Geographical migration and fitness dynamics of Streptococcus pneumoniae

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59–1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.
This work was supported by the Wellcome Trust (grant number WT QQ2016-2021, reference 206194, to S.B., S.L. and S.D.B.); the Bill & Melinda Gates Foundation (under Investment ID INV-003570 to S.A.M., A.v.G., M.d.P., S.D. and S.N.); the NIH (grant number R01AI160780 to H.S.); and the European Research Council (grant number 804744 to H.S. and N.L.). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. We would like to thank all Global Pneumococcal Sequencing project partners; and M. O’Driscoll, S. Farr, and V. Carr for code review.
Peer Reviewed
"Article signat per xx autors/es: Sophie Belman, Noémie Lefrancq, Susan Nzenze, Sarah Downs, Mignon du Plessis, Stephanie W. Lo, The Global Pneumococcal Sequencing Consortium, Lesley McGee, Shabir A. Madhi, Anne von Gottberg, Stephen D. Bentley & Henrik Salje"
Postprint (published version)