MMR

Vaccines

The Official View

HPA: Why is MMR preferable to single vaccines?

To summarise:

• The MMR vaccine has been thoroughly investigated and is very safe
• Single vaccines should not be recommended in the NHS because
  • Single vaccines leave children vulnerable to the diseases for a longer period of time
  • Using single vaccines in this way is experimental
  • There is no evidence on what schedules (spacing) should be used and inadequate evidence of safety and effectiveness of using single vaccines in this way
  • Past experience shows that uptake of single vaccines will be lower. When measles and rubella vaccines were used separately, children continued to get measles and babies were born with congenital rubella. When MMR was introduced, measles and congenital rubella were virtually eliminated
  • It is unfair and unkind to give a child six injections unnecessarily when they can be better protected by just two.
  • Offering single vaccines to parents when all the evidence indicates that this is likely to put children in the UK at risk runs counter to all recent initiatives to make NHS practice evidence-based, following for example the Bristol enquiry and the establishment of the National Institute for Clinical Excellence (NICE)
  • Past experience of a whooping cough vaccine scare in the 1970s shows that if we offer single vaccines, the vaccination programme may collapse, with devastating consequences for children
• If parents do try to get single vaccines from clinics, we urge those parents to ask:
  • exactly which vaccine they are being offered;
  • when and where that vaccine was tested;
  • what the results of those tests were in terms of the safety, potency and purity of the vaccine;
  • what post-vaccination follow-up of their child is offered by the clinic.

IOM

Start here: Adverse Effects of Vaccines: Evidence and Causality ( 2012 ) / 4 Measles, Mumps, and Rubella Vaccine

AUTISM

Epidemiologic Evidence

The committee reviewed 22 studies to evaluate the risk of autism after the administration of MMR vaccine. Twelve studies (Chen et al., 2004; Dales et al., 2001; Fombonne and Chakrabarti, 2001; Fombonne et al., 2006; Geier and Geier, 2004; Honda et al., 2005; Kaye et al., 2001; Makela et al., 2002; Mrozek-Budzyn and Kieltyka, 2008; Steffenburg et al., 2003; Takahashi et al., 2001, 2003) were not considered in the weight of epidemiologic evidence because they provided data from a passive surveillance system lacking an unvaccinated comparison population or an ecological comparison study lacking individual-level data. Five controlled studies (DeStefano et al., 2004; Richler et al., 2006; Schultz et al., 2008; Taylor et al., 2002; Uchiyama et al., 2007) had very serious methodological limitations that precluded their inclusion in this assessment. Taylor et al. (2002) inadequately described the data analysis used to compare autism compounded by serious bowel problems or regression (cases) with autism free of such problems (controls). DeStefano et al. (2004) and Uchiyama et al. (2007) did not provide sufficient data on whether autism onset or diagnosis preceded or followed MMR vaccination. The study by Richler et al. (2006) had the potential for recall bias since the age at autism onset was determined using parental interviews, and their data analysis appeared to ignore pair-matching of cases and controls, which could have biased their findings toward the null. Schultz et al. (2008) conducted an Internet-based case-control study and excluded many participants due to missing survey data, which increased the potential for selection and information bias.

The five remaining controlled studies (Farrington et al., 2001; Madsen et al., 2002; Mrozek-Budzyn et al., 2010; Smeeth et al., 2004; Taylor et al., 1999) contributed to the weight of epidemiologic evidence and are described below.

Taylor et al. (1999) conducted a self-controlled case-series study in children with autistic disorders residing in the North East Thames region of the United Kingdom. The children were identified from computerized special needs or disability registers. A total of 498 children who were born from 1979 through 1998 and had an autism diagnosis before 16 years of age were included in the analysis. After reviewing the clinical records, the investigators confirmed that the autism diagnoses met the criteria of the International Classification of Diseases, 10th revision (ICD-10) in 82 percent of typical autism cases and 31 percent of atypical autism cases (the authors used the term core to describe typical autism, as noted in the methods). The self-controlled analysis investigated the risk of typical or atypical autism diagnosis among 357 cases during two postvaccination periods (12 or 24 months after vaccination). The reference period consisted of time from birth through August 1998, not including the postvaccination risk periods. The relative risk of autism diagnosis within 12 months of MMR vaccination was 0.94 (95% CI, 0.60–1.47) and within 24 months of MMR vaccination was 1.09 (95% CI, 0.79–1.52). The relative risk of autism diagnosis within 12 months and 24 months of vaccination with MMR or single-antigen measles with mumps and rubella was 0.80 (95% CI, 0.53–1.22) and 1.05 (95% CI, 0.76–1.44), respectively. The authors noted the results were similar when the analyses were restricted to confirmed cases of typical or atypical autism. The authors concluded that MMR vaccination is not associated with autism.

Farrington et al. (2001) conducted a reanalysis of the study by Taylor et al. (1999). The two risk periods were changed to autism diagnosis within 59 months and any time after vaccination, and compared to a reference period that consisted of time from birth through 191 months of age or August 1998, whichever occurred first. The analysis was adjusted for both calendar year and age. The relative risk of autism diagnosis within 59 months of vaccination with MMR was 1.24 (95% CI, 0.67–2.27), and with MMR and any measles-containing vaccines was 0.96 (95% CI, 0.52–1.77). The relative risk of autism diagnosis any time after vaccination with MMR was 1.06 (95% CI, 0.49–2.30), and with MMR and any measles-containing vaccines was 2.03 (95% CI, 0.80–5.18). The authors concluded that there is no association between MMR or measles-containing vaccines and autism diagnosis any time after vaccination.

Madsen et al. (2002)2 conducted a retrospective cohort study in children born in Denmark from January 1991 through December 1998. The children were enrolled from the Danish Civil Registration System, which stores personal identification information for all residents, and linked records to five other national registries. MMR vaccination data were obtained from the National Board of Health; autism diagnosis was derived from the Danish Psychiatric Central Register. The National Hospital Registry and Danish Medical Birth Registry provided birth weight and gestational age information, and data on socioeconomic status and mother’s education came from Statistics Denmark. Autism diagnoses were based on criteria from the ICD-10; the diagnostic codes were separated into cases of autistic disorder or other autistic-spectrum disorders. Children with congenital rubella or an inherited genetic condition (fragile X syndrome, Angelman’s syndrome, or tuberous sclerosis) were excluded from the analysis. A total of 537,303 children were included in the cohort, of which 316 had an autistic disorder diagnosis and 422 had an autistic-spectrum disorder diagnosis. Follow-up began at 1 year of age and continued through December 31, 1999, or the date of autism diagnosis, diagnosis of other associated conditions, emigration, or death. Children who were vaccinated with MMR contributed 1,647,504 person-years of follow-up, and those not vaccinated contributed 482,360 person-years. Relative risks were calculated and adjusted for age, calendar period, sex, birth weight, gestation age, mother’s education, and socioeconomic status. The adjusted relative risk of autism diagnosis after MMR vaccination was 0.92 (95% CI, 0.68–1.24) and of other autistic spectrum disorders after MMR vaccination was 0.83 (95% CI, 0.65–1.07). The authors concluded that MMR vaccination is not associated with an increased risk of autistic disorder or other autistic-spectrum disorders.

Smeeth et al. (2004) conducted a case-control study in children (born between 1973 and 1999) enrolled in the General Practice Research Database (GPRD) from June 1987 through December 2001. The study included 991 cases with a recorded diagnosis of autism and 303 cases with other pervasive developmental disorder diagnosis. A total of 4,469 controls were individually matched to cases on year of birth (within 1 year), sex, and general practice. The study excluded cases and controls that were not enrolled in the database for at least 12 months before the diagnosis or index date (date that control was same age as matched case at time of diagnosis). MMR vaccination data were abstracted from the GPRD records, and the case or control status was concealed during the assessment. The unadjusted odds ratio for autism diagnosis after MMR vaccination was 0.77 (95% CI, 0.60–0.98). After adjustment for the age at which participants joined the GPRD, the odds ratio was 0.88 (95% CI, 0.67–1.15). The authors concluded that MMR vaccination is not associated with an increased risk of autism.

Mrozek-Budzyn et al. (2010) conducted a case-control study in children identified in the general practitioner records in the Malopolska Province of Poland. The study included 96 cases and 192 matched controls. The cases were diagnosed with childhood or atypical autism by a child psychiatrist according to the ICD-10 criteria. Two controls were matched to each case on year of birth, gender, and physician’s practice. Vaccination histories and the date of autism diagnosis were extracted from the physician’s records. Date of onset of symptoms was derived from parental interview. If MMR or single-antigen measles vaccination preceded the onset of symptoms, cases were classified as vaccinated. Controls were considered vaccinated if they received an MMR or single-antigen measles vaccine before the age of symptom onset observed in the matched case. The analysis adjusted for mother’s age, medication during pregnancy, gestation time, perinatal injury, and 5-minute Apgar scale score. The adjusted odds ratio for autism diagnosis after MMR vaccination was 0.17 (95% CI, 0.06–0.52). The adjusted odds ratio for autism diagnosis after single-antigen measles or MMR vaccination was 0.28 (95% CI, 0.10–0.76). The authors concluded that administration of MMR or single-antigen measles vaccine is not associated with an increased risk of autism in children.

Weight of Epidemiologic Evidence

Three unique studies (Madsen et al., 2002; Smeeth et al., 2004; Taylor et al., 1999) were judged to have negligible limitations; all reported null associations (on average) between MMR vaccination and subsequent autism diagnosis (or onset) and the overall precision was high. A separate report (Farrington et al., 2001) using the same population and methods as Taylor et al. (1999) reported a null association (moderate precision) between MMR vaccination and subsequent onset or diagnosis of the regressive subtype of autism. The fifth study (Mrozek-Budzyn et al., 2010) also found no association between measles or MMR immunization using a hospital-based case-control design with appropriate methods for matching and analysis. This study was rated as having serious limitations because it did not provide information on medical conditions among the controls and relied on medical record abstraction for immunization dates and autism diagnosis dates. Overall, the studies were reasonably valid, and provided consistent and precise evidence supporting no increased risk. See Table 4-5 for a summary of the studies that contributed to the weight of epidemiologic evidence.

The committee has a high degree of confidence in the epidemiologic evidence based on four studies with validity and precision to assess an association between MMR vaccine and autism; these studies consistently report a null association.

Mechanistic Evidence

The committee identified four publications reporting autism developing after the administration of MMR vaccine. Three publications did not provide evidence beyond temporality, some too long (Frenkel et al., 1996; Spitzer et al., 2001; Wakefield et al., 1998).3 Long latencies between vaccine administration and development of behavioral symptoms make it impossible to rule out other possible causes. In addition, the committee identified an editorial by Sharrard (2010) in which a temporal relationship between administration of a measles, mumps, and rubella vaccine and the development of autism was attributed to one patient reported in Verity et al. (2010). However, as reported in the original article and affirmed in a subsequent letter to the editor (Verity et al., 2011) the vaccinee did not develop autism, a fact that was misreported in the editorial by Sharrard. Two publications studied the association between MMR vaccination and autism with enteropathy (Hornig et al., 2008; Peltola et al., 1998). The authors reported a temporal relationship between vaccine administration and development of gastrointestinal disturbances but did not report autism after vaccination. The publications did not contribute to the weight of mechanistic evidence.

Weight of Mechanistic Evidence

The committee assesses the mechanistic evidence regarding an association between MMR vaccine and autism as lacking.

Causality Conclusion

Conclusion 4.8: The evidence favors rejection of a causal relationship between MMR vaccine and autism.

Japan Study - Not The Knock-Out Punch Some Say It Is

Summary

When in Japan MMR was replaced by single vaccines, ASD incidence rose instead of falling.

Pro-MMR view is that this is strong proof that MMR in itself is no less safe than single vaccines from an ASD viewpoint.

Anti-MMR view is that the single vaccine spacing was so close that interference effects are not significantly less than for MMR, so it actually proves nothing. Also that the specific form of ASD they posit a link to ("regressive autism") was not going to be picked up properly by the study since the ASD diagnosing was done at 3m and 18m, and the MMR vaccine administered at 12m - these time intervals not being able to detect the specific form of regressive autism that is at issue here.

Agreed Facts

Monovalent measles vaccine was introduced in Japan in 1978 and was recommended to be given at 12 - 72 months of age. Rubella vaccine was introduced in 1977 and was recommended for junior high school female students. An MMR vaccination programme was launched in April 1989 for children aged between 12 and 72 months with the majority receiving the vaccine by 18 months of age. There was no mumps vaccine used in Japan before the introduction of MMR.

It is notable that various brands of MMR vaccine were licensed in Japan, some of them containing the mumps Urabe AM9 strain. Due to increasing public and professional concern about reported incidences of meningitis following MMR, public confidence declined over the years following its introduction and MMR vaccine uptake fell. Subsequent studies confirmed that the Urabe AM9 mumps vaccine was causally associated with meningitis. This resulted in the termination of the MMR programme in April 1993, and no child in the current study received MMR from 1992 onwards. The Urabe AM9 mumps vaccine was discontinued and replaced with a strain of mumps vaccine which did not cause meningitis. Single measles, mumps, and rubella vaccines replaced the combined vaccine in 1993 in a new immunisation schedule, which was formalised the following year. The recommendation was for Japanese children to receive monovalent measles, mumps and rubella vaccines to be given to infants spaced by a period of not less than four weeks.

Abstract Of The Japan Paper

No effect of MMR withdrawal on the incidence of autism: a total population study.

Honda H, Shimizu Y, Rutter M.

Source: Yokohama Rehabilitation Center, Yokohama, Japan. honda@yokohama.email.ne.jp

Abstract

BACKGROUND: A causal relationship between the measles, mumps, and rubella (MMR) vaccine and occurrence of autism spectrum disorders (ASD) has been claimed, based on an increase in ASD in the USA and the UK after introduction of the MMR vaccine. However, the possibility that this increase is coincidental has not been eliminated. The unique circumstances of a Japanese MMR vaccination program provide an opportunity for comparison of ASD incidence before and after termination of the program.

METHODS: This study examined cumulative incidence of ASD up to age seven for children born from 1988 to 1996 in Kohoku Ward (population approximately 300,000), Yokohama, Japan. ASD cases included all cases of pervasive developmental disorders according to ICD-10 guidelines.

RESULTS: The MMR vaccination rate in the city of Yokohama declined significantly in the birth cohorts of years 1988 through 1992, and not a single vaccination was administered in 1993 or thereafter. In contrast, cumulative incidence of ASD up to age seven increased significantly in the birth cohorts of years 1988 through 1996 and most notably rose dramatically beginning with the birth cohort of 1993.

CONCLUSIONS: The significance of this finding is that MMR vaccination is most unlikely to be a main cause of ASD, that it cannot explain the rise over time in the incidence of ASD, and that withdrawal of MMR in countries where it is still being used cannot be expected to lead to a reduction in the incidence of ASD.

Wakefield's Response

Commentary

Andrew J Wakefield FRCS FRCPath and Carol Stott PhD

Honda and colleagues present a fascinating report on the cumulative incidence (numbers of new cases with time) of autistic spectrum disorders (ASDs) in the Kohoku Ward, Yokohama, Japan, for children born 1988 to 1996. The study seeks to examine the relationship between ASD and MMR vaccination. Japan is unique since MMR was introduced in 1989 and discontinued in April 1993. Honda et. al. see this as providing an ideal opportunity to test whether there is a causal association between MMR exposure and incidence of ASDs. They predict that, if MMR causes autism, stopping MMR should result in a subsequent decline in incidence. This was not seen. In fact, there was a striking rise in the incidence of ASDs in this population over time, with a marked rise postdating the removal of MMR. The authors state that their finding 'implies that MMR could not cause a substantial proportion of cases of autism'.

In conducting a study of this kind it is important to consider the background against which earlier hypotheses relating to the possible association between measles containing vaccines such as MMR, bowel disease and childhood developmental disorders were formulated, and according to which any relevant data should be interpreted.

The above notwithstanding, the authors of the Japanese study are confident in the completeness of ascertainment of ASD cases, the accuracy and precision of their screening, and the quality of diagnostic services for developmental disorders. Given this level of confidence in the incidence figures, the data merit further scrutiny in light of Japan's unique experience with the vaccines of interest.

Background

In 1998 one of us (AJW) made a recommendation in relation to how parents might wish to protect their child from the relevant infections - measles, mumps and rubella - by vaccination. This recommendation was based upon published scientific studies from my own laboratory together with an extensive examination of safety studies conducted in relation to measles vaccine either given alone or in combination with the other viral vaccines. The recommendations were that consideration should be given to (i) having M, M and R separately as the individual component vaccines and (ii) allowing an interval of one year between the vaccines.

The basis for these recommendations came from the following observations.

• First, that the safety studies of MMR vaccine were inadequate, a conclusion subsequently endorsed by independent scientific review.
• Second, that there was clear evidence from the early clinical trials of MMR, of 'interference' between the component viruses in the combined vaccine, an influence apparently mediated through an altered immune response to the vaccines when given together. The safety consequences of this 'interference' are completely unknown since they have not been investigated as they should have been.
• Third, that children that had experienced concurrent natural measles (or single measles vaccine) and natural mumps infections within the same year were at significantly greater risk of later inflammatory bowel disease . The latter finding is consistent with a natural 'interference' phenomenon that potentially increases the risk of long term measles virus infection and delayed disease. It is quite possible that this effect could operate for an interval of one year or more between exposure to two different viruses. Measles virus and measles vaccines can suppress the immune system for a prolonged period after exposure . This effect is exemplified by the excess mortality and immunosuppression associated with potent measles vaccines, observed in developing countries, which led to these vaccines being abandoned3.

Having established this background, one can examine the relevant events in Japan.

Vaccination policy and policy change in Japan

Monovalent measles vaccine was introduced in Japan in 1978 and was recommended to be given at 12 - 72 months of age. Rubella vaccine was introduced in 1977 and was recommended for junior high school female students. An MMR vaccination programme was launched in April 1989 for children aged between 12 and 72 months with the majority receiving the vaccine by 18 months of age. There was no mumps vaccine used in Japan before the introduction of MMR.

It is notable that various brands of MMR vaccine were licensed in Japan, some of them containing the mumps Urabe AM9 strain. Due to increasing public and professional concern about reported incidences of meningitis following MMR, public confidence declined over the years following its introduction and MMR vaccine uptake fell. Subsequent studies confirmed that the Urabe AM9 mumps vaccine was causally associated with meningitis. This resulted in the termination of the MMR programme in April 1993, and no child in the current study received MMR from 1992 onwards. The Urabe AM9 mumps vaccine was discontinued and replaced with a strain of mumps vaccine which did not cause meningitis. Single measles, mumps, and rubella vaccines replaced the combined vaccine in 1993 in a new immunisation schedule, which was formalised the following year. The recommendation was for Japanese children to receive monovalent measles, mumps and rubella vaccines to be given to infants spaced by a period of not less than four weeks.

Against the background of this changing vaccination policy the cumulative incidence curve of ASD in this population is very interesting (see Figure One).

The Japanese study does not tell us anything about the incidence of ASD prior to 1988; this can be estimated (overestimated) from prevalence data shown in Figure 1. Following the introduction of MMR there was a rise in annual incidence of ASDs from less that 25 per 10,000 population before MMR to 85.9 (95% Confidence Intervals 55.3 - 116.5) for children born in 1990. The incidence subsequently declined to 55.8 (32.0 - 79.6) for children born in 1991.

The incidence then rose again sharply, to a level of 161 (121.8-200.8) in 1994. During these years the single vaccine policy gained further acceptance as public and professional confidence was restored following the removal of the Urabe mumps vaccine. The authors note that beyond 1994 the Kohuku Ward was redistricted but claim no effect of this on interpretation of the data. It is interesting to note, however, that the confidence intervals on the point estimates of ASD incidence increase in parallel with this demographic change. A result of this is that the precision of the point estimates appears to have been compromised after this time. ASD incidence beyond 1994 is, therefore, is not as accurate as preceding years.

The multiphasic shape of the incidence curve is strikingly different from that seen in the UK (fig 2) and the US (fig 3) where distributions are primarily monophasic (i.e. a continuous rise). The shape of the Japanese graph would be consistent with an influence of an additional factor(s) on the evolution of an environmentally induced disease where, overall, exposure to the cause was increasing over time.

In light of the biological nature of viral interactions and the protracted effects on the immune system of measles exposure in particular (either as natural infection or vaccination) it is evident that, although MMR vaccine itself was discontinued in this infant population beyond 1993, for all practical purposes, because of the behaviour of these viruses, children vaccinated according to the recommended schedule were still receiving 'M-M-R' at age one year. In other words the administration of the separate vaccines in close temporal proximity amounts, in biological terms, to overlapping exposure. Such close proximity of exposure is clearly atypical and something that would have been very rare with natural infection to measles, mumps and rubella viruses. The Japanese data are therefore not at odds with the original interpretation and the subsequent recommendations referred to earlier. They are entirely consistent with what is known about the behaviour of these viruses. The authors of the Japanese study make the error of examining MMR as an isolated exposure without giving any consideration to the arguments that have been put forward or the data upon which those arguments were based.

In light of these observations the data could be interpreted as indicating a major influence of the pattern of exposure to these vaccine viruses on ASD incidence in this Japanese population. Moreover, it suggests a possible re-challenge effect of close temporal exposure to these vaccine viruses on ASD incidence at the population level, whereby the exposure has been introduced, removed and then re-introduced. Nonetheless the interpretation by Public Health authorities that this is the 'last word on the subject' and that these data prove that MMR is safe is misleading and suggests a very limited perspective of the issues and a misunderstanding of the previously published concerns that have guided the research of those involved with the examining the safety of measles vaccines. Enthusiasm to exonerate the MMR vaccine is no excuse for misrepresenting the published basis for the safety concerns.

Regressive autism: methodological flaws

It is also worth commenting on one major methodological flaw in the paper. The original description by Wakefield et al and subsequent studies others indicate that any potentially causal relationship between MMR and ASD relates to a regressive form of autism, in which the child developed normally prior to exposure.

In the study of Honda et al, children underwent routine developmental assessment at 3 months and 18 months of age, while the recommended schedule for MMR vaccination was 12 months of age. The authors define regression as demonstrable loss of skills after 18 months of age. Therefore children who have developed normally for the first year of life, who then receive an MMR at 12 months of age and who subsequently regress over the course of the next 6 months, will be misclassified as non-regressive cases when in fact quite the opposite may be the case. Misclassification of the children's autism of this kind will render meaningless, the authors sub-analysis in relation to regression. This is supported to the extent that the shape of the respective incidence curves in the sub-groups is similar. Therefore, the regression data do not merit further consideration.

The authors conclusion that their 'findings indicate that simply terminating MMR vaccination programs will not lead to a reduction in the incidence of ASD' is self-evident. The original recommendation however made no such naïve claim. The recommendations were based on empirical data, which indicated a serious adverse effect of close temporal exposure to two or more of these vaccines. The Japanese data give no reason to change theses recommendations.

Side-Effects

15 Feb 2013: Cochrane: Vaccines for measles, mumps and rubella in children

The highest risk of association with aseptic meningitis was observed within the third week after immunisation with Urabe-containing MMR (risk ratio (RR) 14.28; 95% confidence interval (CI) from 7.93 to 25.71) and within the third (RR 22.5; 95% CI 11.8 to 42.9) or fifth (RR 15.6; 95% CI 10.3 to 24.2) weeks after immunisation with the vaccine prepared with the Leningrad-Zagreb strain.

A significant risk of association with febrile seizures and MMR exposure during the two previous weeks (RR 1.10; 95% CI 1.05 to 1.15) was assessed in one large person-time cohort study involving 537,171 children aged between three months and five year of age. Increased risk of febrile seizure has also been observed in children aged between 12 to 23 months (relative incidence (RI) 4.09; 95% CI 3.1 to 5.33) and children aged 12 to 35 months (RI 5.68; 95% CI 2.31 to 13.97) within six to 11 days after exposure to MMR vaccine.

An increased risk of thrombocytopenic purpura within six weeks after MMR immunisation in children aged 12 to 23 months was assessed in one case-control study (RR 6.3; 95% CI 1.3 to 30.1) and in one small self controlled case series (incidence rate ratio (IRR) 5.38; 95% CI 2.72 to 10.62). Increased risk of thrombocytopenic purpura within six weeks after MMR exposure was also assessed in one other case-control study involving 2311 children and adolescents between one month and 18 years (odds ratio (OR) 2.4; 95% CI 1.2 to 4.7).

Exposure to the MMR vaccine was unlikely to be associated with autism, asthma, leukaemia, hay fever, type 1 diabetes, gait disturbance, Crohn's disease, demyelinating diseases, bacterial or viral infections.

febrile seizure

NHS: 25 to 33 excess per 100,000

2%-5% children have at least one anyway at some point. Mostly age range 6m to 3y. Eg more than 1,000 per 100,000 yearly.

thrombocytopenic purpura

Idiopathic thrombocytopenic purpura and MMR vaccine: 5 in 100,000

Great Ormond St: Idiopathic thrombocytopenic purpura information

Baseline is 4 in 100,000 per year

Low platelet count (eg poor clotting). It is usually a self-limiting disorder which recovers spontaneously after 6-8 weeks. But it can continue for years.

measles

CDC:

• 2 in 1,000 death rate (can be as high as 1 in 4 in a developing country)
• 4-5% pneumonia (biggest killer for young children)
• 10% ear infections
• 1 in 1,000 encephalitis
• 4-11 in 100,000 get (fatal) SSPE (subacute sclerosing panencephalitis), 18 in 100,000 if measles when < 1 year old