title: Increased sensitivity of NS1 ELISA by heat dissociation in acute dengue 4 cases.
abstract: Dengue is an acute febrile illness considered the major arboviral disease in terms of morbidity, mortality, economic impact and dissemination worldwide. Brazil accounts for the highest notification rate, with circulation of all four dengue serotypes. The NS1 antigen is a dengue highly conserved specific soluble glycoprotein essential for viral replication and viability that can be detected 0 to 18 days from the onset of fever (peak first 3 days). It induces a strong humoral response and is known as a complement-fixing antigen. Lower NS1 test sensitivity occurs in secondary dengue infections probably due to immune complex formation impairing antigen detection by ELISA.
  
  
  
  We compared the sensitivity of NS1 ELISA in heat dissociated and non-dissociated samples from 156 RT-PCR confirmed acute dengue-4 cases from 362 prospectively enrolled patients.
  
  
  
  Secondary infections accounted for 83.3% of cases. NS1 ELISA was positive in 42.5% and indeterminate in 10.2% of dengue-4 cases. After heat dissociation, 7 negative and 16 indeterminate samples turned positive, increasing the overall test sensitivity to 57.7%.
  
  
  
  Although it is time consuming and requires the use of specific laboratory equipment, NS1 ELISA combined with heat dissociation could be a slightly better alternative for triage in suspected dengue cases.
authors.affiliation: National Institute of Infectious Diseases Evandro Chagas, Laboratory of Clinical Epidemiology, Oswaldo Cruz Foundation, Av. Brasil, 4036 sala 201 A - Manguinhos, Rio de Janeiro, CEP: 21040-361, Brazil. sibellebuonora@gmail.com.
authors.forename: Sibelle Nogueira
authors.initials: SN
authors.lastname: Buonora
authors.affiliation: Oswaldo Cruz Institute, Instituto Oswaldo Cruz - Pavilhão Hélio e Peggy Pereira, Flavivirus Laboratory, Oswaldo Cruz Foundation, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro, CEP: 21040-900, Brazil.
authors.forename: Flavia Barreto
authors.initials: FB
authors.lastname: Dos Santos
authors.affiliation: Germano Sinval Faria Teaching Primary Care Center, National School of Public Health, Oswaldo Cruz Foundation, Rua Leopoldo Bulhões, 1480 - Bonsucesso, Rio de Janeiro, CEP: 21041-210, Brazil.
authors.forename: Regina Paiva
authors.initials: RP
authors.lastname: Daumas
authors.affiliation: National Institute of Infectious Diseases Evandro Chagas, Laboratory of Clinical Epidemiology, Oswaldo Cruz Foundation, Av. Brasil, 4036 sala 201 A - Manguinhos, Rio de Janeiro, CEP: 21040-361, Brazil.
authors.forename: Sonia Regina Lambert
authors.initials: SR
authors.lastname: Passos
authors.affiliation: Oswaldo Cruz Institute, Instituto Oswaldo Cruz - Pavilhão Hélio e Peggy Pereira, Flavivirus Laboratory, Oswaldo Cruz Foundation, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro, CEP: 21040-900, Brazil.
authors.forename: Manoela Heringer
authors.initials: MH
authors.lastname: da Silva
authors.affiliation: Oswaldo Cruz Institute, Instituto Oswaldo Cruz - Pavilhão Hélio e Peggy Pereira, Flavivirus Laboratory, Oswaldo Cruz Foundation, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro, CEP: 21040-900, Brazil.
authors.forename: Monique Rocha
authors.initials: MR
authors.lastname: de Lima
authors.affiliation: Oswaldo Cruz Institute, Instituto Oswaldo Cruz - Pavilhão Hélio e Peggy Pereira, Flavivirus Laboratory, Oswaldo Cruz Foundation, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro, CEP: 21040-900, Brazil.
authors.forename: Rita Maria Ribeiro
authors.initials: RM
authors.lastname: Nogueira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D060085:Coinfection / Q000276:immunology / Q000821:virology; D003430:Cross-Sectional Studies; D003715:Dengue / Q000175:diagnosis* / Q000503:physiopathology; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D005334:Fever / Q000175:diagnosis / Q000821:virology; D006023:Glycoproteins / Q000097:blood / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D017361:Viral Nonstructural Proteins / Q000097:blood / Q000276:immunology*; D055815:Young Adult
chemical_list: D006023:Glycoproteins; C000621009:NS1 protein, Dengue virus type 4; D017361:Viral Nonstructural Proteins
keywords: Accuracy; DENV-4; Dengue diagnosis; Immune complex dissociation; NS1 ELISA