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Background
The plague ravaged much of the ancient world during the dark ages. In spite of modern medicine, the disease has not been eradicated and still remains a public health threat. Yersinia infection has several forms including pneumonia, diarrhea, and sepsis.
Yersinia is a small rod-shaped, Gram-negative bacterium. It is not part of the native human flora but is found in animals such as cats, dogs, birds, and pigs as well as almost every environmental location such as lakes and rivers. Infection is usually through ingestion of contaminated food or water products and the onset of symptoms usually occurs between 24 and 48 hours. The most frequent symptoms include diarrhea, abdominal pain, and fever.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Plague (Y. pestis)
YersinosisINCIDENCE Common AGE RANGE-MEDIAN All
Very young and very old increased susceptibilityAll GEOGRAPHY Common in Northern Europe, Scandinavia, and Japan TRANSFUSION RELATED Transfusion-mediated Yersinia enterocolitica septicemia in an adult patient with beta-thalassemia.
Roussos A, Stambori M, Aggelis P, Kanavaki S, Garzonis P, Makarona M, Kapralos C, Karambela S, Dalamaga A, Ferti A.
Department of Internal Medicine, General Hospital Sotiria, Athens, Greece.
Scand J Infect Dis 2001;33(11):859-60 Abstract quote
We report a case of transfusion-mediated Yersinia enterocolitica septicemia in a 43-y-old woman with homozygous beta-thalassemia.
Two h after transfusion of 3 units of red blood cells the patient suffered high-grade fever and shaking chills. Y. enterocolitica serotype O3 grew in blood cultures. Prolonged treatment with i.v. ceftriaxone plus ciprofloxacin led to a favorable outcome. Transfusion-associated Y. enterocolitica septicemia has not previously been reported in an adult beta-thalassemic patient from the Mediterranean area.
Our report is particularly important, because of the high incidence of chronically transfused thalassemic patients in Mediterranean countries.
DISEASE ASSOCIATIONS CHARACTERIZATION HLA-B27
PATHOGENESIS CHARACTERIZATION ENTEROCOLITICIN Characterization of enterocoliticin, a phage tail-like bacteriocin, and its effect on pathogenic Yersinia enterocolitica strains.
Strauch E, Kaspar H, Schaudinn C, Dersch P, Madela K, Gewinner C, Hertwig S, Wecke J, Appel B.
Robert Koch Institut, 13353 Berlin, Germany.
Appl Environ Microbiol 2001 Dec;67(12):5634-42 Abstract quote
Yersinia enterocolitica 29930 (biogroup 1A; serogroup O:7,8) produces a bacteriocin, designated enterocoliticin, that shows inhibitory activity against enteropathogenic strains of Y. enterocolitica belonging to serogroups O:3, O:5,27 and O:9.
Enterocoliticin was purified, and electron micrographs of enterocoliticin preparations revealed the presence of phage tail-like particles. The particles did not contain nucleic acids and showed contraction upon contact with susceptible bacteria. Enterocoliticin addition to logarithmic-phase cultures of susceptible bacterial strains led to a rapid dose-dependent reduction in CFU.
Calorimetric measurements of the heat output of cultures of sensitive bacteria showed a complete loss of cellular metabolic activity immediately upon addition of enterocoliticin. Furthermore, a dose-dependent efflux of K(+) ions into the medium was determined, indicating that enterocoliticin has channel-forming activity.
VIRULENCE FACTORS 40-50 MDal plasmid encodes most of the other virulence associated phenotypes
Present in almost all the pathogenic Yersinia species
Plasmids are homologous
Invasion of epithelial cells by Yersinia pestis: evidence for a Y. pestis-specific invasin.
Cowan C, Jones HA, Kaya YH, Perry RD, Straley SC.
Department of Microbiology and Immunology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0298, USA
Infect Immun 2000 Aug;68(8):4523-30 Abstract quote
The causative agent of plague, Yersinia pestis, is regarded as being noninvasive for epithelial cells and lacks the major adhesins and invasins of its enteropathogenic relatives Yersinia enterocolitica and Yersinia pseudotuberculosis. However, there are studies indicating that Y. pestis invades and causes systemic infection from ingestive and aerogenic routes of infection.
Accordingly, we developed a gentamicin protection assay and reexamined invasiveness of Y. pestis for HeLa cells. By optimizing this assay, we discovered that Y. pestis is highly invasive. Several factors, including the presence of fetal bovine serum, the configuration of the tissue culture plate, the temperature at which the bacteria are grown, and the presence of the plasminogen activator protease Pla-encoding plasmid pPCP1, were found to influence invasiveness strongly. Suboptimal combinations of these factors may have contributed to negative findings by previous studies attempting to demonstrate invasion by Y. pestis. Invasion of HeLa cells was strongly inhibited by cytochalasin D and modestly inhibited by colchicine, indicating strong and modest respective requirements for microfilaments and microtubules. We found no significant effect of the iron status of yersiniae or of the pigmentation locus on invasion and likewise no significant effect of the Yops regulon. However, an unidentified thermally induced property (possibly the Y. pestis-specific capsular protein Caf1) did inhibit invasiveness significantly, and the plasmid pPCP1, unique to Y. pestis, was essential for highly efficient invasion. pPCP1 encodes an invasion-promoting factor and not just an adhesin, because Y. pestis lacking this plasmid still adhered to HeLa cells.
These studies have enlarged our picture of Y. pestis biology and revealed the importance of properties that are unique to Y. pestis.
VIRULENCE GENES Application of high-density array-based signature-tagged mutagenesis to discover novel Yersinia virulence-associated genes.
Karlyshev AV, Oyston PC, Williams K, Clark GC, Titball RW, Winzeler EA, Wren BW.
Department of Infectious Diseases, London School of Hygiene and Tropical Medicine, University of London, London WC1E 7HT, United Kingdom
Infect Immun 2001 Dec;69(12):7810-9 Abstract quote
Yersinia pestis, the causative agent of plague, and the enteropathogen Yersinia pseudotuberculosis have nearly identical nucleotide similarity yet cause markedly different diseases.
To investigate this conundrum and to study Yersinia pathogenicity, we developed a high-density oligonucleotide array-based modification of signature-tagged mutagenesis (STM). Y. pseudotuberculosis YPIII mutants constructed with the tagged transposons were evaluated in the murine yersiniosis infection model. The DNA tags were amplified using biotinylated primers and hybridized to high-density oligonucleotide arrays containing DNA complementary to the tags. Comparison of the hybridization signals from input pools and output pools identified a mutant whose relative abundance was significantly reduced in the output pool. Sequence data from 31 transposon insertion regions was compared to the complete Y. pestis CO92 genome sequence. The 26 genes present in both species were found to be almost identical, but five Y. pseudotuberculosis genes identified through STM did not have counterparts in the Y. pestis genome and may contribute to the different tropisms in these closely related pathogens. Potential virulence genes identified include those involved in lipopolysaccharide biosynthesis, adhesion, phospholipase activity, iron assimilation, and gene regulation. The phospholipase A (PldA) mutant exhibited reduced phospholipase activity compared to the wild-type strain and in vivo attenuation of the mutant was confirmed.
The combination of optimized double tag sequences and high-density array hybridization technology offers improved performance, efficiency, and reliability over classical STM and permits quantitative analysis of data.
LABORATORY/
RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC LABORATORY MARKERS CULTURE A rapid and sensitive method for the detection of Yersinia enterocolitica strains from clinical samples.
Hussein HM, Fenwick SG, Lumsden JS.
Institute of Veterinary, Animal and Biomedical Sciences, College of Science, Massey University, Palmerston North, New Zealand.
Lett Appl Microbiol 2001 Dec;33(6):445-9 Abstract quote
AIMS: To compare three culture methods to detect Yersinia enterocolitica from oral or rectal swabs from experimentally infected pigs.
METHODS AND RESULTS: The three methods used were: direct plating on Cefsulodin-Irgasan-Novobiocin (CIN) agar, cold enrichment in phosphate buffered saline (PBS) followed by plating on CIN agar and selective enrichment with Luria-Bertani-Bile Salts Irgasan (LB-BSI) followed by plating on CIN agar. Selective enrichment with LB-BSI produced the highest recovery rate (63%), when compared with cold enrichment (52%) and plating on CIN agar alone (43%). Selective enrichment with LB-BSI was significantly (P < 0.02) more sensitive than direct plating on CIN agar and more sensitive than cold enrichment (P < 0.1).
CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: Selective enrichment with LB-BSI was more sensitive than the widely accepted method of cold enrichment and it reduced the time required for detection of Y. enterocolitica by three weeks. Selective enrichment with LB-BSI was also compatible with a multiplex PCR technique.
IMMUNOASSAY Identification of Yersinia-infected blood donors by anti-Yop IgA immunoassay.
Kendrick CJ, Baker B, Morris AJ, O'Toole PW.
Institute of Veterinary, Massey University, Palmerston North, New Zealand.
Transfusion 2001 Nov;41(11):1365-72 Abstract quote
BACKGROUND: From 1991 through 1996, nine transfusion-related cases of septicemia and endotoxemia occurred in New Zealand, a rate approximately 80 times that in the United States. Eight cases involved the transfusion of Yersinia enterocolitica-infected blood and one involved Serratia liquefaciens-infected blood. Six of the recipients died. Donor exclusion by recent gastrointestinal illness failed to prevent the four most recent such infections, and it has led to an estimated 3- to 5-percent rate of donor deferral.
STUDY DESIGN AND METHODS: An antigen preparation containing the released proteins (Yops) of Y. enterocolitica was used to establish an EIA to detect IgA directed against these proteins in donated blood. The assay was tested with serum from donors in transfusion-related endotoxemia cases, subjects who were stool culture-positive for Y. enterocolitica, and 495 healthy volunteer blood donors.
RESULTS: The assay detected anti-Yop IgA in the donors of all 6 infected units tested. Ninety-six percent of culture-positive subjects tested positive, whereas there was 70-percent positivity with a commercial immunoassay based on lipopolysaccharide. Five percent of random donors tested positive; only one of these had Y. enterocolitica present in a stool sample, and none were bacteremic.
CONCLUSION: The anti-Yop immunoassay used in this study could be applied to reduce the risk of posttransfusion endotoxic shock caused by Y. enterocolitica.
PCR Detection of Pathogenic Yersinia enterocolitica by a Rapid and Sensitive Duplex PCR Assay.
Wannet WJ, Reessink M, Brunings HA, Maas HM.
J Clin Microbiol 2001 Dec;39(12):4483-6 Abstract quote
A duplex PCR assay targeting the ail and 16S rRNA genes of Yersinia enterocolitica was developed to specifically identify pathogenic Y. enterocolitica from pure culture. Validation of the assay was performed with 215 clinical Yersinia strains and 40 strains of other bacterial species.
Within an assay time of 4 h, this assay offers a very specific, reliable, and inexpensive alternative to the conventional phenotypic assays used in clinical laboratories to identify pathogenic Y. enterocolitica.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL ARTHRITIS Y. enterocolitica
Y. pseudotuberculosisGASTROENTERITIS Y. enterocolitica
Y. pseudotuberculosisLIMB ISCHEMIA
- Persistent Yersinia pestis antigens in ischemic tissues of a patient with septicemic plague.
Guarner J, Shieh WJ, Chu M, Perlman DC, Kool J, Gage KL, Ettestad P, Zaki SR.
Infectious Diseases Pathology Activity, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Hum Pathol. 2005 Jul;36(7):850-3. Abstract quote
In November 2002, a couple from New Mexico traveled to New York where both had fever and unilateral inguinal adenopathy. The husband was in septic shock when he sought medical care and was admitted to an intensive care unit, where he developed ischemic necrosis of his feet which later required bilateral amputation. Yersinia pestis was grown from his blood.
Immunohistochemical assays using anti-Y pestis antibodies demonstrated multiple bacteria and granular antigens in and around vessels of the ischemic amputation tissues obtained 20 days after initiation of antibiotics; however, no evidence of Y pestis was present in viable tissues.
Immunohistochemical evidence of Y pestis inside vessels of gangrenous feet in this patient underscores the importance of adequate excision of necrotic or partially necrotic tissues because antibiotics cannot be effectively delivered to necrotic and poorly perfused tissues.LYMPHADENITIS PLAGUE Y. pestis
SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE Immunohistochemical Detection of Yersinia pestis in Formalin-Fixed, Paraffin-Embedded Tissue
Jeannette Guarner, MD
Wun-Ju Shieh, MD, PhD
Patricia W. Greer, MT
Jean-Marc Gabastou, PhD
May Chu, PhD
Edward Hayes, MD
Kurt B. Nolte, MD
and Sherif R. Zaki, MD, PhDAm J Clin Pathol 2002;117:205-209 Abstract quote
Yersinia pestis infection usually is limited to lymph nodes (bubo); rarely, if bacteria are aerosolized, pneumonic plague occurs.
We developed an immunohistochemical assay using a monoclonal anti–fraction 1 Y pestis antibody for formalin-fixed tissues. We studied 6 cases using this technique. Respiratory symptoms were prominent in 2 cases; histologically, one showed intra-alveolar inflammation, and the other had alveolar hemorrhage and edema.
By using the immunohistochemical assay, we found intact Yersinia and granular bacterial antigen staining in alveoli, bronchi, and blood vessels. Of the remaining cases, 2 had septicemia and 2 had a bubo. Pathologic changes included lymphocyte depletion, necrosis, edema, and foamy macrophages in lymph nodes; multiple abscesses in the spleen; fibrin thrombi in glomeruli; and unremarkable lungs. By using the immunohistochemical assay, we identified intact bacteria inside monocytes and granular antigen staining in blood vessels. The immunohistochemical assay provided a fast, nonhazardous method for diagnosing plague.
The immunohistochemical assay localizes bacteria, retaining tissue morphologic features, and can help define transmission mechanisms.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES ACUTE APPENDICITIS CROHN'S DISEASE Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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Last Updated August 19, 2005
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