3/100 person years (2.94 to 3.75)). One case was reported to national surveillance for every 1.4 laboratory identifications, 6.2 stools sent for laboratory investigation, 23 cases presenting to general practice, and 136 community cases. The ratio of cases in the community to cases reaching national surveillance was lower for bacterial pathogens (salmonella 3.2:1, campylobacter 7.6:1) than for viruses (rotavirus 35:1, small round structured viruses 1562:1). There were many cases for which no organism was identified., Conclusions: Infectious intestinal disease occurs in 1 in 5 people each year, of whom 1 in 6 presents to a general practitioner. The proportion of cases not recorded by national laboratory surveillance is large and varies widely by microorganism. Ways of supplementing the national laboratory surveillance system for infectious intestinal diseases should be considered.

On the afternoon of Friday 22 November 1996, Lanarkshire Health Board s Public Health Department became aware of 15 cases of possible Escherichia coli O157 infection (five of which had been confirmed microbiologically) in residents of the town of Wishaw i

Data from the surveillance scheme of all general outbreaks of infectious intestinal disease in England and Wales reported to or otherwise identified, by the Public Health Laboratory Service Communicable Disease Surveillance Centre (CDSC) in 1992 and 1994 were used to describe the epidemiology of outbreaks of infectious intestinal disease in residential institutions. Outbreaks in residential institutions accounted for 22% (282/1275) of all outbreaks with most, 95% (268/282), occurring in homes for the elderly. The commonest pathogens in these 282 outbreaks were small round structured viruses 48% (132), salmonellas 17% (49). Clostridium perfringens 8% (23), rotavirus 5% (15) and Shigella sonnei 2% (6). The mode of transmission was described as mainly person to person in 71% (200 outbreaks) and mainly foodborne in 21% (58 outbreaks). The mean duration of outbreaks was 9 days. Duration of outbreaks varied with both the mode of transmission and the pathogen involved. The mean attack rate was 37%. Illness was reported in 5872 people. One or more individuals were admitted to hospital in 22% of outbreaks. Twenty-six deaths were reported, of which 18 were attributed to salmonellosis. Outbreaks in residential institutions are common. Attack rates are high and outbreaks are often prolonged, with high morbidity and mortality. There is a need for effective infection control policies which include appropriate training of staff, simple surveillance systems and readily available expert advice to ensure outbreaks are rapidly controlled.

Data from the surveillance scheme of general outbreaks of infectious intestinal disease in England and Wales, reported to the PHLS Communicable Disease Surveillance Centre (CDSC), were used to review 1280 of the 1594 outbreaks identified between 1 January 1992 and 31 December 1994 for which a minimum data set was captured. The number of outbreaks reported in each regional health authority ranged from 31 in Mersey to 221 in Yorkshire. The commonest pathogens reported were salmonellas in 32% (412) of outbreaks, small round structured virus (SRSV) in 27% (342), Clostridium perfringens in 7% (90), and Shigella sonnei in 4% (46). The main mode of transmission was described as foodborne in 50% (642), over half of which were caused by salmonellas, and person to person in 39% (496), over half of which were caused by SRSV. Most outbreaks transmitted from person to person occurred in hospitals and in residential institutions for elderly people. Outbreaks lasted from one to 217 days (median five days) and their duration varied with the pathogen. The median attack rate was 37%. Illness was reported in 34,158 people, 751 of whom (2%) were admitted to hospital. There were 55 deaths, 28 of which were associated with salmonella and 12 with SRSV. Most of the outbreaks reported and the associated morbidity and mortality could have been prevented by following standard food hygiene practices, implementing infection control policies, and ensuring that food entering kitchens was of the highest microbiological quality possible.

This report describes why the 1994 measles/rubella immunisation campaign was necessary, reviews its implementation, and provides information on its impact in Scotland where 60,504 children were immunised. Data on suspected adverse reactions to the measles/rubella vaccine are also presented. A large UK measles epidemic was predicted by independent researchers, and action in response was planned in accordance with the recommendations of the Joint Committee on Vaccination and Immunisation. As a result, the epidemic predicted for England and Wales was averted and the epidemic which had occurred in the West of Scotland was prevented from spreading to the East. Laboratory-confirmed cases of measles and rubella are now rare in all parts of the UK, especially in the age group targeted by the campaign. Most reported adverse reactions were mild and self-limiting: only one child per 6,700 vaccinated in the UK was reported to have suffered any adverse reaction. Immediate, serious reactions were either allergic or were described as convulsions (most associated with immediate syncope); all of these children recovered fully. Later onset neurological problems were reported at rates no higher than expected from normal population incidence.

Twenty-eight outbreaks of infectious intestinal disease, reported as being transmitted mainly by the person to person route, were identified in association with retail catering premises, such as hotels, restaurants, and public houses, in England and Wales between 1992 and 1994. Five thousand and forty-eight people were at risk in these outbreaks and 1234 were affected. Most of the outbreaks (over 90%) occurred in hotels. Small round structured viruses were the most commonly detected pathogens. Diarrhoea and vomiting were common symptoms and most of the outbreaks occurred in the summer months. Control measures to contain infectious individuals and improved hygiene measures are necessary to contain such outbreaks.

The aetiology of sporadic campylobacter infection was investigated by means of a multicentre case-control study. During the course of the study 598 cases and their controls were interviewed. Conditional logistic regressional analysis of the data collected showed that occupational exposure to raw meat (odds ratio [OR] 9.37; 95% confidence intervals [CI] 2.03, 43.3), having a household with a pet with diarrhoea (OR 2.39; CI 1.09, 5.25), and ingesting untreated water from lakes, rivers and streams (OR 4.16; CI 1.45, 11.9) were significant independent risk factors for becoming ill with campylobacter. Handling any whole chicken in the domestic kitchen that had been bought raw with giblets, or eating any dish cooked from chicken of this type in the home (OR 0.41-0.44; CI 0.24, 0.79) and occupational contact with livestock or their faeces (OR 0.44; CI 0.21, 0.92) were significantly associated with a decrease in the risk of becoming ill with campylobacter.

We have analysed data from the surveillance scheme of general foodborne outbreaks of infectious intestinal disease in England and Wales reported to, or otherwise identified by, the PHLS Communicable Disease Surveillance Centre in 1992 and 1993. Data were available about 458 outbreaks, 197 (43%) in commercial catering premises (restaurants, cafés, hotels, public houses, and canteens), 77 (17%) associated with food prepared in private houses, and 58 (13%) in hospitals and residential institutions. Salmonellas and Clostridium perfringens were responsible for 340 outbreaks (74%) and no pathogen was identified in 55 outbreaks (12%). Organisms associated with the highest mean attack rates were Staphylococcus aureus (66%) and C. perfringens (53%). Eleven thousand people were reported to be il and 362 were admitted to hospital. There were 15 deaths, 13 of which were associated with salmonellosis. A specified food was suspected to be the vehicle of infection in 204 outbreaks (45%). Possible contributory factors were identified in 277 (61%), most commonly inappropriate storage, cross contamination, and inadequate heat treatment. Reducing the incidence of food poisoning will depend on concerted action on farms, in abattoirs and food processing plants, in wholesale and retail outlets, and in kitchens.