Incidence of Dengue Virus Infection in School-Aged Children in Puerto Rico: A Prospective Seroepidemiologic Study

D. Fermín Argüello National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; Office of the Director, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado; University of Puerto Rico School of Medicine, San Juan, Puerto Rico; Food and Drug Administration, Silver Spring, Maryland; Sanofi Aventis, Paris, France; Sanofi Pasteur, Lyon, France

Search for other papers by D. Fermín Argüello in
Current site
Google Scholar
PubMed
Close
,
Kay M. Tomashek National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; Office of the Director, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado; University of Puerto Rico School of Medicine, San Juan, Puerto Rico; Food and Drug Administration, Silver Spring, Maryland; Sanofi Aventis, Paris, France; Sanofi Pasteur, Lyon, France

Search for other papers by Kay M. Tomashek in
Current site
Google Scholar
PubMed
Close
,
Luz Quiñones National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; Office of the Director, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado; University of Puerto Rico School of Medicine, San Juan, Puerto Rico; Food and Drug Administration, Silver Spring, Maryland; Sanofi Aventis, Paris, France; Sanofi Pasteur, Lyon, France

Search for other papers by Luz Quiñones in
Current site
Google Scholar
PubMed
Close
,
Manuela Beltran National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; Office of the Director, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado; University of Puerto Rico School of Medicine, San Juan, Puerto Rico; Food and Drug Administration, Silver Spring, Maryland; Sanofi Aventis, Paris, France; Sanofi Pasteur, Lyon, France

Search for other papers by Manuela Beltran in
Current site
Google Scholar
PubMed
Close
,
Luz Acosta National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; Office of the Director, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado; University of Puerto Rico School of Medicine, San Juan, Puerto Rico; Food and Drug Administration, Silver Spring, Maryland; Sanofi Aventis, Paris, France; Sanofi Pasteur, Lyon, France

Search for other papers by Luz Acosta in
Current site
Google Scholar
PubMed
Close
,
Luis M. Santiago National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; Office of the Director, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado; University of Puerto Rico School of Medicine, San Juan, Puerto Rico; Food and Drug Administration, Silver Spring, Maryland; Sanofi Aventis, Paris, France; Sanofi Pasteur, Lyon, France

Search for other papers by Luis M. Santiago in
Current site
Google Scholar
PubMed
Close
,
Brad J. Biggerstaff National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; Office of the Director, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado; University of Puerto Rico School of Medicine, San Juan, Puerto Rico; Food and Drug Administration, Silver Spring, Maryland; Sanofi Aventis, Paris, France; Sanofi Pasteur, Lyon, France

Search for other papers by Brad J. Biggerstaff in
Current site
Google Scholar
PubMed
Close
,
Enid J. Garcia-Rivera National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; Office of the Director, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado; University of Puerto Rico School of Medicine, San Juan, Puerto Rico; Food and Drug Administration, Silver Spring, Maryland; Sanofi Aventis, Paris, France; Sanofi Pasteur, Lyon, France

Search for other papers by Enid J. Garcia-Rivera in
Current site
Google Scholar
PubMed
Close
,
Wellington Sun National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; Office of the Director, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado; University of Puerto Rico School of Medicine, San Juan, Puerto Rico; Food and Drug Administration, Silver Spring, Maryland; Sanofi Aventis, Paris, France; Sanofi Pasteur, Lyon, France

Search for other papers by Wellington Sun in
Current site
Google Scholar
PubMed
Close
,
Laurence Pollissard-Gadroy National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; Office of the Director, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado; University of Puerto Rico School of Medicine, San Juan, Puerto Rico; Food and Drug Administration, Silver Spring, Maryland; Sanofi Aventis, Paris, France; Sanofi Pasteur, Lyon, France

Search for other papers by Laurence Pollissard-Gadroy in
Current site
Google Scholar
PubMed
Close
,
Christine Luxemburger National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; Office of the Director, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado; University of Puerto Rico School of Medicine, San Juan, Puerto Rico; Food and Drug Administration, Silver Spring, Maryland; Sanofi Aventis, Paris, France; Sanofi Pasteur, Lyon, France

Search for other papers by Christine Luxemburger in
Current site
Google Scholar
PubMed
Close
, and
Elizabeth Hunsperger National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; Office of the Director, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado; University of Puerto Rico School of Medicine, San Juan, Puerto Rico; Food and Drug Administration, Silver Spring, Maryland; Sanofi Aventis, Paris, France; Sanofi Pasteur, Lyon, France

Search for other papers by Elizabeth Hunsperger in
Current site
Google Scholar
PubMed
Close
Restricted access

Dengue is a potentially fatal acute febrile illness caused by the mosquito-borne dengue viruses (DENV-1 to -4). To estimate DENV seroincidence in school-aged children, a 1-year prospective cohort study was conducted in Patillas, Puerto Rico; 10- to 18-year-olds (N = 345) were randomly selected from 13 public schools. At enrollment, 49.8% of the entire cohort had DENV immunoglobulin G (IgG) anti-DENV antibodies, and there were individuals with neutralizing antibodies specific to each of the four DENV. The mean age of participants with incident DENV infection was 13.4 years. The 1-year seroincidence rate was 5.6%, and 61.1% of infections were inapparent. Having IgG anti-DENV at enrollment was associated with seroincidence (risk ratio = 6.8). Acute febrile illnesses during the study period were captured by a fever diary and an enhanced and passive surveillance system in the municipios of Patillas and Guayama. In summary, at enrollment, nearly one-half of the participants had a prior DENV infection, with the highest incidence in the 10- to 11-year-olds, of which most were inapparent infections, and symptomatic infections were considered mild.

Author Notes

* Address correspondence to Elizabeth Hunsperger, CDC Dengue Branch, 1324 Calle Cañada, San Juan, PR 00920-3860. E-mail: enh4@cdc.gov

Financial support: This work was supported, in part, under Cooperative Research and Development Agreement (CRDA) CID-01-138-02 with Sanofi Pasteur, Inc.

Authors' addresses: D. Fermín Argüello, Kay M. Tomashek, Luz Quiñones, Manuela Beltran, Luz Acosta, Luis M. Santiago, and Elizabeth Hunsperger, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico, E-mails: dfmanito@gmail.com, kay.tomashek@nih.gov, luzquinones@hotmail.com, mvb6@cdc.gov, lda9@cdc.gov, and enh4@cdc.gov. Brad J. Biggerstaff, Office of the Director, National Centers for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, E-mail: bkb5@cdc.gov. Enid J. Garcia-Rivera, University of Puerto Rico School of Medicine, San Juan, Puerto Rico, E-mail: enid.garcia3@upr.edu. Wellington Sun, Food and Drug Administration, Silver Spring, MD, E-mail: Wellington.Sun@fda.hhs.gov. Laurence Pollissard-Gadroy, Sanofi Aventis, Paris, France, E-mail: laurencehmp@gmail.com. Christine Luxemburger, Sanofi Pasteur, Lyon, France, E-mail: Christine.Luxemburger@sanofipasteur.com.

  • 1.

    World Health Organization (WHO), 2006. Scientific Working Group on Dengue: Meeting Report. Geneva: WHO.

  • 2.

    Rigau-Perez JG, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV, 1998. Dengue and dengue haemorrhagic fever. Lancet 352: 971977.

  • 3.

    Gubler DJ, Meltzer M, 1999. Impact of dengue/dengue hemorrhagic fever on the developing world. Adv Virus Res 53: 3570

  • 4.

    Halstead SB, 2005. More dengue, more questions. Emerg Infect Dis 11: 740741.

  • 5.

    Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint GR, Simmons CP, Scott TW, Farrar JJ, Hay SI, 2013. The global distribution and burden of dengue. Nature 496: 504507.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Likosky WH, Calisher CH, Michelson AL, Correa-Coronas R, Henderson BE, Feldman RA, 1973. An epidemiologic study of dengue type 2 in Puerto Rico, 1969. Am J Epidemiol 97: 264275.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Rigau-Perez JG, Vorndam AV, Clark GG, 2001. The dengue and dengue hemorrhagic fever epidemic in Puerto Rico, 1994–1995. Am J Trop Med Hyg 64: 6774.

  • 8.

    Rigau-Perez JG, Ayala-Lopez A, Garcia-Rivera EJ, Hudson SM, Vorndam V, Reiter P, Cano MP, Clark GG, 2002. The reappearance of dengue-3 and a subsequent dengue-4 and dengue-1 epidemic in Puerto Rico in 1998. Am J Trop Med Hyg 67: 355362.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Tomashek KM, Rivera A, Muñoz-Jordan JL, Hunsperger E, Santiago L, Padro O, Garcia E, Sun W, 2009. Description of a large island-wide outbreak of dengue in Puerto Rico, 2007. Am J Trop Med Hyg 81: 467474.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Neff JM, Morris L, Gonzalez-Alcover R, Coleman PH, Lyss SB, Negron H, 1967. Dengue fever in a Puerto Rican community. Am J Epidemiol 86: 162184.

  • 11.

    Waterman SH, Novak RJ, Sather GE, Bailey RE, Rios I, Gubler DJ, 1985. Dengue transmission in two Puerto Rican communities in 1982. Am J Trop Med Hyg 34: 625632.

  • 12.

    Morens DM, Rigau-Perez JG, Lopez-Correa RH, Moore CG, Ruiz-Tiben EE, Sather GE, Chiriboga J, Eliason DA, Casta-Velez A, Woodall JP, 1986. Dengue in Puerto Rico, 1977: public health response to characterize and control an epidemic of multiple serotypes. Am J Trop Med Hyg 35: 197211.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Rodriguez-Figueroa L, Rigau-Perez JG, Suarez EL, Reiter P, 1995. Risk factors for dengue infection during an outbreak in Yanes, Puerto Rico in 1991. Am J Trop Med Hyg 52: 496502.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    O'Leary DR, Rigau-Perez JG, Hayes EB, Vorndam AV, Clark GG, Gubler DJ, 2002. Assessment of dengue risk in relief workers in Puerto Rico after Hurricane Georges, 1998. Am J Trop Med Hyg 66: 3539.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Ramos MM, Arguello DF, Luxemburger C, Quinones L, Munoz JL, Beatty M, Lang J, Tomashek KM, 2008. Epidemiological and clinical observations on patients with dengue in Puerto Rico: results from the first year of enhanced surveillance—June 2005–May 2006. Am J Trop Med Hyg 79: 123127.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Martin DA, Muth DA, Brown T, Johnson AJ, Karabatsos N, Roehrig JT, 2000. Standardization of immunoglobulin M capture enzyme-linked immunosorbent assays for routine diagnosis of arboviral infections. J Clin Microbiol 38: 18231826.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Miagostovich MP, Nogueira RM, dos Santos FB, Schatzmayr HG, Araujo ES, Vorndam V, 1999. Evaluation of an IgG enzyme-linked immunosorbent assay for dengue diagnosis. J Clin Virol 14: 183189.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Vorndam V, Beltran M, 2002. Enzyme-linked immunosorbent assay-format microneutralization test for dengue viruses. Am J Trop Med Hyg 66: 208212.

  • 19.

    World Health Organization (WHO), 1997. Dengue Haemorrhagic Fever: Diagnosis, Treatment, and Control. Geneva: WHO.

  • 20.

    Särndal C-E, Lundström S, 2005. Estimation in Surveys with Nonresponse. West Sussex, England: Wiley.

  • 21.

    Rigau-Perez JG, Ayala-Lopez A, Vorndam AV, Clark GG, 2001. Dengue activity in Puerto Rico during an interepidemic period (1995–1997). Am J Trop Med Hyg 64: 7583.

  • 22.

    Chappell WA, Calisher CH, Toole RF, Maness KC, Sasso DR, Henderson BE, 1971. Comparison of three methods used to isolate dengue virus type 2. Appl Microbiol 22: 11001103.

  • 23.

    Gubler DJ, Kuno G, Sather GE, Velez M, Oliver A, 1984. Mosquito cell-cultures and specific monoclonal-antibodies in surveillance for dengue viruses. Am J Trop Med Hyg 33: 158165.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Sangkawibha N, Rojanasuphot S, Ahandrik S, Viriyapongse S, Jatanasen S, Salitul V, Phanthumachinda B, Halstead SB, 1984. Risk factors in dengue shock syndrome: a prospective epidemiologic study in Rayong, Thailand. I. The 1980 outbreak. Am J Epidemiol 120: 653669.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Burke DS, Nisalak A, Johnson DE, Scott RM, 1988. A prospective study of dengue infections in Bangkok. Am J Trop Med Hyg 38: 172180.

  • 26.

    Thein S, Aung MM, Shwe TN, Aye M, Zaw A, Aye K, Aye KM, Aaskov J, 1997. Risk factors in dengue shock syndrome. Am J Trop Med Hyg 56: 566572.

  • 27.

    Endy TP, Chunsuttiwat S, Nisalak A, Libraty DH, Green S, Rothman AL, Vaughn DW, Ennis FA, 2002. Epidemiology of inapparent and symptomatic acute dengue virus infection: a prospective study of primary school children in Kamphaeng Phet, Thailand. Am J Epidemiol 156: 4051.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Yoon IK, Rothman AL, Tannitisupawong D, Srikiatkhachorn A, Jarman RG, Aldstadt J, Nisalak A, Mammen MP Jr, Thammapalo S, Green S, Libraty DH, Gibbons RV, Getis A, Endy T, Jones JW, Koenraadt CJ, Morrison AC, Fansiri T, Pimgate C, Scott TW, 2012. Underrecognized mildly symptomatic viremic dengue virus infections in rural thai schools and villages. J Infect Dis 206: 389398.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Balmaseda A, Hammond SN, Tellez Y, Imhoff L, Rodriguez Y, Saborio SI, Mercado JC, Perez L, Videa E, Almanza E, Kuan G, Reyes M, Saenz L, Amador JJ, Harris E, 2006. High seroprevalence of antibodies against dengue virus in a prospective study of schoolchildren in Managua, Nicaragua. Trop Med Int Health 11: 935942.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Thai KTD, Nga TTT, Van Nam N, Phuong HL, Giao PT, Hung LQ, Binh TQ, van Doornum GJJ, de Vries PJ, 2007. Incidence of primary dengue virus infections in southern Vietnamese children and reactivity against other flaviviruses. Trop Med Int Health 12: 15531557.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Balmaseda A, Standish K, Mercado JC, Matute JC, Tellez Y, Saborio S, Hammond SN, Nunez A, Aviles W, Henn MR, Holmes EC, Gordon A, Coloma J, Kuan G, Harris E, 2010. Trends in patterns of dengue transmission over 4 years in a pediatric cohort study in Nicaragua. J Infect Dis 201: 514.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Nguyen TKT, Luxemburger C, Nguyen TT, Pollissard-Gadroy L, Vu TQH, Pham VB, Nguyen NR, Wartel TA, Lang J, 2010. A prospective cohort study of dengue infection in schoolchildren in Long Xuyen, Viet Nam. Trans R Soc Trop Med Hyg 104: 592600.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Restrepo BN, Piedrahita LD, Agudelo IY, Parra-Henao G, Osorio JE, 2012. Frequency and clinical features of dengue infection in a schoolchildren cohort from medellin, Colombia. J Trop Med 2012: 120496.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Endy TP, Nisalak A, Chunsuttitwat S, Vaughn DW, Green S, Ennis FA, Rothman AL, Libraty DH, 2004. Relationship of preexisting dengue virus (DV) neutralizing antibody levels to viremia and severity of disease in a prospective cohort study of DV infection in Thailand. J Infect Dis 189: 9901000.

    • PubMed
    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 240 237 87
Full Text Views 890 18 0
PDF Downloads 171 13 0
 
Membership Banner
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save