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      Guillain-Barré Syndrome and Preceding Infection with Campylobacter, Influenza and Epstein-Barr Virus in the General Practice Research Database

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          Abstract

          Background

          A number of infectious agents have previously been suggested as risk factors for the development of Guillain-Barré syndrome (GBS), but robust epidemiologic evidence for these associations is lacking.

          Methods and Findings

          We conducted a nested case-control study using data from the United Kingdom General Practice Research Database between 1991 and 2001. Controls were matched to cases on general practice clinic, sex, year of birth and date of outcome diagnosis in their matched case. We found positive associations between GBS and infection with Campylobacter, Epstein-Barr virus and influenza-like illness in the previous two months, as well as evidence of a protective effect of influenza vaccination. After correction for under-ascertainment of Campylobacter infection, the excess risk of GBS following Campylobacter enteritis was 60-fold and 20% of GBS cases were attributable to this pathogen.

          Conclusions

          Our findings indicate a far greater excess risk of GBS among Campylobacter enteritis patients than previously reported by retrospective serological studies. In addition, they confirm previously suggested associations between infection due to Epstein-Barr virus infection and influenza-like illness and GBS. Finally, we report evidence of a protective effect of influenza vaccination on GBS risk, which may be mediated through protection against influenza disease, or result from a lower likelihood of vaccination among those with recent infection. Cohort studies of GBS incidence in this population would help to clarify the burden of GBS due to influenza, and any potential protective effect of influenza vaccination.

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          Most cited references35

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          The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study.

          To determine which antecedent infections are specifically associated with the Guillain-Barré syndrome (GBS). Infections with many agents have been reported preceding GBS. Some infections are related to specific clinical and immunologic subgroups in GBS. Most agents were reported in case reports and uncontrolled small series of GBS patients only, and their relation to GBS and its subgroups remains unclear. A serologic study for 16 infectious agents in 154 GBS patients and 154 sex- and age-matched controls with other neurologic diseases. Acute phase, pretreatment samples were used from clinically well-defined GBS patients. The seasonal distribution of serum sampling in the GBS and control group was the same. Multivariate analysis showed that in GBS patients, infections with Campylobacter jejuni (32%), cytomegalovirus (13%), and Epstein-Barr virus (10%) were significantly more frequent than in controls. Mycoplasma pneumoniae infections occurred more often in GBS patients (5%) than in controls in univariate analysis. Infections with Haemophilus influenzae (1%), parainfluenza 1 virus (1%), influenza A virus (1%), influenza B virus (1%), adenovirus (1%), herpes simplex virus (1%), and varicella zoster virus (1%) were also demonstrated in GBS patients, but not more frequently than in controls. C. jejuni infections were associated with antibodies to the gangliosides GM1 and GD1b and with a severe pure motor form of GBS. Cytomegalovirus infections were associated with antibodies to the ganglioside GM2 and with severe motor sensory deficits. Other infections were not related to specific antiganglioside antibodies and neurologic patterns. Recent infections with C. jejuni, cytomegalovirus, Epstein-Barr virus, and M. pneumoniae are specifically related to GBS. The variety of infections may contribute to the clinical and immunologic heterogeneity of GBS.
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            Campylobacter jejuni infection and Guillain-Barré syndrome.

            Although infection with Campylobacter jejuni is recognized as a common antecedent of the Guillain-Barré syndrome, the clinical and epidemiologic features of this association are not well understood. We performed a prospective case-control study in a cohort of patients with Guillain-Barré syndrome (96 patients) or Miller Fisher syndrome (7 patients) who were admitted to hospitals throughout England and Wales between November 1992 and April 1994. Bacteriologic and serologic techniques were used to diagnose preceding C. jejuni infection. There was evidence of recent C. jejuni infection in 26 percent of the patients with Guillain-Barré or Miller Fisher syndrome, as compared with 2 percent of household controls and 1 percent of age-matched hospital controls (P < 0.001). Of the 27 patients with C. jejuni infection, 19 (70 percent) reported having had a diarrheal illness within 12 weeks before the onset of the neurologic illness. No specific serotypes were associated with Guillain-Barré syndrome. C. jejuni infection was slightly more common in men (P = 0.14) and was more likely to be associated with a pure motor syndrome and a slower recovery (P = 0.03). The patients with preceding C. jejuni infection were more likely to have acute axonal neuropathy or axonal degeneration in association with acute inflammatory demyelinating polyradiculoneuropathy, and they had greater disability after one year (P = 0.02). C. jejuni infection was significantly associated with a poor outcome even after correction for other factors associated with a poor prognosis. Infection with C. jejuni often precedes the Guillain-Barré syndrome and is associated with axonal degeneration, slow recovery, and severe residual disability.
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              Study of infectious intestinal disease in England: rates in the community, presenting to general practice, and reported to national surveillance. The Infectious Intestinal Disease Study Executive.

              To establish the incidence and aetiology of infectious intestinal disease in the community and presenting to general practitioners. Comparison with incidence and aetiology of cases reaching national laboratory based surveillance. Population based community cohort incidence study, general practice based incidence studies, and case linkage to national laboratory surveillance. 70 general practices throughout England. 459 975 patients served by the practices. Community surveillance of 9776 randomly selected patients. Incidence of infectious intestinal disease in community and reported to general practice. 781 cases were identified in the community cohort, giving an incidence of 19.4/100 person years (95% confidence interval 18.1 to 20.8). 8770 cases presented to general practice (3.3/100 person years (2.94 to 3.75)). One case was reported to national surveillance for every 1.4 laboratory identifications, 6.2 stools sent for laboratory investigation, 23 cases presenting to general practice, and 136 community cases. The ratio of cases in the community to cases reaching national surveillance was lower for bacterial pathogens (salmonella 3.2:1, campylobacter 7.6:1) than for viruses (rotavirus 35:1, small round structured viruses 1562:1). There were many cases for which no organism was identified. Infectious intestinal disease occurs in 1 in 5 people each year, of whom 1 in 6 presents to a general practitioner. The proportion of cases not recorded by national laboratory surveillance is large and varies widely by microorganism. Ways of supplementing the national laboratory surveillance system for infectious intestinal diseases should be considered.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS ONE
                plos
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2007
                4 April 2007
                : 2
                : 4
                : e344
                Affiliations
                [1 ]Infectious Disease Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
                [2 ]Environmental and Enteric Diseases Department, Health Protection Agency Centre for Infections, London, United Kingdom
                [3 ]Division of Medicine and Neuroscience, School of Medicine, University of Manchester, Salford, United Kingdom
                [4 ]Department of Primary Care and Population Sciences, University College, London, London, United Kingdom
                US Naval Medical Research Center Detachment/Centers for Disease Control, United States of America
                Author notes
                * To whom correspondence should be addressed. E-mail: clarence.tam@ 123456lshtm.ac.uk

                Conceived and designed the experiments: LR CT SO IP AI AH. Analyzed the data: CT. Wrote the paper: LR CT SO.

                Article
                07-PONE-RA-00585R2
                10.1371/journal.pone.0000344
                1828628
                17406668
                71a1353e-55b9-442a-b9c1-a66fd031ef91
                Tam et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 9 January 2007
                : 12 March 2007
                Page count
                Pages: 6
                Categories
                Research Article
                Infectious Diseases
                Virology/Vaccines
                Infectious Diseases/Bacterial Infections
                Infectious Diseases/Epidemiology and Control of Infectious Diseases
                Infectious Diseases/Gastrointestinal Infections
                Infectious Diseases/Viral Infections
                Neurological Disorders/Peripheral Neuropathies
                Public Health and Epidemiology/Epidemiology
                Public Health and Epidemiology/Immunization
                Public Health and Epidemiology/Infectious Diseases

                Uncategorized
                Uncategorized

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