Canadian Medical Association Journal 1996; 155: 1423-1426
[résumé]
Paper reprints may be obtained from: Dr. John Furesz, 180520 The Driveway, Ottawa ON K2P 1C8; telephone and fax 613 234-0690
© 1996 Canadian Medical Association (text and abstract/résumé)
[Table of contents]
Risk factors for vaccine failure
In the United States measles vaccine prevented an estimated 52 million cases during the first 20 years of use, and the rates of measles-related encephalitis and death declined by more than 99% compared with the rates during the prevaccine era.3 By 1978 it was believed that measles could be eliminated from the United States in the near future.4 Nevertheless, continued measles outbreaks have induced public health authorities to re-examine vaccination strategies. In the United States the number of measles cases increased more than fourfold during 1989 compared with 1988, and 40% of the 1989 cases occurred in vaccinated children, thus representing vaccine failures.5 Because the vaccine is not 100% effective (no vaccine is), there will always be some vaccinees (10% or less) who remain susceptible. For instance, in a study reported in this issue (see pages 1407 to 1413) Drs. Penny A. Sutcliffe and Elizabeth Rea found a measles attack rate of 8% in a secondary school population of which 94% had been vaccinated.
Vaccine failures can be primary (the immune response never develops) or secondary (immunity develops initially but wanes over time). Primary vaccine failure can be attributed to either an inactive vaccine or an inadequate host response. Inactivation of the live virus in the vaccine can be caused by the lack of an effective stabilizer or by improper handling. The introduction in 1979 of a good stabilizer rendered the measles vaccine quite resistant to heat and thus reduced the risk of vaccine failure caused by improper handling. Therefore, the main cause of vaccine failure is an inadequate host response to a single dose. Our understanding of the causes of inadequate host response is limited, but we can anticipate that even with a vaccine coverage of 96% to 98% the few susceptible people that remain are sufficient to sustain several generations of measles transmission.
As far as secondary vaccine failures are concerned, various epidemiologic studies demonstrated that there were no significant differences in measles attack rates when the interval from vaccination to exposure varied from 03 years to 1012 years (i.e., the immunity did not decline).[6] This was confirmed by measles antibody studies that showed that antibodies persisted up to 16 years after immunization, and although about 13% of vaccinees lost detectable antibodies they showed a secondary or anamnestic response when they were revaccinated, which suggested that they were still immune.[6] However, from a public health perspective the question is whether infected people with low vaccine-acquired antibody titres are infectious. If so, boosting immunity by revaccination is desirable.
The main known risk factor for primary vaccine failure is age at vaccination.[1] Because the persistence of maternal antibodies interferes with the success of measles immunization and the persistence of these antibodies varies in different populations, the age at which optimal seroconversion rates are obtained also varies. In developing countries seroconversion rates over 95% can be obtained among infants less than 1 year of age. In developed countries seroprevalence studies showed higher seropositivity rates among infants vaccinated at 13 months of age or older than among those vaccinated at 12 months.[1] Epidemiologic studies such as Sutcliffe and Rea's confirm the age dependency of the response to vaccination by finding higher attack rates among people vaccinated at 12 to 14 months than among those vaccinated at 15 months or older. Some data indicate that infants vaccinated before 1 year of age have altered immunity to measles; when revaccinated at an older age, infants who do not respond to the first dose have low antibody titres that disappear quickly. However, in measles outbreaks these children have usually been found to be protected against the disease.[1]
Other, less important risk factors such as unreliable vaccination records and underreporting of measles cases (because of the occurrence of mild measles) may be potential sources of bias in studies of measles outbreaks.[7]
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Two-dose vaccination policy
Publicized outbreaks in highly vaccinated groups have raised questions about the value of measles vaccination programs and created confusion about the efficacy of the vaccine. The apparent paradox is that as vaccination rates rise to high levels in a population, measles becomes a disease of vaccinated people. Because of the failure rate of the vaccine and the uniquely high transmissibility of the measles virus, the currently available vaccine used in a single dose is unlikely to eliminate measles. Therefore, the rationale for a two-dose strategy is that in a well-vaccinated population it will increase herd immunity levels above the outbreak threshold level. One may anticipate that a second dose will reduce the number of primary and secondary vaccine failures. In 1982 Finland launched a comprehensive immunization program to eliminate measles, mumps and rubella (MMR) by vaccinating children 14 to 18 months old and 6 years old, as well as selected groups of older children and young adults.[8] This strategy resulted in the virtual elimination of all three diseases by 1993. In addition to the use of a safe, effective combination vaccine, several factors (e.g., vaccine delivery, a national system of child health centres, surveillance and serologic testing) led to success. Sweden also introduced this program in 1982, with the result that the measles incidence rate fell dramatically, from 129 per 100 000 in 1974 77 to 1 per 100 000 in 1988.[2] In response to continued measles outbreaks in 198586 in school-age populations, a two-dose measles vaccination program was recommended in the United States in 1989.9 This schedule called for a first dose at 1215 months of age and a second dose at either 46 years or 1112 years. After the 1989 to 1991 outbreaks, which showed a shift to preschoolers and infants less than 15 months old, measles incidence rates decreased to an all-time low in 1993.10 A further decrease was observed in 1995.[11]
Despite the overall decline in the incidence rate of measles after the introduction of routine vaccination in the late 1960s, widespread epidemics occurred in Canada in 1986 and 1989, even in highly vaccinated populations.[2] However, the National Advisory Committee on Immunization (NACI) recommended the continuation of the one-dose policy, along with mandatory school-age proof of vaccination or measles and strategies for outbreak control.[12,13] By the end of 1992, after large outbreaks of measles had occurred in several provinces, it became obvious that the old policy had to be changed. Participants at a national consensus conference on measles endorsed the goal to eliminate indigenous measles in Canada by the year 2005.[14] It was recognized that this would require near-universal uptake of the initial dose of vaccine, as well as new programs to deliver a second dose before school entry. NACI subsequently advocated a routine two-dose vaccination schedule in 1993.[14] This includes a primary dose combined with mumps and rubella vaccines (i.e., the MMR combined vaccine) on or as soon as practicable after the first birthday. The second dose of vaccine should be given as the MMR vaccine at 4 to 6 years of age, before school entry.
Although many developed and developing countries have adopted the two-dose vaccination schedule, data on the effectiveness of this policy are still limited. However, Sutcliffe and Rea's findings clearly demonstrate that two doses administered before the measles outbreak examined in their study conferred significant protection. The 7.7% attack rate was reduced to 1.0%, and if the entire school population had received a second dose the number of cases during the outbreak could have been reduced by 87%. However, the administration of a second dose during the outbreak was not protective.
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Strategies for eliminating measles
In September 1994, after the Americas were declared to be poliomyelitis-free by the International Commission for the Certification of Poliomyelitis Eradication,[15] delegates to the 24th Pan American Sanitary Conference in Washington set the target of measles elimination for the Western Hemisphere by the year 2000.[16] The Pan American Health Organization's current measles elimination strategy consists of four steps: national measles campaigns, intensification of measles surveillance, strengthening of routine vaccination activities and the implementation of periodic "follow-up" campaigns to eliminate the build-up of susceptible people.[17] Virtually all countries in the Caribbean as well as in Central and South America have already implemented the first three steps. The fourth step has been conducted in Cuba, Belize, Brazil, Peru and, more recently, Jamaica and Guatemala.
Follow-up campaigns are planned in 1996 by almost all countries in Central America, by Chile and by the remaining countries of the English-speaking Caribbean.[17] The almost simultaneous undertaking by the governments of the Americas to implement a one-time measles campaign within a 2-year period resulted in a dramatic reduction of cases in the region.[16] In 1990 close to 250 000 cases were reported; this figure dropped to 5551 in 1995.[17]
In 1995 the United States reported a record low number of measles cases since surveillance was instituted in 1912.[11] The 301 confirmed cases represented a 98.9% reduction compared with the number reported in 1990. Thus, measles virus circulation has been greatly reduced, if not eliminated, in most areas of the United States. The challenge now for the United States and other countries in the Americas is to maintain this interruption of measles transmission, given the ease with which the disease can be imported.
In contrast, the measles cases reported in Canada in 1995 accounted for 41% of the total confirmed cases (laboratory and clinical) and 80% of the total laboratory confirmed cases in the Americas, although Canada's population represents only 3.6% of the total for the region.[17] School-aged children (aged 5 to 19 years) accounted for 83% of the cases. NACI has reviewed the situation as of 1995 and made several recommendations to improve measles control in Canada.[14] These include conducting a one-time catch-up measles vaccination campaign among school-aged children and the implementation of a routine two-dose schedule.
As a result of NACI's strong recommendations, 11 provinces and territories will have implemented a routine two-dose vaccination schedule before the end of 1996.[18] These 11 jurisdictions have indicated that they will use the MMR vaccine for the routine second dose. In the Yukon Territory, the Northwest Territories, British Columbia, Quebec and Newfoundland, this second dose of vaccine is to be given at 18 months of age, whereas in the other six provinces it will be administered at 4 to 6 years of age. Supplementary catch-up programs involving all school children have been completed in six jurisdictions (the Yukon Territory, the Northwest Territories, British Columbia, Ontario, Quebec and Prince Edward Island). The Northwest Territories and British Columbia have used measlesrubella vaccine for the catch-up campaign, whereas the other four jurisdictions have used monovalent measles vaccine. Acceptance rates in all provinces are above 80%. Saskatchewan and Manitoba are also planning to implement a more limited catch-up program, using measlesrubella vaccine.[18] In order to maintain the interruption of measles virus circulation, the main challenge for Canada will be to maintain very high measles vaccination coverage in each successive cohort of newborns. If coverage can be maintained at 95% among infants by their second birthday, the risk of sustained measles transmission will remain low.
With the implementation of these important programs, Canada now joins the other countries of the Americas in their efforts to eliminate measles from the Western Hemisphere by the year 2000.
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References