A new phylodynamic model of Mycobacterium bovis transmission in a multi-host system uncovers the role of the unobserved reservoir.

Multi-host pathogens are particularly difficult to control, especially when at least one of the hosts acts as a hidden reservoir. Deep sequencing of densely sampled pathogens has the potential to transform this understanding, but requires analytical approaches that jointly consider epidemiological and genetic data to best address this problem. While there has been considerable success in analyses of single species systems, the hidden reservoir problem is relatively under-studied. A well-known exemplar of this problem is bovine Tuberculosis, a disease found in British and Irish cattle caused by Mycobacterium bovis, where the Eurasian badger has long been believed to act as a reservoir but remains of poorly quantified importance except in very specific locations. As a result, the effort that should be directed at controlling disease in badgers is unclear. Here, we analyse densely collected epidemiological and genetic data from a cattle population but do not explicitly consider any data from badgers. We use a simulation modelling approach to show that, in our system, a model that exploits available cattle demographic and herd-to-herd movement data, but only considers the ability of a hidden reservoir to generate pathogen diversity, can be used to choose between different epidemiological scenarios. In our analysis, a model where the reservoir does not generate any diversity but contributes to new infections at a local farm scale are significantly preferred over models which generate diversity and/or spread disease at broader spatial scales. While we cannot directly attribute the role of the reservoir to badgers based on this analysis alone, the result supports the hypothesis that under current cattle control regimes, infected cattle alone cannot sustain M. bovis circulation. Given the observed close phylogenetic relationship for the bacteria taken from cattle and badgers sampled near to each other, the most parsimonious hypothesis is that the reservoir is the infected badger population. More broadly, our approach demonstrates that carefully constructed bespoke models can exploit the combination of genetic and epidemiological data to overcome issues of extreme data bias, and uncover important general characteristics of transmission in multi-host pathogen systems.

Trends in Salmonella serovars and antimicrobial resistance in pigs and poultry in Northern Ireland between 1997 and 2016.

BACKGROUND: In the EU, salmonellosis is the second most commonly reported zoonosis. This pattern is reflected in Northern Ireland. Historically, foodborne salmonellosis has largely been attributed to the consumption of poultry products, and as such a number of legislative measures have been introduced by the EC. These policies focus mainly on five target Salmonella serovars. METHODS: Here the authors present a descriptive analysis of 20 years of data from the Northern Ireland National Reference Laboratory for Salmonella. RESULTS: The study's results show, for poultry submissions, a large decrease in the detection of four of the five targeted Salmonella serovars over the study period, with the fifth serovar undetected throughout the study. Additionally, there was an increase in the detection of a number of other non-regulated serovars. In pigs, S Typhimurium, which is among the most common causes of human salmonellosis, was the most commonly isolated serovar. When comparing levels of antimicrobial resistance in S Typhimurium between livestock groups, the authors found a decrease over time in poultry, but an increase in pigs, highlighting the potential significance of pigs in addressing public health concerns. CONCLUSION: The authors conclude that continued surveillance is important in the assessment of control measures at a national and transnational scale.

Liver fluke (Fasciola hepatica) co-infection with bovine tuberculosis in cattle: A prospective herd-level assessment of herd bTB risk in dairy enterprises.

Co-infection of tuberculosis (TB) and helminths is recognized as a significant problem in regions where such pathogens are endemic and chronic cases exist. Co-infection can modulate the immune system leading to interference with diagnostic tests, increased pathological impacts and pathogen persistence. However, research has found that such interactions between pathogens can be context and species specific. Recent studies have suggested that liver fluke, Fasciola hepatica, infection may impact on immunological responses and diagnostics for bovine tuberculosis (bTB; caused by Mycobacterium bovis) in cattle. Where evidence of such interaction exists, there would be an onus on policy makers to adjust eradication programs to minimize impacts. We assessed the association between herd-level bTB breakdown risk and seasonal variation in liver fluke exposure based on 5,753 bulk tank milk (BTM) samples from 1,494 dairy herds across Northern Ireland. BTM was tested by an IDEXX antibody specific enzyme-linked immunosorbent assay (ELISA) using the 'f2' antigen as a detection agent. The ELISA determined the result based on a sample to (known) positive ratio (S/P%) from which binary status and categories of exposure were derived. Associations were tested using multivariable random effects models. Models predicting bTB risk were not improved with the inclusion of liver fluke exposure levels. Variations in modelling liver fluke exposure (S/P%, binary, categories of exposure) and bTB risk (skin test breakdowns, post-mortem confirmed breakdowns, breakdown size and lag effects) also failed to support associations (neither positive nor negative) between the pathogens at herd-level. These results, along with previously published animal-level data from Northern Ireland, suggest that the nexus between bTB and F. hepatica may have small size effects at the population-level. However, our results also highlight the high prevalence of F. hepatica in cattle in our study population, and therefore we cannot fully discount the potential hypothesis of population-level depression of immune response to M. bovis due to co-infection.

Liver fluke (Fasciola hepatica) co-infection with bovine tuberculosis (bTB) in cattle: A retrospective animal-level assessment of bTB risk in dairy and beef cattle.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a persistent problem for cattle industries in endemic countries. The frequency, quality, and performance of tests, and the presence of wildlife reservoirs, have been identified as impediments to eradication. Recently, exposure to helminth infection (Fasciola hepatica) has been associated negatively with the disclosure of bTB. Here, for the first time, we assess impact of concurrent infections of Fasciola hepatica and the disclosure of bTB at the animal-level using large surveillance datasets. We utilized a dataset of 138,566 animal records from an abattoir from Northern Ireland (2011-2013). The presence of F. hepatica infection was assessed from macroscopic tissue inspection at abattoir. Multivariable models were developed to assess co-infection associations with bTB status based on: Single Intradermal Comparative Tuberculin Test (SICTT), lesion, bacteriological confirmation, including either all animals, or only skin-test negative animals (lesions at routine slaughter; LRS; confirmed nonreactors at routine slaughter; cNRs) or positive (reactors) animals alone, respectively. The relationship between skin tuberculin reaction sizes and fluke status was also explored for a subset of animals with field recordings (n = 24,680). Controlling for known risk factors (e.g., climatic, herd, and individual level characteristics), we did not find significant associations between the SICTT (standard or severe interpretation), lesion, nor confirmation status of animals and their liver fluke status. The only exception was a negative association between liver fluke positivity, and LRS or cNRs, respectively; though effect-sizes were small (e.g., LRS Odds-Ratio: 0.87; 95% CI: 0.76-1.00). There was limited evidence of a relationship between tuberculin reaction sizes during SICTT testing and liver fluke infection status. These data do not support the contention that the detection of bTB using skin-tests or reactor postmortem follow-up may be compromised by co-infection at a population level, but the relationship with lesion formation (pathogenesis) may indicate an impact for postmortem surveillance.

Seasonal variation of Fasciola hepatica antibodies in dairy herds in Northern Ireland measured by bulk tank milk ELISA.

Bovine fasciolosis, caused by the infection of the trematode parasite Fasciola hepatica, remains a problem in dairy herds causing significant production losses. In this study, bulk milk tank samples were utilised to generate a comprehensive survey of the variation in liver fluke exposure over the four seasons of 2016 in Northern Ireland (NI). Samples were tested using an antibody ELISA test; within-herd prevalence levels were categorised relative to sample-to-positive ratio (S/P%). Overall, 1494 herds (~ 50% of all active dairy farms in NI) were sampled. In total, 5750 samples were tested with 91% of herds having a sample result for each season. The proportion of herds with evidence of liver fluke exposure was very high across the year, with 93.03% of all bulk milk samples having some indication of liver fluke antibody presence. A high proportion of samples (2187/5750; 38.03%) fell within the highest infection class (indicating high within-herd prevalence). There was significant seasonal variation in the mean S/P%. A multivariable random effect ordinal logit model suggested that the greatest probability of being in a higher infection class was in winter, whilst the lowest was recorded during summer. There was a significant negative association between increasing herd liver fluke infection class and herd size. Furthermore, there was significant variation in infection levels across regions of Northern Ireland, with higher infection levels in northern administrative areas. This study demonstrates the very high liver fluke exposure in this region of Europe, and that risk is not equally distributed spatially or across seasons in dairy herds.

Bovine tuberculosis visible lesions in cattle culled during herd breakdowns: the effects of individual characteristics, trade movement and co-infection.

BACKGROUND: Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a significant problem for livestock industries in many countries worldwide including Northern Ireland, where a test and slaughter regime has utilised the Single Intradermal Comparative Cervical Tuberculin (SICCT) test since 1959. We investigated the variation in post-mortem confirmation based on bTB visible lesion (VL) presence during herd breakdowns using two model suites. We investigated animal-level characteristics, while controlling for herd-level factors and clustering. We were interested in potential impacts of concurrent infection, and therefore we assessed whether animals with evidence of liver fluke infection (Fasciola hepatica; post-mortem inspection), M. avium reactors (animals with negative M. bovis-avium (b-a) tuberculin reactions) or Bovine Viral Diarrhoea Virus (BVDV; RT-PCR tested) were associated with bTB confirmation. RESULTS: The dataset included 6242 animals removed during the 14 month study period (2013-2015). bTB-VL presence was significantly increased in animals with greater b-a reaction size at the disclosing SICCT test (e.g. b-a = 5-9 mm vs. b-a = 0 mm, adjusted Odds ratio (aOR): 14.57; p < 0.001). M. avium reactor animals (b-a < 0) were also significantly more likely to disclose VL than non-reactor animals (b-a = 0; aOR: 2.29; p = 0.023). Animals had a greater probability of exhibiting lesions with the increasing number of herds it had resided within (movement; log-herds: aOR: 2.27-2.42; p < 0.001), if it had an inconclusive penultimate test result (aOR: 2.84-3.89; p < 0.001), and with increasing time between tests (log-time; aOR: 1.23; p = 0.003). Animals were less likely to have VL if they were a dairy breed (aOR: 0.79; p = 0.015) or in an older age-class (e.g. age-quartile 2 vs. 4; aOR: 0.65; p < 0.001). Liver fluke or BVDV variables were not retained in either multivariable model as they were non-significantly associated with bTB-VL status (p > 0.1). CONCLUSIONS: Our results suggest that neither co-infection of liver fluke nor BVDV had a significant effect on the presence of VLs in this high-risk cohort. M. avium tuberculin reactors had a significantly increased risk of disclosing with a bTB lesion, which could be related to the impact of co-infection with M. avium subsp. paratuberculosis (MAP) affecting the performance of the SICCT however further research in this area is required. Movements, test history, breed and age were important factors influencing confirmation in high-risk animals.

Risk factors for failure to detect bovine tuberculosis in cattle from infected herds across Northern Ireland (2004-2010).

Correctly identifying animals that are truly infected with a pathogen using ante-mortem tests is the cornerstone of any disease eradication programme. Failure to identify all infected animals will impede the progress towards controlling and eradicating disease and may also have unforeseen consequences when specific prevention measures are in place to avoid animal-to-animal transmission. In the case of bovine tuberculosis (bTB), the screening ante-mortem test, the Single Comparative Intradermal Tuberculin Test (SCITT), can exhibit moderate sensitivity which can result in a "hidden burden" of infection residing within the population. Using an animal-level dataset relating to the disclosure of infected cattle with Mycobacterium bovis, the causative agent of bTB within infected herds in Northern Ireland, we investigated what factors influenced the probability of an animal being a false-negative when truly infected (using post-mortem (PM) microbiological culture confirmation results to assess infection status). We found that different risk factors affected the probability of a test-negative outcome on infected animals depending on the ante-mortem test or their combination (SICTT and/or interferon gamma (IFN-É£) testing). Using multivariable models, SCITT disclosure performance varied significantly by age, location (region), and production type. The IFN-É£ tests were significantly affected by region or season, but these effects depended on the cut-off used during interpretation of the test which affected the tests characteristics. Parallel use of SCITT and IFN-É£ tests resulted in the least number of false-negatives, and their disclosure was affected by season and age-class. Understanding the factors that lead to the non-disclosure of infected animals is essential to optimise large-scale bTB disease eradication programmes.

Liver fluke (Fasciola hepatica) infection in cattle in Northern Ireland: a large-scale epidemiological investigation utilising surveillance data.

BACKGROUND: Liver fluke (Fasciola hepatica) is a widespread parasite of ruminants which can have significant economic impact on cattle production. Fluke infection status at the animal-level is captured during meat inspection of all animals processed for human consumption within Northern Ireland. These national datasets have not been analysed to assess their utility in uncovering patterns in fluke infection at animal- and herd-levels in Northern Ireland. METHODS: We utilised a dataset of 1.2 million animal records from ~18,000 herds across 3 years (2011-2013) to assess animal- and herd-level apparent prevalence and risk-factors associated with fluke infection. Animal-level apparent prevalence was measured as the proportion of animals exhibiting evidence of fluke infection at slaughter; between herd-level infection prevalence was measured by binary categorisation of herds (infected or not). "Within herd" infection prevalence was measured using the proportion of animals within a herd that showed evidence of fluke infection per year (ranging from 0-100%). "Within herd" infection prevalence at the herd level was investigated using multivariable modelling. RESULTS: At the animal level, the proportion of animals slaughtered that exhibited evidence of infection was 21-25% amongst years. Across herds, the proportion of herds with at least one infected animal, varied between 61 and 65%. However, there was a significant sampling effect at the herd-level; all herds where at least 105 animals slaughtered over the study period exhibited evidence of fluke infection (100%). There was significant variation in terms of within-herd infection prevalence. Risk factors included herd type, long-term weather variation, geographic location (region) and the abattoir. CONCLUSIONS: Liver fluke apparent prevalence was high at the herd-level across years. However, there was lower prevalence at the animal level, which may indicate significant variation in the exposure to fluke infection within herds. The proportion infected within-herds varied significantly in time and space, and by abattoir, herd-type and some weather variables. These data are a useful source of information on a widespread endemic disease, despite known limitations in terms of test performance (low sensitivity). As well as informing on the distribution and severity of liver fluke infection, these analyses will be used to investigate the effect of co-infection on risk for bovine tuberculosis.

Should they stay, or should they go? Relative future risk of bovine tuberculosis for interferon-gamma test-positive cattle left on farms.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is a serious infectious disease that remains an ongoing concern for cattle farming worldwide. Tuberculin skin-tests are often used to identify infected animals (reactors) during test-and-cull programs, however, due to relatively poor sensitivity, additional tests can be implemented in parallel. For example, in Northern Ireland interferon-gamma (IFN-g) testing is used in high-risk herds. However, skin-test negative animals which are positive to the IFN-g test are not required by law to be slaughtered - therefore the final choice for these animals' fate is left with the owner. During this study we investigated whether these animals represented a greater risk of becoming a skin reactor, relative to IFN-g test negative animals from the same herds. Our study population included 1107 IFN-g positive animals from 239 herds. A Cox-proportional hazard model indicated that animals which tested IFN-g positive were 2.31 times (95% CI: 1.92-2.79; P < 0.001) more likely to become a reactor compared with IFN-g negative animals. Animals from dairy herds, and from herds in the south-east, were of higher risk than animals from beef herds and other regions, respectively. Our findings suggest that IFN-g positive animals represent a higher risk of failing a skin-test in the future, indicating the value of IFN-g testing for identifying early-stage infected animals. These IFN-g positive animals are not under any disease restriction, and may move freely (trade), which may put recipient herds at increased risk. Our findings provide important evidence for stakeholders engaged in bTB eradication programs.

Hui and Walter's latent-class model extended to estimate diagnostic test properties from surveillance data: a latent model for latent data.

Diagnostic test sensitivity and specificity are probabilistic estimates with far reaching implications for disease control, management and genetic studies. In the absence of 'gold standard' tests, traditional Bayesian latent class models may be used to assess diagnostic test accuracies through the comparison of two or more tests performed on the same groups of individuals. The aim of this study was to extend such models to estimate diagnostic test parameters and true cohort-specific prevalence, using disease surveillance data. The traditional Hui-Walter latent class methodology was extended to allow for features seen in such data, including (i) unrecorded data (i.e. data for a second test available only on a subset of the sampled population) and (ii) cohort-specific sensitivities and specificities. The model was applied with and without the modelling of conditional dependence between tests. The utility of the extended model was demonstrated through application to bovine tuberculosis surveillance data from Northern and the Republic of Ireland. Simulation coupled with re-sampling techniques, demonstrated that the extended model has good predictive power to estimate the diagnostic parameters and true herd-level prevalence from surveillance data. Our methodology can aid in the interpretation of disease surveillance data, and the results can potentially refine disease control strategies.

Genomic prediction for tuberculosis resistance in dairy cattle.

BACKGROUND: The increasing prevalence of bovine tuberculosis (bTB) in the UK and the limitations of the currently available diagnostic and control methods require the development of complementary approaches to assist in the sustainable control of the disease. One potential approach is the identification of animals that are genetically more resistant to bTB, to enable breeding of animals with enhanced resistance. This paper focuses on prediction of resistance to bTB. We explore estimation of direct genomic estimated breeding values (DGVs) for bTB resistance in UK dairy cattle, using dense SNP chip data, and test these genomic predictions for situations when disease phenotypes are not available on selection candidates. METHODOLOGY/PRINCIPAL FINDINGS: We estimated DGVs using genomic best linear unbiased prediction methodology, and assessed their predictive accuracies with a cross validation procedure and receiver operator characteristic (ROC) curves. Furthermore, these results were compared with theoretical expectations for prediction accuracy and area-under-the-ROC-curve (AUC). The dataset comprised 1151 Holstein-Friesian cows (bTB cases or controls). All individuals (592 cases and 559 controls) were genotyped for 727,252 loci (Illumina Bead Chip). The estimated observed heritability of bTB resistance was 0.23±0.06 (0.34 on the liability scale) and five-fold cross validation, replicated six times, provided a prediction accuracy of 0.33 (95% C.I.: 0.26, 0.40). ROC curves, and the resulting AUC, gave a probability of 0.58, averaged across six replicates, of correctly classifying cows as diseased or as healthy based on SNP chip genotype alone using these data. CONCLUSIONS/SIGNIFICANCE: These results provide a first step in the investigation of the potential feasibility of genomic selection for bTB resistance using SNP data. Specifically, they demonstrate that genomic selection is possible, even in populations with no pedigree data and on animals lacking bTB phenotypes. However, a larger training population will be required to improve prediction accuracies.

Field-isolated genotypes of Mycobacterium bovis vary in virulence and influence case pathology but do not affect outbreak size.

Strains of many infectious agents differ in fundamental epidemiological parameters including transmissibility, virulence and pathology. We investigated whether genotypes of Mycobacterium bovis (the causative agent of bovine tuberculosis, bTB) differ significantly in transmissibility and virulence, combining data from a nine-year survey of the genetic structure of the M. bovis population in Northern Ireland with detailed records of the cattle population during the same period. We used the size of herd breakdowns as a proxy measure of transmissibility and the proportion of skin test positive animals (reactors) that were visibly lesioned as a measure of virulence. Average breakdown size increased with herd size and varied depending on the manner of detection (routine herd testing or tracing of infectious contacts) but we found no significant variation among M. bovis genotypes in breakdown size once these factors had been accounted for. However breakdowns due to some genotypes had a greater proportion of lesioned reactors than others, indicating that there may be variation in virulence among genotypes. These findings indicate that the current bTB control programme may be detecting infected herds sufficiently quickly so that differences in virulence are not manifested in terms of outbreak sizes. We also investigated whether pathology of infected cattle varied according to M. bovis genotype, analysing the distribution of lesions recorded at post mortem inspection. We concentrated on the proportion of cases lesioned in the lower respiratory tract, which can indicate the relative importance of the respiratory and alimentary routes of infection. The distribution of lesions varied among genotypes and with cattle age and there were also subtle differences among breeds. Age and breed differences may be related to differences in susceptibility and husbandry, but reasons for variation in lesion distribution among genotypes require further investigation.

Detectability of bovine TB using the tuberculin skin test does not vary significantly according to pathogen genotype within Northern Ireland.

Strains of many infectious diseases differ in parameters that influence epidemic spread, for example virulence, transmissibility, detectability and host specificity. Knowledge of inter-strain variation can be exploited to improve management and decrease disease incidence. Bovine tuberculosis (bTB) is increasingly prevalent among farmed cattle in the UK, exerting a heavy economic burden on the farming industry and government. We aimed to determine whether strains of Mycobacterium bovis (the causative agent of bTB) identified and classified using genetic markers (spoligotyping and multi-locus VNTR analysis) varied in response to the tuberculin skin test; this being the primary method of bTB detection used in the UK. Inter-strain variation in detectability of M. bovis could have important implications for disease control. The skin test is based on a differential delayed type hypersensitivity (DTH) response to intradermal injections of purified protein derivative (PPD) from M. bovis (PPD-B) and Mycobacterium avium (PPD-A). We searched for an association between skin test response (PPD-B skin rise minus PPD-A skin rise) and M. bovis genotype at the disclosing test in culture-confirmed cases using a field dataset consisting of 21,000 isolates belonging to 63 genotypes of M. bovis from cattle in Northern Ireland. We found no substantial variation among genotypes (estimated responses clustered tightly around the mean) controlling for animal sex, breed and test effects. We also estimated the ratio of skin test detected to undetected cases (i.e. cases only detected at abattoir). The skin test detection ratio varied among abattoirs with some detecting a greater proportion of cases than others but this variation was unrelated to the community composition of genotypes within each abattoir catchment. These two lines of evidence indicate that M. bovis genotypes in Northern Ireland have similar detectability using the skin test.

Whole genome sequencing reveals local transmission patterns of Mycobacterium bovis in sympatric cattle and badger populations.

Whole genome sequencing (WGS) technology holds great promise as a tool for the forensic epidemiology of bacterial pathogens. It is likely to be particularly useful for studying the transmission dynamics of an observed epidemic involving a largely unsampled 'reservoir' host, as for bovine tuberculosis (bTB) in British and Irish cattle and badgers. BTB is caused by Mycobacterium bovis, a member of the M. tuberculosis complex that also includes the aetiological agent for human TB. In this study, we identified a spatio-temporally linked group of 26 cattle and 4 badgers infected with the same Variable Number Tandem Repeat (VNTR) type of M. bovis. Single-nucleotide polymorphisms (SNPs) between sequences identified differences that were consistent with bacterial lineages being persistent on or near farms for several years, despite multiple clear whole herd tests in the interim. Comparing WGS data to mathematical models showed good correlations between genetic divergence and spatial distance, but poor correspondence to the network of cattle movements or within-herd contacts. Badger isolates showed between zero and four SNP differences from the nearest cattle isolate, providing evidence for recent transmissions between the two hosts. This is the first direct genetic evidence of M. bovis persistence on farms over multiple outbreaks with a continued, ongoing interaction with local badgers. However, despite unprecedented resolution, directionality of transmission cannot be inferred at this stage. Despite the often notoriously long timescales between time of infection and time of sampling for TB, our results suggest that WGS data alone can provide insights into TB epidemiology even where detailed contact data are not available, and that more extensive sampling and analysis will allow for quantification of the extent and direction of transmission between cattle and badgers.

Herd-level risk factors for bovine tuberculosis: a literature review.

Bovine tuberculosis (TB), caused by Mycobacterium bovis, is one of the most challenging endemic diseases currently facing government, the veterinary profession, and the farming industry in the United Kingdom and Ireland and in several other countries. The disease has a notoriously complex epidemiology; the scientific evidence supports both cattle-cattle and wildlife-cattle transmission routes. To produce more effective ways of reducing such transmission, it is important to understand those risk factors which influence the presence or absence of bovine TB in cattle herds. Here we review the literature on herd-level risk factor studies. Whilst risk factors operate at different scales and may vary across regions, epidemiological studies have identified a number of risk factors associated with bovine TB herd breakdowns, including the purchase of cattle, the occurrence of bovine TB in contiguous herds, and/or the surrounding area as well as herd size. Other factors identified in some studies include farm and herd management practices, such as, the spreading of slurry, the use of certain housing types, farms having multiple premises, and the use of silage clamps. In general, the most consistently identified risk factors are biologically plausible and consistent with known transmission routes involving cattle-cattle and wildlife-cattle pathways.

Survival from rectal and anal cancers in England and Wales, 1986-2001.

The aim of this study was to investigate the effects of tumour and patient characteristics on trends in the survival of patients with cancer of the anus or rectum in England and Wales. A total of 132,542 adults (15-99 years) who were diagnosed during the 14 years 1986-1999 were followed up to 2001 through the National Health Service Central Register. Relative survival up to 5 years after diagnosis was estimated, using deprivation-specific life tables. Generalised linear models were used to estimate relative excess risks of death, adjusted for patient and tumour characteristics. The results showed that 5-year relative survival was higher in women, younger patients and more affluent patients, and higher for anal cancer than rectal cancer. Survival improved by more than 10% from the late 1980s (around 38%) to the late 1990s (49%). This trend was not explained by changes in the distribution of age, anatomical site, morphology or deprivation. The trend was more marked in younger and more affluent patients, and for adenocarcinoma and epidermoid carcinoma than for tumours with other morphology. The inequality in survival between affluent and deprived patients widened. It is concluded that improvements in survival may reflect improvements in disease stage, diagnostic technique or treatment. Which of these factors contribute to the widening socioeconomic inequalities in survival remains to be elucidated.

Multiple genetic typing of Salmonella enterica serotype typhimurium isolates of different phage types (DT104, U302, DT204b, and DT49) from animals and humans in England, Wales, and Northern Ireland.

Salmonella enterica serotype Typhimurium is a common cause of salmonellosis among humans and animals in England, Wales, and Northern Ireland. Phage types DT104 and U302 were the most prevalent types in both livestock and humans in 2001. In addition, Salmonella serotype Typhimurium DT204b was responsible for a recent international outbreak involving England. A total of 119 isolates from humans (n = 28) and animals or their environment (n = 91), belonging to DT104 (n = 66), U302 (n = 33), DT204b (n = 12), and DT49 (n = 8), were fingerprinted by a combination of well-established genetic methods (pulsed-field gel electrophoresis [PFGE], PstI/SphI [PS] ribotyping, and plasmid profiling). The different techniques identified different degrees of polymorphism (from greatest to least, plasmid profiling [40 types], PS ribotyping [34 types], and PFGE [23 types]). It seems clear that a prevalent genomic clone, as well as a variety of less frequent clones, is present for each of the phage types. In most cases, the prevalent clones appeared within isolates from several animal species and from several geographical locations. We did not find clear evidence of a higher degree of diversity for any of the animal species included, or of any link between isolates from particular animal species and humans. The data presented show the inaccuracy of drawing epidemiological conclusions based on a single fingerprinting method. Strains that share one of the markers do not necessarily belong to the same clone, and a multiple typing approach is required to enable enough discrimination to track strains for epidemiological investigations.