> REGULATORY REPORT

Novel Food-Pathogen Pairs and Associated Outbreaks

Since the establishment of the Coordinated Outbreak Response and Evaluation (CORE) Network in 2011, FDA has investigated numerous outbreaks that involved a unique food-pathogen pair. At the time of the investigations, these outbreaks presented additional challenges. Here, we highlight specific challenges presented by five of these outbreaks, some of the lessons learned, and regulatory/public health actions that resulted from them. Each of these outbreaks provided useful information that has helped guide later outbreak investigations.

Organic Sprouted Chia Seed Powder in 2014:

In 2014, FDA, the U.S. Centers for Disease Control and Prevention (CDC), Canadian health and regulatory officials, and state and local officials investigated an outbreak of Salmonella Newport, Salmonella Hartford, and Salmonella Oranienburg infections. The preliminary epidemiologic investigation identified chia seed powder as an item of interest. From this, the investigators began to narrow the focus by asking more specific questions. CDC and state partners used a supplemental questionnaire focused on the chia powder product and other health food products. Several case patients identified chia seeds or powder produced by a company in California. Investigators engaged with this business and learned that the product was manufactured in Canada. This led to a great deal of coordination and information sharing between U.S. and Canadian authorities. Additionally, the leveraging of state laboratory resources was another vital facet of the investigation. Laboratory testing by state partners isolated the outbreak strains from samples of leftover products collected from ill people’s homes and from unopened retail samples. With increased sampling, more Salmonella serotypes were identified. A traceback investigation identified a Canadian manufacturer as a common supplier of organic sprouted chia powder used in these products. The products were exported to a company in California where they were repackaged for further distribution and retail sale.

On May 28, 2014, FDA, CDC, and the California Department of Public Health warned consumers not to eat products that contained organic sprouted chia seed powder subject to the voluntary recall by the implicated Californian company. FDA and state partners conducted an inspection at the Californian company, and Canadian officials investigated the Canadian manufacturer, but the exact source of contamination could not be determined. Further investigation resulted in recalls of additional brands of chia seed powder products. Canadian partners investigated similar cases of Salmonella infection in several Canadian provinces.

On June 11, 2014, FDA placed the Canadian manufacturer on Import Alert, which informed FDA’s field staff and the public that the agency had enough evidence to allow for detention without physical examination of the product, which appeared to be in violation of FDA regulations and the Federal Food, Drug, and Cosmetic Act of 1938. If a product is detained without physical examination and sufficient evidence is not provided to FDA to overcome the appearance of the violation, it may be refused admission into the United States. For U.S. cases, a total of 31 ill people infected with the outbreak strains of Salmonella Newport (20 people), Salmonella Hartford (7 people), or Salmonella Oranienburg (4 people) were reported from 16 states. The epidemiologic, laboratory, and traceback investigations linked this international outbreak to a novel vehicle, organic sprouted chia seed powder.

“Novel food-pathogen pairs emerge frequently, given that food production practices and consumer behaviors change over time.”

Powdered Meal Replacement Containing a Moringa Leaf Powder Ingredient in 2016:

In 2016, FDA, CDC, and state and local partners investigated a multistate outbreak of Salmonella Virchow infections. The outbreak strain was a new pattern of a rare serotype that was added to the PulseNet database, which is used to compare the DNA fingerprints of bacteria from patients to help identify outbreaks of disease. Twenty-eight of the 30 ill people interviewed reported consuming powdered supplements or meal replacement powders in the week before illness onset. Twenty-seven ill people specifically reported consuming products from a company in Florida. FDA and CDC shared this information with the company’s executives, who then voluntarily recalled its products. Utah state partners confirmed that Salmonella was isolated from an open container of the company’s organic shake product collected from a case patient through pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS). Testing of open containers of the product from ill people’s homes in Utah and Oklahoma by their respective state public health agencies confirmed that Salmonella isolates collected by the states matched the outbreak strain. Epidemiologic and laboratory evidence indicated that products manufactured by the company in Florida were the likely source of this outbreak. However, the investigating agencies wanted to determine which of the many ingredients in the product were contaminated. The investigators prioritized the ingredients for traceback and sampling by focusing on those that were raw or unprocessed. Through this focus, it was discovered that the manufacturer had recently begun using a new supplier of moringa leaf powder. Finally, FDA sampling confirmed the presence of the outbreak strain of Salmonella Virchow in organic moringa leaf powder used in recalled organic shake and meal replacement products. A total of 33 people infected with the outbreak strain of Salmonella Virchow were reported from 23 states.

Soy Nut Butter in 2017:

In 2017, FDA, CDC, and state and local partners investigated an outbreak of Shiga toxin-producing E. coli O157:H7 infections linked to the consumption of a soy nut butter sold by a company in Illinois and produced by a contract manufacturer in Kentucky. Epidemiologic analysis identified that a large number of those reported ill were children who had eaten the product at day care facilities. Following the epidemiologic analysis confirming that sick individuals had consumed this product, investigators engaged with the company marketing the product. The company recalled its soy nut butter products. FDA suspended the food facility registration for the contract manufacturer of the soy nut butter products after an inspection of the contract manufacturer identified insanitary conditions that could lead to E. coli O157:H7 contamination in finished food products. The suspension of the contract manufacturer’s food facility registration meant that no food could leave its facility for sale or distribution. State partners and FDA collected 111 total samples (including product and ingredient samples), with 11 of the state product samples returning positive results for the outbreak strain of E. coli O157:H7. A total of 32 people infected with the outbreak strain of E. coli O157:H7 were reported from 12 states, while 12 people were hospitalized and 9 people developed hemolytic uremic syndrome, a condition that affects the blood and blood vessels and may result in kidney failure.

Fresh Crabmeat Imported from Venezuela in 2018:

In 2018, FDA, CDC, and state and local partners investigated a multistate outbreak of V. parahaemolyticus infections. Of the 24 people interviewed about their food exposure, 22 (92%) reported eating crabmeat in homes or restaurants. Epidemiologic evidence suggested that the case patients were exposed to fresh crabmeat from Venezuela. The traceback investigation identified multiple Venezuelan processors that supplied multiple brands of crabmeat during the outbreak. Based on records, Venezuelan crabmeat was available and could have been consumed by all ill people identified as part of the traceback investigation, but no single company was identified as the source of the outbreak. FDA increased testing of fresh crabmeat from Venezuela as a protective measure. A total of 31 crabmeat samples were collected by FDA and state partners during the response to this incident. FDA did not identify V. parahaemolyticus in any of the samples tested but did identify Salmonella and L. monocytogenes in some crabmeat samples collected at import, and these affected products were refused admission into U.S. commerce. Four Maryland samples were found positive for V. parahaemolyticus, but none of the isolates matched the outbreak strain by WGS. Third-party testing results reported to FDA by crabmeat distributors showed detectable amounts of V. parahaemolyticus in 7 of 170 samples reported to FDA. FDA advised consumers to avoid eating fresh crabmeat from Venezuela, as it may have been contaminated with V. parahaemolyticus. A total of 26 laboratory-confirmed cases of V. parahaemolyticus infection from seven states and the District of Columbia were reported.

“The lessons learned from these atypical outbreaks can help inform the regulatory approach for these foods.”

Products Reported to Contain Kratom in 2018:

In 2018, FDA, CDC, and state and local health officials investigated a multistate outbreak of salmonellosis from multiple serotypes of Salmonella: I 4,[5],12:b:-, Thompson, Okatie, Heidelberg, Weltevreden, and Javiana. Epidemiologic evidence indicated that kratom (Mitragyna speciosa) or kratom-containing products were the likely source of the outbreak, as 76 of 103 (74%) people who were specifically asked about kratom reported consuming it before getting sick. These kratom products were available in many forms, including leaves, pills, capsules, powder, and tea. FDA collected over 81 total kratom and kratom-containing samples of products that were specifically reported by people that got sick or products that were available at the point of sale where people who got sick purchased them. A total of 42 samples collected by FDA were positive for Salmonella, and 24 samples yielded at least one isolate that matched an outbreak strain. State partners collected over 86 total samples, of which 41 samples yielded Salmonella spp. isolates, and 14 samples yielded at least one isolate that matched an outbreak strain. Genetic analysis revealed that many of the isolates were highly related to clinical isolates in the outbreak by PFGE and WGS. The traceback investigation did not converge on a single point of sale, brand, supplier, or country of origin.

The traceback revealed that the case patients were exposed to adulterated kratom and kratom-containing products purchased from a variety of physical retail locations and Internet sites, supporting the hypothesis that multiple contamination events may have occurred. Initially, a specific manufacturer that was identified through the traceback investigation did not comply with FDA’s request to voluntarily cease distribution and recall the products. FDA issued a mandatory recall order for all food products containing powdered kratom that were manufactured, processed, packed, or held by the manufacturer after several of the products were found to contain Salmonella. Following the mandatory recall order, this company recalled the products. A number of other companies did voluntarily recall kratom-containing products. A total of 199 people infected with the outbreak strains of Salmonella were reported from 41 states over the time frame of the active investigation.

Achievements and Challenges

The outbreaks described above were associated with novel food vehicles, that is, those that had not been previously linked to these specific foodborne pathogens. Combined, they were responsible for 321 known illnesses. These outbreaks required a combination of epidemiologic, traceback, and laboratory evidence to conclusively identify the responsible vehicle, as has been typical for other outbreaks. Traditional outbreak investigation tools were employed successfully, and the CORE Network’s platform for collaboration with federal partners, as well as state and local agricultural and public health partners, was instrumental in protecting public health. This platform is highly important in promoting an integrated food safety system that can allow federal, state, and local investigators to successfully investigate both the usual and unusual suspects during foodborne illness outbreaks.

When investigating outbreaks linked to multi-ingredient foods, one of the challenges is determining which ingredient is responsible for the outbreak. One of the most crucial elements in these investigations was the early epidemiologic work to interview ill individuals that took place at the state and/or local level to identify these atypical vehicles and identify the best follow-up questions to ask. Upon initial interview, cases or their surrogates, such as a parent, may not know, remember, or volunteer information regarding consumption of the item of interest. For example, some parents did not initially know their child had consumed soy nut butter at his/her day care facility, some cases did not recall crabmeat in a meal, and some cases would not declare their kratom usage (kratom is illegal in some states). The collaboration of our state partners with CDC allows the identification of potential food vehicles at the national level, the development of targeted questions for case patients regarding specific food items that may be of interest, and information sharing among the health agencies. When narrowing down which ingredient was most likely responsible for the outbreaks, traceback investigations were proven to be valuable tools for federal and state regulatory partners. Laboratory analysis, including analysis of leftover product in ill consumers’ homes, played a very important role in recovering the outbreak isolates from product or environmental samples, helping confirm contamination and narrow the focus of the investigation. As most of the outbreaks described above included a food or food ingredient that was imported into the U.S., FDA increased screening of certain imported foods at the border and implemented Import Alerts. An Import Alert provides information to FDA field staff and the public that the agency has enough evidence to allow for detention without physical examination of products that appear to be in violation of the Federal Food, Drug, and Cosmetic Act. A business may provide evidence to the FDA in an attempt to overcome the appearance of the violation, but if the information is not sufficient, the product is subject to refusal into the United States. FDA’s increased screening at the border and Import Alerts helped prevent contaminated foods from entering the U.S. market.

Lessons Learned

Outbreaks attributed to atypical foods can have lasting impacts on how we investigate future outbreaks. Because of the unique characteristics and ever-changing aspects of the food industry, new risks can emerge. Changes in food production and distribution patterns have led to more opportunities for contamination early in the supply chain, which may lead to wide distribution of contaminated foods or ingredients, and as a result, an increased possibility of multistate foodborne disease outbreaks. By identifying these foods, the root cause of their contamination, or at the very least the potential contamination pathway either by the producer or consumer, federal and state partners can place them on their future outbreak “radar.” For example, CDC and state and local public health investigators may ask about this new food vehicle in their hypothesis-generating questionnaires or other exposure assessment tools. This leads to an expansion of prevention efforts focused on additional foods or firms, and the subsequent investment of resources to prevent future outbreaks. This can happen through increased inspection frequency, environmental sampling at firms, targeted commodity and/or firm sampling, enhanced screening at the border, updated guidance to industry, or public consumer messaging.

Outbreaks linked to previously undocumented food vehicles, such as peanut butter, flour, or ice cream, have in some cases become sentinel outbreaks, leading to the identification of other outbreaks linked to these foods. Thus, initially unusual food-pathogen pairs may subsequently become more common. This may be attributed to a variety of factors, including but not limited to changes in market dynamics, growing and harvesting methods, or consumer consumption patterns. These atypical food-pathogen pairs may also be a result of industry-level shifts in competing agricultural industries and interrelated risk factors, such as the establishment of larger production facilities where diverse food products are produced. These facilities may lead to new routes of pathogen introduction to different foods if proper separation of these food products is not maintained. Food preparation methods by the consumer or points of service can change the risk level of pathogen contamination and have led to novel food vehicles responsible for outbreaks.

Identifying the root cause of outbreaks is important to help determine how to prevent the next one. However, root-cause investigations are especially important in outbreaks of these atypical food-pathogen pairs. As a result of the recent emergence of these food-pathogen pairs as potential outbreak vehicles, public health professionals now consider the previously implicated foods as possible sources in outbreaks and have communicated the risk associated with exposure to them in public health messaging. This may also provide information about the root cause of food contamination, which may indicate other potential unknown food-pathogen pairs and inform future mitigation strategies.

“When investigating outbreaks linked to multi-ingredient foods, one of the challenges is determining which ingredient is responsible for the outbreak.”

Lessons Learned

We will continue to see the emergence of novel food-pathogen pairs as the food supply continues to diversify and new products enter the market. It is important to always consider that many foodborne pathogens can contaminate, survive, and grow under a variety of conditions, so we should not rule out a new food vehicle as the potential cause for a future outbreak. Additionally, conducting timely, in-depth root-cause investigations to clarify the underlying contributing factors and then quickly communicating the results of these root-cause investigations are critical to our goal of primary prevention.

Stelios Viazis, Ph.D., is a member of FDA’s CORE Network and part of the CORE Outbreak Analytics team. Previously, he served as a member of CORE Response, where he coordinated outbreak response efforts as well as the FDA Produce Safety Network, where he served as a Western Region subject-matter expert on the Produce Safety Rule.

Michael C. Bazaco, Ph.D., is a member of FDA’s CORE Network, which manages surveillance, response, and postresponse activities related to illness outbreaks in FDA-regulated human food and cosmetic products. Prior to coming to CORE, he was a member of the FDA Office of Analytics and Outreach, where he was the emerging infectious disease lead.

Douglas Karas, M.A., is the team leader of the FDA’s CORE Network Communications team. He oversees the issuance of public warnings about foodborne illness outbreaks. He has 25 years of experience in communications to include risk and emergency communications and media relations.