Assessment of factors influencing the within-batch seroprevalence of human enteropathogenic Yersinia spp. of pigs at slaughter age and the analogy with microbiology.

The microbiologically and serologically-based prevalence of human enteropathogenic Yersinia spp. at moment of slaughter varies between pig farms due to different herd-level factors. A face-to-face questionnaire concerning a broad range of farm aspects (e.g., management and housing system, biosecurity, and hygiene measurements) was performed on one hundred farms. Factors influencing the seropositivity of 7047 pigs against human pathogenic Yersinia spp. were determined and compared to the microbiology. At the slaughterhouse, pieces of diafragm of on average 70 slaughter pigs per batch were sampled to determine the level of antibodies against enteropathogenic Yersinia spp. After univariable mixed-effect logistic regressions, variables that were related to the seropositivity (p<0.05) were included in a multivariable model (p<0.1). The factors remaining significantly associated in the latter model were an increasing number of piglet suppliers (zero up to eleven suppliers) (Odds Ratio=1.4), a high density of pig farms in the area (high versus low density) (Odds Ratio=2.3), the use of semislatted floors in the fattening pig unit (semi slatted floor versus fully slatted floor) (Odds Ratio=3.8) and the possibility of snout contact in the fattening pig unit (snout contact or not) (Odds Ratio=0.1). Decreasing the risk of infection with human enteropathogenic Yersinia spp. at moment of slaughter or during rearing is possible by changing farm management factors.

[Ill after drinking untreated milk; 'die Amelander Krankheit']. / Ziek na drinken rauwe melk; 'die Amelander Krankheit'.

In 2012 three patients consulted their general practitioner with symptoms of gastro-enteritis with bloody stools. This was caused by drinking untreated milk infected with Campylobacter jejuni. Another patient developed reactive arthritis. He too had drunk untreated milk that had probably been infected with Yersinia enterocolitica. Between 1958 and 1995 many German children living in the region of Cologne developed gastro-enteritis after holidaying on Ameland, one of the Dutch islands. This condition was known as 'die Amelander Krankheit', and was caused by drinking untreated milk that had been infected with Campylobacter jejuni. After instructions to boil the milk before drinking were followed, the illness disappeared. These cases show that consumption of untreated milk can have negative consequences for health. Hence, if patients develop gastroenteritis symptoms after visiting a farm we recommend that the possibility that they may have drunk untreated milk is taken into account.

Yersinia enterocolitica outbreak associated with ready-to-eat salad mix, Norway, 2011.

In 2011, an outbreak of illness caused by Yersinia enterocolitica O:9 in Norway was linked to ready-to-eat salad mix, an unusual vehicle for this pathogen. The outbreak illustrates the need to characterize isolates of this organism, and reinforces the need for international traceback mechanisms for fresh produce.

Adhesins of human pathogens from the genus Yersinia.

Bacteria of the Gram-negative genus Yersinia are environmentally ubiquitous. Three species are of medical importance: the intestinal pathogens Y. enterocolitica and Y. pseudotuberculosis, and the plague bacillus Y. pestis. The two former species, spread by contaminated food or water, cause a range of gastrointestinal symptoms and, rarely, sepsis. On occasion, the primary infection is followed by autoimmune sequelae such as reactive arthritis. Plague is a systemic disease with high mortality. It is a zoonosis spread by fleas, or more rarely by droplets from individuals suffering from pneumonic plague. Y. pestis is one of the most virulent of bacteria, and recent findings of antibiotic-resistant strains together with its potential use as a bioweapon have increased interest in the species. In addition to being significant pathogens in their own right, the yersiniae have been used as model systems for a number of aspects of pathogenicity. This chapter reviews the molecular mechanisms of adhesion in yersiniae. The enteropathogenic species share three adhesins: invasin, YadA and Ail. Invasin is the first adhesin required for enteric infection; it binds to ß(1) integrins on microfold cells in the distal ileum, leading to the ingestion of the bacteria and allows them to cross the intestinal epithelium. YadA is the major adhesin in host tissues. It is a multifunctional protein, conferring adherence to cells and extracellular matrix components, serum and phagocytosis resistance, and the ability to autoagglutinate. Ail has a minor role in adhesion and serum resistance. Y. pestis lacks both invasin and YadA, but expresses several other adhesins. These include the pH 6 antigen and autotransporter adhesins. Also the plasminogen activator of Y. pestis can mediate adherence to host cells. Although the adhesins of the pathogenic yersiniae have been studied extensively, their exact roles in the biology of infection remain elusive.

From bench to bedside: stealth of enteroinvasive pathogens.

Bacterial enteric infections are often associated with diarrhoea or vomiting, which are clinical presentations commonly referred to as gastroenteritis. However, some enteric pathogens, including typhoidal Salmonella serotypes, Brucella species and enteropathogenic Yersinia species are associated with a clinical syndrome that is characterized by abdominal pain and/or fever and is distinct from acute gastroenteritis. Recent insights into molecular mechanisms of the host-pathogen interaction show that these enteric pathogens share important characteristics that explain why the initial host responses associated with these agents more closely resemble host responses to viral or parasitic infections. Host responses contribute to the clinical presentation of disease and improved understanding of these responses in the laboratory is beginning to bridge the gap between bench and bedside.

Severe Yersinia enterocolitica sepsis after blood transfusion.

A 23-year-old male received multiple blood transfusions following complicated thoracic surgery. He developed progressive haemorrhagic shock and multiple organ dysfunction syndrome. Blood cultures grew Yersinia enterocolitica. The patient was proven negative for Yersinia enterocolitica; however, one of the donors was found to be positive. Although strict selection of blood transfusion donors is warranted in the Netherlands, contamination of blood components may still occur and therefore should be considered whenever adverse events occur during or after blood transfusion.

Outbreak of Yersinia enterocolitica serogroup O:9 infection and processed pork, Norway.

An outbreak involving 11 persons infected with Yersinia enterocolitica O:9 was investigated in Norway in February 2006. A case-control study and microbiologic investigation indicated a ready-to-eat pork product as the probable source. Appropriate control measures are needed to address consumer risk associated with this product.

[An outbreak of Yersinia enterocolitica O:9-infection]. / Et utbrudd av Yersinia enterocolitica O:9-infeksjon.

BACKGROUND: Yersiniosis is a zoonosis that is transmitted from pigs to humans. In January 2006 more cases of Yersinia enterocolitica enterocolitis than expected were reported in Norway. The fact that the isolates belonged to the O:9 serogroup, which is rare in Norway, and the geographical and temporal clustering of the cases, pointed to an outbreak. We have conducted a retrospective study of 11 patients who were diagnosed during this outbreak. MATERIAL AND METHODS: The material is based upon applicants' information, patient journals and a questionnaire. In order to disclose the source of infection, a case-control survey was performed. RESULTS: Nine of the 11 patients had enterocolitis and two had septicaemia, both of whom died following a few days of treatment. One patient presented with pseudo- appendicitis while another developed monoarthritis, which persisted for more than three months after the debut of symptoms Treatment with antibiotics was offered in six cases. The case-control analysis indicated that brawn was the probable source of infection. INTERPRETATION: This is the first reported Norwegian outbreak of Y. enterocolitica O:9 disease. The incubation time, disease duration and frequency of intestinal and immunological complications corresponds with previously published data. The frequency of septicaemia exceeds several previously reported outbreaks and retrospective studies of sporadic cases.

Yersinia enterocolitica infection does not confer an increased risk of thyroid antibodies: evidence from a Danish twin study.

Understanding of the aetiological basis of thyroid autoimmunity may be gained by studying the early stages of the disease process. We aimed to (1) investigate the relationship between thyroid antibody status and Yersinia enterocolitica (YE) infection in euthyroid subjects and (2) explore the relative importance of genetic and environmental risk factors in the acquisition of YE infection. The association between thyroid antibody status and YE infection was explored using a case-control design. Furthermore, thyroid antibody-positive twins were compared with their thyroid antibody-negative co-twin. In 468 twins, IgA and IgG antibodies to virulence-associated outer-membrane proteins (YOPs) of YE were measured. Of these, 147 were thyroid antibody-positive (cases). A total of 147 age- and gender-matched twins were chosen as controls. The prevalence of YOP antibodies was lower among thyroid antibody-positive individuals than among controls. Yersinia infection was not associated with a positive thyroid antibody status: the odds ratio (with 95% CI) for YOP IgA-ab was 0.66 (0.42-1.05), P = 0.078 and for YOP IgG-ab it was 0.95 (0.60-1.50), P = 0.816. Within discordant twin pairs, the thyroid antibody-positive twin did not have an increased risk of Yersinia infection compared to the thyroid antibody-negative co-twin [odds ratio: YOP IgA-Ab: 0.94 (0.49-1.83), P = 0.866, and YOP IgG-Ab: 1.35 (0.72-2.53), P = 0.345]; 41% (95% CI 10-67% of the liability of being YOP antibody-positive was due to genetic effects. In conclusion, Yersinia infection does not confer an increased risk of thyroid antibodies. The genetic contribution in the acquisition of Yersinia infection is modest.

Application of comparative phylogenomics to study the evolution of Yersinia enterocolitica and to identify genetic differences relating to pathogenicity.

Yersinia enterocolitica, an important cause of human gastroenteritis generally caused by the consumption of livestock, has traditionally been categorized into three groups with respect to pathogenicity, i.e., nonpathogenic (biotype 1A), low pathogenicity (biotypes 2 to 5), and highly pathogenic (biotype 1B). However, genetic differences that explain variation in pathogenesis and whether different biotypes are associated with specific nonhuman hosts are largely unknown. In this study, we applied comparative phylogenomics (whole-genome comparisons of microbes with DNA microarrays combined with Bayesian phylogenies) to investigate a diverse collection of 94 strains of Y. enterocolitica consisting of 35 human, 35 pig, 15 sheep, and 9 cattle isolates from nonpathogenic, low-pathogenicity, and highly pathogenic biotypes. Analysis confirmed three distinct statistically supported clusters composed of a nonpathogenic clade, a low-pathogenicity clade, and a highly pathogenic clade. Genetic differences revealed 125 predicted coding sequences (CDSs) present in all highly pathogenic strains but absent from the other clades. These included several previously uncharacterized CDSs that may encode novel virulence determinants including a hemolysin, a metalloprotease, and a type III secretion effector protein. Additionally, 27 CDSs were identified which were present in all 47 low-pathogenicity strains and Y. enterocolitica 8081 but absent from all nonpathogenic 1A isolates. Analysis of the core gene set for Y. enterocolitica revealed that 20.8% of the genes were shared by all of the strains, confirming this species as highly heterogeneous, adding to the case for the existence of three subspecies of Y. enterocolitica. Further analysis revealed that Y. enterocolitica does not cluster according to source (host).

Characterization of oral Yersinia enterocolitica infection in three different strains of inbred mice.

Several studies have highlighted differences in the resistances of various mouse strains to intravenous (i.v.) infection with Yersinia enterocolitica. In particular, differences in resistance and immunological response between BALB/c and C57BL/6 mouse strains have been determined. Following i.v infection, C57BL/6 mice are more resistant to Y. enterocolitica than are BALB/c mice. However, because Y. enterocolitica is typically a food-borne pathogen, the oral route of infection more accurately reflects the natural route of infection. Therefore, it was of interest to ascertain if the differences in resistance between mouse strains observed for an i.v. infection can be recapitulated following an oral infection. C57BL/6j, BALB/cj, and 129X1/Svj mouse strains presented no differences in 50% lethal dose (LD(50)) following oral infection with Y. enterocolitica. Subsequent analysis of cytokine levels, bacterial colonization and immune cell populations following oral infection confirmed characteristics previously described following i.v. Y. enterocolitica infection. All tissues analyzed from each mouse strain demonstrated a polarized Th1 cytokine profile and inflammatory cell influx throughout a 7-day course of infection. This immune response was present in all tissues and increased as bacterial colonization progressed. The lack of a differing LD(50) phenotype and common trends in immunological response among the three mouse strains tested suggests that oral infection is a useful model for studying the host response to Y. enterocolitica infection.

The structure of Yersinia pestis V-antigen, an essential virulence factor and mediator of immunity against plague.

The LcrV protein (V-antigen) is a multifunctional virulence factor in Yersinia pestis, the causative agent of plague. LcrV regulates the translocation of cytotoxic effector proteins from the bacterium into the cytosol of mammalian cells via a type III secretion system, possesses antihost activities of its own, and is also an active and passive mediator of resistance to disease. Although a crystal structure of this protein has been actively sought for better understanding of its role in pathogenesis, the wild-type LcrV was found to be recalcitrant to crystallization. We employed a surface entropy reduction mutagenesis strategy to obtain crystals of LcrV that diffract to 2.2 A and determined its structure. The refined model reveals a dumbbell-like molecule with a novel fold that includes an unexpected coiled-coil motif, and provides a detailed three-dimensional roadmap for exploring structure-function relationships in this essential virulence determinant.

Yersinia enterocolitica gastroenteritis among infants exposed to chitterlings--Chicago, Illinois, 2002.

During December 2002-January 2003, the Chicago Department of Public Health (CDPH) investigated a cluster of Yersinia enterocolitica infections reported during a 10-week period among nine Chicago infants aged < or =1 year. This report summarizes the investigation of these cases and underscores the continuing risks for enteric infection among infants exposed to chitterlings (i.e., pork intestines), and the need for health-care providers to be aware of Y. enterocolitica as a cause of gastroenteritis, particularly in black children during traditional winter holiday celebrations.

From pig to pacifier: chitterling-associated yersiniosis outbreak among black infants.

In this case-control study of Yersinia enterocolitica infections among black infants, chitterling preparation was significantly associated with illness (p<0.001). Of 13 samples of chitterlings tested, 2 were positive for Yersinia intermedia and 5 for Salmonella. Decontamination of chitterlings before sale with methods such as irradiation should be strongly considered.

The rovA mutant of Yersinia enterocolitica displays differential degrees of virulence depending on the route of infection.

Yersinia enterocolitica is an invasive enteric pathogen that causes significant inflammatory disease. Recently, we identified and characterized a global regulator of virulence (rovA). When mice are infected orally with the rovA mutant they are attenuated by 50% lethal dose (LD(50)) analysis and have altered kinetics of infection. Most significantly, mice orally infected with the rovA mutant have greatly reduced inflammation in the Peyer's patches compared to those infected with wild-type Y. enterocolitica. However, we present data here indicating that when the rovA mutant bacteria are delivered intraperitoneally (i.p.), they are significantly more virulent than when delivered orally. The i.p. LD(50) for the rovA mutant is only 10-fold higher than that of the wild-type Y. enterocolitica, and there are significant inflammatory responses to the rovA mutant that are evident in the liver and spleen. Altogether, these data suggest that the RovA regulon may be required for the early events of the infection that occur in the Peyer's patches. Furthermore, these data suggest that the RovA regulon may be dispensable for Y. enterocolitica systemic disease and inflammatory responses if the Peyer's patches are bypassed.

Multiple hepatic abscesses due to Yersinia enterocolitica infection secondary to primary haemochromatosis.

A case of hepatic abscesses due to Yersinia enterocolitica in an immunocompetent male is presented. Re-examination after 3 months showed that the patient had primary haemochromatosis. Treatment with repeated phlebotomies was instituted. Two years after the patient was first admitted to hospital. 17.2 g iron had been removed and all haematological and biochemical parameters had returned to normal. Genetic analysis of the patients' two sons showed that one was positive for the chromosome defect found in primary haemochromatosis; further investigation is under progress. A study of the literature showed that prior to this case only 45 cases of hepatic abscess secondary to Yersinia enterocolitica have been registered. Of the 45 reported cases, 64% had underlying haemochromatosis and 29% had diabetes mellitus. The overall mortality was 31%. Mortality before 1987 was 60% (n = 20) and since 1987 it has been 8% (n = 25).