Follow us @PLOSMedicine Twenty pneumococcal serotyping methods put to the test Medical Doctors Express Concern about Healthcare Quality Measures in the United States EMBARGO: November 17th 2015 11am Pacific / 2pm Eastern time Twenty pneumococcal serotyping methods put to the test Many recently developed pneumococcal serotyping methods detect the dominant serotype in a laboratory or field sample, but several fail to detect minor serotypes, according to a study published this week in PLOS Medicine. This investigation of 20 current methods, conducted by Catherine Satzke of the Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Victoria, Australia, and colleagues, indicates that a microarray analysis with culture amplification is a top-performing method, but a cheaper culture and latex sweep method represents a viable alternative. About 800,000 young children, mostly living in low-income countries, die annually from pneumococcal diseases. Vaccine development requires accurate carriage studies with high sensitivity and the ability to detect multiple serotypes in individual samples. Here, in a multi-center comparative study (the PneuCarriage project), researchers used their own methods to serotype “spiked” and field samples containing combinations of Streptococcus pneumoniae bacteria. Fifteen methods detected the major serotype in the spiked samples with ≥70% sensitivity, but only eight detected minor serotypes at the same threshold. For the field samples, a culture microarray method had the best overall performance (95.8% sensitivity and 93.9% Positive Predictive Value (PPV)), while a more affordable culture and latex sweep method that has been used in low-income settings showed promising performance (79.8% sensitivity and 91.4% PPV). This study did not test all currently available serotyping methods, and assessed each method as implemented in a single, well-resourced laboratory. Nevertheless, these findings should help to guide future vaccine planning and evaluation. The authors state, “We envisage that these methods will now be applied to vaccine impact studies in lowincome settings, measuring changes in carriage before and after vaccine introduction in community carriage surveys and/or in children with pneumonia, and monitoring community carriage as a sensitive indicator of herd immunity under various vaccine schedules and levels of coverage.” Research Article Funding: This project was initially funded through the PneumoCarr Consortium (Grant 37875 funded by the Grand Challenges in Global Health Initiative which was supported by The Bill & Melinda Gates Foundation, the Foundation for the National Institutes of Health, the Wellcome Trust, and the Canadian Institutes of Health Research). The PneuCarriage project was subsequently directly funded by The Bill & Melinda Gates Foundation (www.gatesfoundation.org), Grant 52099. This project was also supported by the Murdoch Childrens Research Institute (www.mcri.edu.au) and the Victorian Government's Operational Infrastructure Support Program. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript; except for the specific roles of DCHB, DH and KPK as described in the author contributions. All authors have read, and confirm that they meet, ICMJE criteria for authorship. Competing Interests: 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 & Melinda Gates Foundation, which provided funding for this project. KPK was employed by The Bill & 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). Method group authors have a scientific and/or commercial interest in the performance of their methods, so blinded testing was conducted. Citation: Satzke C, Dunne EM, Porter BD, Klugman KP, Mulholland EK, PneuCarriage project group (2015) The PneuCarriage Project: A Multi-Centre Comparative Study to Identify The Best Serotyping Methods for Examining Pneumococcal Carriage in Vaccine Evaluation Studies. PLoS Med 12(11): e1001903. doi:10.1371/journal.pmed.1001903 Author Affiliations: Pneumococcal Research Group, Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Victoria, Australia Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom PRESS-ONLY PREVIEW OF THE ARTICLE: https://www.plos.org/wp-content/uploads/2015/11/journal.pmed_.1001903.pdf IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER: http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001903 Contact: Catherine Satzke Murdoch Childrens Research Institute Pneumococcal Research Royal Children's Hospital Flemington Rd Parkville, Vic 3052 AUSTRALIA 61 3 8341 6438 catherine.satzke@mcri.edu.au