TY - JOUR
T1 - Evaluation of pneumococcal serotyping of nasopharyngeal-carriage isolates by latex agglutination, whole-genome sequencing (PneumoCaT), and DNA microarray in a high-pneumococcal-carriage-prevalence population in Malawi
AU - Swarthout, Todd D.
AU - Gori, Andrea
AU - Bar-Zeev, Naor
AU - Kamng'Ona, Arox W.
AU - Mwalukomo, Thandie S.
AU - Bonomali, Farouck
AU - Nyirenda, Roseline
AU - Brown, Comfort
AU - Msefula, Jacquline
AU - Everett, Dean
AU - Mwansambo, Charles
AU - Gould, Katherine
AU - Hinds, Jason
AU - Heyderman, Robert S.
AU - French, Neil
N1 - Funding Information:
We thank the individuals who participated in this study. We also thank the local authorities for their support. We are grateful for the hospitality of the QECH ART Clinic, led by Ken Malisita. Our thanks also extend to the MLW laboratory management team, led by Brigitte Denis and George Selemani. We acknowledge financial support from the Bill and Melinda Gates Foundation, USA (grant OPP117653); a project grant jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/ DFID Concordat agreement, also as part of the EDCTP2 program supported by the European Union (grant MR/N023129/1); and a recruitment award from the Wellcome Trust (grant 106846/Z/15/Z). The MLW Clinical Research Program is supported by a Strategic Award from the Wellcome Trust, UK (award 206545/Z/17/Z). The National Institute for Health Research (NIHR) Global Health Research Unit on Mucosal Pathogens received UK aid from the UK Government (project number 16/136/46). The funders had no role in study design, collection, analysis, data interpretation, the writing of the report, or the decision to submit the paper for publication. The corresponding author had full access to the study data and, together with the senior authors, had final responsibility for the decision to submit for publication. T.D.S., A.G., R.S.H., and N.F. are supported by the NIHR Global Health Research Unit on Mucosal Pathogens using UK aid from the UK Government. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Naor Bar-Zeev reports investigator-initiated research grants from GlaxoSmithKline Biologicals and from Takeda Pharmaceuticals outside the submitted work. Jason Hinds is an investigator in studies undertaken on behalf of St George's, University of London or BUGS Bioscience that are sponsored or funded by vaccine manufacturers, including Pfizer, GlaxoSmithKline, and Sanofi Pasteur. He is also a cofounder and shareholder of BUGS Bioscience, a not-for-profit spinout of St George's, University of London. No other authors declare competing interests.
Funding Information:
We acknowledge financial support from the Bill and Melinda Gates Foundation, USA (grant OPP117653); a project grant jointly funded by the UK Medical Research Council
Funding Information:
The funders had no role in study design, collection, analysis, data interpretation, the writing of the report, or the decision to submit the paper for publication. The corresponding author had full access to the study data and, together with the senior authors, had final responsibility for the decision to submit for publication. T.D.S., A.G., R.S.H., and N.F. are supported by the NIHR Global Health Research Unit on Mucosal Pathogens using UK aid from the UK Government. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
Funding Information:
Naor Bar-Zeev reports investigator-initiated research grants from GlaxoSmithKline Biologicals and from Takeda Pharmaceuticals outside the submitted work. Jason Hinds is an investigator in studies undertaken on behalf of St George’s, University of London or BUGS Bioscience that are sponsored or funded by vaccine manufacturers, including Pfizer, GlaxoSmithKline, and Sanofi Pasteur. He is also a cofounder and shareholder of BUGS Bioscience, a not-for-profit spinout of St George’s, University of London. No other authors declare competing interests.
Funding Information:
(MRC) and the UK Department for International Development (DFID) under the MRC/ DFID Concordat agreement, also as part of the EDCTP2 program supported by the European Union (grant MR/N023129/1); and a recruitment award from the Wellcome Trust (grant 106846/Z/15/Z). The MLW Clinical Research Program is supported by a Strategic Award from the Wellcome Trust, UK (award 206545/Z/17/Z). The National Institute for Health Research (NIHR) Global Health Research Unit on Mucosal Pathogens received UK aid from the UK Government (project number 16/136/46).
Publisher Copyright:
Copyright © 2020 Swarthout et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
PY - 2021/1
Y1 - 2021/1
N2 - Accurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for evaluating and formulating pneumococcal vaccines and for informing vaccine policy. For this reason, we evaluated the concordance between pneumococcal serotyping results by latex agglutination, whole-genome sequencing (WGS) with PneumoCaT, and DNA microarray for samples from community carriage surveillance in Blantyre, Malawi. Nasopharyngeal swabs were collected according to WHO recommendations between 2015 and 2017 by using stratified random sampling among study populations. Participants included healthy children 3 to 6 years old (vaccinated with the 13-valent pneumococcal conjugate vaccine [PCV13] as part of the Expanded Program on Immunization [EPI]), healthy children 5 to 10 years old (age-ineligible for PCV13), and HIV-infected adults (18 to 40 years old) on antiretroviral therapy (ART). For phenotypic serotyping, we used a 13-valent latex kit (Statens Serum Institut [SSI], Denmark). For genomic serotyping, we applied the PneumoCaT pipeline to whole-genome sequence libraries. For molecular serotyping by microarray, we used the BUGS Bioscience Senti-SP microarray. A total of 1,347 samples were analyzed. Concordance was 90.7% (95% confidence interval [CI], 89.0 to 92.2%) between latex agglutination and PneumoCaT, 95.2% (95% CI, 93.9 to 96.3%) between latex agglutination and the microarray, and 96.6% (95% CI, 95.5 to 97.5%) between the microarray and PneumoCaT. By detecting additional vaccine serotype (VT) pneumococci carried at low relative abundances (median, 8%), the microarray increased VT detection by 31.5% over that by latex serotyping. To conclude, all three serotyping methods were highly concordant in identifying dominant serotypes. Latex serotyping is accurate in identifying vaccine serotypes and requires the least expertise and resources for field implementation and analysis. However, WGS, which adds population structure, and microarray, which adds multiple-serotype carriage, should be considered at regional reference laboratories for investigating the importance of vaccine serotypes at low relative abundances in transmission and disease.
AB - Accurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for evaluating and formulating pneumococcal vaccines and for informing vaccine policy. For this reason, we evaluated the concordance between pneumococcal serotyping results by latex agglutination, whole-genome sequencing (WGS) with PneumoCaT, and DNA microarray for samples from community carriage surveillance in Blantyre, Malawi. Nasopharyngeal swabs were collected according to WHO recommendations between 2015 and 2017 by using stratified random sampling among study populations. Participants included healthy children 3 to 6 years old (vaccinated with the 13-valent pneumococcal conjugate vaccine [PCV13] as part of the Expanded Program on Immunization [EPI]), healthy children 5 to 10 years old (age-ineligible for PCV13), and HIV-infected adults (18 to 40 years old) on antiretroviral therapy (ART). For phenotypic serotyping, we used a 13-valent latex kit (Statens Serum Institut [SSI], Denmark). For genomic serotyping, we applied the PneumoCaT pipeline to whole-genome sequence libraries. For molecular serotyping by microarray, we used the BUGS Bioscience Senti-SP microarray. A total of 1,347 samples were analyzed. Concordance was 90.7% (95% confidence interval [CI], 89.0 to 92.2%) between latex agglutination and PneumoCaT, 95.2% (95% CI, 93.9 to 96.3%) between latex agglutination and the microarray, and 96.6% (95% CI, 95.5 to 97.5%) between the microarray and PneumoCaT. By detecting additional vaccine serotype (VT) pneumococci carried at low relative abundances (median, 8%), the microarray increased VT detection by 31.5% over that by latex serotyping. To conclude, all three serotyping methods were highly concordant in identifying dominant serotypes. Latex serotyping is accurate in identifying vaccine serotypes and requires the least expertise and resources for field implementation and analysis. However, WGS, which adds population structure, and microarray, which adds multiple-serotype carriage, should be considered at regional reference laboratories for investigating the importance of vaccine serotypes at low relative abundances in transmission and disease.
KW - Africa
KW - Latex agglutination
KW - Methodology
KW - Microarray
KW - Serotyping
KW - Streptococcus pneumoniae
KW - Whole-genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85098486015&partnerID=8YFLogxK
U2 - 10.1128/JCM.02103-20
DO - 10.1128/JCM.02103-20
M3 - Article
C2 - 33087431
AN - SCOPUS:85098486015
SN - 0095-1137
VL - 59
JO - Journal of Clinical Microbiology
JF - Journal of Clinical Microbiology
IS - 1
M1 - e02103-20
ER -
