Foodborne botulism outbreak involving different nationalities during the Rugby World Cup: critical role of credit card data and rapid international cooperation, France, September 2023.

In September 2023, a severe outbreak of type B botulism with fifteen cases was linked to consumption of canned sardines at a restaurant in Bordeaux, France, during the Rugby World Cup. The cases were from seven countries. One death was recorded. Outbreak investigation using credit card data, rapid communication between health authorities of the affected countries and broad media communication allowed identification of cases and exposed persons and prevented further severe outcomes.

A large travel-associated outbreak of iatrogenic botulism in four European countries following intragastric botulinum neurotoxin injections for weight reduction, Türkiye, February to March 2023.

In March 2023, 34 associated cases of iatrogenic botulism were detected in Germany (30 cases), Switzerland (two cases), Austria (one case), and France (one case). An alert was rapidly disseminated via European Union networks and communication platforms (Food- and Waterborne Diseases and Zoonoses Network, EpiPulse, Early Warning and Response System) and the International Health Regulation mechanism; the outbreak was investigated in a European collaboration. We traced sources of the botulism outbreak to treatment of weight loss in Türkiye, involving intragastric injections of botulinum neurotoxin. Cases were traced using a list of patients who had received this treatment. Laboratory investigations of the first 12 German cases confirmed nine cases. The application of innovative and highly sensitive endopeptidase assays was necessary to detect minute traces of botulinum neurotoxin in patient sera. The botulism notification requirement for physicians was essential to detect this outbreak in Germany. The surveillance case definition of botulism should be revisited and inclusion of cases of iatrogenic botulism should be considered as these cases might lack standard laboratory confirmation yet warrant public health action. Any potential risks associated with the use of botulinum neurotoxins in medical procedures need to be carefully balanced with the expected benefits of the procedure.

Countrywide multi-serotype outbreak of Salmonella Bovismorbificans ST142 and monophasic Salmonella Typhimurium ST34 associated with dried pork sausages in France, September 2020* to January 2021.

The French National Reference Centre for Escherichia coli, Shigella and Salmonella (FNRC-ESS) detected two human clusters of 33 cases (median age: 10 years; 17 females) infected by Salmonella enterica serotype Bovismorbificans, ST142, HC5_243255 (EnteroBase HierCC­cgMLST scheme) in September-November 2020 and of 11 cases (median age: 11 years; seven males) infected by S. enterica serotype 4,12:i:-, ST34, HC5_198125 in October-December 2020. Epidemiological investigations conducted by Santé publique France linked these outbreaks to the consumption of dried pork sausages from the same manufacturer. S. Bovismorbificans and S. 4,12:i:- were isolated by the National Reference Laboratory from different food samples, but both strains were identified in a single food sample only by qPCR. Three recalls and withdrawals of dried pork products were issued by the French general directorate of food of the French ministry for agriculture and food in November 2020, affecting eight supermarket chains. A notification on the European Rapid Alert System for Food and Feed and a European urgent enquiry on the Epidemic Intelligence Information System for Food and Waterborne Diseases and Zoonoses (EPIS-FWD) were launched. No cases were reported outside France. Outbreaks caused by multiple serotypes of Salmonella may go undetected by protocols in standard procedures in microbiology laboratories.

Human and animal botulism surveillance in France from 2008 to 2019.

Botulism is a human and animal neurological disease caused by the action of bacterial neurotoxins (botulinum toxins) produced by bacteria from the genus Clostridium. This disease induces flaccid paralysis that can result in respiratory paralysis and heart failure. Due to its serious potential impact on public health, botulism is a closely monitored notifiable disease in France through a case-based passive surveillance system. In humans, this disease is rare, with an average of 10 outbreaks reported each year, mainly due to the consumption of contaminated foods. Type B and to a lesser extend type A are responsible for the majority of cases of foodborne botulism. Each year, an average of 30 outbreaks are recorded on poultry farms, about 20 cases in wild birds and about 10 outbreaks in cattle, involving a large number of animals. Mosaic forms C/D and D/C in birds and cattle, respectively, are the predominant types in animals in France. Types C and D have also been observed to a lesser extent in animals. With the exception of botulinum toxin E, which was exceptionally detected throughout the period in wild birds, the types of botulism found in animal outbreaks are different from those identified in human outbreaks over the last ten years in France and no human botulism outbreaks investigated have been linked to animal botulism. In line with the One Health concept, we present the first integrative approach to the routine surveillance of botulism in humans and animals in France.

Epidemiology of acute gastroenteritis in France from November 2019-August 2021, in light of reported adherence to COVID-19 barrier measures.

Since the start of the COVID-19 pandemic, French health authorities have encouraged barrier measures and implemented three lockdowns to slow SARS-CoV-2 transmission. We aimed to examine the impact of these measures on the epidemiology of acute gastroenteritis (AGE) in France, from November 2019 to August 2021. We describe trends in AGE indicators from syndromic surveillance and a sentinel surveillance network. Additionally, we describe reported AGE illness data from a community based cohort, and frequencies of adherence to COVID-19 barrier measures from repeated quantitative surveys. From week 7 in 2020, all AGE indicators reached the lowest levels observed since the last decade. During the first lockdown, the median incidence rate reported by the sentinel network was 32 per 100,000 inhabitants, 1.9 times lower than the minimum registered during the 2010-2019 period. Low activity persisted until April 2021. Reported illness from the community cohort mirrored these trends. Adherence to COVID-19 barrier measures was highest during the first lockdown, coinciding with the steep decrease in AGE incidence. Among children under 5 years, AGE incidence increased after the third lockdown in June and July 2021, but remained lower than previous winter-season peaks. Our study indicates that a reduction in adherence to COVID-19 barrier measures, and the end of the lockdowns, coincided with an increase in AGE incidence, particularly among young children. We therefore strongly recommend maintaining adherence to barrier measures in order to in order to limit the transmission of AGE related pathogens.

Investigation of an international outbreak of multidrug-resistant monophasic Salmonella Typhimurium associated with chocolate products, EU/EEA and United Kingdom, February to April 2022.

An extensive multi-country outbreak of multidrug-resistant monophasic Salmonella Typhimurium infection in 10 countries with 150 reported cases, predominantly affecting young children, has been linked to chocolate products produced by a large multinational company. Extensive withdrawals and recalls of multiple product lines have been undertaken. With Easter approaching, widespread product distribution and the vulnerability of the affected population, early and effective real-time sharing of microbiological and epidemiological information has been of critical importance in effectively managing this serious food-borne incident.

Salmonella enterica subsp. enterica Welikade: guideline for phylogenetic analysis of serovars rarely involved in foodborne outbreaks.

BACKGROUND: Salmonella spp. is a major foodborne pathogen with a wide variety of serovars associated with human cases and food sources. Nevertheless, in Europe a panel of ten serovars is responsible for up to 80% of confirmed human cases. Clustering studies by single nucleotide polymorphism (SNP) core-genome phylogenetic analysis of outbreaks due to these major serovars are simplified by the availability of many complete genomes in the free access databases. This is not the case for outbreaks due to less common serovars, such as Welikade, for which no reference genomes are available. In this study, we propose a method to solve this problem. We propose to perform a core genome MLST (cgMLST) analysis based on hierarchical clustering using the free-access EnteroBase to select the most suitable genome to use as a reference for SNP phylogenetic analysis. In this study, we applied this protocol to a retrospective analysis of a Salmonella enterica serovar Welikade (S. Welikade) foodborne outbreak that occurred in France in 2016. Finally, we compared the cgMLST and SNP analyses. SNP phylogenetic reconstruction was carried out considering the effect of recombination events identified by the ClonalFrameML tool. The accessory genome was also explored by phage content and virulome analyses. RESULTS: Our findings revealed high clustering concordance using cgMLST and SNP analyses. Nevertheless, SNP analysis allowed for better assessment of the genetic distance among strains. The results revealed epidemic clones of S. Welikade circulating within the poultry and dairy sectors in France, responsible for sporadic and non-sporadic human cases between 2012 and 2019. CONCLUSIONS: This study increases knowledge on this poorly described serovar and enriches public genome databases with 42 genomes from human and non-human S. Welikade strains, including the isolate collected in 1956 in Sri Lanka, which gave the name to this serovar. This is the first genomic analysis of an outbreak due to S. Welikade described to date.

Whole Genome Analysis Detects the Emergence of a Single Salmonella enterica Serovar Chester Clone in Japan's Kanto Region.

In Japan's Kanto region, the number of Salmonella enterica serovar Chester infections increased temporarily between 2014 and 2016. Concurrently with this temporal increase in the Kanto region, S. Chester isolates belonging to one clonal group were causing repetitive outbreaks in Europe. A recent study reported that the European outbreaks were associated with travelers who had been exposed to contaminated food in Morocco, possibly seafood. Because Japan imports a large amount of seafood from Morocco, we aimed to establish whether the temporal increase in S. Chester infections in the Kanto region was associated with imported Moroccan seafood. Short sequence reads from the whole-genome sequencing of 47 S. Chester isolates from people in the Kanto region (2014-2016), and the additional genome sequences from 58 isolates from the European outbreaks, were analyzed. The reads were compared with the complete genome sequence from a S. Chester reference strain, and 347 single nucleotide polymorphisms (SNPs) were identified. These SNPs were used in this study. Cluster and Bayesian cluster analyses showed that the Japanese and European isolates fell into two different clusters. Therefore, Φ PT and I A S values were calculated to evaluate genetic differences between these clusters. The results revealed that the Japanese and European isolates were genetically distinct populations. Our root-to-tip analysis showed that the Japanese isolates originating from one clone had accumulated mutations, suggesting that an emergence of this organism occurred. A minimum spanning tree analysis demonstrated no correlation between genetic and geographical distances in the Japanese isolates, suggesting that the emergence of the serovar in the Kanto region did not involve person-to-person contact; rather, it occurred through food consumption. The d N /d S ratio indicated that the Japanese strain has evolved under positive selection pressure. Generally, a population of bacterial clones in a reservoir faces negative selection pressure. Therefore, the Japanese strain must have existed outside of any reservoir during its emergence. In conclusion, S. Chester isolates originating from one clone probably emerged in the Kanto region via the consumption of contaminated foods other than imported Moroccan seafood. The emerging strain may have not established a reservoir for survival in the food supply chain resulting in its disappearance after 2017.

Contribution of Foods and Poor Food-Handling Practices to the Burden of Foodborne Infectious Diseases in France.

The foodborne disease burden (FBDB) related to 26 major biological hazards in France was attributed to foods and poor food-handling practices at the final food preparation step, in order to develop effective intervention strategies, especially food safety campaigns. Campylobacter spp. and non-typhoidal Salmonella accounted for more than 60% of the FBDB. Approximately 30% of the FBDB were attributed to 11 other hazards including bacteria, viruses and parasites. Meats were estimated as the main contributing food category causing (50-69%) (CI90) of the FBDB with (33-44%), (9-21%), (4-20%) (CI90) of the FBDB for poultry, pork and beef, respectively. Dairy products, eggs, raw produce and complex foods caused each approximately (5-20%) (CI90) of the FBDB. When foods are contaminated before the final preparation step, we estimated that inadequate cooking, cross-contamination and inadequate storage contribute for (19-49%), (7-34%) and (9-23%) (CI90) of the FBDB, respectively; (15-33%) (CI90) of the FBDB were attributed to the initial contamination of ready-to-eat foods-without any contribution from final food handlers. The thorough implementation of good hygienic practices (GHPs) at the final food preparation step could potentially reduce the FBDB by (67-85%) (CI90) (mainly with the prevention of cross-contamination and adequate cooking and storage).

Critical Orientation in the Jungle of Currently Available Methods and Types of Data for Source Attribution of Foodborne Diseases.

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.

Outbreak of Shiga toxin-producing Escherichia coli (STEC) O26 paediatric haemolytic uraemic syndrome (HUS) cases associated with the consumption of soft raw cow's milk cheeses, France, March to May 2019.

We report an outbreak of Shiga toxin-producing Escherichia coli (STEC) associated paediatric haemolytic uraemic syndrome linked to the consumption of raw cow's milk soft cheeses. From 25 March to 27 May 2019, 16 outbreak cases infected with STEC O26 (median age: 22 months) were identified. Interviews and trace-back investigations using loyalty cards identified the consumption of raw milk cheeses from a single producer. Trace-forward investigations revealed that these cheeses were internationally distributed.

Outbreak of Salmonella enterica serotype Poona in infants linked to persistent Salmonella contamination in an infant formula manufacturing facility, France, August 2018 to February 2019.

We describe a Salmonella Poona outbreak involving 31 infant cases in France. Following outbreak detection on 18 January 2019, consumption of rice-based infant formula manufactured at a facility in Spain was identified as the probable cause, leading to a recall on 24 January. Whole genome sequencing analysis linked present outbreak isolates to a 2010-11 S. Poona outbreak in Spain associated with formula manufactured in the same facility, indicating a persistent source of contamination.

Paediatric haemolytic uraemic syndrome related to Shiga toxin-producing Escherichia coli, an overview of 10 years of surveillance in France, 2007 to 2016.

IntroductionHaemolytic uraemic syndrome (HUS) related to Shiga toxin-producing Escherichia coli (STEC) is the leading cause of acute renal failure in young children. In France, HUS surveillance in children aged < 15 years was implemented starting from 1996.AimWe present the results of this surveillance between 2007 and 2016.MethodsA voluntary nationwide network of 32 paediatric departments notifies cases. Two national reference centres perform microbiological STEC confirmation.ResultsOver the study period, the paediatric HUS incidence rate (IR) was 1.0 per 100,000 children-years, with a median of 116 cases/year. In 2011, IR peaked at 1.3 per 100,000 children-years, and decreased to 1.0 per 100,000 children-years in 2016. STEC O157 associated HUS peaked at 37 cases in 2011 and decreased to seven cases in 2016. Cases of STEC O26-associated HUS have increased since 2010 and STEC O80 associated HUS has emerged since 2012, with 28 and 18 cases respectively reported in 2016. Four STEC-HUS food-borne outbreaks were detected (three STEC O157 linked to ground beef and raw-milk cheese and one STEC O104 linked to fenugreek sprouts). In addition, two outbreaks related to person-to-person transmission occurred in distinct kindergartens (STEC O111 and O26).ConclusionsNo major changes in HUS IRs were observed over the study period of 10 years. However, changes in the STEC serogroups over time and the outbreaks detected argue for continuing epidemiological and microbiological surveillance.

Disentangling a complex nationwide Salmonella Dublin outbreak associated with raw-milk cheese consumption, France, 2015 to 2016.

On 18 January 2016, the French National Reference Centre for Salmonella reported to Santé publique France an excess of Salmonella enterica serotype Dublin (S. Dublin) infections. We investigated to identify the source of infection and implement control measures. Whole genome sequencing (WGS) and multilocus variable-number tandem repeat analysis (MLVA) were performed to identify microbiological clusters and links among cases, animal and food sources. Clusters were defined as isolates with less than 15 single nucleotide polymorphisms determined by WGS and/or with identical MLVA pattern. We compared different clusters of cases with other cases (case-case study) and controls recruited from a web-based cohort (case-control study) in terms of food consumption. We interviewed 63/83 (76%) cases; 2,914 controls completed a questionnaire. Both studies' findings indicated that successive S. Dublin outbreaks from different sources had occurred between November 2015 and March 2016. In the case-control study, cases of distinct WGS clusters were more likely to have consumed Morbier (adjusted odds ratio (aOR): 14; 95% confidence interval (CI): 4.8-42) or Vacherin Mont d'Or (aOR: 27; 95% CI: 6.8-105), two bovine raw-milk cheeses. Based on these results, the Ministry of Agriculture launched a reinforced control plan for processing plants of raw-milk cheeses in the production region, to prevent future outbreaks.

Ongoing nationwide outbreak of Salmonella Agona associated with internationally distributed infant milk products, France, December 2017.

On 1 December 2017, an outbreak of Salmonella Agona infections among infants was identified in France. To date, 37 cases (median age: 4 months) and two further international cases have been confirmed. Five different infant milk products manufactured at one facility were implicated. On 2 and 10 December, the company recalled the implicated products; on 22 December, all products processed at the facility since February 2017. Trace-forward investigations indicated product distribution to 66 countries.

Secular trends in incidence of acute gastroenteritis in general practice, France, 1991 to 2015.

We analysed 25 years of general practitioner (GP) visits for acute gastroenteritis (AG) surveillance in France, by the GP Sentinelles network. We searched for time trends of acute gastroenteritis incidence during winter periods. Data from emergency departments and drug reimbursement were additional data sources. A time-series analysis was performed using a generalised additive model for all data sources for the winter period. Virological data were incorporated and compared with the three data sources. The cumulative incidence of GP visits for winter AG exhibited an increasing trend from 1991 until 2008, when it reached 6,466 per 100,000 inhabitants. It decreased thereafter to 3,918 per 100,000 inhabitants in 2015. This decreasing trend was observed for all age groups and confirmed by the generalised additive model. For emergency department visits a decreasing trend was observed from 2004. Drug reimbursement data analyses demonstrated a decreasing trend from when data began in 2009. The incidence reported by GPs and emergency departments was lower following the emergence of norovirus GII.4 2012 (p < 0.0001). Winter AG incidences seem to follow long-term rising and decreasing trends that are important to monitor through continuous surveillance to evaluate the impact of prevention strategies, such as future immunisation against acute viral gastroenteritis.

MLVA for Salmonella enterica subsp. enterica Serovar Dublin: Development of a Method Suitable for Inter-Laboratory Surveillance and Application in the Context of a Raw Milk Cheese Outbreak in France in 2012.

Salmonella enterica subspecies enterica serovar Dublin (S. Dublin) figures among the most frequently isolated Salmonella strains in humans in France. This serovar may affect production and animal health mainly in cattle herds with corresponding high economic losses. Given that the current gold standard method, pulsed-field gel electrophoresis (PFGE), provides insufficient discrimination for epidemiological investigations, we propose a standard operating procedure in this study for multiple-locus variable number tandem repeat analysis (MLVA) of S. Dublin, suitable for inter-laboratory surveillance. An in silico analysis on the genome of S. Dublin strains CT_02021853 was performed to identify appropriate microsatellite regions. Of 21 VNTR loci screened, six were selected and 401 epidemiologically unrelated and related strains, isolated from humans, food and animals were analyzed to assess performance criteria such as typeability, discriminatory power and epidemiological concordance. The MLVA scheme developed was applied to an outbreak involving Saint-Nectaire cheese for which investigations were conducted in France in 2012, making it possible to discriminate between epidemiologically related strains and sporadic case strains, while PFGE assigned only a single profile. The six loci selected were sequenced on a large set of strains to determine the sequence of the repeated units and flanking regions, and their stability was evaluated in vivo through the analysis of the strains investigated from humans, food and the farm environment during the outbreak. The six VNTR selected were found to be stable and the discriminatory power of the MLVA method developed was calculated to be 0.954 compared with that for PFGE, which was only 0.625. Twenty-four reference strains were selected from the 401 examined strains in order to represent most of the allele diversity observed for each locus. This reference set can be used to harmonize MLVA results and allow data exchange between laboratories. This original MLVA protocol could be used easily and routinely for monitoring of serovar Dublin isolates and for conducting outbreak investigations.

Multinational outbreak of travel-related Salmonella Chester infections in Europe, summers 2014 and 2015.

Between 2014 and 2015, the European Centre for Disease Prevention and Control was informed of an increase in numbers of Salmonella enterica serotype Chester cases with travel to Morocco occurring in six European countries. Epidemiological and microbiological investigations were conducted. In addition to gathering information on the characteristics of cases from the different countries in 2014, the epidemiological investigation comprised a matched case-case study involving French patients with salmonellosis who travelled to Morocco that year. A univariate conditional logistic regression was performed to quantify associations. The microbiological study included a whole genome sequencing (WGS) analysis of clinical and non-human isolates of S. Chester of varied place and year of isolation. A total of 162 cases, mostly from France, followed by Belgium, the Netherlands, Spain, Denmark and Sweden were reported, including 86 (53%) women. The median age per country ranged from 3 to 38 years. Cases of S. Chester were more likely to have eaten in a restaurant and visited the coast of Morocco. The results of WGS showed five multilocus sequence types (ST), with 96 of 153 isolates analysed clustering into a tight group that corresponded to a novel ST, ST1954. Of these 96 isolates, 46 (48%) were derived from food or patients returning from Morocco and carried two types of plasmids containing either qnrS1 or qnrB19 genes. This European-wide outbreak associated with travel to Morocco was likely a multi-source outbreak with several food vehicles contaminated by multidrug-resistant S. Chester strains.

Characterization of Clostridium Baratii Type F Strains Responsible for an Outbreak of Botulism Linked to Beef Meat Consumption in France.

INTRODUCTION: A second botulism outbreak due to Clostridium baratii occurred in France in August 2015 and included three patients who had their meal in a restaurant the same day. We report the characterization of C. baratii isolates including whole genome sequencing (WGS). METHODS: Four C. baratii isolates collected in August 2015 from the outbreak 2 were analysed for toxin production and typing as well as for genetic characterization. WGS was done using using the NEBNext Ultra DNA Library Prep kit for Illumina (New England Biolabs) and sequenced on MiSeq machine (Illumina) in paired-end reads of 250 bases. The phylogenetic tree was generated based on the UPGMA method with genetic distances computed by using the Kimura two-parameter model. Evolutionary analyses were conducted in Bionumerics (V.6.6 Applied Maths). RESULTS: Three C. baratii isolates for patient's stools and one isolate from meat produced botulinum neurotoxin (BoNT) type F and retained a bont/F7 gene in OrfX cluster. All isolates were identical according to the WGS. However, phylogeny of the core genome showed that the four C. baratii strains were distantly related to that of the previous C. baratii outbreak in France in 2014 and from the other C. baratii strains reported in databanks. DISCUSSION: The fact that the strains isolated from the patients and meat samples were genetically identical supports that the meat used for the Bolognese sauce was responsible for this second botulism outbreak in France. These isolates were unrelated to that from the first C. baratii outbreak in France in 2014 indicating a distinct source of contamination. WGS provided robust determination of genetic relatedness and information regarding BoNT typing and toxin gene locus genomic localization.