title: International external quality control assessment for the serological diagnosis of dengue infections.
abstract: BACKGROUND
  Dengue is endemic to the tropics and subtropics, and the most frequent of arthropod-borne viral diseases. Reliable diagnosis of dengue infection is important not only in clinical care but also in disease surveillance, the control of outbreaks, and the development of new vaccines. The diagnosis of dengue infection is usually established by a variety of commercial or in-house serological protocols. The European Network for the Diagnostics of Imported Viral Diseases (ENIVD) recognized the need to survey the accuracy of dengue serological diagnostics in current use, and organized an external quality assurance (EQA) study of dengue serological practice in diagnostic laboratories.
  
  
  METHODS
  A 15-sample panel, consisting of sera reactive against dengue plus specificity and negative controls, was sent to 48 laboratories for serological testing. The results returned by the participating laboratories were anonymized, scored, and subjected to comparison and statistical analysis.
  
  
  RESULTS
  Ten laboratories rated all samples correctly with regard to IgM, and only three achieved the full score for IgG detection. The main handicaps in assay performance were suboptimal sensitivity of in-house IgM detection protocols by comparison with better-performing commercial ELISA tests, and the presence of IgG cross-reactivity with heterologous flaviviruses. Differences of detail in the methodology of dengue IgG antibody detection appear to underlie the disparities in accuracy observed between laboratories.
  
  
  CONCLUSIONS
  This EQA study demonstrates that there is room for many laboratories to improve sensitivity in the detection of anti-dengue virus IgM antibodies, against the benchmark set by commercial antibody capture ELISA tests. The EQA shows also that cross-reactivity is a continuing issue, and IgG detection protocols must be optimized to increase their specificity.
authors.affiliation: Robert Koch Institute, Nordufer 20, 13353, Berlin, Germany. Domingo-CarrascoC@rki.de.
authors.forename: Cristina
authors.initials: C
authors.lastname: Domingo
authors.affiliation: National Institute of Health Dr. Ricardo Jorge, Av. Liberdade 5, 2965 575, Águas de Moura, Portugal. m.joao.alves@insa.min-saude.pt.
authors.forename: María Joao
authors.initials: MJ
authors.lastname: Alves
authors.affiliation: Instituto de Salud Carlos III, Carretera de Majadahonda a Pozuelo, Km 2, 28220, Majadahonda, Madrid, Spain. fory@isciii.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: de Ory
authors.affiliation: Robert Koch Institute, Nordufer 20, 13353, Berlin, Germany. TeichmannA@rki.de.
authors.forename: Anette
authors.initials: A
authors.lastname: Teichmann
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, 20359, Hamburg, Germany. schmitz@bnitm.de.
authors.forename: Herbert
authors.initials: H
authors.lastname: Schmitz
authors.affiliation: Biomatrica Inc., 5627 Oberlin Drive, Suite 120, 92121, San Diego, CA, USA. rmuller@biomatrica.com.
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
authors.affiliation: Robert Koch Institute, Nordufer 20, 13353, Berlin, Germany. NiedrigM@rki.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Niedrig
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D003715:Dengue / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D003716:Dengue Virus / Q000276:immunology / Q000302:isolation & purification; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000592:standards; D005060:Europe / Q000453:epidemiology; D006801:Humans; D007753:Laboratories / Q000592:standards; D011237:Predictive Value of Tests; D011785:Quality Assurance, Health Care; D012426:Russia / Q000453:epidemiology; D012698:Serologic Tests / Q000379:methods / Q000592:standards*
chemical_list: D000914:Antibodies, Viral