TY - JOUR
T1 - Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi
AU - Chaguza, Chrispin
AU - Cornick, Jennifer E.
AU - Andam, Cheryl P.
AU - Gladstone, Rebecca A.
AU - Alaerts, Maaike
AU - Musicha, Patrick
AU - Peno, Chikondi
AU - Bar-Zeev, Naor
AU - Kamng'ona, Arox W.
AU - Kiran, Anmol M.
AU - Msefula, Chisomo L.
AU - McGee, Lesley
AU - Breiman, Robert F.
AU - Kadioglu, Aras
AU - French, Neil
AU - Heyderman, Robert S.
AU - Hanage, William P.
AU - Bentley, Stephen D.
AU - Everett, Dean B.
N1 - Funding Information:
This work was supported by the Bill and Melinda Gates Foundation, Wellcome Trust – United Kingdom awards number OPP1023440 (DBE and SDB) and OPP1034556 (RFB, SDB and LM). Activities at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme were supported by a core award number 084679/Z/08/Z from the Wellcome Trust. CC acknowledges PhD Studentship funding from the Commonwealth Scholarship Commission in the UK. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies and the Centers for Disease Control and Prevention (CDC).
Publisher Copyright:
© 2017 The Authors
PY - 2017/8/16
Y1 - 2017/8/16
N2 - Introduction Pneumococcal infections cause a high death toll in Sub Saharan Africa (SSA) but the recently rolled out pneumococcal conjugate vaccines (PCV) will reduce the disease burden. To better understand the population impact of these vaccines, comprehensive analysis of large collections of pneumococcal isolates sampled prior to vaccination is required. Here we present a population genomic study of the invasive pneumococcal isolates sampled before the implementation of PCV13 in Malawi. Materials and methods We retrospectively sampled and whole genome sequenced 585 invasive isolates from 2004 to 2010. We determine the pneumococcal population genetic structure and assessed serotype prevalence, antibiotic resistance rates, and the occurrence of serotype switching. Results Population structure analysis revealed 22 genetically distinct sequence clusters (SCs), which consisted of closely related isolates. Serotype 1 (ST217), a vaccine-associated serotype in clade SC2, showed highest prevalence (19.3%), and was associated with the highest MDR rate (81.9%) followed by serotype 12F, a non-vaccine serotype in clade SC10 with an MDR rate of 57.9%. Prevalence of serotypes was stable prior to vaccination although there was an increase in the PMEN19 clone, serotype 5 ST289, in clade SC1 in 2010 suggesting a potential undetected local outbreak. Coalescent analysis revealed recent emergence of the SCs and there was evidence of natural capsule switching in the absence of vaccine induced selection pressure. Furthermore, majority of the highly prevalent capsule-switched isolates were associated with acquisition of vaccine-targeted capsules. Conclusions This study provides descriptions of capsule-switched serotypes and serotypes with potential to cause serotype replacement post-vaccination such as 12F. Continued surveillance is critical to monitor these serotypes and antibiotic resistance in order to design better infection prevention and control measures such as inclusion of emerging replacement serotypes in future conjugate vaccines.
AB - Introduction Pneumococcal infections cause a high death toll in Sub Saharan Africa (SSA) but the recently rolled out pneumococcal conjugate vaccines (PCV) will reduce the disease burden. To better understand the population impact of these vaccines, comprehensive analysis of large collections of pneumococcal isolates sampled prior to vaccination is required. Here we present a population genomic study of the invasive pneumococcal isolates sampled before the implementation of PCV13 in Malawi. Materials and methods We retrospectively sampled and whole genome sequenced 585 invasive isolates from 2004 to 2010. We determine the pneumococcal population genetic structure and assessed serotype prevalence, antibiotic resistance rates, and the occurrence of serotype switching. Results Population structure analysis revealed 22 genetically distinct sequence clusters (SCs), which consisted of closely related isolates. Serotype 1 (ST217), a vaccine-associated serotype in clade SC2, showed highest prevalence (19.3%), and was associated with the highest MDR rate (81.9%) followed by serotype 12F, a non-vaccine serotype in clade SC10 with an MDR rate of 57.9%. Prevalence of serotypes was stable prior to vaccination although there was an increase in the PMEN19 clone, serotype 5 ST289, in clade SC1 in 2010 suggesting a potential undetected local outbreak. Coalescent analysis revealed recent emergence of the SCs and there was evidence of natural capsule switching in the absence of vaccine induced selection pressure. Furthermore, majority of the highly prevalent capsule-switched isolates were associated with acquisition of vaccine-targeted capsules. Conclusions This study provides descriptions of capsule-switched serotypes and serotypes with potential to cause serotype replacement post-vaccination such as 12F. Continued surveillance is critical to monitor these serotypes and antibiotic resistance in order to design better infection prevention and control measures such as inclusion of emerging replacement serotypes in future conjugate vaccines.
KW - Antibiotic resistance
KW - Capsule switching
KW - Evolution
KW - Population structure
KW - Streptococcus pneumoniae
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U2 - 10.1016/j.vaccine.2017.07.009
DO - 10.1016/j.vaccine.2017.07.009
M3 - Article
C2 - 28711389
AN - SCOPUS:85023601996
SN - 0264-410X
VL - 35
SP - 4594
EP - 4602
JO - Vaccine
JF - Vaccine
IS - 35
ER -