Acute kidney injury associated with Yersinia pseudotuberculosis infection: Forgotten but not gone

BACKGROUND: Yersinia pseudotuberculosis is known to cause fever, gastroenteritis, or acute kidney injury (AKI). There have been several Y. pseudotuberculosis infection outbreaks to date associated with ingestion of contaminated food or unsterile water. While this disease was considered to have practically been eradicated with the improvement in public health, we encountered several cases of AKI associated with Yersinia infection. METHODS: We retrospectively collected data from medical records of patients with suspected Y. pseudotuberculosis infection who visited Seoul National University Children’s Hospital in 2017. RESULTS: There were nine suspected cases of Yersinia infection (six males and three females; age range 2.99–12.18 years). Among them, five cases occurred in May, and seven patients were residing in the metropolitan Seoul area. Three patients had history of drinking mountain water. Every patient first presented with fever for a median of 13 days, followed by gastrointestinal symptoms and oliguria. Imaging studies revealed mesenteric lymphadenitis, terminal ileum wall thickening, and increased renal parenchymal echogenicity. Creatinine levels increased to 5.72 ± 2.18 mg/dL. Urinalysis revealed sterile pyuria, proteinuria, and glycosuria. Oliguria continued for 4 to 17 days, and two patients required dialysis; however, all of them recovered from AKI. Mucocutaneous manifestations developed later. In the diagnostic work-up, Yersinia was isolated from the stool culture in one patient. Anti-Yersinia immunoglobulin (Ig) A and IgG were positive in 6 patients. CONCLUSION: Y. pseudotuberculosis infection is an infrequent cause of interstitial nephritis presenting with AKI. When a patient presents with fever, gastroenteritis, and AKI not resolving despite hydration, the clinician should suspect Y. pseudotuberculosis infection.

Experimental infection with Yersinia pseudotuberculosis in European brown hare (Lepus europaeus, Pallas)

OBJECTIVE@#To investigate clinicopathological, bacteriological and pathological aspects of an experimental infection with Yersinia pseudotuberculosis (Y. pseudotuberculosis) in hares to verify the efficacy of serology for the in vivo diagnosis. Moreover, the pathogenicity of two Y. pseudotuberculosis strains was investigated in order to detect potential differences.@*METHODS@#Twelve European brown hares (Lepus europaeus, Pallas) were experimentally infected per os and via conjunctival mucosae with Y. pseudotuberculosis: six subjects were infected with a strain isolated from a naturally infected hare (YpH) and six subjects with a strain isolated from a naturally infected rabbit (YpR). Two hares were used as negative controls. All animals were subjected to clinical, bacteriological and serological examinations during 9 weeks following the infection and, at the end of the control period, subjects still alive were euthanized and submitted to a complete post mortem examination.@*RESULTS@#All faecal samples collected during the control period were positive for bacteriological examinations and to a PCR for the inv gene of Y. pseudotuberculosis, while only one YpH-infected hare showed a positive haemocultures. From the 2nd to the 9th week post infection (pi), serological analysis revealed specific antibodies with titers ranging from 1:10 to 1:160 in all YpH-infected and two YpR-infected subjects. All the YpH-infected and two YpR-infected hares scored positive for Y. pseudotuberculosis by means of bacteriological investigations. Grossly, suppurative multifocal lesions were detected in liver, spleen, kidney and sub-mandibular lymph nodes in both YpH- and YpR-infected hares and confirmed with histopathology. Pulmonary lesions were observed only in YpH-infected subjects. Immunohistochemistry confirmed the presence of bacterial antigen in all infected animals.@*CONCLUSION@#Results of this study revealed that YpH strain is more pathogenic for hares than the YpR strain; moreover the serological test performed in this study could be used for the diagnosis of pseudotuberculosis in hares, whereas post mortem diagnosis should be confirmed by means of bacteriological examination, PCR, histopathology and immunohistochemistry.

Experimental infection with Yersinia pseudotuberculosis in European brown hare (Lepus europaeus, Pallas)

Objective To investigate clinicopathological, bacteriological and pathological aspects of an experimental infection with Yersinia pseudotuberculosis (Y. pseudotuberculosis) in hares to verify the efficacy of serology for the in vivo diagnosis. Moreover, the pathogenicity of two Y. pseudotuberculosis strains was investigated in order to detect potential differences. Methods Twelve European brown hares (Lepus europaeus, Pallas) were experimentally infected per os and via conjunctival mucosae with Y. pseudotuberculosis: six subjects were infected with a strain isolated from a naturally infected hare (YpH) and six subjects with a strain isolated from a naturally infected rabbit (YpR). Two hares were used as negative controls. All animals were subjected to clinical, bacteriological and serological examinations during 9 weeks following the infection and, at the end of the control period, subjects still alive were euthanized and submitted to a complete post mortem examination. Results All faecal samples collected during the control period were positive for bacteriological examinations and to a PCR for the inv gene of Y. pseudotuberculosis, while only one YpH-infected hare showed a positive haemocultures. From the 2nd to the 9th week post infection (pi), serological analysis revealed specific antibodies with titers ranging from 1:10 to 1:160 in all YpH-infected and two YpR-infected subjects. All the YpH-infected and two YpR-infected hares scored positive for Y. pseudotuberculosis by means of bacteriological investigations. Grossly, suppurative multifocal lesions were detected in liver, spleen, kidney and sub-mandibular lymph nodes in both YpH- and YpR-infected hares and confirmed with histopathology. Pulmonary lesions were observed only in YpH-infected subjects. Immunohistochemistry confirmed the presence of bacterial antigen in all infected animals. Conclusion Results of this study revealed that YpH strain is more pathogenic for hares than the YpR strain; moreover the serological test performed in this study could be used for the diagnosis of pseudotuberculosis in hares, whereas post mortem diagnosis should be confirmed by means of bacteriological examination, PCR, histopathology and immunohistochemistry.

Ribotyping and virulence markers of Yersinia pseudotuberculosis strains isolated from animals in Brazil

Ribotyping and virulence markers has been used to investigate 68 Yersinia pseudotuberculosis strains of serogroups O:1a and O:3. The strains were isolated from clinical material obtained from healthy and sick animals in the Southern region of Brazil. Ribotypes were identified by double digestion of extracted DNA with the restriction endonucleases SmaI and PstI, separation by electrophoresis and hybridization with a digoxigenin-labeled cDNA probe. The presence of the chromosomal virulence marker genes inv, irp1, irp2, psn, ybtE, ybtP-ybtQ, and ybtX-ybtS, of the IS100 insertion sequence, and of the plasmid gene lcrF was detected by polymerase chain reaction. The strains were grouped into four distinct ribotypes, all of them comprising several strains. Ribotypes 1 and 4 presented distinct profiles, with 57.3 percent genetic similarity, ribotypes 2 and 3 presented 52.5 percent genetic similarity, and genetic similarity was 45 percent between these two groups (1/4 and 2/3). All strains possessed the inv, irp1, and irp2 genes. Additionally, strains of serogroup O:1a carried psn, ybtE, ybtP-ybtQ, ybtX-ybtS, and IS100. As expected lcrF was only detected in strains harboring the virulence plasmid. These data demonstrate the presence of Y. pseudotuberculosis strains harboring genotypic virulence markers in the livestock from Southern Brazil and that the dissemination of these bacteria may occur between herds.

Comparative study for Isolation of Yersinia pseudotuberculosis from Water / 대한임상미생물학회지

BACKGROUND: Yersinia pseudotuberculosis is recognized throughout the world as a cause of water-or food born infections in human and animals. Although many attempts have been made to define optimal conditions for the isolation of the organism from water, their isolation yields remain low; therefore, we tried to find an effective method for the recovery of Y. pseudotuberculosis from water. METHODS: Water samples were deliberately contaminated with Y. pseudotuberculosis at various levels and then processed by the following three isolation METHODS: centrifugation, direct filtration, and intracellular culture. For the centrifugation method, the water samples were centrifuged at 5000 rpm for 1 hr and the final precipitates were inoculated in cefsulodin-irgasan-novobiocin(CIN) media. For the filtration method, the water samples were filtered by negative pressure and the filter papers were put directly on CIN media. For the intracellular culture method, the organisms were extracted from the HeLa cells that had been infected with Y. pseudotuberculosis and inoculated on CIN media. We also examined the efficacy of the filtration method after cold enrichment with a mixture of Y. pseudotuberculosis, Escherichia coli, and Citrobacter freundii. RESULTS: With the concentration of 3x10(2)/100 mL, Y. pseudotuberculosis was isolated only by the filtration method; however, none of the culture methods were good enough to recover the organism from the water sample when the concentration was 3x10/100 mL. With cold enrichment, however, the recovery was much more efficient; the organism grew after direct inoculation or after filter inoculation when the starting concentrations were 3x10(2)/100 mL or 3x10/100 mL, respectively. CONCLUSION: A combined use of direct filtration and filter inoculation after cold enrichment is the most effective method to yield Y. pseudotuberculosis isolation. The introduction of effective methods for the isolation of Y. pseudotuberculosis from untreated drinking water would increase the awareness by the public of the health hazard of spring water.

Molecular Relatedness between Isolates Yersinia pseudotuberculosis from a Patient and an Isolate from Mountain Spring Water

A 40-yr-old buddhist monk was admitted to the hospital with abdominal pain, fever, and confusion. He had a history of drinking untreated mountain spring water in his temple, and experienced the above symptoms for several days before admission. In past medical history, he had suffered from hepatic cirrhosis. Yersinia pseudotuberculosis was isolated from his blood and ascitic fluid. The mountain spring water that he had ingested was cultivated and Y. pseudotuberculosis was also isolated. For identification of pathogenic Y. pseudotuberculosis, each isolate from the three sources (blood, ascitic fluid, and drinking water) was also analysed for the inv gene for Y. pseudotuberculosis and the virF gene for virulent plasmid by PCR. All strains were positive for both the virF and the inv genes and also positive for autoagglutination test. For relationship study, each isolate from the three sources was also analysed with serotyping and restriction endonuclease analysis of virulence plasmid DNA (REAP) using BamHI. All belonged to the serotype 4b and REAP pattern D. Thus, all these findings supported that the mountain spring water was the source of the Y. pseudotuberculosis infection in this case.

Comparison of serotypes, restriction enzyme analysis of plasmid DNA pattern and PFGE(pulsed-field gel electrophoresis) patterns of Yersinia pseudotuberculosis isolates in Korea / 대한임상병리학회지

BACKGROUND: Yersinia pseudotuberculosis, a member of genus Enterobactericeae, is a main etiologic organism of diarrhea in childhood. Because a mouse and a unchlorinated spring water are main reservoirs of Y. pseudotuberculosis, the strains from a contaminated spring water and mouse could be involved in human epidemic. The purpose of this study was to investigate a clonality between the strains from patients and those from an unchlorinated spring water and a mouse by restriction enzyme analysis of plasmid DNA and pulsed-field gel electrophoresis (PFGE). METHOD: We isolated 15 Y. pseudotuberculosis strains including 8 isolates from patients (S1-S8), 6 isolates from mountain water (W1-W6), 1 isolate from a mouse (M1) in northeast area of Seoul. Plasmid and chromosomal DNA of all strains were analyzed by REAP with Bam H1 restriction and by PFGE with Xba I restriction , respectively. RESULTS: Restriction enzyme analysis of plasmid DNA was classified into type B and type D. All 7 strains of serotype 15 were classified as type B and 8 strains of serotype 4b were classified as type D. PFGE were classified into 6 different types. Among them, strains of PFGE type I, II, III, IV belong to Y. pseudotuberculosis serotype 15 and Y. pseudotuberculosis 4b strains were classified into PFGE type V, VI. S1 and W1 were classified into PFGE type I . S8, W6 and M1 were classfied into PFGE type VI. CONCLUSIONS: PFGE revealed clonality among strains from patients, a water and a mouse. PFGE was more discriminative than REAP to characterize the Y. pseudotuberculosis outbreaks in Korea.

A Case of yersinia pseudotuberculosis sepsis presenting as multiple liver abscesser in systemic lupus erythematosus / 대한내과학회지

A 40-year-old man with systemic lupus erythematosus (SLE) and diabetes was found to have sepsis with multiple small hepatic abscesses secondary to Yersinia pseudotuberculosis which were detected by computed tomography (CT) scan and blood cultures. Sepsis with Y. pseudotuberculosis is uncommon but usually seen in patients with underlying liver diseases or diabetes. A few of those patients are accompanied by liver abscesses. Those patients with liver abscesses invariably have multiple small abscesses. CT scan of the liver was important in demonstrating the multiple small liver abscesses. Identification of the pathogen on blaod culture and elevated serum antibody titer to Y. pseudotu-berculosis are useful for diagnosis. Although rare, Y. pseudotuberculosis should be also considered as a possible cause in febrile patient with immunocompromised state such as SLE, diabetes or hemochromatosis.

Diagnosis of Yersinia pseudotuberculosis Infection by Enzyme-Linked Immunosorbent Assay / 대한임상병리학회지

BACKGROUND: Diagnostic rate of Yersinia pseudotuberculosis infection by stool culture is low and slide agglutination (SA) method in serum has diagnostic problem due to high false positive rate and cross reaction with other febrile diseases. Therefore we tried to develop first stage whole cell Enzyme-linked immunosorbent assay (ELISA) test against Y. pseudotuberculosis antigen using Korean strains of Y. pseudotuberculosis. METHODS: Korean strains of Y. pseudotuberculosis (serotype:4b and 15) were cultured and cell wall was destroyed by sonifier and used as antigen. Microplate wells were coated with antigen and sera of three group (patient group, control group and adult group) were added and incubated at 37degreesC. Peroxidase conjugated rabbit antihuman IgG and goat antihuman IgM were added and substrate (3,3',5,5'-tetramethylbenzidine) adding was followed. Optical density was measured by spectrophotometer at 450 nm. RESULTS: Patient group (n=22) who has more than 1:80 titer in SA method showed 27.3% positivity in IgG antibody and 63.6% positivity in IgM antibody in noncompetitive sandwich method of ELISA test. Adult group (n=50) showed 26.0% positivity in IgG antibody. Positivity rate of antibody in ELISA test was not correlated with agglutination titer in SA method but both antibodies were positive in 3 cases which have agglutination titer above 1:1280. CONCLUSIONS: Whole cell ELISA test was tried by Y. pseudotuberculosis antigens using serotypes which were isolated in Korea. Positivity rate of both IgG and IgM antibodies by ELISA test was not correlated with agglutination titer of SA method.

Epidemiological Studies of Yersinia pseudotuberculosis Infection by Plasmid DNA Profile Assay / 감염

BACKGROUND: In order to investigate transmission route of Yersinia pseudotuberculosis infection in Korea, we tried epidemiological study among human strains, mountain spring water strain and wild mouse strain which were isolated in north eastern area of Seoul on spring in 1996. METHODS: Plasmid profile (Restriction Endonuclease Analysis of Virulence Plasmid DNA analysis: REAP) assay in addition to serotyping were performed among human strains, mountain spring water strain and wild mouse strains. RESULTS: All isolates were the same O serotype of 4b and the same REAP pattern of type D. CONCLUSION: These results suggested that wild mice (especially Apodemus agrarius) were one of main reservoir of Y. pseudotuberculosis in Korea and their fecal material might contaminate mountain spring water. Most of human infections of Y. pseudotuberculosis were originated from drinking of contaminated mountain spring waters in Korea.

Acute Renal Failure (ARF) Associated with Yersinia Pseudotuberculosis Infection Diagnosed by Polymerase Chain Reaction

The clinical significance of Yersinia pseudotuberculosis (Y. pseudotuberculosis) has recently recognized in various part of the world because it can cause a wide range of clinical problems such as mesenteric lymphadenitis, septicemia, reactive arthritis, terminal ileitis, erythema nodosum and acute renal failure. we experienced a case of acute renal failure associated with Y. pseudotuberculosis infection. We applied a nested polymerase chain reaction method for rapid diagnosis of Y. pseudotuberculosis infection. DNA was extracted from standard strains of Y. pseudotuberculosis, Y. enterocolitica, serial blood samples, urine, and mountain water by phenol-chloroform method. Using specific primers, we amplified inv and ail gene from extracted DNA samples by PCR method. The patient' serotype was Y. pseudotuberculosis 2a and it's titer was 1:40 initially, after 2 weeks the titer increased to 1:160. Stool culture was negative. Inv gene amplification was positive in patient's urine, febrile stage blood, and mountain water. The nested polymerase chain reaction method can be used clinically for rapid diagnosis of Y. pseudotuberculosis infection. So we report here the clinical findings and PCR method of this case with brief review of the literatures.

Yersinia pseudotuberculosis Infection Confirmed by Stool Culture in Children

PURPOSE: The clinical significance of Y. pseudotuberculosis infection has recently recognizd in various part of the world, because it can cause a wide range of clinical problems such as mesenteric lymphadenitis, septicemia, reactive arthritis, terminal ileitis, erythema nodosum, and a cute renal failure. We have experienced 19 children with Y. pseudotuberculosis infection confirmed by stool culture. Our aim in this study was to evaluate clinical charactieristics, age and sex distribution, and source of infection. METHODS: Stools were inoculated on CIN(Cefsulodin-Irgasan-Novobiosin) agar (Difco, USA) and incubated for 48hr at 22 degrees C for isolation of Y. pseudotuberculosis. API 20E and VITEC were used for identification of the isolates. The antimicrobial sensitivity tests were performed by GN S(gram negative sensitive) card. Clinical characteristics were analyzed retrospectively. RESULTS: Retrospective analysis of 19 children with Y. pseudotuberculosis infection who visited our hospital between Jun.1993 and Dec.1993 was performed. The most prevalent age group was 6 to 8 years(42%) and monthly distribution showed November, December, June, and July in order of frequency, respectively. The common symptoms and signs were fever(100%), abdominal pain(100%), rash(74%), s trawberry tongue(53%), vomiting(53%), diarrhea(37%), and desquamation(32%), respectively. Four cases among 9 cases showed multiple mesenteric lymph node enlargements on the abdominal ultrasonogaphy. Serogroups of the isolates from stool specimens were type 5(15/19, 79%), and type 4(4/19, 21%), respectively. Y. pseudotuberculosis was also isolated from 3 samples of untreated drinking water which was thought to be the source of infection. There were no resistance strains against Amikacin, Carbenidlin, Gentamicin, and Trimethoprim/Sulfamethoxazole in the antibiotic susceptibility tests. CONCLUSIONS: In this study, the antibiotic susceptibility against Y. pseudotuberculosis was excellent, although the clinical characteristics were various. We have found that untreated drinking water was an important source of this infection. Further epidemiologic study for this infection should be needed.