title: Spot the difference-development of a syndrome based protein microarray for specific serological detection of multiple flavivirus infections in travelers.
abstract: BACKGROUND
  The family Flaviviridae, genus Flavivirus, holds many of the world's most prevalent arboviral diseases that are also considered the most important travel related arboviral infections. In most cases, flavivirus diagnosis in travelers is primarily based on serology as viremia is often low and typically has already been reduced to undetectable levels when symptoms set in and patients seek medical attention. Serological differentiation between flaviviruses and the false-positive results caused by vaccination and cross-reactivity among the different species, are problematic for surveillance and diagnostics of flaviviruses. Their partially overlapping geographic distribution and symptoms, combined with increase in travel, and preexisting antibodies due to flavivirus vaccinations, expand the need for rapid and reliable multiplex diagnostic tests to supplement currently used methods.
  
  
  OBJECTIVE
  We describe the development of a multiplex serological protein microarray using recombinant NS1 proteins for detection of medically important viruses within the genus Flavivirus. Sera from clinical flavivirus patients were used for primary development of the protein microarray.
  
  
  RESULTS
  Results show a high IgG and IgM sensitivity and specificity for individual NS1 antigens, and limited cross reactivity, even within serocomplexes. In addition, the serology based on this array allows for discrimination between infection and vaccination response for JEV vaccine, and no cross-reactivity with TBEV and YFV vaccine induced antibodies when testing for antibodies to other flaviviruses.
  
  
  CONCLUSIONS
  Based on these data, multiplex NS1-based protein microarray is a promising tool for surveillance and diagnosis of flaviviruses.
authors.affiliation: Erasmus Medical Centre, Viroscience Department, Rotterdam, The Netherlands; National Institute for Public Health and Environment, Center for Infectious Diseases Research and Screening, Bilthoven, The Netherlands.
authors.forename: Natalie B
authors.initials: NB
authors.lastname: Cleton
authors.affiliation: National Institute for Public Health and Environment, Center for Infectious Diseases Research and Screening, Bilthoven, The Netherlands.
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Godeke
authors.affiliation: National Institute for Public Health and Environment, Center for Infectious Diseases Research and Screening, Bilthoven, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Reimerink
authors.affiliation: Erasmus Medical Centre, Viroscience Department, Rotterdam, The Netherlands.
authors.forename: Mathias F
authors.initials: MF
authors.lastname: Beersma
authors.affiliation: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: H Rogier van
authors.initials: HR
authors.lastname: Doorn
authors.affiliation: Arbovirus and Imported Viral Diseases Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Franco
authors.affiliation: Erasmus Medical Centre, Viroscience Department, Rotterdam, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Goeijenbier
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Ctra Algete- El Casar, Valdeolmos, Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Jimenez-Clavero
authors.affiliation: Diagnostic & Reference Laboratory, Arboviral Diseases Branch, Division of Vector-Borne Diseases (DVBD), Centers for Disease Control and Prevention (CDC), Fort Collins, Colorado, United States of America.
authors.forename: Barbara W
authors.initials: BW
authors.lastname: Johnson
authors.affiliation: Centre for Biological Threats and Special Pathogens, Robert Koch-Institut, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Niedrig
authors.affiliation: National Reference Centre for Arboviruses and Hemorrhagic Fever Viruses, Department of Microbiology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Papa
authors.affiliation: DIMES-University of Bologna, Unit of Microbiology, Bologna, Italy; The Greater Romagna Area Hub Laboratory, Pievesestina, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Sambri
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands; Departamento de Parasitología, Facultad de Ciencias de la Salud, Universidad de Carabobo, Valencia, Venezuela.
authors.forename: Adriana
authors.initials: A
authors.lastname: Tami
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands; Departamento de Biología, Facultad Experimental de Ciencia y Tecnología, Universidad de Carabobo, Valencia, Venezuela.
authors.forename: Zoraida I
authors.initials: ZI
authors.lastname: Velasco-Salas
authors.affiliation: Erasmus Medical Centre, Viroscience Department, Rotterdam, The Netherlands; National Institute for Public Health and Environment, Center for Infectious Diseases Research and Screening, Bilthoven, The Netherlands.
authors.forename: Marion P G
authors.initials: MP
authors.lastname: Koopmans
authors.affiliation: Erasmus Medical Centre, Viroscience Department, Rotterdam, The Netherlands.
authors.forename: Chantal B E M
authors.initials: CB
authors.lastname: Reusken
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D003429:Cross Reactions; D000939:Epitopes; D005260:Female; D018177:Flavivirus Infections / Q000175:diagnosis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis / Q000379:methods*; D014195:Travel; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; C100315:NS1 protein, Flavivirus; D017361:Viral Nonstructural Proteins