|
1
|
Lai LY, Arshad F, Areia C, Alshammari TM, Alghoul H, Casajust P, Li X, Dawoud D, Nyberg F, Pratt N, Hripcsak G, Suchard MA, Prieto-Alhambra D, Ryan P, Schuemie MJ. Current Approaches to Vaccine Safety Using Observational Data: A Rationale for the EUMAEUS (Evaluating Use of Methods for Adverse Events Under Surveillance-for Vaccines) Study Design. Front Pharmacol 2022; 13:837632. [PMID: 35392566 PMCID: PMC8980923 DOI: 10.3389/fphar.2022.837632] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/08/2022] [Indexed: 12/28/2022] Open
Abstract
Post-marketing vaccine safety surveillance aims to detect adverse events following immunization in a population. Whether certain methods of surveillance are more precise and unbiased in generating safety signals is unclear. Here, we synthesized information from existing literature to provide an overview of the strengths, weaknesses, and clinical applications of epidemiologic and analytical methods used in vaccine monitoring, focusing on cohort, case-control and self-controlled designs. These designs are proposed to be evaluated in the EUMAEUS (Evaluating Use of Methods for Adverse Event Under Surveillance-for vaccines) study because of their widespread use and potential utility. Over the past decades, there have been an increasing number of epidemiological study designs used for vaccine safety surveillance. While traditional cohort and case-control study designs remain widely used, newer, novel designs such as the self-controlled case series and self-controlled risk intervals have been developed. Each study design comes with its strengths and limitations, and the most appropriate study design will depend on availability of resources, access to records, number and distribution of cases, and availability of population coverage data. Several assumptions have to be made while using the various study designs, and while the goal is to mitigate any biases, violations of these assumptions are often still present to varying degrees. In our review, we discussed some of the potential biases (i.e., selection bias, misclassification bias and confounding bias), and ways to mitigate them. While the types of epidemiological study designs are well established, a comprehensive comparison of the analytical aspects (including method evaluation and performance metrics) of these study designs are relatively less well studied. We summarized the literature, reporting on two simulation studies, which compared the detection time, empirical power, error rate and risk estimate bias across the above-mentioned study designs. While these simulation studies provided insights on the analytic performance of each of the study designs, its applicability to real-world data remains unclear. To bridge that gap, we provided the rationale of the EUMAEUS study, with a brief description of the study design; and how the use of real-world multi-database networks can provide insights into better methods evaluation and vaccine safety surveillance.
Collapse
Affiliation(s)
- Lana Yh Lai
- Division of Informatics, Imaging and Data Sciences, University of Manchester, Manchester, United Kingdom
| | - Faaizah Arshad
- Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA, United States
| | - Carlos Areia
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
| | - Thamir M Alshammari
- Medication Safety Research Chair, King Saud University, Riyadh, Saudi Arabia
| | - Heba Alghoul
- Faculty of Medicine, Islamic University of Gaza, Gaza, Palestine
| | - Paula Casajust
- Real-World Evidence, Trial Form Support, Barcelona, Spain
| | - Xintong Li
- Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, United Kingdom
| | - Dalia Dawoud
- Faculty of Pharmacy, Cairo University, Giza, Egypt
| | - Fredrik Nyberg
- School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Nicole Pratt
- Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia
| | - George Hripcsak
- Department of Biomedical Informatics, Columbia University, New York, NY, United States
| | - Marc A Suchard
- Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA, United States.,Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, United States
| | - Dani Prieto-Alhambra
- Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, United Kingdom.,Health Data Sciences, Medical Informatics, Erasmus Medical Center University, Rotterdam, Netherlands
| | - Patrick Ryan
- Department of Biomedical Informatics, Columbia University, New York, NY, United States.,Observational Health Data Analytics, Janssen R&D, Titusville, NJ, United States
| | - Martijn J Schuemie
- Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA, United States.,Observational Health Data Analytics, Janssen R&D, Titusville, NJ, United States
| |
Collapse
|
|
2
|
Di Pietrantonj C, Rivetti A, Marchione P, Debalini MG, Demicheli V. Vaccines for measles, mumps, rubella, and varicella in children. Cochrane Database Syst Rev 2021; 11:CD004407. [PMID: 34806766 PMCID: PMC8607336 DOI: 10.1002/14651858.cd004407.pub5] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012. OBJECTIVES To assess the effectiveness, safety, and long- and short-term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019). SELECTION CRITERIA We included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case-control studies (CCS), interrupted time-series (ITS) studies, case cross-over (CCO) studies, case-only ecological method (COEM) studies, self-controlled case series (SCCS) studies, person-time cohort (PTC) studies, and case-coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE. MAIN RESULTS We included 138 studies (23,480,668 participants). Fifty-one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review. Effectiveness Vaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post-exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence). The effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence). Vaccine effectiveness against rubella, using a vaccine with the BRD2 strain which is only used in China, is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence). Vaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow-up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence). Safety There is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad-Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine-induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses. The analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses. There is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence). Additionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections. AUTHORS' CONCLUSIONS: Existing evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.
Collapse
Affiliation(s)
- Carlo Di Pietrantonj
- Servizio Regionale di Riferimento per l'Epidemiologia, SSEpi-SeREMI, Azienda Sanitaria Locale ASL AL, Alessandria, Italy
| | - Alessandro Rivetti
- Dipartimento di Prevenzione - S.Pre.S.A.L, ASL CN2 Alba Bra, Alba, Italy
| | - Pasquale Marchione
- Signal Management Unit, Post-Marketing Surveillance Department, Italian Medicine Agency - AIFA, Rome, Italy
| | | | - Vittorio Demicheli
- Servizio Regionale di Riferimento per l'Epidemiologia, SSEpi-SeREMI, Azienda Sanitaria Locale ASL AL, Alessandria, Italy
| |
Collapse
|
|
3
|
Agrawal M, Sabino J, Frias-Gomes C, Hillenbrand CM, Soudant C, Axelrad JE, Shah SC, Ribeiro-Mourão F, Lambin T, Peter I, Colombel JF, Narula N, Torres J. Early life exposures and the risk of inflammatory bowel disease: Systematic review and meta-analyses. EClinicalMedicine 2021; 36:100884. [PMID: 34308303 PMCID: PMC8257976 DOI: 10.1016/j.eclinm.2021.100884] [Citation(s) in RCA: 86] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 04/12/2021] [Accepted: 04/16/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Early life exposures impact immune system development and therefore the risk of immune-mediated diseases, including inflammatory bowel disease (IBD). We systematically reviewed the impact of pre-, peri‑, and postnatal exposures up to the age of five years on subsequent IBD diagnosis. METHODS We identified case-control and cohort studies reporting on the association between early life environmental factors and Crohn's disease (CD), ulcerative colitis (UC), or IBD overall. Databases were search from their inception until May 24th, 2019 until July 14th, 2020. We conducted meta-analyses for quantitative review of relevant risk factors that were comparable across studies and qualitative synthesis of the literature for a wide range of early life exposures, including maternal health and exposures during pregnancy, perinatal factors, birth month and related-factors, breastfeeding, hygiene-related factors and social factors, immigration, antibiotics, offspring health, including infections, and passive smoking. PROSPERO registration: CRD42019134980. FINDINGS Prenatal exposure to antibiotics (OR 1.8; 95% CI 1.2-2.5) and tobacco smoke (OR 1.5; 95% CI 1.2-1.9), and early life otitis media (OR 2.1; 95% CI 1.2-3.6) were associated with IBD. There was a trend towards an association between exposure to antibiotics in infancy and IBD (OR: 1.7, 95% CI 0.97, 2.9), supported by positive data on population-based data. Breastfeeding was protective against IBD. Other early life risk factors had no association with IBD, but data were limited and heterogenous. INTERPRETATION Early life is an important period of susceptibility for IBD development later in life. Tobacco smoke, infections and antibiotics were associated positively, and breastfeeding was associated negatively with IBD. Our findings offer an opportunity to develop primary prevention strategies. FUNDING This study did not receive any funding.
Collapse
Affiliation(s)
- Manasi Agrawal
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - João Sabino
- Gastroenterology Division, University Hospital of Leuven, Leuven, Belgium
| | - Catarina Frias-Gomes
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures 2674-514, Portugal
| | - Christen M. Hillenbrand
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Celine Soudant
- Levy Library, The Mount Sinai Medical Center, New York, NY, United States
- Medical Library, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Jordan E. Axelrad
- Division of Gastroenterology, New York University Grossman School of Medicine, New York, NY, United States
| | - Shailja C. Shah
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, United States
- Section of Gastroenterology, Veterans Affairs Tennessee Valley Healthcare System, Nashville campus, Nashville, TN, United States
| | - Francisco Ribeiro-Mourão
- Pediatrics Department, Unidade Local de Saúde do Alto Minho, Viana do Castelo, Portugal
- Pediatrics Department, Centro Materno Infantil do Norte – Centro Hospitalar e Universitário do Porto, Porto, Portugal
- Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
| | - Thomas Lambin
- Department of Gastroenterology, Claude Huriez Hospital, University of Lille, Lille, France
| | - Inga Peter
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Jean-Frederic Colombel
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Neeraj Narula
- Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive, Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Joana Torres
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures 2674-514, Portugal
- Faculdade de Medicina, Universidade de Lisboa, Portugal
- Corresponding author.
| |
Collapse
|
|
4
|
Hemida M, Vuori KA, Moore R, Anturaniemi J, Hielm-Björkman A. Early Life Modifiable Exposures and Their Association With Owner Reported Inflammatory Bowel Disease Symptoms in Adult Dogs. Front Vet Sci 2021; 8:552350. [PMID: 33598486 PMCID: PMC7882719 DOI: 10.3389/fvets.2021.552350] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 01/04/2021] [Indexed: 12/04/2022] Open
Abstract
Background: Inflammatory bowel disease (IBD) is an idiopathic multifactorial disease in humans and dogs, usually assigned to the interactions between genes, gut microbiota, diet, environment, and the immune system. We aimed to investigate the modifiable early life exposures associated with IBD in dogs. Materials and Methods: The study data was extracted from the validated owner-reported DogRisk food frequency questionnaire. This was a cross-sectional questionnaire-based study that tested 21 different early life dietary and environmental, demographic and genetic variables for their association with IBD or not, in adult dogs. A total of 7,015 dogs participated in this study. The study covered early life periods; prenatal, neonatal, early, and late postnatal periods. Two feeding patterns, a non-processed meat-based diet (NPMD) and an ultra-processed carbohydrate-based diet (UPCD) were studied. Data was analyzed using logistic regression analysis with a backward stepwise deletion. Results: From the final models we found that the NPMD during early and late postnatal periods were significantly associated with lower IBD risk later in life. The UPCD during the same periods was associated with a higher risk of IBD incidence. Also, the maternal diet during the neonatal period showed a non-significant trend of lower IBD risk in the offspring with the NPMD and a higher IBD risk with the UPCD. Additionally, the normal body weight of puppies during the first 6 months of age was associated with a lower risk of IBD in adulthood while, slim puppies associated significantly with IBD in adulthood. From the non-modifiable background variables, we identified the maternal history of IBD as the strongest risk factor for later incidence of IBD. Furthermore, male dogs were twice as likely to develop IBD as female dogs were. Conclusions: It is reassuring for owners to know that they themselves can have an impact on their dog's health. A high-fat, low-carbohydrate NPMD exposure during early life, and a normal body condition in puppyhood were significantly associated with less IBD in adult dogs. The opposite was true for UPCD exposure and abnormal body condition score in 6 month old puppies.
Collapse
Affiliation(s)
- Manal Hemida
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.,Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Kristiina A Vuori
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Robin Moore
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Johanna Anturaniemi
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Anna Hielm-Björkman
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| |
Collapse
|
|
5
|
Di Pietrantonj C, Rivetti A, Marchione P, Debalini MG, Demicheli V. Vaccines for measles, mumps, rubella, and varicella in children. Cochrane Database Syst Rev 2020; 4:CD004407. [PMID: 32309885 PMCID: PMC7169657 DOI: 10.1002/14651858.cd004407.pub4] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012. OBJECTIVES To assess the effectiveness, safety, and long- and short-term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019). SELECTION CRITERIA We included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case-control studies (CCS), interrupted time-series (ITS) studies, case cross-over (CCO) studies, case-only ecological method (COEM) studies, self-controlled case series (SCCS) studies, person-time cohort (PTC) studies, and case-coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE. MAIN RESULTS We included 138 studies (23,480,668 participants). Fifty-one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review. Effectiveness Vaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post-exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence). The effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence). Vaccine effectiveness against rubella is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence). Vaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow-up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence). Safety There is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad-Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine-induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses. The analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses. There is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence). Additionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections. AUTHORS' CONCLUSIONS Existing evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.
Collapse
Affiliation(s)
- Carlo Di Pietrantonj
- Azienda Sanitaria Locale ASL AL, Servizio Regionale di Riferimento per l'Epidemiologia, SSEpi-SeREMI, Via Venezia 6, Alessandria, Italy, 15121
| | - Alessandro Rivetti
- ASL CN2 Alba Bra, Dipartimento di Prevenzione - S.Pre.S.A.L, Via Vida 10, Alba, Piemonte, Italy, 12051
| | - Pasquale Marchione
- Italian Medicine Agency - AIFA, Signal Management Unit, Post-Marketing Surveillance Department, Via del Tritone 181, Rome, Italy, 00187
| | | | - Vittorio Demicheli
- Azienda Sanitaria Locale ASL AL, Servizio Regionale di Riferimento per l'Epidemiologia, SSEpi-SeREMI, Via Venezia 6, Alessandria, Italy, 15121
| |
Collapse
|
|
6
|
Abstract
Autism is a developmental disability that can cause significant social, communication, and behavioral challenges. A report published in 1998, but subsequently retracted by the journal, suggested that measles, mumps, and rubella (MMR) vaccine causes autism. However, autism is a neurodevelopmental condition that has a strong genetic component with genesis before one year of age, when MMR vaccine is typically administered. Several epidemiologic studies have not found an association between MMR vaccination and autism, including a study that found that MMR vaccine was not associated with an increased risk of autism even among high-risk children whose older siblings had autism. Despite strong evidence of its safety, some parents are still hesitant to accept MMR vaccination of their children. Decreasing acceptance of MMR vaccination has led to outbreaks or resurgence of measles. Health-care providers have a vital role in maintaining confidence in vaccination and preventing suffering, disability, and death from measles and other vaccine-preventable diseases.
Collapse
Affiliation(s)
- Frank DeStefano
- Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30329, USA;
| | - Tom T Shimabukuro
- Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30329, USA;
| |
Collapse
|
|
7
|
Seyedian SS, Nokhostin F, Malamir MD. A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. J Med Life 2019; 12:113-122. [PMID: 31406511 PMCID: PMC6685307 DOI: 10.25122/jml-2018-0075] [Citation(s) in RCA: 404] [Impact Index Per Article: 67.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 01/27/2019] [Indexed: 12/11/2022] Open
Abstract
Ulcerative colitis (UC) and Crohn's disease (CD) are classified as chronic inflammatory bowel diseases (IBD) which have similar symptoms and lead to digestive disorders and inflammation in the digestive system. The reason why they occur is still a mystery. A number of factors can be attributed to the prevalence of CD and UC, some of which include geographical location, inappropriate diet, genetics, and inappropriate immune response. Both diseases are more often diagnosed in urban areas compared to rural areas and both have their own challenges and side effects, but the patients can still have a good quality of life. Given the fact that the prevalence of this disease is higher at younger ages and that it disrupts half the life of the patient, it will, most likely, become a major health problem in the near future, even in developing countries. By reviewing valid scientific resources and evaluating new methods of addressing this disease, the present study aims to provide researchers and patients with new insights into this field and facilitate access to new treatments.
Collapse
Affiliation(s)
- Seyed Saeid Seyedian
- Alimentary Tract Research Center, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
| | - Forogh Nokhostin
- Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mehrdad Dargahi Malamir
- Faculty of Medicine, Medical doctor of Internal Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| |
Collapse
|
|
8
|
Carroll MW, Kuenzig ME, Mack DR, Otley AR, Griffiths AM, Kaplan GG, Bernstein CN, Bitton A, Murthy SK, Nguyen GC, Lee K, Cooke-Lauder J, Benchimol EI. The Impact of Inflammatory Bowel Disease in Canada 2018: Children and Adolescents with IBD. J Can Assoc Gastroenterol 2018; 2:S49-S67. [PMID: 31294385 PMCID: PMC6512244 DOI: 10.1093/jcag/gwy056] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 10/30/2018] [Indexed: 12/15/2022] Open
Abstract
Canada has among the highest rates of childhood-onset IBD in the world. Over 7000 children and youth under 18 years old are living with IBD in Canada, and 600 to 650 children under 16 years old are diagnosed annually. While the peak age of onset of IBD is highest in the second and third decades of life, over the past two decades incidence has risen most rapidly in children under 5 years old. The treatment of children with IBD presents important challenges including therapeutic choices, risk of adverse events to medications, psychosocial impact on the child and family, increased cost of health care and the implications of the transition from pediatric to adult care. Despite the unique circumstances faced by children and their families, there is a lack of research to help understand the causes of the rising incidence and the best therapies for children with IBD. Scientific evidence—and specifically clinical trials of pharmaceuticals—are too often extrapolated from adult research. Health care providers must strive to understand the unique impact of childhood-onset IBD on patients and families, while researchers must expand work to address the important needs of this growing patient population. Highlights Key Summary Points Gaps in Knowledge and Future Research Directions
Collapse
Affiliation(s)
- Matthew W Carroll
- Canadian Gastro-Intestinal Epidemiology Consortium Ottawa, Canada.,Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - M Ellen Kuenzig
- Canadian Gastro-Intestinal Epidemiology Consortium Ottawa, Canada.,Children's Hospital of Eastern Ontario IBD Centre, Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - David R Mack
- Canadian Gastro-Intestinal Epidemiology Consortium Ottawa, Canada.,Children's Hospital of Eastern Ontario IBD Centre, Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Anthony R Otley
- Canadian Gastro-Intestinal Epidemiology Consortium Ottawa, Canada.,Division of Gastroenterology and Nutrition, Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Anne M Griffiths
- Canadian Gastro-Intestinal Epidemiology Consortium Ottawa, Canada.,SickKids IBD Centre, The Hospital for Sick Children, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Gilaad G Kaplan
- Canadian Gastro-Intestinal Epidemiology Consortium Ottawa, Canada.,Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta Canada
| | - Charles N Bernstein
- Canadian Gastro-Intestinal Epidemiology Consortium Ottawa, Canada.,University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Alain Bitton
- Canadian Gastro-Intestinal Epidemiology Consortium Ottawa, Canada.,McGill IBD Centre of Excellence, McGill University Health Centre, Montreal, Quebec, Canada
| | - Sanjay K Murthy
- Canadian Gastro-Intestinal Epidemiology Consortium Ottawa, Canada.,Ottawa Hospital Research Institute, Department of Medicine and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Geoffrey C Nguyen
- Canadian Gastro-Intestinal Epidemiology Consortium Ottawa, Canada.,Mount Sinai Hospital Centre for IBD, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Kate Lee
- Crohn's and Colitis Canada, Toronto, Ontario, Canada
| | | | - Eric I Benchimol
- Canadian Gastro-Intestinal Epidemiology Consortium Ottawa, Canada.,Children's Hospital of Eastern Ontario IBD Centre, Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| |
Collapse
|
|
9
|
Bate A, Chuang-Stein C, Roddam A, Jones B. Lessons from meta-analyses of randomized clinical trials for analysis of distributed networks of observational databases. Pharm Stat 2018; 18:65-77. [PMID: 30362223 DOI: 10.1002/pst.1908] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Revised: 09/13/2018] [Accepted: 09/20/2018] [Indexed: 12/20/2022]
Abstract
Networks of constellations of longitudinal observational databases, often electronic medical records or transactional insurance claims or both, are increasingly being used for studying the effects of medicinal products in real-world use. Such databases are frequently configured as distributed networks. That is, patient-level data are kept behind firewalls and not communicated outside of the data vendor other than in aggregate form. Instead, data are standardized across the network, and queries of the network are executed locally by data partners, and summary results provided to a central research partner(s) for amalgamation, aggregation, and summarization. Such networks can be huge covering years of data on upwards of 100 million patients. Examples of such networks include the FDA Sentinel Network, ASPEN, CNODES, and EU-ADR. As this is a new emerging field, we note in this paper the conceptual similarities and differences between the analysis of distributed networks and the now well-established field of meta-analysis of randomized clinical trials (RCTs). We recommend, wherever appropriate, to apply learnings from meta-analysis to help guide the development of distributed network analyses of longitudinal observational databases.
Collapse
Affiliation(s)
- Andrew Bate
- Pfizer, Tadworth, UK.,New York University, New York, NY, USA
| | | | | | | |
Collapse
|
|
10
|
Beleni AI, Borgmann S. Mumps in the Vaccination Age: Global Epidemiology and the Situation in Germany. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2018; 15:ijerph15081618. [PMID: 30065192 PMCID: PMC6121553 DOI: 10.3390/ijerph15081618] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 07/26/2018] [Accepted: 07/27/2018] [Indexed: 11/18/2022]
Abstract
Vaccination against mumps virus (MuV) (mostly measles-mumps-rubella) is routinely performed in more than 120 countries and has resulted in a distinct decrease of mumps incidence. However, alteration of mumps epidemiology has been observed in several countries after implementation of the vaccine but is sparsely documented. Moreover, outbreaks have occurred after starting vaccination, even in highly vaccinated populations. In the former German Democratic Republic (DDR) mumps was a notifiable disease but vaccination against mumps was not implemented. In the five eastern German states forming the DDR until 1990, mumps was not notifiable until 2001. Except for the lack of reporting between 1990–2000, data from Eastern Germany allow analysis of mumps epidemiology after initiating the vaccination campaign. For the period from 2001 to 2016 the data show that the incidence of mumps dropped notably after initiating vaccines, and was accompanied by an increase of the median age of patients with mumps. In Eastern Germany, no outbreaks were noted, while several outbreaks occurred in Western Germany, possibly due to a lower vaccination rate. Further literature analysis revealed that outbreaks were facilitated by waning immunity and crowding. Nevertheless, although vaccination prevented infection, the course of illness, once infected, was sometimes more complicated. In comparison to non-vaccinated populations, high rates of complicated courses occurred and were marked by orchitis, due to higher age of mumps patients. Therefore, refusing vaccination against mumps increases the risk of severe courses when living in a vaccinated population.
Collapse
Affiliation(s)
- Andrea-Ioana Beleni
- Department of Urology and Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
| | - Stefan Borgmann
- Department of Infectious Diseases and Infection Control, Hospital of Ingolstadt, D-85049 Ingolstadt, Germany.
| |
Collapse
|
|
11
|
Abstract
Inflammatory bowel diseases consisting of Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the gastrointestinal tract. In addition to genetic susceptibility and disturbances of the microbiome, environmental exposures forming the exposome play an important role. Starting at birth, the cumulative effect of different environmental exposures combined with a predetermined genetic susceptibility is thought to cause inflammatory bowel disease. All these environmental factors are part of a Western lifestyle, suiting the high incidence rates in Europe and the United States. Whereas receiving breastfeeding, evidence of a Helicobacter pylori infection and vitamin D are important protective factors in Crohn's disease as well as ulcerative colitis, increased hygiene, experiencing a bacterial gastroenteritis in the past, urban living surroundings, air pollution, the use of antibiotics, nonsteroidal anti-inflammatory drugs, and oral contraceptives are likely to be the most important risk factors for both diseases. Current cigarette smoking yields a divergent effect by protecting against ulcerative colitis but increasing risk of Crohn's disease, whereas former smoking increases chances of both diseases. This review gives a clear overview of the current state of knowledge concerning the exposome. Future studies should focus on measuring this exposome yielding the possibility of combining all involved factors to one exposome risk score and our knowledge on genetic susceptibility.
Collapse
|
|
12
|
Dutta AK, Chacko A. Influence of environmental factors on the onset and course of inflammatory bowel disease. World J Gastroenterol 2016; 22:1088-1100. [PMID: 26811649 PMCID: PMC4716022 DOI: 10.3748/wjg.v22.i3.1088] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 09/24/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023] Open
Abstract
Numerous environmental factors have been linked with inflammatory bowel disease. These include smoking, diet, hygiene, drugs, geographical and psychosocial factors. These factors may either increase the risk of or protect against developing this condition and can also affect the course of illness in a positive or negative manner. A number of studies have examined the influence of environmental factors on inflammatory bowel diseases as a whole as well as on ulcerative colitis and Crohn’s disease separately. As there are differences in the pathogenesis of ulcerative colitis and Crohn’s disease, the effect of environmental factors on their onset and course is not always similar. Some factors have shown a consistent association, while reports on others have been conflicting. In this article we discuss the current evidence on the roles of these factors on inflammatory bowel disease, both as causative/protective agents and as modifiers of disease course.
Collapse
|
|
13
|
Sankar P, Cho MK, Monahan K, Nowak K. Reporting Race and Ethnicity in Genetics Research: Do Journal Recommendations or Resources Matter? SCIENCE AND ENGINEERING ETHICS 2015; 21:1353-1366. [PMID: 25407312 DOI: 10.1007/s11948-014-9596-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2008] [Accepted: 09/15/2014] [Indexed: 06/04/2023]
Abstract
Appeals to scrutinize the use of race and ethnicity as variables in genetics research notwithstanding, these variables continue to be inadequately explained and inconsistently used in research publications. In previous research, we found that published genetic research fails to follow suggestions offered for addressing this problem, such as explaining the basis on which these labels are assigned to populations. This study, an analysis of genetic research articles using race or ethnicity terms, explores possible features of journals that are associated with improved reporting of race and ethnicity in genetic research. A journal's expressed commitment to improving how race and ethnicity are used in genetic research, demonstrated by an editorial or in its instructions to authors, was the strongest predictor of following recommendations about reporting race and ethnicity. Journal impact factor had only a limited positive effect on attention to these issues, suggesting that editorial resources associated with higher impact factor journals are not sufficient to improve practices. Our findings reiterate that race and ethnicity variables are used inconsistently in genetic research, but also shed light on how journals might improve practices by highlighting the need for scientists to carefully scrutinize the use of these variables in their work.
Collapse
Affiliation(s)
- Pamela Sankar
- Department of Medical Ethics and Health Policy, University of Pennsylvania, 3401 Market Street, Suite 320, Philadelphia, PA, 19104, USA.
| | - Mildred K Cho
- Stanford Center for Biomedical Ethics, Stanford University, 1215 Welch Road, Modular A, Stanford, CA, 94305-5417, USA.
| | - Keri Monahan
- Department of Medical Ethics and Health Policy, University of Pennsylvania, 3401 Market Street, Suite 320, Philadelphia, PA, 19104, USA.
| | - Kamila Nowak
- Jefferson Medical College, 1025 Walnut Street, Philadelphia, PA, 19107, USA.
| |
Collapse
|
|
14
|
Malik TA. Inflammatory Bowel Disease: Historical Perspective, Epidemiology, and Risk Factors. Surg Clin North Am 2015; 95:1105-22, v. [PMID: 26596917 DOI: 10.1016/j.suc.2015.07.006] [Citation(s) in RCA: 132] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Inflammatory bowel disease (IBD) describes a group of closely related yet heterogeneous predominantly intestinal disease processes that are a result of an uncontrolled immune mediated inflammatory response. It is estimated that approximately one and a half million persons in North America have IBD. Pathogenesis of IBD involves an uncontrolled immune mediated inflammatory response in genetically predisposed individuals to a still unknown environmental trigger that interacts with the intestinal flora. There continues to be an enormous amount of information emanating from epidemiological studies providing expanded insight into the occurrence, distribution, determinants, and mechanisms of inflammatory bowel disease.
Collapse
Affiliation(s)
- Talha A Malik
- Department of Medicine-Gastroenterology, University of Alabama at Birmingham, 1808 7th Avenue South, BDB 391, Birmingham, AL 35294, USA; Department of Epidemiology, University of Alabama at Birmingham, 1808 7th Avenue South, BDB 391, Birmingham, AL 35294, USA.
| |
Collapse
|
|
15
|
Vaccination and Risk for Developing Inflammatory Bowel Disease: A Meta-Analysis of Case-Control and Cohort Studies. Clin Gastroenterol Hepatol 2015; 13:1405-15.e1; quiz e130. [PMID: 25956840 DOI: 10.1016/j.cgh.2015.04.179] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Revised: 04/21/2015] [Accepted: 04/22/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Environmental factors may play a key role in the pathogenesis of inflammatory bowel disease (IBD). Whether vaccination is associated causally with IBD is controversial. We performed a meta-analysis of case-control and cohort studies on the association between vaccination and the risk for IBD. METHODS Studies and abstracts investigating the relationship between vaccination and subsequent risk for developing IBD were reviewed. Childhood or adult immunizations with any vaccine type, at any dose, and with any vaccine schedule were used as inclusion criteria. RESULTS Eleven studies were included in the systematic review and meta-analysis: 8 case-control studies and 3 cohort studies. Studied vaccines were bacille Calmette-Guérin), vaccines against diphtheria, tetanus, smallpox, poliomyelitis, pertussis, H1N1, measles, rubella, mumps, and the combined measles, mumps, and rubella vaccine. Only a few details about vaccine type or route of administration were found in studies. Overall, there was no association between childhood immunization and risk for developing IBD: bacille Calmette-Guérin, relative risk (RR) of 1.04 (95% confidence interval [CI], 0.78-1.38), diphtheria, RR of 1.24 (95% CI, 0.80-1.94), tetanus, RR of 1.27 (95% CI, 0.77-2.08), smallpox, RR of 1.08 (95% CI, 0.70-1.67), poliomyelitis, RR of 1.79 (95% CI, 0.88-3.66), an measles containing vaccines, RR of 1.33 (95% CI, 0.31-5.80) in cohort studies, and RR of 0.85 (95% CI, 0.60-1.20) in case-control studies. Subgroup analysis for Crohn's disease (CD) and ulcerative colitis (UC) found an association between the poliomyelitis vaccine and risk for developing CD (RR, 2.28; 95% CI, 1.12-4.63) or UC (RR, 3.48; 95% CI, 1.2-9.71). The RR of developing IBD after H1N1 vaccination was 1.13 (95% CI, 0.97-1.32). CONCLUSIONS Results of this meta-analysis show no evidence supporting an association between childhood immunization or H1N1 vaccination in adults and risk of developing IBD. The association between the poliomyelitis vaccine and the risk for CD or UC should be analyzed with caution because of study heterogeneity.
Collapse
|
|
16
|
Abstract
IBD, comprising Crohn's disease and ulcerative colitis, is a chronic immunologically mediated disease at the intersection of complex interactions between genetics, environment and gut microbiota. Established high-prevalence populations of IBD in North America and Europe experienced the steepest increase in incidence towards the second half of the twentieth century. Furthermore, populations previously considered 'low risk' (such as in Japan and India) are witnessing an increase in incidence. Potentially relevant environmental influences span the spectrum of life from mode of childbirth and early-life exposures (including breastfeeding and antibiotic exposure in infancy) to exposures later on in adulthood (including smoking, major life stressors, diet and lifestyle). Data support an association between smoking and Crohn's disease whereas smoking cessation, but not current smoking, is associated with an increased risk of ulcerative colitis. Dietary fibre (particularly fruits and vegetables), saturated fats, depression and impaired sleep, and low vitamin D levels have all been associated with incident IBD. Interventional studies assessing the effects of modifying these risk factors on natural history and patient outcomes are an important unmet need. In this Review, the changing epidemiology of IBD, mechanisms behind various environmental associations and interventional studies to modify risk factors and disease course are discussed.
Collapse
Affiliation(s)
- Ashwin N Ananthakrishnan
- Massachusetts General Hospital Crohn's and Colitis Centre, 165 Cambridge Street, 9th Floor, Boston, MA 02114, USA
| |
Collapse
|
|
17
|
Shaw SY, Blanchard JF, Bernstein CN. Early childhood measles vaccinations are not associated with paediatric IBD: a population-based analysis. J Crohns Colitis 2015; 9:334-8. [PMID: 25716176 DOI: 10.1093/ecco-jcc/jjv029] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Early childhood vaccinations have been hypothesized to contribute to the emergence of paediatric inflammatory bowel disease [IBD] in developed countries. Using linked population-based administrative databases, we aimed to explore the association between vaccination with measles-containing vaccines and the risk for IBD. METHODS This was a case-control study using the University of Manitoba IBD Epidemiology Database [UMIBDED]. The UMIBDED was linked to the Manitoba Immunization Monitoring System [MIMS], a population-based database of immunizations administered in Manitoba. All paediatric IBD cases in Manitoba, born after 1989 and diagnosed before March 31, 2008, were included. Controls were matched to cases on the basis of age, sex, and region of residence at time of diagnosis. Measles-containing vaccinations received in the first 2 years of life were documented, with vaccinations categorized as 'None' or 'Complete', with completeness defined according to Manitoba's vaccination schedule. Conditional logistic regression models were fitted to the data, with models adjusted for physician visits in the first 2 years of life and area-level socioeconomic status at case date. RESULTS A total of 951 individuals [117 cases and 834 controls] met eligibility criteria, with average age of diagnosis among cases at 11 years. The proportion of IBD cases with completed vaccinations was 97%, compared with 94% of controls. In models adjusted for physician visits and area-level socioeconomic status, no statistically significant association was detected between completed measles vaccinations and the risk of IBD (adjusted odds ratio [AOR]: 1.5; 95% confidence interval [CI]: 0.5-4.4; p = 0.419]. CONCLUSIONS No significant association between completed measles-containing vaccination in the first 2 years of life and paediatric IBD could be demonstrated in this population-based study.
Collapse
Affiliation(s)
- Souradet Y Shaw
- Inflammatory Bowel Disease Clinical and Research Centre, Department of Community Health Sciences, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - James F Blanchard
- Inflammatory Bowel Disease Clinical and Research Centre, Department of Community Health Sciences, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Charles N Bernstein
- Department of Community Health Sciences, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada Department of Community Health Sciences, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
| |
Collapse
|
|
18
|
Chaudrey K, Salvaggio M, Ahmed A, Mahmood S, Ali T. Updates in vaccination: recommendations for adult inflammatory bowel disease patients. World J Gastroenterol 2015; 21:3184-96. [PMID: 25805924 PMCID: PMC4363747 DOI: 10.3748/wjg.v21.i11.3184] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 11/16/2014] [Accepted: 01/30/2015] [Indexed: 02/06/2023] Open
Abstract
Treatment regimens for inflammatory bowel disease (IBD) incorporate the use of a variety of immunosuppressive agents that increase the risk of infections. Prevention of many of these infections can be achieved by the timely and judicious use of vaccinations. IBD patients tend to be under-immunized. Some of the contributing factors are lack of awareness regarding the significance of vaccinating IBD patients, misperception about safety of vaccinations in immunocompromised patients, ambiguity about the perceived role of the gastroenterologist in contrast to the primary care physician and unavailability of vaccination guidelines focused on IBD population. In general, immunocompetent IBD patients can be vaccinated using standard vaccination recommendations. However there are special considerations for IBD patients receiving immunosuppressive therapy, IBD travelers and pregnant women with IBD. This review discusses current vaccination recommendations with updates for adult IBD patients. Centers for Disease Control and Prevention 2013 vaccination guidelines with 2014 updates and the Advisory Committee on Immunization Practices recommendations have been highlighted as a primary source of recommendations.
Collapse
|
|
19
|
Banaszkiewicz A, Radzikowski A, Albrecht P. Immunisation in children and adolescents with inflammatory bowel disease. Adv Med Sci 2015; 60:144-7. [PMID: 25689276 DOI: 10.1016/j.advms.2014.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2014] [Revised: 11/27/2014] [Accepted: 11/28/2014] [Indexed: 10/24/2022]
Abstract
Inflammatory bowel disease (IBD) patients may be at a higher risk for developing infections due to underlying disease, malnutrition, surgery, or immunosuppressive therapy. Therefore, protecting this group against infections is of particular importance. Immunisation against vaccine-preventable diseases is strongly recommended. This article for the first time summarises data on immunogenicity and safety of vaccines in IBD children and provides an update on some important issues regarding immunisation in these group of children.
Collapse
|
|
20
|
McNeil MM, Gee J, Weintraub ES, Belongia EA, Lee GM, Glanz JM, Nordin JD, Klein NP, Baxter R, Naleway AL, Jackson LA, Omer SB, Jacobsen SJ, DeStefano F. The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety. Vaccine 2014; 32:5390-8. [PMID: 25108215 PMCID: PMC6727851 DOI: 10.1016/j.vaccine.2014.07.073] [Citation(s) in RCA: 177] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2014] [Revised: 07/08/2014] [Accepted: 07/21/2014] [Indexed: 11/27/2022]
Abstract
The Vaccine Safety Datalink (VSD) is a collaborative project between the Centers for Disease Control and Prevention (CDC) and 9 health care organizations. Established in 1990, VSD is a vital resource informing policy makers and the public about the safety of vaccines used in the United States. Large linked databases are used to identify and evaluate adverse events in over 9 million individuals annually. VSD generates rapid, important safety assessments for both routine vaccinations and emergency vaccination campaigns. VSD monitors safety of seasonal influenza vaccines in near-real time, and provided essential information on the safety of influenza A (H1N1) 2009 monovalent vaccine during the recent pandemic. VSD investigators have published important studies demonstrating that childhood vaccines are not associated with autism or other developmental disabilities. VSD prioritizes evaluation of new vaccines; searches for possible unusual health events after vaccination; monitors vaccine safety in pregnant women; and has pioneered development of biostatistical research methods.
Collapse
Affiliation(s)
- Michael M McNeil
- Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States.
| | - Julianne Gee
- Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States
| | - Eric S Weintraub
- Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States
| | - Edward A Belongia
- Marshfield Clinic Research Foundation, Marshfield, WI, United States
| | - Grace M Lee
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, United States
| | - Jason M Glanz
- Institute for Health Research, Kaiser Permanente, Denver, CO, United States
| | - James D Nordin
- HealthPartners Institute for Education and Research, Minneapolis, MN, United States
| | - Nicola P Klein
- Vaccine Study Center, Kaiser Permanente of Northern California, Oakland, CA, United States
| | - Roger Baxter
- Vaccine Study Center, Kaiser Permanente of Northern California, Oakland, CA, United States
| | - Allison L Naleway
- Center for Health Research, Kaiser Permanente Northwest, Portland, OR, United States
| | | | - Saad B Omer
- Kaiser Permanente Center for Health Research, Atlanta, GA, United States
| | - Steven J Jacobsen
- Department of Research and Evaluation, Kaiser Permanente of Southern California, Pasadena, United States
| | - Frank DeStefano
- Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States
| |
Collapse
|
|
21
|
Yusung S, Braun J. Molecular mimicry, inflammatory bowel disease, and the vaccine safety debate. BMC Med 2014; 12:166. [PMID: 25238056 PMCID: PMC4167146 DOI: 10.1186/s12916-014-0166-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Accepted: 08/29/2014] [Indexed: 01/26/2023] Open
Abstract
Preventive immunization has provided one of the major advances in population health during the past century. However, a surprising cultural phenomenon is the emergence of concerns about immunization safety, in part due to prominently controversial biomedical studies. One ongoing theoretical safety concern is the possibility of human molecular mimicry by measles, mumps, rubella (MMR) antigens. The study of Polymeros et al. in this BMC Medicine presents a systematic evaluation and refutation of this safety concern. This provides significant new scientific evidence in support of the safety of pediatric vaccines, which will inform the ongoing policy and cultural understanding of this important public health measure.
Collapse
|
|
22
|
Demicheli V, Rivetti A, Debalini MG, Di Pietrantonj C. Vaccines for measles, mumps and rubella in children. ACTA ACUST UNITED AC 2013. [DOI: 10.1002/ebch.1948] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
|
|
23
|
|
|
24
|
|
|
25
|
Salisbury DM, Martin RM, Van Damme P, Lopalco PL. Immunization in Europe. Vaccines (Basel) 2013. [DOI: 10.1016/b978-1-4557-0090-5.00068-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
|
|
26
|
Cabré E, Domènech E. Impact of environmental and dietary factors on the course of inflammatory bowel disease. World J Gastroenterol 2012; 18:3814-22. [PMID: 22876032 PMCID: PMC3413052 DOI: 10.3748/wjg.v18.i29.3814] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2012] [Revised: 03/26/2012] [Accepted: 03/29/2012] [Indexed: 02/06/2023] Open
Abstract
Besides their possible effects on the development of inflammatory bowel disease (IBD), some environmental factors can modulate the clinical course of both ulcerative colitis (UC) and Crohn’s disease (CD). This review is mainly devoted to describing the current knowledge of the impact of some of these factors on the outcome of IBD, with special emphasis on smoking and diet. Although the impact of smoking on the susceptibility to develop CD and UC is firmly established, its influence on the clinical course of both diseases is still debatable. In CD, active smoking is a risk factor for postoperative recurrence. Beyond this clinical setting, smoking cessation seems to be advantageous in those CD patients who were smokers at disease diagnosis, while smoking resumption may be of benefit in ex-smokers with resistant UC. The role of dietary habits on the development of IBD is far from being well established. Also, food intolerances are very frequent, but usually inconsistent among IBD patients, and therefore no general dietary recommendations can be made in these patients. In general, IBD patients should eat a diet as varied as possible. Regarding the possible therapeutic role of some dietary components in IBD, lessons should be drawn from the investigation of the primary therapeutic effect of enteral nutrition in CD. Low-fat diets seem to be particularly useful. Also, some lipid sources, such as olive oil, medium-chain triglycerides, and perhaps omega-3 fatty acids, might have a therapeutic effect. Fermentable fiber may have a role in preventing relapses in inactive UC.
Collapse
|
|
27
|
Wagner J, Sim WH, Lee KJ, Kirkwood CD. Current knowledge and systematic review of viruses associated with Crohn's disease. Rev Med Virol 2012; 23:145-71. [PMID: 22674582 DOI: 10.1002/rmv.1720] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2012] [Revised: 04/09/2012] [Accepted: 04/11/2012] [Indexed: 12/21/2022]
Abstract
The aetiology of Crohn's disease (CD) is currently unknown. A viral trigger was proposed more than 40 years ago and has been the focus of many investigations. We summarised the current literature surrounding the association between viruses and CD and conducted a systematic review of all studies investigating this association quantitatively. Studies were identified by searching for 13 specific virus names or the general term 'virus' and 'Crohn's disease' in search engines PubMed and OVID. A total of 1315 studies were identified, of which 78 studies had a laboratory result. Of the 78, 46 case-control studies met all the inclusion criteria for forest plot analysis. The most common viruses studied were EBV, CMV and measles virus (MV). Forest plot analysis for each virus was carried out (fitted using random effects) and identified evidence of an association between CD and CMV (risk ratio [RR] 1.602, 95% confidence interval [CI] 1.069 to 2.400) with some suggestion that EBV may also be associated with CD (RR 1.366, 95% CI 0.996 to 1.873). However, there was evidence of large heterogeneity in the results from the identified studies for EBV. There was little evidence of an association with CD for MV, human herpes virus 6, human herpes virus 8, human simplex virus, varicella-zoster virus, mumps virus, Rubella virus, rotavirus, norovirus and adenovirus. There is still some question around whether CD is associated with the presence of a currently known virus.
Collapse
Affiliation(s)
- Josef Wagner
- Enteric Virus Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia.
| | | | | | | |
Collapse
|
|
28
|
Abstract
BACKGROUND Mumps, measles and rubella (MMR) are serious diseases that can lead to potentially fatal illness, disability and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. OBJECTIVES To assess the effectiveness and adverse effects associated with the MMR vaccine in children up to 15 years of age. SEARCH METHODS For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, PubMed (July 2004 to May week 2, 2011) and Embase.com (July 2004 to May 2011). SELECTION CRITERIA We used comparative prospective or retrospective trials assessing the effects of the MMR vaccine compared to placebo, do nothing or a combination of measles, mumps and rubella antigens on healthy individuals up to 15 years of age. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed methodological quality of the included studies. One review author arbitrated in case of disagreement. MAIN RESULTS We included five randomised controlled trials (RCTs), one controlled clinical trial (CCT), 27 cohort studies, 17 case-control studies, five time-series trials, one case cross-over trial, two ecological studies, six self controlled case series studies involving in all about 14,700,000 children and assessing effectiveness and safety of MMR vaccine. Based on the available evidence, one MMR vaccine dose is at least 95% effective in preventing clinical measles and 92% effective in preventing secondary cases among household contacts.Effectiveness of at least one dose of MMR in preventing clinical mumps in children is estimated to be between 69% and 81% for the vaccine prepared with Jeryl Lynn mumps strain and between 70% and 75% for the vaccine containing the Urabe strain. Vaccination with MMR containing the Urabe strain has demonstrated to be 73% effective in preventing secondary mumps cases. Effectiveness of Jeryl Lynn containing MMR in preventing laboratory-confirmed mumps cases in children and adolescents was estimated to be between 64% to 66% for one dose and 83% to 88% for two vaccine doses. We did not identify any studies assessing the effectiveness of MMR in preventing rubella.The highest risk of association with aseptic meningitis was observed within the third week after immunisation with Urabe-containing MMR (risk ratio (RR) 14.28; 95% confidence interval (CI) from 7.93 to 25.71) and within the third (RR 22.5; 95% CI 11.8 to 42.9) or fifth (RR 15.6; 95% CI 10.3 to 24.2) weeks after immunisation with the vaccine prepared with the Leningrad-Zagreb strain. A significant risk of association with febrile seizures and MMR exposure during the two previous weeks (RR 1.10; 95% CI 1.05 to 1.15) was assessed in one large person-time cohort study involving 537,171 children aged between three months and five year of age. Increased risk of febrile seizure has also been observed in children aged between 12 to 23 months (relative incidence (RI) 4.09; 95% CI 3.1 to 5.33) and children aged 12 to 35 months (RI 5.68; 95% CI 2.31 to 13.97) within six to 11 days after exposure to MMR vaccine. An increased risk of thrombocytopenic purpura within six weeks after MMR immunisation in children aged 12 to 23 months was assessed in one case-control study (RR 6.3; 95% CI 1.3 to 30.1) and in one small self controlled case series (incidence rate ratio (IRR) 5.38; 95% CI 2.72 to 10.62). Increased risk of thrombocytopenic purpura within six weeks after MMR exposure was also assessed in one other case-control study involving 2311 children and adolescents between one month and 18 years (odds ratio (OR) 2.4; 95% CI 1.2 to 4.7). Exposure to the MMR vaccine was unlikely to be associated with autism, asthma, leukaemia, hay fever, type 1 diabetes, gait disturbance, Crohn's disease, demyelinating diseases, bacterial or viral infections. AUTHORS' CONCLUSIONS The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunisation with the MMR vaccine cannot be separated from its role in preventing the target diseases.
Collapse
Affiliation(s)
- Vittorio Demicheli
- Servizio Regionale di Riferimento per l’Epidemiologia, SSEpi-SeREMI - Cochrane Vaccines Field, Azienda Sanitaria Locale ASL AL,Alessandria, Italy.
| | | | | | | |
Collapse
|
|
29
|
Hansen TS, Jess T, Vind I, Elkjaer M, Nielsen MF, Gamborg M, Munkholm P. Environmental factors in inflammatory bowel disease: a case-control study based on a Danish inception cohort. J Crohns Colitis 2011; 5:577-84. [PMID: 22115378 DOI: 10.1016/j.crohns.2011.05.010] [Citation(s) in RCA: 125] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2010] [Revised: 05/19/2011] [Accepted: 05/26/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND The role of environmental factors in development of inflammatory bowel disease (IBD) remains uncertain. The aim of the present study was to assess a number of formerly suggested environmental factors in a case-control study of an unselected and recently diagnosed group of patients with IBD and a control group of orthopaedic patients. METHODS A total of 123 patients diagnosed with Crohn's disease (CD) and 144 with ulcerative colitis (UC) in Copenhagen (2003-2004) were matched 1:1 on age and gender to 267 orthopaedic controls. Participants received a questionnaire with 87 questions concerning environmental factors prior to IBD/orthopaedic admission. Odds ratios (OR) were calculated by logistic regression. RESULTS Being breastfed >6 months (OR, 0.50; 95% CI, 0.23-1.11) and undergoing tonsillectomy (OR, 0.49; 95% CI, 0.31-0.78) decreased the odds for IBD, whereas appendectomy decreased the odds for UC only (OR, 0.29; 95% CI, 0.12-0.71). Vaccination against pertussis (OR, 2.08; 95% CI, 1.07-4.03) and polio (OR, 2.38; 95% CI, 1.04-5.43) increased the odds for IBD, whereas measles infection increased the odds for UC (OR, 3.50; 95% CI, 1.15-10.6). Low consumption of fibres and high consumption of sugar were significantly associated with development of CD and UC. Smoking increased the risk for CD and protected against UC. CONCLUSION Among Danish patients with CD and UC belonging to an unselected cohort, disease occurrence was found to be associated both with well-known factors such as smoking and appendectomy, and with more debated factors including breastfeeding, tonsillectomy, childhood vaccinations, childhood infections, and dietary intake of fibres and sugar.
Collapse
Affiliation(s)
- Tanja Stenbaek Hansen
- Gastrointestinal Unit, Medical Section, Herlev University Hospital, Statens Serum Institut, Copenhagen, Denmark
| | | | | | | | | | | | | |
Collapse
|
|
30
|
Ali-Khan SE, Krakowski T, Tahir R, Daar AS. The use of race, ethnicity and ancestry in human genetic research. THE HUGO JOURNAL 2011; 5:47-63. [PMID: 22276086 PMCID: PMC3237839 DOI: 10.1007/s11568-011-9154-5] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/04/2011] [Revised: 04/27/2011] [Accepted: 06/17/2011] [Indexed: 01/04/2023]
Abstract
Post-Human Genome Project progress has enabled a new wave of population genetic research, and intensified controversy over the use of race/ethnicity in this work. At the same time, the development of methods for inferring genetic ancestry offers more empirical means of assigning group labels. Here, we provide a systematic analysis of the use of race/ethnicity and ancestry in current genetic research. We base our analysis on key published recommendations for the use and reporting of race/ethnicity which advise that researchers: explain why the terms/categories were used and how they were measured, carefully define them, and apply them consistently. We studied 170 population genetic research articles from high impact journals, published 2008-2009. A comparative perspective was obtained by aligning study metrics with similar research from articles published 2001-2004. Our analysis indicates a marked improvement in compliance with some of the recommendations/guidelines for the use of race/ethnicity over time, while showing that important shortfalls still remain: no article using 'race', 'ethnicity' or 'ancestry' defined or discussed the meaning of these concepts in context; a third of articles still do not provide a rationale for their use, with those using 'ancestry' being the least likely to do so. Further, no article discussed potential socio-ethical implications of the reported research. As such, there remains a clear imperative for highlighting the importance of consistent and comprehensive reporting on human populations to the genetics/genomics community globally, to generate explicit guidelines for the uses of ancestry and genetic ancestry, and importantly, to ensure that guidelines are followed.
Collapse
Affiliation(s)
- Sarah E. Ali-Khan
- McLaughlin-Rotman Centre for Global Health, University Health Network and University of Toronto, 101 College St, Suite 406, Toronto, ON M5G 1L7 Canada
| | - Tomasz Krakowski
- McLaughlin-Rotman Centre for Global Health, University Health Network and University of Toronto, 101 College St, Suite 406, Toronto, ON M5G 1L7 Canada
| | - Rabia Tahir
- McLaughlin-Rotman Centre for Global Health, University Health Network and University of Toronto, 101 College St, Suite 406, Toronto, ON M5G 1L7 Canada
| | - Abdallah S. Daar
- McLaughlin-Rotman Centre for Global Health, University Health Network and University of Toronto, 101 College St, Suite 406, Toronto, ON M5G 1L7 Canada
- Department of Public Health Sciences and of Surgery, University of Toronto, Toronto, ON M5S 1A8 Canada
- McLaughlin Centre for Molecular Medicine, University Health Network and University of Toronto, Toronto, ON M5S 1A1 Canada
- Grand Challenges Canada, http://www.grandchallenges.ca
| |
Collapse
|
|
31
|
Rahier JF, Moutschen M, Van Gompel A, Van Ranst M, Louis E, Segaert S, Masson P, De Keyser F. Vaccinations in patients with immune-mediated inflammatory diseases. Rheumatology (Oxford) 2010; 49:1815-27. [PMID: 20591834 PMCID: PMC2936949 DOI: 10.1093/rheumatology/keq183] [Citation(s) in RCA: 141] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2009] [Revised: 05/11/2010] [Indexed: 12/20/2022] Open
Abstract
Patients with immune-mediated inflammatory diseases (IMID) such as RA, IBD or psoriasis, are at increased risk of infection, partially because of the disease itself, but mostly because of treatment with immunomodulatory or immunosuppressive drugs. In spite of their elevated risk for vaccine-preventable disease, vaccination coverage in IMID patients is surprisingly low. This review summarizes current literature data on vaccine safety and efficacy in IMID patients treated with immunosuppressive or immunomodulatory drugs and formulates best-practice recommendations on vaccination in this population. Especially in the current era of biological therapies, including TNF-blocking agents, special consideration should be given to vaccination strategies in IMID patients. Clinical evidence indicates that immunization of IMID patients does not increase clinical or laboratory parameters of disease activity. Live vaccines are contraindicated in immunocompromized individuals, but non-live vaccines can safely be given. Although the reduced quality of the immune response in patients under immunotherapy may have a negative impact on vaccination efficacy in this population, adequate humoral response to vaccination in IMID patients has been demonstrated for hepatitis B, influenza and pneumococcal vaccination. Vaccination status is best checked and updated before the start of immunomodulatory therapy: live vaccines are not contraindicated at that time and inactivated vaccines elicit an optimal immune response in immunocompetent individuals.
Collapse
Affiliation(s)
- Jean-François Rahier
- Department of Gastroenterology, Cliniques Universitaires UCL Mont Godinne, Yvoir, Department of Infectious Diseases, University of Liege, Liege, Clinical Department, Institute of Tropical Medicine Antwerp, Antwerp, Laboratory Medicine, University Hospital Leuven, Department of Gastroenterology, CHU, University of Liege, Liege, Department of Dermatology, University Hospital Leuven, Leuven de Duve Institute, Université Catholique de Louvain, Brussels and Department of Rheumatology, Ghent University, Ghent, Belgium
| | - Michel Moutschen
- Department of Gastroenterology, Cliniques Universitaires UCL Mont Godinne, Yvoir, Department of Infectious Diseases, University of Liege, Liege, Clinical Department, Institute of Tropical Medicine Antwerp, Antwerp, Laboratory Medicine, University Hospital Leuven, Department of Gastroenterology, CHU, University of Liege, Liege, Department of Dermatology, University Hospital Leuven, Leuven de Duve Institute, Université Catholique de Louvain, Brussels and Department of Rheumatology, Ghent University, Ghent, Belgium
| | - Alfons Van Gompel
- Department of Gastroenterology, Cliniques Universitaires UCL Mont Godinne, Yvoir, Department of Infectious Diseases, University of Liege, Liege, Clinical Department, Institute of Tropical Medicine Antwerp, Antwerp, Laboratory Medicine, University Hospital Leuven, Department of Gastroenterology, CHU, University of Liege, Liege, Department of Dermatology, University Hospital Leuven, Leuven de Duve Institute, Université Catholique de Louvain, Brussels and Department of Rheumatology, Ghent University, Ghent, Belgium
| | - Marc Van Ranst
- Department of Gastroenterology, Cliniques Universitaires UCL Mont Godinne, Yvoir, Department of Infectious Diseases, University of Liege, Liege, Clinical Department, Institute of Tropical Medicine Antwerp, Antwerp, Laboratory Medicine, University Hospital Leuven, Department of Gastroenterology, CHU, University of Liege, Liege, Department of Dermatology, University Hospital Leuven, Leuven de Duve Institute, Université Catholique de Louvain, Brussels and Department of Rheumatology, Ghent University, Ghent, Belgium
| | - Edouard Louis
- Department of Gastroenterology, Cliniques Universitaires UCL Mont Godinne, Yvoir, Department of Infectious Diseases, University of Liege, Liege, Clinical Department, Institute of Tropical Medicine Antwerp, Antwerp, Laboratory Medicine, University Hospital Leuven, Department of Gastroenterology, CHU, University of Liege, Liege, Department of Dermatology, University Hospital Leuven, Leuven de Duve Institute, Université Catholique de Louvain, Brussels and Department of Rheumatology, Ghent University, Ghent, Belgium
| | - Siegfried Segaert
- Department of Gastroenterology, Cliniques Universitaires UCL Mont Godinne, Yvoir, Department of Infectious Diseases, University of Liege, Liege, Clinical Department, Institute of Tropical Medicine Antwerp, Antwerp, Laboratory Medicine, University Hospital Leuven, Department of Gastroenterology, CHU, University of Liege, Liege, Department of Dermatology, University Hospital Leuven, Leuven de Duve Institute, Université Catholique de Louvain, Brussels and Department of Rheumatology, Ghent University, Ghent, Belgium
| | - Pierre Masson
- Department of Gastroenterology, Cliniques Universitaires UCL Mont Godinne, Yvoir, Department of Infectious Diseases, University of Liege, Liege, Clinical Department, Institute of Tropical Medicine Antwerp, Antwerp, Laboratory Medicine, University Hospital Leuven, Department of Gastroenterology, CHU, University of Liege, Liege, Department of Dermatology, University Hospital Leuven, Leuven de Duve Institute, Université Catholique de Louvain, Brussels and Department of Rheumatology, Ghent University, Ghent, Belgium
| | - Filip De Keyser
- Department of Gastroenterology, Cliniques Universitaires UCL Mont Godinne, Yvoir, Department of Infectious Diseases, University of Liege, Liege, Clinical Department, Institute of Tropical Medicine Antwerp, Antwerp, Laboratory Medicine, University Hospital Leuven, Department of Gastroenterology, CHU, University of Liege, Liege, Department of Dermatology, University Hospital Leuven, Leuven de Duve Institute, Université Catholique de Louvain, Brussels and Department of Rheumatology, Ghent University, Ghent, Belgium
| |
Collapse
|
|
32
|
Smith MJ, Woods CR. On-time vaccine receipt in the first year does not adversely affect neuropsychological outcomes. Pediatrics 2010; 125:1134-41. [PMID: 20498176 DOI: 10.1542/peds.2009-2489] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVES To determine whether children who received recommended vaccines on time during the first year of life had different neuropsychological outcomes at 7 to 10 years of age as compared with children with delayed receipt or nonreceipt of these vaccines. METHODS Publicly available data, including age at vaccination, from a previous VaccineSafety Datalink study of thimerosal exposure and 42 neuropsychological outcomes were analyzed. Vaccine receipt was defined as timely when each vaccine was received within 30 days of the recommended age. Associations between timeliness and each outcome were tested in univariate analyses. Multivariable regression models were constructed for further assessment of the impact of timeliness on neuropsychological outcomes after adjustment for potential confounders. Secondary analyses were performed on a subset of children with the highest and lowest vaccine exposures during the first 7 months of life. RESULTS Timely vaccination was associated with better performance on 12 outcomes in univariate testing and remained associated with better performance for 2 outcomes in multivariable analyses. No statistically significant differences favored delayed receipt. In secondary analyses, children with the greatest vaccine exposure during the first 7 months of life performed better than children with the least vaccine exposure on 15 outcomes in univariate testing; these differences did not persist in multivariable analyses. No statistically significant differences favored the less vaccinated children. CONCLUSIONS Timely vaccination during infancy has no adverse effect on neuropsychological outcomes 7 to 10 years later. These data may reassure parents who are concerned that children receive too many vaccines too soon.
Collapse
Affiliation(s)
- Michael J Smith
- University of Louisville School of Medicine, Division of Pediatric Infectious Diseases, 571 S Floyd St, Suite 321, Louisville, KY 40202, USA.
| | | |
Collapse
|
|
33
|
Carbonnel F, Jantchou P, Monnet E, Cosnes J. Environmental risk factors in Crohn's disease and ulcerative colitis: an update. ACTA ACUST UNITED AC 2009; 33 Suppl 3:S145-57. [DOI: 10.1016/s0399-8320(09)73150-1] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
|
|
34
|
Abstract
In October 2007, Dr Robert Sears, in response to growing parental concerns about the safety of vaccines, published The Vaccine Book: Making the Right Decision for Your Child. Sears' book is enormously popular, having sold >40000 copies. At the back of the book, Sears includes "Dr Bob's Alternative Vaccine Schedule," a formula by which parents can delay, withhold, separate, or space out vaccines. Pediatricians now confront many parents who insist that their children receive vaccines according to Sears' schedule, rather than that recommended by the American Academy of Pediatrics, the Centers for Disease Control and Prevention, and the American Academy of Family Physicians. This article examines the reasons for the popularity of Sears' book, deconstructs the logic and rationale behind its recommendations, and describes how Sears' misrepresentation of vaccine science misinforms parents trying to make the right decisions for their children.
Collapse
Affiliation(s)
- Paul A Offit
- Vaccine Education Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
| | | |
Collapse
|
|
35
|
Moran N, Shickle D, Richardson E. European citizens' opinions on immunisation. Vaccine 2008; 26:411-8. [PMID: 18093700 PMCID: PMC7131435 DOI: 10.1016/j.vaccine.2007.11.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2006] [Revised: 08/14/2007] [Accepted: 11/04/2007] [Indexed: 11/28/2022]
Abstract
As part of a larger study exploring how European citizens' balance issues of public and private interest and the extent to which they are prepared to accept State intervention on a range of public health issues, focus group participants were asked whether childhood immunisation should be a matter of parental choice or State compulsion. The question was debated in 66 (of 96) focus groups held across 16 European countries in 2003. Discussions focused on the concept of risk, trust in health professionals and the State, upholding the status quo, fears over vaccine safety and perceptions of infectious disease as a 'foreign threat'.
Collapse
Affiliation(s)
- Nicola Moran
- Social Policy Research Unit, University of York, Heslington, York YO10 5DD, United Kingdom.
| | | | | |
Collapse
|
|
36
|
Koloski NA, Bret L, Radford-Smith G. Hygiene hypothesis in inflammatory bowel disease: A critical review of the literature. World J Gastroenterol 2008; 14:165-73. [PMID: 18186549 PMCID: PMC2675108 DOI: 10.3748/wjg.14.165] [Citation(s) in RCA: 136] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The hygiene hypothesis is thought to be a significant contributor to the growing incidence of inflammatory bowel disease (IBD) around the world, although the evidence for specific factors that underlie the hygiene hypothesis in IBD is unclear. We aimed to systematically review the literature to determine which hygiene-related factors are associated with the development of IBD. Publications identified from a broad based MEDLINE and Current Contents search between 1966 and 2007 on key terms relevant to the 'hygiene hypothesis' and IBD including H pylori exposure, helminths, cold chain hypothesis, measles infection and vaccination, antibiotic use, breastfeeding, family size, sibship, urban upbringing, day care attendance and domestic hygiene were reviewed. The literature suggests that the hygiene hypothesis and its association with decreased microbial exposure in childhood probably plays an important role in the development of IBD, although the strength of the supporting data for each of the factors varies considerably. The most promising factors that may potentially be associated with development of IBD include H pylori exposure, helminths, breastfeeding and sibship. However, the vast majority of studies in this area are plagued by serious methodological shortcomings, particularly the reliance on retrospective recall of information making it difficult to truly ascertain the importance of a 'hygiene hypothesis' in IBD. The 'hygiene hypothesis' in IBD is an important area of research that may give clues to the aetiology of this disease. Directions for future research are recommended.
Collapse
|
|
37
|
Salisbury DM, Spika JS. Immunization in Europe. Vaccines (Basel) 2008. [DOI: 10.1016/b978-1-4160-3611-1.50072-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
|
|
38
|
|
|
39
|
Measles vaccine. Vaccines (Basel) 2008. [DOI: 10.1016/b978-1-4160-3611-1.50022-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] Open
|
|
40
|
Bernstein CN, Rawsthorne P, Blanchard JF. Population-based case-control study of measles, mumps, and rubella and inflammatory bowel disease. Inflamm Bowel Dis 2007; 13:759-62. [PMID: 17230540 DOI: 10.1002/ibd.20089] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Previous controversy was generated over the hypothesis that a paramyxovirus such as measles or vaccination against such viruses might be causally associated with inflammatory bowel disease (IBD). We aimed to determine if Crohn's disease (CD) or ulcerative colitis (UC) subjects are more likely to be seropositive for measles, mumps, or rubella than controls. METHODS Using our population-based University of Manitoba IBD Research Registry we recruited CD (n = 235) and UC (n = 137) subjects ages 18-50 years for a study involving detailed questionnaires and venipuncture. We accessed the population-based databases of Manitoba Health (single provincial health insurer) to get age-, gender-, and geography-matched non-IBD controls (n = 310). We used a standard enzyme-linked immunosorbent assay (ELISA) to measure serum antibodies. RESULTS Seropositivity for measles and mumps was similar in controls (98.1%, 78.4%, respectively) as in CD (96.2%, 72.3% respectively) and in UC (95.5%, 74.6%, respectively). However, controls were significantly more likely to be seropositive for rubella (98.1%) than were CD cases (91.0%, P < 0.0002) or UC cases (93.3%, P = 0.01). Males accounted for the significantly lower rates of seropositivity to rubella with CD. While we determined that significantly more controls than CD were vaccinated, we cannot be sure if the increased rate of rubella seropositivity in controls is secondary to wildtype or vaccine-associated infection. CONCLUSIONS These data suggest there is no association of having acquired measles, mumps, or rubella (by natural infection or through vaccination) and CD or UC. If anything, these data may suggest some protective effect of having acquired rubella infection or vaccine against acquiring CD.
Collapse
Affiliation(s)
- Charles N Bernstein
- University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, Winnipeg, Manitoba, Canada.
| | | | | |
Collapse
|
|
41
|
Abstract
Crohn's disease and ulcerative colitis are idiopathic inflammatory bowel disorders. In this paper, we discuss how environmental factors (eg, geography, cigarette smoking, sanitation and hygiene), infectious microbes, ethnic origin, genetic susceptibility, and a dysregulated immune system can result in mucosal inflammation. After describing the symbiotic interaction of the commensal microbiota with the host, oral tolerance, epithelial barrier function, antigen recognition, and immunoregulation by the innate and adaptive immune system, we examine the initiating and perpetuating events of mucosal inflammation. We pay special attention to pattern-recognition receptors, such as toll-like receptors and nucleotide-binding-oligomerisation-domains (NOD), NOD-like receptors and their mutual interaction on epithelial cells and antigen-presenting cells. We also discuss the important role of dendritic cells in directing tolerance and immunity by modulation of subpopulations of effector T cells, regulatory T cells, Th17 cells, natural killer T cells, natural killer cells, and monocyte-macrophages in mucosal inflammation. Implications for novel therapies, which are discussed in detail in the second paper in this Series, are covered briefly.
Collapse
Affiliation(s)
- Daniel C Baumgart
- Department of Medicine, Division of Gastroenterology and Hepatology, Charité Medical Centre, Virchow Hospital, Medical School of the Humboldt-University of Berlin, 13344 Berlin, Germany.
| | | |
Collapse
|
|
42
|
Abstract
Use of race and ethnicity terms in genetic research continues to generate controversy. Despite differing opinions about their basis or relevance, there is some agreement that investigators using these terms should: explain why the terms or categories were used, define them carefully, and apply them consistently. An important question is whether these recommendations are reflected in practice. Here we addressed this question based on 330 randomly selected articles published between 2001 and 2004 that reported on genetic research and used one or more words from a defined list of race, ethnicity, or population terms. The recommendation that authors using race or ethnicity terms explain the basis for assigning them to study populations was met infrequently (9.1%), and articles that used race and ethnicity as variables were no more likely than those that used them only to label a sample to provide these details. No article defined or discussed the concepts of race or ethnicity. With limited exceptions, current practice does not reflect repeated recommendations for using race or ethnicity terms in genetic research. This study provides a baseline against which to measure future trends.
Collapse
Affiliation(s)
- Pamela Sankar
- Department of Medical Ethics; Center for Bioethics; Leonard Davis Institute for Health Economics, University of Pennsylvania, Philadelphia, PA 19130, USA.
| | | | | |
Collapse
|
|
43
|
Jantchou P, Monnet E, Carbonnel F. [Environmental risk factors in Crohn's disease and ulcerative colitis (excluding tobacco and appendicectomy)]. ACTA ACUST UNITED AC 2006; 30:859-67. [PMID: 16885870 DOI: 10.1016/s0399-8320(06)73333-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
A rapid increase in the incidence of Crohn's disease and ulcerative colitis in developed countries, the occurrence of Crohn's disease in spouses, and a lack of complete concordance in monozygotic twins are strong arguments for the role of environmental factors in inflammatory bowel disease (IBD). Research in the field of environmental factors in IBD is based upon epidemiological (geographical and case-control), clinical and experimental studies. The role of two environmental factors has clearly been established in IBD. Smoking is a risk factor for Crohn's disease and a protective factor for ulcerative colitis; appendectomy is a protective factor for ulcerative colitis. Many other environmental factors for IBD have been investigated, including infectious agents, diet, drugs, stress and social status. They are detailed in the present review. Among them, atypical Mycobacteria, oral contraceptives and antibiotics could play a role in Crohn's disease. To date, three hypotheses associate environmental factors with the pathophysiology of IBD (loss of tolerance of intestinal immune system towards commensal bacterial flora): the hygiene, infection and cold chain hypotheses. Much work remains to be done to identify risk factors for IBD. Research identifying environmental factors that might cause a predisposition to IBD is useful. It may lead to disease prevention in subjects who are genetically predisposed and disease improvement in patients.
Collapse
|
|
44
|
Autret-Leca E, Bensouda-Grimaldi L, Jonville-Béra AP, Beau-Salinas F. Pharmacovigilance des vaccins. Arch Pediatr 2006; 13:175-80. [PMID: 16343870 DOI: 10.1016/j.arcped.2005.10.020] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2005] [Accepted: 10/19/2005] [Indexed: 11/20/2022]
Abstract
Safety of vaccines must be excellent to make vaccine's strategy acceptable, since it usually has a deferred individual benefit but immediate adverse drug reactions (ADRs). Pharmacovigilance of vaccines after their marketing is crucial because, prior to its availability on the market, the size of clinical trials is insufficient to identify rare or deferred adverse effects. The Pharmacovigilance is based on "spontaneous reporting" of ADRs to the Pharmacovigilance Regional Centre (PVRC) which establishes a relationship between each drug taken by the patient and the ADRs occurrence (imputability). This method is crucial to generate alerts, but under-estimates the real frequency of ADRs (1 to 10% of severe ADRs are reported). Thus pharmacoepidemiology studies are necessary to confirm the alerts identified by spontaneous reporting. ADRs can be specific, related to the antigen of an attenuated alive virus vaccine (lymphocyte meningitis after anti-mumps vaccine) or non-specific, related to a component different from the antigen (aluminium hydroxide involved in the "macrophagic myofasciitis", allergic reactions to neomycin, latex, egg or gelatine). Importance of Pharmacovigilance of vaccines is illustrated. Data, especially case-control studies, about the relationship between multiple sclerosis and hepatitis B vaccine are summarised. Data about the relationship between Crohn's disease or autism and MMR vaccine are analysed. As vaccines are used in healthy people, their safety must be excellent to be accepted. To monitor them after their marketing is the unique way to detect rare ADRs. This surveillance is made through reporting of ADRs to the PVRC. However, an active and intensive surveillance of ADRs as the one set up from the marketing of Prevenar should be systematic.
Collapse
Affiliation(s)
- E Autret-Leca
- Service de Pharmacologie, Hôpital Bretonneau, Université François-Rabelais de Tours, Centre Régional de Pharmacovigilance et d'Information sur le Médicament, CHRU de Tours, 2, boulevard Tonnellé, 37044 Tours, cedex 09, France.
| | | | | | | |
Collapse
|
|
45
|
Lamhonwah AM, Ackerley C, Onizuka R, Tilups A, Lamhonwah D, Chung C, Tao KS, Tellier R, Tein I. Epitope shared by functional variant of organic cation/carnitine transporter, OCTN1, Campylobacter jejuni and Mycobacterium paratuberculosis may underlie susceptibility to Crohn’s disease at 5q31. Biochem Biophys Res Commun 2005; 337:1165-75. [PMID: 16246312 DOI: 10.1016/j.bbrc.2005.09.170] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2005] [Accepted: 09/27/2005] [Indexed: 12/19/2022]
Abstract
Campylobacter jejuni and Mycobacterium paratuberculosis have been implicated in the pathogenesis of Crohn's disease. The presence of bacterial metabolites in the colonic lumen causing a specific breakdown of fatty acid oxidation in colonic epithelial cells has been suggested as an initiating event in inflammatory bowel disease (IBD). l-Carnitine is a small highly polar zwitterion that plays an essential role in fatty acid oxidation and ATP generation in intestinal bioenergetic metabolism. The organic cation/carnitine transporters, OCTN1 and OCTN2, function primarily in the transport of l-carnitine and elimination of cationic drugs in the intestine. High-resolution linkage disequilibrium mapping has identified a region of about 250kb in size at 5q31 (IBD5) encompassing the OCTN1 and -2 genes, to confer susceptibility to Crohn's disease. Recently, two variants in the OCTN1 and OCTN2 genes have been shown to form a haplotype which is associated with susceptibility to Crohn's. We show that OCTN1 and OCTN2 are strongly expressed in target areas for IBD such as ileum and colon. Further, we have now identified a nine amino acid epitope shared by this functional variant of OCTN1 (Leu503Phe) (which decreases the efficiency of carnitine transport), and by C. jejuni (9 aa) and M. paratuberculosis (6 aa). The prevalence of this variant of OCTN1 (Phe503:Leu503) is 3-fold lower in unaffected individuals of Jewish origin (1:3.44) compared to unaffected individuals of non-Jewish origin (1:1). We hypothesize that a specific antibody raised to this epitope during C. jejuni or M. paratuberculosis enterocolitis would cross-react with the intestinal epithelial cell functional variant of OCTN1, an already less efficient carnitine transporter, leading to an impairment of mitochondrial beta-oxidation which may then serve as an initiating event in IBD. This impairment of l-carnitine transport by OCTN1 may respond to high-dose l-carnitine therapy.
Collapse
Affiliation(s)
- Anne-Marie Lamhonwah
- Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ont., Canada
| | | | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Abstract
BACKGROUND Public debate over the safety of the trivalent measles, mumps and rubella (MMR) vaccine, and the resultant drop in vaccination rates in several countries, persists despite its almost universal use and accepted effectiveness. OBJECTIVES We carried out a systematic review to assess the evidence of effectiveness and unintended effects associated with MMR. SEARCH STRATEGY We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to December 2004), EMBASE (1974 to December 2004), Biological Abstracts (from 1985 to December 2004), and Science Citation Index (from 1980 to December 2004). Results from reviews, handsearching and from the consultation of manufacturers and authors were also used. SELECTION CRITERIA Eligible studies were comparative prospective or retrospective trials testing the effects of MMR compared to placebo, do-nothing or a combination of measles, mumps and rubella antigens on healthy individuals up to 15 years of age. These studies were carried out or published by 2004. DATA COLLECTION AND ANALYSIS We identified 139 articles possibly satisfying our inclusion criteria and included 31 in the review. MAIN RESULTS MMR was associated with a lower incidence of upper respiratory tract infections, a higher incidence of irritability, and similar incidence of other adverse effects compared to placebo. The vaccine was likely to be associated with benign thrombocytopenic purpura, parotitis, joint and limb complaints, febrile convulsions within two weeks of vaccination and aseptic meningitis (mumps) (Urabe strain-containing MMR). Exposure to MMR was unlikely to be associated with Crohn's disease, ulcerative colitis, autism or aseptic meningitis (mumps) (Jeryl-Lynn strain-containing MMR). We could not identify studies assessing the effectiveness of MMR that fulfilled our inclusion criteria even though the impact of mass immunisation on the elimination of the diseases has been largely demonstrated. AUTHORS' CONCLUSIONS The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunisation with MMR cannot be separated from its role in preventing the target diseases.
Collapse
Affiliation(s)
- V Demicheli
- Servizo Sovrazonale di Epidemiologia, ASL 20, Via Venezia 6, Alessandria, Piemonte, Italy 15100.
| | | | | | | |
Collapse
|
|
47
|
Affiliation(s)
- Valerie Seagroatt
- Unit of Health-Care Epidemiology, Department of Public Health, University of Oxford, Oxford OX3 7LF.
| |
Collapse
|
|
48
|
Schattner A. Consequence or coincidence? The occurrence, pathogenesis and significance of autoimmune manifestations after viral vaccines. Vaccine 2005; 23:3876-86. [PMID: 15917108 DOI: 10.1016/j.vaccine.2005.03.005] [Citation(s) in RCA: 157] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2004] [Revised: 02/02/2005] [Accepted: 03/04/2005] [Indexed: 12/27/2022]
Abstract
BACKGROUND Viruses and virus-induced lymphokines may have an important role in the pathogenesis of autoimmunity (Schattner A. Clin Immunol Immunopathol; 1994). The occurrence and significance of autoimmune manifestations after the administration of viral vaccines remain controversial. METHODS Medline search of all relevant publications from 1966 through June 2004 with special emphasis on search of each individual autoimmune manifestation and vaccination, as well as specifically searching each viral vaccine for all potential autoimmune syndromes reported. All relevant publications were retrieved and critically analyzed. RESULTS The most frequently reported autoimmune manifestations for the various vaccinations, were: hepatitis A virus (HAV)--none; hepatitis B virus (HBV)--rheumatoid arthritis, reactive arthritis, vasculitis, encephalitis, neuropathy, thrombocytopenia; measles, mumps and rubella vaccine (MMR)--acute arthritis or arthralgia, chronic arthritis, thrombocytopenia; influenza--Guillain-Barre syndrome (GBS), vasculitis; polio--GBS; varicella--mainly neurological syndromes. Even these 'frequent' associations relate to a relatively small number of patients. Whenever controlled studies of autoimmunity following viral vaccines were undertaken, no evidence of an association was found. CONCLUSIONS Very few patients may develop some autoimmune diseases following viral vaccination (in particular - arthropathy, vasculitis, neurological dysfunction and thrombocytopenia). For the overwhelming majority of people, vaccines are safe and no evidence linking viral vaccines with type 1 diabetes, multiple sclerosis (MS) or inflammatory bowel disease can be found.
Collapse
Affiliation(s)
- Ami Schattner
- Department of Medicine, University of Cambridge, School of Clinical Medicine, Level 5, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
| |
Collapse
|
|
49
|
Abstract
While tremendous advances have improved the understanding of inflammatory bowel disease, with regard to environmental risk factors as well as the biochemical nature of the inflammatory process, a determination of primary etiology remains elusive. Numerous theories have been proposed in the past century concerning the cause of Crohn's disease and ulcerative colitis with implications for specific therapies. On further study, most of these ideas and therapies have failed to be accurate in theory or therapeutic approach. Others remain untested or are the focus of current investigation and controversy. This paper reviews the dominant theories of primary etiology. These hypotheses include infectious causes such as Mycobacteria paratuberculosis and measles. Allergic and nutritionally related causes have been the focus of considerable research. Microparticles, which is part of the concept behind toothpaste as a cause, have been suggested more broadly to be the principal factor initiating Crohn's disease. Several of these concepts rely on the idea that there is an increased intestinal permeability that is the central defect leading to Crohn's disease. Rather than being an excessive T cell driven process, Crohn's has been suggested to be an innate immune deficiency, leading to the use of colony stimulating factors to augment the intestinal barrier function and innate immunity. A variety of changes in the gut flora, ranging from a basic dysbiosis to the absence of helminths, have been proposed as the root cause of inflammatory bowel disease.
Collapse
Affiliation(s)
- Joshua R Korzenik
- IBD Center, Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
| |
Collapse
|
|
50
|
Sands BE, Cuffari C, Katz J, Kugathasan S, Onken J, Vitek C, Orenstein W. Guidelines for immunizations in patients with inflammatory bowel disease. Inflamm Bowel Dis 2004; 10:677-92. [PMID: 15472534 DOI: 10.1097/00054725-200409000-00028] [Citation(s) in RCA: 164] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
During the past 2 decades, medical therapy for Crohn's disease (CD) and ulcerative colitis (UC) has grown to incorporate a variety of immunesuppressing agents. At the same time, basic insights into the aberrant mucosal immune response underlying inflammatory bowel disease (IBD) have expanded dramatically. The interplay of host susceptibility to infection and the safety and efficacy of immunization for vaccine-preventable diseases has been explored in other immune-mediated disease states but only rarely in IBD. The purpose of this review is to formulate best-practice recommendations for immunization in children and adults with IBD by considering the effects of the IBD disease state and its treatments on both the safety and efficacy of immunization. To do so, we first considered the routine recommendations for immunization of children, adults and distinct populations at increased risk for vaccine-preventable disease. Because it was rarely possible to examine direct data on safety and efficacy of immunization in IBD populations, we relied to a large extent upon extrapolation from similar populations and from knowledge of basic mechanisms. The literature suggests that efficacy of immunization may be diminished in some patients whose immune status is compromised by immune suppression. However, except for live agent vaccines, most immunizations may be safely administered to patients with IBD even when immune compromised. Conversely, protection against vaccine-preventable illness may be of even greater benefit to those at risk for morbid or lethal complications of infections because of an immune compromised state. We conclude that for most patients with IBD, recommendations for immunization do not deviate from recommended schedules for the general population.
Collapse
Affiliation(s)
- Bruce E Sands
- Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | | | | | | | | | | | | |
Collapse
|