What are the adverse effects of vaccines?

A study incorporating over 12,000 prior peer reviewed publications, addressing the question of vaccine safety, is due for release by the National Academies of Science. The study attempts to understand adverse effects of vaccines and to assign causality to supposed negative outcomes. The 667 page study covers a large number of vaccines. And yes, it addresses autism.

The study cataloged about 60 distinct adverse effects across 8 categories of vaccine treatments, two of which contain multiple vaccines, for a total of 12 distinct vaccines, as well as more general injection-related events (which occur independently of what is being injected).

The evidence used in this study come primarily from two sources: Epidemiologic data and clinical or other biological studies (which the study refers to as "mechanistic"). The epidemiologic findings from previous studies indicate that there may be an effect of interest, provides information about its frequency or link to various risk categories, and allows an assessment of the likelihood that the putative effect is really linked to the vaccine, as opposed to showing up by coincidence. An example of this might be the question of severe flu-like illness as an effect of getting a flu shot. Since people tend to get their flu shots at the beginning of flu season or later, there is a certain chance that they will actually have the flu at the time they get the shot, or some other similar illness. If one person tells you "I got the flu shot once and it gave me the flu" you have not learned anything about the link between flu shots and flu-like side effects. You need to see if among a large number of people a disproportionate number get severe flu-like symptoms after they've gotten the shot.

The clinical or biological studies address the mechanism of the effect. No matter what the epidemiological evidence may be, if there is not a sensible biological mechanism behind an effect, it is hard to say what is happening, or even to verify that anything is happening at all. Chance alone allows for what would seem like an inordinate number of instance of a particular effect. In other words, if you look at a possible side effect for a particular medical treatment in 100 studies, it may well "show up" as sample-wide phenomenon in one or two case by chance, with nothing actually happening biological; A false positive. But if there is a known underlying biological mechanism, then the epidemiological data can be more sensibly assessed, and if the biological model that emerges from these "mechanistic" studies is sufficiently detailed, it might be possible to improve the field studies by collecting more appropriate data.

Each of these categories of information, epidemiologic and mechanistic, were assessed for each putative link between vaccination and adverse effect. Each study was assessed for its strength with respect to sample size, research design, or other factors. The result of this was a measure of "weight-of-evidence" for each type of study. These were then combined into a third assessment about the causal relationship between the vaccine and the effect.

For epidemiologic evidence, the following categories were used:

• High: Two or more studies with negligible methodological limitations that are consistent in terms of the direction of the effect, and taken together provide high confidence.
• Moderate: One study with negligible methodological limitations, or a collection of studies generally consistent in terms of the direction of the effect, that provides moderate confidence.
• Limited: One study or a collection of studies lacking precision or consistency that provides limited, or low, confidence.
• Insufficient: No epidemiologic studies of sufficient quality.

For mechanistic evidence, the categories were:

• Strong: One or more cases in the literature, for which the committee concludes the vaccine was a contributing cause of the adverse event, based on an overall assessment of attribution in the available cases and clinical, diagnostic, or experimental evidence consistent with relevant biological response to vaccine.
• Intermediate: At least two cases, taken together, for which the committee concludes the vaccine may be a contributing cause of the adverse event, based on an overall assessment of attribution in the available cases and clinical, diagnostic, or experimental evidence consistent with relevant biological response to vaccine. On occasion, the committee reviewed evidence consisting of at least two cases that, taken together, while suggestive, are nonetheless insufficient to conclude that the vaccine may be a contributing cause of the adverse event. This evidence has been categorized as "low-intermediate."
• Weak: Insufficient evidence from cases in the literature for the committee to conclude the vaccine may be a contributing cause of the adverse event, based on an overall assessment of attribution in the available cases and clinical, diagnostic, or experimental evidence consistent with relevant biological response to vaccine.
• Lacking: No clinical, diagnostic, or experimental evidence consistent with relevant biological response to vaccine, regardless of the presence of individual cases in the literature.

The categories used for causation were:

• Evidence convincingly supports a causal relationship --This applies to relationships in which the causal link is convincing, as with the oral polio vaccine and vaccine-associated paralytic polio.
• Evidence favors acceptance of a causal relationship--Evidence is strong and generally suggestive, although not firm enough to be described as convincing or established.
• Evidence is inadequate to accept or reject a causal relationship--The evidence is not reasonably convincing either in support of or against causality; evidence that is sparse, conflicting, of weak quality, or merely suggestive--whether toward or away from causality--falls into this category. Where there is no evidence meeting the standards described above, the committee also uses this causal conclusion.
• Evidence favors rejection of a causal relationship--The evidence is strong and generally convincing, and suggests there is no causal relationship.

The results of this study support 14 specific adverse event relationships with vaccines ranked in the "convincingly supported" category (shown in the table below). In all but one case, this was based on strong mechanistic evidence along with epidemiologic evidence of either limited confidence of insufficient. This probably means that in many cases there is a real link but the occurrence of the event is rare.

The "favors acceptance" category four links between vaccine and adverse effect.

Convincingly supported links are:

Varicella Vaccine:

• Disseminated Oka VZV without other organ involvement (got chicken pox)
• Disseminated OK VZV with subsequent infection resulting in Pneumonia, Menningitis, or Hepatitis (got chickenbox, bad)
• Vaccine strain viral reactivation without other organ involvement
• Vaccine Strain viral reactivation with subsequent infection resulting in menningitis or encephalitis
• Anaphylaxis (a multi-system immune reaction, very variable but considered dangerous)

MMR Vaccine:

• Measles Inclusion Body encaphalitis
• Ferbile seizures
• Anaphylaxis

Influenza Vaccine:

• Anaphylaxis

Hepatitis A Vaccine

• Nothing Noted

Hepatitis B Vaccine:

• Anaphylaxi

s

HPV Vaccine:

• Nothing noted

DT-IT and aP containing vaccines:

• Anaphylaxis

Meningococcal Vaccine:

• Anaphylaxis

Injection-related events:

• Deltoid Bursitis (arm hurts)
• Syncope (fainting

)

Keep in mind that most of these effects are rare and many are minor. The main effect linked to these vaccines is immunity to a potentially deadly disease.

You are probably wondering about autism. I'll give you the study's results directly (keep in mind that this is an uncorrected proof):

The committee reviewed 22 studies to evaluate the risk of autism after the administration of MMR vaccine. Twelve studies...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 ... had very serious methodological limitations that precluded their inclusion in this assessment. The five remaining controlled studies contributed to the weight of epidemiologic evidence.

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 was 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 (PDD) 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 was 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.

So, from an epidemiological perspective, there is no link between MMR and autism. But what about the mechanistic studies? There were ...

... 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). 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.

In the end, the committee was able to comfortably reject a connection between MMR vaccination and autism.

__________________
Source:

Stratton, Kathleen, Andrew Ford, Erin Rusch, and Ellen Wright Clayton,
Editors; Committee to Review Adverse Effects of Vaccines; Institute of
Medicine. 2011 (uncorrected proof). Adverse Effects of Vaccines: Evidence and Causality. The Ntional Academies Press. Washington DC