The relationship of Campylobacter jejuni infection and the development of Guillain-Barré syndrome

Campylobacter jejuni is recognized as the most common infectious agent associated with the development of Guillain-Barré syndrome. Available information on the complete genome sequence of C. jejuni NCTC 11168 has helped researchers to identify polysaccharide capsules as well as genetic mechanisms in the synthesis of ganglioside-like cell surface molecules in this bacteria. Toxins may contribute to the host's inflammatory response seen in Guillain-Barré syndrome.     

Campylobacter enteritis and the Guillain-Barré syndrome

Campylobacter jejuni is one of the most common causes of bacterial gastroenteritis in the United States and worldwide with approximately 2.4 million infections per year in the United States. A now clearly recognized sequelae following Campylobacter infection is the Guillain-Barré syndrome, an acute immune-mediated attack on the peripheral nervous system. How Campylobacter induces Guillain-Barré syndrome is the subject of intense investigation, and this article discusses some of the recent advances in our understanding of the clinical, epidemiologic, and pathogenic features of the disease.     

Oral Campylobacter species: Initiators of a subgroup of inflammatory bowel disease?

In recent years, a number of studies detected a significantly higher prevalence of Campylobacter species such as Campylobacter concisus (C. concisus) in intestinal biopsies and fecal samples collected from patients with inflammatory bowel disease (IBD) compared to controls. Most of these Campylobacter species are not of zoonotic origin but are human oral Campylobacter species. Bacterial species usually cause diseases in the location where they colonize. However, C. concisus and other oral Campylobacter species are associated with IBD occurring at the lower parts of the gastrointestinal tract, suggesting that these Campylobacter species may have unique virulence factors that are expressed in the lower parts of the gastrointestinal tract.     

Is there a risk of cancer development after Campylobacter infection?

Abstract

Objective. All Campylobacter jejuni species produce a genotoxin, which induce DNA double strand breaks, could lead to an increased risk of cancer especially in the gastro-intestinal tract. Material and methods. All individuals in Stockholm County who tested positive with C. jejuni between 1989 and 2006 were included. The cohort was followed-up until December 31, 2007 for the occurrence of cancer, overall and site specific. Standard incidence ratios (SIR) with 95% confidence intervals (CI) were calculated by comparisons with the background population. Results. There were 16,276 individuals who tested positive for C. jejuni generating 124,387 person years. Excluding the first year of follow-up the overall risk for cancer did neither differ from that expected SIR = 0.95 (95% CI 0.82–1.09) nor after10 years or more of follow-up; SIR = 0.91 (95% CI 0.71–1.16). There was no increased risk for cancer in the gastro-intestinal tract, but there were significantly increased risks for melanomas SIR = 1.84 (95% CI 1.27–2.57) and squamous cell skin cancer SIR = 1.52 (95% CI 1.01–2.19) while a significantly decreased risk of respiratory cancers among males SIR = 0.32 (95% CI 0.12–0.70) was observed. Conclusions. Our results indicate no excess risks of malignancies following an infection by C. jejuni at least during the first decade. Furthermore, the finding of a decreased risk of respiratory cancers could be of interest, if the results are reproduced in future studies in other populations.     

Campylobacter concisus: an emerging pathogen?

Only about half the cases of intestinal infectious disease have a routinely detectable causative agent diagnosed. Increasingly, evidence indicates that Campylobacter species other than C. jejuni and C. coli are associated with such cases. However, evidence is less clear, from epidemiological studies, for the pathogenic nature of these unusual campylobacters. This is particularly true for organisms like C. concisus and is compounded by poor methods for routine recovery and identification. Moreover, the application of typing methods for C. concisus has indicated a heterogeneous population and there is preliminary evidence to suggest differences in the pathogenic potential of strain types. However, considerable further work is needed with more discriminatory genotyping methods, before accurate assessment of the risk of C. concisus infection to human health can be determined.     

Can Campylobacter jejuni play a role in development of celiac disease？ A hypothesis

Celiac disease (CD) is an entropathy with malabsortive condition in which an allergic reaction to the cereal grain-protein (gluten) causes small intestine mucosal injury. CD is a multifactorial disorder in which both genetic and environmental factors contribute to the disease development. Mechanisms have been described to explain the pathology of CD. T cells specific for multiple gluten peptides are found in virtually all patients. Generation of such a broad T cell response may be a prerequisite for disease development. CD is associated with multiple extraintestinal presentations, including neurological deficits. Recent studies have shown a significant correlation between anti-ganglioside antibodies and neurological disorders in patients with underlying CD. Gangliosides are glycosphingolipids which are abundant in nervous system and in other tissues including gastrointestinal tract. It is not known what triggers the release of anti-ganglioside antibodies in people with gluten sensitivity. But, the mechanism is likely to involve the intestinal immune system response to ingested gliadin, a component of wheat gluten. Studies showed that mechanisms different from gluten exposure may be implicated in antibody formation, and other environmental factors may also exist. In addition, considering the fact that genetic predisposition dysregulating mucosal immune responses in the presence of certain environmental triggers like gastrointestinal infections may be strong etiological factors for developing chronic intestinal inflammation including CD, the hypothesis raised in our mind that antiganglioside antibody formation in CD may play a role not only in development of neurological complications in celiac patients, but also in development of CD itself. As presence of Campylobacter jejuni in other diseases with antigangliosides antibody formation has been established, we propose the possible role of Campylobacter jejuni in development of CD in association with other genetic and environmental factors by the mechanism that molecular mimicry of gangliosides-like epitopes common to both lipo-polysacharide coats of certain strains of Campylobacter jejuni and gangliosides in cell structure of gastrointestinal mucosa may cause an autoimmune response and consequently lead to atrophy and degeneration of mucosa possibly by apoptosis.     

Surveillance of human Campylobacter infections in France--part 1--which data? A study of microbiological laboratories, 2000

The frequency of Campylobacter infections in humans, their potential severity, and the existence of preventive measures justify the implementation of a surveillance system for these infections. Before the implementation of the surveillance system, a survey of the Campylobacter diagnostic practices in the laboratories was performed. In the laboratories that responded, most investigated for Campylobacter at least once in 1999. Identification of the Campylobacter species was carried out by 86% of hospital laboratories and 37% of private laboratories. Antibiotic sensitivity tests were carried out by 75% and 32% of them respectively. Many laboratories test for Campylobacter in stool samples using comparable methods showing the feasibility of a surveillance system.     

When does the good of the group override the advantage of the individual?

In a system of N populations of n reproductive individuals apiece, in which each population has constant variance v² and lasts L generations, group selection on a quantitative character has a reasonable chance of overriding selection within populations if (and only if) the populations never exchange migrants, each population is founded by colonists from a single parent population, and the number of populations exceeds the effective number of reproductive individuals per population. If each population derives from a single parent population, then the exchange of a single successful migrant per population per L generations can triple the strength of group selection required to overcome a given selection within populations. If populations exchange no migrants, then the derivation of one in every N populations from two equally represented parents (while the others all derive from a single parent) doubles the strength of group selection required to prevail. Group selection is accordingly likely to be effective only in certain categories of parasites.     

Stochastic simulations of the exponential-beta function as an assessment of the validity of the choice of the Wagner-Nelson method for the analysis of ¹³C-octanoic acid breath tests

A compartmental model that generates the exponential-beta function μkβ(1 - e(-kt))(β - 1)?e(-kt) in order to run stochastic simulations has been constructed. The mathematical considerations that lead to the development of the model and the comparison of its performance with real data sets obtained from the studies of gastric emptying in healthy volunteers using 13C-octanoic acid breath tests are demonstrated. Stochastic simulations have been used to introduce randomness. These confirmed the choice of an exponential-beta function to model the physiological system, as agreement was obtained between experimental and theoretical data. The comparisons were made by visual inspection only, as the intention was to demonstrate that the stochastic exponential-β model would generate the full range of observed curve shapes.     

Anterior fissure of the right liver — the third door of the liver

Background/Purpose

Although the anterior segment of the liver has been divided into segments 8 and 5, we have, during surgical or interventional procedures, occasionally encountered patients in whom the right anterior portal vein does not bifurcate into the superior and inferior branches. Thus, the in vivo anatomy of the right liver was reevaluated to clarify the segmental anatomy.

Methods

We evaluated the hepatic venous and portal ramification patterns, using three-dimensional images reconstructed from computed tomography. In addition, liver volumetry was performed.

Results

All branches arising from the anterior trunk were divided into two groups: the right ventral portal branches (RVP) and the right dorsal portal branches (RDP), and the anterior fissure vein crossed between the RVP and RDP. The ventral and dorsal regions of the anterior segment were approximately equal from a volumetric point of view.

Conclusions

The anterior segment seems to be divided into the ventral and dorsal segments by the anterior fissure, and we propose a reclassification of the right liver that divides the right liver into three segments. Dissection of the parenchyma along the anterior fissure makes the third door of the liver open, resulting in the exposing of all Glissonian pedicles of the right liver. The introduction of our segmental anatomy and surgical procedure will allow more systematic and limited liver resections.     

Molecular population genetic analysis of Campylobacter jejuni HS:19 associated with Guillain-Barré syndrome and gastroenteritis

Infection with Campylobacter jejuni serotype HS:19 is associated with the development of Guillain-Barré syndrome (GBS). To determine whether a particular HS:19 clone is associated with GBS, multilocus enzyme electrophoresis (MLEE) was used to analyze a worldwide collection of isolates. There were 34 electropherotypes (ETs) in 3 phylogenetic clusters among 83 C. jejuni isolates. Cluster I contained all HS:19 strains, and a single ET (ET4) accounted for most HS:19 strains. HS:19 strains did not occur in any of the other clusters. ET4 contained isolates from different geographic locations, indicating global spread of this clone. Furthermore, ET4 contained isolates from patients with uncomplicated enteritis and GBS, as well as isolates from animal sources. The results of this study show that HS:19 strains comprise a clonal, although not monomorphic, population, which is distinct from non-HS:19 strains within C. jejuni. A unique clone associated with GBS was not identified by use of MLEE.     

Absence of clonality of Campylobacter jejuni in serotypes other than HS:19 associated with Guillain-Barré syndrome and gastroenteritis

Guillain-Barré syndrome (GBS) is recognized as a complication that occurs after Campylobacter infection. Certain Penner serotypes, such as HS:19, are linked particularly to GBS in some parts of the world, and there is good evidence for restricted genetic diversity in these isolates. However, GBS also occurs after Campylobacter infection due to other serotypes. Therefore, we asked whether Campylobacter jejuni non-HS:19 serotypes associated with GBS have a clonal structure and differ from strains isolated from patients with Campylobacter gastroenteritis. A worldwide selected population of C. jejuni non-HS:19 strains associated with GBS and gastroenteritis was analyzed by use of multilocus enzyme electrophoresis, automated ribotyping, pulsed-field gel electrophoresis, and flagellin gene typing. The results show that these isolates represent a heterogenic population and do not constitute a unique population across serotypes. No epidemiologic marker for GBS-associated strains was identified.     

Campylobacter pylori in alcoholic hemorrhagic “gastritis”

Previously we have shown that alcohol- associated subepithelial hemorrhages histologically represent localized superficial mucosal hemorrhage, with edema in the surrounding mucosa. We studied the relationship between Campylobacter pylori (CP)and histology in gastric subepithelial hemorrhages from 20 actively drinking alcoholic patients. Biopsies of the hemorrhagic lesions and adjacent mucosa 1 and 3 cm away were taken with a jumbo forceps. Biopsy slides were coded and randomized before histologic scoring and examination for CP. CP was present in 15/20 (75%)biopsies of subepithelial hemorrhages and in 32/40 (80%)biopsies from surrounding mucosa. The mean hemorrhage score was not significantly different in biopsies of subepithelial hemorrhages with and without CP (2.7±0.4 vs 3.2±0.4)and the edema scores in adjacent, nonhemorrhagic mucosa were similar in specimens with and without CP (2.0±0.3 vs 1.6±0.5).The inflammatory cell density was significantly greater in CP-positive biopsies than in CP-negative specimens (2.0±0.2 vs 0.5±0.2, P<0.05)with the mononuclear cell and neutrophil scores contributing equally to the overall inflammatory cell score. Almost a quarter of CP-positive specimens (11/47)had no inflammation. The mean score for lining epithelial abnormalities was also significantly higher in biopsy specimens positive for CP (1.7±0.2 vs 0.5±0.3, P<0.05).In conclusion, CP is present in 75% of alcohol- associated subepithelial hemorrhages, but its prevalence is similar in adjacent, nonhemorrhagic mucosa. No relationship exists between the presence of CP and the characteristic histologic abnormalities of these subepithelial hemorrhages.Supported in part by DK grant AM 17328 from the National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases.