343 Rubella January 2013 Green Book Chapter 28 v2 0 28 Rubella notifiable the disease

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January 2013

Green Book Chapter 28 v2_0




The disease

Rubella is a mild disease caused by a togavirus. There may be a mild prodromal 

illness involving a low-grade fever, malaise, coryza and mild conjunctivitis. 

Lymphadenopathy involving post-auricular and sub-occipital glands may 

precede the rash. The rash is usually transitory, erythematous and mostly seen 

behind the ears and on the face and neck. Clinical diagnosis is unreliable as the 

rash may be fleeting and is not specific to rubella.

Rubella is spread by droplet transmission. The incubation period is 14 to 21 

days, with the majority of individuals developing a rash 14 to 17 days after 

exposure. Individuals with rubella are infectious from one week before 

symptoms appear to four days after the onset of the rash.

Complications include thrombocytopaenia (the rate may be as high as one in 

3000 infections) and post-infectious encephalitis (one in 6000 cases) (Lokletz 

and Reynolds, 1965; Plotkin and Orenstein, 2004). In adults, arthritis and 

arthralgia may occasionally be seen after rubella infection; chronic arthritis has 

rarely been reported (Plotkin and Orenstein, 2004).

Maternal rubella infection in pregnancy may result in fetal loss or in congenital 

rubella syndrome (CRS). CRS presents with one or more of the following:

  cataracts and other eye defects 


  cardiac abnormalities 


  retardation of intra-uterine growth 

  inflammatory lesions of brain, liver, lungs and bone marrow. 

Infection in the first eight to ten weeks of pregnancy results in damage in up 

to 90% of surviving infants; multiple defects are common. The risk of damage 

declines to about 10 to 20% with infection occurring between 11 and 16 weeks 

gestation (Miller et al., 1982). Fetal damage is rare with infection after 16 weeks 

of pregnancy, with only deafness being reported following infections up to 20 




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weeks of pregnancy. Some infected infants may appear normal at birth but 

perceptive deafness may be detected later (Miller et al., 1982; Plotkin and 

Orenstein, 2004).

History and epidemiology of the disease

Before the introduction of rubella immunisation, rubella occurred commonly 

in children, and more than 80% of adults had evidence of previous rubella 

infection (Morgan Capner et al., 1988). 

Rubella immunisation was introduced in the UK in 1970 for pre-pubertal 

girls and non-immune women of childbearing age to prevent rubella 

infection in pregnancy. Rather than interrupting the circulation of rubella, 

the aim of this strategy was to directly protect women of childbearing age 

by increasing the proportion with antibody to rubella; this increased from 

85 to 90% before 1970 to 97 to 98% by 1987 (Vyse et al., 2002). 

Surveillance for congenital rubella was established in 1971 to monitor the 

impact of the vaccination programme. During the period 1971–75 there 

were an average of 48 CRS births and 742 terminations annually in the UK 

(Tookey and Peckham, 1999) (see Figure 28.1). 

Although the selective immunisation policy was effective in reducing the 

number of cases of CRS and terminations of pregnancy, cases of rubella in 

pregnancy continued to occur. This was mainly because the few women who 

remained susceptible to rubella could still acquire rubella infection from their 

own and/or their friends’ children.

Universal immunisation against rubella, using the measles, mumps and 

rubella (MMR) vaccine, was introduced in October 1988. The aim of this 

policy was to interrupt circulation of rubella among young children, thereby 

protecting susceptible adult women from exposure. At the same time, rubella 

was made a notifiable disease. A considerable decline in rubella in young 

children followed the introduction of MMR, with a concomitant fall in 

rubella infections in pregnant women – from 167 in 1987 to one in 2003.

A seroprevalence study in 1989 showed a high rate of rubella susceptibility in 

school-age children, particularly in males (Miller et al., 1991). In 1993, there 

was a large increase in both notifications and laboratory-confirmed cases of 

rubella. Many of the individuals affected would not have been eligible for MMR 

or for the rubella vaccine. For this reason, the combined measles-rubella (MR) 

vaccine was used for the schools campaign in November 1994 (see Chapter 




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21). At that time, insufficient stocks of MMR were available to vaccinate all of 

these children against mumps. Over 8 million children aged between 5 and 16 

years were immunised with the MR vaccine. 

In October 1996, a two-dose MMR schedule was introduced and the 

selective vaccination policy of teenage girls ceased. A single dose of 


rubella-containing vaccine as used in the UK confers around 95 to 100% 

protection against rubella (Plotkin and Orenstein, 2004).

In Finland, a two-dose MMR schedule was introduced in 1982; high coverage 

of each dose has been achieved consistently. Indigenous measles, mumps and 

rubella have been eliminated since 1994 (Peltola et al., 1994). The United 

States introduced its two-dose schedule in 1989 and, in 2000, announced that 

it had interrupted endemic transmission (Plotkin and Orenstein, 2004, Chapter 

20). MMR is now routinely given in over 100 countries, including those in the 

European Union, North America and Australasia. 

A further resurgence of rubella was observed in the UK in 1996. Many of these 

cases occurred in colleges and universities in males who had already left 

school before the 1994 MR campaign (Vyse et al., 2002). Sporadic rubella 

Figure 28.1  Congenital rubella syndrome births (source: National Congenital 

Rubella Surveillance Programme 1971–2004) and rubella-associated 

terminations (source: Office for National Statistics 1971–2003)

CRS births (England,

Scotland and Wales)


(disease or contact, England

and Wales only)


71 73 75 77 79 81 83 85 87 89 91 93 95 97 99 ’01 03





















Fig 28.1

Number of


Number of





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cases have been reported since then, mainly linked to imported cases (Health 

Protection Agency website).

Since 1991, only around one-third of CRS infants have been born to UK-born 

women who acquired infection in the UK. The remaining two-thirds of CRS 

infants were born to women who were themselves born overseas. Of these, 

around one-half acquired infection overseas, mostly during early pregnancy, in 

their country of origin. The remaining women acquired infection in the UK, 

usually within two years of arrival (Rahi et al., 2001; Tookey and Peckham, 

1999; Tookey et al., 2002; Tookey, 2004). This latter observation is explained 

by higher susceptibility rates among some minority ethnic groups in the UK 

who had not been infected or immunised before coming to this country 

(Tookey et al., 2002). 

The MMR vaccination

MMR vaccines are freeze-dried preparations containing live, attenuated strains 

of measles, mumps and rubella viruses. The three attenuated virus strains are 

cultured separately in appropriate media and mixed before being lyophilised. 

These vaccines contain the following:


Each 0.5ml dose of reconstituted vaccine contains:


not less than 103.0 cell culture infective dose




) of the Schwarz 

measles virus


not less than 103.7 CCID


 of the RIT 4385 mumps virus 


not less than 103.0 CCID


 of the Wistar RA 27/3 rubella virus strains.


Each 0.5ml dose when reconstituted contains not less than the equivalent of:


1000 tissue culture infective dose




) of the more attenuated 

Enders line of the Edmonston strain of measles virus 

 20,000 TCID


 of mumps virus (Jeryl Lynn® Level B strain) 


1000 TCID


 of rubella virus (Wistar RA 27/3 strain). 

MMR vaccine does not contain thiomersal or any other preservatives. The  

vaccine contains live organisms that have been attenuated (modified). MMR is 

recommended when protection against measles, mumps and/or rubella is 





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The unreconstituted vaccine and its diluent should be stored in the original 

packaging at +2˚C to +8˚C and protected from light. All vaccines are sensitive 

to some extent to heat and cold. Heat speeds up the decline in potency of most 

vaccines, thus reducing their shelf life. Effectiveness cannot be guaranteed for 

vaccines unless they have been stored at the correct temperature. Freezing may 

cause increased reactogenicity and loss of potency for some vaccines. It can 

also cause hairline cracks in the container, leading to contamination of the 


The vaccines should be reconstituted with the diluent supplied by the 

manufacturer and either used within one hour or discarded. 


Rubella vaccine is only available as part of a combined product (MMR). 

Priorix is supplied as a whitish to slightly pink pellet of lyophilised vaccine 

for reconstitution with the diluent supplied. The reconstituted vaccine must be 

shaken well until the pellet is completely dissolved in the diluent.

MMRVaxPRO is supplied as a lyophilised powder for reconstitution with the 

diluent supplied. The reconstituted vaccine must be shaken gently to ensure 

thorough mixing. The reconstituted vaccine is yellow in colour and should only 

be used if clear and free from particulate matter.

Dosage and schedule

Two doses of 0.5ml at the recommended interval (see below).


Vaccines are routinely given intramuscularly into the upper arm or anterolateral 

thigh. However, for individuals with a bleeding disorder, vaccines should be 

given by deep subcutaneous injection to reduce the risk of bleeding. 

MMR vaccine can be given at the same time as other vaccines such as DTaP/ 

IPV, Hib/MenC and hepatitis B. The vaccine should be given at a separate site, 

preferably in a different limb. If given in the same limb, they should be given 

at least 2.5cm apart (American Academy of Pediatrics, 2003). See chapter 11 

for the routine childhood immunisation schedule. If MMR cannot be given at 

the same time as an inactivated vaccine, it can be given at any interval before 




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or after. The site at which each vaccine is given should be noted in the child’s 


MMR should ideally be given at the same time as other live vaccines, such as 

BCG. If live vaccines are given simultaneously, then each vaccine virus will 

begin to replicate and an appropriate immune response is made to each 

vaccine. After a live vaccine is given, natural interferon is produced in response 

to that vaccine. If a second live vaccine is given during this response, the 

interferon may prevent replication of the second vaccine virus. This may 

attenuate the response to the second vaccine. Based on evidence that MMR 

vaccine can lead to an attenuation of the varicella vaccine response (Mullooly 

and Black, 2001), the recommended interval between live vaccines is currently 

four weeks. For this reason, if live vaccines cannot be administered 

simultaneously, a four-week interval is recommended. 

Four weeks should be left between giving MMR vaccine and carrying out 

tuberculin testing. The measles vaccine component of MMR can reduce the 

delayed-type hypersensitivity response. As this is the basis of a positive 

tuberculin test, this could give a false negative response.

When MMR is given within three months of receiving blood products, such as 

immunoglobulin, the response to the measles component may be reduced. This 

is because such blood products may contain significant levels of measles- 

specific antibody, which could then prevent vaccine virus replication. Where 

possible, MMR should be deferred until three months after receipt of such 

products. If immediate measles protection is required in someone who has 

recently received a blood product, MMR vaccine should still be given. To 

confer longer-term protection, MMR should be repeated after three months. 

Where rubella protection is required for post-partum women who have 

received anti-D immunoglobulin, no deferral is necessary as the response to 

the rubella component is normally adequate (Edgar and Hambling, 1977; 

Black et al., 1983). Blood transfusion around the time of delivery may inhibit 

the rubella response and, therefore, a test for rubella antibody should be 

undertaken six to eight weeks after vaccination. The vaccination should be 

repeated if necessary.


Equipment used for vaccination, including used vials or ampoules, should be 

disposed of at the end of a session by sealing in a proper, puncture-resistant 

‘sharps’ box (UN-approved, BS 7320).




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Recommendations for the use of the vaccine

The objective of the immunisation programme is to provide two doses of 

MMR vaccine at appropriate intervals for all eligible individuals. 

Over 90% of individuals will seroconvert to measles, mumps and rubella 

antibodies after the first dose of the MMR vaccines currently used in the UK 

(Tischer and Gerike, 2000). Antibody responses from pre-licence studies may 

be higher, however, than clinical protection under routine use. Evidence shows 

that a single dose of measles-containing vaccine confers protection in around 

90% of individuals for measles (Morse et al., 1994; Medical Research Council, 

1977). A single dose of a rubella-containing vaccine confers around 95 to 

100% protection (Plotkin and Orenstein, 2004). A single dose of a mumps-

containing vaccine used in the UK confers between 61% and 91% 

protection against mumps (Plotkin and Orenstein, 2004). A more recent study 

in the UK suggested that a single dose of MMR is around 64% effective 

against mumps (Harling et al., 2005). 

Therefore, two doses of MMR are required to produce satisfactory protection 

against measles, mumps and rubella. 

MMR is recommended when protection against measles, mumps and/or 

rubella is required. MMR vaccine can be given irrespective of a history of 

measles, mumps or rubella infection. There are no ill effects from immunising 

such individuals because they have pre-existing immunity that inhibits 

replication of the vaccine viruses.

Children under ten years of age

The first dose of MMR should be given between 12 and 13 months of age (i.e. 

within a month of the first birthday).  Immunisation before one year of age 

provides earlier protection in localities where the risk of measles is higher, but 

residual maternal antibodies may reduce the response rate to the vaccine. The 

optimal age chosen for scheduling children is therefore a compromise between 

risk of disease and level of protection. 

If a dose of MMR is given before the first birthday, either because of travel to 

an endemic country, or because of a local outbreak, then this dose should be 

ignored, and two further doses given at the recommended times between 12 

and 13 months of age (i.e. within a month of the first birthday) and at three 

years four months to five years of age (see chapter 11).





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A second dose is normally given before school entry but can be given routinely 

at any time from three months after the first dose. Allowing three months 

between doses is likely to maximise the response rate, particularly in young 

children under the age of 18 months where maternal antibodies may reduce the 

response to vaccination (Orenstein et al., 1986; Redd et al., 2004; de Serres et 

al., 1995). Where protection against measles is urgently required, the second 

dose can be given one month after the first (ACIP, 1998). If the child is given 

the second dose less than three months after the first dose and at less than 

18 months of age, then the routine pre-school dose (a third dose) should be 

given in order to ensure full protection. 

Children aged ten years or over and adults 

All children should have received two doses of MMR vaccine before they 

leave school. The teenage (school-leaving) booster session or appointment is 

an opportunity to ensure that unimmunised or partially immunised children are 

given MMR. If two doses of MMR are required, then the second dose should 

be given one month after the first. 

MMR vaccine can be given to individuals of any age.

  Entry into college, 

university or other higher education institutions, prison or military service 

provides an opportunity to check an individual’s immunisation history. Those 

who have not received MMR should be offered appropriate MMR immunisation. 

All seronegative women of childbearing age who need to be protected against 

rubella should be offered MMR vaccine. Satisfactory evidence of protection 

would include documentation of having received two doses of rubella- 

containing vaccine or a positive antibody test for rubella. 

The decision on when to vaccinate other adults needs to take into 

consideration the past vaccination history, the likelihood of an individual 

remaining susceptible and the future risk of exposure and disease:


  individuals who were born between 1980 and 1990 may not be protected 

against mumps but are likely to be vaccinated against measles and 

rubella. They may never have received a mumps-containing vaccine 

or had only one dose of MMR, and had limited opportunity for 

exposure to natural mumps. They should be recalled and given MMR 

vaccine. If this is their first dose, a further dose of MMR should be 

given from one month later. 




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  individuals born between 1970 and 1979 may have been vaccinated 

against measles and many will have been exposed to mumps and rubella 

during childhood. However, this age group should be offered MMR 

wherever feasible, particularly if they are considered to be at high risk 

of exposure. Where such adults are being vaccinated because they have 

been demonstrated to be susceptible to at least one of the vaccine 

components, then either two doses should be given, or there should 

be evidence of seroconversion to the relevant antigen. 

  individuals born before 1970 are likely to have had all three natural 

infections and are less likely to be susceptible. MMR vaccine should be 

offered to such individuals on request or if they are considered to be at 

high risk of exposure. Where such adults are being vaccinated because 

they have been demonstrated to be susceptible to at least one of the 

vaccine components, then either two doses should be given or there 

should be evidence of seroconversion to the relevant antigen. 

Individuals with unknown or incomplete vaccination


Children coming from developing countries will probably have received a 

measles-containing vaccine in their country of origin but may not have 

received mumps or rubella vaccines (www-nt.who.int/immunization_monitor

ing/en/globalsummary/countryprofileselect.cfm). Unless there is a reliable 

history of appropriate immunisation, individuals should be assumed to be 

unimmunised and the recommendations above should be followed. Individuals 

aged 18 months and over who have not received MMR should receive two 

doses at least one month apart. An individual who has already received one 

dose of MMR should receive a second dose to ensure that they are protected.

Healthcare workers

Protection of healthcare workers is especially important in the context of their 

ability to transmit measles or rubella infections to vulnerable groups. While 

they may need MMR vaccination for their own benefit, on the grounds 

outlined above, they also should be immune to measles and rubella for the 

protection of their patients.

Satisfactory evidence of protection would include documentation of:


  having received two doses of MMR, or 

  positive antibody tests for measles and rubella.




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Individuals who are travelling or going to reside abroad 

All travellers to epidemic or endemic areas should ensure that they are fully 

immunised according to the UK schedule (see above). 


There are very few individuals who cannot receive MMR vaccine. When there 

is doubt, appropriate advice should be sought from a consultant paediatrician, 

immunisation co-ordinator or consultant in communicable disease control 

rather than withholding the vaccine.

The vaccine should not be given to:


  those who are immunosuppressed (see chapter 6 for more detail) 

  those who have had a confirmed anaphylactic reaction to a previous dose 

of a measles-, mumps- or rubella-containing vaccine 

  those who have had a confirmed anaphylactic reaction to neomycin 

or gelatin

  pregnant women.

Anaphylaxis after MMR is extremely rare (3.5 to 14.4 per million doses) 

(Bohlke et al., 2003; Patja et al., 2000; Pool et al., 2002; D’Souza et al., 2000). 

Minor allergic conditions may occur and are not contraindications to further 

immunisation with MMR or other vaccines. A careful history of that event will 

often distinguish between anaphylaxis and other events that are either not due 

to the vaccine or are not life-threatening. In the latter circumstances, it may be 

possible to continue the immunisation course. Specialist advice must be sought 

on the vaccines and circumstances in which they could be given. The lifelong 

risk to the individual of not being immunised must be taken into account.


Minor illnesses without fever or systemic upset are not valid reasons to 

postpone immunisation. If an individual is acutely unwell, immunisation 

should be postponed until they have fully recovered. This is to avoid confusing 

the differential diagnosis of any acute illness by wrongly attributing any sign 

or symptoms to the adverse effects of the vaccine. 

Idiopathic thrombocytopaenic purpura

Idiopathic thrombocytopaenic purpura (ITP) has occurred rarely following 

MMR vaccination, usually within six weeks of the first dose. The risk of 




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developing ITP after MMR vaccine is much less than the risk of developing it 

after infection with wild measles or rubella virus. 

If ITP has occurred within six weeks of the first dose of MMR, then blood should 

be taken and tested for measles, mumps and rubella antibodies before a second dose 

is given. Serum should be sent to the Health Protection Agency (HPA) Virus 

Reference Laboratory (Colindale), which offers free, specialised serological testing 

for such children. If the results suggest incomplete immunity against measles, 

mumps or rubella, then a second dose of MMR is recommended. 

Allergy to egg

All children with egg allergy should receive the MMR vaccination as a 

routine procedure in primary care (Clark et al., 2010). Recent data suggest 

that anaphylactic reactions to MMR vaccine are not associated with 

hypersensitivity to egg antigens but to other components of the vaccine (such 

as gelatin) (Fox and Lack, 2003). In three large studies with a combined total 

of over 1000 patients with egg allergy, no severe cardiorespiratory reactions 

were reported after MMR vaccination (Fasano et al., 1992; Freigang et al., 

1994; Aickin et al., 1994; Khakoo and Lack, 2000). Children who have had 

documented anaphylaxis to the vaccine itself should be assessed by an 

allergist (Clark et al., 2010). 

Pregnancy and breast-feeding

There is no evidence that rubella-containing vaccines are teratogenic. In the 

USA, UK and Germany, 661 women were followed through active surveillance, 

including 293 who were vaccinated (mainly with single rubella vaccine) in the 

high-risk period (i.e. the six weeks after the last menstrual period). Only 16 

infants had evidence of infection and none had permanent abnormalities 

compatible with CRS (Best et al., 2004). However, as a precaution, MMR 

vaccine should not be given to women known to be pregnant. If MMR vaccine 

is given to adult women, they should be advised to guard against pregnancy for 

one month. 

Termination of pregnancy following inadvertent immunisation should not be 

recommended (Tookey et al., 1991). The potential parents should be given 

information on the evidence of lack of risk from vaccination in pregnancy. 

Surveillance of inadvertent MMR administration in pregnancy is being 

conducted by the HPA Immunisation Department, to whom such cases should 

be reported (Tel: 020 8200 4400). 




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Pregnant women who are found to be susceptible to rubella should be 

immunised with MMR after delivery. 

Breast-feeding is not a contraindication to MMR immunisation, and MMR 

vaccine can be given to breast-feeding mothers without any risk to their baby. 

Very occasionally, rubella vaccine virus has been found in breast milk, but this 

has not caused any symptoms in the baby (Buimovici-Klein et al., 1997; 

Landes et al., 1980; Losonsky et al., 1982). The vaccine does not work when 

taken orally. There is no evidence of mumps and measles vaccine viruses being 

found in breast milk.

Premature infants

It is important that premature infants have their immunisations at the appropriate 

chronological age, according to the schedule (see chapter 11). 

Immunosuppression and HIV

MMR vaccine is not recommended for patients with severe immunosuppression 

(see Chapter 6) (Angel et al., 1996). MMR vaccine can be given to HIV- 

positive patients without or with moderate immunosuppression (as defined in 

Table 28.1).

Further guidance is provided by the Royal College of Paediatrics and Child 

Health (www.rcpch.ac.uk), the British HIV Association (BHIVA) Immunisation 

guidelines for HIV-infected adults (BHIVA, 2006) and the Children’s HIV 

Association of UK and Ireland (CHIVA) immunisation guidelines 



Neurological conditions

The presence of a neurological condition is not a contraindication to 

immunisation. If there is evidence of current neurological deterioration, 

including poorly controlled epilepsy, immunisation should be deferred until 

the condition has stabilised. Children with a personal or close family history 

Table 28.1  CD4 count/µl (% of total lymphocytes) 


<12 months 

1–5 years  

6–12 years   >12 years

No suppression 






(15–24%) (25%) (25%)


750–1499  500–999 200–499 200–499 


(15–24%)  (15–24%) (15–24%) (15–24%)


<750  <500 <200 <200 


suppression  (<15%)  (<15%) (<15%) (<15%)




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of seizures should be given MMR vaccine. Advice about likely timing of any 

fever and management of a fever should be given. Doctors and nurses should 

seek specialist paediatric advice rather than refuse immunisation.

Adverse reactions 

Adverse reactions following the MMR vaccine (except allergic reactions) are 

due to effective replication of the vaccine viruses with subsequent mild illness. 

Such events are to be expected in some individuals. Events due to the measles 

component occur six to 11 days after vaccination. Events due to the mumps 

and rubella components usually occur two to three weeks after vaccination but 

may occur up to six weeks after vaccination. These events only occur in 

individuals who are susceptible to that component, and are therefore less 

common after second and subsequent doses. Individuals with vaccine- 

associated symptoms are not infectious to others.

Common events

Following the first dose of MMR vaccine, malaise, fever and/or a rash may 

occur, most commonly about a week after immunisation, and last about two to 

three days. In a study of over 6000 children aged one to two years, the 

symptoms reported were similar in nature, frequency, time of onset and 

duration to those commonly reported after measles vaccine alone (Miller et al., 

1989). Parotid swelling occurred in about 1% of children of all ages up to four 

years, usually in the third week. 

Adverse reactions are considerably less common after a second dose of MMR 

vaccine than after the first dose. One study showed no increase in fever or rash after 

re-immunisation of college students compared with unimmunised controls (Chen 

et al., 1991). An analysis of allergic reactions reported through the US Vaccine 

Adverse Events Reporting System in 1991–93 showed fewer reactions among 

children aged six to 19 years, considered to be second-dose recipients, than among 

those aged one to four years, considered to be first-dose recipients (Chen et al., 

1991). In a study of over 8000 children there was no increased risk of convulsions, 

rash or joint pain in the months after the second dose of the MMR vaccination 

given between four and six years of age (Davis et al., 1997). 

Rare and more serious events

Febrile seizures are the most commonly reported neurological event following 

measles immunisation. Seizures occur during the sixth to eleventh day in one 

in 1000 children vaccinated with MMR – a rate similar to that reported in the 

same period after measles vaccine. The rate of febrile seizures following MMR 

is lower than that following infection with measles disease (Plotkin and 




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Orenstein, 2004). There is good evidence that febrile seizures following MMR 

immunisation do not increase the risk of subsequent epilepsy compared with 

febrile seizures due to other causes (Vestergaard et al., 2004). 

One strain of mumps virus (Urabe) in an MMR vaccine previously used in the 

UK was associated with an increased risk of aseptic meningitis (Miller et al., 

1993). This vaccine was replaced in 1992 (Department of Health, 1992) and is 

no longer licensed in the UK. A study in Finland using MMR containing a 

different mumps strain (Jeryl Lynn), similar to those used currently in MMR 

in the UK, did not identify any association between MMR and aseptic 

meningitis (Makela et al., 2002).

Because MMR vaccine contains live, attenuated viruses, it is biologically 

plausible that it may cause encephalitis. A recent large record linkage study in 

Finland looking at over half a million children aged between one and seven 

years did not identify any association between MMR and encephalitis (Makela 

et al., 2002). 

ITP is a condition that may occur following MMR and is most likely due to the 

rubella component. This usually occurs within six weeks and resolves 

spontaneously. ITP occurs in about one in 22,300 children given a first dose of 

MMR in the second year of life (Miller et  al., 2001). If ITP has occurred 

within six weeks of the first dose of MMR, then blood should be taken and 

tested for measles, mumps and rubella antibodies before a second dose is given 

(see above).

Arthropathy (arthralgia or arthritis) has also been reported to occur rarely after 

MMR immunisation, probably due to the rubella component. If it is caused by 

the vaccine, it should occur between 14 and 21 days after immunisation. Where 

it occurs at other times, it is highly unlikely to have been caused by 

vaccination. Several controlled epidemiological studies have shown no excess 

risk of chronic arthritis in women (Slater, 1997). 

All suspected adverse reactions to vaccines occurring in children, or in 

individuals of any age after vaccines labelled with a black triangle (▼), should 

be reported to the Commission on Human Medicines using the Yellow Card 

scheme. Serious, suspected adverse reactions to vaccines in adults should be 

reported through the Yellow Card scheme. 




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Other conditions reported after vaccines containing

measles, mumps and rubella

Following the November 1994 MR immunisation campaign, only three cases 

of Guillain-Barré syndrome (GBS) were reported. From the background rate, 

between one and eight cases would have been expected in this population over 

this period. Therefore, it is likely that these three cases were coincidental and 

not caused by the vaccine. Analysis of reporting rates of GBS from acute 

flaccid paralysis surveillance undertaken in the WHO Region of the Americas 

has shown no increase in rates of GBS following measles immunisation 

campaigns when 80 million children were immunised (da Silveira et al., 1997). 

In a population that received 900,000 doses of MMR, there was no 

increased risk of GBS at any time after vaccinations (Patja et al., 2001). 

This evidence refutes the suggestion that MMR causes GBS. 

Although gait disturbance has been reported after MMR, a recent 

epidemiological study showed no evidence of a causal association between 

MMR and gait disturbance (Miller et al., 2005).

In recent years, the postulated link between measles vaccine and bowel disease 

has been investigated. There was no increase in the incidence of inflammatory 

bowel disorders in those vaccinated with measles-containing vaccines 

compared with controls (Gilat et al., 1987; Feeney et al., 1997). No increase 

in the incidence of inflammatory bowel disease has been observed since the 

introduction of MMR vaccination in Finland (Pebody et al., 1998) or in the 

UK (Seagroatt, 2005).

There is overwhelming evidence that MMR does not cause autism (www.iom.

edu/report.asp?id=20155). Over the past seven years, a large 

number of studies have been published looking at this issue. Such studies 

have shown:

  no increased risk of autism in children vaccinated with MMR compared 

with unvaccinated children (Farrington et al., 2001; Madsen and 

Vestergaard, 2004) 

  no clustering of the onset of symptoms of autism in the period following 

MMR vaccination (Taylor et al., 1999; De Wilde et al., 2001; Makela 

et al., 2002)

  that the increase in the reported incidence of autism preceded the use of 

MMR in the UK (Taylor et al., 1999)




January 2013

Green Book Chapter 28 v2_0

  that the incidence of autism continued to rise after 1993, despite the 

withdrawal of MMR in Japan (Honda et al., 2005)

  that there is no correlation between the rate of autism and MMR vaccine 

coverage in either the UK or the USA (Kaye et al., 2001; Dales et al., 


  no difference between the proportion of children developing autism after 

MMR who have a regressive form compared with those who develop 

autism without vaccination (Fombonne, 2001; Taylor et al., 2002; 

Gillberg and Heijbel, 1998)

  no difference between the proportion of children developing autism after 

MMR who have associated bowel symptoms compared with those who 

develop autism without vaccination (Fombonne, 2001; Fombonne, 1998; 

Taylor et al., 2002)

  that no vaccine virus can be detected in children with autism using the 

most sensitive methods available (Afzal et al., 2006).

For the latest evidence, see the Department of Health’s website: www.dh.gov.



It has been suggested that combined MMR vaccine could potentially overload 

the immune system. From the moment of birth, humans are exposed to 

countless numbers of foreign antigens and infectious agents in their everyday 

environment. Responding to the three viruses in MMR would use only a tiny 

proportion of the total capacity of an infant’s immune system (Offit et al., 

2002). The three viruses in MMR replicate at different rates from each other 

and would be expected to reach high levels at different times. 

A study examining the issue of immunological overload found a lower rate of 

admission for serious bacterial infection in the period shortly after MMR 

vaccination compared with other time periods. This suggests that MMR does not 

cause any general suppression of the immune system (Miller et al., 2003).

Management of cases, contacts and outbreaks


Prompt notification of measles, mumps and rubella to the local health protection 

unit (HPU) is required to ensure public health action can be taken promptly. 

Notification should be based on clinical suspicion and should not await 

laboratory confirmation. Since 1994, few clinically diagnosed cases are 




January 2013

Green Book Chapter 28 v2_0

subsequently confirmed to be true measles, mumps or rubella. Confirmation 

rates do increase, however, during outbreaks and epidemics.

The diagnosis of measles, mumps and rubella can be confirmed through 

non-invasive means. Detection of specific IgM in oral fluid (saliva) samples, 

ideally between one and six weeks after the onset of rash or parotid swelling, 

has been shown to be highly sensitive and specific for confirmation of these 

infections (Brown et al., 1994; Ramsay et al., 1991; Ramsay et al., 1998). It is 

recommended that oral fluid samples should be obtained from all notified 

cases, other than during a large epidemic. Advice on this procedure can be 

obtained from the local HPU. 

Infants with suspected congenital rubella infection should be reported to the 

National Congenital Rubella Surveillance Programme, either directly to the 

Institute of Child Health (Tel: 020 7905 2604) or via the British Paediatric 

Surveillance Unit (Tel: 020 7323 7911). 

Protection of contacts with MMR

Antibody response to the rubella component of MMR vaccine does not 

develop soon enough to provide effective prophylaxis after exposure to 

suspected rubella. Even where it is too late to provide effective post-exposure 

prophylaxis with MMR, the vaccine can provide protection against future 

exposure to all three infections. Therefore, contact with suspected measles, 

mumps or rubella provides a good opportunity to offer MMR vaccine to 

previously unvaccinated individuals. If the individual is already incubating 

measles, mumps or rubella, MMR vaccination will not exacerbate the 

symptoms. In these circumstances, individuals should be advised that a 

rubella-like illness occurring shortly after vaccination is likely to be due to 

natural infection. If there is doubt about an individual’s vaccination status, 

MMR should still be given as there are no ill effects from vaccinating those 

who are already immune.

Protection of contacts with immunoglobulin

Human normal immunoglobulin is not routinely used for post-exposure 

protection from rubella since there is no evidence that it is effective. It is 


recommended for the protection of pregnant women exposed to rubella. It 

should only be considered when termination of pregnancy is 

unacceptable. Serological follow-up of recipients is essential.




January 2013

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To prevent or attenuate an attack:

Dose: 750mg


  MMRVaxPRO® – manufactured by Sanofi Pasteur MSD.

  Priorix® – manufactured by GlaxoSmithKline.

These vaccines are supplied by Healthcare Logistics (Tel: 0870 871 1890) as 

part of the national childhood immunisation programme.

In Scotland, supplies should be obtained from local childhood vaccine holding 

centres. Details of these are available from Scottish Healthcare Supplies (Tel: 

0131 275 6154). 

In Northern Ireland, supplies should be obtained from local childhood vaccine 

holding centres. Details of these are available from the regional pharmaceutical 

procurement service (Tel: 02890 552368).


Human normal immunoglobulin

England and Wales:

Health Protection Agency, Centre for Infections

(Tel: 020 8200 6868).


Blood Transfusion Service

(Tel: 0141 3577700).

Northern Ireland: 

Public Health Laboratory, Belfast City Hospital 

(Tel: 01232 329241).0


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Afzal MA, Ozoemena LC, O’Hare A et al. (2006) Absence of detectable measles virus 

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Green Book Chapter 28 v2_0

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Document Outline

  • The disease 
  • The MMR vaccination 
  • Recommendations for the use of the vaccine 
  • Contraindications 
  • Precautions 
  • Adverse reactions  
  • Management of cases, contacts and outbreaks 
  • Supplies 
  • Adverse reactions  
  • Management of cases, contacts and outbreaks 
  • Supplies 
  • References  

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