Drivers and Constraints – application of molecular typing in surveillance of foodborne diseases in EU/EEA Johanna Takkinen, on behalf of ECDC FWD team Head of programme Food- and Waterborne Diseases and Zoonoses European Centre for Disease Prevention and Control (ECDC) Uppsala Health Summit, 11 October 2017

Salmonella Stanley: alert in 2012 29 June 2012: Urgent inquiry by Belgium: significant increase of non-travel-related S. Stanley infections in humans: since beginning of 2012, 26 cases reported, of which 10 cases between 11-25 June On 29 June 2012, the National Reference Centre for Salmonella in Belgium reported through the Epidemic Intelligence Information System for Food and Waterborne Diseases (EPIS-FWD) platform a significant increase of non travel-related Salmonella Stanley infections (S. Stanley) in 2012 with 26 cases since the beginning of the year and more recently, 10 cases between 11 and 25 June. The baseline observed during previous years was 3 to 6 S. Stanley cases annually on average. The 20 strains typed showed indistinguishable XbaI-PFGE profile and resistance to nalidixic acid. EPIS: information exchange platform linking PH authorities in the EU, with the aim to timely detect FWD outbreaks and facilitate their assessment. Between 2007 and 2011, 2 611 cases of S. Stanley infection were reported through the European Surveillance System (TESSy). Most of these S. Stanley cases are travel related outside the EU. The XbaI-PFGE pattern of the outbreak strain was shared through EPIS-FWD and compared with historical molecular typing data of human S. Stanley strains at the EU level (previously known as PulseNet Europe data, up to 2006) and with national human typing data in the EU Member States. Preliminary results from the comparison with historical datasets showed a high diversity of S. Stanley among human isolates in Europe. New PFGE. Respectively on 03 and 11 July, Germany and Hungary replied to the urgent inquiry reporting an increase in number of non-travel related cases in the first semester of 2012. By the end of July, 64 S. Stanley cases (36 cases in Hungary, 20 cases in Belgium and eight cases in Germany) shared the outbreak XbaI-PFGE profile. Retrospective investigations in Hungary showed that cases with the outbreak XbaI-PFGE profile were identified since August 2011.   In July 2012, ECDC launched an EU-wide investigation of this multistate outbreak of S. Stanley. 03 July: Germany reports an increase of non-travel-related S. Stanley cases 11 July: Hungary reports an increase of non-travel-related S. Stanley cases Launch of multistate investigations

Public health risk assessments Salmonella Stanley contamination in turkey primary production To raise awareness about this event and communicate about the preliminary findings: July, Aug, Sep EC request of a joint ECDC –EFSA risk assessment => 3rd RRA published on 21 Sep 2012 EC request for an update => 2nd RRA published on 29 Aug 2012 EC request on 20 July => 1st RRA published on 27 July 2012

Salmonella Stanley – prolonged multi-country outbreak, April 2014 - ..... 42 cases in Q1, PFGE type same as in 2012, consumption of turkey kebab, meat from HU and AT fattening turkey farms =>RASFF 8 April 2014 S. Stanley in turkeys, EFSA: 2004-2010 2011 2012 291 796 Non-travel related S. Stanley cases, Jan 2011 – Dec 2013, TESSy (N=938)* Almost two years later, Austria launched an Urgent Inquiry, 42 cases were identified in April compared to 12 cases in the previous years’ first quarter. The same pulsotype as the earlier outbreak strain in 2011-2012 was detected in 12 tested patients. Nine of 42 cases (21%) had consumed kebab made of turkey meat, epidemiological and trace back investigation revealed that the meat was produced in Hungary using turkey meat from HU and AT fattening turkey farms. A RASFF was issued by AT food safety authority. After the peak in August in 2012, the non-travel-related case numbers declined but started to increase again in March 2013 peaking again in August.The first joint ECDC-EFSA Rapid risk assessment had been published in September 2012 and the second was published in May 2014. S. Stanley isolations from turkeys increased sharply from zero between 2004-2010 to almost 800 in 2012 suggesting gradual spread of the serotype in turkey farms in Europe. 1st UI in 2012 10 countries *http://http://ecdc.europa.eu/en/publications/Publications/salmonella-stanley-multi-country-outbreak-assessment-8-May-2014.pdf

Whole genome sequencing of selected S Whole genome sequencing of selected S. Stanley isolates: continuous source, Oct 2016 N=273

Could this outbreak have been prevented?

Salmonella legislation Regulation 2160/2003 Countries required to monitor Salmonella target serovars in poultry: breeding flocks, laying hens, broilers, breeding and fattening turkeys - Community targets for reduction of zoonoses and zoonotic agents in specified animal populations, including turkeys for all Salmonella serotypes of public health significance: ‘whether any serotype shows a rapid and recent ability to spread and to cause disease in humans and animals’ Regulation 1190/2012 Reduction target for EU: S. Enteritidis and S. Typhimurium in turkeys < 1%

Prevalence of Salmonella serotypes in turkey production chain in 2010 (EFSA monitoring) and 2006-2007 (baseline survey) No evidence of S. Stanley contamination S. Stanley appeared in turkey food chain in 2011 (first positive isolates reported to EFSA)

S. Stanley – persistent multi-country strain 19 August 2015: AT 115 cases with 2012 outbreak PFGE profile; turkey kebab suspected: single retailor in SK 17 December 2015: BE 27 cases: 18 human + one turkey meat isolate with 2012 outbreak PFGE profile On 19 August 2015, AT launched an Urgent Inquiry reporting an increase of Stanley cases with the same pulsotype as detected in the outbreaks since 2011. Existing TESSy typing data revealed that a signal of a cluster was identified through the molecular surveillance in Q1-2014. On 17 December 2015, BE launched an UI Three deaths reported to TESSy in 2013-2014

S. Stanley – lessons learned Does specific food legislation prevent control measures? What is enough evidence of a public health risk? Slow response => mandate needed from EC for trace-back at EU level Concept of ”endemic strains” not valid with WGS

Discussion WGS confirmed a multi-country outbreak with cases at least from five countries WGS helped to delineate outbreak: no linked cases in six countries; three originally replied possible increases WGS data generated in multiple sites was comparable but vehicle of infection not identified => Alert too late => Lack of epidemiological information => Lack of comparison of WGS data with food sector

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