Differential Mortality by Measles Vaccine Titer and Sex

Abstract

Mortality was evaluated in 1972 children who had received measles vaccines at 6-11 months of age that were 10-fold (medium titer) or 100-fold (high titer) greater than standard titer. Mortality among boys did not differ by vaccine titer and was similar to mortality in children who received standard-titer vaccine. Girl recipients of high-titer vaccine had somewhat greater mortality than girls who received medium-titer vaccine (risk ratio = 1.71, 95% confidence interval = 0.91-3.24). Increased mortality was associated with high-titer vaccine for girls but not for boys (P = .04). There was no evidence of selection bias or preferential health care by sex that might explain the differential mortality. This mortality pattern has been noted in two other populations with high background infant and childhood mortality. The biologic basis for this effect on mortality has not been determined. Data from this and other studies have resulted in discontinuation of the use of high-titer measles vaccines.

Reduced Risk of Neonatal Respiratory Infections Among Breastfed Girls but Not Boys

“…Clearly, colostrum and breast milk are rich in cellular and acellular factors that could be important to neonatal respiratory immunity. 19 Sex differences in early immunity can be inferred from differential responses to measles vaccine, 20 as well as differential risks of various neonatal infection syndromes (sepsis, meningitis, urinary tract infection, and pustulosis) [21][22][23][24] and pathogen-defined childhood infectious diseases (enteroviruses, adenoviruses, and respiratory syncytial virus, among others). [25][26][27] However, work remains to be done to understand the specific ways in which such differences contribute to neonatal systemic and mucosal immunity in the prevention and amelioration of respiratory disease.…”

Human Parainfluenza Virus Type 3 (PIV3) Expressing the Hemagglutinin Protein of Measles Virus Provides a Potential Method for Immunization against Measles Virus and PIV3 in Early Infancy

“…By using another approach, the measles vaccine virus was administered parenterally at a 10-to 100-fold-increased dose (38). This improved seroconversion in infants 4 to 6 months of age, but there was an associated increase in mortality in the high-titer vaccine recipients later in infancy (22,28,38).…”

Modulation of disease, T cell responses, and measles virus clearance in monkeys vaccinated with H-encoding alphavirus replicon particles

“…Atypical measles is associated with anamnestic production of large amounts of nonprotective, low avidity, complement-fixing antibody leading to immune complex deposition in multiple sites (8,9). A high-titer live attenuated vaccine also proved problematic when given to 4-to 6-month-old infants because of an unexplained increase in all-cause mortality in vaccinated girls (10)(11)(12).…”