Article

No evidence for links between autism, MMR and measles Virus

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Abstract

We examined whether, in the UK, there is an increased risk of autism (AD) following exposures, in early life, to: (1) wild measles; (2) live attenuated measles, alone or in combination as MMR; and (3) the alteration of the mumps strain within MMR. We conducted time trend analyses of 2407 AD subjects born between 1959-93; and for comparison, 4640 Down's syndrome (DS) subjects born between 1966-93. Between 1968-86, we correlated variations in AD and DS births with wild measles incidence. Between 1959-93, we tested for abrupt changes in the long-term AD birth trend for the effects of introducing: (1) monovalent measles vaccines in 1968; (2) MMR immunization in 1988; and (3) the 'overnight switch' from mixed use of Urabe MMR to exclusive use of Jeryl-Lynn MMR in 1992. Incidence rate ratios (IRRs) were used as measures of association. We found no significant association between AD births and exposure (prenatal and postnatal up to 18 months age) to population rates of measles infections, and no 'step-up' increase in AD births associated with the introduction of monovalent measles and MMR vaccines, and changing mumps strain. An unexpected reduction in AD births of 21% (95% CI 6.9-33.3%; P=0.005) among the post-1987 birth cohorts was detected. No increased risk of AD following exposures to wild measles and vaccinations with monovalent measles, and Urabe or Jeryl-Lynn variants of MMR was detected. The precise meaning of the detected AD births reduction is unclear. Our study cannot exclude rare complications of MMR, given its correlational design.

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... Undeterred by the scientific consensus that vaccines are safe and effective, unsubstantiated claims doubting their safety still occur to this day. Perhaps the most famous case is the multiple times disproved [1,2,3] myth that the MMR vaccine causes autism. However, outbreaks and deaths resulting from objections to vaccines continue to happen [4,5], with the anti-vaccination movement gaining media attention as a result. ...
... The values of the comparison range from 0 to 1, where 1 is an exact match and 0 is no match. 1 It optimizes the modularity score in a greedy manner to calculate the communities. The modularity is a benefit function that measures the quality of a particular division of a network into communities. ...
Preprint
Vaccine hesitancy has been recognized as a major global health threat. Having access to any type of information in social media has been suggested as a potential powerful influence factor to hesitancy. Recent studies in other fields than vaccination show that access to a wide amount of content through the Internet without intermediaries resolved into major segregation of the users in polarized groups. Users select the information adhering to theirs system of beliefs and tend to ignore dissenting information. In this paper we assess whether there is polarization in Social Media use in the field of vaccination. We perform a thorough quantitative analysis on Facebook analyzing 2.6M users interacting with 298.018 posts over a time span of seven years and 5 months. We used community detection algorithms to automatically detect the emergent communities from the users activity and to quantify the cohesiveness over time of the communities. Our findings show that content consumption about vaccines is dominated by the echo-chamber effect and that polarization increased over years. Communities emerge from the users consumption habits, i.e. the majority of users only consumes information in favor or against vaccines, not both. The existence of echo-chambers may explain why social-media campaigns providing accurate information may have limited reach, may be effective only in sub-groups and might even foment further polarization of opinions. The introduction of dissenting information into a sub-group is disregarded and can have a backfire effect, further reinforcing the existing opinions within the sub-group.
... Novel vaccines are being developed for pregnant women. Monitoring their benefits and risks in resource-poor countries, will require enhanced collaborations with harmonized methodologies (distributed data networks) that take full advantage of current information technologies [42]. Evidence-based policy-making is currently driven by the gold standard of randomized trials. ...
... Several epidemiological investigations tested both claims. Ecological studies showed in various countries that underlying trends in rates of autism (equivalent to PDD: Pervasive Developmental Disorders, and to ASD: Autism Spectrum Disorders) were not correlated to trends in MMR coverage [41], to the introduction or discontinuation of monovalent measles vaccines and later introduction of MMR [42], to increased use, and to discontinuation of inclusion of the preservative thimerosal in most vaccine preparations [41]. Controlled observational studies (case-control and cohort studies) equally failed to show that past exposure to MMR vaccination was higher in children with autism compared to controls [43]; similarly, infants and toddlers exposed to MMR or to thimerosal-containing vaccines in various doses, when followed up several years later, were not an increased risk of developing autism, findings that extended to their siblings [44,45]. ...
Article
Full-text available
Vaccines are everywhere hugely successful but are also under attack. The reason for the latter is the perception by some people that vaccines are unsafe. However that may be, vaccine safety, life any other scientific subject, must be constantly studied. It was from this point of view that a meeting was organized at the Wellcome Trust in London in May 2019 to assess some aspects of vaccine safety as subjects for scientific study. The objective of the meeting was to assess what is known beyond reasonable doubt and conversely what areas need additional studies. Although the meeting could not cover all aspects of vaccine safety science, many of the most important issues were addressed by a group of about 30 experts to determine what is already known and what additional studies are merited to assess the safety of the vaccines currently in use. The meeting began with reviews of the current situation in different parts of the world, followed by reviews of specific controversial areas, including the incidence of certain conditions after vaccination and the safety of certain vaccine components. Lastly, information about the human papillomavirus vaccine was considered because its safety has been particularly challenged by vaccine opponents. The following is a summary of the meeting findings. In addition to this summary, the meeting organizers will explore opportunities to perform studies that would enlarge knowledge of vaccine safety.
... Undeterred by the scientific consensus that vaccines are safe and effective, unsubstantiated claims doubting their safety still occur to this day. Perhaps the most famous case is the multiple times disproved [1,2,3] myth that the MMR vaccine causes autism. However, outbreaks and deaths resulting from objections to vaccines continue to happen [4,5], with the anti-vaccination movement gaining media attention as a result. ...
... The values of the comparison range from 0 to 1, where 1 is an exact match and 0 is no match. 1 It optimizes the modularity score in a greedy manner to calculate the communities. The modularity is a benefit function that measures the quality of a particular division of a network into communities. ...
Article
Background: Vaccine hesitancy has been recognized as a major global health threat. Having access to any type of information in social media has been suggested as a potential influence on the growth of anti-vaccination groups. Recent studies w.r.t. other topics than vaccination show that access to a wide amount of content through the Internet without intermediaries resolved into major segregation of the users in polarized groups. Users select information adhering to theirs system of beliefs and tend to ignore dissenting information. Objectives: The goal was to assess whether users' attitudes are polarized on the topic of vaccination on Facebook and how this polarization develops over time. Methods: We perform a thorough quantitative analysis by studying the interaction of 2.6 M users with 298,018 Facebook posts over a time span of seven years and 5 months. We applied community detection algorithms to automatically detect the emergence of communities accounting for the users' activity on the pages. Also, we quantified the cohesiveness of these communities over time. Results: Our findings show that the consumption of content about vaccines is dominated by the echo chamber effect and that polarization increased over the years. Well-segregated communities emerge from the users' consumption habits i.e., the majority of users consume information in favor or against vaccines, not both. Conclusion: The existence of echo chambers may explain why social-media campaigns that provide accurate information have limited reach and be effective only in sub-groups, even fomenting further opinion polarization. The introduction of dissenting information into a sub-group is disregarded and can produce a backfire effect, thus reinforcing the pre-existing opinions within the sub-group. Public health professionals should try to understand the contents of these echo chambers, for example by getting passively involved in such groups. Only then it will be possible to find effective ways of countering anti-vaccination thinking.
... However, even as the strength of this connection diminished, it remained a topic of interest for researchers [49]. Similar findings apply to the measles virus [74]. ...
Article
Full-text available
This paper offers an in-depth exploration of the intricate relationship between environmental factors and autism spectrum disorder (ASD), with a special emphasis on seasonality. It reviews existing research, providing a comprehensive summary of findings and highlighting the multifaceted dimensions of several environmental factors influencing the etiology of ASD. The discussion encompasses various elements, including birth months, maternal health, dietary choices, and vitamin D deficiency, delving into the intricate interplay of seasonality with environmental influences such as viral infections and solar radiation. The present study raises essential questions regarding the timing of environmental influences and the factors contributing to the rising prevalence of ASD. Ultimately, it underscores the need for future epidemiological research to incorporate more extensive investigations of environmental risk factors and employ advanced statistical analyses. This comprehensive overview contributes to a deeper understanding of how environmental factors, particularly seasonality, may be linked to the occurrence of ASD and its increasing prevalence, recognizing the multifaceted and diverse nature of these interactions.
... However, even as the strength of this connection diminished, it remained a topic of interest for researchers [49]. Similar findings apply to the measles virus [67]. ...
Preprint
Full-text available
This paper offers an in-depth exploration of the complex relationship between seasonality and Autism Spectrum Disorder (ASD). It reviews existing research, providing a comprehensive summary of findings and highlighting the multifaceted dimensions of seasonality as an environmental factor that influences the etiology of ASD. The discussion encompasses various factors, including birth months, maternal health, dietary choices, and vitamin D deficiency, and delves into the intricate interplay of seasonality with environmental influences such as viral infections and solar radiation. The present study raises essential questions regarding the timing of environmental influences and the factors contributing to the rising prevalence of ASD. Ultimately, it underscores the need for future epidemiological research to incorporate more extensive investigations of environmental risk factors and employ advanced statistical analyses. This comprehensive overview contributes to a deeper understanding of how seasonality factors may be linked to the occurrence of ASD and its increasing prevalence, recognizing the multifaceted and diverse nature of these interactions.
... Despite this, an anti-vaccine sentiment is widespread. 1 The recent growth of the anti-vaccine movement has mostly been caused by increasing concerns about the safety of vaccines which find their root in a famous and yet disproven study linking MMR vaccine (for measles, mumps and rubella) to autism. 2,3 Then, the invention and rapid growth of social media allowed fake news and misinformation to spread faster than ever. 4 This unwittingly provided a platform for anti-vaccine supporters to spread their beliefs, and the ongoing COVID-19 pandemic has been providing a fertile ground for the circulation of myths and conspiracy theories about vaccines. ...
Article
Full-text available
Widely circulating anti-vaccine misinformation online has been constituting a large obstacle for the success of COVID-19 vaccination campaigns and for the well-being of people during the pandemic. In this paper we discuss strategies to mitigate negative effects of online anti-vaccine contents on public health and to prevent hesitant individuals from falling prey of the traps set by anti-vaccine disinformation spreaders. Here we discuss the importance of filling information voids and understanding trends and concerns that shape the vaccine debate, and we highlight the relevance of building resilience to vaccine misinformation by strengthening public health and digital literacy.
... Table 2 summarizes the most common environmental factors cited in the literature. As the evidence supporting causality is lacking and inconclusive, 18,19 further studies are needed. ...
Article
Sources of data: This article is based on key recent published literature including international guidelines and relevant reviews and meta-analyses. Authors have also supplemented this material with their own clinical experience. Areas of agreement: There is an agreement that autism spectrum disorder (ASD) have a strong hereditary component. There is also a consensus that the reported prevalence estimates have increased in the last 5 years. There is strong support for using the broader spectrum disorder conceptualization of the DSM-5. Areas of controversy: Higher public awareness of ASD has generated several controversial theories of causation. We review a number of environmental risk factors receiving media attention including: vaccines, mercury, heavy metal exposure and Selective Serotonin Uptake Inhibitors (SSRIs). Popular yet controversial treatment interventions are discussed. Early diagnostic screening tools are also addressed. Growing points: There is increasing scientific interest in identifying biomarkers of autism with potential for early diagnosis, prognostic indicators and predictive treatment responses. We review evidence from genetics, neuroimaging and eye tracking as candidate biomarkers. Area timely for developing research: Family studies point to a strong hereditary component in the aetiology of autism. However these studies have not established 100% concordance rates, suggesting a role for environmental factors. The gene–environment interplay has not received enough attention in scientific research. This represents an important new avenue for research in ASD.
... Numerous other studies often cited as disproving a link between ASD and vaccines in fact did not address risk of ASD diagnosis from vaccine at all and instead measured co-morbid conditions that are not part of the formal diagnosis of ASDs [159][160][161][162][163][164][165]. Titles and abstracts from such studies sometimes include misleading statements (eg: Peltola analyzed no data on autism, yet the study is entitled "No evidence for measles, mumps, and rubella vaccine-associated inflammatory bowel disease or autism") [166]. ...
Article
Full-text available
Neurodevelopmental disorders, including Autism Spectrum Disorders, have a complex biological and medical basis involving diverse genetic risk and myriad environmental exposures. Teasing apart the role of specific stressors is made challenging due to the large number of apparently contributing associations, gene X environment interactions and phenomimicry [1]. Historically, these conditions have been rare, making causality assessment at the population level infeasible. Only a few vaccines have been tested for association with autism, and it has been shown that improved diagnosis only explains a percentage of the increase in diagnosis. Now, the rates are so high in some countries that public school programs cannot handle the large numbers of special needs students, and professionals are quitting their jobs due to security concerns. Here, I review evidence of the pathophysiology of autism that reconciles the apparent paradox between the high degree of causal heterogeneity in environmental toxins, the absence of common "autism gene," and the high degree of genetic concordance (heritability) of ASD and ASD-like traits. In brief, the sampling of environmental toxins, and thus the environmental toxin sampling liability for ASD varies among families involving different local exposures following injury to normal cellular endoplasmic detoxification and mitochondrial processes from toxic metals. The literature strongly supports that autism is most accurately seen as an acquired cellular detoxification deficiency syndrome with heterogeneous genetic predisposition that manifests pathophysiologic consequences of accumulated, run-away cellular toxicity. At a more general level, it is a form of a toxicant-induced loss of tolerance of toxins, and of chronic and sustained ER overload (ER hyper stress), contributing to neuronal and glial apoptosis via the unfolded-protein response (UPR). Inherited risk of impaired cellular detoxification and circulating metal retoxification in neurons and glial cells accompanied by chronic UPR is key. This model explains the aberrant protein disorder observed in ASD; the great diversity of genes that are found to have low, but real contributions to ASD risk and the sensitivity of individuals with ASD to environmental toxins. The hindrance of detoxification and loss of cellular energetics leads to apoptosis, release of cytokines and chronic neuroinflammation and microglial activation, all observed hallmarks of ASD. Interference with the development of normal complex (redundant) synapses leads to a pathological variation in neuronal differentiation, axon and dendrite outgrowth, and synaptic protein expression. The most general outcomes are overall simplification of gross synaptic anatomy and, neurofunctionally, a loss of inhibitory feedback and aberrations in long-term connections between distant regions of the brain. Failed resolution of the ER stress response leads to re-distribution of neurotoxic metals, and the impaired neurocellular processes lead to subsequent accumulation of a variety of additional types of toxins with secondary, sometime life-threatening comorbidities such as seizures, with overlapping (not mutually exclusive) causality. Reduction of exposure to toxins known to cause mitopathy (mercury) and endoplasmic reticulum dysfunction (mercury and aluminum) during pregnancy and during the early years of development will reduce the risk of ER overload and ER hyper stress, and of ASD diagnosis. This knowledge has immediate clinical translational relevance: post-vaccination symptoms should be heeded as a sign of susceptibility to toxin; Vitamin D can be increased to drive the healthy early phases of the UPR, and mutations in ASD genes encoding proteins with high intrinsic disorder may contraindicate the use of aluminum and mercury for carriers of risk alleles. Clinicians should be alert to a patient’s Vitamin D receptor (BSM) mutational status prior to recommending increased doses. Approaches to improving overall brain health in autistics must be de-stigmatized and given high priority. Reduction of lifetime exposures of industrial and agricultural toxins will improve brain health for the entire human population. Purely genetic studies of ASD, and studies that do not include vaccination as an environmental exposure with potential liability and interactions with genes, are unethical. To qualify as science, studies must test plausible hypotheses, and the absence of association from poorly designed, unethically executed, and underpowered and unsound whole-population association studies have been harmful distractions in the quest for understanding. Skilled paediatricians and ob/gyns will seek evidence of genetic predisposition to environmental susceptibility in the form of non-synonymous substitutions in brain proteins that require ER-folding, and they will provide informed cautions on exposures (from all sources) to environmental toxins to patients and parents of patients with signs of metal and chemical sensitivity. To aid in this, a list of ASD environmental susceptibility protein-encoded genes is presented. A clinical Exome sequence test, followed by loss of function prediction analysis, would point to individuals most susceptible to vaccine metal-induced ER hyper stress leading to failed cellular detoxification.
... Numerous other studies often cited as disproving a link between ASD and vaccines in fact did not address risk of ASD diagnosis from vaccine at all and instead measured co-morbid conditions that are not part of the formal diagnosis of ASDs [159][160][161][162][163][164][165]. Titles and abstracts from such studies sometimes include misleading statements (eg: Peltola analyzed no data on autism, yet the study is entitled "No evidence for measles, mumps, and rubella vaccine-associated inflammatory bowel disease or autism") [166]. ...
... 93,97 Preterm neonates are a group in whom the prevalence of ASDs later in childhood is much higher than in term neonates. 98 The issue of vaccines as responsible for the increased prevalence of ASDs has been disproven by many scientific studies, [99][100][101] and the original study was proven to be a fraud, 102 although it has given rise to multiple articles, web-sites, and even mystery novels. 103 One fact seems to be clear: several unfavorable perinatal and neonatal factors are clearly associated with the development of autism. ...
... In [22], from the viewpoint of parents, how to make decision on Measles-Mumps-Rubella (MMR) vaccination for their children? Although scientific evidences showed that the MMR vaccine is very safe [12], there are still vaccine sceptics. There are other publications discussing the strategies against influenza [13,15,20,24], smallpox [4], chickenpox [16], measles [22], rubella [23] and other infectious diseases. ...
Article
Full-text available
One crucial condition for the uniqueness of Nash equilibrium set in vaccination games is that the attack ratio monotonically decreases as the vaccine coverage level increasing. We consider several deterministic vaccination models in homogeneous mixing population and in heterogeneous mixing population. Based on the final size relations obtained from the deterministic epidemic models, we prove that the attack ratios can be expressed in terms of the vaccine coverage levels, and also prove that the attack ratios are decreasing functions of vaccine coverage levels. Some thresholds are presented, which depend on the vaccine efficacy. It is proved that for vaccination games in homogeneous mixing population, there is a unique Nash equilibrium for each game.
... Additionally, increased public awareness of -red flags‖ of autism in young has contributed to greater numbers of young children being identified on the spectrum. Claims of rising prevalence attributed to environmental exposure of toxins through vaccinations have repeatedly been unfounded (Chen, Landau, Sham, & Fombonne, 2004;Richler, Bishop, Kleinke, & Lord, 2006). ...
Article
This dissertation focuses on the design and implementation of an early intervention protocol—the Early Social Interaction-Community Outreach Project (ESI-CO)—for families with limited education and limited income. The project was modified from an existing parent-mediated intervention, the Early Social Interaction Project (Wetherby & Woods, 2006), to increase participation from a population that historically has been underserved, and to place greater emphasis on the influences of family environment and experiences of caregivers of children with ASD. Specific aims of the project were to 1) apply empirically supported methods for promoting treatment attendance, adherence, and retention in the specified population; and 2) provide preliminary outcome data that includes descriptive, quantitative, and qualitative analyses of the experiences of participating families. Participants were 14 families from the Southeast Michigan region. Families received 24 in-home treatment sessions over the course of 5 months with an additional 3 months of resource support. Data were collected and analyzed using a mixed- methods approach. A single-subject multiple baseline design was used to measure caregivers’ acquisition of strategies to facilitate their child’s social engagement and communication, while additional data were collected qualitatively to assess caregivers’ satisfaction with the intervention. Eight families completed the intervention, yielding an attrition rate of 38%. This rate was higher than most other reported autism interventions, but lower than what is typically reported in research with low-income populations. Data are presented on the first four families to complete the intervention. Caregivers demonstrated acquisition of treatment strategies with generalization of skills to activities and families were assisted in identifying and enrolling in community autism resources. Overall, caregivers reported positive experiences with the intervention. The ESI-CO study yields promising results in promoting positive change in families from underserved populations. Future directions will include the recruitment of a larger sample and modifications to the research and intervention design to afford the examination of mediating and moderating factors affecting caregiver and child outcome. Results from the project will contribute to the development of treatment services that are accessible and appropriate for families from diverse socioeconomic backgrounds.
... In order to be thorough it should be mentioned that the mumpsmeasles-rubella vaccine had been considered as a possible cause of autistic disorders but epidemiological and case-control studies deny any increased risk caused by vaccination [100][101][102]. Therefore, this kind of vaccination cannot be considered as a risk factor for the development of autism. ...
Article
Full-text available
Journal of Psychiatry J o u rn al of Psy ch ia tr y 2378-5756 Abstract The causes of pervasive developmental disorders have yet to be resolved. Needless to say, the etiology is complex as are the individual factors, especially in regard to autism. Certain findings may be integrated into early coherent models, but the heterogeneity of findings remains a central feature of autism. The present review examines contemporary areas of research and a few prominent theories specifically dealing with autism. The areas under scrutiny are divided into common academic compartments, such as biological, environmental. Autism represents a very timely topic due to its rising incidence in the population as well as changes in previous concepts occurring at this time. Besides the neurological, biological and epidemiological factors contributing and possibly initiating this disorder we discuss the possible involvement of endogenous morphine, especially in regard to depression and limbic functions. Lastly, we advance the theory that dysfunctional mitochondria appear to be involved in autism as well, explaining the widespread occurrence of its characteristics within the construct of susceptibility to stress and trauma. Thus, the diffuse manifestations of Pervasive Developmental Disorder occur potentially by altering energy processes.
... Our finding of no increased risk of PDD in individuals who received MMR vaccine compared with those not vaccinated was consistent with previous studies that showed no temporal relation between MMR vaccination and the development of PDD within individuals, 7,28,29,39-42 and the negative findings from studies that compared incidence rates of PDD with MMR vaccine coverage. 7,28,29,[43][44][45][46][47] We have found no convincing evidence that MMR vaccination increases the risk of autism or other PDDs. No significant association has been found in rigorous studies in a range of different settings. ...
... Environmental triggers have also been implicated; however, research has supported this to a lesser degree. Vaccines have widely been suggested as a possible trigger for the onset of ASDs; however, well-designed investigations have not supported this hypothesis 3,6,38,39,40 . Other environmental factors, including viruses, extreme prenatal stress and the presence of environmental toxins, may warrant further investigation. ...
Research
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Nachshen, J., Garcin, N., Moxness, K., Tremblay, Y., Hutchinson, P., Lachance, A., Beaurivage, M., Breitenbach, M., Bryson, S., Burack, J., Caron, C., Condillac, R. A., Cornick, A., Ouellette-Kuntz, H., Joseph, S., Rishikof, E., Sladeczek, I. E., Steiman, M., Tidmarsh, L., Zwaigenbaum, L., Fombonne, E., Szatmari, P., Martin-Storey, A., & Ruttle, P.L. (2008). Screening, Assessment, and Diagnosis of Autism Spectrum Disorders in Young Children: Canadian Best Practice Guidelines. Miriam Foundation, Montreal, Quebec.
... WoM disseminates stories on vaccine scares [1], epidemic status [2] and public health interventions [3]; its impact may go both ways. Spread of misperceptions on the relative risks and benefits of vaccination may decrease the vaccination coverage [4,5], while concerns that vaccine would be in short supply may increased compliance with vaccination programs [3]. ...
Article
Full-text available
We propose a model describing the synergetic feedback between word-of-mouth (WoM) and epidemic dynamics controlled by voluntary vaccination. We combine a game-theoretic model for the spread of WoM and a compartmental model describing SIR disease dynamics in the presence of a program of voluntary vaccination. We evaluate and compare two scenarios, depending on what WoM disseminates: (1) vaccine advertising, which may occur whether or not an epidemic is ongoing and (2) epidemic status, notably disease prevalence. Understanding the synergy between the two strategies could be particularly important for organizing voluntary vaccination campaigns. We find that, in the initial phase of an epidemic, vaccination uptake is determined more by vaccine advertising than the epidemic status. As the epidemic progresses, epidemic status become increasingly important for vaccination uptake, considerably accelerating vaccination uptake toward a stable vaccination coverage.
... If there was an association between MMR and autism, rates of autism should have increased when MMR immunization uptake was going up, and conversely. Taylor et al 9 investigated this possibility in a London study where they found no evidence that the massive introduction of MMR in the U.K. in 1988 was associated with a step-up in the rates of autism, a finding subsequently replicated in the same country by Chen et al. 10 In addition, a case series analysis conducted by these researchers failed to document a clustering of onset of autism following MMR immunization. Other ecological studies were conducted by Kaye et al 11 who showed that rates of autism in the U.K. increased between 1988 and 1993, at a time when there was no change in the uptake of MMR in the population. ...
Article
Introduction Over the last seven years, a controversy has developed about the possible etiological role of immunization with respect to autism. The controversy has involved two separate hypotheses. The first hypothesis posited a link between the Measles-Mumps-Rubella (MMR) immunization and autism, and more specifically between the measles component of the MMR vaccine and autism. The second hypothesis involved the exposure of young children through the immunization schedule to excessive amounts of thimerosal, a mercury-based chemical used since the 1930s to stabilize vaccine preparation. These two hypotheses are different, since there is no thimerosal in the MMR vaccine (and never was). Accordingly, each of these hypotheses has given rise to two separate research endeavours, which are summarized below. Recent Research Results The MMR hypothesis In 1998, the publication by a prestigious medical journal of a small case series of 12 children presenting in a gastroenterology department in a London hospital raised the possibility of a new syndrome associating intestinal symptoms, loss of acquired skills and regression in the course of the development, and autism. 1 These children were presumably normal before the regression, which occurred within 14 days of the MMR immunization according to retrospective parental reports. However, no attempts were made to corroborate these retrospective accounts. Neurological investigations showed no signs of brain inflammation or disorder associated with this clinical picture. Endoscopies found lymphoid nodular hyperplasia and chronic colitis, both non-specific inflammatory lesions from the intestine. In the years following this initial report, Wakefield changed his hypothesis and postulated that atypical patterns of exposure to measles virus were a risk for chronic intestinal inflammation and for autistic enterocolitis, a presumably new syndrome. Persistent measles virus infection was thought to increase gut permeability and allow intake of neurotoxins in the body. In susceptible children, MMR would therefore increase the risk of intestinal infection and developmental regression. 2 Wakefield further hypothesized that the widespread use of MMR since the 1970s had been responsible for the epidemic of autism in the world. 3 Several of these predictions have been tested, using a range of different epidemiological designs.
... If the broader society understood the scientific method there would be no autism-vaccine controversy (see, for example, (Chen et al., 2004, Honda et al., 2005, Hornig et al., 2008, Nicol, 2007. The scientific results are clear and have been for a long time, yet many people including celebrities (with Jenny McCarthy leading the way) are still arguing that vaccines cause autism. ...
... Additionally, increased public awareness of -red flags‖ of autism in young has contributed to greater numbers of young children being identified on the spectrum. Claims of rising prevalence attributed to environmental exposure of toxins through vaccinations have repeatedly been unfounded (Chen, Landau, Sham, & Fombonne, 2004;Richler, Bishop, Kleinke, & Lord, 2006). ...
... There have been numerous large scale studies since Wakefield's allegations. [22][23][24] These studies have found no link between the MMR vaccine and the development of autistic spectrum disorders. ...
Article
Chiropractors, as with other primary healthcare clinicians, are often faced with a child whom they suspect may have symptoms of autism, often previously undiagnosed. As such, it is important that there is familiarity with the symptoms, primary of which are difficulties in communicating or relating to other people. Although there is no known cause for autism, various potential aetiologies are under investigation. A number of abnormalities are found in multiple systems and functions in the autistic individual who presents a number of management challenges. Some researchers have discovered a laterality of the atlas in children with autism and there are various suggestions as to why removing upper cervical dysfunction may have a positive effect on the symptoms of autism. This paper offers a systematic review of the condition with emphasis on the elements pertinent to the manual therapist.
... The scientific and medical community rose to this challenge and the MMR vaccine could now arguably be the most studied and investigated vaccine in history, with studies conducted worldwide. At least three systematic reviews, including a Cochrane review, (Demicheli et al, 2005;Jefferson et al, 2003;Wilson et al, 2003) and numerous studies (Afzal et al, 1998;Black et al, 2002;Chen et al, 2004;Farrington et al, 2001;Honda et al, 2005;Kaye et al, 2001;Madsen et al, 2002;Mäkelä et al, 2002;Peltola et al, 1998;Smeeth et al, 2004;Takahashi et al, 2003;Taylor et al, 2002) have been conducted to investigate a causal association between MMR, autism and bowel disorder. ...
Article
One of the biggest challenges to professionals involved in immunisation delivery in recent years has been the controversy surrounding the safety of the measles, mumps and rubella (MMR) vaccine. This article explores the history of the vaccine, the controversy and its impact on uptake rates. In discussion potential winners and losers are considered with the conclusion being that there are very few winners among the affected healthcare professionals, children, parents, the NHS and UK government .
... However, by the time of this survey (autumn 2004), a large body of further research had been published that has been unable to find evidence of any causal link (see, e.g. Chen et al., 2004;Farrington et al., 2001;Kaye et al., 2001). Finally, there was some confusion about what actually comprised ASD, with one respondent considering Attention Deficit/Hyperactivity Disorder (AD/HD) to be part of the autistic spectrum. ...
Article
How social workers perceive autistic spectrum disorders (ASD) will inevitably impact upon how they assess the needs of children with ASD and their families, and upon the types of service or interventions they seek to provide to meet those needs. However, little is known of social workers’ understanding of the condition. Using a research instrument devised by Mavropoulou and Padeliadu (2000), a study was carried out of all social workers working with disabled children in an English local authority. The results showed that though many workers had a good understanding of some aspects of the condition, there was also confusion about some key facts concerning ASD, the characteristics of ASD and scientific terminology, an inaccurate understanding of intervention approaches, and a more positive attitude towards the ability of generic services to meet need than was supported by the literature. Implications are discussed in terms of the provision of services to families of children with ASD in the UK, and the limitations of this study are recognized
... However, systematic reviews have failed to identify any clear association between ASD and susceptibility to viral infections or gastrointestinal or other disorders. [71][72][73][74] Nevertheless, it is clear that diagnosing physical problems in people who cannot adequately describe feelings of pain or distress presents many challenges, and there is evidence that undiagnosed or inappropriately treated physical symptoms may be the cause of aggressive, self-injurious, or other challenging behaviours. 75 ...
Article
Chapter
As the central topic of this book, it is important to clarify what echo chamber means. One of the definitions is a condition when a person is only surrounded by opinions similar to their own. Consider the case of American politics. If a person comes from an area where the Republican Party constantly wins the local and national election, it is very common for them to have most of their closest people to be Republican Party supporters too. This results in the person to not be exposed with opinions that support Democratic Party.
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Autism is a complex developmental disorder and is characterized by deficits in social skills and behavior. Regarding the aetiology, there is no single cause but many theories that try to explain the appearance of autism. These causes could take many forms, such as defective genes, chromosomal abnormalities, metabolic disorders, infectious viruses. Any possible cause could affect the vital system involved in autism, whether or not it affects other systems (Frith, 1994). Developments in genetics identify the relationship between genes and autism, while exploring whether exposure to chemicals "enhances" autistic behavior. An indirect demonstration of "triggering" an autistic behavior due to exposure to chemicals stems from studies demonstrating the body's sensitivity to substances such as lead, ethyl alcohol and methyl mercury (Landrigan, 2010). This paper aims to present and expose research and studies, through the bibliographic review, on the environmental factors that affect or not affect the manifestation of autism.
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Cases of autistic disorder (autism) have frequently been reported in association with congenital rubella and other infections. These observations stimulated further investigation into markers of immune function in autism. Postinfectious and autoimmune mechanisms of pathophysiology have been proposed. This review comprehensively addresses immune findings to date, including the role of viruses, neuroimmune factors, cellular and humoral immunity, immunogenetics, and immunotherapy in relation to autism. Although numerous immune abnormalities have been identified in autism, inconsistent results have often been reported. To date, research in this area has largely involved small, uncontrolled studies. In order to bring clarity to this field, high-quality, systematic research is needed to explore the role of neuroimmunologic factors in autism.
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Autism, as any other pervasive developmental disorder, is the object of a large number of studies at present time. However, its aetiology is still unknown. Its heterogeneous manifestations, together with a diversity of clinical criteria and results from research, make its study a difficult task, and correspondingly, the application of preventive strategies in order to minimize its effects. The goal of this article is to offer an actual view of autism and to give answers to questions that still remain about it. In an effort to clear up its fickle symptomatology, a review of the most important authors and the main emergent lines of research in the scientific production are presented, as well as its prevalence and etiopathogeny.
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This chapter describes the establishment and ongoing implementation of Metropolitan Atlanta Developmental Disabilities Study (MADDS) and Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP) that are used a public health framework for understanding developmental disabilities. To providing ongoing estimates of prevalence that are useful for policy, prevention, and intervention planning, MADDSP facilitates epidemiologic studies to investigate risk and other factors associated with developmental disabilities. The chapter demonstrates the utility of MADDS and MADDSP data to address important public health issues. Such activities help in identifying gaps and help develop future research and policy priorities.
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Autism spectrum disorders (ASDs) affect an estimated 1% of children in the United States. The etiology is probably multifactorial, including genetic components and exposure to infections, toxins, and other environmental factors, particularly unfavorable perinatal and neonatal conditions. There has been an increase in the frequency of diagnosis of ASDs over the last 20 years with a parallel increase in the use of obstetric diagnostic ultrasound, with prenatal ultrasound exposure mentioned as the possible main etiology for autism "epidemics." Central nervous system alterations have been described in ASDs, and certain similar changes have been described in animals after exposure to ultrasound. However, analysis of in utero exposure in humans has failed to show harmful effects in neonates or children, particularly in school performance, attention disorders, and behavioral changes. There is no independently confirmed peer-reviewed published evidence that a cause-effect relationship exists between in utero exposure to clinical ultrasound and development of ASDs in childhood. Ultrasound is a form of energy with effects in the tissues it traverses, and its use should be restricted to medical indications, by trained professionals, for as short a period and as low an intensity as compatible with accurate diagnosis.
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A mass immunization campaign with a Urabe-containing measles-mumps-rubella vaccine was carried out in 1997 in the city of Salvador, northeastern Brazil, with a target population of children aged 1–11 years. There was an outbreak of aseptic meningitis following the mass campaign. Cases of aseptic meningitis were ascertained through data collected from the records of children admitted to the local referral hospital for infectious diseases between March and October of 1997, using previously defined eligibility criteria. Vaccination histories were obtained through home visits of telephone calls. Eighty-seven cases fulfilled the study criteria. Of those, 58 cases were diagnosed after the vaccination campaign. An elevated risk of aseptic meningitis was observed 3 weeks after Brazil's national vaccination day compared with the risk in the prevaccination period (relative risk = 14.3; 95% confidence interval: 7.9, 25.7). This result was confirmed by a case series analysis (relative risk = 30.4; 95% confidence interval: 11.5, 80.8). The estimated risk of aseptic meningitis was 1 in 14, 000 doses. This study confirms a link between measles-mumps-rubella vaccination and aseptic meningitis. The authors discuss the implications of this for the organization and planning of mass immunization campaigns. Am J Epidemiol 2000;151:524–30.
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There is substantial evidence that the genetic liability to autism confers a risk for a range of more subtle social and communication impairments, as well as stereotyped and repetitive behaviours. Recent research suggests that increased expression of particular personality traits may be a manifestation of the liability to autism. To investigate this we examined the personality traits of the adult relatives of 99 autistic and 36 Down's syndrome probands, using the informant version of the Modified Personality Assessment Schedule. There was significantly increased expression of the traits anxious, impulsive, aloof, shy, over-sensitive, irritable and eccentric among the autism relatives with evidence of different profiles for male and female relatives and for parents and adult children. Factor analysis revealed three broad groups of traits, two of which ('withdrawn' and 'difficult') appeared to reflect impairments in social functioning and a third group of anxiety related traits ('tense'). Each of these factors differed in their pattern of associations with the factor we termed 'withdrawn' showing a similar pattern of association to that found for other autism related conditions. The 'tense' factor appeared in part to be related to the burden of caring for an autistic child. This study confirms the finding that particular personality traits may aggregate in the family members of autistic individuals and furthermore that some of these traits may be a manifestation of the liability to autism.
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To determine the knowledge, attitudes, and practices among health professionals regarding the measles, mumps, and rubella (MMR) vaccine, particularly the second dose. Self administered postal questionnaire survey. North Wales Health Authority, 1998. Participants: 148 health visitors, 239 practice nurses, and 206 general practitioners. Respondents' views on MMR vaccination, including their views on the likelihood of an association with autism and Crohn's disease and on who is the best person to give advice to parents, whether they agree with the policy of a second dose of the vaccine, and how confident they are in explaining the rationale behind the second dose. Concerning the second dose of the vaccine, 48% of the professionals (220/460) had reservations and 3% (15) disagreed with the policy of giving it. Over half the professionals nominated health visitors as the best initial source of advice on the second vaccine. 61% of health visitors (86/140), compared with 46% of general practitioners (73/158), reported feeling very confident about explaining the rationale of a two dose schedule to a well informed parent, but only 20% (28/138) would unequivocally recommend the second dose to a wavering parent. 33% of the practice nurses (54/163) stated that the MMR vaccine was very likely or possibly associated with Crohn's disease and 27% (44/164) that it was associated with autism. Nearly a fifth of general practitioners (27/158) reported that they had not read the MMR section in the "green book," and 29% (44/152) reported that they had not received the Health Education Authority's factsheet on MMR immunisation. Knowledge and practice among health professionals regarding the second dose of the MMR vaccine vary widely. Many professionals are not aware of or do not use the good written resources that exist, though local educational initiatives could remedy this.
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A link has been postulated between measles-mumps-rubella (MMR) vaccine and a form of autism that is a combination of developmental regression and gastrointestinal symptoms that occur shortly after immunization. This hypothesis has involved 3 separate claims: 1) that there is new phenotype of autism involving regression and gastrointestinal symptoms, 2) that this new variant is responsible for the alleged rise of autism rates, and 3) that this phenotype is associated with biological findings suggestive of the persistence of measles infection. We tested the first of these claims. If this new "autistic enterocolitis" syndrome had some validity, then 1 or several of the following 6 predictions should be supported by empirical data: 1) childhood disintegrative disorder has become more frequent, 2) the mean age of first parental concern for autistic children who are exposed to MMR is closer to the mean immunization age than in children who are not exposed to MMR, 3) regression in the development of children with autism has become more common in MMR-vaccinated children, 4) the age of onset for autistic children with regression clusters around the MMR immunization date and is different from that of autistic children without regression, 5) children with regressive autism have distinct symptom and severity profiles, and 6) regressive autism is associated with gastrointestinal symptoms and/or inflammatory bowel disorder. Three samples were used. Epidemiologic data on 96 children (95 immunized with MMR at a median age of 13.5 months) who were born between 1992 and 1995 and had a pervasive developmental disorder diagnosis as reported in a recent UK survey (post-MMR sample) were compared with data from 2 previous clinical samples (1 pre-MMR [n = 98] and 1 post-MMR [n = 68]) of autistic patients. All patients were assessed with the standardized Autism Diagnostic Interview (ADI), allowing rigorous comparison of age at first parental concerns and rates of regression across samples. Reliability was excellent on ADI scores, age of parental concern, and developmental regression. Furthermore, data on bowel symptoms and disorders were available in the epidemiologic survey from both pediatric and parental sources, and immunization dates were obtained from computerized records. The prevalence of childhood disintegrative disorder was 0.6/10 000 (95% confidence interval: 0.02-3.6/10 000); this very low rate is consistent with previous estimates and is not suggestive of an increased frequency of this form of pervasive developmental disorder in samples of children who are immunized with MMR. There was no difference in the mean age at first parental concern between the 2 samples exposed to MMR (19.3 and 19.2 months) and the pre-MMR sample (19.5 months). Thus, MMR immunization was not associated with a shift toward an earlier age for first parental concerns. Similarly, the rate of developmental regression reported in the post-MMR sample (15.6%) was not different from that in the pre-MMR sample (18.4%); therefore, there was no suggestion that regression in the developmental course of autism had increased in frequency since MMR was introduced. In the epidemiologic sample, the subset of autistic children with regression had no other developmental or clinical characteristics, which would have argued for a specific, etiologically distinct phenotype. Parents of autistic children with developmental regression detected the first symptoms at a very similar age (19.8 months) to those of autistic children without regression (19.3 months). Moreover, the mean intervals from MMR immunization to parental recognition of autistic symptoms were comparable in autistic children with or without regression (248 vs 272 days; not significant). In the epidemiologic sample, gastrointestinal symptoms were reported in 18.8% of children. Constipation was the most common symptom (9.4%), and no inflammatory bowel disorder was reported. Furthermore, there was no association between developmental regression and gastrointestinal symptoms (odds ratio: 0.63; 95% confidence interval: 0.06-3.2; not significant), and only 2.1% of the sample experienced both problems, a rate that did not exceed chance expectations. No evidence was found to support a distinct syndrome of MMR-induced autism or of "autistic enterocolitis." These results add to the recent accumulation of large-scale epidemiologic studies that all failed to support an association between MMR and autism at population level. When combined, the current findings do not argue for changes in current immunization programs and recommendations.
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The uptake of the combined measles, mumps and rubella immunisation (MMR) in Britain has fallen since 1998, when a link was hypothesised with the development of bowel disorders and childhood autism. Despite reassurances about the safety of MMR, uptake levels remain lower than optimal. We need to understand what influences parents' decisions on whether to accept MMR or not so that health professionals can provide a service responsive to their needs. To investigate what influences parents' decisions on whether to accept or refuse the primary MMR immunisation and the impact of the recent controversy over its safety. Qualitative study using focus group discussions. Forty-eight parents, whose youngest child was between 14 months and three years old, attended groups at community halls in six localities in Avon and Gloucestershire. Purposive sampling strategy was used to include parents from a variety of socioeconomic backgrounds. Three groups comprised parents who had accepted MMR and three groups comprised parents who had refused MMR. Data analysis used modified grounded theory techniques incorporating the constant comparative method. All parents felt that the decision about MMR was difficult and stressful, and experienced unwelcome pressure from health professionals to comply. Parents were not convinced by Department of Health reassurances that MMR was the safest and best option for their children and many had accepted MMR unwillingly. Four key factors influenced parents' decisions: (a) beliefs about the risks and benefits of MMR compared with contracting the diseases, (b) information from the media and other sources about the safety of MMR, (c) confidence and trust in the advice of health professionals and attitudes towards compliance with this advice, and (d) views on the importance of individual choice within Government policy on immunisation. Parents wanted up-to-date information about the risks and benefits of MMR to be available in advance of their immunisation appointment. Many parents did not have confidence in the recommendations of health professionals because they were aware that GPs needed to reach immunisation targets. Most parents would, however, welcome more open discussion about immunisation with health professionals.
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Objectives: To investigate whether measles, mumps, and rubella (MMR) vaccination is associated with bowel problems and developmental regression in children with autism, looking for evidence of a "new variant" form of autism. Design: Population study with case note review linked to independently recorded vaccine data. Setting: Five health districts in north east London. Participants: 278 children with core autism and 195 with atypical autism, mainly identified from computerised disability registers and born between 1979 and 1998. Main outcome measures: Recorded bowel problems lasting at least three months, age of reported regression of the child's development where it was a feature, and relation of these to MMR vaccination. Results: The proportion of children with developmental regression (25% overall) or bowel symptoms (17%) did not change significantly (P value for trend 0.50 and 0.47, respectively) during the 20 years from 1979, a period which included the introduction of MMR vaccination in October 1988. No significant difference was found in rates of bowel problems or regression in children who received the MMR vaccine before their parents became concerned about their development (where MMR might have caused or triggered the autism with regression or bowel problem), compared with those who received it only after such concern and those who had not received the MMR vaccine. A possible association between non-specific bowel problems and regression in children with autism was seen but this was unrelated to MMR vaccination. Conclusions: These findings provide no support for an MMR associated "new variant" form of autism with developmental regression and bowel problems, and further evidence against involvement of MMR vaccine in the initiation of autism.
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A new form of inflammatory bowel disease (ileocolonic lymphonodular hyperplasia) has been described in a cohort of children with developmental disorder. This study investigates the presence of persistent measles virus in the intestinal tissue of these patients (new variant inflammatory bowel disease) and a series of controls by molecular analysis. Formalin fixed, paraffin wax embedded and fresh frozen biopsies from the terminal ileum were examined from affected children and histological normal controls. The measles virus Fusion (F) and Haemagglutinin (H) genes were detected by TaqMan reverse transcription polymerase chain reaction (RT-PCR) and the Nucleocapsid (N) gene by RT in situ PCR. Localisation of the mRNA signal was performed using a specific follicular dendritic cell antibody. Seventy five of 91 patients with a histologically confirmed diagnosis of ileal lymphonodular hyperplasia and enterocolitis were positive for measles virus in their intestinal tissue compared with five of 70 control patients. Measles virus was identified within the follicular dendritic cells and some lymphocytes in foci of reactive follicular hyperplasia. The copy number of measles virus ranged from one to 300,00 copies/ng total RNA. The data confirm an association between the presence of measles virus and gut pathology in children with developmental disorder.
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It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism. We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish Civil Registration System, which assigns a unique identification number to every live-born infant and new resident in Denmark. MMR-vaccination status was obtained from the Danish National Board of Health. Information on the children's autism status was obtained from the Danish Psychiatric Central Register, which contains information on all diagnoses received by patients in psychiatric hospitals and outpatient clinics in Denmark. We obtained information on potential confounders from the Danish Medical Birth Registry, the National Hospital Registry, and Statistics Denmark. Of the 537,303 children in the cohort (representing 2,129,864 person-years), 440,655 (82.0 percent) had received the MMR vaccine. We identified 316 children with a diagnosis of autistic disorder and 422 with a diagnosis of other autistic-spectrum disorders. After adjustment for potential confounders, the relative risk of autistic disorder in the group of vaccinated children, as compared with the unvaccinated group, was 0.92 (95 percent confidence interval, 0.68 to 1.24), and the relative risk of another autistic-spectrum disorder was 0.83 (95 percent confidence interval, 0.65 to 1.07). There was no association between the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder. This study provides strong evidence against the hypothesis that MMR vaccination causes autism.
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The hypothesis that direct exposure to or clinical illness with measles, rubella, mumps or chickenpox may play a causal role in autism has been evaluated. The study subjects were 163 cases of autism and their 355 unaffected siblings. Medical data relating to prenatal life and early infancy were obtained by interviewing the parents, and from medical records. Medical records were found for only about half the instances In which a pertinent illness or exposure was reported in the home Interview. However, there was no evidence of systematic bias In recall on the part of parents when reporting on an index case. When medical records and parental statements were both available they were relatively consonant. Increased frequency of combined illness and exposure was seen for the cases relative to their sibling controls with regard to prenatal measles, rubella and mumps and to postnatal mumps. Yet the proportion of cases with histories of viral experience during the periods of interest was small, indicating that these four viruses were unlikely to have played a major role In any substantial proportion of the cases. Some associations were noted with parental histories of other infections during gestation or infancy. Again, however, the proportion of cases that could be accounted for by any of these associations, even if causal, is small.
Article
Measles, mumps and rubella (MMR) vaccination was included in the Danish childhood vaccination programme in 1987. During the following 10-y period, 550 notification records of adverse events after MMR vaccination at 15 mo of age have been registered, and a total of 41 notifications have included “gait disturbance”. This corresponds to a frequency of 8 per 100 000 doses of MMR vaccine used for 15-mo-old children. The symptoms and signs are characteristic of cerebellar ataxia. In 28 notifications, the descriptions by the doctors included only “gait disturbance”, while in 13 an additional interpretation was included. Thirty-two parents (78%) filled in a questionnaire and 26 (63%) agreed to participate in a clinical follow-up study. The gait disturbance symptoms mainly occurred 7–14 d after the vaccination, and the duration was median 1–2 wk (range 1 d to more than 4 mo). One-third of the children had symptoms lasting more than 2 wk. Significantly more children with long duration of symptoms had some kind of complaint or clinical signs at the follow-up in 1997. Gait disturbance registered after MMR vaccination seems to be more frequent than hitherto reported. Most cases are mild and short-lasting and a longer duration of symptoms seems to be predictive of late sequelae. A clinical diagnosis of cerebellar ataxia after MMR and the exact frequency of this adverse event remains to be tested in prospective studies.
Article
Parents of children with autism often report problems associated with obtaining a diagnosis of their child's condition, family support, information, and appropriate services. To evaluate any changes in the situation over the last two decades, the families of all members of the West Midlands Autistic Society, age 19 years and below, were asked to fill in a questionnaire that covered aspects of detection, diagnosis, help and information received, and educational provision. Responses were obtained from 127 families, the children of whom formed an older group ages 10 years and above (n=67) and a younger group ages 9 years and below (n=61). Findings show that there have been improvements for the younger group in some areas, such as earlier referral, diagnosis, and statementing. However, the situation with respect to advice given by professionals and the support and provision available after referral is still much the same as that experienced by families of the older group of children. Many difficulties and hurdles remain which hinder parents and children on the path to care in autism.
Article
It has been reported that measles virus may be present in the intestine of patients with Crohn''s disease. Additionally, a new syndrome has been reported in children with autism who exhibited developmental regression and gastrointestinal symptoms (autistic enterocolitis), in some cases soon after MMR vaccine. It is not known whether the virus, if confirmed to be present in these patients, derives from either wild strains or vaccine strains. In order to characterize the strains that may be present, we have carried out the detection of measles genomic RNA in peripheral mononuclear cells (PBMC) in eight patients with Crohn''s disease, three patients with ulcerative colitis, and nine children with autistic enterocolitis. As controls, we examined healthy children and patients with SSPE, SLE, HIV-1 (a total of eight cases). RNA was purified from PBMC by Ficoll-paque, followed by reverse transcription using AMV; cDNAs were subjected to nested PCR for detection of specific regions of the hemagglutinin (H) and fusion (F) gene regions. Positive samples were sequenced directly, in nucleotides 8393–8676 (H region) or 5325–5465 (from noncoding F to coding F region). One of eight patients with Crohn disease, one of three patients with ulcerative colitis, and three of nine children with autism, were positive. Controls were all negative. The sequences obtained from the patients with Crohn''s disease shared the characteristics with wild-strain virus. The sequences obtained from the patients with ulcerative colitis and children with autism were consistent with being vaccine strains. The results were concordant with the exposure history of the patients. Persistence of measles virus was confirmed in PBMC in some patients with chronic intestinal inflammation.
Article
The hypothesis that direct exposure to or clinical illness with measles, rubella, mumps or chickenpox may play a causal role in autism has been evaluated. The study subjects were 163 cases of autism and their 355 unaffected siblings. Medical data relating to prenatal life and early infancy were obtained by interviewing the parents, and from medical records. Medical records were found for only about half the instances in which a pertinent illness or exposure was reported in the home interview. However, there was no evidence of systematic bias in recall on the part of parents when reporting on an index case. When medical records and parental statements were both available they were relatively consonant. Increased frequency of combined illness and exposure was seen for the cases relative to their sibling controls with regard to prenatal measles, rubella and mumps and to postnatal mumps. Yet the proportion of cases with histories of viral experience during the periods of interest was small, indicating that these four viruses were unlikely to have played a major role in any substantial proportion of the cases. Some associations were noted with parental histories of other infections during gestation or infancy. Again, however, the proportion of cases that could be accounted for by any of these associations, even if causal, is small.
Article
Rates of birth in the general population show seasonal fluctuations for reasons that are ill understood. Variations from these general population patterns have been reported for several psychiatric conditions and used as the basis for aetiological hypotheses. In this paper, the evidence for alterations in the expected seasonal fluctuation in birth dates of autistic people is evaluated. A national sample of 1435 autistic individuals and a clinic sample of 196 subjects are compared to general population figures and to 121 sibling controls. Compared with the general population, the national sample showed significant deviations from the expected rate of birth by month. In the clinic sample, differences from the anticipated monthly pattern were only evident when this sample was compared to the sibling controls. A variety of models for seasonal trends, including year quarters, temperature and sine wave forms, were fitted to these variations but no consistent picture emerged.
Article
Clarkson J A (Ross Institute, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK) and Fine P E M. The efficiency of measles and pertussis notification in England and Wales. International Journal of Epidemiology 1985, 14: 153–168. This paper examines methods for estimating the efficiency of measles and pertussis notification with particular reference to England and Wales. Crude estimates are obtained from a comparison of annual numbers of births and notifications, and this approach is modified to include detailed age-specific data. Other sources of data, notably the Hospital In-Patient Enquiry, are used to give detailed estimates over time. These analyses provide evidence for a strong positive correlation between notification efficiency and incidence for both diseases and for a dramatic fall in the notification efficiency for pertussis between 1957 and 1976. This decrease is of particular interest insofar as it could explain in part the apparent fall in size of successive pertussis epidemics during that period. It is estimated that since 1976 the spotter practices of the Royal College of General Practitioners General Practice Research Unit have been approximately 1.5 times more efficient at reporting measles and 2.5 times more efficient at reporting pertussis than the national average for reporting to the Office of Population Censuses and Surveys. Finally it is noted that estimates of notification efficiency are positively correlated with the assumed level of vaccine efficacy, and that all these methods require assumptions concerning the proportion of vaccinations which are recorded, the proportion of vaccinations which are successful in immunizing the recipient, and the proportion of the population which ultimately contracts the infection. In general, measles notification in England and Wales is considerably better than that for pertussis, being of the order of 40–60% for the former and only 5–25% for the latter.
Article
Individual components of cognitive disability were assessed in the siblings of 41 autistic probands and compared with similar measures from a control group of siblings of Down's syndrome individuals. The results showed a significant familial clustering of cognitive disabilities in the siblings of autistic probands. These cognitive impairments included disturbances in expressive and receptive language, specific learning disabilities, and varying degrees of mental subnormality.
Article
Fine P E M [Ross Institute, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom] and Clarkson J A. Measles in England and Wales—II: The impact of the Measles Vaccination Programme on the distribution of immunity in the population. International Journal of Epidemiology 1982, 11: 15–25. Measles notification and vaccination data for England and Wales are analysed to reveal trends in age-specific incidence and immunity levels in successive cohorts born since 1950. A method for cumulating infection and vaccination experience is described in detail. The analysis reveals that there was a trend towards lower incidence rates of measles, and towards younger average age of cases, for the 10 years prior to commencement of the national immunization programme in 1968. Since the immunization programme began, there has been a dramatic and complicated shift in the age pattern of measles immunity in the population, such that some young age groups are now better protected, but some older age groups less well protected, than they were before the programme. These trends are discussed with critical attention to the possibility that they may reflect biases in the available data. It is concluded that the number of susceptibles over 10 years of age is increasing, and that this could have appreciable public health implications in the years to come. It appears that the total number of individuals susceptible to measles has remained relatively constant, between 4 and 4.5 million, before and after the immunization programme. Though consistent with basic theory, this maintenance of constant overall number of susceptibles has not been demonstrated before. Because the implications of these analyses are important for the strategy of measles control, it is important that appropriate serological surveys be carried out in order to assess the validity of the findings.
Article
We examined the relationship between the number of autistic patients, obtained from the register of the National Autism Society (NAS), born each month between January 1953 and December 1988 in England, and the occurrence of influenza epidemics one to nine months before birth. The relative risk of developing autism, for exposure to influenza during gestation, was assessed by a Poisson regression model. Our results indicate that exposure to influenza epidemics during gestation is not associated with autism.
Article
Family history data on 99 autistic and 36 Down's syndrome probands are reported. They confirmed a raised familial loading for both autism and more broadly defined pervasive developmental disorders in siblings (2.9% and 2.9%, respectively, vs 0% in the Down's group) and also evidence for the familial aggregation of a lesser variant of autism, comprising more subtle communication/social impairments or stereotypic behaviours, but not mental retardation alone. Between 12.4 and 20.4% of the autism siblings and 1.6% and 3.2% of the Down's siblings exhibited this lesser variant, depending on the stringency of its definition. Amongst autistic probands with speech, various features of their disorder (increased number of autistic symptoms; reduced verbal and performance ability) as well as a history of obstetric complications, indexed an elevation in familial loading. No such association was seen in the probands without speech, even though familial loading for the lesser variant in this subgroup, was significantly higher than in the Down's controls. The findings suggest that the autism phenotype extends beyond autism as traditionally diagnosed; that aetiology involves several genes; that autism is genetically heterogeneous; and that obstetric abnormalities in autistic subjects may derive from abnormality in the foetus.
Article
Cases of aseptic meningitis associated with measles/mumps/rubella vaccine were sought in thirteen UK health districts following a reported cluster in Nottingham which suggested a risk of 1 in 4000 doses, substantially higher than previous estimates based on cases reported by paediatricians (4 per million). Cases were ascertained by obtaining vaccination records of children with aseptic meningitis diagnosed from cerebrospinal fluid samples submitted to Public Health Laboratories or discharged from hospital with a diagnosis of viral meningitis. Both methods identified vaccination 15-35 days before onset as a significant risk factor and therefore indicative of a causal association. With both, half the aseptic meningitis cases identified in children aged 12-24 months were vaccine-associated with onset 15-35 days after vaccine. The study confirmed that the true risk was substantially higher than suggested by case reports from paediatricians, probably about 1 in 11,000 doses. However, the possibility that the aseptic meningitis induced by vaccination was largely asymptomatic and a chance laboratory finding in children investigated for other clinical conditions, particularly febrile convulsions, could not be excluded. Comparison of national reports of virus-positive mumps meningitis cases before and after the introduction of this vaccine indicated that the risk from wild mumps was about 4-fold higher than from vaccine. Altogether, 28 vaccine-associated cases were identified, all in recipients of vaccines containing the Urabe mumps strain. The absence of cases in recipients of vaccine containing the Jeryl Lynn strain, despite its 14% market share, suggested a higher risk from Urabe vaccine. A prospective adverse event surveillance system using the study methods is currently being established to assess the risk, if any, from the Jeryl Lynn strain which is now the only mumps vaccine used in the UK.
Article
We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.
Article
Several studies have shown familial aggregation of some axis I psychiatric disorders in families ascertained through a single autistic proband. In this study the authors examined the rate of axis I psychiatric disorders in nonautistic relatives from multiple-incidence autism families and the possible relationship of these disorders to the broad autism phenotype. The rates of axis I psychiatric disorders, assessed by using semistructured and family history interviews, were compared in parents, grandparents, and aunts and uncles ascertained through 25 families of multiple-incidence autism probands and 30 families of probands with Down's syndrome. The possible association between selected psychiatric disorders and the broad autism phenotype, assessed directly through semistructured interviews and observational rating measures, was also examined in the two groups of parents. The parents of the autistic probands had significantly higher rates of major depressive disorder and social phobia than the parents of the Down's syndrome probands. The high rate of depression in the parents of the autistic probands was consistent with the high rates of depression and anxiety detected in the grandparents and aunts and uncles in the autism families by family history. There was no evidence of an association, within individuals, between either depression or social phobia and the broad autism phenotype. Relatives of autistic individuals have high rates of major depression and social phobia that are not associated with the broad autism phenotype and cannot be explained by the increased stress associated with raising an autistic child. Alternative mechanisms and the scientific and clinical implications of these findings are discussed.
Article
The delays in notifying infectious diseases can have implications on the efficiency of public health intervention, and allowance should be made when interpreting time trends. Data on notification delays of 15 diseases over 30 years in nine Health Authorities in England are presented. Measles is the most rapidly notified (a median delay of five days between onset and notification) and tuberculosis the slowest (median two months). The notification delay has varied between diseases, between Districts and also over time, and appears to have increased in recent years. The differences are attributed to the relative ratity, acuteness and difficulty of diagnosis of the disease, to administrative differences between Districts and to changes in incidence over time.
Article
We undertook an epidemiological study to investigate whether measles, mumps, and rubella (MMR) vaccine may be causally associated with autism. Children with autism born since 1979 were identified from special needs/disability registers and special schools in eight North Thames health districts, UK. Information from clinical records was linked to immunisation data held on the child health computing system. We looked for evidence of a change in trend in incidence or age at diagnosis associated with the introduction of MMR vaccination to the UK in 1988. Clustering of onsets within defined postvaccination periods was investigated by the case-series method. We identified 498 cases of autism (261 of core autism, 166 of atypical autism, and 71 of Asperger's syndrome). In 293 cases the diagnosis could be confirmed by the criteria of the International Classification of Diseases, tenth revision (ICD10: 214 [82%] core autism, 52 [31%] atypical autism, 27 [38%] Asperger's syndrome). There was a steady increase in cases by year of birth with no sudden "step-up" or change in the trend line after the introduction of MMR vaccination. There was no difference in age at diagnosis between the cases vaccinated before or after 18 months of age and those never vaccinated. There was no temporal association between onset of autism within 1 or 2 years after vaccination with MMR (relative incidence compared with control period 0.94 [95% CI 0.60-1.47] and 1.09 [0.79-1.52]). Developmental regression was not clustered in the months after vaccination (relative incidence within 2 months and 4 months after MMR vaccination 0.92 [0.38-2.21] and 1.00 [0.52-1.95]). No significant temporal clustering for age at onset of parental concern was seen for cases of core autism or atypical autism with the exception of a single interval within 6 months of MMR vaccination. This appeared to be an artifact related to the difficulty of defining precisely the onset of symptoms in this disorder. Our analyses do not support a causal association between MMR vaccine and autism. If such an association occurs, it is so rare that it could not be identified in this large regional sample.
Article
Measles, mumps and rubella (MMR) vaccination was included in the Danish childhood vaccination programme in 1987. During the following 10-y period, 550 notification records of adverse events after MMR vaccination at 15 mo of age have been registered, and a total of 41 notifications have included "gait disturbance". This corresponds to a frequency of 8 per 100,000 doses of MMR vaccine used for 15-mo-old children. The symptoms and signs are characteristic of cerebellar ataxia. In 28 notifications, the descriptions by the doctors included only "gait disturbance", while in 13 an additional interpretation was included. Thirty-two parents (78%) filled in a questionnaire and 26 (63%) agreed to participate in a clinical follow-up study. The gait disturbance symptoms mainly occurred 7-14 d after the vaccination, and the duration was median 1-2 wk (range 1 d to more than 4 mo). One-third of the children had symptoms lasting more than 2 wk. Significantly more children with long duration of symptoms had some kind of complaint or clinical signs at the follow-up in 1997. Gait disturbance registered after MMR vaccination seems to be more frequent than hitherto reported. Most cases are mild and short-lasting and a longer duration of symptoms seems to be predictive of late sequelae. A clinical diagnosis of cerebellar ataxia after MMR and the exact frequency of this adverse event remains to be tested in prospective studies.
Article
Several disorders have been attributed to measles-mumps-rubella (MMR) vaccination during the past decade. The aim of this prospective follow-up study was to identify serious adverse events causally related to MMR vaccination. When the MMR vaccination program was launched in Finland in 1982, a countrywide surveillance system was set up to detect serious adverse events associated with MMR. To obtain detailed case histories vaccinees' clinical charts were reviewed. Serum samples were analyzed to trace concurrent infections. All hospitals and health centers in Finland from 1982 through 1996. Immunization of 1.8 million individuals and consumption of almost 3 million vaccine doses by the end of 1996 gave rise to 173 potentially serious reactions claimed to have been caused by MMR vaccination. In all, 77 neurologic, 73 allergic and 22 miscellaneous reactions and 1 death were reported, febrile seizure being the most common event. However, 45% of these events proved to be probably caused or contributed by some other factor, giving an incidence of serious adverse events with possible or indeterminate causal relation with MMR vaccination of 5.3 per 100,000 vaccinees or 3.2 per 100,000 vaccine doses. Causality between immunization and a subsequent untoward event cannot be estimated solely on the basis of a temporal relation. Comprehensive analysis of the reported adverse reactions established that serious events causally related to MMR vaccine are rare and greatly outweighed by the risks of natural MMR diseases.
Article
To estimate changes in the risk of autism and assess the relation of autism to the mumps, measles, and rubella (MMR) vaccine. Time trend analysis of data from the UK general practice research database (GPRD). General practices in the United Kingdom. Children aged 12 years or younger diagnosed with autism 1988-99, with further analysis of boys aged 2 to 5 years born 1988-93. Main outcome measures: Annual and age specific incidence for first recorded diagnoses of autism (that is, when the diagnosis of autism was first recorded) in the children aged 12 years or younger; annual, birth cohort specific risk of autism diagnosed in the 2 to 5 year old boys; coverage (prevalence) of MMR vaccination in the same birth cohorts. The incidence of newly diagnosed autism increased sevenfold, from 0.3 per 10 000 person years in 1988 to 2.1 per 10 000 person years in 1999. The peak incidence was among 3 and 4 year olds, and 83% (254/305) of cases were boys. In an annual birth cohort analysis of 114 boys born in 1988-93, the risk of autism in 2 to 5 year old boys increased nearly fourfold over time, from 8 (95% confidence interval 4 to 14) per 10 000 for boys born in 1988 to 29 (20 to 43) per 10 000 for boys born in 1993. For the same annual birth cohorts the prevalence of MMR vaccination was over 95%. Because the incidence of autism among 2 to 5 year olds increased markedly among boys born in each year separately from 1988 to 1993 while MMR vaccine coverage was over 95% for successive annual birth cohorts, the data provide evidence that no correlation exists between the prevalence of MMR vaccination and the rapid increase in the risk of autism over time. The explanation for the marked increase in risk of the diagnosis of autism in the past decade remains uncertain.
Article
Considerable concern has been generated in the lay and medical communities by a theory that increased measles-mumps-rubella (MMR) immunization among young children may be the cause of an apparent marked increase in autism occurrence. To determine if a correlation exists in secular trends of MMR immunization coverage among young children and autism occurrence. Retrospective analyses of MMR immunization coverage rates among children born in 1980-1994 who were enrolled in California kindergartens (survey samples of 600-1900 children each year) and whose school immunization records were reviewed to retrospectively determine the age at which they first received MMR immunization; and of autism caseloads among children born in these years who were diagnosed with autism and were enrolled in the California Department of Developmental Services regional service center system. Measles-mumps-rubella immunization coverage rates as of ages 17 months and 24 months and numbers of Department of Developmental Services system enrollees diagnosed with autism, grouped by year of birth. Essentially no correlation was observed between the secular trend of early childhood MMR immunization rates in California and the secular trend in numbers of children with autism enrolled in California's regional service center system. For the 1980-1994 birth cohorts, a marked, sustained increase in autism case numbers was noted, from 44 cases per 100 000 live births in the 1980 cohort to 208 cases per 100 000 live births in the 1994 cohort (a 373% relative increase), but changes in early childhood MMR immunization coverage over the same time period were much smaller and of shorter duration. Immunization coverage by the age of 24 months increased from 72% to 82%, a relative increase of only 14%, over the same time period. These data do not suggest an association between MMR immunization among young children and an increase in autism occurrence.
Article
Parents and physicians are understandably concerned about the causes and treatment of autism, a devastating disease that affects the entire family. Although much has been learned about autism, there are many gaps in our knowledge about what causes the disorder and how it can be prevented. Autistic symptoms occur along a spectrum, often referred to as autistic spectrum disorder (ASD). Concern has been raised about a possible association between measles-mumps-rubella (MMR) vaccine and inflammatory bowel disease (IBD) and ASD, especially autism with regression. Also, increased requests for educational services related to ASD have raised concerns about possible increases in the incidence of ASD. On June 12-13, 2000, the American Academy of Pediatrics (AAP) convened a conference titled "New Challenges in Childhood Immunizations" in Oak Brook, Illinois. At this conference, parents, practitioners, and scientists presented information and research on MMR vaccine and ASD. Attendees included representatives from select AAP committees and sections as well as federal and other organizations that address related issues. The multidisciplinary panel of experts reviewed data on what is known about the pathogenesis, epidemiology, and genetics of ASD and the available data on hypothesized associations with IBD, measles, and MMR vaccine. Supplemental information was requested from authors who have proposed the hypotheses and other experts in relevant areas. Autism is a complex disorder of uncertain and probably multiple etiologies. Genetic predisposition to ASD may involve as many as 10 genes. Many experts believe that the abnormal brain development in autism occurs before 30 weeks' gestation in most instances. In utero rubella is a known cause of autism. Animal model data support the biologic plausibility that exposure to yet unrecognized infectious or other environmental agents could cause ASD. Several factors may contribute to apparent increases in incidence of ASD in recent years. Most data indicate increased recognition and reporting as primary factors, but the epidemiologic data are insufficient to determine if there has been a true increase in the incidence of ASD. Increased reporting of ASD in recent years has occurred long after the introduction of MMR vaccine in the United States in 1971 and widespread use of this vaccine in the 1970s for routine immunization of children at 12 to 15 months of age. Appropriate detailed studies are needed to define the true incidence and prevalence of ASD. Epidemiologic studies in Europe indicate no association between MMR vaccine and ASD. Some children with ASD have gastrointestinal symptoms, but an increased rate of any specific gastrointestinal disorder in children with ASD has not been established. Studies to detect evidence of measles virus in intestinal tissue specimens from patients with IBD or autism with gastrointestinal symptoms have not used uniform techniques. Several laboratories have found no evidence of measles viruses in tissue specimens from patients with IBD, but 2 groups have found evidence of measles virus using different techniques. A group that found evidence of measles virus in affected tissue specimens from patients with IBD has also reported detecting portions of measles virus in peripheral blood lymphocytes and intestinal tissue specimens from patients with autism and gastrointestinal disorders. Finding a portion of a virus using molecular techniques does not constitute evidence for a causal relationship, because some viruses persist in unaffected hosts. Additional controlled studies in several laboratories are needed to determine if portions of measles virus persist in intestinal and other tissues of people with and without gastrointestinal disease and/or ASD. Although the possible association with MMR vaccine has received much public and political attention and there are many who have derived their own conclusions based on personal experiences, the available evidence does not support the hypothesis that MMR vaccine causes autism or associated disorders or IBD. Separate administration of measles, mumps, and rubella vaccines to children provides no benefit over administration of the combination MMR vaccine and would result in delayed or missed immunizations. Pediatricians need to work with families to ensure that children are protected early in the second year of life from these preventable diseases. Continued scientific efforts need to be directed to the identification of the causes of ASD.
Article
A study of 12 children with pervasive developmental disorders (PDD) claimed that a new variant of autism, induced by immunization with the combined measles, mumps and rubella vaccine, was responsible for increasing rates of PDD worldwide. Subsequent studies from the same authors claimed to have identified evidence of the persistence of measles virus in peripheral blood white cells and gut biopsies. These studies were criticized because they lacked clear definition of the clinical phenotype and independent replication of the findings.
Article
This paper was commissioned by the committee on the Effectiveness of Early Education in Autism of the National Research Council (NRC). It provides a review of epidemiological studies of pervasive developmental disorders (PDD) which updates a previously published article (The epidemiology of autism: a review. Psychological Medicine 1999; 29: 769-786). The design, sample characteristics of 32 surveys published between 1966 and 2001 are described. Recent surveys suggest that the rate for all forms of PDDs are around 30/10,000 but more recent surveys suggest that the estimate might be as high as 60/10,000. The rate for Asperger disorder is not well established, and a conservative figure is 2.5/10,000. Childhood disintegrative disorder is extremely rare with a pooled estimate across studies of 0.2/10,000. A detailed discussion of the possible interpretations of trends over time in prevalence rates is provided. There is evidence that changes in case definition and improved awareness explain much of the upward trend of rates in recent decades. However, available epidemiological surveys do not provide an adequate test of the hypothesis of a changing incidence of PDDs.
Testimony before Congressional Oversight Committee on Autism and Immunization. Hearing before committee on government reform House representative 107th Congress, 2nd sessionStatus of research into vaccine safety and autism '. Series no
  • A Krigsman
Krigsman, A. (2002). Testimony before Congressional Oversight Committee on Autism and Immunization. Hearing before committee on government reform House representative 107th Congress, 2nd session 19 June 2002, on 'Status of research into vaccine safety and autism '. Series no. 107/12, US Government Printing Office : Washington, DC.
Immunisation against Infectious Disease. Standing Medical Advisory Committee, p. 8. Department of Health
  • Department Of Health
Department of Health (1972). Immunisation against Infectious Disease. Standing Medical Advisory Committee, p. 8. Department of Health : London.