National Center for Emerging and Zoonotic Infectious Diseases FSIS & CDC Working Together for Rapid Response and Action: The Transformation of Surveillance and Outbreak Investigation for Foodborne and Enteric Pathogens Ian Williams, PhD, MS Chief, Outbreak Response and Prevention Branch Division of Foodborne, Waterborne and Environmental Diseases National Center for Emerging Zoonotic and Infectious Diseases FSIS Seminar March 22, 2017
InterAgency Agreement (IAA) Background • Established in FY07 • Three goals listed in FY16 – National outbreak detection and response will be fully coordinated between the responding federal, state, and local agencies – Implement metrics, performance measures, and best practices for foodborne outbreak response – Provide assistance to state and local health departments for outbreak response 2
Overall Impact of IAA on National Outbreak Response Activities • Ensured close collaboration between CDC and FSIS • Ensured that Foodborne Outbreak Response and Management (InFORM) meetings and PulseNet/OutbreakNet Regional Meetings were held • Helped continue the Foodborne Diseases Centers for Outbreak Response Enhancement (FoodCORE) and OutbreakNet Enhanced projects • Helped develop approaches to detection and investigation of multistate foodborne disease outbreaks • Ensured successful investigations of FSIS regulated products 3
Targeted CDC Programs to Address Gaps in Foodborne Disease Outbreak Response Capacity OutbreakNet OutbreakNet Enhanced Foodborne Diseases Centers for Outbreak Response Enhancement (FoodCORE) Integrated Food Safety Centers of Excellence
FoodCORE Centers of Excellence Providing Support Building Capacity for Other Health Departments in Participating Health Departments ~ ~ Collaborations across: Collaborations among: Health Departments Laboratorians Academia Epidemiologists Environmental Health Specialists OutbreakNet Enhanced Model Technical Additional Funding for Practices Assistance Participating Health Departments ~ Collaborations with CoEs OutbreakNet/NORS Epi Support
FoodCORE Started in late 2009 10 participating sites Improve Lab, Epi, and Share Lessons EH Capacity Learned as Model Practices Measure Success through Metrics
OutbreakNet Enhanced Started in 2015 18 participating sites Partner Build on FoodCORE with a Center Successes of Excellence – Focus on Epi Capacity Measure Success through Metrics Expanding to Additional Sites
Collaboration and Integration InFORM Conference - tenth annual OutbreakNet meeting Joint national conference with Lab, Epi, and EH November 17-20, 2015 in Phoenix, AZ Joint PulseNet/OutbreakNet Regional Meetings during FY17 Regional meeting with Lab, Epi, and EH OutbreakNet Quarterly Calls All-state partner calls with range of topics OWL calls – wise persons cal on selected topics
Impact of IAA on National Outbreak Response Activities Critical in making OutbreakNet and FoodCORE fully functional Paved the way for the implementation of the 11 OutbreakNet Enhanced sites during FY15 and expansion to 18 sites in FY16. Working together during 2016 we investigated over 200 multistate clusters > 6,500 culture-confirmed enteric illnesses, resulting in over 900 hospitalizations and approximately 25 deaths In any given week, we were investigating an average of 41 clusters with a range of 21 to 57 clusters per week Fifteen major foodborne and zoonotic outbreak investigations (13 foodborne and 2 enteric zoonotic) FSIS-regulated products mplicated and recalled included pork and beef products 35 individual web postings which were viewed over 2.5 million times The investigations of these outbreaks led to important short-term and long-term preventive measures that are making the food supply safer
W HOLE G ENOME S EQUENCING (WGS): T RANSFORMING S URVEILLANCE AND O UTBREAK I NVESTIGATION FOR F OODBORNE AND E NTERIC P ATHOGENS
Foodborne Diseases in the United States: A Changing Landscape Food production and distribution has changed substantially over the last several decades Fewer food producers, but with wider distribution On average, food comes from farther away More “ready-to-eat” and industrially produced foods
Foodborne Diseases in the United States: A Changing Landscape “Classic” Foodborne Outbreak Disseminated Foodborne Outbreak
Detecting Outbreaks with PulseNet Subtyping enteric bacteria is essential to identifying highly disseminated outbreaks PulseNet laboratory network established in 1996 Bacteria collected from ill people undergo DNA “fingerprinting” using pulse-field gel electrophoresis (PFGE) = Bacteria with the same “fingerprint” are more likely to come from a common source
PulseNet Groups Together Cases Most Likely To Share a Cause for Their Illnesses 14
PulseNet In Transition PulseNet is transitioning from PFGE to WGS MLVA PFGE WGS PFGE WGS 2010 2018 1996 2005 Modified from Carleton and Gerner-Smidt In Preparation: PulseNet International Vision for the Implementation (ASM Microbe July 2016) of WGS for Global Foodborne disease Surveillance
Conceptual Framework for PFGE Subtyping “Cut” Sites Bacterial Genome PFGE Genome “ Fragments ” Patterns Analogous to comparing two books based on the number of words in each chapter
Strengths and Limitations of PFGE-Based Subtyping Successful over the last 20 years in detecting highly disseminated outbreaks – Would not have otherwise been detected – Would have been detected later Limitations to PFGE-based subtyping – Some PFGE patterns common, limiting utility – PFGE patterns are indirectly reflective of underlying genetic relatedness of bacteria – Related bacteria can appear different by PFGE and vice versa
2010 Outbreak of Salmonella Enteritidis Infections Linked to Shell Eggs Most common PFGE pattern in the PulseNet database 3,578 illnesses reported during the outbreak period 1,639 presumed to be unrelated “baseline” cases Complicated investigation into the source
WGS Provides a Higher Resolution View of the Bacterial Genome All “Cut” Positions Sites PFGE only gives information at a WGS has the ability to give us “cut” site via the banding pattern information at every position in the bacterial genome Analogous to comparing two books based on all the words in the book
Incorporation of Whole Genome Sequencing Techniques into Multistate Foodborne Outbreaks In September 2013, CDC began prospectively sequencing all clinical isolates from listeriosis cases – Collaboration between numerous federal and state agencies – Near real-time results (<1 week for patient isolates) WGS also being performed on selected Salmonella and E. coli isolates – Consensus process between lab and epi on what to sequence/analyze – To answer specific investigation questions
Public Health Impact of WGS on Listeriosis Outbreak Investigations 120 Pre-WGS (Sept 2012–Aug 2013) 103 100 WGS Year 1 (Sept 2013–Aug 2014) 80 WGS Year 2 (Sept 2014–Aug 2015) 60 WGS Year 3 (Sept 2015-Aug 2016) 42 40 21 20 19 17 20 14 13 9 8 6 6 6 5 5 4 4 3 2 0 0 No. of clusters No. of clusters No. of outbreaks Median no. of No. of cases detected detected sooner solved cases per cluster linked to food or only by WGS* (food source or outbreak source identified)
WGS Impact on Outbreak Investigations Grouped isolates with different PFGE patterns into single clusters Blue Bell listeriosis outbreak Determined the source of older unsolved illnesses/clusters Karoun Dairies Cheese listeriosis outbreak Demonstrated that some PFGE-defined clusters did not consist of highly related isolates Salmonella Typhimurium pseudo-cluster with high mortality Refined outbreak case definitions Multidrug-Resistant Salmonella I 4,[5],12:i:- and Salmonella Infantis Infections Linked to Pork Linked sporadic illnesses to contaminated food Two listeriosis cases linked to raw milk Identified outbreaks following product testing Listeriosis illnesses linked to bagged salad Helped understand the ecology of pathogen reservoirs Multidrug-Resistant Salmonella Heidelberg Infections Linked to Foster Farms Brand Chicken
What Is an Outbreak? PFGE model has focuses on illnesses “exceeding baseline” – More cases than expected over a specified time period – Interpretation affected by how common the PFGE pattern is – Many “background” cases may be included in an investigation WGS model throws out the idea of a baseline? – Groups isolates that are highly likely to share a common source – More analogous to seeing an outbreak with a novel PFGE pattern
Changing Notion of Sporadic Illness Listeriosis linked to frozen vegetables • 9 cases in 3 years These illnesses are not sporadic, but are endemic disease that previously appeared sporadic because of limitations in investigation tools Listeriosis linked to ice cream • 10 cases in 5 years
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