Response to Rubella Vaccine Among Seronegative Children with Congenital Rubella

E. RICHARD STIEHM (UCLA Center for the Health Sciences, Los Angeles, Calif.): Many patients with rubella syndrome have a systemic immunologic deficiency. Were your sero-negative rubella patients tested for their response to other antigens to exclude a nonspecific diminution of antibody response, rather than specific tolerance to rubella virus? Dr. FLORMAN: Several of our children by history had had regular measles vaccination. It was possible for us to test their sera and find that they had responded with perfectly fine titers of antibody against rubeola. JANET HARDY (Johns Hopkins Hospital, Baltimore, Md.): Dr. FLORMAN and his associates have attempted to answer some interesting and important questions. Individual variation in response to immunologic stimuli may perhaps lead to the emergence of a number of different answers. In this regard I would like to comment on a patient followed by Dr. JOHN BORDLEY and me, with the help of Dr. JOHN SEVER. This was a child born early in 1964 whose mother presumably had inapparent rubella approximately one-third the way through her pregnancy. She has a history of exposure. When her child was just over 1 year of age her serum rubella HAI titer was 1:512. At this age the child was found to have a severe hearing loss (50 dB in the right ear, 80–90 dB in the left ear), small body size, and mild peripheral pulmonic stenosis. His rubella HAI titer was 1:128; further serologic determinations at 30 and 36 months of age showed no detectable HAI antibody in a dilution of 1:4, nor did he have neutralizing antibody at 30 months. At 5 years of age he was exposed to, and developed, clinical rubella, with lymphadenopathy and rash. Attempted viral isolation 5 days after the appearance of the rash was not successful but some 3–4 weeks later his rubella HAI titer was 1:512. Subsequently, he experienced a further depression of auditory sensitivity and he now has a severe hearing loss in both ears. He is a highly intelligent child—IQ 137 (Leiter nonverbal test) and there is no question about the validity of the test results. One further comment pertains to our experience in an epidemiologic study carried out in 1967 by Dr. JOHN GRANT, Maryland State Department of Health. This study was a survey of all the children born in 1964 in several areas in Frederick County, Maryland to determine the number of children with congenital rubella. Of some 600 children screened, 8–10 had defects compatible with congenital rubella, but more than 50% had no rubella HAI antibody. This points out the problem of the limited usefulness of serologic study in the retrospective diagnosis of congenital infection in both the clinical and epidemiologic setting. Dr. FLORMAN: I think you have touched on the really crucial point, and that is: are these children who are seronegative susceptible to reinfection by wild virus? Your case is very pertinent. JOSEPH W.ST.GEME, Jr. (UCLA Medical School, Harbor General Hospital, Torrance, Calif.): Is it possible that these children have very low levels of neutralizing antibody? Dr. FLORMAN: We have not yet tested these children who no longer have detectable HI antibody for the presence of neutralizing antibody. Dr. HARDY: May I comment on that? Because we have, and there is no neutralizing antibody. PEARAY L. OGRA (State University of New York, Buffalo, Buffalo, N.Y.): I would like to raise one question in regard to the disappearance of rubella virus antibody in these children. It has been reported in the past that there are children with congenital rubella syndrome who do not have any detectable neutralizing or hemagglutinizing antibody in the newborn period. Is it possible that some of these children who had no detectable HI antibody after 6 months—that the preexisting serum antibody was all transplacently acquired maternal antibody—failed to have an immunological response to start with? Secondly, did you try by any means to identify immunologically the immunoglobulin class with which this antibody activity was associated? Presence of γM antibody would suggest active fetal production rather than maternal transport. Dr. FLORMAN: As you noticed in our charts, we excluded all determinations on patients' sera except those that were obtained after 6 months of age, because we too were concerned that the determinations done earlier might represent transplacentally acquired antibody. Consequently, all these children had responded with detectable levels of antibody earlier in life, even those who by the age of 2–5 years had lost it. DOUGLAS E. Cox (Wayne State University Medical School and Children's Hospital of Michigan, Detroit, Mich.): Is your twin, which was discordant for congenital rubella and became seronegative before 5 years of age, dizygous by placentation and membranes or by difference in some genetic marker? (Subsequent communication with the authors (viz., Dr. Louis Z. COOPER) has confirmed clear documentation of dizygosity by both criteria.)