On December 26, 2017, PulseNet, the national molecular subtyping network for foodborne disease surveillance, detected a cluster of 14 cases of S. enterica serotype I 4,[5],12:b:- infection from 10 states. Bacterial isolates were characterized using pulsed-field gel electrophoresis (PFGE), a subtyping method that produces a DNA fingerprint that can be used to define outbreak strains. The PFGE pattern associated with the outbreak strain was uncommon in the PulseNet database, indicating bacterial isolates were likely associated with a common source.

The initial outbreak case definition was an infection with the outbreak strain of Salmonella I 4,[5],12:b:- in a person with illness onset after October 1, 2017. However, as product testing and epidemiological evidence was evaluated, strains with other PFGE patterns associated with illness were identified. Not all Salmonella strains that were identified through product testing were added to the case definition.

These additional Salmonella strains were assessed for links to outbreak illnesses based on three criteria: whether the PFGE pattern was currently or previously investigated as part of a multistate Salmonella outbreak; whether the number of human clinical isolates with the PFGE pattern uploaded in the previous 60 days was greater than expected; or whether the strain was isolated from both patient and leftover product samples collected from the ill person’s home. The final outbreak case definition included a laboratory-confirmed infection with the outbreak strains of Salmonella serotypes I 4,[5],12:b:-, Heidelberg, Javiana, Okatie, Thompson or Weltevreden with an illness onset date during January 1, 2017 to May 8, 2018.

Federal and state partners reviewed exposures reported during initial patient interviews, which included questions about food and animal exposures within the 7 days preceding illness onset. A common exposure across all the initial cases was not identified; however, exposure to an uncommon powdered kratom product was noted by a single patient. After additional interviews revealed similar exposures, a set of questions was developed to systematically capture details of kratom and other botanical product exposures including brand, variety, and place of purchase. Local and state health investigators conducted patient interviews through telephone during the outbreak investigation. Interview responses were sent to the CDC for analysis.

State health investigators collected kratom-containing products from patient homes and from retail locations where patients reported purchasing product. Samples of product were tested for Salmonella at state public health and partner laboratories; isolates were serotyped and PFGE was performed using standard PulseNet protocols (Ribot et al, 2006). Product isolate PFGE data were uploaded to the PulseNet national database and were compared with human clinical isolates using BioNumerics software (Applied Maths, Sint-Martens-Latem, Belgium).

State and local health agencies collected detailed information regarding product type, purchase location, date, and packaging. Regulatory officials at the state and federal level used this information to identify product suppliers and collect purchase records to delineate product supply chains. FDA and state investigators visited product packaging facilities and conducted inspections.

A total of 199 cases were identified from 41 states (Fig. 1). The most common Salmonella serotype among cases was I 4,[5],12:b:- (n = 83), followed by Thompson (n = 59 illnesses), Okatie (n = 28), Javiana (n = 17), Weltevreden (n = 6), and Heidelberg (n = 6). Patients ranged in age from <1 to 75 years (median 38) and 92 of 191 patients (48%) were female. Fifty-four patients were hospitalized, and no deaths were reported. Illnesses were reported as early as January 2017, but a marked increase in the number of detected cases began in October 2017 (Fig. 2).

On February 9, 2018, CDC and state partners held a tele-conference to discuss exposures reported during routine patient interviews. Officials with the North Dakota Department of Health described an exposure to kratom powder reported during one of these routine interviews. Although investigators were unfamiliar with kratom powder, it was reminiscent of other low moisture powdered botanical products (e.g., moringa powder and chia powder) recently linked to national Salmonella outbreaks (Gambino-Shirley et al, 2018; Harvey et al, 2017).

Kratom became a vehicle of interest because it was an unusual exposure, previous outbreaks demonstrated plant-derived powders, such as kratom, were biologically plausible, and the North Dakota patient was adamant kratom was the source of their illness. The kratom hypothesis strengthened on February 12, 2018, when a second patient from Utah, reported consuming kratom during reinterview. Based on information provided by the North Dakota patient, health officials in Utah contacted the second patient to ask specifically about kratom use, since that exposure was not mentioned during the initial interview.

Subsequent patient interviews conducted by state and local officials included detailed questions on kratom use. Data from interviews quickly bolstered the kratom hypothesis and by mid-February 2018, epidemiological evidence indicated kratom was the likely source of the outbreak with 8 (73%) of 11 patients reporting kratom consumption. In total, state and local officials were able to assess kratom use for 113 patients and 85 (75%) reported consuming kratom before illness onset. Among patients with available information, consumption of loose powdered kratom was the predominant form reported (46 patients), followed by preformed capsules (14 patients); 1 patient reported consuming a bottled kratom drink. A majority (52%) of patients reported purchasing kratom from retail locations, whereas others reported purchasing kratom from online sources. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.*

On February 14, 2018, officials from the North Dakota Department of Health isolated the initial outbreak strain of Salmonella I 4,[5],12:b:- from leftover kratom provided by the patient who first reported kratom use. These laboratory findings confirmed the epidemiological link between kratom consumption and illness.

During February through May 2018, officials in several states collected kratom from patient homes and from retail locations to test for Salmonella contamination. Overall, 21 Salmonella serotypes and 85 PFGE patterns were isolated from kratom products by state and FDA laboratories. Most Salmonella serotypes isolated from kratom yielded a single PFGE pattern and were not associated with human illness, but outbreak strains of Salmonella serotypes I 4,[5],12:b:-, Heidelberg, Javiana, Okatie, Thompson, and Weltevreden were identified. The FDA conducted extensive kratom testing and Salmonella was detected in 33 of 66 (50%) kratom samples tested, some yielding more than one Salmonella serotype (FDA, 2018a).

Strains of serotype Okatie with the outbreak PFGE pattern isolated from kratom in Oregon were associated with a previously investigated but unsolved multistate outbreak of Salmonella illnesses in early 2018. Initial patient interviews did not identify kratom as a potential source, but reinterview during this investigation established an epidemiological link between patients and kratom consumption.

FDA traced back kratom products purchased from 7 online and 9 physical location points of sale (POS), where 24 patients reportedly purchased kratom. As kratom products contaminated with Salmonella were identified during the investigation, FDA conducted online surveillance and purchased products for label review and laboratory analysis. Online products were sold as capsules, liquids, or powder. Powder package sizes ranged from 28 g to 1 kg. Some POS sold other botanical products, other consumer goods, encapsulation machines, and empty capsules. Although many accepted credit card payments, some POS only accepted wire transfers, cash on delivery, or cryptocurrency. Some online and physical POS included a disclaimer that the products did not come with directions for use (e.g., “sold as bulk product with no instructions”) or were not intended for human consumption.

In response to the outbreak, FDA and state regulatory agencies coordinated recall activities among retail suppliers and distributors of kratom products linked to human illness. In total, 13 initial and expanded recalls occurred during March–June 2018 due to this outbreak investigation involving 67 kratom products from 26 distributors. Notably, on April 2, 2018, FDA ordered the first mandatory recall of food product in U.S. history, an authority granted by the 2011 Food Safety Modernization Act, to remove kratom from the market due to the risk of Salmonella infection (FDA, 2018b). This unprecedented action by FDA was in response to a company’s refusal to voluntarily recall kratom products linked to illness.

CDC, FDA, and state agencies issued public health alerts and social media statements warning consumers of the risk of Salmonella infection from kratom and providing information on active kratom recalls and specific products that tested positive for Salmonella (CDC, 2018; FDA, 2018a). These warnings were updated routinely to provide consumers with relevant health information to guide decision-making and health behaviors. Both CDC and FDA advised consumers to avoid ingesting kratom products to reduce their risk of Salmonella infection.