LONG TERM FOLLOW-UP AFTER HIGH TITER MEASLES VACCINE

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We propose to evaluate recipients of high titer measles vaccines for evidence of long-term adverse effects by comparing them with recipients of lower titer vaccines for survival, nutritional status, and immunologic parameters. These children received high, medium, and standard titer (approximately 105.4, 104.5, and 103.5 pfu/dose, respectively) measles vaccines in 1987-1989. A followup study in 1991 revealed increased mortality among female high titer vaccine recipients. We propose to determine if the increased mortality among high titer vaccines recipients has persisted for more than 3 years after vaccination and if differences in nutritional status and immunologic parameters can be detected among survivors by sex and dose of vaccine received. We anticipate identifying approximately 1500-1700 of the original study children, including 600-700 children who receive high titer vaccines. The children will be monitored for mortality and the development of illnesses over a 3 1/2 year period. Skin tests for delayed type hypersensitivity to 7 antigens will be performed on 600 children (300 high titer recipients). Additional immunologic studies will be performed on a block randomized sample (by sex and vaccine dose) of 300 children in the first year including total white blood count and differential, peripheral blood mononuclear cell phenotyping to determine the percent CD4, CD8, CD3, NK, CD45RA, and CD45RO positive cells. Lymphocyte proliferation will be determined before and after exposure to mitogens (PHA and anti-CD3) and antigens (measles and tetanus), and T cell cytokine production (IL-2, IL-4, IFN- gamma) will be measured. Additional cells will be frozen in RNA-zol at - 70 degrees for subsequent mRNA and cytokine mRNA analysis and cells will be provided to Dr. Peter Dowling for PCR-Rt to detect persistent infections. Plasma will be tested for measles antibody and aliquots of cells and plasma will be preserved for future studies. Up to 300 additional children will be studied in the second year and in subsequent years, as indicated from the results of the first year studies. These data will allow us to detect persistent immunologic differences and to obtain better understanding of the pathogenesis for delayed onset increased mortality following high titer vaccines. This study will provide information that will be important for the development and evaluation of new measles vaccines.