Estimating the contribution of different age strata to vaccine serotype pneumococcal transmission in the pre vaccine era: a modelling study

Abstract

Background Herd protection through interruption of transmission has contributed greatly to the impact of pneumococcal conjugate vaccines (PCVs) and may enable the use of cost-saving reduced dose schedules. To aid PCV age targeting to achieve herd protection, we estimated which population age groups contribute most to vaccine serotype (VT) pneumococcal transmission. Methods We used transmission dynamic models to mirror pre-PCV epidemiology in England and Wales, Finland, Kilifi in Kenya and Nha Trang in Vietnam where data on carriage prevalence in infants, pre-school and school-aged children and adults as well as social contact patterns was available. We used Markov Chain Monte Carlo methods to fit the models and then extracted the per capita and population-based contribution of different age groups to VT transmission. Results We estimated that in all settings, < 1-year-old infants cause very frequent secondary vaccine type pneumococcal infections per capita. However, 1–5-year-old children have the much higher contribution to the force of infection at 51% (28, 73), 40% (27, 59), 37% (28, 48) and 67% (41, 86) of the total infection pressure in E&W, Finland, Kilifi and Nha Trang, respectively. Unlike the other settings, school-aged children in Kilifi were the dominant source for VT infections with 42% (29, 54) of all infections caused. Similarly, we estimated that the main source of VT infections in infants are pre-school children and that in Kilifi 39% (28, 51) of VT infant infections stem from school-aged children whereas this was below 15% in the other settings. Conclusion Vaccine protection of pre-school children is key for PCV herd immunity. However, in high transmission settings, school-aged children may substantially contribute to transmission and likely have waned much of their PCV protection under currently recommended schedules.

Pneumococcal exposure routes for infants, a nested cross-sectional survey in Nha Trang, Vietnam

“…Similar to their key role in pneumococcal transmission generally [22,[26][27][28], we find that 2-6 year old children are the likely main transmitters of pneumococcal infection to infants. This has important implications for the optimal design of pneumococcal vaccination strategies, particularly those that aim to sustain herd protection while reducing direct protection in infancy [10]: while the exact duration of protection from pneumococcal conjugate vaccines remains relatively uncertain [29], booster dose schedules may induce longer lasting protection and hence may be preferred in settings with high carriage prevalence in older children and hence a potentially high contribution to the pneumococcal infection pressure from that age group [30].…”

“…We have previously shown that pneumococcal infection risk is correlated with the frequency of physical contacts [5,6]. Here we expand that notion by including the probability that contacts are infected with pneumococci, similar to how age stratified dynamic mathematical models are constructed [3,22,23], and thus provide direct evidence for the value of social contact structure as a proxy for disease transmission routes in mathematical models. Furthermore, we suggest that the combination of social contacts and age dependent infection probabilities provides a simple and useful method to identify likely transmission routes, without the need for more complex mathematical modelling or the need for longitudinal data collection [24,25].…”

Re-emergence of Invasive Pneumococcal Disease in Germany during the Spring and Summer of 2021

“…The first age group to rebound to the pre-pandemic baseline was 0-to 4-year-olds, possibly reflecting this group's role in population-wide transmission of pneumococci. (22,23) Despite a sharp drop in the number of cases in 2020 and the first quarter of 2021, the proportion of vaccine serotypes remained consistent, both overall and stratified by age group and by geographic regional group. The southernmost regional group, consisting of two large federal states, exceeded baseline IPD cases in July, as did four additional federal states.…”

Vaccine strategies to reduce the burden of pneumococcal disease in HIV-infected adults in Africa.

“…However, herd immunity is the result of a complex interplay of factors including bacterial physiology, booster dose coverage, the average age of pneumococcal carriage, duration of vaccine protection against the carriage, and social mixing patterns [ 88–90 ]. Additionally, the high average age of carriage, intense social mixing, and the waning of PCV protection against carriage (estimated half-life is 4–6 years) may imply that, in some settings, older children are a key source of pneumococcal transmission and are not fully protected in a 2p+1 schedule [ 91 , 92 ]. A school entry PCV booster dose may be necessary to interrupt transmission and increase herd protection [ 91 ].…”