title: Characterisation of Invasive Streptococcus pneumoniae Isolated from Cambodian Children between 2007 - 2012.
abstract: BACKGROUND
  The 13-valent pneumococcal vaccine (PCV13) was introduced in Cambodia in January 2015. There are limited data concerning the common serotypes causing invasive pneumococcal disease (IPD). Knowledge of the circulating pneumococcal serotypes is important to monitor epidemiological changes before and after vaccine implementation.
  
  
  METHODS
  All episodes of IPD defined by the isolation of Streptococcus pneumoniae from blood, cerebrospinal fluid or other sterile site in Cambodian children admitted to the Angkor Hospital for Children in Siem Reap, Northwestern Cambodia, between 1st January 2007 and 1st July 2012 were retrospectively studied. Streptococcus pneumoniae isolates that could be retrieved underwent phenotypic typing and whole genome sequencing.
  
  
  RESULTS
  There were 90 Cambodian children hospitalized with IPD with a median (IQR) age of 2.3 years (0.9-6.2). The case fatality was 15.6% (95% CI 8-23). Of 50 Streptococcus pneumoniae isolates available for further testing, 46% were penicillin non-susceptible and 8% were ceftriaxone non-susceptible, 78% were cotrimoxazole resistant, 30% were erythromycin resistant and 30% chloramphenicol resistant. There were no significant changes in resistance levels over the five-year period. The most common serotypes were 1 (11/50; 22%), 23F (8/50; 16%), 14 (6/50; 12%), 5 (5/50; 10%) and 19A (3/50; 6%). Coverage by PCV7, PCV10 and PCV13 was 44%, 76% and 92% respectively. We identified novel multilocus sequence types and resistotypes using whole genome sequencing.
  
  
  CONCLUSIONS
  This study suggests IPD is an important disease in Cambodian children and can have a significant mortality. PCV13 coverage of the serotypes determined in studied strains was high and consistent with another recent study. The phenotypic resistance patterns observed were similar to other regional studies. The use of whole genome sequencing in the present study provides additional typing and resistance information together with the description of novel sequence types and resistotypes.
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Angkor Hospital for Children, Siem Reap, Cambodia.|Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Catrin E
authors.identifier: http://orcid.org/0000-0002-8639-9846
authors.initials: CE
authors.lastname: Moore
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Adam
authors.initials: A
authors.lastname: Giess
authors.affiliation: Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Sona
authors.initials: S
authors.lastname: Soeng
authors.affiliation: Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Poda
authors.initials: P
authors.lastname: Sar
authors.affiliation: Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Varun
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Pheakdey
authors.initials: P
authors.lastname: Nhoung
authors.affiliation: Microbiology Department, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Rachel
authors.initials: R
authors.lastname: Bousfield
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.|Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Paul
authors.initials: P
authors.lastname: Turner
authors.affiliation: Angkor Hospital for Children, Siem Reap, Cambodia.|Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Nicole
authors.initials: N
authors.lastname: Stoesser
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.|Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.|School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Parry
mesh_terms: D000293:Adolescent; D002160:Cambodia; D002648:Child; D002675:Child, Preschool; D004269:DNA, Bacterial; D024881:Drug Resistance, Bacterial; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D011008:Pneumococcal Infections / Q000382:microbiology*; D017422:Sequence Analysis, DNA; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*
chemical_list: D004269:DNA, Bacterial