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Vaccine-Preventable DiseasesMeaslesThe epidemiology of measles in Canada has been discussed in the feature section "Measles Elimination in Canada." The disease has a worldwide distribution, although marked reductions in its incidence have been reported in many countries where measles vaccine has been widely used for many years. It continues to be a common disease in many parts of the world, particularly in developing countries where it is a major killer of children < 5 years of age. Infection with the measles virus generally leads to more severe disease in infants and adults than in young children. Complications include otitis media, pneumonia, and encephalitis. In Canada, measles mortality is estimated at one per 3,000 cases for all age groups. Mortality can be as high as 5% to 10% in the very young and malnourished. Deaths occur mainly in children < 5 years of age, mostly due to pneumonia and occasionally encephalitis. Prior to the introduction of measles vaccine, an estimated 300,000 to 400,000 cases of measles occurred annually, mostly in children. The incidence of measles in the pre-vaccine era peaked at 768 cases per 100,000 population in 1935; multiple peaks of lesser magnitude occurred at 2- to 4-year intervals. In the immediate post-vaccine period, measles was not reportable nationally; however, when reporting began again in 1969, the incidence had dropped significantly. More recently, from 1986 to 1995, the annual incidence of reported measles has ranged between 0.7 and 58.5 cases per 100,000 population. In 1993, 203 measles cases (0.7 per 100,000 population) were reported in Canada; this represents an almost 15-fold decrease in incidence compared to 1992. This was also the lowest total reported for any year since national notification began in 1924. However, the incidence of reported measles in 1994 increased about 2.5 times over that in 1993 and, in 1995, 4.4 times over that in 1994. Increased incidence in 1994 was mainly reported from Quebec and Ontario; however, the incidence in 1995 was largely due to widespread outbreaks in Ontario which accounted for more than 95% of the cases. The median age of measles cases during the 1995 outbreak was 10 years old. The majority of cases (83%) occurred in school-aged children (aged 5 to 19 years); 33% among those aged 10 to 14 years, 30% among those aged 5 to 9 years, and 21% in those aged 15 to 19 years. Almost 90% of the cases whose immunization histories were reviewed had documented measles immunization with one vaccine, 3.9% were not eligible for immunization (born before 1957 or < 12 months of age), and immunization status was unknown for 4.5%. The magnitude of the 1995 outbreak in Canada and its relevance to measles elimination activities in all countries of the Americas are discussed in the feature section on measles. In particular, it is important to note that mass catch-up campaigns and the implementation of routine two-dose measles immunization programs across Canada in 1996 have stopped the circulation of the measles virus. A provisional total of 315 cases was reported from January to November 1996. This puts Canada in a very good position to achieve its goal of eliminating measles by 2005, and allows for the potential elimination of measles by 2000 as per the PAHO goal. 1998 Update: In 1997, Canada recorded 581 confirmed cases of measles. In 1998, that number decreased to 12, the lowest number ever recorded nationally in Canada. In 1998, all cases were reported to Health Canada through an e-mail based surveillance system. For a measles case to be considered confirmed at the national level, it has to satisfy the following case definition.
OR
All 12 reported cases were confirmed in the laboratory by testing for measles-specific IgM antibodies and verified by the national Working Group on Measles Elimination in Canada (WGMEC). One specimen for measles virus isolation was collected and identified as MVi/Montreal.CAN/19.98 [D5]. The median age at onset of rash was five years (age range younger than one year to 33 years) with a 7:5 female to male ratio. Only two cases were known to require hospitalization. Vaccine histories were available for nine of the 12 confirmed cases. Seven cases received the first vaccine and two had not. Of the two unvaccinated cases, one was not vaccinated because of a history of egg allergy (Egg allergy is no longer considered a contraindication to immunization with MMR. See Canadian Immunization Guide - 1998 [5th edition], page 122) and one had "missed" the appointment for immunization. For those vaccinated cases, two received the vaccine before the first birthday while living outside canada. Only one of nine received a second dose of measles, mumps and rubella (MMR) vaccine. The cases were distributed across the country and, unlike the majority of cases in 1997 (1), were not related to outbreaks (Table 7).
*Preliminary data Five of the confirmed measles cases in 1998 travelled outside Canada seven to 21 days before the onset of rash. Only one case had an identified contact with another measles case and that was in an individual who was exposed outside Canada. One additional case is to be reviewed by WGMEC because it was laboratory confirmed by two separate laboratory tests, but not by the IgM capture assay currently used by Health Canada. Four additional reports were received on patients exhibiting clinical symptoms but without confirmatory laboratory work to support the diagnosis. Documentation on three of the four 'clinical' cases indicates that the caregiver refused and/or the clinician was unable or unwilling to collect a serum sample. No specimens for measles virus isolation were collected.
In summary, as the country moves towards the goal to eliminate indigenous measles, it is important to sustain and even improve current immunization coverage for all susceptible populations. As well, clinicians must be urged to maintain a high index of suspicion for measles, to report all suspect cases rapidly and to confirm all suspect cases. Most cases meeting the clinical case definition will NOT be measles because of the nonspecificity of the clinical definition; therefore, only cases with laboratory confirmation or epidemiological links to a confirmed case can be considered a case. WGMEC strongly urges that serological specimens be collected for all suspect cases as well as nasopharyngeal or throat and/or urine specimens for virus isolation. Measles Vaccine Live measles virus vaccines are prepared from Edmonston B "further attenuated" strains (e.g., Moraten, Edmonston-Zagreb, Schwarz, Connaught strains). They are available alone, in combination with live rubella vaccine (MR) or with mumps and rubella vaccines (MMR). Measles vaccines are generally prepared in chick fibroblast cell cultures, except for MoRu-Viraten Berna®, which is grown in human fibroblasts. All preparations may contain traces of antibiotics (e.g., neomycin) and stabilizer such as gelatin. Consult the product monograph for details. Efficacy The efficacy of the measles vaccine increases with age at immunization. The main mechanism explaining poor efficacy in children immunized at an early age is the interference by maternal antibody. These antibodies are transferred from the mother to the fetus in utero, and their levels slowly decrease after birth. Most infants have lost their maternal antibody by 12 months of age, but studies have shown that immunization at 15 months of age gives higher protection. Maternal antibodies are not the unique factor in vaccine failure, as the protection appears to reach a plateau after 15 months of age. The efficacy of a single dose given at 12 or 15 months is estimated to be 85% to 95%. With a second dose, almost 100% of children are protected. Recommended Usage Infants and children For routine immunization, two doses of measles vaccine should be given. Infants should receive a first dose combined with mumps and rubella vaccines (MMR) shortly after their first birthday; the second dose should be given at least 4 weeks after the first and before school entry. It is convenient to link this dose with other routinely scheduled immunizations. Options include giving it with the next scheduled immunization at 18 months of age, with school entry immunization at 4 to 6 years, or at any intervening age that is practicable (such as entry to day care). For routine second doses, MMR vaccine is preferred because a proportion of children will also benefit from enhanced protection against rubella and mumps. Two doses of vaccine given 4 weeks apart are recommended for children who
Vaccine may be recommended for children < 12 months of age if they are at high risk of exposure to measles or are travelling abroad to an area where measles is common; measles vaccine alone or as MMR may be given as early as 6 months of age. Under these circumstances, or if vaccine was inappropriately given before the child's first birthday, such children should receive two additional doses of MMR after the first birthday. Post-exposure use: Susceptible individuals > 12 months of age who are exposed to measles may be protected from disease if measles vaccine is given within 72 hours after exposure. There are no known adverse effects of vaccine given to people incubating measles. IG given within 6 days after exposure can modify or prevent disease and may be used for this purpose in infants < 12 months of age, people for whom vaccine is contraindicated, or those for whom more than 72 hours but less than 1 week have elapsed since exposure (for IG dose see page 33 of the Guide). Unless it is contraindicated, individuals who receive IG should receive measles vaccine later, at the intervals specified in Table 7 on page 34 of the Guide. Adults Routine immunization is recommended for adults born after 1970 without a history of disease. In the 1998 edition of the Canadian Immunization Guide, this cut-off was changed from 1957 to 1970 because the epidemiology of measles in Canada since 1989 has demonstrated that cases are very rare in adults born before that year. This observation is explained by the relatively free circulation of measles virus in Canada up until the early 1970s, which allowed most people born before then to acquire measles. Although the vaccine was licensed for use in both Canada and the U.S. in 1963, it was used on a large scale in Canada only in the early 1970s, as compared with the mid 1960s in the U.S. Furthermore, in 1976, age at immunization was raised to 15 months in the U.S. while it remained at 12 months in Canada. The greater proportion of primary vaccine failures associated with a younger age at immunization permitted the large outbreaks of measles observed until the recent introduction of the two-dose schedule. A small proportion of adults born since 1970 are still vulnerable, and this proportion is greater among younger adults. Epidemiologic data show that settings with large concentrations of young adults, such as colleges and universities, permit transmission of measles. Thus, vaccine should be administered to adults born since 1970 who attend such institutions or who are expected to be at higher risk of measles exposure than the general population, for example, during travel or outbreaks. Although two doses of vaccine or documented proof of disease are generally needed as evidence of complete protection, the administration of a single dose of vaccine to adults without such proof appears satisfactory. In fact, most adults without proof of immunity are already immune, and a single dose of vaccine will raise that proportion close to 100%. The benefit of a second dose 1 month later is limited, because the main cause of vaccine failure (anti-measles maternal antibody) is not a problem in adults. One additional dose of vaccine should be offered only to adults born since 1970 who are at the greatest risk of exposure and who have not already received two doses or had natural measles infection. These people include
Dosage The dose of measles vaccine, either alone or in combination with rubella and mumps vaccine (MMR), is 0.5 mL. For unidose vials, the whole content of the vial should be injected after reconstitution (0.5-0.7 mL). Route of Administration The vaccine should be administered subcutaneously. Vaccine Storage Requirements Measles-containing vaccine should be stored in the refrigerator at a temperature of 2o C to 8o C. Once reconstituted, the vaccine should be administered promptly. Simultaneous Administration with Other Vaccines Measles-containing vaccine can be given concurrently with other childhood vaccines such as combined diphtheria, pertussis, tetanus, polio or Haemophilus influenzae type b vaccines. Separate injections are required at different anatomic sites. When administered with other live vaccines, like varicella vaccine, measles-containing vaccine should be given at the same time or separated by a minimum 4-week interval. Adverse Reactions Measles vaccine produces a mild, non-transmissible and usually subclinical infection. Fever, with or without rash, may be seen in about 5% to 10% of individuals 7 to 10 days after administration. Fever may occasionally trigger a seizure in susceptible children, such as those who have previously had convulsions or whose siblings or parents have a history of convulsions. However, the risk is low, and the benefit of immunizing children greatly outweighs any potential risk associated with febrile seizures. Transient thrombocytopenia occurs, rarely, during the month after immunization. Adverse reactions are less frequent after the second dose of vaccine and tend to occur only in those not protected by the first dose. Encephalitis has been reported in association with administration of live attenuated measles vaccine at a frequency of approximately 1 per million doses distributed in North America, which is so rare that it is uncertain whether vaccine is the cause. Nevertheless, the reported incidence is much lower than that observed with the natural disease (approximately 1 per 1,000 cases). There has been a dramatic decline in the incidence of SSPE since the introduction of widespread measles immunization. To date, no cases from whom measles virus was isolated had a vaccine strain. If MMR is used, reactions to the mumps and rubella components may be encountered (see pages 167 and 203 of the Guide). Despite reports of an association between MMR vaccine and autism or inflammatory bowel disease, rigorous studies have confirmed the lack of causality (see General Cautions and Contraindications, page 7 of the Guide. Therefore, separate administration of the different components of MMR is strongly discouraged, as it will give no health benefit, will increase the proportion of children who fail to receive all three antigens and/or delay achieving complete protection against all three diseases, and will cause unnecessary pain and distress to children. Contraindications Measles vaccine (or MMR) is contraindicated in individuals with a previous anaphylactic reaction to a measles-containing vaccine. If there is a compelling reason to reimmunize such individuals, MMR skin testing and graded challenge in an appropriately equipped facility can be considered. However, the possibility of a hypersensitivity reaction to the MMR skin test or during the graded challenge must be considered. Administration of measles vaccine or MMR should be deferred if there is any severe acute illness. However, immunization should not be delayed because of minor acute illness, with or without fever. Although there is no known risk from measles vaccine administered during pregnancy, it should not be given to pregnant women. Since measles vaccine may contain trace amounts of neomycin, people who have experienced anaphylactic reactions to topically or systemically administered neomycin should not receive measles vaccine. Measles vaccine may also contain gelatin as a stabilizer, and so those who have had severe allergic reactions to gelatin or gelatincontaining products should be immunized with great caution. Measles vaccine is contraindicated in most people whose immune system is impaired as a result of disease or therapy (for HIV, see the section below and Vaccination in Immunocompromised Hosts, on page 20 of the Guide). Precautions Tuberculosis may be exacerbated by natural measles infection, but there is no evidence that measles vaccine has such an effect. Measles immunization can suppress a positive tuberculin skin test for several weeks. If skin testing for tuberculosis is required, it should be done on the same day as immunization or delayed for 6 or more weeks. MMR is indicated for most infants infected with HIV whose immune function at 12 to 15 months of age is compatible with safe MMR immunization (1994 Pediatric HIV Classification categories E, N1, A1). Consultation with an expert is required in the case of HIV-infected children to determine the presence or absence of significant immunodeficiency in individual cases. Measles re-vaccination may still be appropriate for HIV-infected people with moderate immunodeficiency if there is a high risk of measles in the local community or travel to an area where measles is endemic. Consultation with local public health authorities will help determine the local level of measles activity and risk to travellers abroad. Because the response to prior immunization may be impaired, HIV-infected children should receive IG after recognized exposures to measles. When other susceptible people with immune deficiencies are exposed to measles, passive immunization with IG should be given as soon as possible (see page 33 of the Guide . It is desirable to immunize close contacts of immunocompromised individuals in order to minimize the latter's risk of exposure to measles. Clinical studies have demonstrated that egg allergy should no longer be considered a contraindication to immunization with MMR. In people who have a history of anaphylactic hypersensitivity to hens' eggs (urticaria, swelling of the mouth and throat, difficulty in breathing or hypotension), measles vaccine can be administered in the routine manner without prior skin testing. However, this should take place where adequate facilities are available to manage anaphylaxis. Those at risk should be observed for 30 minutes after immunization for any sign of allergic reaction. No special precautions are necessary for children with minor egg hypersensitivity who are able to ingest small quantities of egg uneventfully or who are given measlesrubella vaccine free of avian protein. No special measures are necessary for children who have never been fed eggs before MMR immunization. Prior egg ingestion should not be a prerequisite for MMR immunization (see Anaphylaxis section, page 14 of the Guide ). For travellers, care must be taken in the timing of immunization when IG is also required (see Table 7, page 34 of the Guide). Outbreak Control A full discussion of measles outbreak control is beyond the scope of this chapter. Readers are referred to the statement on outbreak control issued by the Advisory Committee on Epidemiology.With the current two-dose schedule for measles vaccine, large outbreaks of measles are not expected to recur. However, because many countries have lower immunization coverage, measles will continue to be imported into Canada. Imported cases will result in limited transmission of measles, usually among unvaccinated children and young adults who have not received two doses of vaccine. Control interventions in schools or other facilities had little impact when Canada was using a single-dose program. With the two-dose strategy and high vaccine coverage, the benefits of control interventions are likely to be negligible except in settings where vaccine coverage is known to be low. Thus, before any intervention is started, suspected measles cases should be promptly confirmed by culture or serology. If cases are confirmed, contacts should be informed that measles is circulating and advised to update their immunization status if necessary. For practical purposes, all students attending the same school or facility should be considered contacts. Immunization within 72 hours of exposure will usually prevent measles and is not known to produce adverse effects. Should an individual already be immune or infected by measles virus, there is no increased risk of adverse reactions from immunization with live measles vaccine or with MMR. Selected References Advisory Committee on Epidemiology. Guidelines for control of measles outbreaks in Canada. CCDR 1995;21:189-95. Bell A, King A, Pielak K et al. Epidemiology of measles outbreak in British Columbia-February 1997. CCDR 1997;23:49-51. De Serres G, Boulianne N, Meyer F et al. Measles vaccine efficacy during an outbreak in a highly vaccinated population: incremental increase in protection with age at vaccination up to 18 months. Epidemiol Infect 1995;115:315-23. De Serres G, Gay NJ, Paddy C et al. Epidemiology of transmissible diseases after elimination . Am J Epidemiol 2000;151(1):1039-48. De Serres G, Sciberras J, Naus M et al. Protection after two doses of measles vaccine is independent of interval between doses. J Infect Dis 1999;180:187-90. Gay NJ, De Serres G, Farrington CP et al. Elimination of measles from the United States: an assessment through basic surveillance data . J Infect Dis 2002, in press. Halsey NA, Hyman SL. Measles-mumps-rubella vaccine and autistic spectrum disorder: report from the New Challenges in Childhood Immunizations Conference convened in Oak Brook, Illinois, June 12-13, 2000 . Pediatrics 2001;107:E84 Institute of Medicine, Immunization Safety Review Committee (Stratton K, Gable A, Shetty P et al, eds.). Measles-mumps-rubella vaccine and autism. Washington DC: National Academy Press, 2001. King A, Varughese P, De Serres G et al. The epic of measles in Canada: from endemic to epidemic to elimination: measles in Canada. J Infect Dis 2002, in press. Markowitz L, Albrecht P, Orenstein WA et al. Persistence of measles antibody after revaccination. J Infect Dis 1992;166:205-08. McLean ME, Walsh PJ, Carter AO et al. Measles in Canada - 1989. CCDR 1990;16:213-18. Osterman JW, Melnychuk D. Revaccination of children during school-based measles outbreaks: potential impact of a new policy recommendation . Can Med Assoc J 1992;146:929-36. Ratnam S, Chandra R, Gadag V. Maternal measles and rubella antibody levels and serologic response in infants immunized with MMRII vaccine at 12 months of age. J Infect Dis 1993;168:1596-98. Ratnam S, West R, Gadag V et al. Immunity against measles in school aged children: implications for measles revaccination strategies. Can J Public Health 1996;87:407-10. Strauss B, Bigham M. Does measles-mumps-rubella (MMR) vaccination cause inflammatory bowel disease and autism? CCDR 2001;27:65-72. Wong T, Lee-Han H, Bell B et al. Measles outbreak in Waterloo area, Ontario, 1990-1991. CCDR 1991;17:219-24. |
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