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Ingrosso DMF, Primavera M, Samvelyan S, Tagi VM, Chiarelli F. Stress and Diabetes Mellitus: Pathogenetic Mechanisms and Clinical Outcome. Horm Res Paediatr 2023; 96:34-43. [PMID: 35124671 DOI: 10.1159/000522431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 02/01/2022] [Indexed: 11/19/2022] Open
Abstract
Evidence suggests that psychological and physical stress are relevant triggering factors for the onset of type 1 diabetes (T1D) and type 2 diabetes (T2D). The underlying mechanisms involve a complex neuroendocrine structure, involving the central nervous system and the periphery. Psychological stress leads to an increase of serum glucocorticoid concentrations and catecholamines release increasing the insulin need and the insulin resistance. According to the β-cell stress hypothesis, also causes of increased insulin demand, such as rapid growth, overweight, puberty, low physical activity, trauma, infections, and glucose overload, are potentially relevant factors in development of T1D. It has also been demonstrated that chronic stress and obesity form a vicious circle which leads to a definitive metabolic failure, increasing the risk of developing T2D. In this review, we will provide the most recent data concerning the role of stress in the outcomes of T1D and T2D, with a focus on the role of physical and psychological stress on the onset of T1D.
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Affiliation(s)
| | | | - Sona Samvelyan
- Paediatric Outpatient Department No. 122, Moscow, Russian Federation
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Immunomodulatory Effect of Vitamin D and Its Potential Role in the Prevention and Treatment of Type 1 Diabetes Mellitus-A Narrative Review. Molecules 2018; 24:molecules24010053. [PMID: 30586887 PMCID: PMC6337255 DOI: 10.3390/molecules24010053] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Revised: 12/14/2018] [Accepted: 12/21/2018] [Indexed: 12/16/2022] Open
Abstract
Type 1 diabetes mellitus is a chronic autoimmune disease associated with degeneration of pancreatic β-cells that results in an inability to produce insulin and the need for exogenous insulin administration. It is a significant global health problem as the incidence of this disorder is increasing worldwide. The causes are still poorly understood, although it certainly has genetic and environmental origins. Vitamin D formed profusely in the skin upon exposure to sunlight, as well as from dietary sources, exhibits an immunomodulatory effect based on gene transcription control. Indeed, vitamin D can downregulate mechanisms connected with adaptive immunity, induce immunological tolerance and decrease auto-aggression-related inflammation. These properties provide the basis for a preventive and therapeutic role of vitamin D. As many studies have demonstrated, appropriate supplementation with vitamin D reduces the risk of autoimmune diseases, including type 1 diabetes mellitus, and alleviates disease symptoms in patients. The aim of this narrative review is to present the molecular mechanisms for the vitamin D immunomodulatory effect as well as review human clinical studies on the use of vitamin D as adjuvant therapy in type 1 diabetes mellitus.
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Mustonen N, Siljander H, Peet A, Tillmann V, Härkönen T, Ilonen J, Hyöty H, Knip M. Early childhood infections precede development of beta-cell autoimmunity and type 1 diabetes in children with HLA-conferred disease risk. Pediatr Diabetes 2018; 19:293-299. [PMID: 28597957 DOI: 10.1111/pedi.12547] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Revised: 04/13/2017] [Accepted: 05/09/2017] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND The etiology of type 1 diabetes (T1D) is largely unknown. Infections and microbial exposures are believed to play a role in the pathogenesis and in the development of islet autoimmunity in genetically susceptible individuals. OBJECTIVE To assess the relationships between early childhood infections, islet autoimmunity, and progression to T1D in genetically predisposed children. METHODS Children with human leukocyte antigen (HLA)-conferred disease susceptibility (N=790; 51.5% males) from Finland (n = 386), Estonia (n = 322), and Russian Karelia (n = 82) were observed from birth up to the age of 3 years. Children attended clinical visits at the age of 3, 6, 12, 18, 24, and 36 months. Serum samples for analyzing T1D-associated autoimmune markers were collected and health data recorded during the visits. RESULTS Children developing islet autoimmunity (n = 46, 5.8%) had more infections during the first year of life (3.0 vs 3.0, mean rank 439.1 vs 336.2; P = .001) and their first infection occurred earlier (3.6 vs 5.0 months; P = .005) than children with no islet autoimmunity. By May 2016, 7 children (0.9%) had developed T1D (progressors). Compared with non-diabetic children, T1D progressors were younger at first infection (2.2 vs 4.9 months; P = .004) and had more infections during the first 2 years of life (during each year 6.0 vs 3.0; P = .001 and P = .027, respectively). By 3 years of age, the T1D progressors had twice as many infections as the other children (17.5 vs 9.0; P = .006). CONCLUSIONS Early childhood infections may play an important role in the pathogenesis of T1D. Current findings may reflect either differences in microbial exposures or early immunological aberrations making diabetes-prone children more susceptible to infections.
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Affiliation(s)
- N Mustonen
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland
| | - H Siljander
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland
| | - A Peet
- Department of Pediatrics, University of Tartu and Tartu University Hospital, Tartu, Estonia
| | - V Tillmann
- Department of Pediatrics, University of Tartu and Tartu University Hospital, Tartu, Estonia
| | - T Härkönen
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland
| | - J Ilonen
- Immunogenetics Laboratory, University of Turku and Turku University Hospital, Turku, Finland
| | - H Hyöty
- Department of Virology, School of Medicine, University of Tampere, Tampere, Finland.,Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland
| | - M Knip
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.,Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
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Abstract
The incidence of type 1 diabetes has risen considerably in the past 30 years due to changes in the environment that have been only partially identified. In this Series paper, we critically discuss candidate triggers of islet autoimmunity and factors thought to promote progression from autoimmunity to overt type 1 diabetes. We revisit previously proposed hypotheses to explain the growth in the incidence of type 1 diabetes in light of current data. Finally, we suggest a unified model in which immune tolerance to β cells can be broken by several environmental exposures that induce generation of hybrid peptides acting as neoautoantigens.
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Affiliation(s)
- Marian Rewers
- Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA
| | - Johnny Ludvigsson
- Division of Pediatrics, Department of Clinical and Experimental Medicine, Medical Faculty, Linköping University and Linköping University Hospital, Linköping, Sweden.
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Abstract
Chronic hepatitis B virus infection affects about 400 million people around the globe and causes approximately one million deaths a year. Since the discovery of interferon-α as a therapeutic option the treatment of hepatitis B has evolved fast and management has become increasingly complicated. The amount of viral replication reflected in the viral load (HBV-DNA) plays an important role in the development of cirrhosis and hepatocellular carcinoma. The current treatment modalities for chronic hepatitis B are immunomodulatory (interferons) and antiviral suppressants (nucleoside and nucleotide analogues) all with their own advantages and limitations. An overview of the treatment efficacy for both immunomodulatory as antiviral compounds is provided in order to provide the clinician insight into the factors influencing treatment outcome. With nucleoside or nucleotide analogues suppression of viral replication by 5-7 log10 is feasible, but not all patients respond to therapy. Known factors influencing treatment outcome are viral load, ALT levels and compliance. Many other factors which might influence treatment are scarcely investigated. Identifying the factors associated with response might result in stopping rules, so treatment could be adapted in an early stage to provide adequate treatment and avoid the development of resistance. The efficacy of compounds for the treatment of mutant virus and the cross-resistance is largely unknown. However, genotypic and phenotypic testing as well as small clinical trials provided some data on efficacy in this population. Discontinuation of nucleoside or nucleotide analogues frequently results in viral relapse; however, some patients have a sustained response. Data on the risk factors for relapse are necessary in order to determine when treatment can be discontinued safely. In conclusion: chronic hepatitis B has become a treatable disease; however, much research is needed to tailor therapy to an individual patient, to predict the sustainability of response and determine the best treatment for those failing treatment.
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Affiliation(s)
- W F Leemans
- Department of Gastroenterology and Hepatology, Room H 437, Erasmus MC, University Medical Center Rotterdam's-Gravendijkwal 230, Rotterdam, The Netherlands
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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.
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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.
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Abstract
BACKGROUND A link between childhood vaccinations and the development of type 1 diabetes has been proposed. METHODS We evaluated a cohort comprising all children born in Denmark from January 1, 1990, through December 31, 2000, for whom detailed information on vaccinations and type 1 diabetes was available. Using Poisson regression models, we estimated rate ratios according to vaccination status, including the trend associated with the number of doses, among all children and in a subgroup of children who had siblings with type 1 diabetes. Given recent claims of clustering of cases of diabetes two to four years after vaccination, we also estimated rate ratios during the period after vaccination. RESULTS Type 1 diabetes was diagnosed in 681 children during 4,720,517 person-years of follow-up. The rate ratio for type 1 diabetes among children who received at least one dose of vaccine, as compared with unvaccinated children, was 0.91 (95 percent confidence interval, 0.74 to 1.12) for Haemophilus influenzae type b vaccine; 1.02 (95 percent confidence interval, 0.75 to 1.37) for diphtheria, tetanus, and inactivated poliovirus vaccine; 0.96 (95 percent confidence interval, 0.71 to 1.30) for diphtheria, tetanus, acellular pertussis, and inactivated poliovirus vaccine; 1.06 (95 percent confidence interval, 0.80 to 1.40) for whole-cell pertussis vaccine; 1.14 (95 percent confidence interval, 0.90 to 1.45) for measles, mumps, and rubella vaccine; and 1.08 (95 percent confidence interval, 0.74 to 1.57) for oral poliovirus vaccine. The development of type 1 diabetes in genetically predisposed children (defined as those who had siblings with type 1 diabetes) was not significantly associated with vaccination. Furthermore, there was no evidence of any clustering of cases two to four years after vaccination with any vaccine. CONCLUSIONS These results do not support a causal relation between childhood vaccination and type 1 diabetes.
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Affiliation(s)
- Anders Hviid
- Danish Epidemiology Science Centre, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
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Affiliation(s)
- Philippe Duclos
- Immunization Safety Priority Project, Department of Vaccines and Biologicals, Health Technology and Pharmaceuticals, World Health Organization, 20 Avenue Appia, CH-1211 Geneva 27, Switzerland.
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Duclos P. Safety of immunisation and adverse events following vaccination against hepatitis B. Expert Opin Drug Saf 2003; 2:225-31. [PMID: 12904102 DOI: 10.1517/14740338.2.3.225] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Hepatitis B vaccines (HBVs) are composed of highly purified preparations of hepatitis B virus surface antigen (HBsAg). An adjuvant, either aluminium phosphate or aluminium hydroxide, is added to the vaccines, which are sometimes preserved with thiomersal. In placebo-controlled studies, common side effects other than local reactions were reported no more frequently among vaccine recipients than among individuals receiving a placebo. A number of controversial adverse events have, however, been purported to be associated with HBVs, including rheumatoid arthritis (RA), diabetes, demyelinating diseases (e.g., multiple sclerosis [MS]), chronic fatigue syndrome, and more recently, lymphoblastic leukaemia. In addition, the safety of the thiomersal and aluminium contained in the vaccine has also been under close scrutiny. These issues have been reviewed by a number of country-specific or international independent review committees such as that of the US Institute of Medicine (IOM) and the World Health Organization's (WHO) Global Advisory Committee on Vaccine Safety (GACVS). Upon review of the scientific evidence, none of the serious allegations have so far been confirmed. On the contrary, scientific evidence has accumulated to disprove many of the allegations. In particular, the IOM committee has concluded that the evidence favoured rejection of a causal relationship between HBV administered to adults and incident MS or MS relapse. Whilst it is important to continue monitoring some of the safety issues, there is no evidence to suggest that the WHO should consider altering its recommendation that all countries should have universal infant and/or adolescent immunisation programmes. The risks of hepatitis B vaccination are only theoretical in comparison with clear benefits in terms of cirrhosis and cancer prevention, and the HBV remains one with an excellent safety profile.
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Affiliation(s)
- Philippe Duclos
- Department of Vaccines and Biologicals, Health Technology and Pharmaceuticals, World Health Organization, Geneva, 20 Avenue Appia, CH-1211 Geneva 27, Switzerland.
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Abstract
The end of the 20th century saw the realization of a goal that was previously only dreamed about: the near elimination of many deadly infectious diseases through universal vaccination. As one disease after another has been driven from memory, it is vaccination programs themselves that have come to occupy the public's mind. With increased scrutiny comes the promise that vaccines will become even safer, but there is also the threat that ill-founded concerns will result in reduced immunization rates, and diseases will resurge. This article reviews scientific data relating to current vaccine safety concerns.
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Affiliation(s)
- G S Marshall
- Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky 40202-3818, USA
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DeStefano F, Mullooly JP, Okoro CA, Chen RT, Marcy SM, Ward JI, Vadheim CM, Black SB, Shinefield HR, Davis RL, Bohlke K. Childhood vaccinations, vaccination timing, and risk of type 1 diabetes mellitus. Pediatrics 2001; 108:E112. [PMID: 11731639 DOI: 10.1542/peds.108.6.e112] [Citation(s) in RCA: 81] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVES To evaluate suggested associations between childhood vaccinations, particularly against hepatitis B and Haemophilus influenzae type b, and risk of developing type 1 diabetes; and to determine whether timing of vaccination influences risk. METHODS We conducted a case-control study within 4 health maintenance organizations (HMOs) that participate in the Vaccine Safety Datalink project of the Centers for Disease Control and Prevention. Study eligibility was restricted to children who met the following criteria: 1) born during 1988 through 1997; 2) HMO member since birth; 3) continuously enrolled for first 6 months of life; and 4) at least 12 months of HMO membership before diabetes incidence date (or index date for controls) unless incidence date was before 12 months of age. All 4 HMOs maintain registries of their members who have diabetes, and we used the registries to identify potential cases of diabetes. We conducted chart reviews to verify that potential cases met the World Health Organization epidemiologic case definition for type 1 diabetes mellitus (ie, a physician's diagnosis of diabetes plus treatment with daily insulin injections). We defined the incidence date of diabetes as the first date that the child received a diagnosis of diabetes. We attempted to match 3 controls to each case. Controls had the same eligibility criteria as cases and were matched to individual cases on HMO, sex, date of birth (within 7 days), and length of health plan enrollment (up to the incidence or index date). The index date for controls was defined as the incidence date of the case to which the control was matched. Chart abstraction was performed by trained chart abstractors using standardized forms. In addition to complete vaccination histories, the chart abstraction forms for both cases and controls included information on sociodemographic characteristics, selected medical conditions, history of breastfeeding, and family medical history. We used conditional logistic regression to estimate the odds ratio (OR) of diabetes associated with vaccination, with vaccine exposure defined as before the diabetes incidence date (or index date for controls). RESULTS Two hundred fifty-two confirmed cases of diabetes and 768 matched controls met the study eligibility criteria. The OR (95% confidence interval) for the association with type 1 diabetes was 0.28 (0.07-1.06) for whole cell pertussis vaccine (predominantly in combination as diphtheria, tetanus toxoids and pertussis vaccine), 1.36 (0.70-2.63) for measles-mumps-rubella, 1.14 (0.51-2.57) for Haemophilus influenzae type b, 0.81 (0.52-1.27) for hepatitis B vaccine, 1.16 (0.72-1.89) for varicella vaccine, and 0.92 (0.53-1.57) for acellular pertussis-containing vaccines. Compared with children who had not received hepatitis B vaccine, the OR of diabetes was 0.51 (0.23-1.15) for children vaccinated at birth and 0.86 (0.54-1.35) for those first vaccinated against hepatitis B at 2 months of age or later. Race and ethnicity and family history of diabetes were independently associated with risk of type 1 diabetes, but adjustment for these factors did not materially alter the ORs for any of the vaccines. CONCLUSIONS In this large, population-based, case-control study, we did not find an increased risk of type 1 diabetes associated with any of the routinely recommended childhood vaccines. Our study adds to previous research by providing data on newer vaccines, including hepatitis B, acellular pertussis, and varicella vaccines. For the older vaccines, our results are generally in agreement with previous studies in not finding any increased risks. Ours is the first epidemiologic study to evaluate the possibility that timing of vaccination is related to risk of clinical diabetes in children. Our results on hepatitis B vaccine do not support the hypothesis; risk of type 1 diabetes was not different between infants vaccinated at birth and those who received their first vaccination later in life. The results of our study and the preponderance of epidemiologic evidence do not support an association between any of the recommended childhood vaccines and an increased risk of type 1 diabetes. Suggestions that diabetes risk in humans may be altered by changes in the timing of vaccinations also are unfounded.
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Affiliation(s)
- F DeStefano
- National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia 30341-3724, USA.
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Abstract
The safety of vaccines is an issue that has been with us ever since Jenner, and it will not go away. The author argues that despite what may seem a waste of energy, most proposed relationships between vaccines and reactions must be thoroughly investigated, as some have been proved correct. Investigations that show the putative relationship to be incorrect serve as examples of scientific rigor, which are valuable for the public. The author draws eight lessons for the future from our recent experiences.
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Affiliation(s)
- S A Plotkin
- Wistar Institute, University of Pennsylvania, Aventis Pasteur, 4650 Wismer Road, Doylestown, PA 18901, USA.
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Dennehy PH. Active immunization in the United States: developments over the past decade. Clin Microbiol Rev 2001; 14:872-908, table of contents. [PMID: 11585789 PMCID: PMC89007 DOI: 10.1128/cmr.14.4.872-908.2001] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The Centers for Disease Control and Prevention has identified immunization as the most important public health advance of the 20th century. The purpose of this article is to review the changes that have taken place in active immunization in the United States over the past decade. Since 1990, new vaccines have become available to prevent five infectious diseases: varicella, rotavirus, hepatitis A, Lyme disease, and Japanese encephalitis virus infection. Improved vaccines have been developed to prevent Haemophilus influenzae type b, pneumococcus, pertussis, rabies, and typhoid infections. Immunization strategies for the prevention of hepatitis B, measles, meningococcal infections, and poliomyelitis have changed as a result of the changing epidemiology of these diseases. Combination vaccines are being developed to facilitate the delivery of multiple antigens, and improved vaccines are under development for cholera, influenza, and meningococcal disease. Major advances in molecular biology have enabled scientists to devise new approaches to the development of vaccines against diseases ranging from respiratory viral to enteric bacterial infections that continue to plague the world's population.
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Affiliation(s)
- P H Dennehy
- Division of Pediatric Infectious Diseases, Rhode Island Hospital, Providence, Rhode Island 02903, USA.
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Abstract
In order for vaccinations to 'work', the immune system must be stimulated. The concern that immunizations may lead to the development of autoimmune disease (AID) has been questioned. Since AID occur in the absence of immunizations, it is unlikely that immunizations are a major cause of AID. Epidemiological studies are needed, however, to assess whether immunizations may increase the risk in some susceptible individuals. This paper discusses the evidence for and against vaccination as a risk factor for AID. Evidence for immunizations leading to AID come from several sources including animal studies, single and multiple case reports, and ecologic association. However more rigorous investigation has failed to confirm most of the allegations. Unfortunately the question remains difficult to address because for most AIDs, there is limited knowledge of the etiology, background incidence and other risk factors for their development. This information is necessary, in the absence of experimental evidence derived from controlled studies, for any sort of adequate causality assessment using the limited data that are available. Several illustrative examples are discussed to highlight what is known and what remains to be explored, and the type of epidemiological evidence that would be required to better address the issues. Examples include the possible association of immunization and multiple sclerosis (and other demyelinating diseases), type 1 diabetes mellitus, Guillain-Barre Syndrome, idiopathic thrombocytopenic purpura, and rheumatoid arthritis.
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Affiliation(s)
- R T Chen
- Vaccine Safety and Development Activity, National Immunization Program, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
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Chen RT, DeStefano F, Pless R, Mootrey G, Kramarz P, Hibbs B. Challenges and controversies in immunization safety. Infect Dis Clin North Am 2001; 15:21-39, viii. [PMID: 11301817 DOI: 10.1016/s0891-5520(05)70266-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
No vaccine is perfectly safe or effective. As diseases such as diphtheria and polio fade, vaccine safety concerns, especially alleged links between vaccinations and several chronic illnesses, have become increasingly prominent in the media and to the public. This article reviews the current scientific evidence on several recent vaccine safety controversies. It also provides information on how various safety research is conducted, some of the concurrent challenges, and finally, some guidance on communicating with patients on vaccine risks.
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Affiliation(s)
- R T Chen
- National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
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Abstract
Both genetic and environmental factors contribute to the development of autoimmunity. Animals and humans exposed to natural infections have a reduced rate of autoimmune diseases. There is increasing evidence that immune stimulation prevents autoimmune diseases. Our hypothesis is that the process of the development of pathogenic cells involved in autoimmunity can be modulated by early stimulation of the immune system in autoimmunity prone individuals This allows for the upregulation of cytokines and growth factors that influence the generation of regulatory cells involved in autoimmunity. As we live in a 'cleaner environment' the decreasing chances of natural infection in the general population may contribute to the induction of autoimmunity because the developing immune system is not exposed to stimulation that may be necessary to generate regulatory cells involved in the modulation and prevention of autoimmunity. Immunization with certain vaccines may provide an alternative approach to stimulate the immune system to modulate or prevent the generation of pathogenic cells involved in autoimmunity by induction of regulatory cells.
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Affiliation(s)
- B Singh
- Department of Microbiology & Immunology, University of Western Ontario and John P. Robarts Research Institute, London, Ontario, N6A 5C1, Canada.
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