Abstract
Predicting how pathogen populations will change over time is challenging. Such has been the case with Streptococcus pneumoniae, an important human pathogen, and the pneumococcal conjugate vaccines (PCVs), which target only a fraction of the strains in the population. Here, we use the frequencies of accessory genes to predict changes in the pneumococcal population after vaccination, hypothesizing that these frequencies reflect negative frequency-dependent selection (NFDS) on the gene products. We find that the standardized predicted fitness of a strain estimated by an NFDS-based model at the time the vaccine is introduced enables to predict whether the strain increases or decreases in prevalence following vaccination. Further, we are able to forecast the equilibrium post-vaccine population composition and assess the invasion capacity of emerging lineages. Overall, we provide a method for predicting the impact of an intervention on pneumococcal populations with potential application to other bacterial pathogens in which NFDS is a driving force.
Footnotes
↵† Co-senior authors
Pamela P Martinez pmartinez{at}hsph.harvard.edu, Brian J Arnold brianjohnarnold{at}gmail.com, Lindsay R Grant lgrant10{at}jhu.edu, Jukka Corander jukka.corander{at}medisin.uio.no, Christophe Fraser christophe.fraser{at}bdi.ox.ac.uk, Nicholas J Croucher n.croucher{at}imperial.ac.uk, Laura Hammitt lhammitt{at}jhu.edu, Raymond Reid rreid2{at}jhu.edu, Mathuram Santosham msantosham{at}jhu.edu, Robert R Weatherholtz rweathe1{at}jhu.edu, Stephen D Bentley sdb{at}sanger.ac.uk, Katherine L O’Brien obrienk{at}who.int, Marc Lipsitch mlipsitc{at}hsph.harvard.edu, William P Hanage whanage{at}hsph.harvard.edu
Revised figures and analysis, additional data set added, revised supplemental material