Japanese study is more evidence that MMR does not cause autismBMJ 2005; 330 doi: https://doi.org/10.1136/bmj.330.7491.558-a (Published 10 March 2005) Cite this as: BMJ 2005;330:558
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The problems with the Honda/Rutter MMR/autism paper from Japan are only just the start of this. The fact of a dip in autism followed by a large rise when vaccinations increased over 150% in 1993 in Japan (according to official Japanese government figures) is actually evidence of at least two things. It is strong evidence of a causal association between the combination of vaccines and autism-like and related disorders.
It is also evidence of the existence of a dechallenge/rechallenge case series at a population level. Now that is beyond any doubt powerful. The dechallenge occurred by taking MMR away with a positive dip in autism on a population level. This was followed by a rechallenge with a positive rise in autism by reintroducing the single vaccines in place of the MMR. The single vaccines were meant to be administered at 4 week intervals, but according to an NHS publication, Japanese children received them on the same day.
As a psychistrist, unlike average clinicians, Sir Michael Rutter should be no stranger to the strength of dechallenge and rechallenge as proof and here is proof at a population level. This should serve to establish the position irrefutably. However, some would deny the earth is spherical to defend the religion of vaccination. So we could also follow up with clinical studies of adverse drug reactions, applying standard causality assessments over a large population.
Do we hear the stampede of Japanese feet rushing to carry out these studies to save little Japanese babies from a life of brain damage? Or do we hear the sound of a nib scratching out another headline grabbing 'research' paper to claim there is no dechallenge or rechallenge and no evidence of a causal link after Sir Michael's paper, yet another, bites the dust?
One aspect of this paper is wholly unclear. How and why did the Sir Michael Rutter, an English psychiatrist, come to be a co-author on a medical paper by Japanese authors in Japan which concerns Japanese children in Japan, under a Japanese vaccination schedule. All of this seems to have been ignored when the authors commented on the position in England and the USA? There is also no declaration regarding the funding provided for this paper nor any indication of the conflicting interests of the author.
To Email Clifford Miller:
Insert the '@' sign in the email address below instead of the text '[insert an '@' sign here]'
bmj050331[insert an '@' sign here]millercompany.demon.co.uk
Competing interests: Close relative with life-threatening food allergy.
Competing interests: No competing interests
It is not very clear exactly what expertise Sir Michael Rutter brought to the Japanese study. To recap:
"He told the Eye that as he was not an immunologist he could not comment on the suggestion that giving three separate vaccines a short time apart was the same as administering the MMR triple vaccine. But he added that although it was unfortunate that there was little relevant material published on any possible interference between vaccine components, immunologists whom he had consulted doubted that this was a significant issue". 
On the other hand he also seems remarkably non-commital about other possible causes and scale of the problem:
"Prof Rutter said that one good thing that had come out of Dr Wakefield's controversial 1998 paper that raised the MMR alarm, which he believed should not have been published in that form in the Lancet, was that it triggered much useful autism research.
"Some experts convinced of a real rise in autism across the developed world - rather than as many still maintain, better diagnosis and detection - were now looking for an unknown environmental trigger that might interact with an unknown genetic risk. He said that while the MMR could fit that environmental profile, he claimed his and other researchers work showed it did not fit the pattern."
So we are faced with the curiosity that as of 2005 Professor Sir Michael Rutter is still uncertain whether there is an autism epidemic or not, vague about the causes if there is, but convinced if there is - without having personally examined the science - that MMR is not implicated.
Whether he has sufficient scientific grounds for taking sides?
Why - as the leading member of child psychiatric profession in the UK for the last three decades - he did not start to take urgent action in the late 1980s to find out what might be going awry, and why even now all these years later it does not seem of greater urgency?
Why, apart from the MMR issue, researchers were looking for "an unknown environmental trigger" rather than very obviously known one like mercury?
 MMR, The link effect, Private Eye No 1129, 1-15 April 2005, p.27.
Competing interests: Parent of an autistic child
Competing interests: No competing interests
"One of the co-authors of the Honda paper was Professor Sir Michael Rutter, of the Institute of Psychiatry, who had prepared a draft report for GlaxoSmithKline, one of the defendant drug companies in the UK litigation but who was not retained by them. He told the Eye that as he was not an immunlogist he could not comment on the suggestion that giving three separate vaccines a short time apart was the same as administerng the MMR triple vaccine. But he added that although it was unfortunate there was little relevant material published on any possible interference between vaccine components, immunologists whom he had consulted doubted that this was a significant issue" 
What might be considered odd in the circumstances is not what Sir Michael's immunologist associates thought but the fact that the paper never addressed Andrew Wakefield's hypothesis that it was not the triple vaccine but the simultaneity of the vaccines which posed a particular threat to the immune system. Everyone will in fact recall that it was Andrew Wakefield's suggestion back in 1998 that the vaccines be administered at year intervals. It was for this reason that Wakefield was able to look at the pattern reported in the Japan study and find strong support for his scientific view rather than the converse . It would obviously be helpful, even at this late stage if Sir Michael and his co- authors could explain - if they were were attempting to refute Wakefield - as opposed to some other hypothesis, why this was not mentioned. Clearly this did not emerge in any of the media coverage, and might be thought highly misleading.
 Private Eye, No.1129, 1 April-15 April 2005, 'The link effect', p.27.
 Andrew Wakefield and Carol Stott, 'Japanese study is the strongest evidence yet for a link between MMR and autism', http://www.redflagsweekly.com/articles/2005_mar06_2.html
Competing interests: Parent of an autistic child
Competing interests: No competing interests
It is very apparent that the Japanese study is a classic example of poor epidemiology, as I demonstrate in http://bmj.bmjjournals.com/cgi/eletters/330/7483/112-d#99926. Presented with so many such articles, many authors of Rapid Responses to a variety of issues connected with vaccination and especially with MMR vaccination, have questioned the validity of evidence based on epidemiology (e.g. John Stone and Clifford Miller).
However is such evidence invalid? In other words, is epidemiology a science and how useful is it? Let's look at an issue other than the MMR and perhaps the penny will drop. I believe that an epidemiological study of the DPT vaccine is an example that can answer this.
Let’s first have a look at the definition of “epidemiology” (yes, you guessed it, I am quoting from my well-worn Taber’s Cyclopedic Medical Dictionary) and let’s have a look at the best published examples of validity of good epidemiology.
“Epidemiology. Science concerned with defining and explaining the interrelationships of factors that determine disease frequency and distribution”.
* * * * *
DPT (diphtheria, pertussis and tetanus)
For a long time DPT and Polio vaccines were the only vaccines administered to small children. Reactions and ineffectiveness were the subject of literally thousands of papers demonstrating and/or denying them. The most quoted epidemiological data were those from the USA, Japan, Sweden and the UK.
Even though DPT is a 3 in one vaccine (diphtheria, pertussis. and tetanus), the vast majority of papers dealing with reactions and questions of the effectiveness or otherwise singled out the P (pertussis) as assumed to be the most reactogenic component.
USA: in my opinion, to start with, the best representative article dealing with epidemiological data to quote is that by Hutchins et al. (1988) who reported on the (then) current epidemiology of pertussis in the United States. I will mostly quote verbatim and juxtapose their data against their conclusions.
By the way, the original data on which any study is based are published for that very purpose, namely that they serve to provide evidence for the conclusions of the authors and are available for any reader to re-calculate and re-analyse. It is an accepted and legitimate way of analysing published scientific evidence.
Hutchins et al. (1988) wrote “The incidence of pertussis in the United States decreased rapidly during the 20th century, with the most impressive decreases resulting from the widespread use of DTP vaccine since the late 1940’s”.
If we pause there and look at their Figure 1, showing the incidence and mortality from pertussis in the USA between 1922 and 1987, we see that the most impressive fall in both the incidence and mortality was at the time when there was no mass administration of pertussis vaccine in any form.
In contrast to this, when vaccination compliance levels increased substantially, the incidence increased substantially, and the mortality remained stationery. To quote Hutchins et al. (1988): “As a result of immunization laws, vaccine coverage levels against pertussis at school entry have been greater since 1980. During the period 1980-1986, a total of 17,396 cases of pertussis were reported to CDC by weekly telephone reports. The annual incidence of reported pertussis rose during this period from 0.5 cases per 100,000 population to 1.7/100,000. Infants less than 12 months of age had the highest average annual incidence, estimated at 32 cases per 100,000. Children 1-4 years of age accounted for 25% of all cases but had an average annual incidence of only 1/7th that of infants. The incidence rates for all age groups increased consistently between 1982 and 1986. The most impressive relative increases occurred among older adolescents and persons 20 years at age and older. In 1986, 10% of reported cases were in this age group compared to only 5% in 1982. Rates of hospitalisation and complications such as pneumonia, seizures, and encephalopathy associated with pertussis were highest in children less than 6 months of age and declined progressively with increasing age. In addition, the mortality ratio was highest in the same age group.”
Lets’ now further discuss the above data and statements.
Point 1 . The authors ascribe the documented fall in the incidence of pertussis to the introduction of vaccination in the late 1940s. They do not give any vaccination compliance figures, however, it is a well-known fact that the incidence of all infections diseases including pertussis, fell consistently in the last 100 years due to better nutrition, better vitamin C status and better hygiene. The role of vaccination as a cause of this fall cannot be implied or documented. Very few people vaccinated their children during most of that decline because most people could not afford to pay for it. Also, the fall occurred all over the world due to the natural dynamics of diseases and improvements in public health, irrespective of vaccination and in many cases despite vaccination. The best examples are tuberculosis and smallpox. As another example, bubonic plague and scarlet fever disappeared without any, even selective vaccination.
Point 2. The truth seeps through the veil of disclaimers when Hutchins et al. (1988) wrote that between 1980-1986 the incidence of reported cases or pertussis increased [practically more than two-fold] from 0.5/100,000 population to 1.7/100,000, with infants less than 1 year with the highest average annual incidence. With some qualifications as above, this fact is indisputable.
To reiterate, the graph is striking in that it first shows a steady downward trend in the pertussis incidence from 1922 until 1978. Immediately after this the decline in the incidence of pertussis halted and reversed, changing into a consistent sharp incline (taking into account the normal, natural 3-4 year cycle of peaks and troughs that occurs with that disease).
So, what happened in 1978? Let’s quote Hutchins et al. (1988: 105): “In 1978 a nationwide childhood immunization initiative was begun. Individual states passed legislation requiring proof of immunization for school entry at 5-6 years of age. By early 1980, 42 of 50 states, plus the district of Columbia, passed legislation requiring 3 doses of DPT for school entry”. However, 5-6 years of age was not the age when children started their vaccinations with DPT (and polio may I add): they started between 6 to 8 weeks of the babies’ age.
The real meaning of this major epidemiological event? Epidemics of whooping cough occurred straight after vaccination and vaccination pushed the pertussis age down to the most vulnerable age of 6-8 weeks and below 6 months. Another publication (Marchant et al. 1994) demonstrated the highest incidence of whooping cough in the USA between 6 weeks to 4 months of age, i.e. mainly straight after the first and second doses of DPT (Fig 2). These authors also missed the real meaning of their own results, because in the abstract to their article they wrote that the highest incidence of pertussis was in 1 month old infants and declined progressively thereafter. Their graph does show high incidence in the first months of life, but the highest incidence is between 6-8 weeks and 4 months. The high incidence of pertussis within the first month of life shows another important phenomenon, namely the lack of transplacentally transmitted immunity because these were babies born to mothers who had been vaccinated as babies and children. It is a well-established fact that mothers who were vaccinated as babies and children have poor or no transplacentally-transmitted immunity which is normally present, provided to us by Nature, to protect very small babies against any infectious disease (Mulholland 1993) . Vaccination not only destroys the immunity of the recipient, it also has a generational effect by destroying the transplacentally transmitted immunity.
Thus the epidemiology of whooping cough in the USA demonstrated that vaccination with DPT vaccine not only did not speed up the natural downward trend in the pertussis incidence, it caused a marked upswing with the introduction of mandatory vaccination (when practically all babies were vaccinated as soon as they reached 6-8 weeks of age) and maintained a steady upward trend in the incidence in the years to follow.
Further published data support this observed fact. Sutter and Cochi (1992) studied the incidence of whooping cough in the USA based on hospitalisations and mortality and concluded that the incidence of whooping cough in the United States based on those figures may be up to 125,000 cases per year, while also stating that in the year 1934 the highest recorded morbidity of pertussis was 265,265 cases. The meaning: the figure of 125,000 cases per year represents the average pre-vaccine level of the incidence. Sutter and Cochi (1992) concluded “…there is substantial underreporting of pertussis, that severe complications of pertussis (including hospitalizations) are reported preferentially to the CDC, and that the national health impact of pertussis based on these indicators is considerably higher than previously published reports have suggested.”
Conclusions: the enforced vaccination against pertussis resulted in ever increasing incidence of whooping cough in the US. Not only that, vaccination pushed the disease into the most vulnerable age group between 6-8 week to 6 months and destroyed the transplacentally- transmitted immunity.
Sweden Sweden stopped pertussis vaccination altogether in 1979 after the 1977-78 world-wide epidemic of whooping cough in which about 84% of Swedish children who got whooping cough were fully vaccinated and the compliance reached about the same percentage.
We may hear that it was because the Swedish DPT vaccine became less effective due to some changes in its production designed to lower its reactogenicity, This allegedly also lowered its efficacy and resulted in the high incidence of whooping cough in the vaccinated children. This explanation has no foundation because if vaccinated children do not get whooping cough in the interepidemic period it is not due to the efficacy of the vaccine - it is only due to the natural dynamics of the disease (for more detail see below), Not all unvaccinated children get whooping cough in every epidemic, most actually do not. The same factor that prevents all unvaccinated children from getting the disease also protects the vaccinated, it is not the administered vaccine. In other words, in the interepidemic years the vaccine seemed effective, but that was a mistaken explanation.
A ten year follow up of the age distribution of whooping cough in the P-unvaccinated Swedish children revealed the return back to the normal (and beneficial) age distribution of this disease: according to a graph published by Isacson et at. (1993; p. 288. Figure 1) there was no incidence of’ whooping cough in small babies (below the age of one year) and the majority of cases occurred between 5 and 10 years of age.
Whooping cough became a mild disease with no deaths (Taranger 1982). Several year old children can take a bout of whooping cough without much trouble; it is the small babies in whom pertussis is a potentially dangerous disease. So Sweden achieved without any P vaccine what the Americans and others cannot achieve with mandatory and/or high vaccination compliance.
The incidence of whooping cough in pertussis-vaccinated Swedish children was the same as in other countries such as the UK. Taranger (1982) wrote “During 1977-79, 19,000 cases of pertussis (but no deaths) were notified by district medical officers in Sweden. Sweden has a population of about 8 million so this figure is about the same as the number of notified cases in England and Wales during the same period, where 102,000 cases (and 28 deaths) were reported in a population of about 50 million.” In addition to this, parents reported that in a random sample of 743 children born in 1974 - nearly all of whom had three injections of a Swedish-made triple vaccine and 39.4% had already had whooping cough when they began at school at vaccination era. 48.9% of 2000 children born in 1949 had contracted pertussis before the age of eight years.
Despite their success without any pertussis vaccination, Sweden trialled several Japanese-style acellular whooping cough vaccines; the first time in 1986-87 which resulted in the Swedish authorities withdrawing their license application because: “The Division of Drugs judges that the efficacy of the vaccine may be lower than that of whole- cell vaccines. The uncertainty about a possible association with deaths due to serious bacterial infections, which occurred among vaccinated children, has also contributed to the recommendation made by the Division of Drugs of comparative trials between acellular pertussis vaccines and well-known whole-cell vaccines.”
The second series of Swedish trials with several acellular vaccines was in 1990-1995.
According to Olin (1995) “The number of cases accumulated in the Stockholm 1 trial exceeds the number of cases assumed in the sample size calculations. Already in early 1993 the number of cases fitting the primary case definition among children who have received three trial doses, had reached that expected by the planned date of termination in May 1995. Because of this, trial follow-up will be terminated ahead of time, in January 1995.”
In other words, while the small babies without any pertussis vaccine were spared the disease, now they contracted pertussis immediately after being given the trial doses of the acellular pertussis vaccines. This is understandable because whooping cough is a toxin-mediated disease (Pittman 1984).
This is even more important when one considers that between 30% and 80% of the yearly cohort (some 30,000 arid 80,000 respectively out of close to 100,000) of live births participated in the trials of the acellular pertussis vaccines in Sweden.
Sweden resumed whooping cough vaccination of small babies with the acellular P vaccine. Now they are experiencing epidemics of whooping cough in these small babies. The comment of doctors: the vaccine stopped being effective. According to a newspaper report (Kvalsposten Monday 1 November 2004) ‘The vaccine no longer stops whooping cough”. “Whooping cough is making advances in the world 40 years after most industrialised countries began vaccination programmes. The reason seems to be that the vaccine loses effect over time, said researchers in the USA at a medical convention organised by the American Society of Microbiology. The experts were unanimous in recommending countries to start administering booster vaccines to teenagers. Last year 13 infants in the USA died of whooping cough. The deaths usually occur in children whose parents chose not to vaccinate [how does this jell with the above statement that the vaccine lost its effectiveness?] or whose children are too young to have received the jabs.” This quotation shows the outrageous way the desperate provaccinators are commenting on their own failures.
Totally unvaccinated children do not die from whooping cough, unless they are small babies in the first month of life and contracted whooping cough from their fully vaccinated mothers (that failed to provide a much needed transplacentally transmitted immunity because they were vaccinated as babies] and/or siblings who suffered whooping cough at the time of their birth and coupled with treatment mismanagement. Four such deaths were reported by Williams et al. (1998). Four babies, aged 16 days, 4 weeks and two 5 weeks were described as dying from whooping cough. But did they die from whooping cough or something else?
To cut a long story short. all of these babies younger than the vaccination age of 2 months, contracted the disease from their fully vaccinated mothers and/or siblings who suffered whooping cough at the crucial time (later showed by bacteriology). They were all doing quite well until they were admitted in hospital and put on intravenous antibiotics, and not just one, two, and started deteriorating straight after and died. In my well-considered personal opinion, they did not die from whooping cough, they died from those powerful antibiotics administered intravenously.
Japan. Epidemiology of pertussis would not be complete without reporting on the situation in Japan. In this country, not only have they mostly no qualms about using the word “cause” when talking about reactions to vaccines, but they also had specific dynamics in the age of administration of vaccination and withdrawal of certain vaccines. Pertussis was one such vaccine.
Noble et al. (1987) reported on acellular and whole-cell pertussis vaccination in Japan. They wrote: “Whole-cell pertussis vaccines came into use in Japan in 1947, and their administration became mandatory. . .Vaccination consisted of three doses given approximately one to two months apart beginning at approximately 3 months of age, with a booster dose approximately one year after the third dose. The reported incidence of pertussis in Japan fell rapidly after the introduction of the vaccine (Fig 1); deaths decreased correspondingly. Concerns about reactions to smallpox vaccine prompted the Japanese government in 1970 to organize a system for receiving and reviewing claims for injuries associated with vaccinations carried under the Preventive Immunization Law. Implementation of the compensation system subsequently served to draw attention to adverse events associated with pertussis vaccine, and continued use of pertussis vaccine was questioned, particularly in light of the low incidence of reported cases of pertussis in Japan between 1970 and 1975. In a two-month period in winter of 1974-1975, two infants died within 24 hours after receiving diphtheria and tetanus toxoids and pertussis vaccine (DTP). While these events were being investigated, recommendations were made for temporary suspension of the use of DTP. Two months later, routine use of DTP vaccine was again recommended. However, the recommended age at initial administration was raised from 3 months to 2 years as a precautionary measure to avoid other COINCIDENTAL (the emphasis is mine) occurrences: also it was believed that incidence of adverse events caused by, and temporally associated with, pertussis vaccine might be higher during infancy.” At the same time, a Pertussis Vaccine Group was formed to accelerate research and development of improved pertussis vaccine which resulted in the development of acellular vaccines and their introduction in 1981.
No matter what Noble et al. (1987) wrote about a significant increase in the reported incidence of whooping cough, reaching a peak in 1979 (which, as we know, was part of that world-wide regular pertussis epidemic (see above), surprisingly they also wrote “The overall reported incidence of pertussis was higher in 1984 than in the early 1970s, in spite of higher reported coverage levels with vaccine”. In fact, it was three times as high than in 1971-1974. This seemingly paradoxical and contradictory fact is clearly seen in Noble et al.’s (1987) Figure 2: 1352: even though there also seems a perfect fit with the high vaccine uptake rate and low incidence of pertussis between 1966 and 1974, there is a clear direct relationship between a sharply increased vaccine uptake and an equally sharp increase in the reported cases of whooping cough between 1976-1979. Figure 1 in Noble et al. (1987) also supports my analysis of the data.
United Kingdom. When the first media reports in mid 1974 revealed the concern about a possible link between DPT and brain damage, the UK parents stopped vaccinating. The compliance fell down to 30% or even 10%. Contrary to the usual statements from the assortment of the Health Departments all over the world about an alleged epidemic that followed, it was actually followed by the lowest incidence of whooping cough and the longest interepidemic period (Fine and Clarkson 1982). The authors wrote that, although overall pertussis incidence fell in England and Wales after the introduction of mass vaccination in the fifties (as we would expect it to do simply as a continuation of the downward trend that had already been occurring), whooping cough epidemics continued to occur regularly every three to four years. The interepidemic period did not decrease after the 1974/75 low uptake of the vaccine.
When the normal 3-4 year epidemic arrived in 1978, the vaccination compliance by then increased to about 30-60%. However, even so, the age distribution was still beneficial, with only low incidence in babies below the age of one and in 1 year olds and the majority of cases occurring between 2 and 4 years. The same has been observed in former West Germany at the time when there was no national vaccination programme and the compliance was low. Miller and Farrington (1988) wrote “The age distribution [in the Rhine area of former West Germany] was similar to that of cases reported in the UK during 1978 when vaccine uptake was at its lowest with the highest proportion occurring in children aged 2-4 years”. The message is loud and clear: stop vaccinating and not only the age distribution of whooping cough will return back to normal, and small babies will be spared this unpleasant disease, but children will reap the benefit of developing natural immunity at a less vulnerable age. It will also cut out serious damage including deaths caused by the vaccine. This, by the way, is documented by the Japanese epidemiology: shifting the vaccination age to 2 years resulted in the overall infant mortality improving vastly: Japan zoomed from 17th place (high infant mortality rate) to first place in the world.
One point must be addressed, namely that all industrialised countries such as above, claimed success with pertussis vaccination between 1970 and 1975. Without going into any more detail, this was the time when a documented fall in vaccination compliance and natural dynamics of whooping cough resulted in a very long inter-epidemic period with a very low incidence of this disease. With the exception of Japan, no other countries (including the USA) had mandatory vaccination, so the low incidence occurred irrespective of vaccination compliance. However, the UK experienced a major fall in compliance after the first reports of brain damage linked to the pertussis vaccine administration were reported by the media in mid 1974 and Japan stopped vaccinating below 2 years. The world wide low incidence of whooping cough was generally usurped by provaccinators as caused by vaccination. For the reasons outlined above this was totally unwarranted. Indeed, in all vaccinating countries, the incidence of whooping cough increased dramatically after the vaccination compliance increased equally dramatically either due to mandatory vaccination laws (such as in Japan and USA) or due to a documented increased push for vaccination, such as experienced in the UK (Barrie 1983).
Ditchburn (1979) described the incidence of “… whooping cough after stopping pertussis immunisation” in an outbreak which occurred in 1977.
“An epidemic of whooping cough occurred in a rural practice in Shetland, containing 144 children under 16. Before July 1974 all children were immunised against pertussis, but after this date immunisation was stopped. Of the 134 children studied, 93 had been immunised. Sixty-four of the children developed whooping cough. The incidence of infection was similar in those who had and who had not been immunised. The incidence was also similar in those born before and after July 1974. There is no evidence to support the routine use of pertussis immunisation in rural Shetland.”
Interestingly, all of the first eight cases had received pertussis immunisation.
These few examples illustrate that truthful epidemiology of a disease definitely is a very useful and true reflection of the situation. Sometimes, one has to read between the lines and evaluate the data correctly (and not be confused by the incorrect evaluation by the authors) - in other words separate the grain from the chaff.
Hutchins SS, Cochi SL, Brink EW, Patriarca PA et al. 1988. Current epidemiology of pertussis in the United States. Tokai J exp clin Med: 13 (Suppl): 103-109.
Marchant CD, Loughlin AM, Lett SM, Todd CW et al. 1994. Pertussis in Massachusetts, 1981-1991: Incidence, serologic diagnosis and vaccine effectiveness. J infect Dis: 169:1297-1305.
Sutter RW and Cochi SL. 1992. Pertussis hospitalizations and mortality in the United States, 1985-1988. JAMA; 267(3): 386-391.
Isacson J, Trollfors B, Taranger J, Zakriksson G and Lagergard T. 1993. How common is whooping cough in a nonvaccinating country? Pediatr infect Dis J; 12: 284-288.
Taranger J. 1982. Mild clinical course of pertussis in Swedish infants today. Lancet (June 12): 1300.
Olin P. 1995. Acellular pertussis vaccines - a question of efficacy - J Hosp Infection; 30 (Supplement): 502-507.
Pittman, M. 1984. The concept of pertussis as a toxin-mediated disease. Pediatric infectious Disease: 3(5): 467-486.
Williams GD, Matthews NT, Choong RKC, and Ferson MJ. 1998. Infant pertussis deaths in New South Wales 1996-1997. Med J Australia; 168: 281- 283.
Noble GR, Bernier SH. Esber EC, Hardegree MC et al. 1987. Acellular and whole-cell pertussis vaccines in Japan. JAMA;257(10): 1351-1356.
Fine PEM, and Clarkson JA. 1982. Recurrence of whooping cough: possible implication for the assessment of vaccine efficacy. Lancet 1: 666 -669.
Miller E, and Farrington CP. 1988. The current epidemiology of pertussis in the developed world: UK and West Germany. Tokai J exp clin Med: 13 (Suppl): 97-101.
Barrie H. 1983. Campaign of terror, Am J Dis Child: 137:022-923.
Ditchburn RK, 1979. Whooping cough after stopping pertussis immunisation. BMJ; 1: 1601-1603.
Competing interests: None declared
Competing interests: No competing interests
How can Andrew Cole refer to the Japanese research study Honda et al 2005 as “the strongest proof yet that the MMR vaccination does not cause autism” when it is based on the naive hypothesis that the continuing rise in ASD after withdrawal of the MMR vaccine is incompatible with the causal hypothesis – to the exclusion of many other factors that might have contributed heavily to the continual rise in incidence of ASDs despite withdrawal of MMR in 1993.
Takahashi et al 2003 (1), although a small study that requires larger follow-up, makes two very important observations. The team found a “statistically significant association of ASD with monovalent measles immunisation, non-mumps and non-rubella immunisation” and that “results suggest a decreased risk of developing ASD with MMR compared to monovalent antigens”.
Taking Honda et al together with Takahashi et al, one might suspect that
1. Replacing MMR vaccine with monovalent measles vaccine may be expected to cause a rise in the incidence of ASD and
2. If monovalent measles vaccine poses a significant risk of ASD then MMR, which contains the equivalent of a monovalent measles component, might also be expected to pose a risk of ASD.
The rate of increase in ASD throughout the period of Honda et al, 1988-96, might not result solely from any increase attributable to monovalent vaccines but also to other as yet unspecified agents and any alterations to the criteria for diagnosis under review through that period and beyond.
Thimerosal, and therefore ethyl mercury, is suspected of causing ASD. If this is the case, the study period being for children born between 1988 and 1996 includes children born between 1988 and 1992 who may have received MMR vaccine, and up to 150ug mercury in scheduled DTP (3 doses of 25ug in first year of life) and Japanese Encephalitis (JE) vaccines (3 doses of 25ug between 3 and 4 years of age), whereas those born between 1993 and 1996 would be likely to have received monovalent vaccines and no MMR (banned in April 1993) vaccine plus a potential for up to 75 ug mercury as they would not have attained the age for JE vaccination (3 to 4 years of age) before study end 1996.
Also statistics show there was considerable parental concern over MMR vaccines prior to withdrawal as uptake dropped from almost 70% in 1988 to 1.8% in 1992 – and some parents may have become suspicious of other vaccines during the study period confusing the study outcome.
In addition to ethyl mercury there are other potential agents of cause of ASDs and other adverse effects within the MMR and M, M and R vaccines. They range from the attenuated viruses themselves (measles virus was found in autists and not controls by Singh et al and Wakefield et al; MMR vaccine virus was found in the brains of autists and not controls by Singh et al; rubella virus has long been associated as congenital rubella with autism) and adjuvants such as neomycin (2) which is a highly toxic antibiotic and gelatine (3) which has caused anaphylaxis after MMR vaccination. If MMR and monovalent vaccines cause ASDs the constituents must be investigated and adjuvants might feature more highly if, as Takahashi et al suggests, monovalent vaccines carry greater risk of causing ASD; each child may have received several monovalent jabs instead of a single MMR jab.
To complicate analysis further, the Japanese MMR vaccines used at the time of these studies were of different types and might present separate risks for causing ASDs. Kimura et al 1996 (4) shows that Standard MMR was associated with 16.6 cases of aseptic meningitis/10,000 recipients compared to Biken MMR which had 0 cases/10,000, Takeda MMR with 11.6/10,000 and Kitasato MMR with 3.2 cases/10,000 recipients of the vaccine. One might reasonably expect any risk of ASD to vary with vaccine type.
Rather than an uninterrupted increase in incidence of ASD from 1988 to 1996 as the conclusion suggests, the incidence varied considerably during the 8 years covered. The 47.6 (per 10,000) 1992-3 incidence almost returned when it dropped from 85.9/10,000 in 1990 back to 55.8 and 63.3 respectively in 1991 and 1992. In 1993 it jumps to 96.7, then to 161.3 in 1994, then falls back to settle at 115.3 and 117.2 in 1995 and 1996. I see no scientific merit in ignoring those considerations and concluding that a rise in incidence from 47.6 to 117.2 over 8 years when MMR was withdrawn in 1993 proves that MMR had no part to play in that increase. Important statistical variations may have been ignored.
Children born between 1988 and 1992 might have lesser risk of ASD from MMR compared with monovalent vaccines but a greater risk from a potential 150ug mercury intake which contrasts with the 1993-96 cohort who may have realised a greater risk of ASD from the monovalent vaccines but a lesser risk of mercury-induced ASD from a lesser potential intake of 75ug mercury. Other vaccines carrying additional toxic burdens might add to the risk such as the 6 or more doses of neomycin injected via varicella, rubella, OPV, mumps and measles vaccines and 4 doses of gelatine injected with mumps, measles, rubella and varicella vaccines. These variables might eventually explain why Honda et al’s incidence rate is not of constant increase.
Contrary to Cole’s and Evan Harris’s rather overenthusiastic acceptance of Honda et al 2005, when one considers both the Honda and Takahashi studies one must surely suspect that both MMR and monovalent/single antigen vaccines are probable causes of ASDs. If that is the case all haste is required from Members of Parliament and the Health Protection Agency to direct that identification of the risk posed by MMR and monovalent vaccines to our children is a national priority.
1. "An epidemiological Study on Japanese Autism concerning Routine Childhood Immunisation History" by Takahashi H et al, Jpn. J. Infect. Dis 2003; 56: 114-117
2. Kwittken PL et al “MMR vaccine and neomycin allergy”, American Journal of diseases of children 1993; 147(2): 128-9
3. Kelso JM et al “Anaphylaxis to measles mumps and rubella vaccine mediated by IgE to gelatine”, Journal of Allergy & Clinical Immunology 1993; 91(4): 867-72
4. Kimura M et al “Adverse events associated with measles mumps and rubella (MMR) vaccines in Japan”, Acta Paediatrica Japonica 1996; 38(3): 205-11
Competing interests: None declared
Competing interests: No competing interests
Evan Harris says "you can't prove a negative" but you cannot prove anything with epidemiology, so why do we have epidemiological study after epidemiological study, rather than the investigation of intestinal and neurological symptoms to which Dr Harris is apparently so implacably opposed ?
 Annabel Ferriman, 'MP raises new allegations against Andrew Wakefield', 27 March 2004: http://bmj.bmjjournals.com/cgi/content/full/328/7442/726-a
Competing interests: Parent with an autistic child
Competing interests: No competing interests
I only pose once again the question why we are not looking clinically at the affected children, and instead at yet another magnificent epidemiological survey. Since when do we go to the databanks to find out what is wrong with individual children? Why is this the correct response rather than that adopted by Andrew Wakefield in his 1998 study, and subsequently?
Every new study is launched amidst immense publicity, well before anyone with expert independent knowledge has had a chance to examine it and comment. By that time the media circus has moved on. So the criticisms are made but the public seldom get to hear about them directly, however suspicious they are. To date not a single one has withstood scrutiny, or at least shows what it says it does. And it does not look as if this one will be any different. A week on two commentaries - which should really be the basis of further discussion - have been published by Red Flags Weekly, by Andrew Wakefield and Carol Stott, and F Edward Yazbak 
Early comments were also published in Rapid Responses under
by myself, Hilary Butler and Aasa Reidak (all dated 5 March). Perhaps the most striking single emerging point is that when MMR was abandoned in Japan it was largely replaced not by three staggered injections, but three separate injections administered in the same visit. The study therefore sheds no light on Andrew Wakefield's original proposition that it was advisable to space the shots a year apart, but this point is not acknowledged and would seem to invalidate its main claim. I think the authors, and other MMR proponents, should be prepared to discuss this point.
No information is provided about how the study was funded.
Competing interests: Parent of an autistic child
Competing interests: No competing interests