Thimerosal-containing Vaccines Research Articles

Examples of Outcome Reporting Bias in Vaccine Studies: Illustrating How Perpetuating Medical Consensus Can Impede Progress in Public Health.

Introduction: Outcome reporting bias in vaccine studies is a widespread problem among all researchers who have a tendency to report selective results and conclusions that support their beliefs and values or those of sponsoring agencies. Especially during the COVID-19 pandemic, this bias surfaced through the unprecedented proliferation of conflicting vaccine studies. Many researchers strongly recommend and report on the safety and effectiveness of the COVID-19 vaccine. Those researchers who embrace the COVID-19 vaccine and vaccines, in general, are often dismissive of other researchers who present views that differ from medical orthodoxy and oppose medical consensus.Methods: The aim of this analysis is to critically evaluate seven vaccine studies using qualitative and/or quantitative approaches to identify outcome reporting bias and assess its potential impact on the stated conclusions that align with medical consensus. Four studies claim to have found no association between autism and (a) blood levels of mercury, (b) measles, mumps, and rubella (MMR) vaccine, and (c) thimerosal-containing vaccines. Three other studies claim no association exists between infant mortality rate and the number of vaccine doses, universal varicella vaccination and herpes zoster, and pandemic influenza vaccines and fetal losses.Results: The presence of outcome reporting bias and independent reanalysis demonstrated an impact on both the direction and magnitude of the observed effect - raising questions concerning the robustness of the original study design and conclusions and challenging the current medical consensus. Medical consensus has exonerated vaccines as having any causal relationship to autism spectrum disorders (ASDs), yet no other reasonable cause has been proposed. Medical consensus attributes significant ASD increases to better case ascertainment and broadened clinical diagnosis. According to 2018 data, an estimated 1 in 44 eight-year-olds has been identified with ASD. From 1990 to 2019, there have been an estimated two million new cases of ASD in the US, with lifetime social costs exceeding $7 trillion (in 2019 dollars). Can perpetuating medical consensus impede the advancement of public health? Or has it already done so?Conclusions: Conflicts of interest (e.g., financial) that abound between health regulatory agencies and the pharmaceutical industry impact what is ultimately reckoned as medical consensus. Outcome reporting bias that is inherent to all researchers to some degree, obscures medical and scientific truth. Advancement of public health requires that researchers have integrity and an openness and willingness to collaborate to resolve contradictory findings. In fact, it is usually through meticulous, rigorous, scientific investigation of contradictory findings that medical science has advanced and contributed to improvements in public health - since medical consensus and orthodoxy can be incorrect.

The role of epidemiology in informing United States childhood immunization policy and practice

One of the ten greatest public health achievements is childhood vaccination because of its impact on controlling and eliminating vaccine-preventable diseases (VPDs). Evidence-based immunization policies and practices are responsible for this success and are supported by epidemiology that has generated scientific evidence for informing policy and practice. The purpose of this report is to highlight the role of epidemiology in the development of immunization policy and successful intervention in public health practice that has resulted in a measurable public health impact: the control and elimination of VPDs in the United States. Examples in which epidemiology informed immunization policy were collected from a literature review and consultation with experts who have been working in this field for the past 30 years. Epidemiologic examples (e.g., thimerosal-containing vaccines and the alleged association between the measles, mumps, and rubella (MMR) vaccine and autism) are presented to describe challenges that epidemiologists have addressed.Finally, we describe ongoing challenges to the nation’s ability to sustain high vaccination coverage, particularly with concerns about vaccine safety and effectiveness, increasing use of religious and philosophical belief exemptions to vaccination, and vaccine hesitancy. Learning from past and current experiences may help epidemiologists anticipate and address current and future challenges to respond to emerging infectious diseases, such as COVID-19, with new vaccines and enhance the public health impact of immunization programs for years to come.

Thimerosal-containing vaccines and deficit in child development: Population-based study in southern Brazil

BackgroundThe discussion on the safety of thimerosal-containing vaccines (TCVs) and their impact on child development it́s very relevant. Methods: This is a cohort study with mother-child dyads who received prenatal care in the Unified Health System. The domains of motor, cognitive and language development were evaluated in children between 24 and 36 months of age. Data on vaccination were obtained through the child's immunization record. A linear regression analysis was carried out considering possible confounders. Results: In bivariate analyses, motor and language development were associated with TCVs (p < 0.05). However, in the multivariate analysis, this association was not maintained (p > 0.05). These results indicate that the use of TCVs is not associated with child development. The importance of this study is summarized in transmitting relevant information regarding public health, based on reliable data.

Methyl and Ethylmercury elicit oxidative stress and unbalance the antioxidant system in Saccharomyces cerevisiae

Methylmercury (MeHg) and Ethylmercury (EtHg) are toxic to the central nervous system. Human exposure to MeHg and EtHg results mainly from the consumption of contaminated fish and thimerosal-containing vaccines, respectively. The mechanisms underlying the toxicity of MeHg and EtHg are still elusive. Here, we compared the toxic effects of MeHg and EtHg in Saccharomyces cerevisiae (S. cerevisiae) emphasizing the involvement of oxidative stress and the identification of molecular targets from antioxidant pathways. Wild type and mutant strains with deleted genes for antioxidant defenses, namely: γ-glutamylcysteine synthetase, glutathione peroxidase, catalase, superoxide dismutase, mitochondrial peroxiredoxin, cytoplasmic thioredoxin, and redox transcription factor Yap1 were used to identify potential pathways and proteins from cell redox system targeted by MeHg and EtHg. MeHg and EtHg inhibited cell growth, decreased membrane integrity, and increased the granularity and production of reactive species (RS) in wild type yeast. The mutants were predominantly less tolerant of mercurial than wild type yeast. But, as the wild strain, mutants exhibited higher tolerance to MeHg than EtHg. Our results indicate the involvement of oxidative stress in the cytotoxicity of MeHg and EtHg and reinforce S. cerevisiae as a suitable model to explore the mechanisms of action of electrophilic toxicants.

Microbial structure and function in infant and juvenile rhesus macaques are primarily affected by age, not vaccination status

Although thimerosal, an ethylmercury-based preservative, has been removed from most pediatric vaccines in the United States, some multidose vaccines, such as influenza vaccines, still contain thimerosal. Considering that a growing number of studies indicate involvement of the gut microbiome in infant immune development and vaccine responses, it is important to elucidate the impact of pediatric vaccines, including thimerosal-containing vaccines, on gut microbial structure and function. Here, a non-human primate model was utilized to assess how two vaccine schedules affect the gut microbiome in infants (5–9 days old) and juveniles (77–88 weeks old) through 16S ribosomal RNA sequencing and metabolomics analyses of the fecal samples. Two treatment groups (n = 12/group) followed either the vaccine schedule that was in place during the 1990s (intensive exposure to thimerosal) or an expanded schedule administered in 2008 (prenatal and postnatal exposure to thimerosal mainly via influenza vaccines), and were compared with a control group (n = 16) that received saline injections. The primary impact on gut microbial structure and function was age. Although a few statistically significant impacts of the two common pediatric vaccine schedules were observed when confounding factors were considered, the magnitude of the differences was small, and appeared to be positive with vaccination.

The risk of neurodevelopmental disorders following Thimerosal-containing Hib vaccine in comparison to Thimerosal-free Hib vaccine administered from 1995 to 1999 in the United States.

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) = 2.75, p < 0.02), developmental delay (OR = 5.39, p < 0.01), psychomotor disorder (OR = 2.38, p < 0.03), and neurodevelopmental disorder in general (OR = 2.70, p < 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 (OR = 2.52, p < 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.

Heterogeneity of Multimedia Exposures to Neurotoxic Elements (Al, As, Cd, Pb, Mn, and Hg) in Breastfed Infants from Porto Velho, Brazil.

Infant exposure to neurotoxic elements is a public health issue that needs monitoring with regard to breast milk composition. We studied six neurotoxic elements in breast milk samples at different stages of lactation in mothers from Porto Velho, Brazil. We used a flow-injection mercury system (FIMS) to determine total Hg concentrations and an inductively coupled plasma optical emission spectrometer (ICP-OES) to determine the concentrations of Al, As, Cd, Pb, and Mn in 106 donors of a human milk bank. Association rules analyses were applied to determine the pattern of binary and ternary mixtures of the measured exposants. The metal concentration was mostly below the limit of detection (LOD) for Cd (99%), Pb (84%), and Hg (72%), and it was above the LOD for As (53%), Mn (60%), and Al (82%), respectively. Median concentrations (dry weight) of Al, As, Hg, Mn, and Pb were 1.81μg/g, 13.8ng/g, 7.1ng/g, 51.1ng/g, and 0.43μg/g, respectively. Al is singly the most frequent element to which infants are exposed. Occurring binary combination (>LOD) was 56% for Al-Mn, 41% for Al-As, 22% for Al-Hg, and 13% for Al-Pb. In 100% of neonates, exposure to Al-ethylmercury (EtHg) occurred through immunization with thimerosal-containing vaccines (TCV). Association rules analysis revealed that Al was present in all of the multilevel combinations and hierarchical levels and that it showed a strong link with other neurotoxic elements (especially with Mn, As, and Hg). (a) Nursing infants are exposed to combinations of neurotoxicants by different routes, dosages, and at different stages of development; (b) In breastfed infants, the binary exposures to Al and total Hg can occur through breast milk and additionally through TCV (EtHg and Al);

Increased risk for an atypical autism diagnosis following Thimerosal-containing vaccine exposure in the United States: A prospective longitudinal case-control study in the Vaccine Safety Datalink

BackgroundThimerosal is an organic-mercury (Hg)-containing compound (49.55% Hg by weight) historically added to many multi-dose vials of vaccine as a preservative and still added to some vaccines today. Concerns about the toxic effects from Thimerosal-containing childhood vaccines and the risk of an atypical autism diagnosis were evaluated in this study. MethodsA hypothesis-testing, prospective longitudinal, case-control study assessed exposure to Hg from Thimerosal-containing hepatitis B vaccines (TM-HepB) among cases diagnosed with atypical autism (n=164) and controls (n=15,216). Automated medical records for subjects born from 1991 to 2000 and continuously enrolled in the Vaccine Safety Datalink (VSD) database were examined. ResultsCases diagnosed with atypical autism were statistically significantly more likely to have received greater overall and dose-dependent exposures to Hg from TM-HepB vaccines administered within the first month of life, first two months of life, and first six months of life than the controls. Similar phenomena were observed when cases and controls were separated by gender. ConclusionsRoutine childhood vaccination is an important public health tool to reduce infectious diseases. The present study provides important epidemiological evidence significantly associating increasing Hg exposure from Thimerosal-containing childhood vaccines and the subsequent risk of atypical autism diagnosis, and suggests that Thimerosal should be eliminated from vaccines.

Thimerosal exposure and disturbance of emotions specific to childhood and adolescence: A case-control study in the Vaccine Safety Datalink (VSD) database

ABSTRACTBackground: This study evaluated Thimerosal-containing childhood vaccines and the risk of a diagnosis called disturbance of emotions specific to childhood and adolescence (ED). Thimerosal is an organic-mercury (Hg)-containing compound used in some vaccines.Methods: A hypothesis-testing prospective, longitudinal case-control study evaluated Hg exposure from Thimerosal in hepatitis B vaccines administered at specific times within the first 6 months of life and its association with medically diagnosed ED (313.xx) (n = 517) in children born between 1991–2000 in comparison to controls (n = 27 491) in the Vaccine Safety Datalink (VSD) database.Results: Cases diagnosed with ED were significantly more likely than controls to have received increased Hg exposure within the first month of life (odds ratio (OR) = 1.3384), the first 2 months of life (OR = 1.3367) and the first 6 months of life (OR = 2.37). When the data were separated by gender, similar significant adverse effects were observed for males, but not females. On a per microgram Hg basis, cases diagnosed with ED were significantly more likely than controls to have received increased exposure within the first 6 months of life (OR = 1.025 per microgram Hg).Conclusions: The results show a significant relationship between Hg exposure from Thimerosal-containing childhood vaccines and the subsequent risk of an ED diagnosis.

A Two-Phase Case-Control Study of Autism Risk Among Children Born From the Late 1990s Through the Early 2000s in the United States.

BackgroundThis study evaluated the hypothesis that the 1999 recommendation by the American Academy of Pediatrics (AAP) and US Public Health Service (PHS) to reduce exposure to mercury (Hg) from Thimerosal in US vaccines would be associated with a reduction in the long-term risk of being diagnosed with autism.Material/MethodsA two-phase assessment utilizing a case (n=73) -control (n=11,783) study in the Vaccine Adverse Event Reporting System (VAERS) database (for hypothesis generating) and a more rigorous, independent matched case (n=40) -control (n=40) study (hypothesis testing) was undertaken.ResultsAnalysis of the VAERS database using logistic regression revealed that the odds ratio (OR) for being an autism case in the VAERS database significantly decreased with a more recent year of vaccination in comparison to controls (OR=0.65) from 1998 to 2003. Sex-separated analyses revealed similar significant effects for males (OR=0.62) and females (OR=0.71). Analyses of the matched case-control data revealed, using the t-test statistic, that the mean date of birth among cases diagnosed with an autism spectrum disorder (ASD) (2000.5±1.2) was significantly more in the past than in controls (2001.1±1.3). Logistic regression also revealed that the OR for being diagnosed with ASD significantly decreased with a more recent date of birth in comparison to controls (OR=0.67) from 1998–2003.ConclusionsThis study reveals that the risk of autism during from the late1990s to early 2000s in the US significantly decreased with reductions in Hg exposure from Thimerosal-containing childhood vaccines, but future studies should examine this phenomenon in other US populations. Vaccine programs have significantly reduced the morbidity and mortality associated with infectious disease, but Thimerosal should be removed from all vaccines.

Current progress on understanding the impact of mercury on human health

Mercury pollution and its impacts on human health is of global concern. The authors of this paper were members of the Plenary Panel on Human Health in the 12th International Conference on Mercury as a Global Pollutant held in Korea in June 2015. The Panel was asked by the conference organizers to address two questions: what is the current understanding of the impacts of mercury exposure on human health and what information is needed to evaluate the effectiveness of the Minamata Convention in lowering exposure and preventing adverse effects. The authors conducted a critical review of the literature published since January 2012 and discussed the current state-of-knowledge in the following areas: environmental exposure and/or risk assessment; kinetics and biomonitoring; effects on children development; effects on adult general populations; effects on artisanal and small-scale gold miners (ASGM); effects on dental workers; risk of ethylmercury in thimerosal-containing vaccines; interactions with nutrients; genetic determinants and; risk communication and management. Knowledge gaps in each area were identified and recommendations for future research were made. The Panel concluded that more knowledge synthesis efforts are needed to translate the research results into management tools for health professionals and policy makers.

Additional comments to "Potential health consequences of applying mercury-containing skin-lightening creams during pregnancy and lactation periods".

Exposure through human skin from application of skin lightening creams and soaps (SLCS) based on mercury salts has often escaped attention of environmental scientists. The skin absorption of Hg from an adult on a daily basis in this type of exposure, depending on the product used, can be higher than Hg originated from dental amalgam filling, Thimerosal-containing flu vaccine, and fish-methylmercury. Hg from SLCS is retained more in brain of albino than pigmented animals. Therefore, environmental Hg scientists should be aware of this important but often neglected source of low-dose Hg exposure during pregnancy and lactation when measuring adverse health effects on child growth and development.

Mercury levels and human health in the Amazon Basin

Context: Environmental mercury in the Amazon mostly originates from geochemical sources with some from artisanal gold mining (AGM). Geochemical-originated methylmercury (MeHg) reaches the aquatic food chain, ending up in fish. Inorganic Hg used in AGM is responsible for localised environmental contamination and occupational exposure of adults. In addition to this, iatrogenic ethylmercury (EtHg) derived from Thimerosal-containing vaccines (TCVs) exposes immunised infants.Objective: To understand Hg exposure in the Amazon in relation to environmental fish-MeHg exposure, occupational AGM activities and low-doses of TCV-EtHg.Methods: Medline and Thomson-Reuter Web of Science were searched to retrieve and select papers addressing Hg exposure and human health.Results and conclusion: Environmental-Hg studies addressed health effects associated with birth weight, infant linear growth and neurodevelopment, while, in adults, environmental and occupational studies addressed immune and neurological issues. No widespread clinical toxicity was reported due to fish-MeHg. However, mixed results associated with Hg exposure can be found. Reducing children’s exposure to EtHg is possible using Thimerosal-free vaccines, but it is difficult to interfere with fish consumption without consequences to riverine subsistence populations. Policies to diminish Hg exposure should focus on controlling and/or curbing widespread use of Hg (in gold amalgamation) and promotion of Thimerosal-free vaccines for pregnant women and young children.

Traditional living in the Amazon: Extended breastfeeding, fish consumption, mercury exposure and neurodevelopment

Background: Features of traditional living in the Amazon Basin (high fish consumption and long breastfeeding) are likely to expose children to Mercury (Hg).Aim: To study neurodevelopment in 690 children in relation to prolonged breastfeeding and mercury exposure.Subjects and methods: Three groups of breastfeeding children were formed: Group 1 (breastfed for 6 months), Group 2 (7–12 months) and Group 3 (extending up to 24 months). Neurodevelopment was assessed as age of walking, age of talking and the Bayley Scales of Infant Development–BSID. Mercury exposure was assessed from Thimerosal-containing vaccines and fish consumption from hair Hg (HHg).Results and conclusions: HHg increased in children and decreased in mothers at 24 months. Frequency of fish consumption was significantly correlated with maternal HHg at birth (Spearman’s r = 0.8583; p = 0.0001); likewise, there was a significant correlation between duration of breastfeeding and children’s HHg (Spearman’s r = 0.15; p = 0.0018). Extended breastfeeding did not influence the Mental Development Index–MDI or Psychomotor Development Index–PDI, but maternal education and HHg (marker of fish consumption) interacted positively and significantly with both. Frequency of maternal fish consumption and education had a positive association with BSID scores; it is speculated that maternal education and nutrients in fish have an opposing effect on Hg exposure.

Impact of organic mercury exposure and home delivery on neurodevelopment of Amazonian children.

In the transitioning Amazon, we addressed birth environment (home vs hospital) and associated perinatal organic-Hg exposures: methylmercury (MeHg) from maternal fish consumption and ethylmercury (EtHg) from pediatric Thimerosal-containing vaccines (TCVs) taken systematically during hospital delivery. We studied 365 children in relation to linear growth at 60 months and neurodevelopment (milestone achievements, Bayley Scale of Infant Development/BSID at 24 months, and Stanford-Binet intelligence tests at 60 months). Mothers delivered in hospitals vs those gave birth at home had significantly (p<0.0001) lower hair-Hg (HHg) concentrations (12.2 vs 23.9μg/g respectively) and shorter length of breastfeeding (8.5 vs 9.7 months respectively). Home-born children had significantly (p<0.0001) higher HHg (7.1μg/g) than hospital-born children (4.6μg/g). Hospital-born children also had significantly earlier (p<0.0001) hepatitis B vaccine than home-born children (1.5 vs 24.1days respectively) and higher (p<0.0001) exposures to total TCV-EtHg (75.8 vs 49.3μg respectively). Neither anthropometric indices nor neurodevelopment (except for fluid reasoning) were directly affected by birth environment. The percentage of hospital-born children with BSID (MDI or PDI) scores <80 was not significantly different from those born at home. In spite of the differences in HHg and EtHg levels between hospital-born and home-born children, no impact on neurodevelopment was observed.

Thimerosal-Preserved Hepatitis B Vaccine and Hyperkinetic Syndrome of Childhood.

(1) Background: Hyperkinetic syndrome of childhood (HKSoC) is an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) category in which the majority of the children are also diagnosed under the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR), where the umbrella term is “Attention-Deficit and Disruptive Behavior Disorders”. The diagnostic criteria for HKSoC are developmentally inappropriate inattention, hyperactivity, and impulsivity. Some studies have implicated mercury (Hg) exposure as a risk factor. (2) Methods: This hypothesis testing study; using the Vaccine Safety Datalink; assessed the toxicological effects of bolus exposure to organic-Hg from Thimerosal-containing vaccines (TCVs) by examining the relationship between Thimerosal-preserved hepatitis B vaccines (TM-HepB) given at varying levels and at specific intervals in the first six months after birth and the risk of a child being diagnosed with HKSoC. (3) Results: Children diagnosed with HKSoC were significantly more likely to be exposed to increased organic-Hg from TM-HepB doses given within the first month (odds ratio = 1.45; 95% confidence interval (CI) = 1.30–1.62); within the first two months (odds ratio = 1.43; 95% CI = 1.28–1.59); and within the first six months (odds ratio = 4.51; 95% CI = 3.04–6.71) than controls. (4) Conclusion: The results indicate that increasing organic-Hg exposure from TCVs heightens the risk of a HKSoC diagnosis.

Neurodevelopment of Amazonian children exposed to ethylmercury (from Thimerosal in vaccines) and methylmercury (from fish)

Few studies have addressed co-occurring methylmercury (MeHg) from maternal origin and ethylmercury (EtHg) from Thimerosal-containing vaccines (TCVs) during infant's neurodevelopment. We studied children (n=1139) from the Western Amazon based on combined (low, intermediate, and high) exposure to chronic MeHg from fish consumption and acute TCV- EtHg. Neurodevelopment outcomes were age of walking and age of talking, and the Bayley Scale of Infant Development (BSID). The Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) were measured at six and 24 months of age. Median hair-Hg (HHg) at birth was 6.4µgg−1 in mothers, and 1.94µgg−1 in newborns; total (pregnancy and infancy) EtHg exposure ranged from 0 to 187.5µg. The combined (MeHg+EtHg) exposure showed significant differences for MDI but not for PDI; however, there was a significant decrease in both MDI and PDI scores at 24 months. The increase in BSID delays (scores <80) between six and 24 months was not discernible with regards to EtHg or MeHg exposure. We found a statistically significant increase in neurodevelopmental (BSID) delays related to the combined exposure to Hg (MeHg>EtHg). Neurodevelopment delays due to low-doses of organic mercury (albeit undiscernible) are not predictable but can be avoided by choosing low-Hg fish and providing Thimerosal-free vaccines.

Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology.

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.

A longitudinal cohort study of the relationship between Thimerosal-containing hepatitis B vaccination and specific delays in development in the United States: Assessment of attributable risk and lifetime care costs

Epidemiological evidence suggests a link between mercury (Hg) exposure from Thimerosal-containing vaccines and specific delays in development. A hypothesis-testing longitudinal cohort study (n=49,835) using medical records in the Vaccine Safety Datalink (VSD) was undertaken to evaluate the relationship between exposure to Hg from Thimerosal-containing hepatitis B vaccines (T-HBVs) administered at specific intervals in the first 6months of life and specific delays in development [International Classification of Disease, 9th revision (ICD-9): 315.xx] among children born between 1991 and 1994 and continuously enrolled from birth for at least 5.81years. Infants receiving increased Hg doses from T-HBVs administered within the first month, the first 2months, and the first 6months of life were significantly more likely to be diagnosed with specific delays in development than infants receiving no Hg doses from T-HBVs. During the decade in which T-HBVs were routinely recommended and administered to US infants (1991–2001), an estimated 0.5–1million additional US children were diagnosed with specific delays in development as a consequence of 25μg or 37.5μg organic Hg from T-HBVs administered within the first 6months of life. The resulting lifetime costs to the United States may exceed $1 trillion.

Pediatric Vaccines and Neurodevelopment: Primate Study Finds No Adverse Behavioral Effects

Vaccination has successfully reduced the incidence and prevalence of many infectious diseases. However, in the absence of outbreaks, a perception has developed that vaccinations themselves may present a greater risk than the diseases they prevent.1 Although evaluations of the existing data have failed to identify links between vaccination and negative health outcomes,2,3 there remain some public concerns about a potential link with autism spectrum disorders. These concerns are primarily due to the expansion of the infant immunization schedule and exposure to thimerosal, once used as a preservative in some vaccines.1 In this issue of EHP, the authors of a detailed exploration of neurodevelopment, learning, and social behavior in macaques report no adverse developmental and behavioral effects associated with the full pediatric vaccine schedule.4 Thimerosal is broken down in the body to thiosalicylate and ethylmercury.5 The latter is related to neurotoxic methylmercury, and estimates of health risks were based on the assumption—later disproved6—that ethyl- and methylmercury have similar toxicity profiles.5 With the exception of inactivated influenza vaccine, thimerosal has been removed from or reduced to trace amounts (≤ 1 µg/dose) in all vaccines routinely recommended for children under 6 years of age.7 Nevertheless, concerns persist, and vaccination rates have declined in some populations, with subsequent reemergence of diseases such as the recent outbreak of measles originating in California.8 Results from a study of macaque neurodevelopment bolster the body of evidence that routine pediatric vaccines are safe for human children. “The main impetus behind the study was that while individual pediatric vaccines underwent the required clinical safety testing, the cumulative exposure to multiple thimerosal-containing vaccines had not been examined,” says study coauthor Laura Hewitson, director of research at the Johnson Center for Child Health and Development in Austin, Texas. The current study scrutinized neurodevelopment in macaques, whose nervous system development follows a similar trajectory to humans. Macaques also have learning and memory processes and social interactions that mimic those observed in humans. Seventy-nine macaques were assigned to six vaccination groups: 1) controls—animals received saline injections only; 2) MMR—animals received only the measles, mumps, and rubella vaccine, which has never contained thimerosal; 3) TCV—animals received all the thimerosal-containing vaccines administered routinely to children in the 1990s9 but no MMR vaccine; 4) 1990s Pediatric—animals received all pediatric vaccines administered in the 1990s, including TCVs and MMR, on the schedule recommended for children; 5) 1990s Primate—animals received all pediatric vaccines administered in the 1990s on an accelerated schedule to match macaque development; and 6) 2008—animals received the expanded immunization schedule in place as of 2008,10 which is similar to the current schedule. Between birth and 12 months of age, animals were tested for neonatal reflexes, object permanence (a measure of early memory development), discrimination learning strategies (ability to respond differently to different stimuli), and social behaviors. Animals also were systematically observed and rated for their level and characteristics of exploration, social withdrawal, play behavior, and aggression. The investigators found that animals within each dosing group showed similar development of neonatal reflexes and object permanence. There was a slight indication that the TCV and 1990s Primate groups performed better in some learning tests, and some of the experimental groups demonstrated fewer negative social behaviors than the control group. However negative behaviors were rarely observed in any group, and learning and social development overall appeared normal.4 “Some analyses suggested a beneficial effect of the thimerosal exposure,” says Neal Halsey, director of the Institute for Vaccine Safety at the Johns Hopkins Bloomberg School of Public Health. However, says Halsey (who was not involved in the study), there currently is no plausible biologic mechanism to explain those associations, which makes it more likely they were found by chance. “Most importantly, in terms of the behavioral data, we saw virtually no negative behaviors across all study groups,” says Hewitson. “That speaks to the hypothesis of thimerosal directly affecting behavior,” she says. “The fact that we didn’t see an increase in negative behaviors is reassuring.”