N O T I F I A B L E
22.1.1 Measles is an acute viral illness transmitted via droplet infection. Clinical features include, coryza, conjunctivitis, bronchitis, Koplik spots, rash and fever. The incubation period is about ten days, with a further two to four days before the rash appears. It is highly infectious from the beginning of the prodromal period to four days after the appearance of the rash. Measles is a notifiable disease.
22.1.2 Fulfilment of criteria of a case definition is not a requirement for notification of measles but recent experience shows that few cases, notified according to clinical diagnosis, are measles. Correctly diagnosed cases tend to be those occurring in older children and in outbreaks. The presence of the following features may improve the accuracy of clinical diagnosis: rash for at least three days, fever for at least one day, and at least one of the following - cough, coryza or conjunctivitis.
22.1.3 The diagnosis of measles (and mumps and rubella) can now be confirmed through non-invasive means. Detection of specific IgM in saliva samples, ideally taken from three days after the onset of rash or parotid swelling, has been shown to be highly sensitive and specific for confirmation of these infections, when compared with serological tests used as standards. Whenever possible, saliva samples should be obtained from all notified cases. Advice on this procedure can be obtained from the local Consultant in Communicable Disease Control, or Public Health Laboratory or Consultant in Public Health Medicine (CPHM) Communicable Disease and Environmental Health (CD & EH) in Scotland.
22.1.4 Complications of measles have been reported in one in 15 notified cases, and include otitis media, bronchitis, pneumonia, convulsions and encephalitis. Encephalitis has an incidence of one in 5000 cases, has a mortality of about 15%, and 20% to 40% of survivors have residual neurological sequelae. Electro-encephalographic changes have been reported after apparently uncomplicated measles as well as in cases with frank encephalitis. Complications are more common and severe in poorly nourished and chronically ill children; it is therefore particularly important that such children should be immunised against measles.
22.1.5 Case fatality rates for measles are age-related. They are high in children under one year of age, are lowest in children aged 1 to 9 years and then rise again with advancing age. Before 1988, more than half the acute measles deaths occurred in previously healthy children who had not been immunised.
22.1.6 In children receiving immunosuppressive treatment, particularly for leukaemia, measles was a major cause of morbidity and mortality. Between 1970 and 1983, 19 children in remission from acute lymphatic leukaemia died from measles, and of 51 children who died in their first remission in 1974-84, measles was the cause of death in nearly a third.
22.1.7 Subacute sclerosing panencephalitis (SSPE) is a rare but fatal late complication of measles infection. Most often it follows early measles infection which may not necessarily have been recognised. Measles immunisation protects against SSPE.
22.1.8 Notification of measles began in England and Wales in 1940, and until the introduction of vaccine in 1968 annual notifications varied between 160,000 and 800,000, the peaks occurring in two year cycles. By the late 1980s, annual notifications had fallen only to between 50,000 and 100,000. This limited effect came about because coverage was never sufficiently high to have an effect on virus transmission. Between 1970 and 1988, there continued to be an average of 13 acute measles deaths each year. In countries where high coverage was achieved shortly after the introduction of measles immunisation, the epidemic cycle was more effectively suppressed and very low levels of measles were observed.
22.1.9 Following the introduction of MMR vaccine in October 1988 and the achievement of coverage levels in excess of 90%, notifications of measles fell progressively to the lowest levels since records began, in 1940. In 1993, there were only 9612 measles notifications. Since 1988, there have been only 11 deaths due to measles recorded in England and Wales. Most of these have been due to neurological conditions and only 4 have been due to acute measles illness.
22.1.10 The high coverage of MMR vaccine and the ensuing reduction of transmission meant that after 1988, children who had not been immunised no longer had the opportunity to be exposed to measles infection and remained susceptible until early teenage. A rising proportion of school age children were therefore susceptible to measles, as confirmed by age stratified sero-epidemiology. Analysis of epidemiological data, by mathematical modelling, predicted the high probability of a major resurgence of measles affecting for the greater part the school age population. Similar measles epidemics had been seen in many other countries following periods of low incidence, achieved through high immunisation coverage.
22.1.11 In 1993, small outbreaks of measles began to occur in England and Wales and predominantly affected secondary school children. In Scotland, a measles epidemic, affecting the west of the country, led to 138 teenagers being admitted to one infectious disease unit alone.
22.1.12 A national immunisation campaign was implemented in November 1994 throughout the United Kingdom. Over 8 million children aged between 5 and 16 years were immunised with measles/ rubella vaccine. As a consequence, susceptibility to measles in the target population fell by about 85% and only very few confirmed cases of measles have occurred in school children. The few confirmed cases that now occur, mostly in adults or children too young to be protected by immunisation, can often be linked to importation of the virus from abroad. Reports of serious adverse reactions to the vaccine were very rare (0.007%).
22.1.13 Mumps is an acute viral illness characterised by parotid swelling which may be unilateral or bilateral; some cases are asymptomatic. The incubation period is 14-21 days and mumps is transmissible from several days before the parotid swelling to several days after it appears. Complications include pancreatitis, oophoritis and orchitis; even when the latter is bilateral there is no firm evidence that it causes sterility. Neurological complications including meningitis and encephalitis may precede or follow parotitis, and can also occur in its absence. Before the introduction of MMR vaccine, mumps was the cause of about 1200 hospital admissions each year in England and Wales. In the under 15 age group it was a common cause of viral meningitis; it can also cause permanent unilateral deafness at any age.
22.1.14 Mumps was made a notifiable disease in the UK in October 1988.
22.1.15 Notifications have fallen progressively; in 1995 there were only 2021 notifications. The incidence of the disease has declined dramatically in all ages, including those too old to have been immunised. Laboratory testing shows that most notified cases are not mumps.
22.1.16 Rubella is a mild infectious disease, previously common among children aged four to nine years. It causes a transient erythematous rash, lymphadenopathy involving post-auricular and suboccipital glands and occasionally in adults, arthritis and arthralgia. Clinical diagnosis is unreliable since the symptoms are often fleeting and can be caused by other viruses; in particular, the rash is not diagnostic of rubella. A history of “rubella” should never be accepted without serological or saliva confirmation (28.1.7). The incubation period is 14- 21 days and the period of infectivity from one week before until four days after the onset of rash.
22.1.17 Maternal rubella infection in the first eight to ten weeks of pregnancy results in fetal damage in up to 90% of infants and multiple defects are common. The risk of damage declines to about 10-20% by 16 weeks and after this stage of pregnancy, fetal damage is rare. Fetal defects include mental handicap, cataract, deafness, cardiac abnormalities, retardation of intra-uterine growth and inflammatory lesions of brain, liver, lungs and bone-marrow. Any combination of these may occur; the only defects which commonly occur alone are perceptive deafness and pigmentary retinopathy following infection after the first eight weeks of pregnancy. Some infected infants may appear normal at birth but perceptive deafness may be detected later. For investigation of suspected rubella or exposure to rubella in pregnant women see 28.1.5.
22.1.18 Before the introduction of rubella immunisation, there were as many as 70 cases of Congenital Rubella Syndrome (CRS) during epidemic years; the ratio of therapeutic abortions to cases of CRS was approximately 10:1.
22.1.19 Rubella immunisation was introduced in the UK in 1970 for pre-pubertal girls and non-immune women with the aim of protecting women of child-bearing age from the risks of rubella in pregnancy. This policy was not intended to prevent the circulation of rubella, but to increase the proportion of women with antibody to rubella; this increased from 85-90% before 1970 to 97-98% by 1987 and has remained at this level.
22.1.20 Although the selective immunisation policy was effective in reducing the number of cases of CRS and terminations of pregnancy, it became apparent that the elimination of rubella in pregnancy could never be achieved by this means. The few remaining rubella susceptible women continued to be exposed to rubella by their own and their friends’ children.
22.1.21 The inclusion of rubella vaccine in 1988, with measles and mumps vaccines, as MMR, was intended to interrupt circulation of rubella amongst young children, thereby protecting susceptible adult women. Rubella was made a notifiable disease in 1988.
22.1.22 A considerable decline in rubella in young children followed but in 1993, there was a large increase in both notifications and laboratory confirmed cases of rubella. Many of these cases occurred in males in colleges and universities. However, there was also an increase in the number of reports of rubella infections in pregnant women. These rose from 2 in 1992 to 23 in 1993; there were 8 in 1995. Outbreaks of rubella have continued predominantly in young males and there will continue to be a small number of infections in pregnant women, through contact with young men in this country or acquired abroad.
22.1.23 Sero-epidemiological surveillance has showed high levels of susceptibility to rubella in males aged 10-40 years compared to women of this age. This difference had resulted from the effect of the selective rubella immunisation programme which was targeted only at females. The inclusion of rubella vaccine with measles vaccine in the national immunisation campaign of 1994 has reduced susceptibility to rubella in males aged up to 16 years by about 85%. This will prevent these males from transmitting rubella to susceptible pregnant women in the future. Outbreaks of rubella, as presently being seen, can be expected to stop.
22.1.24 For reporting of CRS, see 28.9.
22.2.1 This is a freeze-dried preparation containing live attenuated measles, mumps and rubella viruses. It must be stored in the dry state at 2-8°C (not frozen) and protected from light. It should be reconstituted with the diluent supplied by the manufacturer and used within one hour. Immunisation provides protection for around 90% of recipients for measles and mumps and over 95% for rubella. Vaccine-induced antibody to rubella has been shown to persist for at least 18 years in the absence of endemic disease. Since the vaccine viruses are not transmitted, there is no risk of infection from vaccinees.
22.2.2 One vaccine is currently available: MMR II (Merck); Enders’ Edmonston strain measles, RA 27/3 rubella, Jeryl Lynn mumps.
22.2.3 Single antigen measles, mumps and rubella vaccines are available. (See 28.7 for rubella vaccine supplies).
0.5ml is given by intramuscular or deep subcutaneous injection.
22.4.1 Evidence shows that a single dose of MMR vaccine confers protection in around 90% of individuals for measles and mumps and 95% for rubella. Therefore, if 92% of children are given MMR vaccine, with 90% efficacy for the measles component, only 83% are protected from each year’s birth cohort. The accumulation over time of these susceptible children is sufficient to allow the re-emergence of epidemics of measles. This potential for epidemics can be prevented with a two dose programme.
22.4.2 Beginning 1 October 1996, all children, except those with a valid contraindication, should receive 2 doses of MMR vaccine. These are recommended to be given shortly after the first birthday and before school entry.
22.4.3 MMR vaccine should be given irrespective of a history of measles, mumps or rubella infection.
22.4.4 MMR vaccine can be given to children of any age whose parents request it, and no opportunity should be missed to ensure that this is done. If the primary immunisations of DTP, polio and Hib have not been completed by the time that MMR vaccine is due, they can be given at the same time using separate syringes and different sites. For maximum effect, vaccine must be given soon after the first birthday.
22.4.5 If parents do not wish MMR vaccine to be given at the same time as other injected vaccines, then OPV should be given with MMR and the child recalled for the other vaccines as soon as possible; in these circumstances no three week interval between immunisations is necessary.
22.4.6 When children who have not received their first dose of MMR attend for their pre-school boosters (DT and polio vaccines), they should be offered the first MMR and arrangements made for a second dose to be given three months after the first dose.
22.4.7 There is a group of children who were too young to be included in the measles rubella immunisation campaign of 1994 and who have already been given their pre-school boosters. These children should be recalled and given MMR vaccine. Similarly, any children known not to have received measles and rubella vaccine, should be offered MMR vaccine.
22.4.8 When children attend for their school leaving immunisations, there is an opportunity to check that all recommended immunisations have been completed. Boys and girls who have not had measles and rubella vaccine, should be offered MMR vaccine. There is no contraindication to the simultaneous administration of MMR, Td and OPV.
22.4.9 MMR vaccine can be given to non-immune adults and should be considered for those in long-term institutional care who may not have developed immunity. Entry into college, university or other centres for further education provides an opportunity to check the immunisation history. Students who have not received MR or MMR vaccine should be offered MMR immunisation.
22.4.10 Children with a personal or close family history of convulsions should be given MMR vaccine, provided the parents understand that there may be a febrile response. As for all children, advice for reducing fever should be given. Doctors should seek specialist paediatric advice rather than refuse immunisation. Dilute immunoglobulin as formerly used with measles vaccine for such children is no longer used since it may inhibit the immune response to the rubella and mumps components.
22.4.11 Unimmunised children in the following groups are at particular risk from measles infection and should be immunised with MMR vaccine:
22.4.12 As vaccine-induced measles antibody develops more rapidly than that following natural infection, MMR vaccine can be used to protect susceptible contacts during a measles outbreak. To be effective the vaccine must be administered within three days of exposure. If there is doubt about a child’s immunity, vaccine should be given since there are no ill effects from vaccinating individuals who are already immune. Immunoglobulin is available for individuals for whom vaccine is contraindicated (22.9.1). NB. Antibody responses to the rubella and mumps components of MMR vaccine are too slow for effective prophylaxis after exposure to these infections.
22.4.13 Re-immunisation is necessary when vaccine has been given before 12 months of age.
22.4.14 Measles virus inhibits the response to tuberculin, so that a false negative tuberculin test may be found for up to a month following MMR vaccine.
22.4.15 HIV positive individuals may be given MMR vaccine in the absence of contraindications.
22.5.1 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. During the sixth to eleventh days after vaccine, febrile convulsions occurred in 1/1000 children, the rate previously reported in the same period after measles vaccine. Parotid swelling occurred in about 1% of children of all ages up to four years, usually in the third week and occasionally later.
22.5.2 Up until September 1992, MMR vaccines containing the Urabe strain of mumps virus were in routine use. These vaccines were found to be rarely associated with mumps meningitis, most often occurring around three weeks after immunisation. No cases have been confirmed in association with the presently used Jeryl Lynn mumps vaccine. When mumps virus is isolated from the cerebro-spinal fluid, laboratory tests can distinguish between wild and vaccine strains. Advice should be sought from the National Institute for Biological Standards and Control (Tel. 01707 654753).
22.5.3 Thrombocytopenia, which usually resolves spontaneously, occurs in about 1 in 24,000 children given a first dose of MMR at 12 - 15 months.
22.5.4 Arthropathy (arthralgia or arthritis) has been reported to occur rarely after MMR immunisation. If it occurs other than 14-21 days after immunisation, it is unlikely to have been caused by the vaccine.
22.5.5 Because MMR vaccine contains live attenuated viruses, it is biologically plausible for it to cause cases of encephalitis. However, a recent review of the published evidence on encephalitis, and measles or MMR immunisation, concluded that the evidence is inadequate to accept or reject a causal relationship between measles or mumps vaccine and encephalitis or encephalopathy. This suggests that if there is a risk of encephalitis or encephalopathy, induced by the vaccine, it is exceptionally small.
22.5.6 23 cases of neurological disease following measles immunisation were investigated in the United States between 1965 and 1967. 18 cases were characterised as ‘encephalitis’. The interval from immunisation to the onset of symptoms ranged from 3 to 24 days. The estimated rate of encephalitis within a four week period of measles immunisation was 1.5 cases per 1 million distributed doses of vaccine. The background rate of encephalitis (unrelated to immunisation) was 2.8 cases per 1 million children for any 4 week period. The authors of the study concluded that "no single clinical or epidemiological characteristic appears consistently in the reports of cases of possible neurological sequelae of measles immunisation".
22.5.7 After a second dose of MMR vaccine, adverse reactions are considerably less common than after the first dose. One study showed no increase in fever or rash after re-immunisation of college students compared to unimmunised controls. Only 3 cases of thrombocytopenia were reported in association with the immunisation of over 8 million children in the November 1994 measles/rubella campaign. This suggests that the risk in children receiving a second dose is considerably less than in children receiving a first dose. An analysis of adverse reactions reported through the US Vaccine Adverse Events Reporting System in 1991-93 showed fewer reactions among children aged 6 to 19 years, considered to be second dose recipients, than among those aged 1-4 years, considered first dose recipients.
22.5.8 Three cases of Guillain-Barré syndrome (GBS) were reported following the November 1994 MR immunisation campaign. Between one and eight cases would have been expected in this population over this period of time in the absence of an immunisation campaign. Analysis of reporting rates of GBS from acute flaccid paralysis surveillance undertaken in the Region of the Americas has shown no increase in rates of GBS following measles immunisation campaigns when over 70 million children were immunised. It was concluded from this evidence that measles immunisation does not cause GBS.
22.5.9 Parents should be told about possible symptoms after immunisation and given advice for reducing fever, including the use of paracetamol in the period five to ten days after immunisation. They should also be reassured that post-immunisation symptoms are not infectious.
22.5.10 Serious reactions should be reported to the Committee on Safety of Medicines using the yellow card system.
There is increasing evidence that MMR vaccine can be given safely to children even when they have previously had an anaphylactic reaction (generalised urticaria, swelling of the mouth and throat, difficulty in breathing, hypotension or shock) following food containing egg. A combined total of 1265 patients from 16 studies has been reported. None of 284 patients with histories of egg hypersensitivity confirmed by oral challenge, had any adverse reactions. MMR was administered safely to 1209 patients with positive skin tests to egg. There were only 2 reports of symptoms suggestive of anaphylaxis (0.16%). The combined data indicate that over 99% of children who are allergic to eggs can safely receive MMR vaccine. Dislike of egg, or refusal to eat it, is not a contraindication. If there is concern, paediatric advice should be sought with a view to immunisation under controlled conditions such as admission to hospital as a day case.
MMR vaccines are supplied by Farillon (Tel. 01708 379000) as part of the National Childhood Immunisation Programme. MMR II (Merck); Enders’ Edmonston strain measles, RA 27/3 rubella, Jeryl Lynn mumps. Pasteur Merieux MSD Ltd (Tel. 01628 773200)
Children and adults with compromised immunity (7.3.1 to 7.3.7) who come into contact with measles should be given human normal immunoglobulin (HNIG) as soon as possible after exposure. Testing for measles antibody may delay the administration of HNIG and neither immunisation nor low level antibody guarantees immunity to measles in the immunocompromised. Children under 12 months in whom there is a particular reason to avoid measles, (such as recent severe illness), can also be given immunoglobulin; MMR vaccine should then be given after an interval of at least three months, at around the usual age.
Dose:
| To prevent an attack: | |
| Age | Dose |
| Under 1 year | 250 mg |
| 1-2 years | 500 mg |
| 3 and over | 750 mg |
| To allow an attenuated attack: | |
| Under 1 year | 100 mg |
| 1 year or over | 250 mg |
An interval of at least three months must be allowed before subsequent MMR immunisation.
Dilute immunoglobulin as previously used with measles vaccine for children with a history of convulsions is no longer used since it may inhibit the immune response to rubella and mumps.
HNIG is no longer used for post-exposure protection since there is no evidence that it is effective. Mumps-specific immunoglobulin is no longer available.
Post-exposure prophylaxis does not prevent infection in non-immune contacts and is therefore not recommended for the protection of pregnant women exposed to rubella. It may however reduce the likelihood of clinical symptoms which may possibly reduce the risk to the fetus. It should only be used when termination of pregnancy for proved rubella infection is unacceptable to the pregnant woman, when it should be given as soon as possible after exposure; serological follow-up of recipients is essential.
Dose: 750 mg
22.10 Supplies of HNIG:
Communicable Disease Surveillance Centre. Tel. 0181 200 6868 Public Health Laboratories, England and Wales. Blood Transfusion Service, Scotland (see 18.13 for telephone numbers). Bio Products Laboratory Tel. 0181 905 1818. Northern Ireland: Public Health Laboratory, Belfast City Hospital, Tel. 01232 329241. Immuno, Tel. 01732 458101. (Gammabulin). Pharmacia and Upjohn Ltd, Tel. 01908 661101(Kabiglobulin).
Severity of notified measles. Miller C L. BMJ 1978; i: 1253. Deaths from measles. Miller C L. BMJ 1985; 290: 443-444. Mortality and morbidity caused by measles in children with malignant disease attending four major treatment centres: a retrospective view. Gray M, Hann I M, Glass S, Eden O B, Morris Jones P, Stevens R F. BMJ 1987; 295: 19-22. Measles serology in children with a history of measles in early life. Adjaye N, Azad A, Foster M, Marshall W C, Dunn H. BMJ 1983; 286: 1478. Live measles vaccine: a 21 year follow up. Miller C L. BMJ 1987; 295: 22-24. Safe administration of mumps/measles/rubella vaccine in egg-allergic children. Greenberg M A, Birx D L. J. Pediatrics 1988; 113: 504-6. Safe immunisation of allergic children against measles, mumps and rubella. Juntenen-Backman K, Peltola H, Backman A, Salo O P. Am. J. Dis. Children 1987; 141: 1103-5. 22 Measles, Mumps and Rubella Immunisation against Infectious Disease 143 Virus meningitis and encephalitis in 1979. Noah N D, Urquart A M. J. Infection 1980; 2: 379-83. Big bang for immunisation. Editorial. Sir John Badenoch. BMJ 1988; 297: 750-1. Surveillance of antibody to measles, mumps and rubella by age. Morgan-Capner P, Wright J, Miller C L, Miller E. BMJ 1988; 297: 770-2. Surveillance of symptoms following MMR vaccine in children. Miller C L et al. Practitioner 1989; 233: 69-73. Mumps meningitis and MMR vaccination. Lancet 1989, ii: 1015-1016. Mumps viruses and mumps, measles, and rubella vaccine. Forsey T, Minor P D. BMJ 1989; 299: 1340. Egg hypersensitivity and measles/mumps/rubella vaccine administration. Beck S A, Williams L W, Shirrell M, Burks A W Paediatrics 1991; 88: 5: 913-917. Vaccine safety versus vaccine efficacy in mass immunisation programmes Nokes D J, Anderson R M Lancet 1991: 338: 1309-1312 Safe administration of the measles vaccine to children allergic to eggs. James J M, Burks A W, Robertson P K, Sampson H A. N Eng J Med; 1995;332:19,1262-1266. Measles in 1995 - transmission interrupted in schoolchildren. Communicable Disease Report 1995;5(21): Adverse events following measles-mumps-rubella and measles vaccinations in college students. Chen R T et al. Vaccine 1991;9:297-9. Rubella surveillance to June 1994: third joint report from the PHLS and the National Congenital Rubella Surveillance Programme. Miller E et al. CDR Review 1994;4(R12):R146-52. The epidemiology of subacute sclerosing panencephalitis in England and Wales, 1970 to 1989. Miller C, Farrington C P and Harbert K. International J of Epidemiology 1992;21:998-1006. Risk of aseptic meningitis after measles, mumps and rubella vaccine in UK children. Miller E et al. Lancet 1993;341:979-82. An outbreak of measles in Trafford. Richardson J A, Quigley C. CDR Review 1994;4(R6):R73-5. Complications of mumps vaccines. Balraj V, Miller E. Reviews in Medical Virology 1995;5:219-27. Adverse Events Associated with Childhood Vaccines -Evidence Bearing on Causality. Stratton K R, Howe C J and Johnston R B. Institute of Medicine, National Academy Press, Washington D.C. 1994 : p130. A new method for active surveillance of adverse events from diphtheria/tetanus/pertussis and measles/mumps/rubella vaccines. Farrington P, Pugh S, Colville A, Flower A, Nash J, Morgan-Capner P, Rush M, Miller E Lancet 1995; 345;567-569 Salivary diagnosis of measles: A study of notified cases in the United Kingdom, 1991-93 Brown D, Ramsay M, Richards A, Miller E BMJ 1994, 308 1015-1017 Measles in secondary school children; implications for vaccination policy Calvert N, Cutts F, Miller E, Brown D, Munro J CDR 1994; 4; No. 6, R70-R73 Adverse Reactions to Measles/Rubella Vaccine Current Problems in Pharmacovigilance 1995; 21: pp 9-10. For rubella references see Chapter 28.