Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi

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 pne...

Täydet tiedot

Bibliografiset tiedot
Päätekijät: Chaguza, C, Cornick, J, Andam, C, Gladstone, R, Alaerts, M, Musicha, P, Peno, C, Bar-Zeev, N, Kamng'ona, A, Kiran, A, Msefula, C, McGee, L, Breiman, R, Kadioglu, A, French, N, Heyderman, R, Hanage, W, Bentley, S, Everett, D
Aineistotyyppi: Journal article
Kieli:English
Julkaistu: Elsevier 2017
_version_ 1826256923357347840
author Chaguza, C
Cornick, J
Andam, C
Gladstone, R
Alaerts, M
Musicha, P
Peno, C
Bar-Zeev, N
Kamng'ona, A
Kiran, A
Msefula, C
McGee, L
Breiman, R
Kadioglu, A
French, N
Heyderman, R
Hanage, W
Bentley, S
Everett, D
author_facet Chaguza, C
Cornick, J
Andam, C
Gladstone, R
Alaerts, M
Musicha, P
Peno, C
Bar-Zeev, N
Kamng'ona, A
Kiran, A
Msefula, C
McGee, L
Breiman, R
Kadioglu, A
French, N
Heyderman, R
Hanage, W
Bentley, S
Everett, D
author_sort Chaguza, C
collection OXFORD
description 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.
first_indexed 2024-03-06T18:09:57Z
format Journal article
id oxford-uuid:02ab0dba-b4e6-48ae-9e7f-d359d7729154
institution University of Oxford
language English
last_indexed 2024-03-06T18:09:57Z
publishDate 2017
publisher Elsevier
record_format dspace
spelling oxford-uuid:02ab0dba-b4e6-48ae-9e7f-d359d77291542022-03-26T08:42:02ZPopulation genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in MalawiJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:02ab0dba-b4e6-48ae-9e7f-d359d7729154EnglishSymplectic Elements at OxfordElsevier2017Chaguza, CCornick, JAndam, CGladstone, RAlaerts, MMusicha, PPeno, CBar-Zeev, NKamng'ona, AKiran, AMsefula, CMcGee, LBreiman, RKadioglu, AFrench, NHeyderman, RHanage, WBentley, SEverett, DINTRODUCTION: 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.
spellingShingle Chaguza, C
Cornick, J
Andam, C
Gladstone, R
Alaerts, M
Musicha, P
Peno, C
Bar-Zeev, N
Kamng'ona, A
Kiran, A
Msefula, C
McGee, L
Breiman, R
Kadioglu, A
French, N
Heyderman, R
Hanage, W
Bentley, S
Everett, D
Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi
title Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi
title_full Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi
title_fullStr Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi
title_full_unstemmed Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi
title_short Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi
title_sort population genetic structure antibiotic resistance capsule switching and evolution of invasive pneumococci before conjugate vaccination in malawi
work_keys_str_mv AT chaguzac populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT cornickj populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT andamc populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT gladstoner populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT alaertsm populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT musichap populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT penoc populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT barzeevn populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT kamngonaa populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT kirana populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT msefulac populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT mcgeel populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT breimanr populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT kadioglua populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT frenchn populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT heydermanr populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT hanagew populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT bentleys populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi
AT everettd populationgeneticstructureantibioticresistancecapsuleswitchingandevolutionofinvasivepneumococcibeforeconjugatevaccinationinmalawi