title: Rapid diagnostic tests for dengue virus infection in febrile Cambodian children: diagnostic accuracy and incorporation into diagnostic algorithms.
abstract: BACKGROUND
  Dengue virus (DENV) infection is prevalent across tropical regions and may cause severe disease. Early diagnosis may improve supportive care. We prospectively assessed the Standard Diagnostics (Korea) BIOLINE Dengue Duo DENV rapid diagnostic test (RDT) to NS1 antigen and anti-DENV IgM (NS1 and IgM) in children in Cambodia, with the aim of improving the diagnosis of DENV infection.
  
  
  RESULTS
  We enrolled children admitted to hospital with non-localised febrile illnesses during the 5-month DENV transmission season. Clinical and laboratory variables, and DENV RDT results were recorded at admission. Children had blood culture and serological and molecular tests for common local pathogens, including reference laboratory DENV NS1 antigen and IgM assays. 337 children were admitted with non-localised febrile illness over 5 months. 71 (21%) had DENV infection (reference assay positive). Sensitivity was 58%, and specificity 85% for RDT NS1 and IgM combined. Conditional inference framework analysis showed the additional value of platelet and white cell counts for diagnosis of DENV infection. Variables associated with diagnosis of DENV infection were not associated with critical care admission (70 children, 21%) or mortality (19 children, 6%). Known causes of mortality were melioidosis (4), other sepsis (5), and malignancy (1). 22 (27%) children with a positive DENV RDT had a treatable other infection.
  
  
  CONCLUSIONS
  The DENV RDT had low sensitivity for the diagnosis of DENV infection. The high co-prevalence of infections in our cohort indicates the need for a broad microbiological assessment of non-localised febrile illness in these children.
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Carter
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Kate R
authors.initials: KR
authors.lastname: Emary
authors.forename: Catrin E
authors.initials: CE
authors.lastname: Moore
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; Angkor Hospital for Children, Siem Reap, Kingdom of Cambodia.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Moore
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Parry
authors.affiliation: Angkor Hospital for Children, Siem Reap, Kingdom of Cambodia.
authors.forename: Soeng
authors.initials: S
authors.lastname: Sona
authors.affiliation: Angkor Hospital for Children, Siem Reap, Kingdom of Cambodia.
authors.forename: Hor
authors.initials: H
authors.lastname: Putchhat
authors.affiliation: Angkor Hospital for Children, Siem Reap, Kingdom of Cambodia.
authors.forename: Sin
authors.initials: S
authors.lastname: Reaksmey
authors.affiliation: Angkor Hospital for Children, Siem Reap, Kingdom of Cambodia.
authors.forename: Ngoun
authors.initials: N
authors.lastname: Chanpheaktra
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Nicole
authors.initials: N
authors.lastname: Stoesser
authors.affiliation: Biological and Environmental Sciences, University of Stirling, Stirling, United Kingdom.
authors.forename: Andrew D M
authors.initials: AD
authors.lastname: Dobson
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.affiliation: Angkor Hospital for Children, Siem Reap, Kingdom of Cambodia.
authors.forename: Varun
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Blacksell
mesh_terms: D000465:Algorithms; D002160:Cambodia; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000175:diagnosis* / Q000401:mortality / Q000821:virology; D003716:Dengue Virus / Q000276:immunology*; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D005334:Fever / Q000175:diagnosis / Q000821:virology; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D007223:Infant; D008297:Male; D015995:Prevalence; D011446:Prospective Studies; D011933:Reagent Kits, Diagnostic; D056910:Republic of Korea; D012680:Sensitivity and Specificity; D017361:Viral Nonstructural Proteins / Q000276:immunology*
chemical_list: D007075:Immunoglobulin M; D011933:Reagent Kits, Diagnostic; D017361:Viral Nonstructural Proteins