Evaluation of a Performance-Based Expert Elicitation: WHO Global Attribution of Foodborne Diseases.

For many societally important science-based decisions, data are inadequate, unreliable or non-existent, and expert advice is sought. In such cases, procedures for eliciting structured expert judgments (SEJ) are increasingly used. This raises questions regarding validity and reproducibility. This paper presents new findings from a large-scale international SEJ study intended to estimate the global burden of foodborne disease on behalf of WHO. The study involved 72 experts distributed over 134 expert panels, with panels comprising thirteen experts on average. Elicitations were conducted in five languages. Performance-based weighted solutions for target questions of interest were formed for each panel. These weights were based on individual expert's statistical accuracy and informativeness, determined using between ten and fifteen calibration variables from the experts' field with known values. Equal weights combinations were also calculated. The main conclusions on expert performance are: (1) SEJ does provide a science-based method for attribution of the global burden of foodborne diseases; (2) equal weighting of experts per panel increased statistical accuracy to acceptable levels, but at the cost of informativeness; (3) performance-based weighting increased informativeness, while retaining accuracy; (4) due to study constraints individual experts' accuracies were generally lower than in other SEJ studies, and (5) there was a negative correlation between experts' informativeness and statistical accuracy which attenuated as accuracy improved, revealing that the least accurate experts drive the negative correlation. It is shown, however, that performance-based weighting has the ability to yield statistically accurate and informative combinations of experts' judgments, thereby offsetting this contrary influence. The present findings suggest that application of SEJ on a large scale is feasible, and motivate the development of enhanced training and tools for remote elicitation of multiple, internationally-dispersed panels.

Attributing foodborne salmonellosis in humans to animal reservoirs in the European Union using a multi-country stochastic model.

A Bayesian modelling approach comparing the occurrence of Salmonella serovars in animals and humans was used to attribute salmonellosis cases to broilers, turkeys, pigs, laying hens, travel and outbreaks in 24 European Union countries. Salmonella data for animals and humans, covering the period from 2007 to 2009, were mainly obtained from studies and reports published by the European Food Safety Authority. Availability of food sources for consumption was derived from trade and production data from the European Statistical Office. Results showed layers as the most important reservoir of human salmonellosis in Europe, with 42·4% (7 903 000 cases, 95% credibility interval 4 181 000-14 510 000) of cases, 95·9% of which was caused by S. Enteritidis. In Finland and Sweden, most cases were travel-related, while in most other countries the main sources were related to the laying hen or pig reservoir, highlighting differences in the epidemiology of Salmonella, surveillance focus and eating habits across the European Union.

Risk ranking of pathogens in ready-to-eat unprocessed foods of non-animal origin (FoNAO) in the EU: initial evaluation using outbreak data (2007-2011).

Foods of non-animal origin (FoNAO) are consumed in a variety of forms, being a major component of almost all meals. These food types have the potential to be associated with large outbreaks as seen in 2011 associated with VTEC O104. In order to identify and rank specific food/pathogen combinations most often linked to human cases originating from FoNAO in the EU, a semi-quantitative model was developed using seven criteria: strength of associations between food and pathogen based on the foodborne outbreak data from EU Zoonoses Monitoring (2007-2011), incidence of illness, burden of disease, dose-response relationship, consumption, prevalence of contamination and pathogen growth potential during shelf life. The top ranking food/pathogen combination was Salmonella spp. and leafy greens eaten raw followed by (in equal rank) Salmonella spp. and bulb and stem vegetables, Salmonella spp. and tomatoes, Salmonella spp. and melons, and pathogenic Escherichia coli and fresh pods, legumes or grains. Despite the inherent assumptions and limitations, this risk model is considered a tool for risk managers, as it allows ranking of food/pathogen combinations most often linked to foodborne human cases originating from FoNAO in the EU. Efforts to collect additional data even in the absence of reported outbreaks as well as to enhance the quality of the EU-specific data, which was used as input for all the model criteria, will allow the improvement of the model outputs. Furthermore, it is recommended that harmonised terminology be applied to the categorisation of foods collected for different reasons, e.g. monitoring, surveillance, outbreak investigation and consumption. In addition, to assist future microbiological risk assessments, consideration should be given to the collection of additional information on how food has been processed, stored and prepared as part of the above data collection exercises.

Using surveillance and monitoring data of different origins in a Salmonella source attribution model: a European Union example with challenges and proposed solutions.

Microbial subtyping approaches are commonly used for source attribution of human salmonellosis. Such methods require data on Salmonella in animals and humans, outbreaks, infection abroad and amounts of food available for consumption. A source attribution model was applied to 24 European countries, requiring special data management to produce a standardized dataset. Salmonellosis data on animals and humans were obtained from datasets provided by the European Food Safety Authority. The amount of food available for consumption was calculated based on production and trade data. Limitations included different types of underreporting, non-participation in prevalence studies, and non-availability of trade data. Cases without travel information were assumed to be domestic; non-subtyped human or animal records were re-identified according to proportions observed in reference datasets; missing trade information was estimated based on previous years. The resulting dataset included data on 24 serovars in humans, broilers, laying hens, pigs and turkeys in 24 countries.

Source attribution of human campylobacteriosis in Denmark.

SUMMARY This study assesses the contribution of different sources of human campylobacteriosis in Denmark using two different source-attribution approaches. In total, 794 non-human isolates and 406 isolates from human cases (domestic, travel related, and cases with unknown travel history) were collected. Isolates were characterized by multilocus sequence typing, flaA typing and susceptibility to antibiotics. Both models used indicate that the major burden of human campylobacteriosis in Denmark originates from the domestic broiler chicken reservoir. The second most important reservoir was found to be cattle. The Asymmetric Island model attributed 52% [95% credibility interval (CrI) 37-67] to Danish chicken, 17% (95% CrI 3-33) to imported chicken, and 17% (95% CrI 7-28) to cattle. Similarly, the Campylobacter source-attribution model apportioned 38% (95% CrI 28-47) to Danish chicken, 14% (95% CrI 10-18) to imported chicken, and 16% (95% CrI 7-25) to cattle. The addition of flaA type as an extra discriminatory typing parameter did not change the attribution of cases markedly.

Source attribution of human campylobacteriosis using a meta-analysis of case-control studies of sporadic infections.

Campylobacter spp. is a widespread and important cause of human illness worldwide. Disease is frequently associated with foodborne transmission, but other routes of exposure, such as direct contact with live animals and person-to-person transmission, are also recognized. Identifying the most important sources of human disease is essential for prioritizing food safety interventions and setting public health goals. Numerous case-control studies of sporadic infections of campylobacteriosis have been published. These studies investigated a variety of potential risk factors for disease, often using different methodologies and settings. Systematic reviews (SRs) consist of a formal process for literature review focused on a specific research question, and include the identification of relevant literature, quality assessment of relevant studies, summarization or statistical analysis of data, and conclusions. With the objective of identifying the most important risk factors for human sporadic campylobacteriosis, we performed a SR of case-control studies of human sporadic cases and a meta-analysis of the obtained results. A combined SR focusing on Salmonella and Campylobacter studies was performed and the results analysed separately. From 1295 identified references, 131 passed the relevance screening, 73 passed the quality assessment stage, and data was extracted from 72 studies. Of these, 38 focused on campylobacteriosis. Information on exposures of cases and controls, and estimated odds ratios for investigated risk factors were collected and analysed. In the meta-analysis, heterogeneity between the studies and possible sources of bias were investigated, and pooled odds ratios for identified risk factors were estimated. Results suggest that travelling abroad, eating undercooked chicken, environmental sources, and direct contact with farm animals were significant risk factors for campylobacteriosis. Sub-analyses by geographical region, age group, and study period were performed, and differences were discussed.

Source attribution of human salmonellosis using a meta-analysis of case-control studies of sporadic infections.

Salmonella is an important cause of human illness. Disease is frequently associated with foodborne transmission, but other routes of exposure are recognized. Identifying sources of disease is essential for prioritizing public health interventions. Numerous case-control studies of sporadic salmonellosis have been published, often using different methodologies and settings. Systematic reviews consist of a formal process for literature review focused on a research question. With the objective of identifying the most important risk factors for salmonellosis, we performed a systematic review of case-control studies and a meta-analysis of obtained results. Thirty-five Salmonella case-control studies were identified. In the meta-analysis, heterogeneity between studies and possible sources of bias were investigated, and pooled odds ratios estimated. Results suggested that travel, predisposing factors, eating raw eggs, and eating in restaurants were the most important risk factors for salmonellosis. Sub-analyses by serotype were performed when enough studies were available.

The effects, costs and benefits of Salmonella control in the Danish table-egg sector.

A public plan for eradicating Salmonella in Danish table-egg production was implemented in 1996. During 2002, the poultry industry took over the responsibility of the programme. The proportion of infected layer flocks was reduced from 13.4% in 1998 to 0.4% in 2006. The public-health impact of the plan has been quite marked. In 1997, 55-65% of the 5015 cases of human salmonellosis were estimated to be associated with eggs. In 2006, these figures were reduced to 1658 and 5-7%, respectively. Based on an assessment of the number of human cases attributable to table eggs, we used probabilistic modelling to estimate the avoided societal costs (health care and lost labour), and compared these with the public costs of control. The probable avoided societal costs during 1998-2002 were estimated to be 23.3 million euros (95% CI 16.3-34.9), and the results showed a continuous decreasing cost-benefit ratio reaching well below 1 in 2002. Further reductions in the primary production based on effective surveillance and control are required to ensure continued success.

Towards an integrated approach in supporting microbiological food safety decisions.

Decisions on food safety involve consideration of a wide range of concerns including the public health impact of foodborne illness, the economic importance of the agricultural sector and the food industry, and the effectiveness and efficiency of interventions. To support such decisions, we propose an integrated scientific approach combining veterinary and medical epidemiology, risk assessment for the farm-to-fork food chain as well as agricultural and health economy. Scientific advice is relevant in all stages of the policy cycle: to assess the magnitude of the food safety problem, to define the priorities for action, to establish the causes for the problem, to choose between different control options, to define targets along the food chain and to measure success.

The occurrence and epidemiology of Salmonella in European pig slaughterhouses.

This study was part of an international research project entitled SALINPORK (FAIR CT-950400) initiated in 1996. The objectives were to investigate the occurrence of Salmonella in pig slaughterhouses and to identify risk factors associated with the contamination of pig carcasses. Data was collected from 12 slaughterhouses in five European countries. Isolates were characterized by serotyping, phage typing and antimicrobial susceptibility. In one country, no Salmonella was found. Salmonella was isolated from 5.3% of 3485 samples of pork and from 13.8% of 3573 environmental samples from the seven slaughterhouses in the four remaining countries. The statistical analyses (multi-level logistic regression) indicated that the prevalence was significantly higher during the warmer months and that the environmental contamination increased during the day of slaughter. The polishing (OR 3.74, 95% CI 1.43-9.78) and pluck removal (OR 3.63, 95% CI 1.66-7.96) processes were found to contribute significantly to the total carcass contamination, the latter especially if the scalding water also was contaminated. To reduce carcass contamination, it is recommended to ensure sufficiently high temperatures of scalding water (62 degrees C) and appropriate cleaning and disinfection of the polishing equipment at least once a day in order to reduce the level of carcass contamination and consequently the prevalence of Salmonella in pork.

The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of interstitial cystitis.

PURPOSE: The presence of leukotriene D4 receptors in human detrusor myocytes and increased urinary leukotriene E4 in patients with interstitial cystitis and detrusor mastocytosis imply a role for cysteinyl containing leukotrienes as proinflammatory mediators in this disease. We examined the efficacy of the cysteinyl leukotriene 1 receptor antagonist montelukast for treating patients with interstitial cystitis and detrusor mastocytosis. MATERIALS AND METHODS: Ten women in whom interstitial cystitis was diagnosed according to National Institute of Diabetes and Digestive and Kidney Diseases criteria and who also had detrusor mastocytosis with a minimum of 28 mast cells per mm.2 muscle tissue were included in this study. Patients received a single dose of montelukast daily for 3 months. The efficacy of treatment was determined by 24-hour urinary frequency, nocturia and pain using visual analog scales. RESULTS: After 1 month of montelukast treatment there was a statistically significant decrease in 24-hour urinary frequency, nocturia and pain which persisted during the 3 months of treatment. After 3 months 24-hour urinary frequency had decreased from 17.4 to 12 voidings (p = 0.009), nocturia had decreased from 4.5 to 2.8 (p = 0.019) and pain had decreased from 46.8 to 19.6 mm. on a visual analog scale (p = 0.006). No side effects were observed during treatment. CONCLUSIONS: Montelukast treatment resulted in significant improvement in urinary frequency and pain. Its efficacy for decreasing urinary frequency and pain imply a role of leukotriene receptor antagonists for managing interstitial cystitis but further placebo controlled clinical studies are needed.

Trends and seasonal variations in the occurrence of Salmonella in pigs, pork and humans in Denmark, 1995-2000.

A mandatory programme monitoring the occurrence of Salmonella in pork at slaughterhouses and a serological monitoring of slaughter-pig herds has been implemented in Denmark since 1993 and 1995, respectively. All results are stored in a central database. From this, aggregated weekly results of serological and bacteriological samples collected in the period between January 1995 and July 2000 were extracted. In addition, the reported weekly incidence of human infections with S. Typhimurium covering the same time period was obtained. The times series were analysed for trends and cyclic variations by seasonal decomposition. The association between the incidence in humans and the prevalence of Salmonella in pigs and pork, and prevailing weather conditions, were analysed by using a general linear (glm) and a general additive model (gam). Explanatory variables were lagged to account for time elapsed between sampling, consumption, incubation period and case registration. The results of the seasonal decomposition showed an overall declining trend in all three time series. All time series exhibited a double peaked annual cycle. The seasonal variation of the prevalence in pork and the human incidence had a very similar course. The variables that were both biologically meaningful and statistically significant in both regression models were the prevalence in pork sampled 4 to 5 weeks before case registration, the seroprevalence, measured as the average prevalence of week 15 to 35 before case registration, and the air temperature lagged at 2 and 3 weeks. Limitations on inferences from overall surveillance data are discussed.

The action of cysteinyl-leukotrienes on intracellular calcium mobilization in human detrusor myocytes.

OBJECTIVE: To investigate the presence of leukotriene D4 receptors in fura-2-loaded human detrusor smooth muscle cells (DSMCs) by examining the ability of leukotriene D4 to raise intracellular-free Ca2+ concentration ([Ca2+]i), to determine the origin of the leukotriene D4-mediated rise in [Ca2+]i and to investigate whether the specific leukotriene D4 receptor antagonist montelukast inhibits the Ca2+ response induced by leukotriene D4. MATERIALS AND METHODS: Detrusor muscle biopsies were obtained from patients with benign noninvasive bladder diseases undergoing cystoscopy. DSMCs were isolated using an explant technique and maintained in culture. Only primary cultures or cells passaged up to three times were used for experiments. DSMCs were characterized with immunohistochemical staining and their identity confirmed by transmission electron microscopy. [Ca2+]i was measured in single DSMCs using the Ca2+ probe fura-2 and fluorescence-ratio microscopy. RESULTS: Immunohistochemical staining showed that 80-99% of the cells were positive for smooth muscle alpha-actin. The ultrastructural features of the cultured cells were those of smooth muscle cells and showed no differentiation in a fibroblastic or myofibroblastic direction. Leukotriene D4 increased the level of [Ca2+]i in a dose-dependent manner. Calcium was mobilized almost exclusively from intracellular Ca2+ stores. There was a dose-dependent inhibition of the increase in [Ca2+]i by montelukast. CONCLUSION: The present study is the first to show the presence of specific leukotriene D4 receptors in human detrusor myocytes. This may have implications for a potential pathophysiological role of leukotriene D4 in patients with interstitial cystitis and other functional or inflammatory bladder disorders.