Dramatic declines in measles resulted from the introduction of vaccination with a single dose of measles-containing vaccine (MCV) in the United States in the 1960s; however, control of measles outbreaks remained difficult. In response to outbreaks in schools with high one dose MCV coverage, the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics recommended in December 1989 that a second dose of measles-containing vaccine be given routinely to school age children, either at school entry (ACIP) or at age 11 to 12 years (American Academy of Pediatrics).1,2
The second dose policy has been implemented incrementally; 46 states now require schoolchildren to have a second dose for entry to either elementary or middle schools. In many states with second dose requirements, some cohorts of schoolchildren are not covered. These cohorts contain children who are younger than the age at which a second dose is required or children who were older than the targeted age and who, in addition, have not been offered a "catch-up" vaccination. Questions about the effectiveness of the second dose policy have not been fully answered, including whether children who have received two doses of MCV are better protected than single dose recipients and at what age the second dose of MCV should be given.
In December, 1994, a multistate measles outbreak followed exposure in a Las Vegas children's arcade during the Thanksgiving holiday (November 21 to 22, 1994). A 6-year-old boy with a history of one measles vaccination returned from Las Vegas to Mesa County, CO, on November 28, 1994, and developed a rash on December 4. The boy was a first grade student in Elementary School A and attended Day Care B after school. Sixty-one additional cases, including 16 at School A and 6 at Day Care B, occurred in the ensuing outbreak.
The Colorado measles vaccination law requires receipt of one dose for entry to kindergarten and, since 1992, two doses for entry to seventh grade; personal, religious and medical exemptions are allowed. Many students at School A had previously received second doses of MCV. We investigated the outbreak to evaluate the effect of preexisting second dose coverage.
Case ascertainment. Reporting of measles cases was enhanced by use of the local media and by active surveillance of local emergency rooms. All suspected measles cases were investigated by personnel from the Mesa County Health Department (MCHD) or the Colorado Department of Public Health. Subjects who met the clinical case definition were tested for measles IgM antibody by an antigen capture IgM assay developed by the CDC.3
Case definition. Cases were classified according to a clinical case definition (an illness with generalized rash for ≥3 days, fever ≥101°F and cough, coryza or conjunctivitis), a laboratory criterion (a positive serologic test for measles IgM antibody) and the results of case investigation. A confirmed case required laboratory confirmation or had to meet the clinical case definition and be epidemiologically linked to a confirmed case.4
Immunization data.Cases. The vaccination status was defined as the number of doses of MCV received 14 days or more before onset of rash.
Estimated preoutbreak school age coverage. School immunization records were reviewed at the beginning of the outbreak; these records were based on physician documentation. Available school coverage reports were used to estimate grade-specific coverage by number of doses for all Mesa County schools.
Estimated postcampaign school age coverage. Data on the number of doses of MCV administered were obtained from the MCHD and a sample of private providers. Doses administered by the MCHD were tabulated by age of the recipient; this age distribution was extended to the total number of doses. Children of each age cohort were considered to attend a single grade; i.e. 6 year olds, Grade 1. Grade-specific coverage was calculated by adding the estimated number of administered doses to the preoutbreak coverage.
Statistical analysis. We compared immunization rates and measles attack rates by class and vaccination status at School A and Day Care B. The effectiveness of one and two doses of measles vaccine in preventing measles was estimated by logistic regression in the SAS software program.5,6
The Mesa County measles outbreak. Three generations of cases followed the index case (Fig. 1). The first generation consisted of 25 cases with rash onsets from December 12 to December 18, 1994. These cases occurred predominantly in children who attended School A (14 cases) or Day Care B (6 cases). The second generation consisted of 27 cases with rash onsets from December 22, 1994, to January 3, 1995. Ten cases occurred in preschool age children, 5 in school age children (including 2 additional students at School A and a student at High School C who had rash onset on December 31) and 12 cases in adults age 18 to 42 years. The third generation consisted of 9 cases with rash onset from January 9 to January 13, 1995. Of these, 5 cases were among children <5 years old who did not attend day care, one was in a school age child and 3 were among adults. Of the 62 cases in the outbreak, 24 cases were confirmed by a positive serologic test for anti-measles IgM antibody and 38 cases were epidemiologically linked to a laboratory-confirmed case.
Measles attack rates (calculated with county population data) were 2-fold higher among children age 5 to 7 years (3.0 cases/1000) than among more highly vaccinated groups, such as children age 8 to 11 years (1.3 cases/1000), many of whom had received a second dose of MCV in 1991. There were no cases among children age 12 to 14 years, the age group for which a second dose had been required. Two cases (0.4/1000 population) occurred among adolescents 15 to 18 years of age; this age group had not been subject to a two dose requirement and neither case had received two doses.
Elementary School A. School A had 625 pupils in grades from kindergarten to fifth grade; 16 students had never been vaccinated with MCV, 320 had received 1 dose of MCV before the outbreak and 289 had received 2 doses. Most of the second doses had been administered during a measles immunization campaign in 1991; therefore second dose coverage was higher in Grades 3 to 5 (72%) than in Grades K to 2 (21%, P < 0.05, chi square) (Table 1). The attack rate in unvaccinated children (7 of 16, 44%) was higher than in those with 1 dose (10 of 320, 3%) or 2 doses (0 of 289, 0%). Measles vaccine was highly effective in preventing measles; treating doses of vaccine as an ordinal variable, each dose of measles vaccine independently decreased the likelihood of acquiring measles with P = 0.001 for the comparison of 1 vs. 0 dose and P = 0.003 for the comparison of 2 vs. 1 dose. Estimated vaccine effectiveness was 92% for 1 dose and 100% for 2 doses. The measles attack rate among unvaccinated children was not significantly different in Grades 3 to 5 (60%) from Grades K to 2 (36%, P = 0.60, chi square), suggesting that differential exposure between grades was not a major confounding factor.
Day Care B. Age and MCV immunization status were known for 37 of 41 children who were potentially exposed. The 4 children whose vaccination status was unknown did not contract measles. Three of 3 (100%) unimmunized children developed measles, compared with 3 of 33 (9%) with 1 dose (P < 0.05, chi square) and 0 of 1 with 2 doses. Estimated vaccine effectiveness of 1 dose in the day care was 91% (95% confidence interval, 73 to 97%).
High School C. High school C's catchment area included the area served by Elementary School A. One case in a School C student occurred in the second generation of the outbreak; however, rash onset occurred during the Christmas holiday, minimizing the potential for exposure of other students. No additional cases were reported in School C.
Outbreak control. A policy excluding from attending school children who could not show proof of two doses of MCV was implemented at Elementary School A and Day Care B on December 12. An immunization clinic was held December 13, 1994, raising second dose coverage in the school to 96%. A two dose requirement was imposed on High School C in the week of January 5 and second dose coverage reached 99%. Second dose coverage at other schools and preschools was raised by a voluntary campaign with the incentives of free vaccination, publicity about the potential for serious morbidity associated with measles and publicity that if cases occurred at a school, exclusion of students lacking documentation of two doses of MCV would be mandatory.
Estimated school age coverage.Preoutbreak. School coverage reports were available from 22 of the 37 schools in Mesa County, representing 9 727 (53%) of the 18 356 school age children. Average second dose coverage at the onset of the outbreak was 21% (range, 19 to 25%) in Grades K to 2, 61% (range, 59 to 65%) in Grades 3 to 6, 93% (range, 89 to 97%) in Grades 7 to 9 and 23% (range, 20 to 25%) in Grades 10 to 12.
Postcampaign. A total of 9946 doses of measles vaccine were reported to have been administered by public and private providers from December 5, 1994, to January 26, 1995; 8400 doses were administered by MCHD and private providers reported administration of an additional 1546 doses. The age distribution of the vaccinated individuals was estimated from the records for 7490 (89%) of the doses given by MCHD. Estimated postcampaign two dose coverage was 84% in Grades K to 2, 89% in Grades 3 to 6, 100% in Grades 7 to 9 and 63% in Grades 10 to 12.
The significantly lower attack rate in this outbreak among children who had received two doses of measles vaccine provides evidence that a two dose strategy might achieve a level of immunity sufficient to prevent measles in schools and supports the recommendation in 1989 of second doses for school age children. During 1985 to 1988 persistent school outbreaks demonstrated that even a completely implemented one dose strategy would fail because of high contact rates in schools and the high contagiousness of measles.7-10 Limited data suggested improved protection among recipients of two doses of MCV,8,11 but data directly demonstrating the effectiveness of a two dose policy in preventing school outbreaks were not available.
Recent outbreaks in 1996 in Utah, Alaska, Texas and Washington,12-14 and in 1998 in Alaska,15 occurred primarily among school age children who received only one dose of MCV; these children were from age cohorts not covered by two dose requirements. In the Alaska outbreaks the attack rate among schoolchildren who had received two doses of MCV was lower than among one dose recipients or unvaccinated children. Colorado has a two dose requirement for children entering middle school. This requirement has prevented high school and college outbreaks, which occurred frequently in the late 1980s; however, the presence of large numbers of undervaccinated elementary school age children permitted the Mesa County outbreak to occur. The absence of cases among the elementary school children who had received two doses suggests that administering the second dose at elementary school entry will help prevent the persistence of school age cohorts with substantial numbers of susceptible children.
Once measles virus is introduced, vaccination requirements that cover essentially every child with two doses of MCV appear to be necessary to prevent school outbreaks. School A was not protected by herd immunity despite 95% one dose and >45% two dose coverage; measles cases occurred among unvaccinated children even in grades with very high two dose coverage.
In 1998 ∼53% of US schoolchildren were covered by state requirements for two doses of MCV (CDC, unpublished data, 1998). The ACIP has recommended that the requirement for a second dose of MCV should be implemented among all school age children by 2001.16 Until that goal is achieved schools with cohorts of undervaccinated children are at risk for outbreaks. A high level of second dose coverage in all cohorts of school children and college students is likely to be necessary to sustain elimination of indigenous transmission of measles in the United States.
This work was supported by funding from the US Centers for Disease Control and Prevention, Atlanta, GA.
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