Abstract
Pneumococcal conjugate vaccination has proved highly effective in eliminating vaccine-type pneumococcal carriage and disease. However, the potential adverse effects of serotype replacement remain a major concern when implementing routine childhood pneumococcal conjugate vaccination programmes. Applying a concise predictive model, we present a ready-to-use quantitative tool to investigate the implications of serotype replacement on the net effectiveness of vaccination against invasive pneumococcal disease (IPD) and to guide in the selection of optimal vaccine serotype compositions. We utilise pre-vaccination data on pneumococcal carriage and IPD and assume partial or complete elimination of vaccine-type carriage, its replacement by non-vaccine-type carriage, and stable case-to-carrier ratios (probability of IPD per carriage episode). The model predicts that the post-vaccination IPD incidences in Finland for currently available vaccine serotype compositions can eventually decrease among the target age group of children <5 years of age by 75%. However, due to replacement through herd effects, the decrease among the older population is predicted to be much less (20–40%). We introduce a sequential algorithm for the search of optimal serotype compositions and assess the robustness of inferences to uncertainties in data and assumptions about carriage and IPD. The optimal serotype composition depends on the age group of interest and some serotypes may be highly beneficial vaccine types in one age category (e.g. 6B in children), while being disadvantageous in another. The net effectiveness will be improved only if the added serotype has a higher case-to-carrier ratio than the average case-to-carrier ratio of the current non-vaccine types and the degree of improvement in effectiveness depends on the carriage incidence of the serotype. The serotype compositions of currently available pneumococcal vaccines are not optimal and the effectiveness of vaccination in the population at large could be improved by including new serotypes in the vaccine (e.g. 22 and 9N).
Highlights
The bacterial pathogen Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide
For a given vaccine composition, corresponding either to a current or a prospective vaccine, we show in detail how the net effectiveness of vaccination under serotype replacement depends on the invasiveness of the vaccine types relative to that of the non-vaccine types
Each rectangle represents one individual serotype with the area equaling to its invasive pneumococcal disease (IPD) incidence, obtained as product of carriage incidence and case-tocarrier ratio
Summary
The bacterial pathogen Streptococcus pneumoniae (the pneumococcus) is a major cause of morbidity and mortality worldwide. Three different PCVs have been in use: PCV7 (with vaccine serotypes 4, 14, 6B, 9V, 18C, 19F and 23F), PCV10 (additional serotypes 1, 5 and 7F) and PCV13 (additional serotypes 3, 6A and 19A). Despite the successes of PCVs against their respective vaccine types, the overall public health impact of pneumococcal conjugate vaccination remains less clear. The lost VT carriage has almost invariably been replaced by non-vaccine-type (NVT) carriage [4,5]. Depending on the invasive potential of the serotypes involved, replacement in carriage leads to a varying degree of replacement in disease and may have undesirable implications on the overall pneumococcal disease burden in the population at large
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
