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APPENDIX 2

Yersinia enterocolitica • Direct contact with animal sources, particularly pigs Likelihood of Secondary Transmission: Disease Agent: • Person-to-person transmission is rare. However, con- • enterocolitica tamination of food by an infected food handler and Disease Agent Characteristics: nosocomial infections have been described.

• Gram-negative, facultatively anaerobic, to At-Risk Populations: , nonmotile, nonspore-forming, facul- • Infants and children have the highest risk of symp- tatively intracellular bacterium tomatic infection. • Order: Enterobacteriales; Family: Enterobacteriacea • Individuals with advanced liver disease and syn- • Size: 0.5-0.8 ¥ 1.0-2.0 mm dromes associated with iron overload have the • Nucleic acid: The genome of is highest risk of septicemic disease. 4616 kb of DNA. • Rural populations and those living in cooler temper- • Growth of Y. enterocolitica is enhanced by cold ate zones enrichment and exposure to 4°C for a period of time, • Certain racial and ethnic groups through exposure to and the organism is capable of growth at 4°C. particular foods and food preparation methods Disease Name: Vector and Reservoir Involved: • • Domestic animals (livestock) are the important Priority Level: animal reservoir. The major animal reservoir for strains that cause human illness is pigs. • Scientific/Epidemiologic evidence regarding blood safety: Low/Moderate; decreased frequency of Blood Phase: transfusion-associated cases over the past 10 years • Prolonged or recurrent bacteremia occurs in some • Public perception and/or regulatory concern regard- individuals after acute or chronic symptomatic or ing blood safety: Very low subclinical infection. • Public concern regarding disease agent: Absent • Persistent infection, when present, lasts for weeks in most instances, but it can persist for several years. Background: Survival/Persistence in Blood Products: • Y. enterocolitica is identified throughout the world, and is isolated from multiple environmental sources, • Full shelf life and beyond for whole blood and RBCs including water, contaminated foods, and a wide • Although significant bacterial growth increases over range of wild and domestic animals. Foodborne out- time, has been described with RBCs stored for breaks are recognized. as short a period as 14 days. • It is an infrequently recognized cause of and • can survive in phagocytic cells and abdominal pain in the US but is relatively more com- extracellularly. monly identified in northern Europe. Infections have • Plasma depletion typical of RBC units reduces or pre- been documented in other parts of the world, includ- vents complement-mediated killing of serum sensi- ing South America, Africa, and Asia, but Y. entero- tive Y. enterocolitica. colitica is not considered an important cause of • Time-dependent lysis of white blood cells releases tropical diarrhea. additional organisms and senescence of RBCs • Y. enterocolitica is highly heterogeneous and can be releases iron that stimulates and supports growth. divided into several bioserotypes, only a few of which • Variability in growth and survival in blood products are known to be associated with human disease. Most among serotypes may be related to serum resistance Y. enterocolitica strains causing human yersiniosis at storage temperatures and their capacity to bind belong to bioserotypes 1B/O:8, 2/O:5,27, 2/O:9, iron. 3/O:3, and 4/O:3. Transmission by Blood Transfusion: • Inefficient isolation methods have compromised ac- curate estimation of the prevalence of Y.enterocolitica • Multiple case reports (>30) of transfusion- disease. transmission of Y. enterocolitica from asymptomatic donors have occurred since 1975 (lack of reports prior Common Human Exposure Routes: to that may have been a result of shorter storage times • Ingestion of contaminated foods (plants or animal in use), including from autologous transfusion. Y. origin) enterocolitica accounts for more than half the cases of

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sepsis arising from transfusion of RBCs. At least one the elderly, and patients with iron overload. Septice- case of a transfusion reaction due to Y. enterocolitica mic patients may develop metastatic abscesses, contaminating a pooled platelet concentrate has endocarditis, and mycotic aneurysms. been reported. Severity of Clinical Disease: • Clinical disease symptoms in transfusion recipients may be a result of endotoxemia and/or subsequent • Primary septicemic transfusion-related Y. entero- growth of the organism. colitica infection is a severe disease.

Cases/Frequency in Population: Mortality:

• Estimated incidence in the US for 2003 was 0.4 per • Death is uncommon with naturally acquired 100,000, with highest rates among infants and young infection. children. These incidence rates are for symptomatic • High for Y. enterocolitica bacteremia related to disease accompanied by positive stool culture. transfusion; approximately 50% mortality rate • Incidence of subclinical and asymptomatic infections is unknown. Chronic Carriage: • Transfusion-transmitted Y. enterocolitica infection • Metastatic infections after bacteremia can cause sub- may be decreasing in recent years possibly because of acute and chronic infections, especially among high- interventions, such as leukoreduction, or because risk individuals. incidence of infection in the community is • Chronic infection after acute gastrointestinal infec- decreasing. tion has been alleged on the basis of persisting Incubation Period: gastrointestinal signs and symptoms, persistently positive serologies, and the development of rheu- • Food-borne gastroenteritis, typically 2-5 days matic syndromes. Microbiologic documentation that • In most cases of transfusion-associated yersiniosis, viable organisms persist in these patients is generally fever and hypotension occurred 1-2 hours after the not provided. start of transfusion of contaminated blood. Treatment Available/Efficacious: Likelihood of Clinical Disease: • Rate of asymptomatic gastrointestinal infection is • Susceptible to a variety of antimicrobial agents unknown. including , fluoroquinolones, • High in blood recipients who received a transfusion , tetracyclines, and trimethoprim- with a unit containing Y. enterocolitica sulfamethoxazole Primary Disease Symptoms: Agent-Specific Screening Question(s): • accounts for two-thirds of reported • No specific question is in use. cases of symptomatic Y. enterocolitica infections. This • Not indicated because of the low incidence of is characterized by fever, diarrhea, nausea, vomiting, transfusion-associated Yersinia sepsis and abdominal pain lasting 1-3 weeks. Patients with • Questions about recent gastrointestinal illness have mesenteric adenitis and/or terminal ileitis have fever, been documented to lack sensitivity and specificity. right lower quadrant pain and tenderness, and leuko- Laboratory Test(s) Available: cytosis, and as many as 10% may undergo operation for suspected . • No FDA-licensed blood donor screening test exists. • A reactive polyarthritis, lasting less than a year in • Options for serologic tests include EIAs that screen general has been specifically related to the presence for antibody, especially IgM, directed to virulence of HLA-B27 in individuals with yersiniosis. Ankylos- plasmid-mediated outer proteins. ingspondylitisrarelydevelops.Reiter’ssyndrome(arth- • Direct detection: Yersinia species grow well on media ritis, urethritis, and conjunctivitis) also has been that support the growth of . reported and is associated with HLA-B27 antigen. • Culture of whole blood and RBCs for Y. enterocolitica • Exudative pharyngitis is seen with Y. enterocolitica may be negative despite spiking of the blood with infections. In one outbreak in the US, 8% of viable organisms. Intracellular sequestration has patients presented with acute pharyngitis and fever, been hypothesized to account for such negative without accompanying diarrhea. cultures. • Y. enterocolitica septicemia is uncommon but severe • Other techniques that have been used include and often fatal. It is most often reported in patients IFA, electrochemiluminescence, and NAT-based with underlying immunocompromising conditions, detection methods.

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Currently Recommended Donor Deferral Period: • Discarding units of 25 days or older has also been suggested, but this would result in significant reduc- • No FDA Guidance or AABB Standard exists. tion in supply of RBCs for transfusion. • The length of a deferral period for a donor with diag- • Storage of RBCs at 0°C has been proposed as a way to nosed and resolved Y. enterocolitica gastroenteritis is delay and reduce growth of Y. enterocolitica. unclear. In the absence of any chronic disease mani- festations, it may be acceptable to consider such a Suggested Reading: donor as eligible when fully recovered, either sponta- 1. Allain JP, Bianco C, Blajchman MA, Brecher ME, neously or after treatment. Busch M, Leiby D, Lin L, Stramer S. Protecting the blood supply from emerging : the role of Impact on Blood Availability: inactivation. Transfus Med Rev 2005;19: • Agent-specific screening question(s): Not applicable 110-26. • Laboratory test(s) available: Not applicable 2. Arduino MJ, Bland LA, Tipple MA, Aguero SM, Favero MS, Jarvis WR. Growth and endotoxin production of Impact on Blood Safety: Yersinia enterocolitica and Enterobacter agglomerans • Agent-specific screening question(s): Not applicable in packed erythrocytes. J Clin Microbiol 1989;27: • Laboratory test(s) available: Not applicable 1483-5. 3. Bradley RM, Gander RM, Patel SK, Kaplan HS. In- Leukoreduction Efficacy: hibitory effect of 0°C storage on the proliferation of Yersinia enterocolitica in donated blood. Transfusion • The effectiveness of leukoreduction in reducing 1997;37:691-5. transmission and clinical cases of Y. enterocolitica is 4. Feng P, Keasler SP, Hill WE. Direct identification of unknown. Yersinia enterocolitica in blood by polymerase chain • In laboratory studies, leukocyte reduction filtration reaction amplification. Transfusion 1992;32:850-4. can reduce Y. enterocolitica contamination by remov- 5. Gibb AP,Martin KM, Davidson GA, Walker B, Murphy ing bacteria-laden phagocytic cells. Prefiltration WG. Modeling the growth of Yersinia enterocolitica in storage at room temperature allows for free organ- donated blood. Transfusion 1994;34:304-10. isms to be phagocytized by WBCs prior to filtration. 6. Grossman BJ, Kollins P,Lau PM, Perreten JL, Bowman Pathogen Reduction Efficacy for Plasma Derivatives: RJ, Malcolm S, Palko WM. Screening blood donors for gastrointestinal illness: a strategy to eliminate carriers • Specific data indicate that the multiple steps in the of Yersinia enterocolitica. Transfusion 1991;31:500-1. fractionation process are robust and capable of inac- 7. Hogman CF, Engstrand L. Factors affecting growth of tivating and/or removing bacteria at concentrations Yersinia enterocolitica in cellular blood products. that may be present in plasma. Transfus Med Rev 1996;10:259-75. 8. Kuehnert MJ, Jarvis WR, Schaffer DA, Chaffin DJ. Other Prevention Measures: Platelet transfusion reaction due to Yersinia entero- • Visual examination of units of blood looking for gross colitica. JAMA 1997;278:550. contamination is unlikely to be sensitive. 9. Kuehnert MJ, Roth VR, Haley NR, Gregory KR, Elder • Testing of RBC units of 25 days or older for endotoxin KV, Schreiber GB, Arduino MJ, Holt SC, Carson LA, or screening for bacteria by stained smear has been Banerjee SN, Jarvis WR. Transfusion-transmitted bac- proposed, but rapid and reliable tests are not terial infection in the United States, 1998 through available. 2000. Transfusion 2001;41:1493-9.

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