title: Diagnostic performance of near-patient testing for influenza.
abstract: BACKGROUND
  Rapid diagnosis of influenza is important for controlling outbreaks and starting antiviral therapy. Direct antigen detection (DAD) is rapid, but lacks sensitivity, whereas nucleic acid amplification testing (NAT) is more sensitive, but also more time-consuming.
  
  
  OBJECTIVE
  To evaluate the performance of a rapid isothermal NAT and two DADs.
  
  
  METHODS
  During February-May 2014, we tested 211 consecutive patients with influenza-like illness using a commercial isothermal NAT (Alere™ Influenza A&B) as well as the DAD Sofia(®) Influenza A+B and BinaxNOW(®) Influenza A&B for detection of influenza-A and -B virus. RespiFinder-22(®) a commercial multiplex NAT served as reference test. Serial 10-fold dilutions of influenza-A and -B cell culture supernatants were examined. Another 225 patient samples were tested during December 2014-February 2015.
  
  
  RESULTS
  Compared to RespiFinder-22(®), the isothermal NAT Alere™ Influenza A&B, and the DAD Sofia(®) Influenza A+B and BinaxNOW(®) Influenza A&B had sensitivities of 77.8%, 59.3% and 29.6%, and specificities of 99.5%, 98.9% and 100%, respectively, for the first 211 patient samples. Alere™ Influenza A&B showed 85.7% sensitivity and 100% specificity in the second cohort. Isothermal NAT was 10-100-fold more sensitive compared to DAD for influenza virus culture supernatants with a lower limit of detection of 5000-50,000 copies/mL. The average turn-around time (TAT) of isothermal NAT and DADs was 15min, but increased to 110min for Alere™ Influenza A&B, 30min for BinaxNOW(®) Influenza A&B, and 45min for Sofia(®) Influenza A+B, when analyzing batches of 6 samples.
  
  
  CONCLUSIONS
  Simple sample processing and a TAT of 15min render isothermal NAT Alere™ Influenza A&B suitable for sequential near-patient testing, but the TAT advantage is lost when testing of larger series.
authors.affiliation: Division of Infection Diagnostics, Department Biomedicine (Haus Petersplatz), University of Basel, Switzerland.
authors.forename: Christiane
authors.initials: C
authors.lastname: Beckmann
authors.affiliation: Division of Infection Diagnostics, Department Biomedicine (Haus Petersplatz), University of Basel, Switzerland; Transplantation & Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel, Switzerland; Infectious Disease & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland. Electronic address: hans.hirsch@unibas.ch.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Hirsch
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007223:Infant; D007251:Influenza, Human / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D019095:Point-of-Care Systems; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013997:Time Factors; D055815:Young Adult
keywords: Antigen detection; Community-acquired respiratory virus; Influenza virus; Isothermal PCR; Nucleic acid amplification testing (NAT); Turn-around time (TAT)