Passive Measles Immunity Wanes Quickly in Infants

Veronica Hackethal, MD

November 21, 2019

It has long been thought that the transference of antibodies from the mother across the placenta during pregnancy confers passive immunity to measles for newborns and infants, but new research suggests that this immunity may quickly wane in newborns.

For most (92%) of the 3-month-old newborns, antibody levels were no longer high enough to protect them from measles, and by 6 months, that percentage had risen to 100%.

The study was published online November 21 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," write author Michelle Science, MD, of the Hospital for Sick Children in Toronto, Canada, and colleagues.

Other studies have investigated this issue, but most have evaluated older infants. What's new about this study is that it focused on the first 6 months of life, Walter Orenstein, MD, of Emory University School of Medicine, Atlanta, Georgia, told Medscape Medical News. Orenstein, who was not involved in the study, is the author of an accompanying commentary with Huong Q. Mclean, PhD, MPH, of the Marshfield Clinic Research Institute in Wisconsin.

Although the study was conducted in Canada — which has not seen a surge in measles outbreaks as in the United States, where measles elimination is at risk — Orenstein thinks the results are applicable to the United States. That's because measles is believed to have been eliminated in both countries since the 1990s.

"Infant passive antibody levels in measles elimination settings are lower than they were in the past before measles was eliminated," Orenstein said.

Two reasons probably account for these low passive antibody levels in infants, he continued. Before measles was eliminated, most mothers developed their immunity to measles when they became infected by wild-type virus, which produces stronger immunity than vaccination does. Also, mothers experienced repeated exposure to the virus as it continued to circulate, which provided a natural immune boost.

Both processes would have resulted in mothers with higher antibody levels, which they passed on to their infants. But once the virus was eliminated, most mothers gained their immunity through vaccination, so their infants likely started out with lower antibody levels. This put them at risk for diminished immunity and for measles infection and its complications, including pneumonia, encephalitis, and death.

Current US guidelines recommend that the first dose of measles vaccine be administered at age 12 to 15 months. Infants as young as 6 months can receive the vaccine if they will be traveling abroad or are at risk for exposure during a local outbreak; however, the earlier dose does not count toward the recommended two doses that should be given on or after the first birthday.

The study raises the question of whether to lower the vaccination age for infants in the United States.

Orenstein and McLean say lowering the age of vaccination would be premature.

"We are not seeing large numbers of measles cases in this age group [of newborns aged 6 months or younger]," Orenstein explained.

The best strategy for protecting very young infants is to encourage vaccine uptake and to prevent exposure to measles from local outbreaks or from cases carried into the country by travelers.

"We need to overcome vaccine hesitancy and get high levels of vaccination at the ages vaccination is recommended," Orenstein stressed. "What's important for clinicians in particular is to work with parents who might be hesitant to get their children vaccinated.

"The other issue is that we have a global interest in helping other countries control and potentially eliminate their measles problem. It's both for humanitarian reasons as well as for our own domestic health security," he added.

The researchers collected blood from 196 full-term infants born between January 2014 and December 2016. They excluded infants with medical conditions that could affect immunity. They then analyzed randomly selected blood samples from infants aged 0 months, 1 month, 2 months, 3 months, 4, months, 5 months, 6 – 9 months, and 9 – 11 months. To test for measles antibodies, they used the gold standard plaque reduction neutralization test (PRNT), rather than the commonly used ELISA test, which produces less accurate results as antibody levels decrease.

During the first month of life, 20% of infants (5/25) had antibody levels that were below the cutoff for protection against measles. By 3 months, that percentage had increased to 92% (22/24), and by 6 months, 100% of infants were no longer protected against measles.

Analyses that were adjusted for infant sex and maternal age showed that for each additional month of infant age, the odds of being susceptible to measles doubled (odds ratio, 2.13 for each additional month increase; 95% confidence interval, 1.52 – 2.97).

For infants born to younger mothers aged 25 years, there was a lower probability of being susceptible to measles at age 1 month, compared with infants born to mothers aged 40 years (∼25% vs ∼40% probability), presumably because maternal immunity wanes with increasing age.

Maternal antibodies transferred in breast milk are thought to support the infant immune system. For infants who received any breast milk, there was a lower probability of being susceptible to measles, compared with those who did not receive breast milk, but the results were not statistically significant (76% vs 58%).

Neither the results with respect to maternal age or the receiving of breast milk were statistically significant (P = 0.31 and P = 0.11, respectively).

The authors explain that the study lacked a large amount of data on maternal age (49%) and breastfeeding status (47%), which could have affected results. Also, the study took place in a single tertiary care hospital, and results may not apply to other settings.

Still, they note that other studies in countries in which measles has been eliminated, such as Belgium and Portugal, have also found that immunity waned very quickly in the first months of life.

The study was supported by the Public Health Ontario Project Initiation Fund. The authors, Mclean, and Orenstein have disclosed no relevant financial relationships.

Pediatrics. Published online November 21 2019. Abstract, Commentary

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