An Overview of Foodborne Sample-Initiated Retrospective Outbreak Investigations and Interagency Collaboration in the United States.

Foodborne outbreak investigations have traditionally included the detection of a cluster of illnesses first, followed by an epidemiologic investigation to identify a food of interest. The increasing use of whole genome sequencing (WGS) subtyping technology for clinical, environmental, and food isolates of foodborne pathogens, and the ability to share and compare the data on public platforms, present new opportunities to identify earlier links between illnesses and their potential sources. We describe a process called sample-initiated retrospective outbreak investigations (SIROIs) used by federal public health and regulatory partners in the United States. SIROIs begin with an evaluation of the genomic similarity between bacterial isolates recovered from food or environmental samples and clusters of clinical isolates while subsequent and parallel epidemiologic and traceback investigations are initiated to corroborate their connection. SIROIs allow for earlier hypothesis generation, followed by targeted collection of information about food exposures and the foods and manufacturer of interest, to confirm a link between the illnesses and their source. This often leads to earlier action that could reduce the breadth and burden of foodborne illness outbreaks. We describe two case studies of recent SIROIs and present the benefits and challenges. Benefits include insight into foodborne illness attribution, international collaboration, and opportunities for enhanced food safety efforts in the food industry. Challenges include resource intensiveness, variability of epidemiologic and traceback data, and an increasingly complex food supply chain. SIROIs are valuable in identifying connections among small numbers of illnesses that may span significant time periods; detecting early signals for larger outbreaks or food safety issues associated with manufacturers; improving our understanding of the scope of contamination of foods; and identifying novel pathogen/commodity pairs.

Salmonella Outbreaks Linked to Beef, United States, 2012-2019.

The Centers for Disease Control and Prevention (CDC) has identified nontyphoidal Salmonella as one of the top five pathogens contributing to foodborne illnesses in the United States. Beef continues to be a common source of Salmonella outbreaks, despite the implementation of interventions at slaughter and processing facilities to reduce contamination of beef. We described Salmonella outbreaks linked to beef in the United States during 2012-2019, examined trends, and identified potential targets for intervention and prevention strategies. We queried CDC's Foodborne Disease Outbreak Surveillance System (FDOSS) for all foodborne nontyphoidal Salmonella outbreaks linked to beef as the single contaminated ingredient or implicated food, with the date of first illness onset from 2012 to 2019. Information on antimicrobial resistance (AR) for outbreak-related isolates was obtained from CDC's National Antimicrobial Resistance Monitoring System (NARMS). We calculated the number of outbreaks, outbreak-related illnesses, hospitalizations, and deaths overall, by beef processing category and Salmonella serotype. During 2012-2019, 27 Salmonella outbreaks were linked to beef consumption, resulting in 1103 illnesses, 254 hospitalizations, and two deaths. The most common category of beef implicated was nonintact raw, ground beef (12 outbreaks, 44%), followed by intact raw (six outbreaks, 22%). Ground beef was responsible for the most illnesses (800, 73%), both of the reported deaths, and was the source of the largest outbreak. AR data were available for 717 isolates from 25 (93%) outbreaks. Nine (36%) of these outbreaks had isolates resistant to one or more of the antibiotics tested by NARMS, of which eight (89%) contained multidrug-resistant isolates. Several outbreaks reported highlight challenges faced during investigations, areas where further research may be warranted, and opportunities to prevent future outbreaks along the farm-to-fork continuum.

An Outbreak Investigation of Salmonella Typhimurium Illnesses in the United States Linked to Packaged Leafy Greens Produced at a Controlled Environment Agriculture Indoor Hydroponic Operation - 2021.

In 2021, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and state partners investigated a multistate outbreak of Salmonella Typhimurium illnesses linked to packaged leafy greens from a controlled environment agriculture (CEA) operation in Illinois. Thirty-one illnesses and four hospitalizations were reported in four states, with a significant epidemiologic signal for packaged leafy greens from Farm A. A traceback investigation for leafy greens included seven points of service (POS) with food exposure data from eight ill people. Each POS was supplied leafy greens by Farm A. FDA investigators observed operations at Farm A and noted that 1) the firm did not consider their indoor hydroponic pond water as agricultural water, 2) condensate dripping from the chiller water supply line inside the building, and 3) unprotected outdoor storage of packaged soilless growth media and pallets used for finished product. FDA collected 25 product, water, and environmental samples from Farm A. The outbreak strain was recovered from a water sample collected from a stormwater drainage basin located on the property adjacent to Farm A. In addition, an isolate of Salmonella Liverpool was recovered from two indoor growing ponds within the same growing house, but no illnesses were linked to the isolate. Farm A voluntarily recalled all implicated products and provided their root cause analysis (RCA) and return-to-market plan to FDA. While the source and route of the contamination were not determined by the RCA, epidemiologic and traceback evidence confirmed the packaged salads consumed by ill persons were produced by Farm A. This was the first investigation of a multistate foodborne illness outbreak associated with leafy greens grown in a CEA operation. This outbreak demonstrated the need for growers using hydroponic methods to review their practices for potential sources and routes of contamination and to reduce food safety risks when identified.

A Multiple-Serotype Outbreak of Salmonella Infections Linked to Kratom, United States, 2017-2018.

In early 2018, we investigated a large national multiple-serotype Salmonella outbreak linked to contaminated kratom, a raw minimally processed botanical substance. Kratom is a plant consumed for its stimulant effects and as an opioid substitute. A case was defined as a laboratory-confirmed Salmonella infection with one of the outbreak strains (serotypes I 4,[5],12:b:-, Heidelberg, Javiana, Okatie, Weltevreden, or Thompson) with illnesses onset during January 11, 2017-May 8, 2018. State and local officials collected detailed information on product consumption and sources. Suspected products were tested for Salmonella and traceback was conducted to determine product distribution chains and suppliers. We identified 199 cases from 41 states; 54 patients were hospitalized. Early interviews indicated kratom was an exposure of interest. Seventy-six (74%) of 103 people interviewed reported consuming kratom in pills, powders, or teas. Multiple serotypes of Salmonella were detected in samples of kratom collected from the homes of the patients and from retail locations. Several companies issued recalls of kratom products due to Salmonella contamination. To the authors' knowledge, this investigation is the first to establish kratom as a vehicle for Salmonella infection. Our findings underscore the serious safety concerns regarding minimally processed botanical substances intended for oral consumption and the challenges in investigating outbreaks linked to novel outbreak vehicles.

A 2019 Outbreak Investigation of Hepatitis A Virus Infections in the United States Linked to Imported Fresh Blackberries.

Globally, hepatitis A virus (HAV) is one of the most common agents of acute viral hepatitis and causes approximately 1.4 million cases and 90,000 deaths annually despite the existence of an effective vaccine. In 2019, federal, state, and local partners investigated a multi-state outbreak of HAV infections linked to fresh blackberries sourced from multiple suppliers in Michoacán, Mexico. A total of 20 individuals with outbreak-related HAV infection were reported in seven states, including 11 hospitalizations, and no deaths. The Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and Nebraska State and Douglas County Health Departments conducted a traceback investigation for fresh blackberries reportedly purchased by 16 ill persons. These individuals reported purchasing fresh blackberries from 11 points of service from September 16 through 29, 2019 and their clinical isolates assessed through next-generation sequencing and phylogenetic analysis were genetically similar. The traceback investigation did not reveal convergence on a common grower or packing house within Mexico, but all of the blackberries were harvested from growers in Michoacán, Mexico. FDA did not detect the pathogen after analyzing fresh blackberry samples from four distributors, one consumer, and from nine importers at the port of entry as a result of increased screening. Challenges included gaps in traceability practices and the inability to recover the pathogen from sample testing, which prohibited investigators from determining the source of the implicated blackberries. This multi-state outbreak illustrated the importance of food safety practices for fresh produce that may contribute to foodborne illness outbreaks.

Multistate outbreak of Salmonella Mbandaka infections linked to sweetened puffed wheat cereal - United States, 2018.

In May of 2018, PulseNet, the national molecular subtyping network for enteric pathogens, detected a multistate cluster of illnesses caused by an uncommon molecular subtype of Salmonella serovar Mbandaka. A case was defined as an illness in a person infected with the outbreak strain of Salmonella Mbandaka with illness onset on or after 3 March 2018 and before 1 September 2018. One-hundred thirty-six cases from 36 states were identified; 35 hospitalisations and no deaths were reported. Ill people ranged in age from <1 year to 95 years (median: 57 years). When standardised questionnaires did not generate a strong hypothesis, opened-ended interviews were performed. Sixty-three of 84 (75%) ultimately reported consuming or possibly consuming a specific sweetened puffed wheat cereal in the week before illness onset. Environmental sampling performed at the cereal manufacturing facility yielded the outbreak strain. The outbreak strain was also isolated from open cereal samples from ill people's homes and from a sealed retail sample. Due to these findings, the brand owner of the product issued a voluntary recall of the cereal on 14 June 2018. Additional investigation of the manufacturing facility identified persistent environmental contamination with Salmonella Mbandaka that was closely genetically related to other isolates in the outbreak. This investigation highlights the ability of Salmonella to survive in low-moisture environments, and the potential for prolonged outbreaks linked to products with long shelf lives and large distribution areas.

Multistate Outbreak of Listeria monocytogenes Infections Linked to Fresh, Soft Hispanic-Style Cheese - United States, 2021.

Listeriosis is a serious infection usually caused by eating food contaminated with the bacterium Listeria monocytogenes. An estimated 1,600 persons become ill with listeriosis each year, among whom approximately 260 die. Persons at higher risk for listeriosis include pregnant persons and their newborns, adults aged ≥65 years, and persons with weakened immune systems. Persons with invasive listeriosis usually report symptoms starting 1-4 weeks after eating food contaminated with L. monocytogenes; however, some persons who become infected have reported symptoms starting as late as 70 days after exposure or as early as the same day of exposure (1). On January 29, 2021, PulseNet, the national molecular subtyping surveillance network coordinated by CDC, identified a multistate cluster of three L. monocytogenes infections: two from Maryland and one from Connecticut (2). CDC, the Food and Drug Administration (FDA), and state and local partners began an investigation on February 1, 2021. A total of 13 outbreak-related cases were eventually identified from four states. All patients reported Hispanic ethnicity; 12 patients were hospitalized, and one died. Rapid food testing and record collection by regulatory agencies enabled investigators to identify a brand of queso fresco made with pasteurized milk as the likely source of the outbreak, leading to an initial product recall on February 19, 2021. Fresh, soft Hispanic-style cheeses made with pasteurized milk are a well-documented source of listeriosis outbreaks. These cheeses can be contaminated with L. monocytogenes unless stringent hygienic controls are implemented, and the processing environment is monitored for contamination (3). U.S. public health agencies should establish or improve communications, including new methods of disseminating information that also effectively reach Hispanic populations, to emphasize the risk from eating fresh, soft Hispanic-style cheeses, even those made with pasteurized milk.

Decisions to attend holiday gatherings during COVID-19 and engagement in key prevention strategies: United States, January 2021.

Gatherings where people are eating and drinking can increase the risk of getting and spreading SARS-CoV-2 among people who are not fully vaccinated; prevention strategies like wearing masks and physical distancing continue to be important for some groups. We conducted an online survey to characterise fall/winter 2020-2021 holiday gatherings, decisions to attend and prevention strategies employed during and before gatherings. We determined associations between practicing prevention strategies, demographics and COVID-19 experience. Among 502 respondents, one-third attended in person holiday gatherings; 73% wore masks and 84% practiced physical distancing, but less did so always (29% and 23%, respectively). Younger adults were 44% more likely to attend gatherings than adults ≥35 years. Younger adults (adjusted prevalence ratio (aPR) 1.53, 95% CI 1.19-1.97), persons who did not experience COVID-19 themselves or have relatives/close friends experience severe COVID-19 (aPR 1.56, 95% CI 1.18-2.07), and non-Hispanic White persons (aPR 1.57, 95% CI 1.13-2.18) were more likely to not always wear masks in public during the 2 weeks before gatherings. Public health messaging emphasizing consistent application of COVID-19 prevention strategies is important to slow the spread of COVID-19.

Multistate Outbreak Investigation of Salmonella Infections Linked to Kratom: A Focus on Traceback, Laboratory, and Regulatory Activities.

ABSTRACT: During spring 2018, the U.S. Food and Drug Administration (FDA), Centers for Disease Control and Prevention, and state and local public health agencies responded to a multistate outbreak of gastrointestinal illnesses caused by multiple Salmonella serovars and associated with consumption of kratom, a product harvested from a tropical tree native to Southeast Asia. The outbreak included 199 case-patients reported by 41 U.S. states, with illness onset dates ranging 11 from January 2017 to 8 May 2018, leading to 54 hospitalizations and no deaths. Case-patients reported purchasing kratom products from physical and online retail points of service (POSs). Products distributed to 16 POSs where 24 case-patients from 17 states purchased kratom were selected for traceback investigation. Traceback revealed that the kratom was imported from several countries, the most common being Indonesia. Local and state officials collected product samples from case-patients and retail POSs. The FDA collected 76 product samples from POSs and distributors, of which 42 (55%) tested positive for Salmonella. The positive samples exhibited a range of pulsed-field gel electrophoresis patterns and whole genome sequence genetic heterogeneity, and 25 (60%) of 42 samples yielded at least one isolate indistinguishable from one or more outbreak-related clinical isolates. Although it does not exclude a possibility of a single contamination source, the extent of genetic diversity exhibited by the Salmonella isolates recovered from product samples and a lack of traceback convergence suggested that kratom was widely contaminated across multiple sites from which it was grown, harvested, and packaged. As a result of the contamination, kratom products were recalled by numerous firms (both voluntarily and mandatory). Epidemiologic, traceback, and laboratory evidence supported the conclusion that kratom products were associated with illnesses.

A Series of Papaya-Associated Salmonella Illness Outbreak Investigations in 2017 and 2019: A Focus on Traceback, Laboratory, and Collaborative Efforts.

ABSTRACT: In 2017 and 2019, five outbreaks of infections from multiple strains of Salmonella linked to the consumption of whole, fresh Maradol papayas were reported in the United States, resulting in 325 ill persons. Traceback, laboratory, and epidemiologic evidence indicated papayas as the likely vehicle for each of these outbreaks and identified the source of papayas. State and U.S. Food and Drug Administration (FDA) laboratories recovered Salmonella from papaya samples from various points of distribution, including at import entry, and conducted serotyping, pulsed-field gel electrophoresis, and phylogenetic analyses of whole genome sequencing data. Federal and state partners led traceback investigations to determine the source of papayas. Four different suppliers of papayas were linked by traceback and laboratory results to five separate outbreaks of Salmonella infections associated with papayas. In 2017, multiple states tested papaya samples collected at retail, and Maryland and Virginia investigators recovered strains of Salmonella associated with one outbreak. FDA collected 183 papaya samples in 2017, and 11 samples yielded 62 isolates of Salmonella. Eleven serotypes of Salmonella were recovered from FDA papaya samples, and nine serotypes were closely related genetically by pulsed-field gel electrophoresis and whole genome sequencing to clinical isolates of four outbreaks, including the outbreak associated with positive state sample results. Four farms in Mexico were identified, and their names were released to the general public, retailers, and foreign authorities. In 2019, FDA collected 119 papaya samples, three of which yielded Salmonella; none yielded the 2019 outbreak strain. Investigators determined that papayas of interest had been sourced from a single farm in Campeche, Mexico, through traceback. This information was used to protect public health through public guidance, recalls, and import alerts and helped FDA collaborate with Mexican regulatory partners to enhance the food safety requirements for papayas imported from Mexico.

Hypothesis Generation During Foodborne-Illness Outbreak Investigations.

Hypothesis generation is a critical, but challenging, step in a foodborne outbreak investigation. The pathogens that contaminate food have many diverse reservoirs, resulting in seemingly limitless potential vehicles. Identifying a vehicle is particularly challenging for clusters detected through national pathogen-specific surveillance, because cases can be geographically dispersed and lack an obvious epidemiologic link. Moreover, state and local health departments could have limited resources to dedicate to cluster and outbreak investigations. These challenges underscore the importance of hypothesis generation during an outbreak investigation. In this review, we present a framework for hypothesis generation focusing on 3 primary sources of information, typically used in combination: 1) known sources of the pathogen causing illness; 2) person, place, and time characteristics of cases associated with the outbreak (descriptive data); and 3) case exposure assessment. Hypothesis generation can narrow the list of potential food vehicles and focus subsequent epidemiologic, laboratory, environmental, and traceback efforts, ensuring that time and resources are used more efficiently and increasing the likelihood of rapidly and conclusively implicating the contaminated food vehicle.

An Overview of Traceback Investigations and Three Case Studies of Recent Outbreaks of Escherichia coli O157:H7 Infections Linked to Romaine Lettuce.

ABSTRACT: Leafy greens contaminated with Shiga toxin-producing Escherichia coli have continued to cause foodborne illness outbreaks in recent years and present a threat to public health. An important component of foodborne illness outbreak investigations is determining the source of the outbreak vehicle through traceback investigations. The U.S. Food and Drug Administration is home to traceback investigation experts who use a standardized process to initiate, execute, and interpret the results of traceback investigations in collaboration with the Centers for Disease Control and Prevention and state and local partners. Traceback investigations of three outbreaks of Shiga toxin-producing E. coli infections linked to romaine lettuce in 2018 and 2019 were examined to demonstrate challenges, limitations, and opportunities for improvement. The three outbreaks resulted in a total of 474 illnesses, 215 hospitalizations, and 5 deaths. These illnesses were linked to the consumption of romaine lettuce from three distinct growing regions in Arizona and California. Some of the challenges encountered included the time it took to initiate a traceback, limited product-identifying information throughout the supply chain, lack of interoperability in record-keeping systems, and comingling of product from multiple suppliers. These challenges led to time delays in the identification of the farm source of the leafy greens and the inability to identify the root cause of contamination. Implementation of technology-enabled traceability systems, testing of these systems, and future regulations to incentivize adoption of traceability systems are some of the initiatives that will help address these challenges by improving traceback investigations and ultimately preventing foodborne illnesses and future outbreaks from occurring.

Two multistate outbreaks of a reoccurring Shiga toxin-producing Escherichia coli strain associated with romaine lettuce: USA, 2018-2019.

Leafy green vegetables are a common source of Shiga toxin-producing Escherichia coli O157:H7 (STEC O157) foodborne illness outbreaks. Ruminant animals, primarily cattle, are the major reservoir of STEC O157. Epidemiological, traceback and field investigations were conducted to identify potential outbreak sources. Product and environmental samples were tested for STEC. A reoccurring strain of STEC O157 caused two multistate outbreaks linked to romaine lettuce in 2018 and 2019, resulting in 234 illnesses in 33 states. Over 80% of patients interviewed consumed romaine lettuce before illness. The romaine lettuce was sourced from two California growing regions: Santa Maria and Salinas Valley in 2018 and Salinas Valley in 2019. The outbreak strain was isolated from environmental samples collected at sites >90 miles apart across growing regions, as well as from romaine-containing products in 2019. Although the definitive route of romaine contamination was undetermined, use of a contaminated agricultural water reservoir in 2018 and contamination from cattle grazing on adjacent land in 2019 were suspected as possible factors. Preventing lettuce contamination from growth to consumption is imperative to preventing illness. These outbreaks highlight the need to further understand mechanisms of romaine contamination, including the role of environmental or animal reservoirs for STEC O157.

Lessons Learned from a Decade of Investigations of Shiga Toxin-Producing Escherichia coli Outbreaks Linked to Leafy Greens, United States and Canada.

Shiga toxin-producing Escherichia coli (STEC) cause substantial and costly illnesses. Leafy greens are the second most common source of foodborne STEC O157 outbreaks. We examined STEC outbreaks linked to leafy greens during 2009-2018 in the United States and Canada. We identified 40 outbreaks, 1,212 illnesses, 77 cases of hemolytic uremic syndrome, and 8 deaths. More outbreaks were linked to romaine lettuce (54%) than to any other type of leafy green. More outbreaks occurred in the fall (45%) and spring (28%) than in other seasons. Barriers in epidemiologic and traceback investigations complicated identification of the ultimate outbreak source. Research on the seasonality of leafy green outbreaks and vulnerability to STEC contamination and bacterial survival dynamics by leafy green type are warranted. Improvements in traceability of leafy greens are also needed. Federal and state health partners, researchers, the leafy green industry, and retailers can work together on interventions to reduce STEC contamination.

Estimating the Incubation Period of Salmonella Urinary Tract Infections Using Foodborne Outbreak Data.

Urinary tract infections (UTIs) are common and may occur in foodborne Salmonella outbreaks. Using data from PulseNet, the U.S. national molecular subtyping network for foodborne disease surveillance, we analyzed the 9781 Salmonella isolates associated with the 110 outbreaks from 2004 to 2013 that included at least one urine isolate. Within each outbreak, we calculated standardized isolation dates, using these dates in a linear mixed model to estimate the difference in incubation period for infections yielding stool versus urine isolates. We estimate that the incubation period for Salmonella UTIs is on average 10.6 (95% confidence interval 6.0-15.2) days longer than for gastrointestinal illness, suggesting that outbreak investigators should interview UTI patients about a longer time period before illness onset to identify sources of infection.

Estimated Community Seroprevalence of SARS-CoV-2 Antibodies - Two Georgia Counties, April 28-May 3, 2020.

Transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is ongoing in many communities throughout the United States. Although case-based and syndromic surveillance are critical for monitoring the pandemic, these systems rely on persons obtaining testing or reporting a COVID-19-like illness. Using serologic tests to detect the presence of SARS-CoV-2 antibodies is an adjunctive strategy that estimates the prevalence of past infection in a population. During April 28-May 3, 2020, coinciding with the end of a statewide shelter-in-place order, CDC and the Georgia Department of Public Health conducted a serologic survey in DeKalb and Fulton counties in metropolitan Atlanta to estimate SARS-CoV-2 seroprevalence in the population. A two-stage cluster sampling design was used to randomly select 30 census blocks in each county, with a target of seven participating households per census block. Weighted estimates were calculated to account for the probability of selection and adjusted for age group, sex, and race/ethnicity. A total of 394 households and 696 persons participated and had a serology result; 19 (2.7%) of 696 persons had SARS-CoV-2 antibodies detected. The estimated weighted seroprevalence across these two metropolitan Atlanta counties was 2.5% (95% confidence interval [CI] = 1.4-4.5). Non-Hispanic black participants more commonly had SARS-CoV-2 antibodies than did participants of other racial/ethnic groups (p<0.01). Among persons with SARS-CoV-2 antibodies, 13 (weighted % = 49.9; 95% CI = 24.4-75.5) reported a COVID-19-compatible illness,* six (weighted % = 28.2; 95% CI = 11.9-53.3) sought medical care for a COVID-19-compatible illness, and five (weighted % = 15.7; 95% CI = 5.1-39.4) had been tested for SARS-CoV-2 infection, demonstrating that many of these infections would not have been identified through case-based or syndromic surveillance. The relatively low seroprevalence estimate in this report indicates that most persons in the catchment area had not been infected with SARS-CoV-2 at the time of the survey. Continued preventive measures, including social distancing, consistent and correct use of face coverings, and hand hygiene, remain critical in controlling community spread of SARS-CoV-2.