according to new research.
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In fact, most of the 196 infants’ maternal measles antibodies had dropped below the protective threshold by 3 months of age – well before the recommended age of 12-15 months for the first dose of MMR vaccine.
The odds of inadequate protection doubled for each additional month of age, Michelle Science, MD, of the University of Toronto and associates reported in Pediatrics.
“The widening gap between loss of maternal antibodies and measles vaccination described in our study leaves infants vulnerable to measles for much of their infancy and highlights the need for further research to support public health policy,” Dr. Science and colleagues wrote.
The findings are not surprising for a setting in which measles has been eliminated and align with results from past research, Huong Q. McLean, PhD, MPH, of the Marshfield (Wis.) Clinic Research Institute and Walter A. Orenstein, MD, of Emory University in Atlanta wrote in an accompanying editorial (Pediatrics. 2019 Nov 21. doi: 10.1542/peds.2019-2541).
However, this susceptibility prior to receiving the MMR has taken on a new significance more recently, Dr. McLean and Dr. Orenstein suggested.
“In light of increasing measles outbreaks during the past year reaching levels not recorded in the United States since 1992 and increased measles elsewhere, coupled with the risk of severe illness in infants, there is increased concern regarding the protection of infants against measles,” the editorialists wrote.
Dr. Science and colleagues tested serum samples from 196 term infants, all under 12 months old, for antibodies against measles. The sera had been previously collected at a single tertiary care center in Ontario for clinical testing and then stored. Measles has been eliminated in Canada since 1998.
The researchers randomly selected 25 samples for each of eight different age groups: up to 30 days old; 1 month (31-60 days); 2 months (61-89 days); 3 months (90-119 days); 4 months; 5 months; 6-9 months; and 9-11 months.
Just over half the babies (56%) were male, and 35% had an underlying condition, but none had conditions that might affect antibody levels. The conditions were primarily a developmental delay or otherwise affecting the central nervous system, liver, or gastrointestinal function. Mean maternal age was 32 years.
To ensure high test sensitivity, the researchers used the plaque-reduction neutralization test (PRNT) to test for measles-neutralizing antibodies instead of using enzyme-linked immunosorbent assay (ELISA) because “ELISA sensitivity decreases as antibody titers decrease,” Dr. Science and colleagues wrote. They used a neutralization titer of less than 192 mIU/mL as the threshold for protection against measles.
When the researchers calculated the predicted standardized mean antibody titer for infants with a mother aged 32 years, they determined their mean to be 541 mIU/mL at 1 month, 142 mIU/mL at 3 months (below the measles threshold of susceptibility of 192 mIU/mL) , and 64 mIU/mL at 6 months. None of the infants had measles antibodies above the protective threshold at 6 months old, the authors noted.
Children’s odds of susceptibility to measles doubled for each additional month of age, after adjustment for infant sex and maternal age (odds ratio, 2.13). Children’s likelihood of susceptibility to measles modestly increased as maternal age increased in 5-year increments from 25 to 40 years.
Children with an underlying conditions had greater susceptibility to measles (83%), compared with those without a comorbidity (68%, P = .03). No difference in susceptibility existed between males and females or based on gestational age at birth (ranging from 37 to 41 weeks).
The Advisory Committee on Immunization Practices permits measles vaccination “as early as 6 months for infants who plan to travel internationally, infants with ongoing risk for exposure during measles outbreaks and as postexposure prophylaxis,” Dr. McLean and Dr. Orenstein noted in their editorial.
They discussed the rationale for various changes in the recommended schedule for measles immunization, based on changes in epidemiology of the disease and improved understanding of the immune response to vaccination since the vaccine became available in 1963. Then they posed the question of whether the recommendation should be revised again.
“Ideally, the schedule should minimize the risk of measles and its complications and optimize vaccine-induced protection,” Dr. McLean and Dr. Orenstein wrote.
They argued that the evidence cannot currently support changing the first MMR dose to a younger age because measles incidence in the United States remains extremely low outside of the extraordinary outbreaks in 2014 and 2019. Further, infants under 12 months of age make up less than 15% of measles cases during outbreaks, and unvaccinated people make up more than 70% of cases.
Rather, they stated, this new study emphasizes the importance of following the current schedule, with consideration of an earlier schedule only warranted during outbreaks.
“Health care providers must work to maintain high levels of coverage with 2 doses of MMR among vaccine-eligible populations and minimize pockets of susceptibility to prevent transmission to infants and prevent reestablishment of endemic transmission,” they concluded.
The research was funded by the Public Health Ontario Project Initiation Fund. The authors had no relevant financial disclosures. The editorialists had no external funding and no relevant financial disclosures.
SOURCE: Science M et al. Pediatrics. 2019 Nov 21. doi: 10.1542/peds.2019-0630.