Nice Essay

Contents Abstract Page 3 Autism Pages 4-7 The Measles Mumps and Rubella (MMR) Vaccine Pages 8-10 Evidence Supporting the Link Between MMR and Autism Pages 11-12 Evidence Abolishing the Link Between MMR and Autism Pages 13-19 Conclusions Pages 20-21 References Pages 22-23 Acknowledgements Page 24 Abstract Considerable concern has been generated as a result of the publication of a paper in 1998 by Andrew Wakefield and colleagues, who postulated an association between autism and childhood immunisation with the measles, mumps and rubella (MMR) vaccine. The passing years have seen a number of media campaigns initiated by the government in an effort to calm the hysterical press and confused families, and to once again restore faith in the MMR vaccine. This paper sets out the facts about autism and measles, mumps and rubella and goes on to critically review the primary evidence surrounding the ‘MMR Debate’. This paper is written with health professionals and parents in mind. Autism ‘Autism’ is word the world is slowly becoming accustomed to hearing. But how many of us can truly say that we know and understand what is meant by the phrase ‘autism’? This section of the report discusses the history, impairments, prevalence and diagnostic criteria of autism. First Accounts Autism was first described by Leo Kanner in 1943 and then again by Asperger in 1944. Both independently used the term ‘autism’ to label a disorder that they described in children whose behaviour followed a category of features (Bishop 1989). At this point, however, there was no attempt to specify defined diagnostic criteria (Bishop 1989). Kanner described two main features in the children he diagnosed to be autistic namely ‘autistic aloneness’ and ‘desire for sameness’. Autistic aloneness refers to the child’s inability to relate to others while ‘desire for sameness’ describes the autistic child’s aversion to change (Smith et al. 2001). In 1978 Rutter suggested that the diagnosis of autism should adopt a structured criterion so as to avoid such chaos as that which reigned for some years after Kanner’s early report (Bishop 1989). While these criterion devised by Rutter have not been without their critics they are widely adopted and form the foundation for the DSM-III and the DSM-III-R (Bishop 1989). The term ‘autism’ is now increasingly being replaced by the concept of a spectrum of autistic disorders, so as to take account of the numerous levels and manifestations of this disorder (Scottish executive 2002). Triad of Impairments Ever since Leo Kanner first described the autistic behaviour pattern, workers in the field have tried to define its essence. This essence has come to be known as the ‘triad of impairments’ affecting social interaction, social communication and imagination (Health Education Board for Scotland 2001). Social Interaction Although most autistic children enjoy certain forms of active physical contact and show attachment on a simple level to parents or carers the child can often appear aloof and indifferent towards others. Often the child will make very little eye contact and initiates interaction only when the help of another is required. It has been suggested that the problem underlying social impairment is lack of the ability to recognise that other people have thoughts and feelings; the absence or impairment of a so-called ‘theory of mind’. Social Communication The problem here is not that the child cannot talk (although a small proportion never develop speech) but that they do not use their vocabularies as tools of social interaction and reciprocal communication. A child can often repeat perfectly what has been said (known as echolalia) but is unable to convey or comprehend information by using words. However, some autistic children are able to ask for their own needs but have difficulty in talking about feelings or thoughts and in understanding the emotions, ideas and beliefs of other people. Imagination In children, inability to play imaginatively with objects or toys or with other children or adults is an outward manifestation of this impairment. Some of these children display a limited range of imaginative activities, which may be pursued repetitively. Some confuse fiction and reality and tell rambling stories they seem to believe are true. The consequence of the impairment of imagination is a very narrow range of repetitive activities or special interests. In addition, their inability to play with other children inevitably means that the autistic child misses out on a vital aspect of development. Prevalence While there appears to be fairly good agreement that autistic spectrum disorder (ASD) affects approximately 60 in every 10, 000 children under 8 years old (Medical Research Council 2001) there is less agreement concerning a rise in prevalence. Recent years have seen divergent views emerging over the question of a rise in autistic spectrum disorders. Table 1 on the following page reviews the literature available concerning the prevalence of ASD’s over the last 20 years. Year Authors Type Measurements Findings 1979 Wing & Gould Study Prevalence (children) 5 per 10,000 children (classic autism)15 per 10,000 (children broader ASD) 1993 Wing Review of 16 studies Prevalence (children) 3.3 to 16 per 10,000 (typical autism) 1993 Ehlers & Gillberg 2-stage total population study Prevalence (children 7-16) Min. 36 per 10,000 children with AS plus equivalent number who did not meet full criteria for ASD 1999 Fombonne Review of 23 studies Prevalence (children) Min. of 18.7 per 10,000 children (all ASD except AS) 1999 Gillberg &Wing Review of epidemiological studies of prevalence of autism Prevalence (children up to 18) 0.7 to 31 per 10,000Estimate made of 1 per 1000 children for classic autism 2000 Powell & Edwards Study of incidence rates 4.8/10,000 p.a. for pre-5 children for “other ASD”3.5/10,000 p.a. for pre-5 children for classic autism 2000 Baird et al. Follow-up population study of prevalence Prevalence (children aged 7) 57.9/10,000 for all ASD’s30.8/10,000 for AD 2000 Centre for Disease Control Survey Prevalence (children 3-10) 67/10,000 for all ASD’s40/10,000 for AD 2001 Chakrabati & Fombonne Prevalence (children 2.5-6.5) 62.6/10,000 for all ASD’s16.8/10,000 for AD45.8/10,000 for other ASD’s including AS Table 1: Reviewing the apparent rise of ASD (Scottish Executive 2002) A review of the literature reveals that ASD’s are considerably more common than previously recognised. However, whether there has been a ‘real’ rise in numbers is unclear. It may be the case that the prevalence of autism has not changed over the years. There have been considerable changes in diagnostic practice as well as public and professional awareness (Scottish Executive 2002). Thus, it could be a combination of these factors and others that create the ‘illusion’ of an increase in autism over the years. Diagnostic Criteria The first symptoms of autism are extremely subtle and thus diagnosis can be extremely complicated. While there are now systematic tools in place for diagnosis, allowing for greater comparability of research studies in the future, we continue to face the disarray posed by the large numbers of studies, which we cannot comfortably contrast due to the different diagnostic criteria employed. The International Classification of Diseases 10th edition (ICD10) is one of the more popular current systems of classification. The table below documents how a child would be diagnosed as having autism using the ICD10. At least 8 of the 16 items must be fulfilled. a. Qualitative Impairments in Reciprocal Social Interaction, as Manifested by at Least 3 of the Following 5:1. Failure adequately to uses eye-to-eye gaze, facial expression, body posture and gesture to regulate social interaction.2. Failure to develop peer relationships3. Rarely seeking and using other people for comfort and affection at times of stress/distress and/offering comfort and affection to others when they are showing distress or unhappiness.4. Lack of shared enjoyment in terms of vicarious pleasure in other peoples’ happiness and /or spontaneous seeking to share their own enjoyment through joint involvement with others.5. Lack of socio-emotional reciprocity. b. Qualitative Impairments in Communication:1. Lack of social usage of whatever language skills are present.2. Impairment in make-believe and social imitative play.3. Poor synchrony and lack of reciprocity in conversational interchange.4. Poor flexibility in language expression and relative lack of creativity and fantasy in thought processes.5. Lack of emotional response to other peoples verbal and non-verbal overtures.6. Impaired use of variations in cadence or emphasis to reflect communicative modulation.7. Lack of accompanying gesture to provide emphasis or aid meaning in spoken communication. c. Restricted, Repetitive and Stereotyped Patterns of Behaviour, Interests and Activities, as Manifested by at Least 2 of the Following 6:1. Encompassing preoccupation with stereotyped and restricted patterns of interest.2. Specific attachments to unusual objects.3. Apparently compulsive adherence to specific non-functional routines or rituals.4. Stereotyped and repetitive motor mannerisms.5. Preoccupations with part-objects or non-functional elements of play material.6. Distress over changes in small, non-functional details of the environment. d. Developmental Abnormalities Must Have Been Present In The first 3 years For The Diagnosis to be Made. Table 2: International Classification of Diseases (ICD-10) issued by the World Health Organisation (WHO1992) Measles, Mumps and Rubella (MMR) Vaccine “Immunisation has been one of the greatest health success stories of the last century.” Dr. Mac Armstrong Chief Medical officer of Scotland Measles Notification of measles began in 1940. The next 28 years saw the occurrence of national epidemics every 2 years, with approximately half a million cases of measles noted each year in the United Kingdom. The measles vaccine was introduced in 1968 and by the mid-1980’s notifications of measles had fallen below 100,000 in any one year (Elliman et al. 2001). Measles is extremely infectious and is transmitted through choughs and sneezes. The complications the measles virus can carry with it are numerous and can be very serious, however, these complications are more common and severe in chronically ill children. Table 3 below lists the problems associated with measles and their prevalence. Ear Infection 1 in 20 Pneumonia/bronchitis 1 in 25 Convulsions 1 in 200 Diarrhoea 1 in 6 Meningitis/encephalitis 1 in 1000 Conditions affecting blood clotting 1 in 6000 Late onset SSPE 1 in 8000 children under 2 years Death 1-2 in 1000 reported cases in recent years Table 3: Complications of measles and their prevalence (Health Education Board for Scotland 2001) Mumps Protection against mumps was first offered with the introduction of the measles, mumps and rubella (MMR) vaccination in October 1988. One year after protection was offered there were 3095 mumps notifications. A decade later, this had fallen to only 216 notifications of mumps. Mumps is an acute viral disease transmitted by respitory droplets. Like measles, mumps can have serious complications, discussed in table 4 below. Death is a rare outcome of mumps. Viral meningitis 1 in 20 Encephalitis 1 in 1000 Inflammation of the testicles 4 in 10 adult males Permanent hearing loss 1 in 20 000 Table 4: Complications of mumps and their prevalence (Health Education Board for Scotland 2001) Rubella The rubella vaccine was introduced in 1970 for immunisation of schoolgirls and susceptible women of childbearing age (Elliman et al. 2001). However, this approach had little affect on the circulation of rubella in the community, therefore, universal protection against rubella was offered through introduction of the MMR vaccine in 1988. Rubella is generally a mild illness. If acquired by mothers in early pregnancy, rubella can have devastating effects on their unborn child. The virus affects all foetal organs and can lead to serious birth defects including learning difficulties, deafness and retardation. The likely outcome of infection in pregnancy is related to the time of gestation. Contraction of rubella can also result in a number of complications, shown in table 5 below: Encephalitis 1 in 6000 Birth defects 90% chance baby will have birth defects if mother catches rubella early in pregnancy. Conditions affecting blood clotting 1 in 3000 Table 5: Complications of rubella and their prevalence (Health Education Board for Scotland 2001) MMR Vaccine MMR is a live vaccine. It contains measles, mumps and rubella viruses that have been modified so that they no longer cause disease symptoms in humans (Medical Research Council 2001). The vaccine contains weakened forms of the natural viruses, which give protection against disease. When injected with the vaccine the child’s immune system responds by making antibodies against the viruses (Health Education Board for Scotland 2001). Moreover, the immune system “remembers” the viruses using special cells called lymphocytes, and so if the child were later infected with the real viruses they are rapidly recognised and the immune system responds quickly to destroy the infection. The first dose of the MMR vaccine is routinely given at around 12-15 months and the second between the ages of 4 and 5 years, as part of the pre-school booster programme (Yazbak 2001). The MMR vaccine has been used for 30 years with an excellent safety record. However, as with all vaccinations there is the chance that the child may be ‘hurt’ by the vaccination i.e. the child may have a reaction to the MMR vaccine that causes damage to the child. This damage may include epilepsy, arthritis, allergies, febrile convulsions, meningitis, SSPE and even death. (Fletcher 2001; Health Education Board for Scotland 2001). There are also some children who cannot have the MMR vaccine for varying reasons. These include children with untreated cancer or diseases of the immune system, those receiving immunosuppressive therapy or high dose steroids, children with allergies to neomycin or kanamycin and those who had a severe reaction to a previous MMR vaccine (Health Education Board for Scotland 2001). Worldwide over 500 million doses of the MMR vaccine have been given since the mid-1970’s (Scottish Executive 2002). The UK alone has distributed approximately 13 million doses since it’s introduction in 1988 (Medical Research Council 2001). Single Vaccinations With the reputation of the MMR vaccine coming under fire in the recent years there has been an increased plea for the availability of single vaccinations. Dr. Andrew Wakefield first raised this issue publicly in a 1998 press interview. The suggestion came from a belief that if children catch measles and mumps within 1 year of each other they are more likely to develop Crone’s disease later. It was also claimed that MMR causes excess diarrhoea compared to single vaccines. With the triple vaccine there is a very low risk of reactions due to there being only 2 separate jags needed for adequate protection. However, giving the vaccines separately would mean a child needing a total of 6 injections to complete course. These children would remain unprotected and at the risk of disease for a longer period of time (Scottish Executive 2002; Health Education Board for Scotland 2001; Elliman et al. 2001). In addition, single vaccinations increase the risk of disease, local reactions at the injection site and trauma to the child, not to mention the risk of missing a dose completely. Thus, the result would be to undermine MMR immunisation, reduce population immunity and increase the risk of children catching these diseases. Evidence Supporting Link Between MMR and Autism The suggestion of a link between the MMR vaccine and autism was first made in a Danish TV programme in 1994, by a mother of twins one of whom had autism, which the mother believed was caused by the MMR vaccine (Health Education Board for Scotland 2001). At that time no scientist had proposed a link. In 1998, Dr. Andrew Wakefield of the Royal Free Hospital in London and his group of researchers published a paper entitled “Illeal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children” in the Lancet. With the publication of this paper the hysteria and confusion, surrounding the MMR vaccine, began. Below is a dissection of Andrew Wakefield’s paper. Unfortunately, despite many attempts to contact Dr. Wakefield he did not reply to any of the questions posed. Thus, instead I have included some comments he has made to the media in recent times, in which he attempts to defend his work. Wakefield 1998 Wakefield’s paper describes 12 children aged between 3 and 10 years of age with developmental and bowel problems. Nine of the 12 children had autism. In eight of these children the onset of their behavioural problems had been linked, either by parental report or by the child’s physician, to the MMR vaccination. Perhaps the most intriguing case Wakefield and colleagues looked at, was one in which a 10 year old boy who received monovalent measles vaccine at 15 months old experienced developmental slowing soon after the vaccination. While these 2 events were not associated at the time, on receipt of the MMR booster at 4.5 years his mother described a ‘remarkable deterioration’ in his behaviour, which she went on to link with the vaccine. The hypothesis put forward by Wakefield and his colleagues was that the MMR vaccine caused a ‘leaky bowel’ allowing a toxin to enter. This effectively prevented the child’s brain from developing normally resulting in autism. Wakefield described this syndrome as “autistic colitis”. The researchers themselves stated that they had not proven this link between autism and the MMR vaccine “We did not prove an association between measles, mumps and rubella vaccine and the syndrome described [autism]…Published evidence is inadequate to show whether there is a change in incidence [of autism] or a link with measles, mumps and rubella vaccine” p641. Moreover, both the editors of the Lancet and one of the co-authors have stated that the study did not set out to investigate the role of MMR in the development of developmental disorder (Scottish Executive 2002). There are however, a number of flaws to this study and multiple potential sources of bias. First and foremost the association between autism and the MMR vaccine was based primarily on parental recall. Thus, recall bias is introduced, as parents are likely to connect changes in their child’s behaviour to a memorable event (MacIntyre 2001). It could be the case that the parents of the children studied, incorrectly recalled the time of onset of the first symptoms, as the first symptoms of autism are extremely subtle, and linked it to the MMR vaccinations as it was given at about the time that symptoms of autism became manifest. Furthermore, Wakefield’s paper does not state how the 9 children with supposed ‘behavioural disorders’ were originally diagnosed. Thus, we have no idea what the criterion for individual diagnosis of ‘autism’ was. The most that is said on the subject is as follows “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” p637. This study was conducted on highly selective sample of patients all of whom were referred to the Royal Free Hospital for gastrointestinal ailments. It is not feasible to generalise results obtained from such a small number of select participants to the rest of the nation, let alone the world. In addition to the aforementioned problems, Wakefield’s studies had no controls, were unbinded and were not designed to test deltiology or harm (MacIntyre 2001). Therefore, a likely explanation of Wakefield’s results could be a mixture of selection bias and chance association. While it may appear the Wakefield is anti-MMR, and it is indeed very easy to make this assumption, Wakefield himself states that he has always and will continue to advocate that children continue to be protected (Sunday Herald 10.02.2002). However, he does believe that parents should be given the choice over how to vaccinate their children. Wakefield asserts that what he’s advocating through this paper is the presence of the “question mark, a question mark that was put there by parents” (Sunday Herald 10.02.2002 p12). Wakefield believes that while his 1998 paper does not prove causation “there is sufficient anxiety that parents must have a choice” (Sunday Herald 10.02.2002 p13). Evidence Abolishing Link Between MMR and Autism When searching for papers concerning the MMR autism debate I found the greatest proportion of papers whose conclusions demolished the link between the MMR vaccine and autism. However, while it was relatively easy to find out which were the primary studies, getting hold of the articles was somewhat more difficult. From the point of view of a concerned parent this obstacle to the information on the subject could prove very frustrating. Each primary source is critically reviewed and discussed below. These studies have been grouped by country of origin. United Kingdom Studies Taylor et al. 1999 An epidemiological study published in the lancet in June 1999 by Brent Taylor and colleagues looked at the immunisation records of 498 autistic children, identified from special needs/disability records, born between 1979 and 1998. The study was set in eight health districts in North Thames. Of the 498 cases identified 261 were diagnosed with core autism, 166 with atypical autism and 71 with Asperger’s syndrome. In 293 cases diagnosis could be confirmed by the criteria of the International Classification of Diseases, tenth revision (ICD10). Moreover, the study is shown to be reliable with inter-rater reliability above 95%. They found reports of autism to be increasing before the introduction of the MMR vaccine and there was no sudden ’step up’ or change in trend of autism after the introduction of MMR; no difference in the age at diagnosis between vaccinated and unvaccinated children; no association between the onset of autism within 18 months after MMR; and no clustering of developmental regression in the months after the MMR vaccination was given. In addition they also noted that uptake of MMR to be the same for autistic children as for the general population. The researchers also looked at the onset of parental concern in 12 time periods, between 1 and 12 months after vaccination. No clustering of parental concern was found, with the exception of one time period, within 6 months after vaccination. They concluded that their findings did not support a causal association between the MMR vaccine and autism due to trends in incidence of autism by birth cohort not being temporally associated with changes in vaccine coverage. “Our results do not support the hypotheses that MMR vaccination is causally related to autism, either its initiation or to the onset of regression.”p2029 While this is a very large population study we must take into account that it was conducted in a very small area of the United Kingdom so we must be careful when generalising the findings reported in this paper to the rest of population. It may be that while MMR coverage did not differ significantly from that in the same birth cohorts in the North East Thames region as a whole this is not to say that it does not vary from other regions throughout Great Britain. In a subsequent publication, in response to a change in hypotheses, Taylor and associates re-analysed their data in relation to the timing of MMR (Farrington et al. 2001). They concluded that there was no evidence of an association was found, providing further evidence against a casual association between MMR vaccination and autistic spectrum disorders. It has been suggested on the ‘Jabs Website’ that the study design used in Taylor’s study is flawed due to the use of case-series analysis, which should only be used with reference to acute events and not chronic events such as autism (Fletcher 2001). Wakefield himself has also criticised the use of this technique by Taylor and colleagues (Wakefield 1999). However, Paddy Farrington the statician working on the paper acknowledges that the case-series method is indeed a valid one to use for “rare chronic disorders of acute onset”(Taylor 1999) Furthermore, Dales et al. (2001) noted that ecological correlations i.e. observations of parallel trends over time, generally speaking, do not constitute strong evidence for a causal association. Kaye et al. 2001 In February 2001 James Kaye and associates published a large-scale study in the British Medical Journal. The study was based in General Practices in the United Kingdom and looked at 305 children, of which 254 were male, aged 12 years or younger diagnosed with autism between 1988 and 1993; with further analysis of boys aged 2 to 5 years also born in this time band. Unfortunately however, analysis was reduced to 114 boys. Approximately 81% of the original subjects were referred to a specialist for the evaluation of their diagnosis of autism. However, the paper does not mention how the remaining 57 participants had been diagnosed. The study reported that there was a seven-fold increase in the diagnosis of autism recorded by UK general practitioners, from 1988 to 1999. Over that same time period there was no change in the proportion of children who had been vaccinated with MMR, which remained at over 95% for the age groups and children in this study. The study authors concluded “the data provided evidence that no correlation exists between the prevalence of MMR vaccination and the rapid increase in the risk of autism over time” due to there being no time correlation existing between the prevalence of the MMR vaccination and the incidence of autism in each birth cohort that they investigated. They go on to acknowledge that the explanation for the notable increase in the incidence of autism throughout the UK remains unexplained. An asset of this study is the use of population-based data in the general practice research database (GPRD) to estimate the birth cohort specific incidence of autism. The data in the GPRD is firmly established to be of high quality and the recording of vaccinations throughout the data are to all intents and purposes complete. However there are also limitations to this study. Kaye and associates did not explore possible explanations for the increase in the incidence of autism over the past decade, nor did they evaluate the full clinical record information from general practitioners, which described the characteristics of children diagnosed with autism. Moreover, it may be the case that Kaye et al. have substantially underestimated autistic spectrum disorders, as the estimated frequency recorded appears to be very low. DeWilde 2001 In March 2001 the British Journal of General Practice published a paper by DeWilde et al. The authors proposed that if there were a close temporal association between MMR vaccination and loss of skills/onset of autistic spectrum disorder then this would be reflected in the increased consultations with the child’s general practitioner. The Doctor’s Independent Network database was used to examine whether children subsequently diagnosed as autistic are more likely to see their GP in the 6 months after MMR vaccination than other non-autistic children. DeWilde et al. concluded that there was no difference in consulting behaviour was seen in the 6 months after the MMR. In addition, the authors commented that any dramatic effect of MMR on behaviour seems unlikely. Perhaps however, parents with autistic children were reluctant to take their children to see the GP for personal or other reasons. This hypothesis was not explored however. Medical Research Council (MRC) 2001 The Medical Research Council was commissioned by the Department of Health to provide a clear picture of what scientific research has revealed about the epidemiology and causes of autism. The report was published in December 2001. The report is split into 6 sections, the bulk of which describes autistic spectrum disorders and their causes. The final section of the report goes on to discuss future research into ASD. Each section of the report answers a question from a ‘lay group’. One such question requires the MRC to examine primary reports, which discuss possible associations between MMR and ASD’s published to date. In looking at these studies the MRC Autism Review concludes that “the current epidemiological evidence does not support the proposed link of MMR to ASD’s” p31. The MRC took account, throughout the review, and in its findings, of relevant “grey” evidence (from parents, case records, and other “non-scientific” sources) in order to gain a more holistic perspective on what is known at present. However, the MRC Review is a very difficult read using technical and ‘jargon’ words throughout the report. Moreover, the report is 91 pages in length making it very laborious to read. Parents may simply not have the time nor the education, which allows them to make sense of the MRC’s findings and recommendations. While the MRC set out to “clarify issues” surrounding the MMR vaccine perhaps they did not fully consider the general public as an audience. Taylor et al. 2002 A further epidemiological study by Taylor and associated investigated evidence of a new variant of autism in relation to the MMR vaccine. This paper was published in February 2002. In total there were 473 participants, 278 children with core autism and 195 with atypical autism, all born between 1979 and 1998. The majority of the subjects were identified from computerised disability registers. Like the previous study classification of autism was made using the criteria of the International Classification of Diseases, tenth revision (ICD10). The study demonstrated that the proportion of children with developmental regression has not changed significantly during the 20 years since 1970. Taylor and colleagues reported evidence to be deficient to support the “new variant” of autism, where MMR is associated with developmental regression. In addition, they found there to be no link between MMR and autism at any time period examined after vaccination. “The single multivariable logistic regression models confirmed no association between MMR vaccination and regression”p327 Information for this study was available from a number of sources including notes from health visitors and hospitals, child development centres and other community records. This level of information allowed a serial record to be made for each child thus creating a fuller picture. However, data were not collected systematically thus the quantity and quality of information gathered was variable. The study also notes the effect of the extensive publicity surrounding the MMR vaccine. In particular it mentions a “bias associated with changes in history given by the parents” p398. The information provided by the parents of the autistic child, therefore, must be treated with considerable care as they may well have been influenced through the media or other such sources. These studies by Taylor and colleagues are the foundation of the Department of Health’s claim that MMR vaccine has no associations with autism. Scottish Executive Report 2002 The report of the ‘MMR expert group’ is one of the most recent papers available. However, at 103 pages long it is not an easy read! The report was established by the Scottish Executive in response to recommendations set out in the Health and Community Care Committee’s report of the enquiry into issues surrounding the alleged relationship between the combined measles, mumps and rubella vaccine and autism. The report itself is split into 6 sections each answering a different question posed to the group. In addition, the report contains a number of specific recommendations to be considered and possibly implemented. The report goes into depth on 3 papers, namely, Taylor et al. (1999), Dales L. (2001) and Peltola et al. (1998). In addition to these, Taylor’s (2002) study was also looked at briefly. The Expert Group have drawn largely on the report of the Medical Research Council published in 2001, and acknowledge that it is this report which provides a substantive and rigorous academic framework for any future work in this area. Unfortunately, reports in the media have undermined the work of the MMR Expert Group. Media speculation brought into question the relationship of the members of the Expert Group and the companies that distribute the MMR vaccine. While any relationship was strongly denied by the Scottish Executive this has perhaps clouded the publics opinion of the report. “The expert group tried to remain immune to the barrage of media speculation about its work and allegations of in-fighting. Such reports may sell newspapers; they were untrue” p2 Ultimately, the MMR Expert group endorsed the view that the combined MMR vaccine is safer than the single dose option. They also concluded that there is no proven link with autism in children and the MMR vaccine. However, the group did call for more research into the causes of autism. North American Study Dales et al. 2001 This paper in the Journal of the American Medical Association by Dales and associates compared time trends in autism and in MMR immunisation coverage in California. This study was a retrospective analysis of MMR immunisation coverage rates among children born in 1980-1994 who were enrolled in California kindergartens. School immunisation records were reviewed to determine retrospectively they age at which they first received the MMR vaccine. Also analysed was the autism caseloads among children born between 1980 and 1994 that were diagnosed with autism and were enrolled in the California Department of Developmental Services regional service centre system. The study showed there to be almost no change in MMR coverage from 1980 through to 1987. There was a modest increase in coverage in the 1988 birth cohort, followed again by a near plateau with modest change over the next 6 years. On the other hand the trend of autistic disorder caseload through to 1994 was increasing. “Essentially no correlations between the secular trend of early childhood MMR immunisation rates in California and the secular trend in numbers of children with autism enrolled in California’s regional service centre system” p1183. Thus, DR. Dales and colleagues concluded that, the lack of correspondence between the trends in MMR coverage and numbers of autistic disorder cases does not support Andrew Wakefield’s hypotheses. The data presented in this paper inevitably has some limitations. It would have been useful to examine individual immunisation and autism records in the same children; however, these could not be linked (Dales et al. 2001). Further, the childhood immunisation coverage data used in this study do not provide the quantification of percentages of children who received the combined MMR vaccine and those who had separate injections of the measles, mumps and rubella components. In addition, due to the system in place in California it is difficult to measure the actual incidence of autism, as it is impossible to know how many children with autism have actually enrolled in the system. Thus, the estimations of children with autism used in this paper are just that, estimations. Finnish Study Peltola et al. 1998 In 1998, Peltola and colleagues published the results of a Finnish study that examined gastro-intestinal symptoms reported prospectively as adverse events in relation to the MMR vaccine. Peltola and colleagues traced children who not only received the MMR vaccine but who also developed gastrointestinal symptoms or signs lasting 24 hours or more at any time, apart from the first hour, following vaccination. The records were further examined to check if these individuals later developed autistic spectrum disorders or other such neurological signs or symptoms. The authors identified 31 cases of gastrointestinal symptoms. They found no child had developed autistic spectrum disorder when followed up for approximately 10 years after vaccination. This report, however, did not examine the relationship of MMR and autism irrespective of gastrointestinal symptoms. Therefore, the study provides us with no useful information on this particular point. Conclusions There are a number of conclusions we can draw from the evidence reviewed. Firstly, it would appear that all epidemiological evidence does not support causal link between the MMR vaccine and “autistic colitis” and autistic spectrum disorders. However, it is important at this point to recognize that these studies cannot prove that the MMR vaccine is safe but can only exclude specified adverse effects with a certain degree of confidence. There are a number of flaws associated with the epidemiological studies, thus leaving room for criticism and concern. While Wakefield has also received numerous criticisms concerning his studies much of this criticism is not in the medical profession, but from those employed by the Department of Health; in other words those who have a policy which is undermined by Wakefield’s work. Nevertheless, it seems highly unlikely that the Department of Health would continue to support the use of a vaccine, which causes more damage to a child than it does good. In the words of Brent Taylor “the scientific argument is over. We are left with the sensation-seeking, hysterical press, confused families (and some confused health professionals) and a few concerned MPs…it’s just a coincidence that MMR was given about the time that symptoms of autism became manifest” (Personal correspondence). Sadly a balanced scientific argument has given way to personal attacks and unreasoned demands for single vaccines. Public confidence in the vaccine has eroded which has lead to a slump in uptake of the vaccine and cases of measles outbreak throughout the United Kingdom. Without a swift change in public opinion measles, mumps and rubella will become commonplace. While the Government have made roads into changing public opinion through their stringent advertising campaigns, this needs to be further enforced. Moreover, Doctors need to present all of the evidence to parents to allow them to make informed decisions. The debate now needs to move past the safety of the MMR vaccine. Children with autism in Britain are ill served by the current fear that MMR causes autism. What of the provisions that need to be made for them and the burden it brings to the children and their families? It is time to leave the MMR debate in the past and focus on possible causes and abnormalities that underlie autism. It is clear from the MRC report that there is a great deal still to be learned concerning autism and this is where we should concentrate our efforts for future research. References Bishop D. V. M. (1989) “Autism, Asperger’s syndrome and semantic-pragmatic disorder: where are the boundaries?” British Journal of Disorders of Communication 24: 107 Dales L., Hammer S. J. and Smith N. J. (2001) “Time trends in autism and in MMR immunisation coverage in California” Journal American Medical Association (JAMA) 285: 1183 DeWilde S., Carey I. M., Richards N., Hilton S. R., Cook D. G. (2001) “Do children who become autistic consult more often after MMR vaccination?” British Journal of General Practice 51: 226 Elliman D. A. C. and Bedford H. E. (2001) “MMR vaccine-worries are not justified” Archives of Disease in Childhood 85: 271 Farrington C. P., Miller E. and Taylor B. (2001) MMR and autism: further evidence against a causal association” Vaccine 19: 3632 Fletcher J. (2001) “The controversial MMR vaccine” www.jabs.org.uk; accessed on May 28th 2002 Health Education Board for Scotland (2001) “The MMR discussion pack an information guide for health professionals and parents” Kaye J. A., del Mar Melero-Montes M. and Jick H. (2001) Measles, mumps and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis” British Medical Journal 322: 460 MacIntyre C. R. and MacIntyre P. B. (2001) “MMR, autism and inflammatory bowel disease: responding to patient concerns using an evidence based framework” Medical Journal of Australia 175: 127 Medical Research Council (2001) “MRC review of autism research epidemiology and causes” Peltola H., Patja A., Leinikki P., Valle M., Davidkin I. and Paunio M. (1998) “No evidence for measles, mumps and rubella vaccine-associated inflammatory bowel disease or autism in a 14 year prospective study” Lancet 351: 1327 Scottish Executive (2002) “Measles, Mumps and Rubella; Report of the MMR Expert Group” Smith P. K., Cowie H. and Blades M. (2001) “Understanding Children’s Development” Blackwell Publishers Taylor B., Miller E., Ragnu L., Andrews N., Simmons A. and Stowe J. (2002) “Measles, mumps and rubella vaccination and bowel problems or developmental regression in children with autism: population study” British Medical Journal 324: 393 Taylor B., Miller E., Farrington C. P., Petropoulos M. C., Farot-Mayaud I., LI Jun and Waight P. A. (1999) “Autism and measles, mumps and rubella vaccine: no epidemiological evidence for a causal association” Lancet 353: 2026 Wakefield A. J., Murch S. H., Anthony A., Linnell J., Casson D. M., Malik M., Berlowitz M., Dhillon A. P., Thomson M. A., Harvey P., Valentine A., Davies S. E. and Walker-Smith J. A. (1998) “Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children” Lancet 351: 637 Wakefield A. J (1999) “MMR vaccination and autism” Lancet 354: 949 Yazbak F. E. (2001) “Measles, mumps and rubella (MMR) vaccine and autism- MMR cannot be exonerated without explaining increased incidence of autism” British Medical Journal 323: 163 Newspaper Article Sunday Herald 10.02.2002 “MMR: Will we ever be sure it’s safe?” Acknowledgements Firstly, I would like to thank Maggie McGonigle for all her advice and help throughout my writing as well as Brent Taylor who kindly gave me some personal feedback on his work and the work of others, and who also suggested a number of articles, which I have used in the review. My biggest thank you is to Lloyd Allanson for the wonderful insights he has given me into the world of autism, and whose drawings feature on the cover.