Evaluation of an Early Two-Dose Measles Vaccination Schedule

Sonja S. Hutchins1,2, Anita Dezayas3, Kristen Le Blond4, Janet Heath5, William Bellini5, Susette Audet6, Judy Beeler6, Wendy Wattigney2 and Lauri Markowitz7

1 Epidemic Intelligence Service, Division of Applied Public Health Training, Epidemiology Program Office, Centers for Disease Control and Prevention, Atlanta, GA.
2 Measles Elimination Activity, National Immunization Program, Centers for Disease Control and Prevention, Atlanta, GA.
3 Special Immunization Program, Dade County Department of Public Health, Miami, FL.
4 ABT Associates, Inc., Cambridge, MA.
5 Measles Virus Section, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA.
6 Laboratory of Pediatric and Respiratory Virus Diseases, Food and Drug Administration, Bethesda, MD.
7 Data Management Division, National Immunization Program, Centers for Disease Control and Prevention, Atlanta, GA.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Vaccination at 6 months of age followed by routine revaccination is recommended when exposure of infants to measles is likely. Dade County, Florida, began this early two-dose schedule during a large epidemic in 1986–1987 (i.e., 22% of cases occurred in infants aged 6–11 months). This schedule was continued routinely in high-risk areas. The effect of an early two-dose schedule on measles prevention in the county was examined by comparing measles vaccination coverage and epidemiology before (1985–1987) and after (1988–1996) the schedule became routine. To assess serologic response, seroprevalence of measles antibody among children aged 4–6 years in 1995 was examined. To evaluate vaccine effectiveness, a case-control study was conducted among preschool-aged children. Among those aged 2 years, vaccination coverage with >=1 dose increased from 75% to 94% in 1996. The number of annual cases declined, and endemic measles transmission reportedly ended after 1993. Seroprevalence of plaque reduction neutralization antibody (titer > 1:120) among those receiving vaccination according to an early two-dose schedule and a single dose at age >=12 months was 94% (95% confidence interval: 89, 98) and 98% (95% confidence interval: 95, 100). In these groups, vaccine effectiveness was comparably high. Early two-dose measles vaccination is associated with improved coverage and a comparably high level of humoral immunity and clinical protection as a single dose at age >=12 months. This strategy can be useful in areas at high risk for measles among infants.

antibodies; immunity; infant; measles; measles vaccine; serologic tests; vaccines

Abbreviations: CDC, Centers for Disease Control and Prevention; EIA, enzyme immunoassay; MN, microneutralization; PRN, plaque reduction neutralization


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The Advisory Committee on Immunization Practices of the US Public Health Service recommends vaccination of infants as young as age 6 months when exposure to measles is considered likely (e.g., outbreaks) (1Go). To assure adequate protection against measles after vaccination at younger than age 1 year, routine revaccination is recommended at age 12–15 months and, since 1989, at age 4–6 years. When exposure to measles is likely, the benefit of an early dose at 6 months of age in preventing disease in infants outweighs potential problems due to lower vaccine efficacy, because infants are at high risk for disease and complications of illness. Besides suboptimal vaccine efficacy, a concern about early vaccination has been possible immunotolerance. Studies conducted during the 1970s and 1980s found a lower serologic response in early-dose vaccinees after revaccination; however, lower protection against measles was not observed (2GoGoGoGoGoGoGoGoGoGoGoGoGoGo–16Go).

The early two-dose schedule has been implemented in the United States in communities with large outbreaks involving infants. After an outbreak of measles ended in 1987 in Dade County, Florida, health officials continued routine implementation of the early two-dose schedule that was initiated during the outbreak. We evaluated routine implementation of the schedule to 1) examine the population-based impact on vaccination coverage and disease incidence, 2) compare the serologic response with that of the standard schedule, and 3) determine vaccine effectiveness of the early two-dose schedule.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Dade County, Florida
According to the 1990 US Census, Dade County (Miami is the major city), located in southeastern Florida, had a population of 1.9 million; 33,523 births were recorded in 1991. Eight percent of the county's population consisted of preschool-aged children younger than age 5 years. Demographic characteristics of the population were highly favorable for the introduction and spread of measles. For instance, there were large immigrant populations from measles-endemic countries, millions of international visitors each year, and a high population density (as many as 10,546 persons per square mile (1 mile = 1.6 km) in Miami).

Early two-dose measles vaccination program in high-risk areas
During 1986–1987, Dade County experienced a large measles outbreak, primarily among preschool-aged children. Of the 257 outbreak-related cases of the disease reported in 1986, three quarters occurred in preschool-aged children, and 22 percent of these were in infants aged 6–11 months (17Go). Moreover, the incidence of disease (232/100,000 population) and the complication rates (33 percent) were highest among children younger than age 1 year compared with older persons. One measles-associated death was reported in an unvaccinated, young child with acquired immunodeficiency syndrome (18Go).

Because of substantial morbidity among young children during the outbreak, the Dade County Department of Public Health began vaccinating infants as young as age 6 months and revaccinating them at age 12–15 months. Children targeted for this early two-dose schedule lived in high-risk zip code areas, which were defined as those in which at least one case of measles was reported (figure 1). Providers receiving free vaccine from the health department were enlisted to implement the recommendation because they served children in the high-risk zip code area. These providers were public health department clinics (6 sites), a county hospital outpatient department, neighborhood health centers (13 sites), and private providers serving children enrolled in Medicaid (as many as 100 physicians).



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FIGURE 1. Geographic distribution of measles cases by zip code, Dade County, Florida, 1986–1987.

 
The high-risk areas of Dade County included 38 of the 76 zip codes in the county, accounting for one half of the county's population. Persons living in these areas had a lower median annual income than the overall median income of the county ($27,000 vs. $31,000). Public health and neighborhood clinics were distributed throughout the high-risk zip codes, as were the private physician offices.

After the outbreak, the early two-dose vaccination schedule was continued. Transmission of measles virus in the county was ongoing, and there was a potential threat of another outbreak.

Definition of the vaccination schedule
An early two-dose schedule was defined as administration of the first dose at age 6–11 months (22–51 weeks) and a second dose at age >=12 months (>=52 weeks). A single, standard dose was defined as given at age >=12 months (>=52 weeks) and a single, early dose was defined as one given at age 6–11 months (22–51 weeks). For the serologic survey, a more restrictive definition was used (as described in the Serologic Study section of this paper). For the present study, the routine second dose of measles vaccine administered at age 4–6 years (recommended after 1989) was not considered, because this requirement did not take effect in Dade County schools until the 1993–1994 school year. This policy was implemented at the end of the study period and is unlikely to have affected our results.

Population-based descriptive study
We conducted a descriptive epidemiologic study of the entire Dade County population from 1985 to 1996 to assess the impact of the early two-dose schedule for high-risk children on population-based vaccination coverage and disease. The 3-year period (1985–1987) before the early two-dose schedule was implemented routinely was defined as the preintervention period and was compared with the 9-year period (1988–1996), the postintervention period, after the routine schedule began. In the county, we examined the annual percentage of preschool-aged children vaccinated against measles as a process measure and the annual number of cases of measles as the outcome measure.

Measles vaccination coverage of preschool-aged children was measured in 1986–1996 by annual, cross-sectional population-based surveys of children aged 2 years. A random sample of 104–114 children born in November of each year was selected from state-based birth certificates. This sample size enabled us to estimate a 95 percent confidence interval with a precision of ±10 percent. Parents or providers were interviewed by telephone or in person to determine the child's date of birth and dates of vaccination. Only dates (at least month and year) from a written record were accepted as evidence of vaccination. To assess how well the early two-dose schedule was implemented, we examined vaccination coverage of children aged 2 years surveyed in 1989 or later because they were eligible for the early two-dose schedule beginning in 1987.

Confirmed measles cases were ascertained from the National Notifiable Disease Surveillance System at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia. A confirmed case had been confirmed serologically or met CDC's standard clinical case definition and was linked epidemiologically to another case that had either been confirmed serologically or met the case definition (19Go). Data collected on each case included the patient's age, sex, zip code of residence, exposure history, clinical information, laboratory results, and vaccination history. To further evaluate the impact on measles control in the county, we examined the epidemiology of confirmed cases for those persons targeted and those not targeted for the early two-dose schedule.

Serologic study
In February–October 1995, to examine humoral immunity after an early two-dose schedule, we assessed the prevalence of measles antibody in high-risk children aged 4–6 years at least 3 years after the last dose of measles vaccine was administered. After the institutional review boards of CDC; ABT Associates, Inc., (Cambridge, Massachusetts); and each study site approved the study and informed consent was obtained from parents, children attending five pediatric clinics were enrolled consecutively in the study before receiving the school-entry dose of measles vaccine. Our target was to enroll at least 200 children who had received vaccine according to the early two-dose schedule and 200 children who had received a standard dose at age 12 months. In addition, we examined the small subset of children who had received only a single, early dose of measles vaccine. Antibody was measured by using three tests, as described previously: 1) an indirect enzyme immunoassay (EIA) that detects measles-specific immunoglobulin to the nucleoprotein antigen, 2) a microneutralization (MN) assay only if EIA antibody was not detected, and 3) a plaque reduction neutralization (PRN) assay (20GoGoGo–23Go). Any EIA or MN antibody is considered protective. We chose the EIA assay because it was widely used and highly practical. Neutralization assays were chosen because of their higher sensitivity (22Go). The PRN assay was considered the most sensitive and was known to have a serologic correlate of protection against measles (titer > 1:120) (23GoGoGo–26Go). A detectable PRN antibody titer was defined as >=1:8.

For this component of the study, definitions of vaccination groups were more restrictive so we could precisely assess the serologic response to vaccination. An early two-dose schedule was defined as the first dose given at age 6–11 months (25–51 weeks) and the second at age 12–18 months (52–82 weeks); a single, standard dose was defined as one given at age 12–18 months (52–82 weeks); and a single, early dose was defined as one administered at age 6 –11 months (25–51 weeks).

Vaccine effectiveness
To evaluate vaccine effectiveness among early two-dose recipients, we conducted a case-control study. Cases were defined as all preschool-aged children aged 15–59 months with confirmed cases of measles reported to the National Notifiable Disease Surveillance System between 1989 and 1996. Unmatched controls were selected from the annual population-based survey of children aged 2 years in Dade County for vaccination status between 1989 and 1996, as outlined previously in the Population-based Descriptive Study section of this paper. Controls could not be matched to cases by age because the age of controls was limited by the study design; that is, the individual survey date was not available to compute the individual ages of controls. Controls were aged 24–30 months at the time of the survey. Both cases and controls were residents of Dade County. Vaccine effectiveness was estimated by subtracting from 1 the exposure odds ratio for vaccinated cases versus vaccinated controls (1 – odds ratio) (27Go). Because measles was exceedingly rare in preschool-aged children during the 8-year study period (annual average, 2 cases/100,000 population), the odds ratio approximated the relative risk.

Statistical methods
Differences in proportions were tested for significance by using either the chi-square or Fisher's exact test. A p value of < 0.05 was defined as statistically significant. PRN titers were log transformed (logarithm base 10) and were compared as reciprocal geometric mean titers by using the two-tailed, unpaired, Student's t test. Multiple logistic regression analysis was performed to estimate exposure odds ratios for vaccinated cases versus vaccinated controls for each vaccination group, adjusting for race/ethnicity. Most analysis was performed by using SAS version 6.12 software (SAS Institute, Inc., Cary, North Carolina). LogXact software (Cytel Software Corporation, Cambridge, Massachusetts) was used to estimate adjusted odds ratios.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Population-based descriptive study
Since the 1986–1987 outbreak in Dade County, the percentage of children aged 2 years who had received at least one dose of measles vaccine increased steadily from 75 percent in 1986 to 97 percent in 1989, when the national measles resurgence began. Since 1989, the percentage vaccinated has been sustained at slightly more than 90 percent (figure 2). Coverage rates during the preintervention period include children who were vaccinated only at age >=12 months, while rates during the postintervention period include children vaccinated at age >=6 months. Of those children aged 2 years surveyed in 1989 or later, 20–40 percent had received an early dose (figure 2). Since one half of the county population aged 2 years lived in high-risk areas, approximately 70 percent of the target population received the early dose. Of those children who received the early dose, most (>=80 percent) had been revaccinated. Although the vaccination schedule was well implemented, a substantial percentage (annual mean, 20 percent) of early-dose recipients each year had not been revaccinated at age 12 months or older, but the percentage was lower in later survey years. Among children aged 2 years in 1989–1996, the rate of vaccination coverage with only a single, early dose was 6 percent (range, 0–10 percent). Overall, the early two-dose schedule was implemented primarily among children living in high-risk zip code areas.



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FIGURE 2. Measles vaccination coverage of children aged 2 years, by year of survey and vaccination history, Dade County, Florida, 1986–1996.

 
Coincident with attaining very high coverage of children aged 2 years during the postintervention period, the total number of reported cases of measles declined substantially (figure 3). Between 1988 and 1991, an annual mean of 40 cases were reported, only 12 percent of the number reported during the 1986–1987 outbreak. Fifty-seven percent of the cases of measles were confirmed epidemiologically, while 43 percent were confirmed serologically. In 1992–1993, the number of cases declined further; 10 or less were reported each year. Since 1993, no cases of the disease have been reported despite investigation of more than 100 suspected cases each year. In addition, complication and hospitalization rates were lower in the postintervention period; no measles-associated deaths were reported. Notably, a large outbreak did not occur during the national measles resurgence from 1989 to 1991 (28Go).



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FIGURE 3. Measles vaccine coverage and number of reported cases of measles, by year and by age of the child (<5 years, >=5 years), Dade County, Florida, 1985–1996.

 
During the preintervention period, the average annual incidence among targeted children was 11/100,000 population; the incidence decreased fivefold to 2/100,000 during the postintervention period. In contrast, during the preintervention period, no case of measles was reported among children in the nontargeted zip code areas; however, during the postintervention period, the incidence was 1/1,000,000. Moreover, the age distribution of cases shifted when the preintervention and postintervention periods were compared. For all ages, the average annual incidence during the postintervention period was lower than during the preintervention period, and the greatest declines (three- to eightfold) occurred among preschool-aged children. Consequently, during the postintervention period, preschool-aged children younger than age 5 years accounted for one half of the cases compared with four fifths during the preintervention period (figure 3). In addition, among cases in high-risk areas, the relative proportion of those among infants aged 6–11 months declined 24 percent from the pre- to the postintervention period. In addition, a higher proportion of cases were classified as international importations during the postintervention period than during the preintervention period (20 vs. 4 percent).

Serologic study
The demographic characteristics of the 484 children in the serologic study were similar to those of children aged 4–6 years living in the high-risk areas of Dade County. Most were Latino or African American (88 percent), had mothers who were born outside of the United States (73 percent), and had mothers who were born in 1957 or later (86 percent). Nearly all children were born at term (97 percent) and had a normal birth weight (92 percent). In general, children in the early two-dose; the single, standard dose; and the single, early dose groups had similar characteristics. Minor differences were found among children in the early two-dose group, who were slightly younger than subjects in the other groups (mean age, 4.4 vs. 4.9 years), and those in the early, single dose group, who were more likely to be Latino than children in the other groups (54 vs. 61 percent). These differences were statistically significant (p < 0.05).

All 209 early two-dose recipients had detectable PRN antibody (titer >= 1:8), and 88 percent had EIA/MN antibody. A similar prevalence of detectable PRN antibody was found in the other vaccination groups (single, standard and single, early dose), although the prevalence of EIA/MN antibody in early two-dose recipients was statistically lower than that in the single, standard dose group (table 1). In addition, although the prevalence of a PRN antibody titer of >1:120 was similar in early two-dose recipients and 234 children vaccinated with a standard dose at age 12–18 months, the reciprocal geometric mean titer was slightly lower in early two-dose recipients: 999 versus 1,440 (p < 0.05) (table 1). Most (84 percent) of the early two-dose recipients received the early dose between age 6 and 8 months. Of the small subset of 41 children who had received only a single dose at age 6–11 months, 98 percent had a detectable PRN antibody, 95 percent had EIA/MN antibody, and 93 percent had PRN titers of >1:120. More than one half (57 percent) of the 41 children who had received a single, early dose were vaccinated at age 6–8 months. Seroprevalence of infants aged 6–8 months was 91 percent with EIA/MN antibody, 96 percent with detectable PRN antibody, and 87 percent with a PRN titer of >1:120. Seroprevalence of infants aged 9–11 months was higher: all 18 infants had EIA/MN antibody and detectable PRN antibody at a titer of >1:120.


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TABLE 1. Seroprevalence of measles antibody, by vaccination history, among children aged 4–6 years, Dade County, Florida, 1995

 
Vaccine effectiveness
During the 8 years of the efficacy study, 48 cases of the disease in children aged 15–59 months (4 cases/10,000 population aged 15–59 months/year) were reported; three of these children were excluded from the study because they did not fit a vaccination group. Approximately one half of the cases of measles were confirmed by serology, and the remaining one half were linked epidemiologically to a serologically confirmed case or one meeting the CDC clinical case definition. Forty-five cases and 698 controls were examined; their mean age was 24 and 27 months, respectively. The proportion of children who were male compared with female (44 vs. 49 percent) and lived in high-risk zip code areas (62 vs. 67 percent) was similar for cases and controls (p >= 0.50). In contrast, slightly more cases were of unknown race or ethnicity, and fewer cases than controls were African American (p = 0.03).

Vaccine effectiveness for children on the early two-dose schedule, after adjustment for race/ethnicity, was 99.5 percent (table 2). Similarly high vaccine efficacy estimates, adjusted for race/ethnicity, were found for children who received a single dose either at age >=12 months (vaccine effectiveness, 99.7 percent) or age 6–11 months (vaccine effectiveness, 97.6 percent). Adjusted and unadjusted estimates were similar.


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TABLE 2. Effectiveness of measles vaccination among preschool-aged children aged 15–59 months, Dade County, Florida, 1989–1996

 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Our study suggests that an early two-dose measles vaccination schedule in high-risk areas of Dade County was effective in preventing and controlling measles in the community. Implementation of this schedule was associated with a reduction in measles morbidity and mortality in the population. In addition, from national reports of adverse events after vaccination, this early two-dose approach was not associated with an increase in reports of side effects.

A direct impact of the early two-dose schedule on measles control is difficult to evaluate, because there was no similar county for comparison of both vaccination coverage data and occurrence of cases of measles during the study period. However, the shift from cases primarily among preschool-aged children to those in older persons, high seroprevalence, and high vaccine effectiveness all support the conclusion that this sustained program in Dade County was effective.

Other changes in the epidemiology of measles in Dade County that support the effectiveness of an early two-dose schedule included a disproportionately large decline in overall measles morbidity among infants aged 6–11 months as the distribution of cases of measles shifted from younger to older children. Moreover, no large outbreak occurred in Dade County during the national measles resurgence of 1989–1991, and endemic measles transmission reportedly ended after 1993. In contrast, three urban centers (Chicago, Illinois; Los Angeles, California; and New York City) that experienced large outbreaks among preschool-aged children in the mid-1980s (1985–1986), similar to Dade County, had another even larger outbreak during the resurgence and continued to report transmission of measles through 1998 (28Go, 29Go).

While the high coverage achieved in the target population may not be attributed solely to the early two-dose schedule because new vaccination strategies in the county were also introduced during the postintervention period, high coverage with only an early dose suggests that the early two-dose schedule explains some of the improvement in coverage. The focus of new strategies was to improve access to vaccination services for all recommended vaccines and vaccine doses during the evenings and weekends in public health clinics and during routine hours in sites with the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). The assumption that those receiving only a single, early dose would not have otherwise received measles vaccine is accurate because these children had no record of receiving other vaccines around the time that the second dose of measles vaccine could have been given. During the 8 years of routine implementation of the early two-dose schedule (1989 to 1996), an average of 20 percent of early-dose recipients each year received only that one dose. On the basis of that proportion, we determined that recipients of a single, early dose contributed a 6 percent increase in coverage among children aged 2 years (from 89 percent with any dose to 95 percent).

Recent studies in the United States and Canada found that 65–100 percent of children will seroconvert after vaccination at age 6 months and 85–90 percent will seroconvert after vaccination at age 9 months, particularly if their mothers were vaccinated and maternal antibody was low or not present when the child was vaccinated (8Go, 9Go, 29GoGoGoGo–33Go). In the present study, however, seroprevalence of measles antibody among those who received a single dose at age 6–8 months was higher (96 percent had PRN antibody, and 87 percent had a PRN titer of >1:120), and it was even higher among those who received it at age 9–11 months (all had detectable antibody at a titer considered protective). If we assume a 95 percent seroconversion rate among children vaccinated at age 12 months or older (89 percent of the population of children aged 2 years) and use a conservative estimate of an 80 percent seroconversion rate among children vaccinated once with an early dose at less than age 12 months (6 percent of the population of children aged 2 years), population immunity among children aged 2 years would have increased 5 percent (from 85 to 90 percent) because of those receiving only a single dose.

The high seroprevalence we found in all vaccination groups likely reflects the serologic response after vaccination, with little or no opportunity for boosting due to exposure to measles disease. During the study period in Dade County, vaccination coverage of children aged 2 years was more than 90 percent, and the occurrence of measles disease was exceedingly rare (annual average, 1 case/1,000,000 population). Thus, the measured humoral immunity among children approximately 3 years after measles vaccination was likely vaccine induced.

Although a lower seroprevalence of PRN antibody considered protective (titer > 1:120) was found among recipients of the early two-dose vaccination or a single, early dose compared with recipients of the standard dose at age 12 months, vaccine effectiveness was similar for all vaccination groups. These findings suggest no difference in clinical protection against measles based on vaccination status, which is supported by other vaccine efficacy studies in the United States that examined the effect of an early two-dose schedule relative to a single dose at age 12 months (13Go, 14Go). These outbreak investigations among school-aged children, which occurred 10 years earlier (1980s), also found lower vaccine effectiveness among children given only a single, early dose.

While findings of very high vaccine efficacy can be biased in a case-control study with a very high attack rate in the vaccinated group, we did not observe such an attack rate (34Go). However, a potential bias in our study is differential exposure to measles among vaccinated and unvaccinated groups because we did not have a sufficient attack rate (5 percent) to assure that groups were composed of freely mixing populations (34Go). This bias seems important only when the attack rate and vaccination coverage of the population are low but not when the attack rate is low and vaccination coverage is high, as was true in our study (34Go). While differential exposure of the vaccinated and unvaccinated groups could have occurred, measles is a highly contagious disease, and the long study period of 8 years in which vaccination coverage was very high and attack rates were very low make significant differences in exposure unlikely. If anything, exposure to measles is probably still higher in high-risk areas than low-risk areas, which leads to underestimation of vaccine effectiveness. During the study period, large immigrant populations from endemic countries lived in the high-risk areas of the county, probably increasing the risk of exposure.

Another bias could have been ascertainment bias from differential reporting of cases of measles to the Dade County Department of Health. However, the public sector is one of the strongest components of the routine measles surveillance system in Dade County, and children in the public sector were most likely to have received the early two-dose schedule (35Go). More reported disease among vaccinated children would also underestimate vaccine effectiveness.

Finally, although we were unable to examine the effect of slightly different ages between preschool-aged cases and controls, and age is known to be associated with vaccination status, vaccine effectiveness is not known to vary by age among preschool-aged children. Thus, the difference in age is unlikely to have confounded the estimate of vaccine effectiveness.

When the effect of the early two-dose schedule and its current role are evaluated, there are many factors to consider, some of which are competing. The early two-dose schedule was effective in controlling measles in Dade County when the risk of measles in the United States was a problem and susceptibility to measles among preschool-aged children was considerable. Specifically, the Dade County program actually began when exposure to measles was high and vaccination coverage of preschool-aged children was suboptimal. Since 1995, vaccination coverage of preschool-aged children in the United States has been very high (90 percent or higher among children aged 2 years), leading to a reduction in overall susceptibility and very low measles incidence. However, susceptibility to measles among infants has increased because most infants are now born to vaccinated mothers and lose maternal antibody at an earlier age (36; National Center for Health Statistics, unpublished data). Susceptibility among young infants is of particular concern because infants have the highest rate of complications (26Go, 37Go).

Measles transmission currently is not endemic in the United States, and the risks and benefits of an early two-dose measles vaccination schedule may differ from those in the past. In the United States and other countries, the optimal age for measles vaccination is based on weighing the benefit of vaccination and the risk of disease, complications of disease, and vaccine failures. For example, many countries in the Americas with a low incidence of measles have increased the age of the first routine dose of measles vaccine from 9 months to 12 months to increase the seroconversion rate. Our findings of the effect of an early two-dose schedule in Dade County strongly support the Advisory Committee on Immunization Practices recommendation to use this schedule when the risk of measles is high among infants (1Go).


    ACKNOWLEDGMENTS
 
The authors are indebted to Patricia Onley and the staff of the Special Immunization Program of the Dade County Public Health Department; Andrea Hassol from ABT Associates, Inc.; and Drs. Lisa Krinsky and Stuart Harris from the South Florida Bioavailability Laboratory for conducting the serologic study. They also thank Bonya Broadnax and Tremayne Mackey for preparing and reporting on the preliminary results; Tara Strine for statistical programming of national measles surveillance data; and Dr. John Livengood, Dr. Mark Papania, Dr. Stephen Redd, Dr. Melinda Wharton, and Mary McCauley of the National Immunization Program, Centers for Disease Control and Prevention, for their scientific and editorial assistance and support.


    NOTES
 
Reprint requests to Dr. Sonja S. Hutchins, National Immunization Program, Information Center, Mail Stop E-61, Centers for Disease Control and Prevention, Atlanta, GA 30333 (e-mail: ssh1{at}cdc.gov).


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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Received for publication April 3, 2001. Accepted for publication August 8, 2001.





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