MMR vaccine: the continuing saga

Current concerns are idiosyncratic: most reviews have confirmed the vaccine's safety

The current low uptake of measles, mumps, and rubella (MMR) vaccine in some parts of the United Kingdom has led to well publicised concerns about the potential for measles outbreaks among primary school entrants. This has coincided with prepublication publicity last week of a paper casting doubts on the adequacy of the evidence which secured the licence for MMR vaccine.1 Understandably some parents and health professionals are confused and anxious and, in an effort to protect their children against measles, have sought single antigen vaccines. We have reviewed the latest developments in this saga and are convinced that such confusion and anxiety about MMR vaccine are unfounded.

The authors of the paper, Wakefield and Montgomery, imply that they have examined all the safety data relating to the licensing of the vaccine1 in the early 1970s (1971 in US and 1972 in UK, not 1975 and 1988 as they say). Although this is their aim, in support of their concerns they also cite studies that postdate the award of licences. Therefore it is surprising that they do not mention the classical Finnish double blind placebo controlled trial among twins.2 This was a rigorous study which reported a low incidence of side effects, including gastrointestinal symptoms. The omission of this important study casts doubt on the completeness and impartiality of their review.

The authors pay much attention to one paper in particular,3 but there are several errors in their interpretation—for example, the period of follow up was six to nine weeks, not four weeks as they state—and their reanalysis is flawed. For example, they incorrectly sum numbers of children with symptoms across each of the time periods presented, thereby arriving at a total in which individuals may be counted twice. We cannot provide a more detailed critical analysis here, but, in view of the lack of systematic rigour in their review, it adds nothing new to the body of evidence on MMR vaccine safety (for a full discussion, see the Department of Health website www.doh.gov.uk).

Since its initial licensing the safety of MMR vaccine has been confirmed by several detailed studies.4^–7 These studies and 30 years of use with postmarketing surveillance of more than 250 million doses in over 40 countries in Europe, north America, and Australasia have formed the basis of the mandatory reviews to which any licence is subject. At each of these reviews the safety of the vaccine has been confirmed.

The most recent study reported was conducted in Finland, where a two dose MMR schedule has been used since 1982.8 Using enhanced passive reporting, the authors monitored serious adverse events in 1.8 million children who received 3 million doses of the vaccine over 14 years. Adverse events, including febrile convulsions, anaphylaxis, urticaria, and encephalitis, were reported, although all were rare and encephalitis occurred at a rate similar to that expected in an unimmunised population. In particular, no cases of autism or inflammatory bowel disease associated with MMR vaccine were reported—as suggested in an earlier paper by Wakefield and colleagues in the Lancet.9 If there were an onset of autism and bowel problems within days of MMR vaccination, as Wakefield et al suggested, this study should have shown cases. Specific hypothesis driven studies have also found no association of MMR vaccine with bowel disease or autism.5^–7

Last week the BMJ reported a study of the attitudes of general practitioners, health visitors, and practice nurses to MMR vaccine in North Wales Health Authority10 shortly after publication of Wakefield et al's 1998 Lancet paper.9 This study showed that a substantial minority of these health professionals, especially practice nurses, were ambivalent about the second dose of MMR; this was mainly a concern about causing distress to preschool children by giving them two injections at once. Some also considered there might be a link between autism, Crohn's disease, and the vaccine, but the finding that many were unaware of established side effects, such as idiopathic thrombocytopenic purpura, indicates that this was a reflection of poor knowledge and insufficient use of resources. For example, a significant proportion said they had not received the Health Education Authority's MMR factsheet and 20% of general practitioners had not read the MMR section of the Green Book.11

Another study has confirmed a lack of knowledge of contraindications to MMR among primary health care professionals12 and suggests little improvement in the intervening 10 years since publication of the Peckham report.13 If professionals advising parents do not use up to date information it can come as no surprise that some parents are confused and anxious.14 Since both studies were conducted a second MMR factsheet has been circulated15 and further evidence of the safety of the vaccine published,4^–7 so we hope that the situation has improved.

Despite doubts about the safety of the MMR vaccine being frequently voiced in the media, vaccine uptake has held up well. The latest data indicate that uptake by the 2nd birthday fell by only 4% to 88% in 1999 and by September 2000 had fallen no further. Whether it will hold up under the latest media onslaught remains to be seen. Incorrect media reports of vaccine uptake “plummeting” could become a self-fulfilling prophecy.

Wakefield and Montgomery's review provides no justification for offering the single antigens.1 But this is not the media's interpretation. However weak the scientific evidence which triggers vaccine safety scares, they provoke anxiety among parents and health professionals which can lead to a decline in vaccine uptake. The pertussis vaccine scare in the 1970s was based on similarly flawed research and resulted in unnecessary suffering and deaths.16 We need urgently to identify and use the most effective methods for training and updating health professionals so that they can respond promptly and appropriately to parents' concerns.

This is not the first time a potentially damaging piece of research related to vaccine safety from the same authors has been discussed in the popular press before most clinicians have a chance to read it in a peer reviewed journal. This practice compounds the difficulties for health professionals in accessing the information needed to answer parents' queries. Moreover, researchers whose findings are likely to cause concern to many, in this case millions, of people have an obligation to ensure that their study is of the highest standard. Unusually the editor of the journal that published the review has also published the referees' comments. These reveal that specialists in immunisation were not included—that too seems to have been an important error of omission.