title: High frequency of pre-existing neutralizing antibody responses in patients with dengue during an outbreak in Central Brazil.
abstract: BACKGROUND
  This study aims to identify dengue neutralizing antibody response in patients with dengue from a well-characterized cohort during an outbreak in central Brazil, 2012-2013.
  
  
  METHODS
  We analyzed paired samples from 40 patients with severe dengue and 20 patients with dengue. Eligibility criteria were: IgM, NS1Ag and/or RT-PCR positivity and positive IgG result. Plaque reduction neutralization test (PRNT50) from DENV-1 to DENV-4 was performed to identify serotype-specific NAbs response. An infecting serotype was defined as ≥4-fold increase in DENV NAbs in paired samples. Monotypic response was classified as PRNT50≥ 1/20 to only one DENV serotype, and multitypic response was considered to be PRNT50≥ 1/20 to two or more serotypes simultaneously.
  
  
  RESULTS
  Patients were mainly adults. Virological dengue infection was confirmed by RT-PCR: DENV-4(n = 14) and DENV-1(n = 10). Forty-four out of 60(73.3 %) patients had NAbs to DENV-4, DENV-1(68.3 %), DENV-2(68.3 %) and DENV-3(61.6 %) respectively. Fifteen percent of the cases presented monotypic response, whereas 85 % had multitypic response. DENV-4 infected-patients presented the greatest difference in PRNT50titers compared with other serotypes. Pre-existing DENV NAbs was not correlated with disease severity. This was the first time that DENV-4 was implicated in an epidemic in the region.
  
  
  CONCLUSIONS
  Our data indicates high exposure of multiple DENV serotypes in all age groups in the pre-dengue vaccine era and also previous to Zika virus introduction in Brazil.
authors.affiliation: Institute of Tropical Pathology and Public Health of Federal University of Goiás, Rua 235, St Universitário, Goiânia, 74.605-050, GO, Brazil. angelafarmaceutica@hotmail.com.|Public Health Laboratory of Secretaria Estadual de Saúde de Goiás (LACEN-GO), Av. Contorno, 3.556, Jd. Bela Vista, 74.853-120, Goiânia, GO, Brazil. angelafarmaceutica@hotmail.com.
authors.forename: Angela Ferreira Lopes
authors.initials: AF
authors.lastname: de Teive E Argolo
authors.affiliation: Pharmacy College of Federal University of Goiás, Av. Universitaria, St. Universitario, 74.605-220, Goiânia, GO, Brazil.
authors.forename: Valéria Christina
authors.initials: VC
authors.lastname: de Rezende Féres
authors.affiliation: Centro de Pesquisas Aggeu Magalhães da Fundação Oswaldo, Av. Prof. Moraes Rego, 1235, Cidade Universitária, 50.670-901, Recife, PE, Brazil.
authors.forename: Marli Tenório
authors.initials: MT
authors.lastname: Cordeiro
authors.affiliation: Institute of Tropical Pathology and Public Health of Federal University of Goiás, Rua 235, St Universitário, Goiânia, 74.605-050, GO, Brazil.
authors.forename: Lucimeire Antonelli
authors.initials: LA
authors.lastname: da Silveira
authors.affiliation: Institute of Tropical Pathology and Public Health of Federal University of Goiás, Rua 235, St Universitário, Goiânia, 74.605-050, GO, Brazil.
authors.forename: Adriana Oliveira
authors.initials: AO
authors.lastname: Guilarde
authors.affiliation: Centro de Pesquisas Aggeu Magalhães da Fundação Oswaldo, Av. Prof. Moraes Rego, 1235, Cidade Universitária, 50.670-901, Recife, PE, Brazil.|Center for Vaccine Research, Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Ernesto Torres
authors.initials: ET
authors.lastname: de Azevedo Marques
authors.affiliation: Centro de Pesquisas Aggeu Magalhães da Fundação Oswaldo, Av. Prof. Moraes Rego, 1235, Cidade Universitária, 50.670-901, Recife, PE, Brazil.
authors.forename: Wayner Vieira
authors.initials: WV
authors.lastname: de Souza
authors.affiliation: Institute of Tropical Pathology and Public Health of Federal University of Goiás, Rua 235, St Universitário, Goiânia, 74.605-050, GO, Brazil.|Centro de Pesquisas Aggeu Magalhães da Fundação Oswaldo, Av. Prof. Moraes Rego, 1235, Cidade Universitária, 50.670-901, Recife, PE, Brazil.
authors.forename: Celina Maria Turchi
authors.initials: CM
authors.lastname: Martelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000235:genetics / Q000276:immunology; D001938:Brazil / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003715:Dengue / Q000453:epidemiology* / Q000276:immunology*; D003716:Dengue Virus / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity; D004196:Disease Outbreaks; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D065288:Serogroup; D019595:Severe Dengue / Q000453:epidemiology / Q000276:immunology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral
keywords: Brazil; Dengue fever; Dengue virus; Neutralizing antibody