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. Author manuscript; available in PMC: 2022 Nov 3.
Published in final edited form as: Food Environ Virol. 2022 Jul 23;14(3):236–245. doi: 10.1007/s12560-022-09527-y

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

Monica McClure 1, Johnson Nsubuga 1, Martha P Montgomery 2, Erin Jenkins 1, Alvin Crosby 1, Daniela Schoelen 1, Colin Basler 2, Sumathi Ramachandran 2, Yulin Lin 2, Guo-liang Xia 2, Yury Khudaykov 2, Vilasini Suktankar 1, Angela Wagley 3, Vincent Thomas 3, Jacquelina Woods 4, Leslie Hintz 1, Janete Oliveira 5, Ana Lilia Sandoval 5, Justin Frederick 6, Blake Hendrickson 7, Laura Gieraltowski 2, Stelios Viazis 1
PMCID: PMC9631456  NIHMSID: NIHMS1845907  PMID: 35871245

Abstract

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.

Keywords: Hepatitis A virus, Foodborne illness outbreak, Blackberries

Introduction

Hepatitis A virus (HAV) is a single-stranded, positive-sense, non-enveloped RNA virus belonging to the Picornaviridae family. HAV has six identified genotypes (I–VI), of which types I, II, and III are of human origin and subdivided into subtypes A and B; I and III are the most commonly isolated from humans (Nainan et al., 2006; Papafragkou & Kulka, 2016; Randazzo & Sánchez, 2020). HAV is mainly transmitted through the fecal–oral route, shed in high numbers, and is highly infectious. HAV is often transmitted through person-to-person contact and less often by contaminated water or food, with produce and ready-to-eat foods being the most common (Papafragkou & Kulka, 2016; Randazzo & Sánchez, 2020). With an incubation period ranging from 15 to 50 days, HAV infections cause acute hepatitis lasting up to 2 months, though some patients may have prolonged or relapsing symptoms for up to 6 months (Lemon & Walker, 2019). Globally, 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 (Kirk et al., 2015a, 2015b). Some recent outbreaks of foodborne HAV infections in the United States have been linked to the consumption of imported pomegranate arils from Turkey (Collier et al., 2014; U.S. Food and Drug Administration, 2013) and frozen strawberries from Egypt (U.S. Food and Drug Administration, 2016).

In 2019, blackberry (Rubus fruticosus) sales in the United States increased by 6% over the previous year, leading to more than $541 million in sales (The Produce Market Guide, 2020). Generally, domestic U.S. production accounts for 20% of the total volume of blackberries in the market, while Mexican production accounts for roughly 78% (Produce Blue Book, 2020). Following the seasonal availability of blackberries, U.S. production has been increasingly supplemented between October and May each year by imports from Mexico, which accounted for 97% of the 222.5 million pounds imported in 2018 and are grown primarily in the state of Michoacán (Produce Blue Book, 2019; Retailer, 2020). There have not been many viral outbreaks specifically linked to the consumption of blackberries, partially because blackberries tend to be combined and packaged with other berries, such as raspberries and blueberries, making it difficult to separate the berries when trying to determine the vehicle for the outbreak (Nasheri et al., 2019; Scavia et al., 2017). There are several factors that may contribute to an increased risk of HAV contamination for berries, including their proximity to the ground during the growing phase, making them susceptible to contaminants such as contaminated water at the pre- or post-harvest stage. Additionally, multiple steps of manipulation from harvest to consumption increase the risk of contamination by infected handlers (Alegbeleye et al., 2018; Nasheri et al., 2019).

In 2019, federal, state, and local partners investigated a multi-state outbreak of HAV infections linked to fresh, conventional blackberries sourced from multiple suppliers from Michoacán, Mexico. Preliminary findings from this investigation have been previously reported elsewhere (U.S. Centers for Disease Control and Prevention, 2019b; U.S. Food and Drug Administration, 2019). Epidemiologic and traceback information pinpointed blackberries as the vehicle early on in the investigation. This multi-state outbreak illustrated the importance of food safety practices for produce that contribute to foodborne illness outbreaks (Commission, 2017; GLOBAL GAP, 2017; U.S. Food and Drug Administration, 2018, 2020, 2022).

Materials and Methods

Epidemiologic Investigation

Hepatitis A is a nationally notifiable disease (U.S. Centers for Disease Control and Prevention, 2019a). In Nebraska, Hepatitis A is an “immediate report,” and an automated electronic laboratory report is sent to public health officials as soon as a positive result is obtained. Each case is investigated using a standardized questionnaire to identify potential sources of exposure and potential for spread, e.g., food handler. On November 5, 2019, the Nebraska Department of Health and Human Services (NDHHS) reported a cluster of three hepatitis A cases to the Centers for Disease Control and Prevention (CDC). Additional cases in other states were identified through notification to health departments and health care providers. Local and state partners interviewed ill persons using a hepatitis A-specific case investigation form to collect demographic information and details for foods, grocery store, and restaurant exposures in the 15–50 days prior to illness onset. The frequency of reported foods consumed by people in the outbreak was compared with food frequencies from the 2006 to 2007 CDC FoodNet Population Survey using a cumulative binomial probability (U.S. Centers for Disease Control and Prevention, 2007). Because the FoodNet Population Survey asks about foods consumed over a 7-day period compared with 35-day exposure period for hepatitis A, we multiplied proportions by 5 (35/7) as a sensitivity analysis. In addition to food exposure, other exposures assessed in the questionnaire include drug use, homelessness, and international travel. An outbreak case was defined as acute HAV infection with illness onset during October 1 through November 30, 2019 with either sequencing related to the outbreak strain (0–1 nucleotide difference) or reported consumption of fresh blackberries purchased at Grocer A or Grocer B during the 15–50 days before illness onset without a more likely, alternative exposure.

Laboratory Investigation

Clinical Isolates

Specimens were submitted to state and federal public health laboratories. The following methods are for specimens tested at the CDC laboratory. Local and state health departments submitted serum specimens positive for immunoglobulin M (IgM) antibody to HAV from ill patients to CDC Division of Viral Hepatitis laboratory for molecular testing. A 349-nucleotide segment of the HAV genome spanning the VP1-P2B junction was reverse transcribed, and the cDNA was PCR amplified and subjected to next-generation sequencing using the CDC developed global hepatitis outbreak and surveillance technology (GHOST) protocol (Ramachandran et al., 2021). Genotyping and phylogenetic analysis based on maximum likelihood algorithms were conducted to determine the relatedness of the sequences from the RNA-positive samples.

Product Samples

FDA collected fresh blackberry samples from three U.S. distributors (Fig. 1), nine importers at the port of entry as a result of increased screening, and one consumer’s home freezer. This individual was not ill with hepatitis A but responded to a public health advisory issued by Douglas County Health Department soliciting consumers to contact NDHHS if they had blackberries from the retail locations identified in the traceback investigation; the consumer purchased Brand A blackberries from Grocer A. Fresh blackberries were analyzed for the presence of HAV using a high pH eluent along with ultracentrifugation for concentration and murine norovirus was utilized as an extraction control. Successful extraction is dependent upon detection of the extraction control and the internal amplification control. None of the samples analyzed showed product inhibition based on the performance these controls (Williams-Woods et al., 2022).

Fig. 1.

Fig. 1

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Traceback diagram for multi-state outbreak of hepatitis A virus infections associated with consumption of fresh, conventional blackberries from Mexico in 2019. Purchases of implicated products are traced from the point of service, through the distribution chain, to distributors and importers. Product originates from the foreign packing houses and farms, denoted on the right side of the diagram

Traceback Investigation

Traceback investigations are used to document the movement of the suspected food vehicle through the supply chain to determine whether it converges on a common source or supplier. A traceback investigation was initiated per standard FDA traceback practices (CIFOR, 2014; Irvin et al., 2021). Optimal cases of ill persons for inclusion in traceback sub-clusters included individuals with illnesses reported by state or local partners and individuals with reported exposure to fresh conventional blackberries within 50 days of becoming ill. Information related to individuals’ exposure to blackberries, including dates, receipts, and purchase documentation were collected for review. Ill persons were identified based on review of their illness history and blackberry purchase information. Blackberry purchase records including but not limited to receipts, invoices, bills of lading, import entry documentation, and other relevant product traceability documents were collected by investigators from points of service (POS), distributors, and importers along the blackberry supply chain. If specific lot information was not available for the purchased product, timelines were constructed using the most likely timeframes capturing the transfer of product from one responsible party to another. For patients with no purchase dates, the average incubation period of 15–50 days prior to illness onset was used to estimate purchase dates. Information relevant to timeline construction collected from implicated firms along the supply chain included stock rotation, delivery frequency, and shelf life of product.

Firm Investigations

FDA and state regulatory partners conducted 12 inspections, comprised of eight distributors/suppliers and four warehouses. Inspections were conducted to obtain traceability information, fresh blackberry handling procedures and sample collection.

Results

Epidemiologic Investigation

As of February 19, 2020, a total of 20 cases of outbreak-related HAV infections were reported in seven states (seven from Nebraska, six from Wisconsin, three from Indiana, and one each from Michigan, Minnesota, Missouri, and Pennsylvania), including 11 hospitalizations (58%), and no deaths (Fig. 2a). Illness onset dates ranged from October 8, 2019 through November 15, 2019 (Fig. 2b). The median age of patients was 50 years (range 14–73 years), and 12 (60%) ill people were female. Sixteen of 20 cases were included as outbreak cases based on sequencing and epidemiologic linkage, four cases were included based on epidemiologic linkage only, and one case was included based on sequencing linkage only. The proportion who reported eating fresh blackberries (19/20, 95%) was significantly higher than the CDC FoodNet Population Survey in which 7% of healthy people reported eating fresh blackberries in the prior week (p < .0001). This difference remained significant in sensitivity analysis (95% versus 35%, p < .0001). Of 17 people with known fresh blackberry purchase location information, 16/17 (94%) purchased fresh blackberries from either Grocer A or Grocer B. One person reported drug use, and none reported homelessness or international travel. The absence of these other risk factors supported the hypothesis that this was a common-source foodborne outbreak caused by HAV. Case patients also recalled blackberries being promoted and on sale at Grocer A (Fig. 1) during the timeframe of likely exposure.

Fig. 2.

Fig. 2

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Hepatitis A virus infections associated with exposure to fresh blackberries purchased from Grocer A or Grocer B by state of residence (a) and date of illness onset (b)

Laboratory Investigation

Clinical Isolates

DNA sequencing was utilized to identify cases that may be related. Of the 20 outbreak cases, a total of 16 clinical specimens were sequenced, and all were determined to be genotype 1A and had highly related (0–1 nucleotide difference) VP1-P2B sequences, forming a distinct outbreak cluster (Fig. 3).

Fig. 3.

Fig. 3

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Phylogenetic tree of hepatitis A virus isolates involved in the outbreak assessed using next-generation sequencing-based global hepatitis outbreak and surveillance technology

Product Samples

FDA and state partners collected fresh blackberry samples from Supplier 1 (IL), Supplier 3 (IL), and Supplier 13 (TX) (Fig. 1). The fresh, conventional blackberries collected and analyzed by FDA were not sourced from lots purchased by the ill persons from point of sale (POS), and thus not representative of the products that caused the outbreak. All samples analyzed by FDA tested negative for the presence of HAV.

Traceback Investigation

FDA and state partners conducted record and information collection at 12 U.S.-based firms. FDA and state and local partners collaborated to complete a traceback investigation for fresh, conventional blackberries purchased by 16 ill persons who reported purchasing fresh blackberries from 11 POS in Indiana, Nebraska, Michigan, Minnesota, Missouri, and Wisconsin between September 16 and 29, 2019 (Fig. 1). Eight of the 16 ill persons selected for traceback provided specific purchase dates for blackberries and for the other half the dates were estimated. Based on traceback records collected, all 10 Grocer A stores received fresh blackberries from a single distribution center, Distributor 1 (IL), owned and operated by Grocer A. A single distributor of fresh blackberries to Grocer B was implicated based on one of the case’s purchase date; Distributor 2 (WI). Traceback records show both distributors received fresh blackberries from multiple suppliers, and one common supplier was identified, Supplier 4 (FL). Blackberry Brand A was the only common brand identified on supply records to the distribution centers. Through the traceback investigation, federal and state partners identified a common brand, Brand A, that was supplied to Grocers A and B. The Brand A blackberries were supplied by one company, Importer 6 (Michoacán, Mexico). The traceback investigation did not reveal convergence on a common grower or packing house within Mexico, since Importer 6 received blackberries from 264 different growers that were located across three municipalities, Miguel Silva, Tacambaro, and Ziracuaretiro, all of which were located approximately 45–65 km from each other, in Michoacán, Mexico.

Public Health and Regulatory Activities

FDA has authority to refuse product offered for import into the United States if it appears, from the examination of samples or otherwise, that the product is adulterated [21 U.S.C. 381(a)]. FDA routinely collects and analyzes samples of imported products to determine if they meet FDA’s food safety standards. During outbreaks, FDA can conduct targeted sampling (increased screening) at import for firms of interest identified through traceback and state or local laboratory information. As a result of traceback findings, a total of seven firms were subjected to increased screening at the port of entry. All of the samples collected and analyzed were negative for HAV.

Public Communication

FDA and CDC provided continuous updates through public advisory web postings that were initially posted on November 20, 2019 and updated on December 3 and 10, 2019 and February 12 and 19, 2020 with specific information on how to handle potential exposure to the implicated fresh blackberries, including recommending consumers consult with their health care provider to determine whether post-exposure prophylaxis (PEP) was indicated. (U.S. Centers for Disease Control and Prevention, 2019b; U.S. Food and Drug Administration, 2019). The Nebraska Department of Health and Human Services also issued public health notifications to inform and protect the public (Nebraska Department of Health & Human Services, 2019).

Discussion

This outbreak represents the first multi-state outbreak of HAV infections in the United States where fresh blackberries were the implicated product. While HAV infections have been commonly linked to frozen and fresh mixed berry products (Collier et al., 2014; U.S. Food and Drug Administration, 2016), this outbreak provides evidence of contamination of fresh blackberries, imported from the state of Michoacán, Mexico, and presents a new potential food vehicle for infection that may be considered in future outbreak investigations. The traceback investigation revealed complexities in identifying a specific farm or source of the blackberries. As a result, FDA officials did not conduct an onsite inspection and environmental assessment at the Mexican fresh blackberry suppliers. Improved traceability of blackberries is needed to determine environmental antecedents and contributing factors to prevent future HAV outbreaks associated with blackberries.

The World Health Organization categorized berries as the second most concerning produce commodity category, after leafy greens (World Health Organization, 2008). A recent review of published foodborne illness outbreaks caused by norovirus and HAV infections around the globe from 1983 to 2018, showed that individual berries and mixed berry exposure, fresh and frozen, were responsible for 94 outbreaks and 23,433 illnesses (Bozkurt et al., 2021). Blackberries implicated in outbreaks are usually identified as a part of berry mixes, but rarely, if ever, implicated on their own. In fact, according to the same review, there was only one published outbreak linked to the consumption of frozen blackberries in Germany in 2005. In 2018, there was an outbreak of 18 laboratory-confirmed HAV infections with genotype 1A reported across Canada, but while a case–control study suggested that the source was either shrimp or blackberries, neither could be confirmed (Smith et al., 2019). This outbreak investigation provides the strongest evidence to date of imported fresh, conventional blackberries as the source of the outbreak. This is of concern since historically, on a commercial level, blackberries are a relatively new crop, but one that is becoming increasingly more common in U.S. markets (Finn & Clark, 2011). Blackberries sold in the United States were initially sourced from California and the Pacific Northwest in the 1990s and subsequently from Mexico in the 2000s, mainly from the states of Michoacán and Jalisco (Finn & Clark, 2011).

The long incubation period for hepatitis A of 15–50 days creates challenges for investigating foodborne hepatitis A outbreaks. Timely identification of outbreak vehicles is important because hepatitis A vaccine should be administered as soon as possible, preferably within 2 weeks of exposure, to all unvaccinated persons aged ≥ 12 months who have recently been exposed to HAV or the identified outbreak vehicle (Nelson et al., 2020). During interviews, ill patients are asked to recall food exposures that span a 5-week period and occurred more than 2 weeks prior to illness onset. Comparison of food consumption with the FoodNet Population Survey is not ideal because of the different exposure period surveyed (7 days) compared with hepatitis A (35 days) and the change in food consumption behaviors since 2006–2007. If a suspected food item is identified, leftover food samples and receipt records from the time of exposure are rarely available. Purchases of the suspected item, such as fresh blackberries, might have occurred at multiple time points, which further complicates traceback. In this investigation, food history recollection was aided by prompt and thorough interviews with patients who tested positive, as well as the prominent display and notable sale of blackberries at the grocery stores. Blackberries may also be easier to identify as a source of illness because it is not as commonly consumed as other fruits, making it more memorable and easier to recall the timeframe for purchase and consumption.

Many of the challenges encountered during the traceback investigation of fresh blackberries have also been described previously during outbreaks linked to other fresh produce commodities (Irvin et al., 2021; Whitney et al., 2021). This investigation revealed multiple gaps in traceability practices. A receiving warehouse (Supplier 7, TX) co-mingled fresh blackberry clam shells they received from Importer 6 (Michoacán, MX), which were sourced from multiple farms and different days of arrival, lots, and batches, to meet customer orders. Additionally, Supplier 1 (IL) sorted blackberries to separate out decaying berries and repackaged them into the same clam shell containers prior to shipment to Distributor 1 (IL). Inadequate records provided by POS and fresh blackberry distributors documenting these practices limited our ability to implicate specific brands and suppliers of fresh blackberries. Several patients in this outbreak lacked purchase or exposure dates. For patients with purchase dates available, they purchased on multiple dates, and the other patients had no purchase dates available. As mentioned earlier, for patients without purchase dates, illness onset dates with an incubation period of 15–50 days were used to estimate the purchase dates. It was observed in this traceback investigation that Brand A blackberries were comprised of blackberries co-mingled from many growers in the state of Michoacán, Mexico, further complicating efforts to determine a common source of this outbreak. This is in line with the previous studies describing the Mexican business models for blackberries in which larger exporting firms have contracts with many smaller growers to provide product for export (Crespo Stupková, 2016). Lastly, the vast majority of Mexican blackberry production is concentrated in the Los Reyes Valley in Michoacán (Crespo Stupková, 2016), further supporting the findings of the traceback investigation and strengthening the focus on blackberry production practices in this agricultural region of Mexico.

Blackberries, and berries in general, could become contaminated by foodborne viral pathogens at the pre- and post-harvest level as documented by past outbreak investigations (Bozkurt et al., 2021). Sources of contamination can include improper handling and violation of sanitary practices during growing, packing, and distribution (Bozkurt et al., 2021; Randazzo & Sánchez, 2020). HAV infection occurs exclusively in humans and thus contamination of produce must occur either directly from an infected person or through fecal-contaminated water. Hepatitis A vaccines are available in Mexico, but universal childhood vaccination for HAV infection is not mandated. This leaves more working age individuals susceptible to HAV infection (López-Gatell et al., 2018; Trujillo-Ochoa et al., 2019). However, in this outbreak, investigators were unable to determine the source of contamination due to the traceback limitations and lack of an on-farm investigation. Additionally, it was unclear whether contamination could have occurred at the growing, packing, or distribution level since there was not a single common grower, packer, or distributor identified. This outbreak showed how complicated traceback of fresh blackberries can be and how it can limit the rest of the investigation. FDA is continuing collaboration with Mexican officials through ongoing education and outreach efforts to the agricultural community (U.S. Food and Drug Administration, 2018). Consequently, FDA had continued to sample imported blackberries from suspected firms identified through the traceback investigation until October 2021 in an effort to prevent further illnesses.

There were several challenges that could explain the lack of recovery of HAV from fresh blackberry samples that were collected during this outbreak investigation. First, the fresh blackberries that were collected for analysis were not representative of the lots of product consumed by the ill persons that comprised the outbreak. The lots of product consumed by the ill persons were no longer available due to their expired shelf life. This could also suggest that the contamination could have been an isolated event and not a wide-spread issue that would have prolonged the contamination of the blackberries and subsequently the infection of additional consumers. One of the most common obstacles in analyzing food linked to outbreaks is that generally, these products have a limited shelf life, or they have been disposed of by consumers or retailers and thus are not available for collection and analysis (Ruscher et al., 2020). This complicates HAV outbreak investigations since ill persons can develop symptoms up to 50 days after consumption of the implicated food. In addition, HAV can withstand most extreme environmental conditions yet it does not propagate in food or the environment and requires a human host (D’Souza et al., 2007). During pre- and/or post-harvest contamination, these viruses are not homogeneously dispersed in foods and thus collecting and analyzing a limited number of samples decreases the probability of detecting contaminated product and usually results in a poor HAV recovery rate (Ruscher et al., 2020). Ultimately, traceback limitations did not allow investigators to determine the original source of the product and as a result, an on-field investigation was not possible. While the root cause of the outbreak was not identified, the contamination of the blackberries by HAV suggests a break down in the adherence to appropriate food safety and health and hygiene practices at the pre- or post-harvest level of the supply chain, as well as the inability to quickly identify and remove the contaminated product from the market. It is important that stakeholders assess the effectiveness of their produce safety systems, deliver the appropriate training to their staff, strive for continuous improvement of their food safety practices, and comply with the U.S. Food Safety Modernization Act (FSMA) Produce Safety Rule (PSR), as appropriate (Julien-Javaux et al., 2019; U.S. Food and Drug Administration, 2018, 2020). Additionally, the FDA has recently proposed to establish traceability recordkeeping requirements for persons who manufacture, process, pack, or hold foods to help the FDA rapidly and effectively identify recipients of those foods to prevent or mitigate foodborne illness outbreaks and address credible threats of serious adverse health consequences or death, that can potentially help minimize the impact of produce contamination on public health (U.S. Food and Drug Administration, 2022).

Conclusions

Epidemiologic and traceback investigations revealed that fresh, conventional blackberries imported from Michoacán, Mexico were the source of this outbreak of HAV infections. The blackberries were traced back to multiple distributors, with convergence to one importer, but could not be linked to a single harvest source. Additionally, the lack of availability of an implicated lot for testing and not being able to detect the pathogen from samples available for testing, limited investigators’ ability to determine the source of the implicated blackberries. The epidemiologic and traceback evidence resulted in increased screening of fresh blackberries imported from seven Mexico firms to prevent contaminated product from entering the U.S. market and protect public health. Produce safety outreach and education efforts are an important component of the United States-Mexico food safety prevention strategy for fresh produce. In 2020, the FDA renewed these efforts by signing a statement of intent with Mexican authorities, creating the U.S.-Mexico Food Safety Partnership, to work together on food safety in both countries, including outbreak prevention and response, regulatory laboratory collaboration, and outreach and training opportunities for produce growers. This investigation demonstrated the strength of public health partnerships at the federal, state, and local level.

Acknowledgements

The response efforts to this outbreak included numerous public health officials at local and state health departments in the United States, who serve as the backbone of any multi-state outbreak investigation. We would like to thank the dedicated public health officials from the Douglas County Health Department and the Nebraska Department of Health and Human Services for identifying the locations where the blackberries were purchased. Special thanks to the FDA emergency response coordinators for assisting with FDA’s traceback and sample collection activities. We also acknowledge Dr. Efstathia Papafragkou for her review of the manuscript.

Funding

No funds, grants, or other support were received.

Footnotes

Disclaimer The findings and conclusions in this report are those of the authors and do not necessarily reflect the official position of the Centers for Disease Control and Prevention, the Food and Drug Administration, or the authors’ affiliated institutions.

Conflict of interest The authors declare that they have no conflict of interest.

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