MMR Vaccine and Autistic-Spectrum Disorders

Controversy with vaccines, adverse reactions of the MMR vaccine and the negative publicity surrounding it SHAPE Measles, Mumps and Rubella Vaccine: Absence of Evidence for Link to Autistic-Spectrum Disorders Henry K. Nguyen, MD Candidate Increased incidence of measles, mumps, and rubella is directly due to controversies regarding the measles, mumps, and rubella vaccine despite the absence of data supporting a correlation between this combined vaccine and development of autism. Correspondence to: Mentor: Dr.

Anshu Kacker 5650 including Abstracts Increased incidence of measles, mumps, and rubella is directly due to controversies regarding the measles, mumps, and rubella vaccine despite the absence of data supporting a correlation between this combined vaccine and development of autism. Methods and materials: A literature search was performed using key phrases, including the search-requisite abbreviation 'MMR' (measles, mumps, rubella), such as: 'autism mmr vaccine', 'colitis mmr vaccine', 'controversy mmr', 'mmr adverse results', 'vaccines autism-spectrum disorders', 'vaccine effects mmr', 'vaccine measles', and 'vaccine rubella'.

The results were compiled, following which appropriate publications were chosen for review and critical analysis. Results: Detailed analysis of publications found in the literature search reveal negative health effects arising from administration of the measles, mumps, and rubella vaccine. These effects include: arthritis, aseptic meningitis, fever, lowered platelet count, rash, seizures, and swelling of glands. However, none of the reported 'side-effects' include autism and/or autism-spectrum disorders.

Conclusions: Following highly publicized reports by Wakefield and colleagues in the United Kingdom and by Geier and Geier in the United States that directly implicated the measles, mumps and rubella vaccine to childhood autism, 'colitis', and neurological disorders, many parents refused vaccine compliance for their children. Although the reports were later retracted, proven fraudulent, and the physicians/scientists discredited along with their work, the observed incidence of these once nearly eradicated diseases rose, particularly measles and mumps.

No causal connection of significance between the vaccine for measles, mumps, and rubella and childhood autism, autism-spectrum disorders, or pervasive developmental disorders was found. ULTRAMINI ABSTRACT: The now-retracted 1998 publication by Wakefield and colleagues suggested a correlation between childhood autism and the measles, mumps, and rubella vaccine. This false report generated controversy as well as directly decreasing vaccine compliance, raising incidence of these diseases. This study evaluates evidence for any potential vaccine -- autism correlation. Table of Contents Abstract & #8230;.

2 Introduction 4 Materials and methods & #8230; Results 10 Discussion & #8230; 17 Conclusion 21 References 22 Appendix 24 Introduction Historical Overview and Background The general public today considers measles, mumps, and rubella to be relatively benign childhood diseases that are almost completely eradicated.

This obliteration of historical diseases (vide infra) came about through an effectively combined measles, mumps, and rubella (MMR) vaccine that is routinely required in the United States for children prior to entering public school kindergarten, in all but the State of Iowa (CDC, 2008; 2014).That is, these diseases were considered to be 'nearly eradicated' until fairly recently, when a controversial set of publications by Wakefield and colleagues (1998) in the United Kingdom, and by Geier and Geier (2004) in the United States, raised a fairly high public furor with concomitant media attention, leading many parents to fear that MMR vaccine utilization could result in autism and/or autism-spectrum disorders in their children.

Historically, measles were reported in approximately 900 CE by Rhazes, a Persian physician, who noted that smallpox and measles were distinct diseases (The College of Physicians of Philadelphia, 2015a, 2015b). As early as 1657, measles were reported in Boston, but not studied in detail until approximately the mid-1700's, when Francis Home first explored the infectivity of this disease in Scotland. His procedure was to expose healthy patients to the blood of infected patients, and this did result in measles transference (The College of Physicians of Philadelphia, 2015a, 2015b).

Measles is a generally short-term disease that often affects children. It results in 'spots' and/or rashes on the patients skin (hence potentially confused with smallpox), oral lesions, and potential complications in adulthood such as myocarditis, pneumonia, and even a severe 'sclerosing panencephalitis' of the sub-acute form, that can result in motor and mental deterioration that may worsen (Gladwin et al., 2014).

In the case of mumps, skin rashes are also observed for child patients, however other significant symptoms can occur, including orchitis (inflammation of the testes), possibly resulting in sterility for post-pubertal males, and parotitis (swelling of one or both parotid glands). In 1934, Goodpasture and Johnson demonstrated that mumps were infective via transmission of saliva from patients having mumps to Rhesus monkeys (The College of Physicians of Philadelphia, 2014).

By 1948, the first vaccine was made from isolated and inactivated mumps virus; this vaccine was, however not long-lasting in the immunity it produced, and by 1970 it had been discontinued. In 1967, the Jeryl Lynn strain of mumps was prepared via tissue culture as an attenuated live version; this licensed version is still in use, and decreases the incidence of mumps by up to 95% (World Health Organization, 2007). A third mild but common childhood disease, the "German Measles," was initially described in 1740 by Friedrich Hoffman (The College of Physicians of Philadelphia, 2015a, 2015b).

In the mid-1800's, the German measles was re-named 'rubella' (little red) following a large outbreak in India. Infectivity was demonstrated by disease transfer from infected to healthy children in 1939 in Japan. The utter seriousness of rubella was unfortunately demonstrated some thirty years later when a rubella outbreak in the United States resulted in thousands of miscarriages, as well as over 3500 children being born both deaf and blind, and another 8000 children being born deaf.

The total, nearly 20,000 infants born with 'congenital rubella syndrome', brought home the highly serious potential consequences for pregnant women exposed to rubella. These arise because the rubella virus can cross the placenta and significantly perturb fetal development. Unfortunately, these highly deleterious consequences might have been at least partially ameliorated had the warnings of public health officials been heeded (The College of Physicians of Philadelphia, 2015a, 2015b) This disaster resulted in stronger efforts towards vaccine development and led to the work by the American physician Stanley A.

Plotkin, who developed a rubella vaccine. According to Greaves and colleagues (1983), the rubella vaccine has an efficacy of up to 90%. While measles and mumps are related as part of the non-segmented, negative RNA-stranded viral family paramyxoviridae (Gladwin et al., 2014), rubella is from the togavirus family of viruses (World Health Organization, n.d.). The paramyxoviruses can induce host cells to fuse and form giant multinucleated cells, as is the case for retroviruses and the herpes virus, due to their fusion protein (Gladwin et al., 2014).

In children, both measles and mumps are far more severe than rubella, which is generally mild, with only a maculopapular rash (World Health Organization, n.d.) that disappears after as short a time as three days. However, the consequences of rubella for an exposed pregnant woman make this disease of significance because it causes very serious congenital effects. Indeed, in terms of potential complications, rubella is by far the most serious of the measles, mumps, and rubella group.

Embryonic cells are targeted during the period of differentiation and there can be effects in the infant such as pulmonary stenosis, septal defects, patent ductus, blindness, cataract formation, deafness and effects upon the central nervous system including retardation (Gladwin et al., 2014). Thus, it can be seen that measles, mumps, and rubella are generally relatively mild childhood diseases, which can have potentially serious long-term detrimental effects upon newborns, adults, and children.

Because these diseases have an extremely high rate of contagion, the scientific community invested considerable effort into development of successful vaccines. By 1963, the first vaccine for measles reached the public, after considerable testing in rhesus monkeys, efficacy research, and safety trials. The initial measles vaccine, by John Enders and colleagues, was used for nearly 12 years, and during that time, nearly 20 million individuals were vaccinated.

Subsequently, in 1969, Merck improved the measles vaccine with a more highly attenuated version that is part of the combined measles, mumps, and rubella (MMR) vaccine in present use (The College of Physicians of Philadelphia, 2015a, 2015b). It was the combination of the separate vaccines into a single, highly effective MMR vaccine that led to the nearly 99% halting of measles in the United States. Thus, it is now possible to prevent the occurrence of the measles, mumps, and rubella diseases at a level that is well over 90% and may approach nearly 100%.

Autism and The Wakefield Controversy In 1998, Wakefield and colleagues published a manuscript in The Lancet, a leading global medical journal. In this report, the group reported that use of the MMR vaccine could be correlated with colitis and autism in children, based on a report of twelve children having autistic-spectrum disorders; eight of these were said to have onset following their MMR vaccination. This paper further described a series of additional symptoms that were typical for the children, and were defined by Wakefield et al.

(1998) as 'autistic enterocolitis'; they further suggested a potential link between the MMR vaccine and the colitis. What perhaps caused the most damage, however, was a press conference in which Wakefield directly implicated the MMR vaccine as being responsible for the autistic enterocolitis. At this time he suggested avoidance of the MMR vaccine or use of the individual vaccines rather than the combined MMR vaccine.

Although the publication by Wakefield and colleagues (1998) was subsequently retracted, and Wakefield was found to have conflicts of interest due to his own vaccine patents (Berger 2004, Deer, n.d.,), the media 'hype' and public attention to the controversy concerning the MMR vaccine has led to a significant decrease in parental willingness in MMR vaccine compliance for their children.

It later turned out (Deer, n.d., and links therein) that even the supposed children studied by Wakefield and colleagues weren't real 'patients; subsequently most of Wakefield's colleagues on the 1998 publication retracted their support for the work. The Geier and Geier (2004) work in the United States, particularly focused on a mercury stabilizing factor (thimerosal) in the MMR vaccine, led to a similar non-compliance with the vaccine for parents in the United States.

As a result, incidence of measles, mumps, and rubella has risen sharply, and what was once a trio of nearly eradicated diseases have begun to return, first in small outbreaks, and now in larger outbreaks putting an unaware population at risk. Indeed, it can be said that due to the near-eradication of MMR, many of the populace, including pregnant women today, are sadly unaware of the consequences of being exposed to rubella and thus the potentially imminent danger for themselves and their unborn offspring.

It should be stated that the MMR vaccine is not without risks, and these have been documented; however, the relatively mild nature of these effects, and their low frequency justifies the potential risks of vaccine administration. As shown in Table 1 below, the World Health Organization (n.d.) has documented the relatively low advent of side effects from the measles vaccine. Most commonly used vaccines, such as those for yellow fever, tuberculosis, rotavirus, polio, and measles, have very low incidence of side effects and/or adverse reactions.

Table 1: Vaccines recommended by WHO (World Health Organization, n.d.) General side effects from the MMR vaccine are relatively minor, including swelling of neck and cheek glands, fever, and a rash that is generally mild (Centers for Disease Control and Prevention, 2008). Other moderate health issues include arthritis (particularly in women), an ephemeral thrombocytopenic purpura, and possibly seizures (Centers for Disease Control and Prevention, 2008). However, the more severe reactions are quite rare in the general populace, again supporting the advantages of the MMR vaccine.

The consequences of administration of the MMR vaccine have been extensively studied, and are not known to include any form(s) of autism-spectrum disorders or colitis. This paper will probe more fully into correlations between autism-spectrum disorders and the MMR vaccine as well as examining adverse effects of the combined vaccine. Materials and Methods The literature research review utilized online search engines: PubMed, the New England Journal of Medicine, and MEDLINE.

The search phrases used included: 'adverse effects mmr', 'adverse effects vaccines', 'autism-spectrum disorders vaccines', 'measles vaccine', 'mmr controversy', 'mmr vaccine autism', 'mmr vaccine colitis', 'mmr vaccine effects', 'mmr vaccine issues', and rubella vaccine'. Additional de-limiters included publication date (after 2000), authorship, design of study, age of population, and size of samples. Initial reading of abstracts was used to help select articles for review; following this screening and selection, articles were read from abstract to conclusion, results to discussion, and methods if the articles were to be in final selection pool.

Exclusion was generally on the basis of date, but exceptions were made. Articles were subdivided into categories concerning research topic and/or research questions as well as study outcomes. Once final selection was made, the evidence table, Section B, Appendix, was prepared. This Table demonstrates sorting by: first author, publication date, evidence level, study design, population of study, intervention where applicable, and results/outcome.

Evidence level was according to the standards set for by the RLRA course director at Medical University of the Americas: Level 1: Controlled randomized trials; Level 2: Non-randomized controlled trial - prospective (pre-planned) study with predetermined eligibility criteria and outcome measures; Level 3: Observational studies with controls - includes retrospective, case-control studies and cohort studies; Level 4: Observational studies without controls - includes cohort studies without controls, case series without controls, case studies without controls (RLRA Syllabus, Medical University of the Americas, 2014).

Appropriate graphs, figures, tables, and charts within this manuscript, with the exception of the material in the Appendix, are from the cited literature. They are used where necessary to enhance this manuscript. Each item added is labeled and properly cited. Results In this section, articles listed in the Evidence Table, Section B.

Of the Appendix, are discussed and evaluated in terms of the hypothesis: Increased incidence of measles, mumps, and rubella is directly due to controversies regarding the measles, mumps, and rubella vaccine despite the absence of data supporting a correlation between this combined vaccine and development of autism. Specifically, the scientific literature was queried to learn the nature of adverse effects associated with the MMR vaccine, if any; and whether the MMR vaccine can be correlated with occurrence of pervasive developmental disorders and/or autistic-spectrum disorders.

As well, the literature was also queried with respect to the impact of the controversy arising from the Wakefield et al. (1998) and Geier (2004) publications in the United Kingdom and the United States, respectively, upon parental compliance with MMR vaccination for their children. Finally, the literature was queried as to how a non-compliant parental response to the controversy had impacted the population in terms of disease incidence for measles, mumps, and rubella.

Actual Adverse Effects of the MMR Vaccine and Effects of Negative Publicity As is only logical given the immense effect upon public health implicated by the use of a public health inoculation program such as the measles, mumps, and rubella vaccine, the potential of side effects of the MMR vaccine has been a topic of considerable scientific investigation.

However, given the extreme controversy engendered by the reports of Wakefield and colleagues (1998) in the United Kingdom, and by Geier and Geier (2004) in the United States, many previous studies have been re-analyzed, and new investigations have taken place. For example, Benjamin et al. (1992) reported that immunized children had a 1.6-fold higher risk of side effects such as limb symptoms and/or arthritis (with a confidence interval of 95%) as compared with non-immunized children.

Furthermore, for those children immunized under age five, and for female children, the relative risk of these side effects was 1.6-fold higher, while that of older children was 0.7-fold higher. While these side effects were temporary, they did require hospitalization for three of the children. Limitations of the work of Benjamin et al. (1992) include memory/reporting/recall bias as well as selection bias. In another investigation, Castro and colleagues (2005) studied the effects of the MMR vaccine on adult populations in Mexico, using two methods for inoculation: aerosol and subcutaneous injection.

In this work, Castro et al. (2005) observed many of the commonly observed side effects, as well as a few that had not previously been noted. These included: allergy, cough, fever, influenza, otitis, post-auricular swelling, and rhinitis, as described in Table 2 (vide infra). Table 2: Post-vaccination Side Effects, patient reported (Castro et al., 2005) The work by Castro and colleagues (2005) revealed no significant differences in the nature of reported side effects that could be correlated with method of vaccine delivery.

Surprising side effects included lethargy and post-auricular swelling (behind the ear); the latter was uniformly painless and unilateral (Castro, et al., 2005). For those cases where 'lethargy' was reported, three patients, a 4.9-fold increase in the seriological response to mumps was observed, relative to only a 4.5-fold increase in antibodies for those patients who did not report lethargy. In a 2004 study, Geier and Geier found that the mercury (thimerosal-stabilizer in the MMR vaccine) could be correlated with development of autism.

According to their baseline measurement, Geier and Geier (2004) reported significantly increased odds for autism-spectrum disorders that correlated with mercury concentrations. At the time, even though the Wakefield controversy had been in the news, the Geier father and son team did not recommend discontinuance of the MMR vaccine, but did suggest the possible use of separate vaccines for each of measles, mumps, and rubella (Geier and Geier, 2004).

In subsequent years, the credentials of this father-son team have been called into question; the younger Geier was found to have falsified his medical credentials, and to be practicing medicine without a license. As well, both father and son were shown to have serious 'conflict of interest', serving as expert witnesses in legal cases involving negative reactions to the measles, mumps, and rubella vaccines.

Indeed, reporters investigating both Wakefield and Geiers discovered that these individuals (Wakefield and the Geiers) were being paid lucrative salaries to act as expert witnesses in a concerted attack against MMR as well as other vaccines (Deer, n.d.; Deer, 2011). Since the release of their paper attacking the MMR vaccine (Geier and Geier, 2004), their manuscript has not only been retracted, but has been wholly discredited (Deer, n.d.; Deer, 2011). The work of Dayan et al.

(2008), was a cross-sectional investigation, addressing measles and mumps outbreaks in adults of college age who had only received a two-dose vaccination in their youth. These data are reported below in Figure 1, illustrating the large increase in mumps incidence, potentially due to the lack of a 3rd vaccination. Dayan and colleagues suggested that the policy for vaccinations be altered to both eliminate mumps and to avert the potential of future outbreaks. As stated previously (vide supra), mumps in post-pubertal males can potentially lead to sterility (Dayan et al. 2008).

Figure 1: Age-related Mumps Incidence (Dayan et al., 2008) The work by Friederichs et al. (2006) was an epidemiological study of all children born in Scotland between 1987 to 2004. This research revealed an increase in delayed MMR vaccination for those children born in or after 1999, that is, subsequent to the Wakefield controversy (Friederichs et al., 2006).

These scientists also found a significant increase in nursery-aged children after 1998; they predicted an overall rate of immunization in Scotland that was over 90%, but remained less than 95%, so that additional immunizations of the population would be required in order to prevent transmission of measles (Friederichs et al., 2006). More specifically, Friederichs et al. (2006) determined that MMR compliance between 1990 and 1998 was greater than 95% annually, with a 95% interval of confidence. Subsequently however, and in direct correlation with the Wakefield et al. (1998) report, MMR compliance had decreased to 91.7% for the year 2000 in Scotland.

For the year 2001 in Scotland, the compliance rate for MMR vaccinations had dropped to 90.4% (Friederichs et al., 2006); these data were reported to have a 95% interval of confidence. A very interesting study by Parker et al. (2006) probed the 'index patient' who caused the largest measles outbreak in the United States within a decade. Apparently, a visiting Romanian young woman (17 years old) who was un-vaccinated and in a state of viral incubation attended a gathering of approximately 500 individuals. Fifty of these 500 individuals lacked immunity to measles, and of these sixteen acquired measles.

Within six weeks, 34 cases of measles had been confirmed (Parker et al., 2006). Of the 34-confirmed cases, approximately 94% were unvaccinated; as well, two patients had been vaccinated but the vaccine failed (Parker et al., 2006). The data from the work of Parker et al. (2006) are shown in Figure 2. Figure 2: Indiana Patients with Measles From Rash Onset (Parker et al., 2006) Correlation Between MMR Vaccine and Pervasive Development Disorders/Autistic-spectrum Disorders The 2004 case-control work of Smeeth et al. (2004) evaluated 4469 controls vs.

1249 patients with autistic-spectrum disorders, in which it was found that typical MMR vaccination was 82.1% for the controls vs. 78% of the autistic-spectrum cases. This result indicated a 0.86 odds ratio, with a 95% confidence interval, for the potential correlation between MMR compliance and subsequent development of autistic-spectrum disorders. These data clearly do not indicate any significant risk for MMR-vaccinated children developing autistic-spectrum disorders. Nonetheless, it was shown by Andrews et al.

(2002) that the onset memory of autistic children's parents tended to be more strongly associated with MMR-inoculation for those diagnoses taking place after the 1998 Wakefield controversy than for similar children diagnosed before the Wakefield et al. (19982) publication and subsequent media coverage. Indeed, Andrews et al. (2002) were able to demonstrate that parental recall of autism and/or autism-spectrum disorder correlating with MMR inoculation was greater following the Wakefield controversy. Further work by Smeeth et al.

(2004), comparing several studies (Figure 3, vide infra) evaluated the potential correlation of MMR-vaccine associated risk of PPD and/or autism and autism-spectrum disorders, and found no evidence of increased risk. Brown et al. (2011), performed a qualitative analysis of parental decision making in the United Kingdom, focusing on the measles, mumps, and rubella vaccine. In this work, performed some ten years after the Wakefield controversy, Brown et al.

(2011) determined that those parents who continue to reject the use of the MMR vaccine tended to have complex and/or extreme views that were overall 'anti-immunization'; in contrast some parents chose separate/single vaccines and reported hearing 'second-hand' about the Wakefield controversy. Furthermore, this study provided insight into the thinking of the parents.

The general descriptions by parents concerning the Wakefield MMR vaccine controversy comprised five topics: (1) prevalence and severity of measles; (2) policies and health professionals; (3) personal and social consequences of a decision concerning the MMR vaccine; (4) information concerning the measles, mumps, and rubella vaccine and potential alternatives to MMR inoculation; and (5) measles, mumps, and rubella infections (Brown et al., 2011). These investigators also made recommendations with respect to the MMR vaccine, including an increased awareness and adaptation by both medical practitioners and for governmental policy, recognizing the altered understandings of parents.

Figure 3: Meta-analysis of research comparing autism-risk between unvaccinated and vaccinated individuals (Smeeth et al., 2004) Demicheli (2012) performed a thorough review of the measles, mumps, and rubella vaccine in terms of its overall effectiveness and safety. This work included: six case series (self-controlled) covering nearly 15 million children, five trials (randomized control), 27 studies of cohorts, 17 case-control studies, one clinical trial that was controlled, five trials that were times-series, one trial that was a case-crossover, and two ecological studies (Demicheli, 2012).

From this analysis, it was estimated that a single dose of the measles, mumps, and rubella vaccine had the likelihood to prevent clinical mumps at about the 69-81% confidence level for the Jeryl Lynn strain of mumps; a single dose of the MMR vaccine had between a 70-75% effectiveness for prevention of clinical mumps of the Urabe strain (Demicheli, 2012). This author also reported that a single dose of the measles, mumps, and rubella vaccine was likely to be 95% efficacious at prevention of clinical measles (Demicheli, 2012).

The study also probed side effects of the vaccine: most importantly, there was no significant correlation between PPD, autism, or Crohn's disease and the measles, mumps, and rubella vaccine.

With respect to other side effects, the risk of thrombocytopenic purpura was 6.3, at a 1.3-30.1 confidence interval; the risk of aseptic meningitis was 14.28 for the Urabe strain of the vaccine, with 95% confidence between 7.93 and 25.71; febrile convulsions occurred for children under the age of five who received the Jeryl Lynn strain of the vaccine (as well as the RIT 4385 strain, the Wistar RA strain, and the Moraten strain) -- 95% confidence interval data for febrile convulsions was 1.05-1.15 with a risk ratio of 1.10.

Additional data on aseptic meningitis for children receiving the Leningrad-Zagreb strains of the vaccine included a risk of 15.6 with a 95% confidence ration at 10.3 -- 24.2 (Demicheli, 2012). Demicheli (2012) proposed the need for more care in both reporting of safety outcomes in studies of the MMR vaccine, as well as more care in design of the measles, mumps, and rubella vaccines (Demicheli, 2012). Discussion Due to the concatenation of the 1998 Wakefield et al.

paper in the United Kingdom, and the 2004 manuscript by Geier and Geier in the United States, there has been well over fifteen years of ongoing controversy concerning the measles, mumps, and rubella vaccine.

Although both papers were retracted, and both groups of scientists (particularly Wakefield) have been discredited, the public understanding of scientific controversies can be somewhat limited, and it is the controversy concerning the putative correlation between the MMR vaccine and autism that has remained at the forefront rather than the fact that no such correlation has ever been found.

Indeed, although it may not be simple to directly determine the number of individuals who have been stricken with measles, mumps, and/or rubella due to these controversies, it is evident that both the prevalence and the incidence of these once nearly banished 'childhood' diseases has risen. As short a time ago as 2000, the Centers for Disease Control (CDC) declared that measles had been eradicated, yet by 2006 Parker et al. (2006) documented a serious measles outbreak, after no outbreaks had occurred since 1996 (The College of Physicians of Philadelphia, 2015a, 2015b).

Research by Dayan et al. (2008), Friederichs et al. (2006), and Parker et al. (2006) all indicate what appears to be an increased incidence of these diseases, alarming many physicians and public health experts given the ready availability and prevalence of the MMR vaccine. While it was not possible for these studies to directly prove an association between increased prevalence and incidence of rubella, mumps, and/or measles and the MMR controversies, it is possible to demonstrate that the patterns of incidence since 1998 have been altered. Clearly the work of Friederichs et al.

(2006) reveals a higher incidence of both mumps and measles following the 1998 Wakefield controversy; in terms of mumps, the work of Dayan et al. (2008) is slightly limited due to the screening system utilized. As shown above in Table 1, there is no commonly used vaccine that is wholly without risk. For the MMR vaccine, certain symptoms and side effects have been known since its first use on a widespread basis. The work by Benjamin et al.

(1992) confirmed the potential risk of children under five years of age, and particularly girls, developing disorders of joints and limbs following the MMR inoculation the work by Demicheli (2012) and Castro et al., (2005) verified the prevalence of milder post-iinoculation symptoms such as rash and fever. Other, more rare side effects of the MMR vaccine include thrombocytopenic purpura, febrile convulsions, and aseptic meningitis, again, all side effects that had been previously documented for the MMR vaccine and were thus corroborated as consistent, low risk potential outcomes of the vaccination.

The extensive work of Demicheli (2012) had limitations only in terms of age for patients and was otherwise thorough and detailed. Based on all of the studies reported herein, it can be stated that the potential side effects and/or adverse effects which can be directly correlated with MMR vaccination include: thromobcytopenic purpura, fever, swelling of glands in cheek and neck, aseptic meningitis, and seizures; in no case was any evidence for PPD, autism, and/or autistic-spectrum disorder demonstrated as a consequence of MMR inoculation.

The work by Geier and Geier, (2004), addressing the correlation between the thimerosol/mercury stabilizer in vaccines and neurological or neurodevelopmental diseases was subsequently found to be fraudulent. This work, however, had a significant impact upon the climate of parental decision-making with respect to MMR compliance, and can readily be stated to have been as important in the United States, if not globally, as was the Wakefield et al. (1998) controversy in the United Kingdom.

Indeed, it is obvious that Wakefield and the Geier duo have certainly been a focal point of what might be called the movement against vaccination compliance. A particular issue in this case, and a side-note, is that there is some media responsibility here, although certainly Deer (n.d.; 2011) did more than his part to reveal the fraudulence in the United Kingdom.

With the modern era of individuals looking up medical issues online, it becomes increasingly important to not only provide clear-cut information concerning medical controversies, but also to explain such issues in lay terms where possible to assist the public education and ultimate parental decision making that may impact far more than their own child.

Although the report by Wakefield and colleagues (1998) was subsequently retracted, by Wakefield as well as 10 of his 12 collaborators, this report nonetheless had a significant impact upon public understanding of the MMR vaccine specifically, and all vaccines in general. The immense incidence of misinformation and pseudo-science and the correlation of the MMR vaccine with onset of autism in vaccinated children has impacted parental decisions concerning vaccination to this day.

Of particular relevance here, the work of Anderberg (2009) demonstrated that it was precisely the more affluent and educated parents who quickly absorbed the Wakefield misinformation and were quicker to halt immunization of their children, and of course communicate with their social sphere. Although Anderberg (2009) could not directly address the parental 'thinking' or rational processes, it was obvious that those who were educated and knew about the Wakefield controversy were more likely to avoid MMR compliance, vs. The lesser educated parents who were unaware of the controversy.

As well, this controversy demonstrated a clear-cut example to the epidemiological community of what is called 'response bias' (also called 'recall bias'). Andrews et al. (2002) reported a study in which the 'onset recall' by parents for their children having autism or PPD (pervasive developmental disorder) was probed. Whereas parents who had vaccinated their children prior to the 1998 Wakefield controversy did not make a connection between MMR inoculation and the onset of the children's condition, the opposite was true in the case of those children diagnosed after the Wakefield controversy.

After 1998 and the Wakefield controversy, parents of children with a PPD or autism diagnosis recalled onset as being not long after MMR compliance (Andrews et al. (2002). On a more positive note, despite the distrust of public health vaccination programs, suspicion regarding vaccine safety, a re-emergence of measles in the U.S. And UK, and a decrease in measles, mumps, and rubella protection due to overall decreased immunizations, there may yet be some cause for optimism. The study by Brown et al.

(2011) showed that the number of parents choosing to not vaccinate their kids is decreasing. It can be inferred that the controversy surrounding the Wakefield and Geier studies may have begun to subside and parents are realizing that the study was retracted and disproven. In terms of the work by Wakefield (1998), the original manuscript has been retracted and proven to be fraudulent (The Lancet, 2010; The BMJ, 2011; The Times, 2004).

As well, Wakefield himself has lost his medical license, and been found guilty of scientific, medical, and ethical conduct; conflict of interest was also proven in that Wakefield sought to discredit the MMR because he himself had a vaccine patent in process. Additionally, of the 12 original co-authors of the 1998 Wakefield work, ten have formally retracted their analysis suggesting a correlation between autism and the MMR vaccine. Even the organization Autism Watch (2015) has turned against Wakefield. Indeed research by Smeeth et al.

(2004) and by Demicheli (2012) provided clear evidence that no correlation between the MMR vaccine and autistic-spectrum disorders could be.