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Measles, Mumps and Rubella (MMR) Vaccinations
Mark Harmon & Ben Sehmer, 2nd year Medicine
Measles, mumps and rubella (German measles) are highly infectious and potentially fatal viral diseases that can be eradicated through the use of the measles, mumps and rubella vaccination (MMR). The vaccine works on an individual level, conditioning a patient’s immune system to quickly recognise and destroy these infections. At a community level, it greatly hinders the spread of the virus from person to person, thus avoiding an epidemic within a society.
Measles on its own is generally a mild disease, but its potential complications are dangerous (Table 1). Initial symptoms arise after an 8-15 day incubation period and resemble those of a cold accompanied by a high fever. Small red spots with white centres, known as Koplik’s spots, may appear on the inside of the cheeks. On the 3rd to 5th day of the disease state, a blotchy, slightly elevated pink rash develops behind the ears, spreading to the face and elsewhere; this lasts 3-5 days. The patient is contagious throughout this period, and the virus can be transmitted by respiratory droplets expelled from the body via a cough or sneeze. Full recovery takes 2-4 weeks. Serious complications are reported in 1 out of every 15 cases.1
Table 1. Chance of measles complications with and without vaccine
Children with cystic fibrosis, congenital heart or kidney disease and Down’s syndrome, for example, must be fully immunised since their risk of infection is far greater than average. Children who do not receive the vaccination because of age, receipt of immunosuppressive treatment for organ transplantation, or contraction of immunosuppressive diseases like leukaemia, depend on "population protection" for their personal safety from measles.1
Mumps also exhibits mild clinical symptoms but potentially severe complications. Symptoms appear 2-3 weeks after exposure and include fever, headache, and vomiting which may precede swelling of the parotid salivary glands. The gland on one side of the face often swells up days before the other; often only one side is affected. The symptoms usually last for 3 days, and the patient remains infectious until the swelling disappears. Complications include a 4-6% chance of viral meningitis, and a 0.1% chance of encephalitis. Inflammation of the testes (orchitis) occurs in 4 of 10 adult male cases. 1
Rubella, also known as German measles, displays similar symptoms to the aforementioned infections. However, its most severe complication in newly pregnant mothers is foetal malformations. Clinical symptoms which appear after a 2-3 week incubation period include headache, sore throat, enlarged lymph nodes in the neck, and a slight fever. A rash of minute pink spots follows. It appears first on the face and then spreads to the neck and the rest of the body. The spots disappear after about a week, but the patient remains infectious for another 3-4 days. If a mother acquires the infection during the early stages of pregnancy or just before conception, there can be devastating effects on the unborn child. The virus may affect all foetal organs and lead to serious birth defects, such as learning disabilities, retardation of intrauterine growth, and inflammatory lesions of the brain, lungs, liver, and bone marrow.1
THE MMR VACCINE AND IMMUNITY
The MMR is a live vaccine which provides individual protection from viral infection. It contains attenuated strains of the measles, mumps and rubella viruses that do not cause disease and are not contagious in humans. The vaccine is developed to produce an immune response sufficient to protect children against the real disease, without causing illness. A child who is vaccinated produces antibodies against the virus which offer immunity. Lymphocytes "remember" the virus and a prompt immune response occurs on re-exposure to the virus. Those who do not become immune after the first dose of the vaccine will have a 90-95% chance of doing so after the second dose.
Another level of protection is population protection, also known as "herd immunity." It is effective on the basis that if an infected individual has contact with others in the community, the infection will not spread, as the chance of encountering an individual who is not immune is very small. 1
It is thought that a single dose of the MMR vaccine gives 90% protection against measles and mumps and 95% protection against rubella. Adding a second dose increases protection to over 99%.
In the years following its introduction, the MMR vaccine has been supplied to over 90% of the population in the UK. It is thought that the combination of a relatively high rate of uptake and the two dose regime make chances increasingly likely that measles will be eradicated in the UK. The World Health Organisation concluded in 1996 that measles eradication is feasible through immunisation.
The Bandolier medical research group (1998) reported definitive evidence showing efficacy of the MMR vaccine based on public health data from Finland.2 Requests for immunisation came from the large number of army conscripts who fell ill. Prior to immunisation, more than a quarter of them contracted clinical mumps, leading to infertility and impaired hearing among their children, with subsequent deafness later in life. Rubella infection was also prominent with 1 case per 1000 annually. It was associated with hearing difficulties and congenital defects in children born to infected pregnant women. Foetal defects included cataracts, heart disease and mental retardation.
As a result, a mass immunisation programme was introduced in 1982 using 1000 child health centres, catch-up programmes and military recruits. Two million people (40% of the population) received 3.5 million doses of the triple MMR vaccine, and coverage was over 95%. A national reporting system for MMR was developed and serological confirmation of reported cases has been a requirement since 1987. The results were conclusive. In the decades preceding the immunisation programme, the number of measles cases equalled approximately 15,000. By 1985, this number had fallen dramatically to a negligible amount and by 1996 was at zero (Figure 1).
The number of cases of mumps and rubella reached tens of thousands per year. Similar to measles trends, the number of confirmed reports dropped sharply after introduction of a immunisation program. After 1997, no cases occurred except for those brought into Finland from outside countries.2
CONTROVERSY OVER MMR VACCINE SAFETY
In 1998, Dr. Andrew J Wakefield and his colleagues at the Royal Free Hospital in London published a paper in The Lancet which hypothesised a connection between the MMR vaccine and autism in children. The study was based on a group of 12 children, 8 of whom had autism and whose parents and physicians noticed a developmental regression after administration of the MMR vaccine. Wakefield also believed that the vaccine caused a leaky bowel and Crohn’s disease, allowing toxins to enter the brain and cause autism. However, results proved inconclusive and sparked furious debate.3
In 1999, immunisation records of 498 individuals with autism between 1979 and 1998 were examined. No change in autism trends after the introduction of the vaccine were found. There were no differences in the age of autism diagnosis between vaccinated and unvaccinated children. Nor was there clustering of developmental regression in the months after vaccination occurred.4
Afzal et al. (1998), concluded that the measles genome was not present in gut mucosal biopsies taken from patients with Crohn’s disease or ulcerative colitis, as was first suggested by Wakefield. Afzal et al. (1998) reported using techniques in which the assay was 1000 – 10000 more sensitive than the assays for infectious viruses. He stated that, "no measles-specific DNA fragments were found in the nested PCR products generated from blood lymphocytes or colonoscopic biopsy specimens of these 30 patients." 5
Similarly, Taylor et al. (1999) reported that neither developmental regression nor bowel problems were associated with MMR vaccination in children with autism. They did not report evidence in support of a "new variant" form of autism as hypothesised earlier by Wakefield et al. (1998). They reviewed the records of 13 children and found that the history given by the parents had changed after the extensive publicity about the MMR vaccine and autism. Records showed that parents reported concerns about their child’s development before their first birthday. However, since the MMR controversy, the patient history for the same child reported the development of symptoms after MMR immunisation. Taylor et al. (1999) noted that data from this patient group must be interpreted carefully due to inconsistencies associated with changes in the history given by the parents.6
Kaye et al. (2001) showed that the risk of autism increased nearly fourfold among boys aged 2-5 years born between 1988 and 1993 who were registered in the UK general practice research database, despite the prevalence of a vaccination coverage of over 95%.7 These data provide evidence against a causal association between the MMR vaccination and the risk of autism.
Autism, a neurobiological disorder that causes behavioural and language problems, is now recognised more often than it was in the past. Statistics taken from the UK indicate that an increase in cases occurred before MMR was introduced. Because parents often noticed the first signs of autism around the same time that the MMR vaccination was administered, there have been fears that the two are linked. Increase in the number of reported autism cases is also connected to the way that autism is now defined (Figure 1). Many forms of autism that were not recognised in the past are now classified as autism disorders.
Figure 1. Autism increase during the years of vaccine distribution.7
AFFECTS OF ADVERSE PUBLICITY IN IRELAND
The adverse publicity surrounding the MMR vaccine and its alleged link with autism and inflammatory bowel disease has affected uptake rates of the vaccine. It is evident that the MMR is the only vaccine that decreased significantly. This coincided with the publication of the paper by Wakefield et al. (1998). Children of vaccination age born at the time of publication have not received their vaccines due to worries by parents surrounding its safety.
Reasons for Poor Uptake Rates
In a recent Irish Times/Market Research Bureau of Ireland (MRBI) poll of people who were asked, "If you had a child who was due to be given the MMR vaccine, would you or would you not bring him for vaccination?" 78% said they would have their child vaccinated.9 However, only 73% of children have received their vaccinations according to the NDSC.8 An additional, 17% of people are either unsure about child immunisation, or have already decided not to vaccinate their children.
Similarly, 78% of Dublin respondents reported that they would vaccinate their children. However the NDSC has reported a 64% vaccination rate.
Differences in opinion on the MMR vaccination were observed among Irish social classes. Eleven percent of middle class (social class ABC1) Irish people were against the vaccination compared to 6% in the lower socio-economic group. The 24 to 34 year old age group were the most likely to list autism as their reason to not vaccinate. The reasons for not vaccinating their children are provided in Table 2.9
There have been other suggestions for the causes of poor uptake rates. Although there was a significant drop in uptake since the paper by Wakefield et al. (1998) was released, figures show that uptake rates in specific regions were low before this date.10,11 One suggestion is that general practitioners (GPs) refused to participate fully in the immunisation programmes that were in place, since they were not paid properly for immunising children. Evidence reveals that in some regions, payments to GPs for vaccinating children were delayed up to two years by health boards.9
Table 2. Reasons for not having the MMR5
Harrington et al. (2000), looked at inaccuracies in record keeping by health authorities and in particular the Eastern Regional Health Authority (ERHA). In this study, they found underestimations made in the region of 8.1 - 21.4% with regard to immunisation uptake levels in the area. Until 1996, immunisation uptake was estimated by totalling the number of completed vaccinations returned in the year and expressing this as a proportion of the population born in the same year. The report further admitted that this method of calculation "could lead to some inaccuracies in the figures if, for example, children did not complete primary vaccination under one year of age."12 Failure of GPs to send back vaccines was also blamed for contributing to the under-recording of true uptake.
POSSIBILITY OF 3 MONOVALENT VACCINES
It is reported that 72% of individuals poled are reluctant to give their child a triple MMR vaccine but would give a single measles shot. A further 15% were uncertain.8 The idea of using monovalent vaccines has been well publicised in the media as of late, and shows that parents believe it would be safer than a single MMR vaccine.
The use of three separate vaccines for measles, mumps and rubella has never been tested as an effective method of immunisation. No studies have been conducted to determine whether or not this approach is safe or effective.1 This theory therefore raises a number of poignant questions: Is this approach any safer overall? Will it offer children the same level of protection that the MMR has given against these diseases? In what order should the vaccines be given? How do we determine how much time to leave between each vaccine?
Unlike the MMR, the monovalent vaccines do not demonstrate a long safety record. Some varieties cause serious concern, in particular, the individual mumps vaccine that contains an ineffective Rubini strain may induce harmful symptoms. More alarming are those vaccines that contain the Urabe strain, which is associated with a higher risk of viral meningitis.13
Concern also exists over the length of time between vaccines, as children would be unprotected and at risk of contracting diseases for which they have not yet been vaccinated against.
If effective immunity to measles, mumps and rubella is to be achieved through vaccination, it is advised that the triple MMR vaccine be taken rather than single doses of each vaccination.
Concerns about vaccine safety such as those reported by Wakefield et al. (1998) have caused public confusion and have lead to a decrease in immunisation use.3 Unfortunately, the effect of decreased immunisation and the overall effect on public health have not yet been established. For measles alone, death rates are 1-2 per 1000 infected people while 1 in 1000 will develop encephalitis.1 If a reduction in vaccination rates results in unvaccinated children developing measles, the consequence of a measles epidemic would far outweigh the chance of reducing autism incidence through refusal of the MMR vaccination.
These common communicable diseases cannot be eliminated if the levels of immunisation in the community fall below a critical value. It is a legitimate concern for those with responsibility for public health to maintain high vaccination rates. The dangers of reducing vaccination on the basis of an unsubstantiated hypothesis are considerable.
To tackle this problem, an advertising and immunisation campaign on the level of the Meningitis C campaign is needed to improve the current slump in uptake rates. The controversy over its link with autism must be clarified and become the subject of a national media campaign using panels of high profile experts to explain this matter to the public.
Responsibility also falls upon GPs and public health nurses to ensure that families are aware of the dangers of these diseases, and to reassure them of the safety of the MMR vaccine.
1. Health Boards Executive. Measles, mumps, rubella (MMR) vaccine discussion pack. Edinburgh 2002. http://www.hebe.ie/pdf/mmr_complete_doc.pdf
2. Bandolier Medical Research Group: http://www.jr2.ox.ac.uk/bandolier/band84/MMR.html
3. Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. The Lancet 1998; 351:637-41.
4. Taylor B, Miller E, Lingam R, et al. Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: population study. BMJ 2002; 324:393-6.
5. Afzal MA, Minor PD, Begley J, et al. Absence of measles-virus genome in inflammatory bowel disease. The Lancet 1998; 351:646-67.
6. Taylor B, Miller E, Farrington CP, et al. Autism and measles, mumps and rubella vaccine: no epidemiological evidence for a causal association. The Lancet 1999; 353:2026-9.
7. Kaye JA, Melero-Montes M, Jick H. Mumps, measles and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis. BMJ 2001; 322:460-3.
8. National Disease Surveillance Centre. Immunisation uptake statistics for Ireland 2002. http://www.ndsc.ie/Publications/Immunisation Uptake Statistics/d621.PDF
9. Houston M. The MMR Vaccine Controversy. The Irish Times 2002 Mar 4; Page 7, 15. Irish Times no sections.
10. Vaccination Coverage Statistics for Children in Northern Ireland. Communicable Diseases Monthly Report 2002; 11:9.
11. Cover Programme: April to June 2002. CDR Weekly 2002: 26;12:39.
12. Harrington P, Shannon WF, Woodman C. Apparent low immunisation uptake in Dublin: under-performance or under-recording? IMJ 2000; 93: 8.
13. Elliman DAC, Bedford HE, Miller E. MMR vaccine - worries are not justified. Arch Dis Childhood 2001; 85:271-4.
14. Heller T, Heller D, Pattison S. Vaccination against mumps, measles and rubella: is there a case for deepening the debate? BMJ 2001; 323:838-840.