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Presented at the 12th International Conference on Predictive Modelling in Food (ICPMF12, Sapporo, Japan)., Project supported by EFSA (PIF GP/EFSA/BIOHAW/2022/01)

This is the protocol for conducting systematic reviews aimed at identifying and extracting information and data on the occurrence of the most important biological hazards in various foods produced and marketed in Europe. Such protocol is employed to periodically update the web application Pathogens in Foods (https://pif.esa.ipb.pt/) through a dedicated database insertion system (https://pathogens-in-food-frontend.vercel.app/)., EU; en; PDF; Pauline.KOOH@anses.fr; ubarron@ipb.pt

This document has been prepared in the context of the EJP-OH CARE (Cross-sectoral framework for quality Assurance Resources for countries in the European Union). This document is part of WP4 : Investigate, benchmark and improve the availability and the quality of the existing data relevant for risk assessment. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 773830.

Le botulisme est une maladie neurologique humaine et animale, le plus souvent d’origine alimentaire, provoquée par l’action de neurotoxines bactériennes (toxines botuliques) produites par la bactérie Clostridium botulinum et qui se manifeste par une paralysie flasque pouvant aller jusqu’à la paralysie respiratoire et l’arrêt cardiaque. Neuf types toxiniques, répartis en une quarantaine de sous-types, sont actuellement connus.En France, le botulisme animal affecte essentiellement les oiseaux (sauvages et domestiques) et les bovins. Chez les volailles, on recense annuellement vingt à trente foyers, majoritairement dus aux types mosaïque C/D (élevages de poulets de chair et de dindes) suivi de D et mosaïque D/C (uniquement dans les élevages de dindes). Chez les bovins, l’incidence sur les 10 dernières années est en moyenne d’une dizaine de foyers par an et les épisodes de botulisme sont dus aux types mosaïque D/C (majoritaire), C, mosaïque C/D et rarement D.Les pertes en élevage liées à ces foyers et les interrogations sur leurs conséquences dans le domaine de la santé publique ont amené les pouvoirs publics à réglementer le botulisme animal en l’intégrant dans la liste des dangers sanitaires de première catégorie pour les espèces animales (arrêté du 29 juillet 2013). Aujourd’hui, cette maladie figure dans une listedes maladies animales réglementées d’intérêt national en application de l’article L. 221-1 du code rural et de la pêche maritime (arrêté du 03 mai 2022). Pour autant, aucune mesure de police sanitaire de portée générale n’a été édictée à ce jour pour gérer les foyers de botulisme animal, et chacun est géré au cas par cas par la direction départementale en charge de la protection des populations (DDPP) concernée, et par la Mission des Urgences Sanitaires (MUS) de la Direction Générale de l’Alimentation (DGAL).Jusqu’à présent, ces services se sont appuyés sur : un rapport sur le botulisme animal publié par l’Agence française de sécurité sanitaire des aliments (Afssa 2002) et un avis rendu en janvier 2009 sur un projet (par la suite abandonné) d’arrêté fixant des mesures techniques et administratives relatives à la lutte contre le botulisme aviaire (Afssa 2009b). Afin de pouvoirdisposer de données actualisées et déterminer des mesures de gestion adaptées aux particularités du botulisme des type C, D et mosaïques C/D ou D/C, la DGAL a saisi l’Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail (Anses) à la fin du mois de juin 2019 via quatre saisines (saisines 2019-SA-0112 à 2019-SA-0115).

Le botulisme est une maladie neurologique humaine et animale, le plus souvent d’origine alimentaire, provoquée par l’action de neurotoxines bactériennes (toxines botuliques) produites par des bactéries du genre Clostridium et qui se manifeste par des paralysies flasques pouvant aller jusqu’à la paralysie respiratoire et l’arrêt cardiaque. Il existe neuf types de toxines botuliques. Les différents types se répartissent en une quarantaine de sous-types.Chez l’être humain, en France, le botulisme est à déclaration obligatoire depuis 1986. Les cas de botulisme sont majoritairement associés aux types B et A et de manière plus exceptionnelle aux types F et E. Il s’agit d’une maladie rare, avec une incidence en France de 11 à 22 cas/an (période 2013-2016, source Santé Publique France - SPF).Le botulisme animal en France concerne essentiellement les oiseaux (sauvages et domestiques) et les bovins. Les cas chez les bovins sont dus aux types mosaïque D/C (majoritaire), C, mosaïque C/D et rarement D. Au niveau national, l’incidence sur les 10 dernières années est en moyenne d’une dizaine de foyers par an. Chez les oiseaux, les types toxiniques en cause sont C, D, mosaïques C/D et D/C et exceptionnellement le type E. Au niveau national, l’incidence est d’environ 25 foyers par an (volailles et avifaune confondues), avec cependant des variations annuelles parfois notables, comme en 2007 (121 foyers décelés) et 2008 (102 foyers).Une sous-estimation est probable, quelle que soit l’espèce animale envisagée, mais surtout pour l’avifaune3 (sauvage et non captive) où la détection des cadavres d’oiseaux est plus difficile.Bien qu’il s’agisse d’un danger sanitaire de première catégorie en santé animale, il n’y a pas à l’heure actuelle de mesures de police sanitaire établies par la règlementation, lors de la confirmation d’un foyer de botulisme animal, ce qui conduit à une gestion au cas par cas par les directions départementales de la protection des populations (DDPP) et la Mission des Urgences Sanitaires (MUS) de la Direction générale de l’Alimentation. Ces services peuvent s’appuyer sur deux documents émis par l’AFSSA : le rapport sur le botulisme animal établi en 2002 et l’avis rendu en janvier 2009 sur un projet d’arrêté fixant des mesures techniques et administratives relatives à la lutte contre le botulisme aviaire. Ce projet d’arrêté n’a pas été finalisé par le ministère. Les rapports et avis cités étant relativement anciens, la Direction générale de l’Alimentation a saisi l’Anses à la fin du mois de juin 2019 via 4 saisines (saisines 2019-SA-0112 à 2019-SA-0115), dont l’objet est une demande d’actualisation des connaissances et des évaluations de risque pour la santé humaine et/ou animale.

With increased interest in source attribution of foodborne pathogens, there is a need to sort and assess the applicability of currently available methods. Herewith we reviewed the most frequently applied methods for source attribution of foodborne diseases, discussing their main strengths and weaknesses to be considered when choosing the most appropriate methods based on the type, quality, and quantity of data available, the research questions to be addressed, and the (epidemiological and microbiological) characteristics of the pathogens in question. A variety of source attribution approaches have been applied in recent years. These methods can be defined as top-down, bottom-up, or combined. Top-down approaches assign the human cases back to their sources of infection based on epidemiological (e.g., outbreak data analysis, case-control/cohort studies, etc.), microbiological (i.e., microbial subtyping), or combined (e.g., the so-called 'source-assigned case-control study' design) methods. Methods based on microbial subtyping are further differentiable according to the modeling framework adopted as frequency-matching (e.g., the Dutch and Danish models) or population genetics (e.g., Asymmetric Island Models and STRUCTURE) models, relying on the modeling of either phenotyping or genotyping data of pathogen strains from human cases and putative sources. Conversely, bottom-up approaches like comparative exposure assessment start from the level of contamination (prevalence and concentration) of a given pathogen in each source, and then go upwards in the transmission chain incorporating factors related to human exposure to these sources and dose-response relationships. Other approaches are intervention studies, including 'natural experiments,' and expert elicitations. A number of methodological challenges concerning all these approaches are discussed. In absence of an universally agreed upon 'gold' standard, i.e., a single method that satisfies all situations and needs for all pathogens, combining different approaches or applying them in a comparative fashion seems to be a promising way forward.

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A case-control study is a powerful approach among epidemiologists to investigate the causal effect of exposure and enteric illness. To combine the associations between sporadic campylobacteriosis and the different food pathways of exposure, the results from relevant case-control studies were extracted and their odds-ratio (OR) measures were meta-analysed within food category partitions by population type, extracting the variability due to both primary studies and model types. In the mixed population, the most important determinants of disease turned out to be: consumption of raw milk (pooted OR=2. 64), poultry (OR=1. 78), raw milk's cheese (OR=1. 72), BBQ meats (OR=1. 67), fast-food composite (OR=1. 59) and raw seafood (OR=1. 50). On the other hand, consumption of raw-egg containing products (OR=4. 85), raw milk (OR=3. 05), pork (OR=2. 34), minced beef (OR=2.27), processed meats (OR=2.18), any composite food eaten out (OR=2.16) and poultry meat (OR=2.08) were found to bear the highest risk of campylobacteriosis in the children population. info:eu-repo/semantics/publishedVersion

The objective of this study was to build a database of the occurrence (both prevalence and counts) of the most important biological hazards in foods commercialised in Europe. For this, systematic literature searches were first conducted for every pathogen; namely, Salmonella, Campylobacter, Shigatoxin-producing Escherichia co//, Listería monocytogenes, Yersinia enterocolitica, Bacillus cereus, Clostridium perfringens, Staphylococcus aureus, Toxoplasma gondií, norovirus, Hepatitis A vírus, Hepatitis E virus, Cryptosporidium ana Giardia duodenalis; and after screening for relevance and methodological quality assessment, data were carefully extracted from the primary studies into a harmonised arrangement consisting of primary study characteristics, food characteristics ana stage within the food chain, microbiological methods, prevalence results, enumeration results and potential for bias. Based on the microbiological survey results extracted from 977 primary studies, the database Pathogens-ln-Foods hás been constructed to facilitate data access and retrieval according to hazard, food class, country or any other relevant variable, with the ability to execute simple statistical calculations. info:eu-repo/semantics/publishedVersion

A case-control study is a powerful approach among epidemiologists to investigate the causal effect of exposure and enteric illness. The objective of this work was to synthesise the associations between risk factors and sporadic salmonellosis by combining results from relevant case-control studies. For the study-specific exposures to be harmonised within a meta-analysis study, a categorisation scheme was developed that hierarchically grouped risk factors into travel, host-specific factors and pathways of exposure. info:eu-repo/semantics/publishedVersion

Os estudos caso-controlo são uma metodologia de investigação em epidemiologia que permitem analisar, de forma retrospectiva, a exposição a factores de risco das doenças entéricas. O objectivo deste trabalho foi sintetizar a associação entre as infecções esporádicas por Salmonella spp. e os factores de risco, através da combinação dos resultados de estudos casocontrolo. Para uniformizar as categorias de exposição, desenvolvemos uma classificação dos eventuais factores de risco, com as seguintes categorias: viagem, especificidades do hospedeiro, transmissão de pessoa a pessoa, contacto com animais, contaminação pelo ambiente e consumo de alimentos. A pesquisa da literatura relevante foi realizada através dos portais da Science Direct, Pubmed, Scielo, 151 Web of Science e Scopus. Em cada estudo caso-controlo, foi recolhida a medida de associação oddsratio (ORs) da doença com a exposição. Os estudos seleccionados foram classificados quanto ao seu potencial de enviesamento, resultante de deficiências do desenho experimental, da selecção da população e dos métodos utilizados na análise dos dados. Foram também extraídas outras características consideradas importantes, tais como: a população, o desenho experimental, a análise estatística dos dados e o(s) factor(es) de risco. Posteriormente, os ORs globais, para cada factor de risco e das rotas de transmissão, foram estimados por modelos de meta-análise com o software R, e hierarquizados. info:eu-repo/semantics/publishedVersion

As doenças gastrointestinais representam um importante problema de saúde pública em todo mundo, desta forma a identificação da origem de transmissão é de grande importância para a avaliação e atribuição de risco. Os estudos epidemiológicos de casocontrolo são usados para identificar os fatores de risco associados à transmissão das doenças. A salmonelose, doença causada por vários serotipos de Salmonella spp., pode ser transmitida ao homem de diversas formas. De uma forma geral, os casos esporádicos de salmonelose não partilham o mesmo fator de risco ou rota de contaminação, de modo que os estudos que medem a relação de probabilidades (“odds ratio”, OR) de qualquer fonte de transmissão podem ocultar os riscos reais tornando-os mais difíceis de detetar (Fullerton et al., 2012). Por exemplo, o frango assado é uma importante fonte de contaminação por Salmonella spp., todavia a maioria das porções de frango não estão contaminadas, de modo que a probabilidade de uma pessoa adquirir salmonelose pelo consumo de frango assado é apenas um pouco superior à das pessoas que não consomem frango assado (controlo). A case-control study is used to identify causal effects of diseases transmission at population level. The objective of this study was to synthesize the association between sporadic salmonellosis and two broad routes of exposure (meat consumption and animals contact) by combining the odds-ratio outcomes extracted from case-control studies found in bibliographic search platforms. A systematic review was conducted through the search engines of Science Direct, Pubmed, Scielo, ISI Web of Science and Scopus. From 69 case-control studies, odds-ratios (ORs), population, design/model/analysis type and probable risk factors were extracted. Subsequently, the global ORs for the transmission routes considered were estimated by mixed-effects metaanalysis models. The obtained results identified that, in the mixed population, consumption of pork is the main source of salmonellosis (pooled OR=2.662), followed by occupational exposure to animals/meat (pooled OR=2.583) and consumption of nonclassified meats, BBQ and game meat (pooled OR=2.442 – 2.459). On the other hand, children were more likely to acquire salmonellosis through contact with farm animals (pooled OR=5,977) followed by consumption of pork meat (pooled OR=3.193) and contact with pets (pooled OR=3.155). A Dra. Ursula Gonzales Barron agradece o apoio financeiro da Fundação para a Ciência e a Tecnologia através do programa Investigador FCT, nível de desenvolvimento (IF/00570). info:eu-repo/semantics/publishedVersion