Epidemiology of and risk factors for mortality due to carbapenemase-producing organisms (CPO) in healthcare facilities.

BACKGROUND: Carbapenemase-producing organisms (CPO) have been largely responsible for the extensive spread of carbapenem resistance, and their prevalence is increasing in many parts of the world. AIM: To evaluate clinical and molecular epidemiology and mortality associated with CPO among patients. METHODS: All CPO from clinical and long-term healthcare surveillance cultures across Scotland in 2003-2017 were reviewed retrospectively. Polymerase chain reaction was used to detect genes coding for carbapenemases. A generalized linear mixed model was used to identify risk factors for mortality. FINDINGS: In total, 290 individuals with CPO were identified. The overall incidence increased over time (P<0.001) from 0.02 to 1.38 per 100,000 population between 2003 and 2017. A total of 243 distinct CPO isolates were obtained from 269 isolations in 214 individuals with available metadata. The majority of the isolates were Enterobacterales (206/243, 84.8%), and Klebsiella pneumoniae (65/206, 31.6%) and Enterobacter cloacae (52/206, 25.2%) were the most common species. VIM (75/243, 30.9%) and NDM (56/243, 23.0%) were the most common carbapenemases. The crude 30-day mortality rate was 11.8% (25/211), while the case fatality rate was 5.7% (12/211). Age >60 years [adjusted odds ratio (aOR) 3.36, 95% confidence interval (CI) 1.06-10.63; P=0.033], presence of non-fermenters (aOR 4.88, 95% CI 1.64-14.47; P=0.005), and systemic infection or organ failure (aOR 4.21, 95% CI 1.38-12.81; P=0.032) were independently associated with 30-day mortality. CONCLUSION: The incidence of CPO in Scotland is low but increasing. Awareness is required that inpatients aged >60 years, patients with systemic infection or organ failure, and patients presenting with non-fermenters are at higher risk of death from CPO.

British Escherichia coli O157 in Cattle Study (BECS): to determine the prevalence of E. coli O157 in herds with cattle destined for the food chain.

Escherichia coli O157 are zoonotic bacteria for which cattle are an important reservoir. Prevalence estimates for E. coli O157 in British cattle for human consumption are over 10 years old. A new baseline is needed to inform current human health risk. The British E. coli O157 in Cattle Study (BECS) ran between September 2014 and November 2015 on 270 farms across Scotland and England & Wales. This is the first study to be conducted contemporaneously across Great Britain, thus enabling comparison between Scotland and England & Wales. Herd-level prevalence estimates for E. coli O157 did not differ significantly for Scotland (0·236, 95% CI 0·166-0·325) and England & Wales (0·213, 95% CI 0·156-0·283) (P = 0·65). The majority of isolates were verocytotoxin positive. A higher proportion of samples from Scotland were in the super-shedder category, though there was no difference between the surveys in the likelihood of a positive farm having at least one super-shedder sample. E. coli O157 continues to be common in British beef cattle, reaffirming public health policy that contact with cattle and their environments is a potential infection source.

Factors affecting the perception of recovery quality in horses after anaesthesia.

REASONS FOR PERFORMING STUDY: A significant effect of gender, experience and background, i.e. an evaluator's relationship with horses as equine anaesthetists, orthopaedic surgeons, practitioners or owners, on perceptions of recovery quality after anaesthesia would reduce the validity of recovery quality scoring systems. OBJECTIVES: To determine the effects of evaluator background, experience and gender on their perceptions of recovery quality; and questionnaire response rate as a function of background. STUDY DESIGN: Cross-sectional survey. METHODS: A total of 440 potential evaluators were invited to evaluate the video-recorded recoveries of 24 horses using a visual analogue scale (VAS) in which 0 = worst, 100 = best possible recovery. A mean score was generated for each of the 1-24 recoveries within each background group. These were compared using Spearman's rank correlation. The effect of gender and experience on VAS scores were analysed using an ordinal logistic regression after scores were categorised into 'intermediate, 'worst' and 'best' recovery categories based on median, 25th and 75th percentile VAS scores, respectively. RESULTS: The overall response rate was 35%. The greatest was from the anaesthetists (78%) followed by surgeons (43%). The response rate among owners and practitioners was 26%. Correlation among VAS scores across all background groups was high (Spearman rank > 0.90; P < 0.001). Among the combined veterinarians, there was no significant gender (P = 0.551) or experience (P = 0.103) effect. Among horse owners, the effect of experience was not significant (P = 0.116) although gender was (P = 0.027). Male horse owners awarded significantly greater scores than females. CONCLUSIONS: When VAS are used to grade recovery quality, neither the background nor the gender of veterinary evaluators affects quality perception. Male owners awarded greater scores than female owners, implying that they are less critical of recovery quality and a gender effect among horse owners must be considered when VAS are used to score recovery quality.

Disease transmission on fragmented contact networks: livestock-associated Methicillin-resistant Staphylococcus aureus in the Danish pig-industry.

Animal trade in industrialised livestock-production systems creates a complex, heterogeneous, contact network that shapes between-herd transmission of infectious diseases. We report the results of a simple mathematical model that explores patterns of spread and persistence of livestock-associated Methicillin-resistant Staphylococcus aureus (LA-MRSA) in the Danish pig-industry associated with this trade network. Simulations show that LA-MRSA can become endemic sustained by animal movements alone. Despite the extremely low predicted endemic prevalence, eradication may be difficult, and decreasing within-farm prevalence, or the time it takes a LA-MRSA positive farm to recover a negative status, fails to break long-term persistence. Our results suggest that a low level of non-movement induced transmission strongly affects MRSA dynamics, increasing endemic prevalence and probability of persistence. We also compare the model-predicted risk of 291 individual farms becoming MRSA positive, with results from a recent Europe-wide survey of LA-MRSA in holdings with breeding pigs, and find a significant correlation between contact-network connectivity properties and the model-estimated risk measure.

Comparison of subjective scoring systems used to evaluate equine laminitis.

This study compared three subjective scoring systems used to assess lameness associated with equine laminitis: (1) visual analogue scale, (2) Obel score and (3) clinical grading system (CGS). Two groups of 12 observers, consisting of equine veterinarians and final-year veterinary students, scored lameness severity after watching video footage of 14 horses on two occasions. Generalizability theory was used to investigate the reliability of the three systems and the effects of observer experience. Overall reliability across all times and observers was high. Intra-observer reliability was higher than inter-observer reliability for all scoring systems, with student reliability being consistently lower than veterinarians, especially for Obel and CGS. All three methods were reasonably reliable tools for assessing lameness, but they were more limited in the hands of inexperienced observers.

Vertical dimensions of suspended horses.

REASONS FOR STUDY: The dimensions of anaesthetised hobbled horses during suspension and transfer onto the operating table are unknown. These data are required for the cost-effective construction of equine surgical facilities. OBJECTIVES: To measure the distance from the toe to dependent back margin (Bsusp) and poll (Psusp) of anaesthetised suspended horses and correlate them with readily obtained measures from standing animals. METHODS: Digital photographs of suspended horses were taken in the anaesthesia induction box at a fixed position that allowed trigonometric determination of Bsusp and Psusp. These values were linked with body mass, height at the withers (Wstand), the length of the crest from the poll to the withers (crest) and of the back (back) from the withers to the crop, by deriving an equine morphological index (EMI) using principal component analysis. The EMI and other linear variables were then subjected to single variable regression analysis. RESULTS: EMI was 0.531mass((kg)) + 0.528Wstand((cm)) + 0.469crest((cm)) + 0.468back((cm)) . Bsusp was most accurately estimated using the expression Bsusp= 118.71 + 0.128EMI while Psusp was most strongly associated with Wstand, i.e. Psusp= 46.9 + 1.01Wstand((cm)) . CONCLUSIONS: The height of suspended horses at the most ventral margin of the back and the poll can be estimated from measures taken from the standing animal. POTENTIAL RELEVANCE: The data will allow the more informed planning and construction of equine surgical facilities in which mechanical hoists are used.

A comparison of four systems for scoring recovery quality after general anaesthesia in horses.

REASON FOR PERFORMING STUDY: The recovery quality scoring systems (RQSSs) in current use have not been critically reviewed for reliability. OBJECTIVE: To examine reliability (reproducibility) of 4 RQSSs when applied to a ranked series. METHODS: A DVD incorporating the recordings of 9 horses recovering from general anaesthesia was evaluated by final year students over 5 days. On Day 1, each evaluator ranked recoveries from 1-9 (1 = best). Over the following 4 days, each evaluator scored the same recoveries using 4 different RQSSs (3 of them in common usage and previously published) applied in random order. The scores from each RQSS were ranked and plotted against the Day 1 ranking of each evaluator to establish the extent of agreement using generalisability theory. The same 9 recoveries were also ranked by 12 experienced equine anaesthetists and the Spearman Rank Correlation coefficient calculated to determine the agreement between experienced and inexperienced evaluators. RESULTS: The recoveries were evaluated by 117 students. All 4 RQSSs were equally reliable with low (<4%) interobserver variability. The main (80%) source of total variation arose from differences between horses. The overall ranking within each RQSS was strongly correlated with Day 1 ranking. There was strong correlation (r = 0.983) between the students' ranking and that established by experienced anaesthetists. Interobserver reliability was similar with all 4 RQSSs. CONCLUSION: All 4 RQSSs studied were similarly reliable. POTENTIAL RELEVANCE: The selection of a universally acceptable RQSS from amongst the 4 examined can be based on criteria other than reliability, e.g. ease of use. This will facilitate wider scale multi-centre studies in recovery quality after anaesthesia in horses.

Exploiting strain diversity to expose transmission heterogeneities and predict the impact of targeting supershedding.

When a few individuals generate disproportionately many secondary cases, targeted interventions can theoretically lead to highly efficient control of the spread of infection. Practical exploitation of heterogeneous transmission requires the sources of variability to be quantified, yet it is unusual to have empirical data of sufficient resolution to distinguish their effects. Here, we exploit extensive data on pathogen shedding densities and the distribution of cases, collected from the same population within the same spatio-temporal window, to expose the comparative epidemiology of independent Escherichia coli O157 strains. For this zoonotic pathogen, which exhibits high-density shedding (supershedding) and heterogeneous transmission in its cattle reservoir, whether targeting supershedding could be an effective control depends critically on the proposed link between shedding density and transmissibility. We substantiate this link by showing that our supershedder strain has nearly triple the R(0) of our non-supershedder strain. We show that observed transmission heterogeneities are strongly driven by superspreading in addition to supershedding, but that for the supershedder strain, the dominant strain in our study population, there remains sufficient heterogeneity in contribution to R(0) from different shedding densities to allow exploitation for control. However, in the presence of substantial within-host variability, our results indicate that rather than seek out supershedders themselves, the most effective controls would directly target the phenomenon of pathogen supershedding with the aim of interrupting or preventing high shedding densities. In this system, multiple sources of heterogeneity have masked the role of shedding densities-our potential targets for control. This analysis demonstrates the critical importance of disentangling the effects of multiple sources of heterogeneity when designing targeted interventions.

Epidemiology of porcine non-specific colitis on Scottish farms.

The objective of this study was to investigate epidemiological risk factors for porcine non-specific colitis (NSC). Forty-seven Scottish pig farms, with and without a clinical history of diarrhoea during the growing period (15-40 kg), were selected. The study included farm visits, clinical inspection of pigs, completion of farm management questionnaires, pathological tests into the cause of the diarrhoea and analysis of the non-starch polysaccharide (NSP) content of feeds. The results from 17 farms designated as NSC and 10 control farms suggest dietary associations with NSC. Farms with NSC fed diets with significantly higher levels of NSPs, especially containing the sugars glucose, arabinose and xylose. Few management factors were identified, although the high prevalence of infectious colitis reduced the power of the study.

Heterogeneous shedding of Escherichia coli O157 in cattle and its implications for control.

Identification of the relative importance of within- and between-host variability in infectiousness and the impact of these heterogeneities on the transmission dynamics of infectious agents can enable efficient targeting of control measures. Cattle, a major reservoir host for the zoonotic pathogen Escherichia coli O157, are known to exhibit a high degree of heterogeneity in bacterial shedding densities. By relating bacterial count to infectiousness and fitting dynamic epidemiological models to prevalence data from a cross-sectional survey of cattle farms in Scotland, we identify a robust pattern: approximately 80% of the transmission arises from the 20% most infectious individuals. We examine potential control options under a range of assumptions about within- and between-host variability in infection dynamics. Our results show that the within-herd basic reproduction ratio, R(0), could be reduced to <1 with targeted measures aimed at preventing infection in the 5% of individuals with the highest overall infectiousness. Alternatively, interventions such as vaccination or the use of probiotics that aim to reduce bacterial carriage could produce dramatic reductions in R(0) by preventing carriage at concentrations corresponding to the top few percent of the observed range of counts. We conclude that a greater understanding of the cause of the heterogeneity in bacterial carriage could lead to highly efficient control measures to reduce the prevalence of E. coli O157.

Modelling the spread of scrapie in a sheep flock: evidence for increased transmission during lambing seasons.

Presence of scrapie infectivity in the placenta suggests the possibility of increased transmission of scrapie during the lambing season. This hypothesis was explored here using a mathematical model of scrapie transmission dynamics which has previously been successfully used to study several scrapie outbreaks in Scottish sheep flocks. It was applied here to the Langlade experimental sheep flock (INRA Toulouse, France), in which a natural scrapie epidemic started in 1993. Extensive data were available, including pedigree, scrapie histopathological diagnoses and PrP genotypes. Detailed simulations of the scrapie outbreak reveal that the observed patterns of seasonality in incidence can not be accounted for by seasonality in demography alone and provide strong support for the hypothesis of increased transmission during lambing. Observations from several other scrapie outbreaks also showing seasonal incidence patterns support these conclusions.

Neighbourhood control policies and the spread of infectious diseases.

We present a model of a control programme for a disease outbreak in a population of livestock holdings. Control is achieved by culling infectious holdings when they are discovered and by the pre-emptive culling of livestock on holdings deemed to be at enhanced risk of infection. Because the pre-emptive control programme cannot directly identify exposed holdings, its implementation will result in the removal of both infected and uninfected holdings. This leads to a fundamental trade-off: increased levels of control produce a greater reduction in transmission by removing more exposed holdings, but increase the number of uninfected holdings culled. We derive an expression for the total number of holdings culled during the course of an outbreak and demonstrate that there is an optimal control policy, which minimizes this loss. Using a metapopulation model to incorporate local clustering of infection, we examine a neighbourhood control programme in a locally spreading outbreak. We find that there is an optimal level of control, which increases with increasing basic reproduction ratio, R(0); moreover, implementation of control may be optimal even when R(0) < 1. The total loss to the population is relatively insensitive to the level of control as it increases beyond the optimal level, suggesting that over-control is a safer policy than under-control.

Factors influencing the shedding of verocytotoxin-producing Escherichia coli O157 by beef suckler cows.

A study was designed to investigate management factors that might influence the shedding of verocytotoxin-producing Escherichia coli (VTEC) O157 by beef cows in Scotland, where there is a particularly high rate of human infection. Thirty-two herds were visited at least monthly over approximately 1 year for collection of fresh faecal pat samples and information on management factors. The faecal pat samples were tested for VTEC O157 by established culture and immunomagnetic separation methods. Questionnaires were completed at the monthly visits to record management factors. Data were analysed using both univariate and multi-factor (GLMM) analysis. Changes in the number of cows in a group, dogs, wild geese, housing, and the feeding of draff (distillers' grains) were statistically significant as risk factors. The event of calving appeared to reduce the likelihood of shedding. Any effects of weaning or turnout were not statistically significant. It appears that the rate of shedding of VTEC O157 is influenced by several factors but possibly the most important of these are the circumstances of animals being housed, or, when outside, the presence of wild geese.

The construction and analysis of epidemic trees with reference to the 2001 UK foot-and-mouth outbreak.

The case-reproduction ratio for the spread of an infectious disease is a critically important concept for understanding dynamics of epidemics and for evaluating impact of control measures on spread of infection. Reliable estimation of this ratio is a problem central to epidemiology and is most often accomplished by fitting dynamic models to data and estimating combinations of parameters that equate to the case-reproduction ratio. Here, we develop a novel parameter-free method that permits direct estimation of the history of transmission events recoverable from detailed observation of a particular epidemic. From these reconstructed 'epidemic trees', case-reproduction ratios can be estimated directly. We develop a bootstrap algorithm that generates percentile intervals for these estimates that shows the procedure to be both precise and robust to possible uncertainties in the historical reconstruction. Identifying and 'pruning' branches from these trees whose occurrence might have been prevented by implementation of more stringent control measures permits estimation of the possible efficacy of these alternative measures. Examination of the cladistic structure of these trees as a function of the distance of each case from its infection source reveals useful insights about the relationship between long-distance transmission events and epidemic size. We demonstrate the utility of these methods by applying them to data from the 2001 foot-and-mouth disease outbreak in the UK.

Pre-exposure of cattle to drug-abbreviated Fasciola hepatica infections: the effect upon subsequent challenge infection and the early immune response.

In this study we examined whether juvenile liver flukes are capable of stimulating protective immune responses in cattle. Four experimental groups of cattle were studied as follows: group A, a positive control, received a primary infection on day 0 and a secondary infection 28 days later; group B also received two infections but the primary infection was terminated by drug treatment on day 5; group C, received infections on days 0, 5 and 10 which were terminated by drug treatments on days 1, 6 and 11 and then a secondary infection on day 28; group D received an infection only on day 28. Juvenile flukes appear to induce protective responses because: (a) group B animals had significantly lower levels of gamma-GT (P<0.05) than group D; (b) both groups B and C exhibited lower parenchymal phase GLDH levels (P=0.006 and 0.041, respectively); and (c) both groups B and C had lower secondary phase eosinophilia (P=0.002 and 0.02, respectively) than those in group D. Sera taken from groups A-C contained antibodies reacting to a variety of proteins in adult fluke somatic antigen and excretory-secretory preparations, particularly to proteins of 52-60, 68-72 and 82-96 kDa. After secondary challenge the antibody responses of group A to these proteins declined while reactivity to proteins of 28-30 kDa increased. Antibody responses to the 28-30 kDa proteins were not detected in groups B-D until 3 weeks later than those observed in group A. Antibody responses to Fasciola hepatica cathepsin L proteases, which are known to induce protection, were monophasic, of the IgG1 isotype only and were not observed prior to secondary challenge in any of the four groups. In contrast, the response to another protective antigen fraction, a high molecular sized haem protein, was of a mixed IgG1/IgG2 nature and was detected within 14 days of primary infection. However, no significant difference in antibody titres to either protein preparation was observed after the secondary infection when groups B and C were compared to group D.

Comparative epidemiology of scrapie outbreaks in individual sheep flocks.

Data recording the course of scrapie outbreaks in 4 sheep flocks (2 in Cheviot sheep and 2 in Suffolks) are compared. For each outbreak the data on scrapie incidence and sheep demography and pedigrees cover periods of years or decades. A key finding is that the incidence of clinical cases peaks in sheep 2-3 years old, despite very different forces-of-infection. This is consistent with age-specific susceptibility of sheep to scrapie, as has been reported for cattle to bovine spongiform encephalopathy and for humans to variant Creutzfeldt-Jakob disease. Scrapie incidence was higher in ewes than rams and at certain times of years, though these effects were not consistent between flocks. There was no evidence for high levels of vertical transmission.

Dynamics of the 2001 UK foot and mouth epidemic: stochastic dispersal in a heterogeneous landscape.

Foot-and-mouth is one of the world's most economically important livestock diseases. We developed an individual farm-based stochastic model of the current UK epidemic. The fine grain of the epidemiological data reveals the infection dynamics at an unusually high spatiotemporal resolution. We show that the spatial distribution, size, and species composition of farms all influence the observed pattern and regional variability of outbreaks. The other key dynamical component is long-tailed stochastic dispersal of infection, combining frequent local movements with occasional long jumps. We assess the history and possible duration of the epidemic, the performance of control strategies, and general implications for disease dynamics in space and time.