Volume 94, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Dengue, a mosquito-borne viral illness caused by dengue virus types (DENV)-1 to DENV-4, is endemic in Puerto Rico. Severe dengue usually occurs in individuals previously infected with DENV or among infants born to previously infected mothers. To describe clinical features of dengue in infants, we retrospectively characterized dengue patients aged < 18 months reported to the Passive Dengue Surveillance System (PDSS) during 1999–2011. To determine frequency of signs, symptoms, and disease severity, case report forms and medical records were evaluated for patients who tested positive for dengue by reverse transcriptase polymerase chain reaction or anti-DENV immunoglobulin Menzyme-linked immunosorbent assay. Of 4,178 reported patients aged < 18 months, 813 (19%) were laboratory positive. Of these, most had fever (92%), rash (53%), bleeding manifestations (52%), and thrombocytopenia (52%). Medical records were available for 145 (31%) of 472 hospitalized patients, of which 40% had dengue, 23% had dengue with warning signs, and 33% had severe dengue. Mean age of patients with severe dengue was 8 months. Anti-DENV immunoglobulin G (IgG) titers were not statistically different in patients with (50%) and without (59%) severe dengue. In this study, one-third of DENV-infected infants met the severe dengue case definition. The role of maternal anti-DENV IgG in development of severe disease warrants further study in prospective cohorts of mother-infant pairs.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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  1. Halstead SB, , 2007. Dengue. Lancet 370: 16441652.[Crossref] [Google Scholar]
  2. World Health Organization, 2009. Dengue Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition. Geneva: World Health Organization. Available at: http://www.who.int/rpc/guidelines/9789241547871/en/. Accessed December 12, 2013. [Google Scholar]
  3. Kliks SC, Nimmanitya S, Nisalak A, Burke DS, , 1988. Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg 38: 411419. [Google Scholar]
  4. Halstead SB, , 1988. Pathogenesis of dengue: challenges to molecular biology. Science 239: 476481.[Crossref] [Google Scholar]
  5. Halstead SB, , 1989. Antibody, macrophages, dengue virus infection, shock, and hemorrhage: a pathogenetic cascade. Rev Infect Dis 11 (Suppl 4): S830S839.[Crossref] [Google Scholar]
  6. Takada A, Kawaoka Y, , 2003. Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. Rev Med Virol 13: 387398.[Crossref] [Google Scholar]
  7. Hawkes RA, , 1964. Enhancement of the infectivity of arboviruses by specific antisera produced in domestic fowls. Aust J Exp Biol Med Sci 42: 465482.[Crossref] [Google Scholar]
  8. Halstead SB, O'Rourke EJ, , 1977. Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody. J Exp Med 146: 201217.[Crossref] [Google Scholar]
  9. Littaua R, Kurane I, Ennis FA, , 1990. Human IgG Fc receptor II mediates antibody-dependent enhancement of dengue virus infection. J Immunol 144: 31833186. [Google Scholar]
  10. Boonnak K, Slike BM, Burgess TH, Mason RM, Wu SJ, Sun P, Porter K, Rudiman IF, Yuwono D, Puthavathana P, Marovich MA, , 2008. Role of dendritic cells in antibody-dependent enhancement of dengue virus infection. J Virol 82: 39393951.[Crossref] [Google Scholar]
  11. Halstead SB, Lan NT, Myint TT, Shwe TN, Nisalak A, Kalyanarooj S, Nimmannitya S, Soegijanto S, Vaughn DW, Endy TP, , 2002. Dengue hemorrhagic fever in infants: research opportunities ignored. Emerg Infect Dis 8: 14741479.[Crossref] [Google Scholar]
  12. Simmons CP, Chau TNB, Thuy TT, Tuan NM, Hoang DM, Thien NT, Lien le B, Quy NT, Hieu NT, Hien TT, McElnea C, Young P, Whitehead S, Hung NT, Farrar J, , 2007. Maternal antibody and viral factors in the pathogenesis of dengue virus in infants. J Infect Dis 196: 416424.[Crossref] [Google Scholar]
  13. Chau TNB, Hieu NT, Anders KL, Wolbers M, Lien le B, Hieu LT, Hien TT, Hung NT, Farrar J, Whitehead S, Simmons CP, , 2009. Dengue virus infections and maternal antibody decay in a prospective birth cohort study of Vietnamese infants. J Infect Dis 200: 18931900.[Crossref] [Google Scholar]
  14. Thein S, Aaskov J, Myint TT, Shwe TN, Saw TT, Zaw A, , 1993. Changes in levels of anti-dengue virus IgG subclasses in patients with disease of varying severity. J Med Virol 40: 102106.[Crossref] [Google Scholar]
  15. Hashira S, Okitsu-Negishi S, Yoshino K, , 2000. Placental transfer of IgG subclasses in a Japanese population. Pediatr Int 42: 337342.[Crossref] [Google Scholar]
  16. Watanaveeradej V, Endy TP, Samakoses R, Kerdpanich A, Simasathien S, Polprasert N, Aree C, Vaughn DW, Ho C, Nisalak A, , 2003. Transplacentally transferred maternal-infant antibodies to dengue virus. Am J Trop Med Hyg 69: 123128. [Google Scholar]
  17. 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. [Google Scholar]
  18. Sharp TM, Hunsperger E, Santiago GA, Muñoz-Jordan JL, Santiago LM, Rivera A, Rodríguez-Acosta RL, Gonzalez Feliciano L, Margolis HS, Tomashek KM, , 2013. Virus-specific differences in rates of disease during the 2010 Dengue epidemic in Puerto Rico. PLoS Negl Trop Dis 7: e2159.[Crossref] [Google Scholar]
  19. Martin DA, Muth DA, Brown T, Johnson AJ, Karabatsos NRJ, , 2000. Standardization of immunoglobulin M capture enzyme-linked immunosorbent assays for routine diagnosis of arboviral infections. J Clin Microbiol 38: 18231826. [Google Scholar]
  20. Santiago GA, Vergne E, Quiles Y, Cosme J, Vazquez J, Medina JF, Medina F, Colón C, Margolis H, Muñoz-Jordán JL, , 2013. Analytical and clinical performance of the CDC real time RT-PCR assay for detection and typing of dengue virus. PLoS Negl Trop Dis 7: e2311.[Crossref] [Google Scholar]
  21. Miagostovich MP, Nogueira RM, dos Santos FB, Schatzmayr HG, Araujo ESVV, , 1999. Evaluation of an IgG enzyme-linked immunosorbent assay for dengue diagnosis. J Clin Virol 14: 183189.[Crossref] [Google Scholar]
  22. World Health Organization, 1997. Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control, 2nd ed. Geneva: World Health Organization. Available at: http://www.who.int/csr/resources/publications/dengue/Denguepublication/en/. Accessed December 12, 2013. [Google Scholar]
  23. Capeding RZ, Brion JD, Caponpon MM, Gibbons RV, Jarman RG, Yoon IK, Libraty DH, , 2010. The incidence, characteristics, and presentation of dengue virus infections during infancy. Am J Trop Med Hyg 82: 330336.[Crossref] [Google Scholar]
  24. Chau TNB, Quyen NTH, Thuy TT, Tuan NM, Hoang DM, Dung NT, Lien le B, Quy NT, Hieu NT, Hieu LT, Hien TT, Hung NT, Farrar J, Simmons CP, , 2008. Dengue in Vietnamese infants–results of infection-enhancement assays correlate with age-related disease epidemiology, and cellular immune responses correlate with disease severity. J Infect Dis 198: 516524.[Crossref] [Google Scholar]
  25. Nguyen TH, Lei H-Y, Nguyen TL, Lin YS, Huang KJ, Le BL, Lin CF, Yeh TM, Do QH, Vu TQ, Chen LC, Huang JH, Lam TM, Liu CC, Halstead SB, , 2004. Dengue hemorrhagic fever in infants: a study of clinical and cytokine profiles. J Infect Dis 189: 221232.[Crossref] [Google Scholar]

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Supplementary PDF

  • Received : 22 May 2015
  • Accepted : 03 Nov 2015
  • Published online : 03 Feb 2016

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