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In 1978, the United States established the objective of completing the basic immunization series of at least 90% of children by age two years by the year 1990. Although state school immunization laws have led to the immunization of over 95% of school enterers (32), the situation among preschoolers is less encouraging. Recent outbreak investigations in many inner city areas have estimated that only 40-60% of children have completed the series by age two years (12, 13, 55). This low coverage among preschoolers is reflected in the recent resurgence of measles (7, 11, 57). In 1990, the number of reported measles cases (provisional total 27, 672) was the highest since 1977 (55, 201 cases reported), compared with a nadir of 1497 cases in 1983. Approximately one half of reported cases in 1990 Were among preschool children; among vaccine-eligible preschoolers aged 16-59 months, 79% were unvaccinated (lOa). There is no mechanism similar to school immunization laws to achieve universal immunization of preschoolers. State day care immunization laws only affect licensed centers, which care for an estimated 20% of children

The United States has achieved over 97% immunization of children by school age and has reduced the incidence of vaccine-preventable diseases by more than 90% since the prevaccination era. However, children often do not receive immunizations at the recommended age, and in densely populated urban areas this delay in immunization has led to epidemics of measles. Correctable deficiencies of the immunization delivery system have been identified in these areas. To respond to needs, the public health infrastructure must be strengthened, and active participation from the private sector must be obtained, both in delivery of immunizations and in assessment of performance. Appropriate action must be stimulated by the provision of timely information on immunization coverage and on indicators of program performance at the local level.

In October 1978, a nationwide initiative to eliminate indigenous measles from the United States by October 1, 1982, was announced. The measles elimination program has three major elements: attaining and maintaining high immunization levels, aggressive and effective surveillance, and vigorous response to cases. In 1980, immunization levels in children entering school for the first time were 96%, indicating that the necessary levels have been attained in the age group. Mechanisms are in place to assure maintenance of these levels; these rely heavily on the use of immunization requirements for school attendance in each state. Aggressive surveillance systems have been developed for each state to detect suspected measles cases as soon as possible after they occur and to investigate them within 24 hr of notification. The clinical definition of measles used is fever of greater than or equal to 101 F (38.3 C); rash of three or more days duration; and cough, coryza, or conjunctivitis. The response to outbreaks involves identifying persons in the area who are at risk of contracting measles, determining those who are possibly susceptible, and ensuring that these persons are vaccinated. In school outbreaks, susceptible students are vaccinated or excluded from school until the outbreak is over. During 1981, measles morbidity reached a record low level of only 3,032 reported cases (provisional total). Epidemic measles occurred in only a few outbreaks of limited size and duration, and endemic cases were restricted to a small number. Imported cases averaged slightly more than two per week, occasionally producing limited outbreaks, but more often resulting in no secondary spread. Transmission of measles has been interrupted in most of the United States. With continued vigorous implementation of the current strategy and with additional measures to lessen the risk of importations, it appears likely that the goal to eliminate indigenous measles transmission will be attained by October 1982.

This paper describes the epidemiological techniques available for measuring vaccine efficacy and recommends a practical approach to their use. The efficacy of vaccines in clinical use can be determined by a variety of means, including screening, outbreak investigations, secondary attack rates in families or clusters, vaccine coverage assessment, and case-control studies. They all offer a means of monitoring vaccine programs under conditions of day-to-day vaccine use. A table summarizes the different techniques for measuring efficacy. The screening technique is the most useful and rapid means of determining whether there is a problem with a vaccine. All that is required is a reliable estimate of the proportion of cases occurring in vaccinated individuals and an estimate of the vaccine coverage in the population at risk. If the estimated efficacy is within expected limits, more detailed studies are not warranted. If the results suggest low efficacy, more rigorous methods are necessary to assess the efficacy more accurately. Of the more accurate methods available, outbreak investigation offers the simplest means of measuring vaccine efficacy and is the preferred technique if the situation permits. The biases inherent in the method can be minimized, particularly if the disease incidence rate is high during the outbreak and accurate records exist. In large populations, the underlying immunization status prior to the outbreak can be estimated using the same cluster sampling method used in coverage assessments. Calculation of secondary attack rates in families is also an excellent and accurate means of measuring vaccine efficacy and is an acceptable alternative to the outbreak investigation. Vaccine coverage methods in endemic areas are best suited to urban areas where the measles incidence rate is high after age 11 months and low before 12 months, and maternal histories of disease are thought to be accurate. Case-control studies are best suited to areas where reliable personal immunization records may be difficult to find but other information, such as clinic records, may be available. No epidemiological method is perfect because it cannot exactly duplicate the experimental conditions of a prospective randomized clinical trial. The most accurate results will be obtained when biases are anticipated and corrective measures are taken whenever possible. Clinical vaccine efficacy determinations are carried out in order to assess whether the observed pattern of illness is consistent with the proper use of a highly effective vaccine. The components of a vaccine efficacy evaluation -- case definition, case ascertainment, and vaccination status determination -- apply to studies on all vaccines.

Since the introduction of acellular pertussis vaccines in Japan late in 1981, more than 20 million doses have been administered, mostly to children 2 years of age and older. Clinical studies indicate that mild local and febrile reactions are less frequent after administration of acellular pertussis vaccines than after whole-cell vaccines. Serious adverse events with sequelae occurred in 2-year-old children at approximately the same low rate during the period 1975 through August 1981, when whole-cell vaccines were used, and during August 1981 through 1984, when acellular vaccines were used exclusively. Five household contact studies have yielded vaccine efficacy estimates ranging from 78% to 92% in children 1 year of age or older. In addition, there has been a continuing decrease in reported pertussis incidence from the epidemic peak in 1979. Additional data on the safety and efficacy of acellular pertussis vaccines administered to infants would be useful in consideration of acellular pertussis vaccine licensure in the United States.

Two hundred fifty-four infants who had received measles vaccine at less than 10 months of age were revaccinated at greater than or equal to 15 months of age, and their immune responses were compared with 129 control infants who received their first doses of measles vaccine at greater than or equal to 15 months of age. Sera were collected at the time of revaccination (study infants) or primary vaccination (control infants), 3 weeks, and 8 months later and tested for antibody by hemagglutination inhibition (HI), enzyme-linked immunosorbent assay (ELISA), and cytopathic effect neutralization (CPEN). Of the 121 study infants who were initially HI negative, 116 (95.9%) made HI antibody 3 weeks postrevaccination compared with 126 (99.2%) of 127 control infants (P = 0.19). Of the 63 study infants with no initial detectable antibody by any of the three tests, 14 (22.2%) had a measles-specific IgM response 3 weeks postrevaccination compared with 37 of 50 (74.0%) randomly chosen control infants. By 8 months after revaccination, the 121 initially HI-negative study infants were significantly less likely to have detectable HI antibodies than control infants (52.1% v 97.6%) (P less than .001). However, 96.7% of these 121 study infants had detectable neutralizing antibody 8 months postrevaccination, an antibody thought to correlate best with protection. This study confirms the altered immune response to revaccination in infants first vaccinated prior to 10 months of age; however, the data suggest that most of these infants were successfully primed and are probably protected after revaccination.

Adults who travel to areas where poliovirus is endemic or epidemic have a statistically small yet potentially important risk of exposure to wild poliovirus. Vaccination is recommended for persons at risk of acquiring poliovirus infection. The vaccination schedule depends on the time remaining before departure and the patient's immunization status.

Since the introduction of acellular pertussis vaccines in Japan late in 1981, more than 20 million doses have been administered, mostly to children 2 years of age and older. Clinical studies indicate that mild local and febrile reactions are less frequent after administration of acellular pertussis vaccines than after whole-cell vaccines. Serious adverse events with sequelae occurred in 2-year-old children at approximately the same low rate during the period 1975 through August 1981, when whole-cell vaccines were used, and during August 1981 through 1984, when acellular vaccines were used exclusively. Five household contact studies have yielded vaccine efficacy estimates ranging from 78% to 92% in children 1 year of age or older. In addition, there has been a continuing decrease in reported pertussis incidence from the epidemic peak in 1979. Additional data on the safety and efficacy of acellular pertussis vaccines administered to infants would be useful in consideration of acellular pertussis vaccine licensure in the United States. ( JAMA 1987;257:1351-1356)