title: Performance of Dengue Diagnostic Tests in a Single-Specimen Diagnostic Algorithm.
abstract: BACKGROUND
  Anti-dengue virus (DENV) immunoglobulin M (IgM) seroconversion has been the reference standard for dengue diagnosis. However, paired specimens are rarely obtained, and the interval for this testing negates its usefulness in guiding clinical case management. The presence of DENV viremia and appearance of IgM during the febrile phase of dengue provides the framework for dengue laboratory diagnosis by using a single serum specimen.
  
  
  METHODS
  Archived paired serum specimens (n = 1234) from patients with laboratory-confirmed dengue from 2005 through 2011 were used to determine the diagnostic performance of real-time reverse transcription polymerase chain reaction (RT-PCR), for detection of DENV serotypes 1-4, and enzyme-linked immunosorbent assays (ELISAs), for detection of DENV nonstructural protein 1 (NS1) antigen and anti-DENV IgM.
  
  
  RESULTS
  During 1-3 days after illness onset, real-time RT-PCR and NS1 antigen testing detected 82%-69% and 90%-84% of cases, respectively, as viremia levels declined, while anti-DENV IgM ELISA detected 5%-41% of cases as antibody appeared. Over the 10-day period of the febrile phase of dengue, the cumulative effect of using these 3 types of tests in a diagnostic algorithm confirmed ≥90% of dengue cases.
  
  
  CONCLUSIONS
  The use of molecular or NS1 antigen tests to detect DENV and one to detect anti-DENV IgM in a single serum specimen collected during the first 10 days of illness accurately identified ≥90% of dengue primary and secondary cases.
authors.affiliation: Dengue Branch, Division of Vector-Borne Diseases, Centers for Diseases Control and Prevention (CDC), San Juan, Puerto Rico.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Hunsperger
authors.affiliation: Dengue Branch, Division of Vector-Borne Diseases, Centers for Diseases Control and Prevention (CDC), San Juan, Puerto Rico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Muñoz-Jordán
authors.affiliation: Dengue Branch, Division of Vector-Borne Diseases, Centers for Diseases Control and Prevention (CDC), San Juan, Puerto Rico.
authors.forename: Manuela
authors.initials: M
authors.lastname: Beltran
authors.affiliation: Dengue Branch, Division of Vector-Borne Diseases, Centers for Diseases Control and Prevention (CDC), San Juan, Puerto Rico.
authors.forename: Candimar
authors.initials: C
authors.lastname: Colón
authors.affiliation: Dengue Branch, Division of Vector-Borne Diseases, Centers for Diseases Control and Prevention (CDC), San Juan, Puerto Rico.
authors.forename: Jessica
authors.initials: J
authors.lastname: Carrión
authors.affiliation: Dengue Branch, Division of Vector-Borne Diseases, Centers for Diseases Control and Prevention (CDC), San Juan, Puerto Rico.
authors.forename: Jesus
authors.initials: J
authors.lastname: Vazquez
authors.affiliation: Dengue Branch, Division of Vector-Borne Diseases, Centers for Diseases Control and Prevention (CDC), San Juan, Puerto Rico.
authors.forename: Luz Nereida
authors.initials: LN
authors.lastname: Acosta
authors.affiliation: Dengue Branch, Division of Vector-Borne Diseases, Centers for Diseases Control and Prevention (CDC), San Juan, Puerto Rico.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Medina-Izquierdo
authors.affiliation: Office of the Director, Division of Vector-Borne Diseases, CDC, Fort Collins, Colorado.
authors.forename: Kalanthe
authors.initials: K
authors.lastname: Horiuchi
authors.affiliation: Office of the Director, Division of Vector-Borne Diseases, CDC, Fort Collins, Colorado.
authors.forename: Brad J
authors.initials: BJ
authors.lastname: Biggerstaff
authors.affiliation: Dengue Branch, Division of Vector-Borne Diseases, Centers for Diseases Control and Prevention (CDC), San Juan, Puerto Rico.
authors.forename: Harold S
authors.initials: HS
authors.lastname: Margolis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000175:diagnosis*; D003716:Dengue Virus / Q000302:isolation & purification*; D003955:Diagnostic Tests, Routine / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D007223:Infant; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D012367:RNA, Viral / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007075:Immunoglobulin M; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins
keywords: NS1 antigen detection; anti-dengue virus IgM; dengue virus; dengue virus molecular diagnostics; dengue virus nonstructural protein 1 (NS1); diagnostics; enzyme-linked immunoassay