TY - JOUR
T1 - The PneuCarriage Project
T2 - A Multi-Centre Comparative Study to Identify the Best Serotyping Methods for Examining Pneumococcal Carriage in Vaccine Evaluation Studies
AU - PneuCarriage project group
AU - Satzke, Catherine
AU - Dunne, Eileen M.
AU - Porter, Barbara D.
AU - Klugman, Keith P.
AU - Mulholland, E. Kim
AU - Vidal, Jorge E.
AU - Sakai, Fuminori
AU - Strachan, Janet E.
AU - Hay Burgess, Deborah C.
AU - Holtzman, Douglas
AU - Boelsen, K.
AU - Habib, Maha
AU - Manning, Jayne
AU - Ortika, Belinda D.
AU - Pell, Casey L.
AU - Smyth, Jenna A.
AU - Antonio, Martin
AU - Klugman, Keith P.
AU - O’Brien, Katherine L.
AU - Robins-Browne, Roy M.
AU - Anthony Scott, J.
AU - Saha, Samir K.
AU - Russell, Fiona M.
AU - Greenhill, Andrew R.
AU - Lehmann, Deborah
AU - Adrian, Peter V.
AU - Madhi, Shabir A.
AU - Rubin, Lorry G.
AU - Rizvi, Atqia
AU - Hinds, Jason
AU - Gould, Katherine A.
AU - Kong, Fanrong
AU - Oftadeh, Shahin
AU - Gilbert, Gwendolyn L.
AU - Feng, Lu
AU - Cao, Boyang
AU - Paranhos-Baccalà, Gláucia
AU - Telles, Jean Noel
AU - Messaoudi, Mélina
AU - Borrow, Ray
AU - Stanford, Elaine
AU - George, Robert
AU - Sheppard, Carmen
AU - Brugger, Silvio D.
AU - Mühlemann, Kathrin
AU - Hilty, Markus
AU - Rivera-Olivero, Ismar A.
AU - de Waard, Jacobus H.
AU - Charalambous, Bambos M.
AU - Leung, Marcus H.
N1 - Funding Information:
I have read the journal's policy and the authors of the manuscript have the following competing interests: DCHB and DH are previous employees of the Bill and Melinda Gates Foundation, which provided funding for this project. KPK was employed by the Bill and Melinda Gates Foundation towards the completion of the project, but was not involved in funding the project. KPK is a member of the Editorial Board of PLOS Medicine. CS and EMD were awarded the Robert Austrian Award which is funded by Pfizer. Authors have served on advisory boards for Merck (CS, KPK, EKM), GSK (KPK, EKM), and Pfizer (KPK). Research group authors have a scientific and/or commercial interest in the performance of their methods, so blinded testing was conducted.
Publisher Copyright:
© 2015 Satzke et al.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Background: The pneumococcus is a diverse pathogen whose primary niche is the nasopharynx. Over 90 different serotypes exist, and nasopharyngeal carriage of multiple serotypes is common. Understanding pneumococcal carriage is essential for evaluating the impact of pneumococcal vaccines. Traditional serotyping methods are cumbersome and insufficient for detecting multiple serotype carriage, and there are few data comparing the new methods that have been developed over the past decade. We established the PneuCarriage project, a large, international multi-centre study dedicated to the identification of the best pneumococcal serotyping methods for carriage studies. Methods and Findings: Reference sample sets were distributed to 15 research groups for blinded testing. Twenty pneumococcal serotyping methods were used to test 81 laboratory-prepared (spiked) samples. The five top-performing methods were used to test 260 nasopharyngeal (field) samples collected from children in six high-burden countries. Sensitivity and positive predictive value (PPV) were determined for the test methods and the reference method (traditional serotyping of >100 colonies from each sample). For the alternate serotyping methods, the overall sensitivity ranged from 1% to 99% (reference method 98%), and PPV from 8% to 100% (reference method 100%), when testing the spiked samples. Fifteen methods had ≥70% sensitivity to detect the dominant (major) serotype, whilst only eight methods had ≥70% sensitivity to detect minor serotypes. For the field samples, the overall sensitivity ranged from 74.2% to 95.8% (reference method 93.8%), and PPV from 82.2% to 96.4% (reference method 99.6%). The microarray had the highest sensitivity (95.8%) and high PPV (93.7%). The major limitation of this study is that not all of the available alternative serotyping methods were included. Conclusions: Most methods were able to detect the dominant serotype in a sample, but many performed poorly in detecting the minor serotype populations. Microarray with a culture amplification step was the top-performing method. Results from this comprehensive evaluation will inform future vaccine evaluation and impact studies, particularly in low-income settings, where pneumococcal disease burden remains high.
AB - Background: The pneumococcus is a diverse pathogen whose primary niche is the nasopharynx. Over 90 different serotypes exist, and nasopharyngeal carriage of multiple serotypes is common. Understanding pneumococcal carriage is essential for evaluating the impact of pneumococcal vaccines. Traditional serotyping methods are cumbersome and insufficient for detecting multiple serotype carriage, and there are few data comparing the new methods that have been developed over the past decade. We established the PneuCarriage project, a large, international multi-centre study dedicated to the identification of the best pneumococcal serotyping methods for carriage studies. Methods and Findings: Reference sample sets were distributed to 15 research groups for blinded testing. Twenty pneumococcal serotyping methods were used to test 81 laboratory-prepared (spiked) samples. The five top-performing methods were used to test 260 nasopharyngeal (field) samples collected from children in six high-burden countries. Sensitivity and positive predictive value (PPV) were determined for the test methods and the reference method (traditional serotyping of >100 colonies from each sample). For the alternate serotyping methods, the overall sensitivity ranged from 1% to 99% (reference method 98%), and PPV from 8% to 100% (reference method 100%), when testing the spiked samples. Fifteen methods had ≥70% sensitivity to detect the dominant (major) serotype, whilst only eight methods had ≥70% sensitivity to detect minor serotypes. For the field samples, the overall sensitivity ranged from 74.2% to 95.8% (reference method 93.8%), and PPV from 82.2% to 96.4% (reference method 99.6%). The microarray had the highest sensitivity (95.8%) and high PPV (93.7%). The major limitation of this study is that not all of the available alternative serotyping methods were included. Conclusions: Most methods were able to detect the dominant serotype in a sample, but many performed poorly in detecting the minor serotype populations. Microarray with a culture amplification step was the top-performing method. Results from this comprehensive evaluation will inform future vaccine evaluation and impact studies, particularly in low-income settings, where pneumococcal disease burden remains high.
UR - http://www.scopus.com/inward/record.url?scp=85000501013&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85000501013&partnerID=8YFLogxK
U2 - 10.1371/journal.pmed.1001903
DO - 10.1371/journal.pmed.1001903
M3 - Article
C2 - 26575033
AN - SCOPUS:85000501013
SN - 1549-1277
VL - 12
JO - PLoS medicine
JF - PLoS medicine
IS - 11
M1 - e1001903
ER -