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Committee: Infectious Disease

Title: Case Definition for Non-pestis Yersiniosis

☐Check this box if this position statement is an update to an existing standardized surveillance case definition.

I. Statement of the Problem Non-pestis Yersiniosis is an infection caused most commonly by the bacteria Yersinia enterocolitica or Yersinia pseudotuberculosis. These bacteria are normal intestinal and oropharyngeal colonizers of swine, and most commonly cause infections in children under 10 years of age or adults over 70 years of age through contaminated food. After Salmonella, Shigella, Campylobacter, and Shiga-toxin producing E. coli, it is the 5th most commonly reported gastrointestinal bacterial illness reported through CDC Foodborne Diseases Active Surveillance Network (FoodNet), which monitors 10 sites in the United States for nine enteric pathogens transmitted through food. The increasing use of culture-independent diagnostic tests (CIDTs) in all parts of clinical medicine, and particularly in gastrointestinal illnesses, has also increased recognition of certain pathogens. Data from 2016 from FoodNet show a 29% increase in culture-confirmed and a 91% increase in CIDT-diagnosed Yersinia infections when compared to the 2013-2015 time frame. In 38 states, Yersinia enterocolitica and/or Yersinia pseudotuberculosis infections are reportable, but no standard national definition exists for confirmed and probable cases. This position statement proposes a standardized case definition for non-pestis Yersiniosis.

II. Background and Justification Yersinia enterocolitica and Yersinia pseudotuberculosis are Gram negative rod-shaped or coccoid organisms that can be isolated from many animals and are most often transmitted to humans from undercooked or contaminated pork. Pathogenic serotypes have also been found in numerous other foods, milk products, and water. Together, infection with either of these organisms is known as non-pestis Yersiniosis. Y. enterocolitica is the more common of the two infections and most often causes gastrointestinal infections that can involve fever, diarrhea that may be bloody, and severe abdominal pain due to inflamed lymph nodes known as mesenteric adenitis. This abdominal pain can be so severe that it mimics appendicitis. Extra-intestinal manifestations include soft tissue abscesses, and post-infectious immune-mediated syndromes such as reactive arthritis and soft tissue swellings called erythema nodosum are also associated with Y. enterocolitica. This organism has also been described rarely as a cause of severe sepsis after transfusions with contaminated red blood cell transfusions. Y. pseudotuberculosis is much less common, but has similar animal reservoirs, transmission patterns, and clinical presentations. Both most commonly infect children less than 10 years of age or older than 70 years of age, have an incubation period from 1-14 days, and illness lasts 7-14 days. The illness is often self-limited, but may require hospitalization (mean 4 days, range 1- 17 days). Diagnosis is via culture, serology, or nucleic acid amplification test (NAT), and may be from specimens including stool, blood, urine, infected tissue, or pus.1 Four multiplex gastrointestinal panel NAT CIDTs are currently commercially available, and three report 90-100% sensitivity for detection of Yersinia in clinical specimens.2 Three closely related species that may cause disease, Yersinia intermedia, Y. fredericksenii, and Y. kristensenii, have high levels of cross-reactivity with the Y. enterocolitca in these NAT CIDTs,3 so laboratories may only report CIDTs to Yersinia genus level. Most strains are susceptible to tetracyclines and gentamicin. There are no vaccines for non-pestis Yersiniosis at this time.1

Historically African-American children under 5 years of age were at highest risk of developing non-pestis Yersiniosis. This was seen particularly in southern communities where chitterlings, a holiday dish made of pig intestines, was a commonly consumed food. Since a public education campaign on food safety was performed in Georgia, children under 5 remain the highest risk group for infection, but there is no longer a predominance of cases in African-American children.4 Overall rates had been decreasing with time until 2016, when a significant increase in both culture-confirmed and NAT CIDT-diagnosed cases was noted.5 Since Yersinia is the 5th most commonly reported enteric bacterial pathogen in FoodNet-monitored sites and does not yet have a standard case definition, it would be beneficial to those 38 states who do have mandatory reporting, and any future jurisdictions

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who wish to expand to include non-pestis Yersiniosis in their reporting for CSTE to create a national case definition for these illnesses.

III. Statement of the desired action(s) to be taken CSTE recommends the following actions:

1. Utilize standard sources (e.g. reporting*) for case ascertainment for non-pestis Yersiniosis. Surveillance for non-pestis Yersiniosis should use the following recommended sources of data to the extent of coverage presented in Table III.

Table III. Recommended sources of data and extent of coverage for ascertainment of cases of non- pestis Yersiniosis. Coverage Source of data for case ascertainment Population-wide Sentinel sites Clinician reporting X Laboratory reporting X Reporting by other entities (e.g., hospitals, veterinarians, pharmacies, poison centers), specify: Death certificates Hospital discharge or outpatient records Extracts from electronic medical records Telephone survey School-based survey Other, specify: 2018 Template *Reporting: process of a healthcare provider or other entity submitting a report (case information) of a condition under public health surveillance TO local or state public health. Note: notification is addressed in a Nationally Notifiable Conditions Recommendation Statement and is the process of a local or state public health authority submitting a report (case information) of a condition on the Nationally Notifiable Conditions List TO CDC.

2. Utilize standardized criteria for case identification and classification (Sections VI and VII and Technical Supplement) for non-pestis Yersiniosis.

Note: this action does NOT add non-pestis Yersiniosis to the Nationally Notifiable Condition List. If requested by CDC, jurisdictions (e.g., States and Territories) conducting surveillance according to these methods may voluntarily submit case information to CDC.

IV. Goals of Surveillance The goals of surveillance are to provide timely and standardized information in order to identify and control any transmission, as well as facilitate comparability in case counts across jurisdictions. This is not a recommendation to require national reporting.

V. Methods for Surveillance: Surveillance for non-pestis Yersiniosis should use the recommended sources of data and the extent of coverage listed in Table III. Data sources for case ascertainment include clinician and laboratory reporting. A positive culture for Y. enterocolitca or Y. pseudotuberculosis is a requirement to be a confirmed case; a positive NAT CIDT for any Yersinia non-pestis species or clinically compatible case with epidemiologic link to a confirmed or probable case is necessary to be a probable case.

VI. Criteria for case ascertainment

A. Narrative: A description of suggested criteria for case ascertainment of non-pestis Yersiniosis

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Report any person or laboratory finding to public health authorities that meets any of the following: Laboratory criteria:

• Isolation of any Yersinia non-pestis species by culture from a clinical specimen OR • Detection of any Yersinia non-pestis species using a CIDT

Criteria for epidemiologic linkage • Any person with fever, diarrhea, or abdominal pain who had recent contact with a laboratory confirmed case of non-pestis Yersiniosis OR • Any person with fever, diarrhea, or abdominal pain who had recent contact with a member of a risk group during an outbreak of non-pestis Yersiniosis

B. Disease-specific data elements to be included in the initial report

In the initial report, please include • Test result, specimen source, and type of test (if CIDT, PCR or antibody test) OR • Brief clinical description including severity of illness, if case required hospitalization, and type of epidemiologic linkage.

VII. Case Definition for Case Classification

A. Narrative: Description of criteria to determine how a case should be classified.

Clinical Criteria An illness with either diarrhea or abdominal pain that may be severe enough to mimic appendicitis.

Note: Extra-intestinal manifestations may also be present, such as abscess, which could be a source for testing, and reactive arthritis and erythema nodosum, which are often immunologic phenomena not directly caused by the infection. These manifestations are not required as part of the clinical criteria.

Laboratory Criteria Confirmatory laboratory evidence: Isolation of Y. enterocolitica or Y. pseudotuberculosis by culture from a clinical specimen.

Presumptive laboratory evidence: Detection of any Yersinia non-pestis species using a NAT CIDT.

Supportive laboratory evidence: N/A

Epidemiologic Linkage A person who has had contact with a case that meets the presumptive or confirmatory laboratory criteria.

Case Classifications Confirmed: A case that meets the confirmed laboratory criteria.

Probable: A case that meets the presumptive laboratory criteria OR A clinically compatible case that is epidemiologically linked to a case meeting confirmatory or presumptive laboratory criteria

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B. Criteria to distinguish a new case of this disease or condition from reports or notifications which should not be enumerated as a new case for surveillance A repeat culture or NAT CIDT result within 365 days of initial report should not be enumerated as a new case for surveillance. When two or more different Yersinia non-pestis species are identified in one or more specimens from the same individual, each should be reported as a separate case.

VIII. Period of Surveillance Surveillance is expected to be on-going.

IX. Data sharing/release and print criteria

CSTE recommends the following case statuses be included in the CDC Print Criteria: ☒Confirmed ☒Probable ☐Suspect ☐Unknown

X. Revision History

N/A

XI. References 1. Woods CR. Other Yersinia Species. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases. Philadelphia, PA: Elsevier Saunders; 2018:1085-1097. 2. Huang RSP, Johnson CL, Pritchard L, Hepler R, Ton TT, Dunn JJ. Performance of the Verigene® enteric pathogens test, Biofire FilmArrayTM gastrointestinal panel and Luminex xTAG® gastrointestinal pathogen panel for detection of common enteric pathogens. Diagn Microbiol Infect Dis. 2016;86(4):336- 339. doi:10.1016/j.diagmicrobio.2016.09.013. 3. Noble MA, Barteluk RL, Freeman HJ, et al. Clinical Significance of Virulence-Related Assay of Yersinia Species. J Clin Micr. 1987;25(5):802-807. 4. Ong KL, Gould LH, Chen DL, et al. Changing Epidemiology of Yersinia enterocolitica Infections: Markedly Decreased Rates in Young Black Children, Foodborne Diseases Active Surveillance Network ( FoodNet ), 1996 – 2009. 2015;54(0 5):S385-S390. 5. Marder EP, Cieslak PR, Cronquiest AB, et al. Incidence and Trends of Infections with Pathogens Transmitted commonly through Food and the Effect of Increasing use of Culture-Independent Diagnostic Tests on Surveillance —Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2013-2016. MMWR Morb Mortal Wkly Rep. 2017;66(15):404-407. doi:http://dx.doi.org/10.15585/mmwr.mm6615a1.

XII. Coordination

Subject Matter Expert (SME) Consultants:

(1) Kirk Smith Enteric Diseases Subcommittee Chair 18-ID-02 4

CSTE [email protected]

(2) Ellyn Marder Surveillance Epidemiologist, FoodNet Centers for Disease Control and Prevention 404-718-4722 [email protected]

(3) Aimee Geissler Epidemiologist, FoodNet Centers for Disease Control and Prevention [email protected]

(4) Logan Ray Epidemiologist, FoodNet Centers for Disease Control and Prevention [email protected]

Agencies for Response (1) Centers for Disease Control and Prevention Robert R. Redfield, MD Director 1600 Clifton Rd Atlanta, GA 30333 404-639-7000 [email protected]

Agencies for Information N/A

XIII. Author Information

Submitting and Presenting Author (1) Dirk Haselow State Epidemiologist Arkansas Department of Health 4815 West Markham Street, Slot 32 Little Rock, AR 72205-3867 501-614-5278 [email protected]

Co-Author: (Complete contact information must be provided for acceptance to review.)

(1) Active Member Associate Member

Sarah Labuda 18-ID-02 5

Epidemic Intelligence Service Officer CDC, Assigned to Arkansas Department of Health 4815 West Markham Street, Slot 32 Little Rock, AR 72205-3867 501-614-5278 [email protected]

(2) Active Member Associate Member

Krisandra Allen Foodborne and Enteric Disease Epidemiologist Washington State Department of Health 1610 NE 150th Street Shoreline, WA 98155 206-418-5440 [email protected]

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Technical Supplement

Table VI. Table of criteria to determine whether a case should be reported to public health authorities.

Criterion Reporting Reporting Disease or Condition Subtype Disease or Condition Subtype Clinical Evidence Fever O Diarrhea O Abdominal pain O Laboratory Evidence Isolation of any Yersinia non-pestis species S by culture from a clinical specimen Detection of any Yersinia non-pestis S species using a CIDT Epidemiological Evidence Person had recent contact with a laboratory O confirmed case of non-pestis Yersinosis Member of a risk group during an outbreak O investigation of non-pestis Yersiniosis 2018 Template Notes: S = This criterion alone is SUFFICIENT to report a case. O = At least one of these “O” (ONE OR MORE) criteria in each category (categories=clinical evidence, laboratory evidence, and epidemiological evidence) in the same column—in conjunction with all “N” criteria in the same column—is required to report a case.

Table VII. Classification Table: Criteria for defining a case of non-pestis Yersiniosis.

Probable Probable Confirmed Clinical Evidence Diarrhea O Abdominal pain O Laboratory Evidence Isolation of Y. enterocolitica or Y. pseudotuberculosis by N culture from a clinical specimen Detection of any Yersinia non-pestis species using a CIDT N Epidemiological Evidence A person who has had contact with a case that meets the O presumptive or confirmatory laboratory criteria Criteria to distinguish a new case Not counted as a new case if occurred within 365 days of N N N initial case 2018 Template Notes: N = All “N” criteria in the same column are NECESSARY to classify a case. A number following an “N” indicates that this criterion is only required for a specific disease/condition subtype (see below). If the absence of a criterion (i.e., criterion NOT present) is required for the case to meet the classification criteria, list the absence of criterion as a necessary component. O = At least one of these “O” (ONE OR MORE) criteria in each category (categories=clinical evidence, laboratory evidence, and epidemiologic evidence) in the same column—in conjunction with all “N” criteria in the same column—is required to classify a case. A number following an “O” indicates that this criterion is only required for a specific disease/condition subtype.

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