RESUMO
BACKGROUND AND AIM: Thimerosal (THIM) is a mercury-containing preservative widely used in many biological and medical products including many vaccines. It has been accused of being a possible etiological factor for some neurodevelopmental disorders such as autistic spectrum disorders (ASDs). In our study, the potential therapeutic effect of montelukast, a leukotriene receptor antagonist used to treat seasonal allergies and asthma, on THIM mice model (ASDs model) was examined. METHODOLOGY: Newborn mice were randomly distributed into three groups: (Group 1) Control (Cont.) group received saline injections. (Group 2) THIM-treated (THIM) group received THIM intramuscular (IM) at a dose of 3000 µg Hg/kg on postnatal days 7, 9, 11, and 15. (Group 3) Montelukast-treated (Monte) group received THIM followed by montelukast sodium (10 mg/kg/day) intraperitoneal (IP) for 3 weeks. Mice were evaluated for growth development, social interactions, anxiety, locomotor activity, and cognitive function. Brain histopathology, alpha 7 nicotinic acetylcholine receptors (α7nAChRs), nuclear factor kappa B p65 (NF-κB p65), apoptotic factor (Bax), and brain injury markers were evaluated as well. RESULTS: THIIM significantly impaired social activity and growth development. Montelukast mitigated THIM-induced social deficit probably through α7nAChRs upregulation, NF-κB p65, Bax, and brain injury markers downregulation, thus suppressing THIM-induced neuronal toxicity and inflammation. CONCLUSION: Neonatal exposure to THIM can induce growth retardation and abnormal social interactions similar to those observed in ASDs. Some of these abnormalities could be ameliorated by montelukast via upregulation of α7nAChRs that inhibited NF-κB activation and significant suppression of neuronal injury and the associated apoptosis.
Assuntos
Acetatos/uso terapêutico , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/tratamento farmacológico , Ciclopropanos/uso terapêutico , Quinolinas/uso terapêutico , Comportamento Social , Sulfetos/uso terapêutico , Timerosal/administração & dosagem , Timerosal/efeitos adversos , Acetatos/administração & dosagem , Acetatos/farmacologia , Animais , Animais Recém-Nascidos , Transtorno Autístico/patologia , Ciclopropanos/administração & dosagem , Ciclopropanos/farmacologia , Crescimento e Desenvolvimento/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/ultraestrutura , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Quinolinas/administração & dosagem , Quinolinas/farmacologia , Sulfetos/administração & dosagem , Sulfetos/farmacologia , Fator de Transcrição RelA/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismoRESUMO
BACKGROUND: Thimerosal has been used as a preservative in many products which may cause contact dermatitis. It is the second most common allergen in positive patch test reactions, though being a clinical irrelevant allergen. Thimerosal-induced contact dermatitis is generally considered to be a delayed-type hypersensitivity reaction, but it is difficult to explain the fact that most patients develop an allergic reaction upon first encounter with thimerosal. Recent studies have demonstrated the association between Mas-related G protein coupled receptor X2 (MRGPRX2) and pseudo-allergic reactions which occur at the first contact with stimulation. This suggests the possibility that thimerosal may cause contact dermatitis via MRGPRX2 mediated mechanism. OBJECTIVES: To investigate the role of Mas-related G-protein coupled receptor B2 (MrgprB2)/MRGPRX2 in contact dermatitis induced by thimerosal. METHODS: Thimerosal induced pseudo-allergic reactions via MrgprB2/ MRGPRX2 were investigated using a novel skin pseudo-allergic reaction mouse model, footpad swelling and extravasation assays in vivo and mast cell degranulation assay in vitro. RESULTS: Thimerosal induced contact dermatitis in dorsal skin and footpad swelling in wild-type mice, but had no significant effect in MrgprB2-knockout mice. Thimerosal-induced dermatitis is characterized by infiltration of inflammatory cells and elevation of serum histamine and inflammatory cytokines, rather than elevation of serum IgE level. Thimerosal increased the intracellular Ca2+ concentration in HEK293 cells overexpressing MrgprB2/MRGPRX2. Downregulation of MRGPRX2 resulted in the reduced degranulation of LAD2 human mast cells. CONCLUSIONS: MrgprB2 mediates thimerosal-induced mast cell degranulation and pseudo-allergic reaction in mice. MRGPRX2 may be a key contributor to human contact dermatitis.
Assuntos
Dermatite de Contato/etiologia , Hipersensibilidade Tardia/etiologia , Mastócitos/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Conservantes Farmacêuticos/toxicidade , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropeptídeos/metabolismo , Timerosal/efeitos adversos , Administração Cutânea , Animais , Degranulação Celular/efeitos dos fármacos , Dermatite de Contato/patologia , Modelos Animais de Doenças , Células HEK293 , Humanos , Hipersensibilidade Tardia/patologia , Masculino , Mastócitos/patologia , Camundongos , Camundongos Knockout , Conservantes Farmacêuticos/administração & dosagem , Receptores Acoplados a Proteínas G/genética , Timerosal/administração & dosagemRESUMO
BACKGROUND: Patch testing is the "gold standard" to identify culprit allergen(s) causing allergic contact dermatitis (ACD), but there are limited studies of patch testing from allergy practice settings. OBJECTIVE: We sought to explore patch test findings in a large academic allergy practice, including patch testing results, history of atopy, location of dermatitis, and referral source. We also wanted to determine whether patch testing using an extended panel, such as the North American screening series, compared with a limited series, such as the Thin-Layer Rapid-Use Epicutaneous (T.R.U.E.) Test, increased the sensitivity. METHODS: A retrospective chart review was conducted of patients referred for patch testing over a 6-year period. RESULTS: A total of 585 patients (mean age 48.7 years, 71.6 % female) underwent patch testing over the 6-year period, of which 369 (63%) had a positive test. Of those who tested positive, 202 (55%) reported a history of atopy. The extremities were the most commonly involved site, followed by the head/neck and trunk. The 5 most common positive allergens were nickel sulfate, gold sodium thiosulfate, methylchloroisothiazolinone, thimerosal, and bacitracin. Three hundred fourteen (53.6%) patients were positive to at least 1 allergen on TRUE testing. Extended screening series identified an additional 10.8% of patients with positive tests who were negative to T.R.U.E. test allergens. CONCLUSION: Patch testing is a valuable diagnostic tool for the practicing allergist and provides early identification of culprit allergens in ACD. Performing an extended screening series such as the North American Contact Dermatitis Group (NACDG) or supplemental panel of allergens increased sensitivity when compared with a limited series.
Assuntos
Alérgenos/administração & dosagem , Dermatite Alérgica de Contato/diagnóstico , Testes do Emplastro , Pele/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacitracina/administração & dosagem , Criança , Pré-Escolar , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/fisiopatologia , Feminino , Tiossulfato Sódico de Ouro/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Níquel/administração & dosagem , Estudos Retrospectivos , Pele/imunologia , Pele/fisiopatologia , Tiazóis/administração & dosagem , Timerosal/administração & dosagemRESUMO
Investigators postulated that early-life exposure to organic mercury (Hg) significantly increases the risk of childhood neurodevelopmental disorders (NDs). The Vaccine Adverse Event Reporting System database was utilized to conduct a hypothesis testing case-control study by evaluating 3486 total adverse event reports reported following Haemophilus influenza type b (Hib) vaccination. Exposed subjects received a Thimerosal-containing formulation (HIBTITER™, Wyeth-Lederle), while unexposed subjects received a Thimerosal-free formulation (PEDVAXHIB™, Merck). Subjects were included if they received either of these two Hib vaccine formulations between 1995 and 1999. Cases were defined as adverse event reports with a reported outcome of autism, developmental delay, psychomotor delay, or NDs in general. Cases with reported outcomes of febrile convulsions, pyrexia, or injection site pain, all of which have no biologically plausible relation to Hg exposure, were also examined. Controls were defined as adverse event reports without any mention of the specific case outcome examined. Cases of reported autism (odds ratio (OR)â¯=â¯2.75, pâ¯<â¯0.02), developmental delay (ORâ¯=â¯5.39, pâ¯<â¯0.01), psychomotor disorder (ORâ¯=â¯2.38, pâ¯<â¯0.03), and neurodevelopmental disorder in general (ORâ¯=â¯2.70, pâ¯<â¯0.001) were each significantly more likely than their respective controls to receive Thimerosal-containing Hib vaccine than Thimerosal-free Hib vaccine. Significant effects for neurodevelopmental disorder in general were observed for males (ORâ¯=â¯2.52, pâ¯<â¯0.005), but not females when separated by gender. For the outcomes that had no biologically plausible relation to Hg exposure, the cases were no more likely than their respective controls to receive Thimerosal-containing Hib vaccine than Thimerosal-free Hib vaccine. This study provides suggestive evidence of an association between Thimerosal and neurodevelopmental outcomes and provides support for carrying out additional well-designed studies examining the association between Thimerosal-containing vaccines and a wide range of neurodevelopmental outcomes.
Assuntos
Vacinas Anti-Haemophilus/administração & dosagem , Transtornos do Neurodesenvolvimento/epidemiologia , Conservantes Farmacêuticos/administração & dosagem , Timerosal/administração & dosagem , Sistemas de Notificação de Reações Adversas a Medicamentos , Cápsulas Bacterianas , Feminino , Humanos , Lactente , Masculino , Razão de Chances , Risco , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: Helicobacter pylori infection is due to the high prevalence in population attracts the clinical interest of researchers in the whole World. It is well known that this microorganism not only resides in the mucosa of the gastrointestinal tract, but is also defined in the periodontal pocket of the oral cavity. THE AIM OF INVESTIGATION: to evaluate Helicobacter pylori diagnostics in the mouth and prove a method of relief of the inflammatory process by applying immunomodulator Imudon. RESULTS. On the basis of obtained results it was found that the inclusion of topical immunomodulator Imudon in the complex therapy of Helicobacter pylori-associated diseases leads to reduction of inflammatory potential through the decrease of the TNFα, IL-6 activity in saliva and to increase the protective properties of saliva as a result of increased levels of mucin, significantly reduces the frequency of relapses in the one year after therapy. CONCLUSION: It is practically important to determine the effectiveness of eradication therapy by the study of the contents of the tooth-gingival pocket for the detection of genetic material of Helicobacter pylori, as well as to include in the complex therapy of Helicobacter pylori-associated diseases of the immune modulator Imudon.
Assuntos
Antígenos de Bactérias/uso terapêutico , Antígenos de Fungos/uso terapêutico , Úlcera Duodenal/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Saliva/metabolismo , Timerosal/uso terapêutico , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antígenos de Bactérias/administração & dosagem , Antígenos de Fungos/administração & dosagem , Combinação de Medicamentos , Quimioterapia Combinada , Úlcera Duodenal/tratamento farmacológico , Úlcera Duodenal/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Interleucina-6/imunologia , Interleucina-6/metabolismo , Masculino , Saliva/imunologia , Timerosal/administração & dosagem , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
A latency period preceding neurotoxicity is a common characteristic in the dose-response relationship induced by organic mercury. Latency periods have typically been observed with genotoxicants in carcinogenesis, with cancer being manifested a long time after the initiating event. These observations indicate that even a very small dose may cause extensive adverse effects later in life, so the toxicity of the genotoxic compound is dose and time-dependent. In children, methylmercury exposure during pregnancy (in utero) has been associated with delays in reaching developmental milestones (e.g., age at first walking) and decreases in intelligence, increasing in severity with increasing exposure. Ethylmercury exposure from thimerosal in some vaccines has been associated, in some studies, with autism and other neurological disorders in children. In this paper, we have examined whether dose-response data from in vitro and in vivo organic mercury toxicity studies fit the Druckrey-Küpfmüller equation c·t(n)=constant (c=exposure concentration, t=latency period), first established for genotoxic carcinogens, and whether or not irreversible effects are enhanced by time of exposure (n≥1), or else toxic effects are dose-dependent while time has only minor influence on the adverse outcome (n<1). The mode of action underlying time-dependent toxicity is irreversible binding to critical receptors causing adverse and cumulative effects. The results indicate that the Druckrey-Küpfmüller equation describes well the dose-response characteristics of organic mercury induced neurotoxic effects. This amounts to a paradigm shift in chemical risk assessment of mercurial compounds and highlights that it is vital to perform toxicity testing geared to investigate time-dependent effects.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Compostos de Metilmercúrio/toxicidade , Síndromes Neurotóxicas , Animais , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Mercúrio/administração & dosagem , Mercúrio/metabolismo , Mercúrio/toxicidade , Compostos de Metilmercúrio/administração & dosagem , Compostos de Metilmercúrio/metabolismo , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Gravidez , Timerosal/administração & dosagem , Timerosal/metabolismo , Timerosal/toxicidade , Testes de Toxicidade/métodos , Testes de Toxicidade/normasRESUMO
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD.
Assuntos
Transtorno Autístico/diagnóstico , Encefalopatias/diagnóstico , Timerosal/administração & dosagem , Vacinas/administração & dosagem , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Animais Recém-Nascidos , Transtorno Autístico/induzido quimicamente , Western Blotting , Encefalopatias/induzido quimicamente , Calbindinas/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Glutamato Descarboxilase/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Imuno-Histoquímica , Macaca mulatta , Masculino , Proteínas dos Microfilamentos/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuropatologia/métodos , Conservantes Farmacêuticos/administração & dosagem , Conservantes Farmacêuticos/efeitos adversos , Timerosal/efeitos adversos , Fatores de Tempo , Vacinação/métodos , Vacinas/efeitos adversosRESUMO
Thiomersal is an organomercury compound known for its antiseptic and antifungal properties and used as an antibacterial agent in pharmaceutical products, including vaccines and other injectable biological products. In recent years, concerns about the possible link between immunization with thiomersal-containing vaccines and autism development have grown. Many case-control and cohort studies have been conducted on a number of populations, and none of them have confirmed the hypothetical relation between thiomersal and increased risk of autism spectrum disorders (ASDs) development. It is also confirmed by the fact, that since 1999, number of thiomersal-containing vaccines used worldwide is decreasing year by year, while the prevalence of ASDs cases is rising. There are no contraindications to the use of vaccines with thiomersal in infants, children and non-pregnant women. The risk of serious complications associated with the development of diseases in unvaccinated individuals far outweighs the potential risk of adverse consequences associated with immunization with thiomersal-containing vaccines.
Assuntos
Transtorno Autístico/induzido quimicamente , Deficiências do Desenvolvimento/induzido quimicamente , Conservantes Farmacêuticos/efeitos adversos , Timerosal/efeitos adversos , Vacinas/efeitos adversos , Transtorno Autístico/prevenção & controle , Criança , Deficiências do Desenvolvimento/prevenção & controle , Hipersensibilidade a Drogas/epidemiologia , Medicina Baseada em Evidências , Humanos , Conservantes Farmacêuticos/administração & dosagem , Timerosal/administração & dosagem , Vacinas/administração & dosagemRESUMO
OBJECTIVE: This case-control study investigated the relationship between the risk of Autism Spectrum Disorder (ASD) onset, and early exposure to the combined Measles-Mumps-Rubella (MMR) vaccine and thimerosal consumption measured from vaccinations in the highly genetically homogenous Japanese population. METHODS: Vaccination histories at 1, 3, 6, 12, 18, 24, and 36 months from birth were investigated in ASD cases (189 samples), and controls (224 samples) matching age and sex in each case. Crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to determine relationship between MMR vaccination and ASD. The differences in mean values of the thimerosal dosage between cases and controls were analyzed using an unpaired t-test. MMR vaccination and thimerosal dosage were also investigated using a conditional multiple-regression model. RESULTS: There were no significant differences in MMR vaccination and thimerosal dosage between cases and controls at any age. Furthermore, the ORs (95% CIs) of MMR vaccination and thimerosal dosage associated with ASD in the conditional multiple regression model were, respectively, 0.875 (0.345-2.222) and 1.205 (0.862-1.683) at age 18 months, 0.724 (0.421-1.243) and 1.343 (0.997-1.808) at 24 months, and 1.040 (0.648-1.668) and 0.844 (0.632-1.128) at 36 months. Thus, there were no significant differences. CONCLUSIONS: No convincing evidence was found in this study that MMR vaccination and increasing thimerosal dose were associated with an increased risk of ASD onset.
Assuntos
Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/epidemiologia , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Vacina contra Sarampo-Caxumba-Rubéola/efeitos adversos , Conservantes Farmacêuticos/efeitos adversos , Timerosal/administração & dosagem , Timerosal/efeitos adversos , Adulto , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Conservantes Farmacêuticos/administração & dosagem , Medição de RiscoRESUMO
BACKGROUND: To evaluate the safety and immunogenicity of the thiomersal-free (TF) and thiomersal-containing (TC) formulations of Hepavax-Gene in healthy Vietnamese neonates. METHODS: A single-blind, randomized, controlled study in Ho Chi Minh City, Vietnam. Healthy infants, born after a normal gestational period (37-42 weeks) to hepatitis B surface antigen-negative mothers, participated in the study. Subjects were randomly allocated in a 1:1 ratio to receive either Hepavax-Gene TC or Hepavax-Gene TF using a standard 0-1-6-month administration schedule. Postvaccination blood samples were taken at months 1, 6 and 7. Parents/legal guardians recorded solicited local and systemic adverse events up to 4 weeks after each vaccination. RESULTS: Very high proportions of subjects were seroprotected. Seroprotection rates at 1, 6 and 7 months were all above 95% using a 10 IU/L cutoff, and were mostly above 90% using a 100 IU/L cutoff. Seroprotection rates between the 2 formulations were equivalent within a 5% margin for either cutoff titer both after 6 and 7 months. There were no significant differences in the number of adverse events reported between the 2 formulations. Safety results were in line with previous reports for Hepavax-Gene. Both formulations of Hepavax-Gene were well tolerated. There were no local adverse events reported in the TF group. No serious adverse events were reported during the study. CONCLUSIONS: The thiomersal-free formulation of Hepavax-Gene was noninferior to the thiomersal-containing formulation of Hepavax-Gene in terms of immunogenicity. There was evidence that the thiomersal-free vaccine was associated with fewer local adverse events.
Assuntos
Vacinas contra Hepatite B/efeitos adversos , Vacinas contra Hepatite B/imunologia , Anti-Infecciosos/administração & dosagem , Química Farmacêutica , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Voluntários Saudáveis , Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos , Método Simples-Cego , Timerosal/administração & dosagem , Vacinação/métodos , VietnãRESUMO
Thimerosal is an organic mercury (Hg)-containing compound (49.55 % Hg by weight) historically added to many multi-dose vials of vaccine as a preservative. A hypothesis testing case-control study evaluated automated medical records in the Vaccine Safety Datalink (VSD) for organic Hg exposure from Thimerosal in Haemophilus influenzae type b (Hib)-containing vaccines administered at specific times within the first 15 months of life among subjects diagnosed with pervasive developmental disorder (PDD) (n = 534) in comparison to controls. The generally accepted biologically non-plausible linkage between Thimerosal exposure and subsequent diagnosis of febrile seizure (n = 5886) was examined as a control outcome. Cases diagnosed with PDD received significantly more organic Hg within the first 6 months of life (odds ratio (OR) = 1.97, p < 0.001) and first 15 months of life (OR = 3.94, p < 0.0001) than controls, whereas cases diagnosed with febrile seizure were no more likely than controls to have received increased organic Hg. On a per microgram of organic Hg basis, cases diagnosed with a PDD in comparison to controls were at significantly greater odds (OR = 1.0197, p < 0.0001) of receiving increasing organic Hg exposure within the first 15 months of life, whereas cases diagnosed febrile seizure were no more likely than controls (OR = 0.999, p > 0.20) to have received increasing organic Hg exposure within the first 15 months of life. Routine childhood vaccination is an important public health tool to reduce the morbidity and mortality associated with infectious diseases, but the present study provides new epidemiological evidence of a significant relationship between increasing organic Hg exposure from Thimerosal-containing vaccines and the subsequent risk of PDD diagnosis in males and females.
Assuntos
Transtornos Globais do Desenvolvimento Infantil , Vacinas Anti-Haemophilus/efeitos adversos , Haemophilus influenzae tipo b , Conservantes Farmacêuticos/efeitos adversos , Convulsões Febris , Timerosal/efeitos adversos , Idade de Início , Estudos de Casos e Controles , Transtornos Globais do Desenvolvimento Infantil/induzido quimicamente , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Transtornos Globais do Desenvolvimento Infantil/mortalidade , Pré-Escolar , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Humanos , Masculino , Conservantes Farmacêuticos/administração & dosagem , Convulsões Febris/induzido quimicamente , Convulsões Febris/diagnóstico , Convulsões Febris/mortalidade , Timerosal/administração & dosagem , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
In 2004, the US Center for Disease Control (CDC) published a paper showing that there is no link between the age at which a child is vaccinated with MMR and the vaccinated children's risk of a subsequent diagnosis of autism. One of the authors, William Thompson, has now revealed that statistically significant information was deliberately omitted from the paper. Thompson first told Dr S Hooker, a researcher on autism, about the manipulation of the data. Hooker analysed the raw data from the CDC study afresh. He confirmed that the risk of autism among African American children vaccinated before the age of 2 years was 340% that of those vaccinated later.
Assuntos
Países em Desenvolvimento , Controle de Medicamentos e Entorpecentes , Disparidades em Assistência à Saúde , Mercúrio/administração & dosagem , Discriminação Social , Timerosal/administração & dosagem , Vacinas/administração & dosagem , HumanosRESUMO
A hypothesis testing case-control study evaluated concerns about the toxic effects of organic-mercury (Hg) exposure from thimerosal-containing (49.55% Hg by weight) vaccines on the risk of neurodevelopmental disorders (NDs). Automated medical records were examined to identify cases and controls enrolled from their date-of-birth (1991-2000) in the Vaccine Safety Datalink (VSD) project. ND cases were diagnosed with pervasive developmental disorder (PDD), specific developmental delay, tic disorder or hyperkinetic syndrome of childhood. In addition, putative non-thimerosal-related outcomes of febrile seizure, failure to thrive and cerebral degenerations were examined. The cumulative total dose of Hg exposure from thimerosal-containing hepatitis B vaccine (T-HBV) administered within the first six months of life was calculated. On a per microgram of organic-Hg basis, PDD (odds ratio (OR) = 1.054), specific developmental delay (OR = 1.035), tic disorder (OR = 1.034) and hyperkinetic syndrome of childhood (OR = 1.05) cases were significantly more likely than controls to receive increased organic-Hg exposure. By contrast, none of the non-thimerosal related outcomes were significantly more likely than the controls to have received increased organic-Hg exposure. Routine childhood vaccination may be an important public health tool to reduce infectious disease-associated morbidity/mortality, but the present study significantly associates organic-Hg exposure from T-HBV with an increased risk of an ND diagnosis.
Assuntos
Deficiências do Desenvolvimento/epidemiologia , Vacinas contra Hepatite B/efeitos adversos , Conservantes Farmacêuticos/efeitos adversos , Timerosal/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estudos de Casos e Controles , Criança , Transtornos Globais do Desenvolvimento Infantil/induzido quimicamente , Transtornos Globais do Desenvolvimento Infantil/epidemiologia , Pré-Escolar , Deficiências do Desenvolvimento/induzido quimicamente , Relação Dose-Resposta a Droga , Feminino , Vacinas contra Hepatite B/administração & dosagem , Humanos , Lactente , Masculino , Conservantes Farmacêuticos/administração & dosagem , Timerosal/administração & dosagem , Transtornos de Tique/induzido quimicamente , Transtornos de Tique/epidemiologia , Estados Unidos/epidemiologiaRESUMO
When addressing toxins, one unmistakable parallel exists between biology and politics: developing children and developing nations are those most vulnerable to toxic exposures. This disturbing parallel is the subject of this critical review, which examines the use and distribution of the mercury (Hg)-based compound, thimerosal, in vaccines. Developed in 1927, thimerosal is 49.55% Hg by weight and breaks down in the body into ethyl-Hg chloride, ethyl-Hg hydroxide and sodium thiosalicylate. Since the early 1930s, there has been evidence indicating that thimerosal poses a hazard to the health of human beings and is ineffective as an antimicrobial agent. While children in the developed and predominantly western nations receive doses of mostly no-thimerosal and reduced-thimerosal vaccines, children in the developing nations receive many doses of several unreduced thimerosal-containing vaccines (TCVs). Thus, thimerosal has continued to be a part of the global vaccine supply and its acceptability as a component of vaccine formulations remained unchallenged until 2010, when the United Nations (UN), through the UN Environment Programme, began negotiations to write the global, legally binding Minamata Convention on Hg. During the negotiations, TCVs were dropped from the list of Hg-containing products to be regulated. Consequently, a double standard in vaccine safety, which previously existed due to ignorance and economic reasons, has now been institutionalised as global policy. Ultimately, the Minamata Convention on Hg has sanctioned the inequitable distribution of thimerosal by specifically exempting TCVs from regulation, condoning a two-tier standard of vaccine safety: a predominantly no-thimerosal and reduced-thimerosal standard for developed nations and a predominantly thimerosal-containing one for developing nations. This disparity must now be evaluated urgently as a potential form of institutionalised discrimination.
Assuntos
Países em Desenvolvimento , Controle de Medicamentos e Entorpecentes , Disparidades em Assistência à Saúde , Mercúrio/administração & dosagem , Discriminação Social , Timerosal/administração & dosagem , Vacinas/administração & dosagem , Disparidades em Assistência à Saúde/ética , Humanos , Direito Internacional , Obrigações Morais , Nações UnidasRESUMO
There are over 165 studies that have focused on Thimerosal, an organic-mercury (Hg) based compound, used as a preservative in many childhood vaccines, and found it to be harmful. Of these, 16 were conducted to specifically examine the effects of Thimerosal on human infants or children with reported outcomes of death; acrodynia; poisoning; allergic reaction; malformations; auto-immune reaction; Well's syndrome; developmental delay; and neurodevelopmental disorders, including tics, speech delay, language delay, attention deficit disorder, and autism. In contrast, the United States Centers for Disease Control and Prevention states that Thimerosal is safe and there is "no relationship between [T]himerosal[-]containing vaccines and autism rates in children." This is puzzling because, in a study conducted directly by CDC epidemiologists, a 7.6-fold increased risk of autism from exposure to Thimerosal during infancy was found. The CDC's current stance that Thimerosal is safe and that there is no relationship between Thimerosal and autism is based on six specific published epidemiological studies coauthored and sponsored by the CDC. The purpose of this review is to examine these six publications and analyze possible reasons why their published outcomes are so different from the results of investigations by multiple independent research groups over the past 75+ years.
Assuntos
Transtorno Autístico/induzido quimicamente , Conservantes Farmacêuticos/efeitos adversos , Timerosal/efeitos adversos , Vacinas/efeitos adversos , Transtorno Autístico/patologia , Humanos , Lactente , Conservantes Farmacêuticos/administração & dosagem , Timerosal/administração & dosagem , Estados UnidosRESUMO
Thimerosal is a vaccine antimicrobial preservative which has long been suspected an iatrogenic factor possibly contributing to neurodevelopmental disorders including autism. The association between infant vaccine thimerosal exposure and autism remains an open question. Although thimerosal has been removed from mandatory childhood vaccines in the United States, thimerosal-preserved vaccines are still widely used outside of the United States especially in developing countries. Notably, thimerosal-containing vaccines are being given to the newborns within the first 12-24 h after birth in some countries. To examine the possible neurotoxic effects of early neonatal exposure to a higher level of thimerosal, FVB mice were subcutaneously injected with thimerosal-mercury at a dose which is 20× higher than that used for regular Chinese infant immunization during the first 4 months of life. Thimerosal-treated mice exhibited neural development delay, social interaction deficiency, and inclination of depression. Apparent neuropathological changes were also observed in adult mice neonatally treated with thimerosal. High-throughput RNA sequencing of autistic-behaved mice brains revealed the alternation of a number of canonical pathways involving neuronal development, neuronal synaptic function, and the dysregulation of endocrine system. Intriguingly, the elevation of anterior pituitary secreting hormones occurred exclusively in male but not in female thimerosal-treated mice, demonstrating for the first time the gender bias of thimerosal-mercury toxicity with regard to endocrine system. Our results indicate that higher dose of neonatal thimerosal-mercury (20× higher than that used in human) is capable of inducing long-lasting substantial dysregulation of neurodevelopment, synaptic function, and endocrine system, which could be the causal involvements of autistic-like behavior in mice.
Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Conservantes Farmacêuticos/toxicidade , Timerosal/toxicidade , Transcriptoma/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Relação Dose-Resposta a Droga , Feminino , Perfilação da Expressão Gênica , Masculino , Camundongos Endogâmicos , Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/psicologia , Conservantes Farmacêuticos/administração & dosagem , Caracteres Sexuais , Timerosal/administração & dosagemRESUMO
BACKGROUND: An inactivated quadrivalent influenza vaccine (QIV) was recently licenced in the US as a thimerosal-free formulation presented in a pre-filled syringe. A multidose presentation is preferred in some settings due to reduced acquisition and cold storage costs. We assessed the immunogenicity and safety of a thimerosal-containing QIV formulated using a new manufacturing process for presentation in multidose vials. METHODS: Two Phase III non-randomized studies separately evaluated inactivated trivalent influenza vaccine (TIV; 2010-2011; historical control) and a QIV (2011-2012). The QIV contained the same strains as the TIV plus an additional B strain. Both vaccines contained thimerosal to allow multidose presentation: this preservative was added to the QIV during the final formulation step using a new process, whereas it was added to the TIV early in the manufacturing process using an established method. The TIV study included 50 and 70 subjects aged 18-60 and >60 years, respectively; the QIV study included 56 subjects in each age stratum. Immunogenicity was assessed using hemagglutination-inhibition (HI) assays. Reactogenicity was assessed during the 4-day post-vaccination periods and unsolicited adverse events (AEs) were assessed during the 21-day post-vaccination periods. RESULTS: The TIV and QIV were immunogenic in both age strata. With the QIV and TIV respectively, the seroconversion rates were 48.2-62.7% and 71.4-83.7% for influenza A, and 33.9-62.5% and 67.3-72.9% for influenza B. With the QIV and TIV respectively, the seroprotection rates were 92.9-98.2% and 98.2-100% for influenza A, and 88.6-100% and 95.9-98.6% for influenza B. Pre-vaccination titers were higher in the QIV versus TIV study which confounds a direct comparison and likely explains the lower seroconversion rates observed in the QIV study. There were no safety concerns raised with TIV or QIV. CONCLUSIONS: The thimerosal-containing QIV formulated using a new process was immunogenic, conforming to regulatory acceptance criteria, with a reactogenicity and safety profile in line with the TIV manufactured using a licensed process. These results support acceptability of a manufacturing process change in which the thimerosal preservative is added at the point at which batches are filled into multidose vials. TRIAL REGISTRATION: These trials were registered at ClinicalTrials.gov: NCT01440387; NCT01153685.
Assuntos
Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/química , Influenza Humana/prevenção & controle , Adolescente , Adulto , Composição de Medicamentos , Feminino , Estudo Historicamente Controlado , Humanos , Vacinas contra Influenza/efeitos adversos , Influenza Humana/imunologia , Masculino , Pessoa de Meia-Idade , Timerosal/administração & dosagem , Timerosal/efeitos adversos , Timerosal/química , Adulto JovemRESUMO
The use of thimerosal preservative in childhood vaccines has been largely eliminated over the past decade in the United States because vaccines have been reformulated in single-dose vials that do not require preservative. An exception is the inactivated influenza vaccines, which are formulated in both multidose vials requiring preservative and preservative-free single-dose vials. As part of an ongoing evaluation by USFDA of the safety of biologics throughout their lifecycle, the infant body burden of mercury following scheduled exposures to thimerosal preservative in inactivated influenza vaccines in the United States was estimated and compared to the infant body burden of mercury following daily exposures to dietary methylmercury at the reference dose established by the USEPA. Body burdens were estimated using kinetic parameters derived from experiments conducted in infant monkeys that were exposed episodically to thimerosal or MeHg at identical doses. We found that the body burden of mercury (AUC) in infants (including low birth weight) over the first 4.5 years of life following yearly exposures to thimerosal was two orders of magnitude lower than that estimated for exposures to the lowest regulatory threshold for MeHg over the same time period. In addition, peak body burdens of mercury following episodic exposures to thimerosal in this worst-case analysis did not exceed the corresponding safe body burden of mercury from methylmercury at any time, even for low-birth-weight infants. Our pharmacokinetic analysis supports the acknowledged safety of thimerosal when used as a preservative at current levels in certain multidose infant vaccines in the United States.
Assuntos
Vacinas contra Influenza/administração & dosagem , Mercúrio/farmacocinética , Timerosal/administração & dosagem , Área Sob a Curva , Carga Corporal (Radioterapia) , Humanos , Lactente , Vacinas contra Influenza/química , Timerosal/análise , Incerteza , Estados UnidosRESUMO
OBJECTIVES: Thiomersal is ethylmercury containing compound. It has been used as a preservative in vaccines since the 1930s because it is very effective in preventing bacterial contamination. Ethylmercury penetrates into growing hair in a similar manner as methylmercury. DESIGN: A total of 48 hair samples were collected from vaccinated dogs. Each sample was accompanied with a questionnaire including data on age, gender, vaccinations. Total mercury content in hair, granules and vaccines was determined by the direct method of cold vapours using an AMA 254 (advance mercury analyser; Altec Ltd., Czech Republic). RESULTS: At first we performed two pre-experiments. In first pre-experiment, the highest value of total mercury content was 0.732 mg.kg-1. The content of total mercury ranged from 0.022 to 0.092 mg.kg-1 in the second pre-experiment. The results were not statistically significant in the pre-experiments. In the main experiment the lowest concentration of total mercury in dog's hair was 0.002 mg.kg-1 and the highest value was 0.560 mg.kg-1. The median value of total mercury ranged from 0.023 to 0.033 mg.kg-1. The results were not statistically significant in the main experiment. Total mercury content in vaccines corresponded with the declared quantity. Rather, results showed mercury content to be correlated with the consumption of feed containing fish. CONCLUSIONS: Thiomersal preservative, contained in vaccine, does not increase content of total mercury in canine hair. Our results have shown that content of mercury in hair depends on fish consumption (fish granules, fish treats and fresh fish).