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A concurrent prospective study was conducted in Rwanda to compare the immunogenicity and safety of live, attenuated measles vaccine in ill and well children. Five hundred and eighteen children aged 8 to 19 months were selected from children attending the acute care and immunization services of two clinics. Two hundred and sixty-seven ill children and 251 well children were enrolled and examined. Serological tests were performed on blood samples obtained before and 40 days after measles immunization. Among the 208 ill children and 215 well children who were seronegative at baseline and had unequivocal follow-up serological results, seroconversion rates were 81% and 80%, respectively. Side effects were modest and were equally frequent in the two study groups (15.4% among ill children versus 15.1% among well children). These results support a change in measles immunization policy in developing countries with respect to immunization of children with acute illnesses. Such a change would make a great contribution to decreasing the enormous burden of measles in the developing world through increased immunization coverage.

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A comparative field trial of three rubella virus vaccines (Cendehill, HPV-77 DE-5, and HPV-77 DK-12) was initiated in 1969 on the islands of Kauai and Hawaii in the state of Hawaii. In 1985, follow-up was reinitiated to assess the long-term durability of vaccine-induced immunity. Enzyme-linked immunosorbent assays of serum specimens from 1290 participants demonstrated seropositive rates of 92.4% and 96.4% at screening levels of 10 (protective level) and 7 (lowest detectable level) IU/mL, respectively. The seropositive rates were not related to reinfection or reimmunizations. These findings indicate that vaccine-induced rubella antibodies are detectable in almost all persons up to 16 years after successful vaccination.

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In 1982, 1,871 (79%) of 2,368 eligible 6th, 10th and 12th grade students in Massachusetts participated in a statewide serosurvey for rubella antibodies. Sera were screened at the Centers for Disease Control (CDC) by a reference hemagglutination inhibition assay at 1:8, equivalent to approximately 15 International Units (IU)/ml. Sera negative by the CDC hemagglutination inhibition assay were retested using an enzyme immunoassay, a passive hemagglutination assay, and a commercial hemagglutination inhibition test. The approximate screening levels were 10 IU/ml, 7.5 IU/ml, and 5 IU/ml, respectively. Overall seroprevalence levels varied from 76.4% screening at 15 IU to 93.1% including seropositives from any of the tests. Persons with a school record of vaccination had significantly higher seroprevalence levels than persons without records. However, only 78.3% of persons with a record had antibody greater than or equal to 15 IU compared with 60.0% without records; considering any detectable antibody, the comparison is 95.6% versus 71.4%. The low titers in vaccinees appeared to be due to a falloff of antibody with time since vaccination. Of students with a single vaccination noted in the record with exact dates, 92.3% who were vaccinated 0-4 years prior to the study had antibody at 15 IU compared with less than 78% of students with antibody who were vaccinated five or more years prior to the study. In contrast, using more sensitive assays, there was no significant decline in seroprevalence with time since vaccination. Revaccination studies and epidemiologic data suggest that almost all persons with detectable antibody whether above or below 15 IU/ml are immune to rubella. Thus, immunity levels in Massachusetts schoolchildren in the 6th, 10th, and 12th grades are probably in excess of 90%.

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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.

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In February 1981, a measles outbreak occurred in a pediatric practice in DeKalb County, GA. The source case, a 12-year-old boy vaccinated against measles at 11 1/2 months of age, was in the office for one hour on the second day of rash, primarily in a single examining room. On examination, he was noted to be coughing vigorously. Seven secondary cases of measles occurred due to exposure in the office. Four children had transient contact with the source patient as he entered or exited through the waiting room; only one of the four had face-to-face contact within 1 m of the source patient. The three other children who contracted measles were never in the same room with the source patient; one of the three arrived at the office one hour after the source patient had left. The risk of measles for unvaccinated infants (attack rate 80%, 4/5) was 10.8 times the risk for vaccinated children (attack rate 7%, 2/27) (P = .022, Fisher exact test, two-tailed). Airflow studies demonstrated that droplet nuclei generated in the examining room used by the source patient were dispersed throughout the entire office suite. Airborne spread of measles from a vigorously coughing child was the most likely mode of transmission. The outbreak supports the fact that measles virus when it becomes airborne can survive at least one hour. The rarity of reports of similar outbreaks suggests that airborne spread is unusual. Modern office design with tight insulation and a substantial proportion of recirculated ventilation may predispose to airborne transmission.

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Serologic techniques for the detection of antibodies to rubella virus provide the approach of choice for laboratory diagnosis of acute and congenital rubella infections and for the determination of rubella immunity status. Rubella serodiagnostic tests currently being used in clinical laboratories are described in this review. Advantages, limitations, and relative sensitivities and specificities of these tests are presented. The reactivity and specificity of rubella antibody tests have been shown to vary from laboratory to laboratory and from one manufacturer's kit to another. The need is clearly apparent for a universally accepted reference standard that will allow sensitivities and alternative assays to be compared directly and a meaningful immune cutoff level to be established. Incorporating such standards into the available rubella tests would eliminate much of the diagnostic uncertainty associated with rubella infections during pregnancy.

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One hundred nineteen women susceptible to rubella received RA27/3 vaccine, 94 received either Cendehill or HPV-77 vaccine, and one received a vaccine of unknown strain in the three months before or after their estimated date of conception. They gave birth to 216 living infants free of abnormalities compatible with the congenital rubella syndrome (CRS). The maximum theoretical risk for CRS for these infants was 1.7%. Four of these infants born to susceptible women had laboratory evidence of subclinical infection (three after receiving Cendehill or HPV-77 vaccines and one after receiving RA27/3 vaccine) but were normal at birth and at subsequent follow-up examinations. Rubella virus was isolated from the products of conception for only 3% (1 of 32) of cases involving susceptible women who received RA27/3 vaccine; the reported rate of virus isolation for Cendehill and HPV-77 vaccine is 20%. The available data indicate that if vaccination occurs within three months of conception, the risk is negligible. However, since the actual risk may not be zero, women known to be pregnant should not be vaccinated, and conception should be avoided for three months after vaccination.

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In 1977, a large rubella outbreak occurred in Hawaii. Because attack rates were high among women of childbearing age, we conducted extensive surveillance efforts to detect both pregnancies complicated by rubella and cases of congenital rubella syndrome (CRS). Initial surveillance included a survey of physicians and hospitals, review of fetal death and birth certificates, and cord blood screening for rubella-specific IgM of infants born following the epidemic. Two years after the outbreak, the medical community was again surveyed to identify affected children who were missed initially. No case of CRS was identified either shortly after the outbreak or in the ensuing two years. In addition, none of the 5,605 cord serum samples obtained was found to contain rubella-specific IgM antibody. Through active surveillance, we received 12 reports of rubella in pregnant women, of whom 11 elected to terminate their pregnancies. The extensive use of therapeutic abortion by exposed women may have prevented the birth of infants with CRS. Surveillance for rubella-related abortions is an important component in assessing the health impact of rubella in a community.

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To document the serological response, 21 seronegative rubella vaccinees (hemagglutination inhibition [HI] titer less than 10) were revaccinated with RA 27/3 rubella vaccine. All demonstrated an anamnestic response. Although RA 27/3 vaccine was an effective booster, antibody boost was not maintained in some persons. Of 15 persons tested, 24 to 27 months after revaccination, six had a significant HI antibody drop (fourfold or greater); only one had lost all detectable HI antibody. Although all 21 study participants were initially HI seronegative by rubella HI testing, 16 (76.2%) possessed neutralization and/or enzyme-linked immunosorbent assay antibodies before revaccination. As more persons with vaccine-induced immunity join the adult population pool, more sensitive test methods may be needed to assess serological status accurately.

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Because the incidence of measles has declined in recent years, the potential for confusion of measles with other morbilliform rashes has increased. Routine serologic testing of suspected cases of measles is recommended but it has been hampered, particularly in young infants and children, by the requirement of performing venipuncture. We have compared measles hemagglutination inhibition antibody testing performed on dried capillary whole blood collected on filter paper strips with testing of serum specimens obtained simultaneously by venipuncture. We assessed overall comparability, diagnostic sensitivity and specificity and acceptability and practicality for field use. Of the 125 capillary-venous sets compared, there was a 4-fold difference in hemagglutination inhibition titer between the two types of specimens in only one set (0.8%). Diagnostic sensitivity using capillary blood was 100% and specificity was 96%. Immunoglobulin M assessments on six capillary-venous sets were in complete agreement (three positive in both, three negative in both). In a pilot program of field use, filter paper blood collection was associated with a 97% (36 of 37) success rate in obtaining specimens from individuals with suspected cases of measles. This method of blood collection and testing is an accurate, feasible and acceptable means for seroconfirmation of measles.

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We conducted a serological and questionnaire study of 755 US Merchant Marine Academy cadets (aged 16 to 29 years) and their parents to determine the cadets' susceptibility rate to measles and rubella and to see if there was any difference in the accuracy of cadet and parental histories of previous infection and vaccination. Approximately 4% of the cadets were susceptibility. We also determined the costs and the effectiveness of three alternative strategies for vaccinating susceptible adolescents and young adults: (1) vaccinating all persons regardless of past history; (2) serologically screening all persons and vaccinating only those who were susceptible; and (3) vaccinating all individuals who do not have physician-documented proof of proper vaccination, past infection (measles only), or serological immunity. The cost savings among the three alternatives are dependent on the proportion of potential vaccinees with records available for review and must be balanced against the proportion of susceptible persons protected by each alternative. We also found that a combined vaccination program for both measles and rubella is less costly than a program aimed at providing immunity to only one of the two diseases.

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A comparative field trial of three live, attenuated rubella virus vaccines (Cendehill, HPV 77 DE-5, and HPV-77 DK-12) was initiated in 1969 on the islands of Kauai and Hawaii in the state of Hawaii. Following initial seroconversion rates of more than 98%, periodic serological testing of the study population was conducted to assess the durability of vaccine-induced immunity. In February 1980, ten years after the initiation of the study, 741 of the 5,153 original susceptible vaccinees were still enrolled in the study. After a drop of approximately 50% in mean hemagglutination-inhibition (HI) titer for each of the vaccine groups during the first four years following vaccination, the HI titer levels for all three groups have been generally stable between years 4 and 10. The frequency of reversion to an HI titer of less than 10 has remained less than 0.5% per year. A measurable HI antibody level has persisted in more than 97% of all vaccines over the ten-year period. This study indicates that when potent rubella vaccine is administered properly, a high seroconversion rate and a high rate of antibody persistence should be expected.

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