Dosage Schedule Linked to Rate of PCV Breakthrough Infections

By Will Boggs MD

February 15, 2020

NEW YORK (Reuters Health) - A dosing schedule that includes three primary doses of pneumococcal conjugate vaccine (PCV) is associated with fewer breakthrough infections in the first year of life than are schedules with two primary doses, according to a new study of surveillance data.

"Our study found that 3 primary doses were better than 2 in the first year of life for preventing breakthrough infections before the booster dose," Dr. Tamera Pilishvili of the Centers for Disease Control and Prevention, in Atlanta, told Reuters Health by email. "But after the first year of life, there were no differences found. For breakthrough infections after the booster dose, there were no differences between 2 versus 3 primary doses at any follow-up period."

The World Health Organization recommends PCV use on a three-dose schedule, either two primary doses with a booster or three primary doses without a booster. In the U.S., a four-dose schedule (three primary and one booster) is licensed for infants.

Using data from the Active Bacterial Core surveillance system, Dr. Pilishvili and colleagues found the rate of PCV7 breakthrough infections per 100,000 person-years in the first year of life was 7.00 with two primary doses compared to 0.32 with three primary doses, a significant difference.

There was no significant difference between the dosing schedules and the rates of breakthrough infections in the second and third years of life, they report in Pediatrics.

Similarly, the rate of PCV13 breakthrough infections per 100,000 person-years in the first year of life was 7.79 with two primary doses versus 0.60 with three, also a significant difference. Rates did not differ significantly between the schedules in the second and third years of life.

Among children receiving booster doses of PCV7, the schedule of two primary doses plus a booster was associated with a significant 9.2-fold rise in the rate of breakthrough infections in the second year of life, compared with the schedule of three primary doses plus a booster.

In contrast, there were no significant differences between the schedules in breakthrough infection rates beyond the first year of life for children receiving PCV13.

"Despite successes in reducing disease burden in settings using 3-dose schedules, practical considerations should be taken into account before adopting a 2+1 schedule," Dr. Pilishvili said. "For example, it should be determined whether this change could lead to increased disparities in coverage and disease among groups at increased risk for pneumococcal disease."

Dr. Sanjay Jayasinghe of the National Center for Immunization Research and Surveillance, in Westmead, and the University of Sydney, both in Australia, who has studied PCV dosing schedules, told Reuters Health by email, "Even if a child has received less than the recommended 4 doses, their risk of breakthrough disease is still low, but it is crucial to give the booster dose on time to ensure best protection regardless of the number of primary doses a child has had. This is important to harness strong herd benefit by reducing asymptomatic carriage in 1-year-olds who are pneumococcal 'super spreaders.'"

"Overall, breakthrough disease following PCV is rare and the large majority of residual invasive pneumococcal disease (IPD) still occurs in those not vaccinated or incompletely vaccinated, so actively promoting PCV is still vital," said Dr. Jayasinghe, who was not involved in the study.

"If some further analysis of this data is undertaken to weigh up the benefits and risks between 3+0 and 2+1 in terms of breakthrough disease, it would be of value, given it is those schedules that WHO recommends," Dr. Jayasinghe said. "Strong surveillance and careful review of disease data is absolutely important to ensure that the dropping of primary doses does not leave infants unduly vulnerable to life-threatening IPD."

SOURCE: Pediatrics, online February 13, 2020.