J. Cowden

Demographic determinants for Campylobacter infection in England and Wales: implications for future epidemiological studies

Despite a significant public health burden the epidemiology of human Campylobacter infection remains blurred. The identification of demographic determinants for Campylobacter infection is therefore essential for identifying potential areas for intervention. Demographic data from an active, population-based sentinel surveillance system for Campylobacter infection (from 2000 until 2003, n=15 907) were compared with appropriate denominator data from the 2001 United Kingdom Census. Incidence was higher in males from birth until the late teens and in females from 20 to 36 years. Age- and gender-specific differences in Campylobacter incidence were observed in different ethnic and socioeconomic groups and hence are all major drivers for Campylobacter infection. Epidemiological studies on Campylobacter infection need to take these factors into consideration during design and analysis. The collation of detailed epidemiological data and its comparison with appropriate denominator data provides a valuable epidemiological tool for studying infection.

Elucidating the Aetiology of Human Campylobacter coli Infections

There has been little research on the determinants of Campylobacter coli infection, despite its contributing up to 10% of human Campylobacter infections. A case-control and two case-case study methods explored the aetiology of C. coli over a one year period across Scotland. The case-control multivariate model found an increased risk of C. coli infection in people older than 19 years (O.R. = 3.352), and during the summer months (O.R. = 2.596), while residing in an urban area decreased the risk (O.R. = 0.546). The first case-case study compared C. coli and C. jejuni cases and also showed a higher risk of C. coli during the summer (O.R. = 1.313) and in people older than 19 years (O.R. = 0.791). Living in an urban area was associated with a reduced risk of infection (O.R. = 0.769). Multi-locus sequence typing (MLST) indicated that sheep and chicken C. coli sequence types (STs) were most frequently found in humans whilst those from cattle and pigs were rarer. MLST diversity was high in isolates from pigs and chicken, intermediate in human isolates, and low in ruminant isolates. The second case-case study used MLST data to ascribe putative sources of infection to the cases. The putative source for 40% of cases was chicken, with 60% acquired from other sources (ruminants 54% and pigs 6%). The case-case analysis also showed that female gender was a risk factor (O.R. = 1.940), which may be explained by females being more likely to prepare poultry in the home. These findings indicate differences between the aetiology of C. coli and C. jejuni infections: this should be taken into account by public health professionals when developing strategies to reduce the burden of human campylobacteriosis.

Geographic determinants of reported human Campylobacter infections in Scotland

BackgroundCampylobacteriosis 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.MethodsData 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.ResultsThe 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).ConclusionsThe 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.

Using sequence data to identify alternative routes and risk of infection: a case-study of campylobacter in Scotland

BackgroundGenetic 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 sourcesMethodsC. 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.ResultsA 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.ConclusionsRather 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.

Identifying the seasonal origins of human campylobacteriosis

Human campylobacteriosis exhibits a distinctive seasonality in temperate regions. This paper aims to identify the origins of this seasonality. Clinical isolates [typed by multi-locus sequence typing (MLST)] and epidemiological data were collected from Scotland. Young rural children were found to have an increased burden of disease in the late spring due to strains of non-chicken origin (e.g. ruminant and wild bird strains from environmental sources). In contrast the adult population had an extended summer peak associated with chicken strains. Travel abroad and UK mainland travel were associated with up to 17% and 18% of cases, respectively. International strains were associated with chicken, had a higher diversity than indigenous strains and a different spectrum of MLST types representative of these countries. Integrating empirical epidemiology and molecular subtyping can successfully elucidate the seasonal components of human campylobacteriosis. The findings will enable public health officials to focus strategies to reduce the disease burden.

Salmonella enterica serovar Agona European outbreak associated with a food company.

We investigated an international outbreak of Salmonella Agona with a distinct PFGE pattern associated with an Irish Food company (company X) producing pre-cooked meat products sold in various food outlet chains in Europe. The outbreak was first detected in Ireland. We undertook national and international case-finding, food traceback and microbiological investigation of human, food and environmental samples. We undertook a matched case-control study on Irish cases. In total, 163 cases in seven European countries were laboratory-confirmed. Consumption of food from food outlet chains supplied by company X was significantly associated with being a confirmed case (mOR 18·3, 95% CI 2·2-149·2) in the case-control study. The outbreak strain was isolated from the companys pre-cooked meat products and production premises. Sufficient evidence was gathered to infer the vehicles of infection and sources of the outbreak and to justify the control measures taken, which were plant closure and food recall.

A large Great Britain-wide outbreak of STEC O157 phage type 8 linked to handling of raw leeks and potatoes

Between December 2010 and July 2011, 252 cases of STEC O157 PT8 stx1 + 2 infection were reported in England, Scotland and Wales. This was the largest outbreak of STEC reported in England and the second largest in the UK to date. Eighty cases were hospitalized, with two cases of haemolytic uraemic syndrome and one death reported. Routine investigative data were used to generate a hypothesis but the subsequent case-control study was inconclusive. A second, more detailed, hypothesis generation exercise identified consumption or handling of vegetables as a potential mode of transmission. A second case-control study demonstrated that cases were more likely than controls to live in households whose members handled or prepared leeks bought unwrapped [odds ratio (OR) 40, 95% confidence interval (CI) 2·08-769·4], and potatoes bought in sacks (OR 13·13, 95% CI 1·19-145·3). This appears to be the first outbreak of STEC O157 infection linked to the handling of leeks.

From diarrhoea to haemolytic uraemic syndrome - when to seek advice.

It is difficult to distinguish between infectious and non-infectious bloody diarrhoea, and between infections with verocytotoxin-producing Escherichia coli (VTEC), such as E. coli O157, and other pathogens. Typically, 10–15 % of VTEC infections quickly progress to haemolytic uraemic syndrome (HUS) (Tarr et al., 2005). To prevent this, cases must be identified more rapidly than possible by microbiological diagnosis. If achieved, this is advantageous for two reasons. Firstly, intravenous volume expansion, even before VTEC is microbiologically identified in such patients, might mitigate the risk of developing oligoanuric forms of HUS which are associated with poorer outcome (Ake et al., 2005). Secondly, secondary spread of VTEC organisms, which is common and occurs early in the course of disease, might be reduced by hospitalizing the paediatric patient or otherwise separating the patient from its sibling (Werber et al., 2008).

Putative household outbreaks of campylobacteriosis typically comprise single MLST genotypes

During a 15-month period in Scotland a small but important number of human Campylobacter cases (3·2%) arose from 91 putative household outbreaks. Of the 26 outbreaks with known strain composition, 89% were composed of the same MLST which supports the potential use of MLST in public health epidemiology. The number of cases associated with household outbreaks is much larger than general outbreaks and there is some evidence to indicate that there may be secondary transmission, although this is relatively rare.

Operationalising factors that explain the emergence of infectious diseases : a case study of the human campylobacteriosis epidemic

A framework of general factors for infectious disease emergence was made operational for Campylobacter utilising explanatory variables including time series and risk factor data. These variables were generated using a combination of empirical epidemiology, case-case and case-control studies, time series analysis, and microbial sub-typing (source attribution, diversity, genetic distance) to unravel the changing/emerging aetiology of human campylobacteriosis. The study focused on Scotland between 1990–2012 where there was a 75% increase in reported cases that included >300% increase in the elderly and 50% decrease in young children. During this period there were three phases 1990–2000 a 75% rise and a 20% fall to 2006, followed by a 19% resurgence. The rise coincided with expansions in the poultry industry, consumption of chicken, and a shift from rural to urban cases. The post-2000 fall occurred across all groups apart from the elderly and coincided with a drop of the prevalence of Campylobacter in chicken and a higher proportion of rural cases. The increase in the elderly was associated with uptake of proton pump inhibitors. During the resurgence the increase was predominantly in adults and the elderly, again there was increasing use of PPIs and high prevalences in chicken and ruminants. Cases associated with foreign travel during the study also increased from 9% to a peak of 16% in 2006 before falling to an estimated 10% in 2011, predominantly in adults and older children. During all three periods source attribution, genetic distance, and diversity measurements placed human isolates most similar to those in chickens. A combination of emergence factors generic for infectious diseases were responsible for the Campylobacter epidemic. It was possible to use these to obtain a putative explanation for the changes in human disease and the potential to make an informed view of how incidence rates may change in the future.