Volume 91, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Humoral immune response against dengue virus (DENV) is an important component in dengue-endemic transmission. We conducted a cross-sectional nested cohort study to determine the seroprevalence and frequency of neutralizing antibodies against DENV serotypes in two endemic localities in the state of Morelos, Mexico. The cohort participants ( = 1,196) were screened to determine previous exposure to DENV. Overall seroprevalence was 76.6% (95% confidence interval [95% CI] = 73.6–79.2), and prevalence of neutralizing antibodies in the 5- to 9-year-old group was 82.5% (95% CI = 67.2–92.7), 45% (95% CI = 29.3–61.5), and 65% (95% CI = 48.3–79.4) for DENV-1, DENV-2, and DENV-3, respectively. For participants older than 10 years, the observed seroprevalence was above 60% for each serotype, except DENV-4 in the 10- to 25-year-old group (42.9%); 81% of humoral responses were multitypic. The outcomes of our study contribute to understanding the immune component of dengue transmission and provide focal information for the evaluation of vaccine candidates under development.


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  1. 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.[Crossref] [Google Scholar]
  2. Sánchez-Burgos GG, López-Alvarado MA, Castañeda-Desales D, Ruiz-Gómez J, Ramos-Castañeda J, , 2008. Prevalence of neutralizing antibodies to dengue virus serotypes in university students from Tabasco, Mexico. Salud Publica Mex 50: 362366.[Crossref] [Google Scholar]
  3. Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, Hunsperger E, Kroeger A, Margolis HS, Martínez E, Nathan MB, Pelegrino JL, Simmons C, Yoksan S, Peeling RW, , 2010. Dengue: a continuing global threat. Nat Rev Microbiol 8 (Suppl): S7S16.[Crossref] [Google Scholar]
  4. Gubler DJ, , 2011. Dengue, urbanization and globalization: the unholy trinity of the 21(st) century. Trop Med Health 39 (Suppl): 311.[Crossref] [Google Scholar]
  5. World Health Organization, 2010. Dengue Guidelines, 2010. Available at: http://www.health.gov.bz/www/index.php/publications/environmental-health/160-environmental-health/322-guidelines-for-dengue-diagnosis-treatment-prevention-and-control. Accessed July 7, 2011. [Google Scholar]
  6. Direccion General de Epidemiologia, Panorama epidemiologico de dengue. 2012. Available at: http://www.dgepi.salud.gob.mx/anuario/html/anuarios.html. Accessed May 15, 2012.
  7. Adams B, Holmes EC, Zhang C, Mammen MP, Jr Nimmannitya S, Kalayanarooj S, Boots M, , 2006. Cross-protective immunity can account for the alternating epidemic pattern of dengue virus serotypes circulating in Bangkok. Proc Natl Acad Sci USA 103: 1423414239.[Crossref] [Google Scholar]
  8. Guzman MG, Kouri G, , 2002. Dengue: an update. Lancet Infect Dis 2: 3342.[Crossref] [Google Scholar]
  9. Teoh BT, Sam SS, Tan KK, Johari J, Shu MH, Danlami MB, Abd-Jamil J, MatRahim N, Mahadi NM, AbuBakar S, , 2013. Dengue virus type 1 clade replacement in recurring homotypic outbreak. BMC Evol Biol 13: 213.[Crossref] [Google Scholar]
  10. Chen R, Vasilakis N, , 2011. Dengue–quo tu et quo vadis? Viruses 3: 15621608.[Crossref] [Google Scholar]
  11. Sabin AB, , 1952. Research on dengue during World War II. Am J Trop Med Hyg 1: 3050. [Google Scholar]
  12. Wahala WM, Silva AM, , 2011. The human antibody response to dengue virus infection. Viruses 3: 23742395.[Crossref] [Google Scholar]
  13. Murphy BR, Whitehead SS, , 2011. Immune response to dengue virus and prospects for a vaccine. Annu Rev Immunol 29: 587619.[Crossref] [Google Scholar]
  14. Montoya M, Gresh L, Mercado JC, Williams KL, Vargas MJ, Gutierrez G, Kuan G, Gordon A, Balmaseda A, Harris E, , 2013. Symptomatic versus inapparent outcome in repeat dengue virus infections is influenced by the time interval between infections and study year. PLoS Negl Trop Dis 7: e2357.[Crossref] [Google Scholar]
  15. Olkowski S, Forshey BM, Morrison AC, Rocha C, Vilcarromero S, Halsey ES, Kochel TJ, Scott TW, Stoddard ST, , 2013. Reduced risk of disease during postsecondary dengue virus infections. J Infect Dis 208: 10231033.[Crossref] [Google Scholar]
  16. Halstead SB, Rojanasuphot S, Sangkawibha N, , 1983. Original antigenic sin in dengue. Am J Trop Med Hyg 32: 154156. [Google Scholar]
  17. Brunkard JM, Robles López JL, Ramirez J, Cifuentes E, Rothenberg SJ, Hunsperger EA, Moore CG, Brussolo RM, Villarreal NA, Haddad BM, , 2007. Dengue fever seroprevalence and risk factors, Texas-Mexico border, 2004. Emerg Infect Dis 13: 14771483.[Crossref] [Google Scholar]
  18. Navarrete-Espinosa J, Acevedo-Vales JA, Huerta-Hernández E, Torres-Barranca J, Gavaldón-Rosas DG, , 2006. Prevalence of dengue and leptospira antibodies in the state of Veracruz, Mexico. Salud Publica Mex 48: 220228.[Crossref] [Google Scholar]
  19. Ndeffo Mbah ML, Durham DP, Medlock J, Galvani AP, , 2014. Country- and age-specific optimal allocation of dengue vaccines. J Theor Biol 342: 1522.[Crossref] [Google Scholar]
  20. Sabchareon A, Wallace D, Sirivichayakul C, Limkittikul K, Chanthavanich P, Suvannadabba S, Jiwariyavej V, Dulyachai W, Pengsaa K, Wartel TA, Moureau A, Saville M, Bouckenooghe A, Viviani S, Tornieporth NG, Lang J, , 2012. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial. Lancet 380: 15591567.[Crossref] [Google Scholar]
  21. Chao DL, Halstead SB, Halloran ME, Longini IM, Jr, 2012. Controlling dengue with vaccines in Thailand. PLoS Negl Trop Dis 6: e1876.[Crossref] [Google Scholar]
  22. Coudeville L, Garnett GP, , 2012. Transmission dynamics of the four dengue serotypes in southern Vietnam and the potential impact of vaccination. PLoS ONE 7: e51244.[Crossref] [Google Scholar]
  23. Halstead SB, , 2006. Dengue in the Americas and Southeast Asia: do they differ? Rev Panam Salud Publica 20: 407415.[Crossref] [Google Scholar]
  24. Tapia-Conyer R, Betancourt-Cravioto M, Méndez-Galván J, , 2012. Dengue: an escalating public health problem in Latin America. Paediatr Int Child Health 32 (Suppl 1): 1417.[Crossref] [Google Scholar]
  25. Douglas DL, DeRoeck DA, Mahoney RT, Wichmann O, , 2013. Will dengue vaccines be used in the public sector and if so, how? Findings from an 8-country survey of policymakers and opinion leaders. PLoS Negl Trop Dis 7: e2127.[Crossref] [Google Scholar]
  26. Martínez-Vega RA, Danis-Lozano R, Velasco-Hernández J, Díaz-Quijano FA, González-Fernández M, Santos R, Román S, Argáez-Sosa J, Nakamura M, Ramos-Castañeda J, , 2012. A prospective cohort study to evaluate peridomestic infection as a determinant of dengue transmission: protocol. BMC Public Health 12: 262.[Crossref] [Google Scholar]
  27. Instituto Nacional de Estadistica y Geografia (INEGI), Censo General de Población y vivienda 2005, 2005. Available at: http://www.inegi.org.mx. Accesses July 8, 2011.
  28. Groen J, Koraka P, Velzing J, Copra C, Osterhaus AD, , 2000. Evaluation of six immunoassays for detection of dengue virus-specific immunoglobulin M and G antibodies. Clin Diagn Lab Immunol 7: 867871. [Google Scholar]
  29. Vasilakis N, Durbin AP, da Rosa AP, Munoz-Jordan JL, Tesh RB, Weaver SC, , 2008. Antigenic relationships between sylvatic and endemic dengue viruses. Am J Trop Med Hyg 79: 128132. [Google Scholar]
  30. Elizondo-Quiroga D, Elizondo-Quiroga A, , 2013. West Nile Virus and its theories, a big puzzle in Mexico and Latin America. J Glob Infect Dis 5: 168175.[Crossref] [Google Scholar]
  31. Rothman AL, , 2011. Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol 11: 532543.[Crossref] [Google Scholar]
  32. van Panhuis WG, Gibbons RV, Endy TP, Rothman AL, Srikiatkhachorn A, Nisalak A, Burke DS, Cummings DA, , 2010. Inferring the serotype associated with dengue virus infections on the basis of pre- and postinfection neutralizing antibody titers. J Infect Dis 202: 10021010.[Crossref] [Google Scholar]
  33. Yamashiro T, Disla M, Petit A, Taveras D, Castro-Bello M, Lora-Orste M, Vardez S, Cesin AJ, Garcia B, Nishizono A, , 2004. Seroprevalence of IgG specific for dengue virus among adults and children in Santo Domingo, Dominican Republic. Am J Trop Med Hyg 71: 138143. [Google Scholar]
  34. Thai KT, Binh TQ, Giao PT, Phuong HL, Hung le Q, Van Nam N, Nga TT, Groen J, Nagelkerke N, de Vries PJ, , 2005. Seroprevalence of dengue antibodies, annual incidence and risk factors among children in southern Vietnam. Trop Med Int Health 10: 379386.[Crossref] [Google Scholar]
  35. Espinoza-Gómez F, Hernández-Suárez CM, Rendón-Ramírez R, Carrillo-Alvarez ML, Flores-González JC, , 2003. Interepidemic transmission of dengue in the city of Colima, Mexico. Salud Publica Mex 45: 365370.[Crossref] [Google Scholar]
  36. Yew YW, Ye T, Ang LW, Ng LC, Yap G, James L, Chew SK, Goh KT, , 2009. Seroepidemiology of dengue virus infection among adults in Singapore. Ann Acad Med Singapore 38: 667675. [Google Scholar]
  37. Braga C, Luna CF, Martelli CM, de Souza WV, Cordeiro MT, Alexander N, de Albuquerque M de F, Júnior JC, Marques ET, , 2010. Seroprevalence and risk factors for dengue infection in socio-economically distinct areas of Recife, Brazil. Acta Trop 113: 234240.[Crossref] [Google Scholar]
  38. Sissoko D, Ezzedine K, Giry C, Moendandzé A, Lernout T, D'Ortenzio E, Pettinelli F, Malvy D, , 2010. Seroepidemiology of dengue virus in Mayotte, Indian Ocean, 2006. PLoS ONE 5: e14141.[Crossref] [Google Scholar]
  39. Stoddard ST, Forshey BM, Morrison AC, Paz-Soldan VA, Vazquez-Prokopec GM, Astete H, Reiner RC, Jr Vilcarromero S, Elder JP, Halsey ES, Kochel TJ, Kitron U, Scott TW, , 2013. House-to-house human movement drives dengue virus transmission. Proc Natl Acad Sci USA 110: 994999.[Crossref] [Google Scholar]
  40. Raghwani J, Rambaut A, Holmes EC, Hang VT, Hien TT, Farrar J, Wills B, Lennon NJ, Birren BW, Henn MR, Simmons CP, , 2011. Endemic dengue associated with the co-circulation of multiple viral lineages and localized density-dependent transmission. PLoS Pathog 7: e1002064.[Crossref] [Google Scholar]
  41. Teixeira M da G, Barreto ML, Costa M da C, Ferreira LD, Vasconcelos PF, Cairncross S, , 2002. Dynamics of dengue virus circulation: a silent epidemic in a complex urban area. Trop Med Int Health 7: 757762.[Crossref] [Google Scholar]
  42. Van Benthem BH, Vanwambeke SO, Khantikul N, Burghoorn-Maas C, Panart K, Oskam L, Lambin EF, Somboon P, , 2005. Spatial patterns of and risk factors for seropositivity for dengue infection. Am J Trop Med Hyg 72: 201208. [Google Scholar]
  43. Trravassos da Rosa AP, Vasconcelos PF, Travassos Da Rosa ES, Rodrigues SG, Mondet B, Cruz AC, Sousa MR, Travassos Da Rosa JF, , 2000. Dengue epidemic in Belem, Para, Brazil, 1996–97. Emerg Infect Dis 6: 298301.[Crossref] [Google Scholar]
  44. Iturrino-Monge R, Avila-Agüero ML, Avila-Agüero CR, Moya-Moya T, Cañas-Coto A, Camacho-Badilla K, Zambrano-Mora B, , 2006. Seroprevalence of dengue virus antibodies in asymptomatic Costa Rican children, 2002–2003: a pilot study. Rev Panam Salud Publica 20: 3943.[Crossref] [Google Scholar]
  45. Adams B, Kapan DD, , 2009. Man bites mosquito: understanding the contribution of human movement to vector-borne disease dynamics. PLoS ONE 4: e6763.[Crossref] [Google Scholar]
  46. Yoon IK, Getis A, Aldstadt J, Rothman AL, Tannitisupawong D, Koenraadt CJM, Fansiri T, Jones JW, Morrison AC, Jarman RG, Nisalak A, Mammen MP, Jr Thammapalo S, Srikiatkhachorn A, Green S, Libraty DH, Gibbons RV, Endy T, Pimgate C, Scott TW, , 2012. Fine scale spatiotemporal clustering of dengue virus transmission in children and Aedes aegypti in rural Thai villages. PLoS Negl Trop Dis 6: e1730.[Crossref] [Google Scholar]
  47. Twiddy SS, Holmes EC, Rambaut A, , 2003. Inferring the rate and time-scale of dengue virus evolution. Mol Biol Evol 20: 122129.[Crossref] [Google Scholar]
  48. Zanotto PM, Gould EA, Gao GF, Harvey PH, Holmes EC, , 1996. Population dynamics of flaviviruses revealed by molecular phylogenies. Proc Natl Acad Sci USA 93: 548553.[Crossref] [Google Scholar]
  49. Lewis JA, Chang GJ, Lanciotti RS, Kinney RM, Mayer LW, Trent DW, , 1993. Phylogenetic relationships of dengue-2 viruses. Virology 197: 216224.[Crossref] [Google Scholar]
  50. Schieffelin JS, Costin JM, Nicholson CO, Orgeron NM, Fontaine KA, Isern S, Michael SF, Robinson JE, , 2010. Neutralizing and non-neutralizing monoclonal antibodies against dengue virus E protein derived from a naturally infected patient. J Virol 7: 28.[Crossref] [Google Scholar]
  51. Graham RR, Juffrie M, Tan R, Hayes CG, Laksono I, Ma'roef C, Erlin Sutaryo Porter KR, Halstead SB, , 1999. A prospective seroepidemiologic study on dengue in children four to nine years of age in Yogyakarta, Indonesia I. studies in 1995–1996. Am J Trop Med Hyg 61: 412419. [Google Scholar]
  52. Kuno G, Gubler DJ, Oliver A, , 1993. Use of ‘original antigenic sin’ theory to determine the serotypes of previous dengue infections. Trans R Soc Trop Med Hyg 87: 103105.[Crossref] [Google Scholar]
  53. Midgley CM, Bajwa-Joseph M, Vasanawathana S, Limpitikul W, Wills B, Flanagan A, Waiyaiya E, Tran HB, Cowper AE, Chotiyarnwong P, Grimes JM, Yoksan S, Malasit P, Simmons CP, Mongkolsapaya J, Screaton GR, , 2011. An in-depth analysis of original antigenic sin in dengue virus infection. J Virol 85: 410421.[Crossref] [Google Scholar]
  54. Simmons M, Burgess T, Lynch J, Putnak R, , 2010. Protection against dengue virus by non-replicating and live attenuated vaccines used together in a prime boost vaccination strategy. Virology 396: 280288.[Crossref] [Google Scholar]

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  • Received : 10 Mar 2014
  • Accepted : 09 Jun 2014
  • Published online : 05 Nov 2014

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