Into the Jungle of Biological Agents of Foodborne Diseases: Time to Put Some Order for the French Risk Manager.

Consumers can be exposed to many foodborne biological hazards that cause diseases with varying outcomes and incidence and, therefore, represent different levels of public health burden. To help the French risk managers to rank these hazards and to prioritize food safety actions, we have developed a three-step approach. The first step was to develop a list of foodborne hazards of health concern in mainland France. From an initial list of 335 human pathogenic biological agents, the final list of "retained hazards" consists of 24 hazards, including 12 bacteria (including bacterial toxins and metabolites), 3 viruses and 9 parasites. The second step was to collect data to estimate the disease burden (incidence, Disability Adjusted Life Years) associated with these hazards through food during two time periods: 2008-2013 and 2014-2019. The ranks of the different hazards changed slightly according to the considered period. The third step was the ranking of hazards according to a multicriteria decision support model using the ELECTRE III method. Three ranking criteria were used, where two reflect the severity of the effects (Years of life lost and Years lost due to disability) and one reflects the likelihood (incidence) of the disease. The multicriteria decision analysis approach takes into account the preferences of the risk managers through different sets of weights and the uncertainties associated with the data. The method and the data collected allowed to estimate the health burden of foodborne biological hazards in mainland France and to define a prioritization list for the health authorities.

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.

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.

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.

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.

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.

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.

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.

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.

Outbreak of Salmonella Enteritidis linked to the consumption of frozen beefburgers received from a food bank and originating from Poland: northern France, December 2014 to April 2015.

A prolonged outbreak of Salmonella enterica serotype Enteritidis occurred in northern France between December 2014 and April 2015. Epidemiological investigations following the initial notification on 30 December 2014 of five cases of salmonellosis (two confirmed S. Enteritidis) in young children residing in the Somme department revealed that all cases frequented the same food bank A. Further epidemiological, microbiological and food trace-back investigations indicated frozen beefburgers as the source of the outbreak and the suspected lot originating from Poland was recalled on 22 January 2015. On 2 March 2015 a second notification of S. Enteritidis cases in the Somme reinitiated investigations that confirmed a link with food bank A and with consumption of frozen beefburgers from the same Polish producer. In the face of a possible persistent source of contamination, all frozen beefburgers distributed by food bank A and from the same origin were blocked on 3 March 2015. Microbiological analyses confirmed contamination by S. Enteritidis of frozen beefburgers from a second lot remaining in cases' homes. A second recall was initiated on 6 March 2015 and all frozen beefburgers from the Polish producer remain blocked after analyses identified additional contaminated lots over several months of production.

A cluster of three cases of botulism due to Clostridium baratii type F, France, August 2015.

A cluster of three cases of food-borne botulism due to Clostridium baratii type F occurred in France in August 2015. All cases required respiratory assistance. Consumption of a Bolognese sauce at the same restaurant was the likely source of contamination. Clostridium baratii was isolated both from stool specimens from the three patients and ground meat used to prepare the sauce. This is the second episode reported in France caused by this rare pathogen.

Community Incidence of Campylobacteriosis and Nontyphoidal Salmonellosis, France, 2008-2013.

Community incidence estimates are necessary to assess the burden and impact of infections on health and to set priorities for surveillance, research, prevention, and control strategies. The current study was performed to estimate the community incidence of campylobacteriosis and nontyphoidal salmonellosis in France from the number of laboratory-confirmed cases reported to the national reference center (NRC). The probabilities of a case in the community visiting a doctor, having a stool sample requested, having a positive laboratory test, and having the case reported to the NRC were estimated using data of national surveillance systems, national hospitalization and health insurance databases, and specific surveys informing about these parameters. Credible intervals (CrI) were calculated using Monte Carlo simulation. In addition, we estimated the number of hospitalizations for both infections in France. The annual community incidence rate in France is estimated at 842 cases per 100,000 (90%CrI 525-1690) for campylobacteriosis and 307 cases per 100,000 (90%CrI 173-611) for salmonellosis. The annual number of hospitalizations is estimated at 5182 for campylobacteriosis and 4305 for salmonellosis. The multiplication factors between cases ascertained by the surveillance system and cases in the community were 115 for campylobacteriosis and 20 for salmonellosis. They are consistent with estimates reported in other countries, indicating a high community incidence of campylobacteriosis and salmonellosis in France.

Acute diarrhea in adults consulting a general practitioner in France during winter: incidence, clinical characteristics, management and risk factors.

BACKGROUND: Data describing the epidemiology and management of viral acute diarrhea (AD) in adults are scant. The objective of this study was to identify the incidence, clinical characteristics, management and risk factors of winter viral AD in adults. METHODS: The incidence of AD in adults during two consecutive winters (from December 2010 to April 2011 and from December 2011 to April 2012) was estimated from the French Sentinelles network. During these two winters, a subset of Sentinelles general practitioners (GPs) identified and included adult patients who presented with AD and who filled out a questionnaire and returned a stool specimen for virological examination. All stool specimens were tested for astrovirus, group A rotavirus, human enteric adenovirus, and norovirus of genogroup I and genogroup II. Age- and sex-matched controls were included to permit a case-control analysis with the aim of identifying risk factors for viral AD. RESULTS: During the studied winters, the average incidence of AD in adults was estimated to be 3,158 per 100,000 French adults (95% CI [2,321 - 3,997]). The most reported clinical signs were abdominal pain (91.1%), watery diarrhea (88.5%), and nausea (83.3%). GPs prescribed a treatment in 95% of the patients with AD, and 80% of the working patients with AD could not go to work. Stool examinations were positive for at least one enteric virus in 65% (95% CI [57 - 73]) of patients with AD with a predominance of noroviruses (49%). Having been in contact with a person who has suffered from AD in the last 7 days, whether within or outside the household, and having a job (or being a student) were risk factors significantly associated with acquiring viral AD. CONCLUSIONS: During the winter, AD of viral origin is a frequent disease in adults, and noroviruses are most often the cause. No preventable risk factor was identified other than contact with a person with AD. Thus, at the present time, reinforcement of education related to hand hygiene remains the only way to reduce the burden of disease.

[Foodborne infections in France]. / Les infections d'origine alimentaire en France.

Prevention and control measures implemented along the human food chain in recent decades have been largely successful, as shown by the dramatic decrease in the incidence of listeriosis and certain Salmonella serotypes. However, foodborne illness continues to be a serious public health threat, due mainly to Salmonella, Listeria monocytogenes and Campylobacter. Infections caused by less frequent micro-organisms such as shigatoxin-producing E. coli are also a concern, because of their serious health consequences and epidemic potential. Surveillance of foodborne illness has revealed several important trends, including a substantial recent increase in infections by monophasic variants of Salmonella typhimurium, a continuing increase in the incidence of Campylobacter infections, and a rapid increase in the frequency and antibiotic resistance of Salmonella and Campylobacter isolates. These developments highlight the importance of epidemiological and microbiological surveillance of humain foodborne infections; as well as the need for very close collaboration among all those responsible for the surveillance of animal health and the human foodchain.

International spread of an epidemic population of Salmonella enterica serotype Kentucky ST198 resistant to ciprofloxacin.

National Salmonella surveillance systems from France, England and Wales, Denmark, and the United States identified the recent emergence of multidrug-resistant isolates of Salmonella enterica serotype Kentucky displaying high-level resistance to ciprofloxacin. A total of 489 human cases were identified during the period from 2002 (3 cases) to 2008 (174 cases). These isolates belonged to a single clone defined by the multilocus sequence type ST198, the XbaI-pulsed-field gel electrophoresis cluster X1, and the presence of the Salmonella genomic island 1 variant SGI1-K. This clone was probably selected in 3 steps in Egypt during the 1990s and the early 2000s and has now spread to several countries in Africa and, more recently, in the Middle East. Poultry has been identified as a potential major vehicle for infection by this clone. Continued surveillance and appropriate control measures should be implemented by national and international authorities to limit the spread of this strain.

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.