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The MMR vaccine: fact versus fiction

Measles is back in the news again, with a rise in cases being blamed on concerns surrounding the safety of the measles, mumps and rubella (MMR) vaccine. Kirsty Armstrong explores the evidence base for a link between MMR and autism and examines some of the potential complications that can be caused by the disease

Kirsty Armstrong
SRN FPcert BSc(Hons) NPDip PGCert Ed PGDip MA Ed
Senior Lecturer, Practitioner in Primary Care, St George's Hospital, London

Between January and November 2008, the number of measles cases exceeded 1,200 in England and Wales (see Figure 1).1 In 2006, there were over 46,000 cases of mumps, mostly in the 14–20 age group.1 Incidence of rubella is more rare, but this is also re-emerging and the Health Protection Agency (HPA) recorded 10 cases in the first three quarters of 2008.1
Until 1997, there was a high uptake of the measles, mumps and rubella (MMR) vaccine. Many people may have forgotten the possible serious complications of these diseases and be unaware of the long-term problems these viruses can cause.

[[Fig 1 MMR]]

Complications of measles
Measles is a serious disease. The rash is an outward manifestation of the virus, which attacks the surfaces inside the chest. Pneumonia following measles occurs in 1–6% of cases.2

Ear infections can occur in 7–9% of cases; diarrhoea in 8% of cases and febrile convulsions in one in 200 cases.2 The most serious complication of measles is encephalitis, which can occur during the measles episode and cause death. The incidence of this is one in every 1,000 cases of measles, but it carries high morbidity and possible mortality.2

Subacute sclerosing panencephalitis (SSPE) is a rare form of encephalitis and occurs several years after the child has recovered from measles. The child loses intellectual ability and usually dies within a short space of time. The risk of developing this disease is 16 times greater if measles is contracted under the age of two, but the occurrence rate is one in every 25,000 cases.2

Measles can kill: from 1940–1968, 100 children died per year from the disease. Between 1970 and 1988, 13 died each year. Two children have died in England since 2006.1

The flawed evidence base
In 1997, Andrew Wakefield courted controversy with a paper that identified a link between autism and the MMR vaccine, and suggested that single vaccines were the only way forward.3 This allegation seriously eroded public confidence in MMR and has reduced the uptake of the vaccine in recent years, resulting in the re-emergence of measles. It has since been revealed that the trial was tiny (including eight children); that Dr Wakefield had been given an advance of $100,000 to aid the introduction of single vaccines into the UK; and that 10 of the other authors working on the trial with Dr Wakefield did not share his views on either the link to autism or the need for single vaccines, and later retracted their claims to this effect.

Recent research
In the year after the original controversial research was published, several studies found no association between the vaccine and the syndromes purported by Dr Wakefield.
Smeeth at al (2004) found no link.4 They used UK GP databases comparing the immunisation status of autistic children with similar children without autism, and found the same proportion had been immunised with MMR. Peltola et al (1994) found no link in children who were followed up over a period of 14 years in Finland.5

In a Japanese study, Honda et al (2005) showed that the autism incidence has continued to rise, despite the cessation of the MMR vaccination in 1993.6 MMR was stopped because the mumps strain (Urabe) was not available in Japan (they will only source it within that country). Japan has had an ongoing measles problem since it went over to single vaccines. It remains the only country in the world routinely using single measles and rubella vaccines (given on the same day).
Madsen et al (2004) reviewed 500,000 children in Denmark (1991–98). The chance of developing autism was the same, whether or not the child had MMR.7

Dr Simon Murch, who collaborated on the Wakefield paper, stated in a press conference: "This link is unproven and measles is a killing infection. If this precipitates a scare and immunisation rates go down, as sure as night follows day, measles will return and children will die."

Major worldwide research over the past ten years, using peer-reviewed population and other methods on large numbers of children, has not demonstrated a scientific link between MMR and autism or inflammatory bowel disease.

Demicelli et al carried out a systematic review to assess the effectiveness and any unintended side-effects associated with the MMR vaccine looking at 139 trials. They found that exposure to the MMR vaccine was unlikely to be associated with Crohn's disease, ulcerative colitis, autism or aseptic meningitis.8

Side-effects of the vaccine
Like all vaccines, MMR has side-effects, but these are much more rare and less serious than the complications of measles.2 The side-effects may include fever and soreness at the injection site.

MMR is a live vaccine; examples of other live vaccines include the BCG (for TB) and the yellow fever vaccine. Side-effects from the MMR vaccine are the "toned down" reactions that you would get if you acquired the disease, ie, attenuated viruses undergoing replication in the body. If you have the vaccine, you will not be exposed to the possible dangerous sequelae of the disease itself, which include SSPE, otitis media, measles pneumonia and meningitis.

The side-effects occur as the viruses reach maturity in the body. This means that when the viral incubation periods of the disease elapse (in six to 11 days), there may be a rash ("mini measles") and in 14–21 days there may be mild parotitis or mumps (swelling of the parotid glands in the neck) and arthralgia or aching joints, as with rubella.

In the 90% of responders (those who build immunity) to the first dose of MMR, these side-effects will not recur on having the second dose. Thus, side-effects are likely to be reduced the more MMRs you have.

There appears to be no increase in side-effects when occasionally a third MMR is required. In France, a measles vaccine is given at nine months, then another two MMRs are given over the age of one year.

Overloading the immune system
The human immune system is immensely strong and can handle the three viruses that comprise the MMR vaccine without any problems.2 Right from birth, babies are colonised with germs and have the ability to cope with them – babies are not born into a sterile environment.

The advantage of being immunised rather than catching the disease is that the vaccine only uses part of the virus germ, which is then "toned down" (attenuated or the virulence removed).

In this way, the challenge to the immune system is less than from the disease, while at the same time, sufficient to produce protection. Gelatine allergy and anaphylaxis to any component of the MMR vaccine are now considered to be the only absolute contraindications to having the vaccine.2

Single vaccines
The original Lancet paper that raised the controversy did not propose separate vaccines, nor did it provide any evidence that separating the vaccines was safer.

If a child were to have all their vaccines separately, this would mean six individual injections (instead of two) and would be unacceptable to many parents and cause unnecessary discomfort for the child.

Delay in reaching final protection for the child puts them at unnecessary risk. The MMR vaccine has been in use for 30 years in the USA and 20 years in the UK. It is probably the most researched vaccine in history.2 Single vaccines have not been researched over the past 30 years and there is no evidence on best intervals, safety and efficacy. No country in the world uses single vaccines with intervals as an alternative to the combined MMR (Japan gives measles and rubella separately, but both on the same day).

Single vaccines are untried and untested and have not undergone the rigorous testing that the MMR vaccine has undergone.

The risks of not immunising
If they are not immunised, a person risks catching measles at an older age, when it can be more painful and recovery time extended.

Low levels of herd immunity against measles, mumps and rubella could mean passing on these diseases to the immuno-compromised, and children who are too young to be immunised.

Mumps is a very unpleasant infection and can cause reduced levels of fertility in males and females as the reproductive organs become inflamed.

Congenital rubella can be disastrous if a mother contracts infection in the early stages of pregnancy. In 2008, in England and Wales there were ten confirmed cases of rubella.1

Your action plan

  • Consider opportunistic immunisation in children who have had only one or no MMR vaccines.
  • Make sure you have up-to-date records on MMR uptake and ensure your practice manager/administration team have searched records appropriately.
  • Take action to ensure all children have had two MMRs and that others at risk are immunised – this includes you as a frontline healthcare worker.

With thanks to Dr Barry Walsh CCDC at SW London HPA for his input.

References
1. Health Protection Agency (HPA). Health Protection Report: Confirmed measles cases in England and Wales – an update to end-November 2008. London: HPA; 2008. Available from: http://www.hpa.org.uk/hpr/archives/2009/news0109.htm#msles
2. Department of Health (DH). Immunisation against infectious disease - 'The Green Book'. London: DH; 2006. Available from: http://www.dh.gov.uk/en/Publichealth/Healthprotection/Immunisation/Green...
3. Wakefield AJ, Murch SH, Anthony A et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 1998;351:637-641
4. Smeeth L, Cook C, Fombonne E et al. MMR vaccination and pervasive developmental disorders: a case control study. Lancet 2004;364(9438):963–9.
5. Peltola H, Heinonen OP, Valle M et al. The elimination of indigenous measles, mumps and rubella from Finland by a 12-year two-dose vaccination program.
N Engl J Med 1994;331(21):1397–402.
6. Honda H, Shimizu Y, Rutter M. No effect of MMR withdrawal on the incidence of autism: a total population study. J Child Psychol Psychiatry 2005;46(6):
572–9.
7. Madsen KM, Vestergaard M. MMR vaccination and autism: what is the evidence for a causal association? Drug Saf 2004;27(12):831–40.
8. Demicheli V, Jefferson T, Rivetti A, Price D. Vaccines for measles, mumps and rubella in children. Cochrane Database Syst Rev 2005;19(4):CD004407.