Modelling the effects of booster dose vaccination schedules and recommendations for public health immunization programs: the case of Haemophilus influenzae serotype b

Abstract

Background Haemophilus influenzae serotype b (Hib) has yet to be eliminated despite the implementation of routine infant immunization programs. There is no consensus regarding the number of primary vaccine doses and an optimal schedule for the booster dose. We sought to evaluate the effect of a booster dose after receiving the primary series on the long-term disease incidence.MethodsA stochastic model of Hib transmission dynamics was constructed to compare the long-term impact of a booster vaccination and different booster schedules after receiving the primary series on the incidence of carriage and symptomatic disease. We parameterized the model with available estimates for the efficacy of Hib conjugate vaccine and durations of both vaccine-induced and naturally acquired immunity.ResultsWe found that administering a booster dose substantially reduced the population burden of Hib disease compared to the scenario of only receiving the primary series. Comparing the schedules, the incidence of carriage for a 2-year delay (on average) in booster vaccination was comparable or lower than that observed for the scenario of booster dose within 1 year after primary series. The temporal reduction of symptomatic disease was similar in the two booster schedules, suggesting no superiority of one schedule over the other in terms of reducing the incidence of symptomatic disease.ConclusionsThe findings underscore the importance of a booster vaccination for continued decline of Hib incidence. When the primary series provides a high level of protection temporarily, delaying the booster dose (still within the average duration of protection conferred by the primary series) may be beneficial to maintain longer-term protection levels and decelerate the decline of herd immunity in the population.Electronic supplementary materialThe online version of this article (10.1186/s12889-017-4714-9) contains supplementary material, which is available to authorized users.

How the Interval Between Primary and Booster Vaccination Affects Long-Term Disease Dynamics

“…There is evidence accumulating that the booster vaccine schedule requires evaluation for several vaccine-preventable diseases to improve the effect of vaccination campaigns 6,7,4 . Previous studies have shown the time interval between the primary vaccination and booster dose could play a vital role in the long-term dynamics of Hib 14 , and a large delay in booster vaccination may result in a longer protection period during lifetime 15 . However, a larger delay may lead to a lower fraction of primaries receiving the booster dose as a results of parental hesitancy and refusal with subsequent increase in the number of unvaccinated and undervaccinated individuals 16,17,18 .…”

Haemophilus influenzae type b disease in the era of conjugate vaccines: critical factors for successful eradication

“…Results from a modeling study also indicated that, overall, the administration of a booster dose within 1 year after the primary series would lead to a further decrease in the incidence of Hib disease compared to the scenario of only a primary vaccination series, at high vaccine coverages (90% or 100%). While deferring the booster dose to 2 years postprimary vaccination is not expected to impact direct protection, the model predicts that carriage of Hib would be reduced [75].…”

“…Anti-PRP concentration ≥5.0 µg/ml has previously been correlated with protection against Hib carriage, indicating also that higher antibody levels are needed for protection against colonization/carriage than against Hib disease [10]. Modeling studies have shown a higher impact on Hib carriage reduction if the booster dose is administered at 2 years versus 1 year post-primary vaccination [75]. However, a head-to-head comparison of the impact on nasopharyngeal carriage provided by different Hib immunization schedules has not been yet performed [67].…”

Invasive Haemophilus influenzae Infections after 3 Decades of Hib Protein Conjugate Vaccine Use

“…The authors concluded that $2 doses of Hib vaccine are needed to achieve high levels of effectiveness (.85%) and a booster could be beneficial, especially if the primary course was incomplete, but there were insufficient data to clearly show superiority of any particular schedule. A modeling study estimated that a primary series plus a booster dose within 1 year would result in greater reduction in the incidence of Hib disease than a primary series without a booster dose (186). However, this assumed high vaccine coverage of 90 to 100%, which has not yet been achieved in many countries.…”

“…However, this assumed high vaccine coverage of 90 to 100%, which has not yet been achieved in many countries. The model also looked at delaying the booster dose for 2 years after the primary vaccination series and found that this had little impact on direct vaccine-induced protection against invasive Hib disease in children who have received Hib vaccine (186). A study in four South American countries (93) concluded that high Hib vaccine coverage resulted in a sustained low incidence of Hib meningitis and nasopharyngeal carriage of Hib with a three-dose primary series of Hib vaccine with or without a booster dose of vaccine in the second year of life.…”