Volume 95, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Dengue is one of the most problematic vector-borne diseases in the Philippines, with an estimated 842,867 cases resulting in medical costs of $345 million U.S. dollars annually. In December 2015, the first dengue vaccine, known as chimeric yellow fever virus–dengue virus tetravalent dengue vaccine, was approved for use in the Philippines and is given to children 9 years of age. To estimate the cost-effectiveness of dengue vaccination in the Philippines, we developed an age-structured model of dengue transmission and vaccination. Using our model, we compared two vaccination scenarios entailing routine vaccination programs both with and without catch-up vaccination. Our results indicate that the higher the cost of vaccination, the less cost-effective the dengue vaccination program. With the current dengue vaccination program that vaccinates children 9 years of age, dengue vaccination is cost-effective for vaccination costs up to $70 from a health-care perspective and up to $75 from a societal perspective. Under a favorable scenario consisting of 1 year of catch-up vaccinations that target children 9–15 years of age, followed by regular vaccination of 9-year-old children, vaccination is cost-effective at costs up to $72 from a health-care perspective and up to $78 from a societal perspective. In general, dengue vaccination is expected to reduce the incidence of both dengue fever and dengue hemorrhagic fever /dengue shock syndrome. Our results demonstrate that even at relatively low vaccine efficacies, age-targeted vaccination may still be cost-effective provided the vaccination cost is sufficiently low.

[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.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Alera MT, Srikiatkhachorn A, Velasco JM, Tac-An IA, Lago CB, Clapham HE, Fernandez S, Levy JW, Thaisomboonsuk B, Klungthong C, Macareo LR, Nisalak A, Hermann L, Villa D, Yoon IK, , 2016. Incidence of dengue virus infection in adults and children in a prospective longitudinal cohort in the Philippines. PLoS Negl Trop Dis 10: e0004337.[Crossref] [Google Scholar]
  2. Shepard DS, Undurraga EA, Halasa YA, , 2013. Economic and disease burden of dengue in southeast Asia. PLoS Negl Trop Dis 7: e2055.[Crossref] [Google Scholar]
  3. Edillo FE, Halasa YA, Largo FM, Erasmo JN, Amoin NB, Alera MT, Yoon IK, Alcantara AC, Shepard DS, , 2015. Economic cost and burden of dengue in the Philippines. Am J Trop Med Hyg 92: 360366.[Crossref] [Google Scholar]
  4. Murrell S, Wu SC, Butler M, , 2011. Review of dengue virus and the development of a vaccine. Biotechnol Adv 29: 239247.[Crossref] [Google Scholar]
  5. Tozan Y, , 2016. Current issues in the economics of vaccination against dengue. Expert Rev Vaccines 15: 110.[Crossref] [Google Scholar]
  6. Sanofi Pasteur, 2015. Sanofi Pasteur's Dengue Vaccine Approved in the Philippines. Lyon, France: Sanofi Pasteur. Available at: http://www.sanofipasteur.com/en/articles/sanofi-pasteur-dengue-vaccine-approved-in-the-philippines.aspx. [Google Scholar]
  7. 2016. Mexico dengue vaccine first. Nat Biotechnol 34: 8. [Google Scholar]
  8. Capeding MR, Tran NH, Hadinegoro SR, Ismail HI, Chotpitayasunondh T, Chua MN, Luong CQ, Rusmil K, Wirawan DN, Nallusamy R, Pitisuttithum P, Thisyakorn U, Yoon IK, van der Vliet D, Langevin E, Laot T, Hutagalung Y, Frago C, Boaz M, Wartel TA, Tornieporth NG, Saville M, Bouckenooghe A, CYD14 Study Group, , 2014. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial. Lancet 384: 13581365.[Crossref] [Google Scholar]
  9. Halstead SB, Russell PK, , 2016. Protective and immunological behavior of chimeric yellow fever dengue vaccine. Vaccine 34: 16431647.[Crossref] [Google Scholar]
  10. Gibbons RV, Kalanarooj S, Jarman RG, Nisalak A, Vaughn DW, Endy TP, Mammen MP, Jr Srikiatkhachorn A, , 2007. Analysis of repeat hospital admissions for dengue to estimate the frequency of third or fourth dengue infections resulting in admissions and dengue hemorrhagic fever, and serotype sequences. Am J Trop Med Hyg 77: 910913. [Google Scholar]
  11. 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: 10261033.[Crossref] [Google Scholar]
  12. Pandey A, Medlock J, , 2015. The introduction of dengue vaccine may temporarily cause large spikes in prevalence. Epidemiol Infect 143: 12761286.[Crossref] [Google Scholar]
  13. Halstead SB, , 2003. Neutralization and antibody-dependent enhancement of dengue viruses. Adv Virus Res 60: 421467.[Crossref] [Google Scholar]
  14. Nagao Y, Koelle K, , 2008. Decreases in dengue transmission may act to increase the incidence of dengue hemorrhagic fever. Proc Natl Acad Sci USA 105: 22382243.[Crossref] [Google Scholar]
  15. Adams B, Boots M, , 2006. Modelling the relationship between antibody-dependent enhancement and immunological distance with application to dengue. J Theor Biol 242: 337346.[Crossref] [Google Scholar]
  16. Johansson MA, Hombach J, Cummings DA, , 2011. Models of the impact of dengue vaccines: a review of current research and potential approaches. Vaccine 29: 58605868.[Crossref] [Google Scholar]
  17. Focks DA, Daniels E, Haile DG, Keesling JE, , 1995. A simulation model of the epidemiology of urban dengue fever: literature analysis, model development, preliminary validation, and samples of simulation results. Am J Trop Med Hyg 53: 489506. [Google Scholar]
  18. Wearing HJ, Rohani P, , 2006. Ecological and immunological determinants of dengue epidemics. Proc Natl Acad Sci USA 103: 1180211807.[Crossref] [Google Scholar]
  19. Coutinho FA, Burattini MN, Lopez LF, Massad E, , 2006. Threshold conditions for a non-autonomous epidemic system describing the population dynamics of dengue. Bull Math Biol 68: 22632282.[Crossref] [Google Scholar]
  20. Ferguson N, Anderson R, Gupta S, , 1999. The effect of antibody-dependent enhancement on the transmission dynamics and persistence of multiple-strain pathogens. Proc Natl Acad Sci USA 96: 790794.[Crossref] [Google Scholar]
  21. Ferguson NM, Donnelly CA, Anderson RM, , 1999. Transmission dynamics and epidemiology of dengue: insights from age-stratified sero-prevalence surveys. Philos Trans R Soc Lond B Biol Sci 354: 757768.[Crossref] [Google Scholar]
  22. Billings L, Schwartz IB, Shaw LB, McCrary M, Burke DS, Cummings DA, , 2007. Instabilities in multiserotype disease models with antibody-dependent enhancement. J Theor Biol 246: 1827.[Crossref] [Google Scholar]
  23. Bianco S, Shaw LB, Schwartz IB, , 2009. Epidemics with multistrain interactions: the interplay between cross immunity and antibody-dependent enhancement. Chaos 19: 043123.[Crossref] [Google Scholar]
  24. Cummings DA, Schwartz IB, Billings L, Shaw LB, Burke DS, , 2005. Dynamic effects of antibody-dependent enhancement on the fitness of viruses. Proc Natl Acad Sci USA 102: 1525915264.[Crossref] [Google Scholar]
  25. Recker M, Blyuss KB, Simmons CP, Hien TT, Wills B, Farrar J, Gupta S, , 2009. Immunological serotype interactions and their effect on the epidemiological pattern of dengue. Proc Biol Sci 276: 25412548.[Crossref] [Google Scholar]
  26. Schwartz IB, Shaw LB, Cummings DA, Billings L, McCrary M, Burke DS, , 2005. Chaotic desynchronization of multistrain diseases. Phys Rev E Stat Nonlin Soft Matter Phys 72: 066201.[Crossref] [Google Scholar]
  27. Wikramaratna PS, Simmons CP, Gupta S, Recker M, , 2010. The effects of tertiary and quaternary infections on the epidemiology of dengue. PLoS One 5: e12347.[Crossref] [Google Scholar]
  28. Billings L, Fiorillo A, Schwartz IB, , 2008. Vaccinations in disease models with antibody-dependent enhancement. Math Biosci 211: 265281.[Crossref] [Google Scholar]
  29. U.S. Department of Commerce, 1996. Population Trends Philippines. U.S. Department of Commerce, 14. Available at: https://www.census.gov/population/international/files/ppt/ppt92-11.pdf. [Google Scholar]
  30. Durham DP, Ndeffo Mbah ML, Medlock J, Luz PM, Meyers LA, Paltiel AD, Galvani AP, , 2013. Dengue dynamics and vaccine cost-effectiveness in Brazil. Vaccine 31: 39573961.[Crossref] [Google Scholar]
  31. Hadinegoro SR, Arredondo-Garcia JL, Capeding MR, Deseda C, Chotpitayasunondh T, Dietze R, Muhammad Ismail HI, Reynales H, Limkittikul K, Rivera-Medina DM, Tran HN, Bouckenooghe A, Chansinghakul D, Cortes M, Fanouillere K, Forrat R, Frago C, Gailhardou S, Jackson N, Noriega F, Plennevaux E, Wartel TA, Zambrano B, Saville M, The CYD-TDV Dengue Vaccine Working Group, , 2015. Efficacy and long-term safety of a dengue vaccine in regions of endemic disease. N Engl J Med 373: 11951206.[Crossref] [Google Scholar]
  32. 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]
  33. Honorio NA, Nogueira RM, Codeco CT, Carvalho MS, Cruz OG, Magalhaes M de A, de Araujo JM, de Araujo ES, Gomes MQ, Pinheiro LS, da Silva Pinel C, Lourenco-de-Oliveira R, , 2009. Spatial evaluation and modeling of dengue seroprevalence and vector density in Rio de Janeiro, Brazil. PLoS Negl Trop Dis 3: e545.[Crossref] [Google Scholar]
  34. 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]
  35. Gubler DJ, , 1998. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 11: 480496. [Google Scholar]
  36. Rodriguez-Barraquer I, Mier-y-Teran-Romero L, Burke DS, Cummings DA, , 2013. Challenges in the interpretation of dengue vaccine trial results. PLoS Negl Trop Dis 7: e2126.[Crossref] [Google Scholar]
  37. Guy B, Jackson N, , 2016. Dengue vaccine: hypotheses to understand CYD-TDV-induced protection. Nat Rev Microbiol 14: 4554.[Crossref] [Google Scholar]
  38. Coudeville L, Baurin N, Vergu E, , 2015. Estimation of parameters related to vaccine efficacy and dengue transmission from two large phase III studies. Vaccine. http://dx.doi.org/10.1016/j.vaccine.2015.11.023. [Google Scholar]
  39. Shepard DS, Undurraga EA, Halasa YA, Stanaway JD, , 2016. The global economic burden of dengue: a systematic analysis. Lancet Infect Dis 16: 935941.[Crossref] [Google Scholar]
  40. Bravo L, Roque VG, Brett J, Dizon R, L'Azou M, , 2014. Epidemiology of dengue disease in the Philippines (2000–2011): a systematic literature review. PLoS Negl Trop Dis 8: e3027.[Crossref] [Google Scholar]
  41. Cerojano T, , 2016. Philippines Launches World's First Mass Dengue Vaccination. Available at: http://bigstory.ap.org/article/3ad36f9ba5984155b829e8878476d562/philippines-launches-worlds-first-mass-dengue-vaccination. Accessed August 27, 2016. [Google Scholar]
  42. Sandoval E, , 2016. First Mass Dengue Vaccination in the World Launched in PHL. MIMS. Alexandra Technopark. Singapore 119967. [Google Scholar]
  43. Rodriguez-Barraquer I, Mier-y-Teran-Romero L, Schwartz IB, Burke DS, Cummings DA, , 2014. Potential opportunities and perils of imperfect dengue vaccines. Vaccine 32: 514520.[Crossref] [Google Scholar]
  44. U.S. Bureau of Labor Statistics, 2007. The Consumer Price Indexes (CPI): All Urban Consumers. Available at: http://stats.bls.gov/cpi/home.htm. Accessed November 26, 2007. [Google Scholar]
  45. Carrasco LR, Lee LK, Lee VJ, Ooi EE, Shepard DS, Thein TL, Gan V, Cook AR, Lye D, Ng LC, Leo YS, , 2011. Economic impact of dengue illness and the cost-effectiveness of future vaccination programs in Singapore. PLoS Negl Trop Dis 5: e1426.[Crossref] [Google Scholar]
  46. Murray CJ, , 1994. Quantifying the burden of disease: the technical basis for disability-adjusted life years. Bull World Health Organ 72: 429445. [Google Scholar]
  47. Dantes HG, Farfan-Ale JA, Sarti E, , 2014. Epidemiological trends of dengue disease in Mexico (2000–2011): a systematic literature search and analysis. PLoS Negl Trop Dis 8: e3158.[Crossref] [Google Scholar]
  48. 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]
  49. Anderson KB, Chunsuttiwat S, Nisalak A, Mammen MP, Libraty DH, Rothman AL, Green S, Vaughn DW, Ennis FA, Endy TP, , 2007. Burden of symptomatic dengue infection in children at primary school in Thailand: a prospective study. Lancet 369: 14521459.[Crossref] [Google Scholar]
  50. Shepard DS, Suaya JA, Halstead SB, Nathan MB, Gubler DJ, Mahoney RT, Wang DN, Meltzer MI, , 2004. Cost-effectiveness of a pediatric dengue vaccine. Vaccine 22: 12751280.[Crossref] [Google Scholar]
  51. Undurraga EA, Betancourt-Cravioto M, Ramos-Castaneda J, Martinez-Vega R, Mendez-Galvan J, Gubler DJ, Guzman MG, Halstead SB, Harris E, Kuri-Morales P, Tapia-Conyer R, Shepard DS, , 2015. Economic and disease burden of dengue in Mexico. PLoS Negl Trop Dis 9: e0003547.[Crossref] [Google Scholar]
  52. Peabody JW, Shimkhada R, Tan C, Jr Luck J, , 2005. The burden of disease, economic costs and clinical consequences of tuberculosis in the Philippines. Health Policy Plan 20: 347353.[Crossref] [Google Scholar]
  53. Undurraga EA, Halasa YA, Shepard DS, , 2013. Use of expansion factors to estimate the burden of dengue in southeast Asia: a systematic analysis. PLoS Negl Trop Dis 7: e2056.[Crossref] [Google Scholar]
  54. Shim E, Galvani AP, , 2009. Impact of transmission dynamics on the cost-effectiveness of rotavirus vaccination. Vaccine 27: 40254030.[Crossref] [Google Scholar]
  55. Atkins KE, Shim E, Carroll S, Quilici S, Galvani AP, , 2012. The cost-effectiveness of pentavalent rotavirus vaccination in England and Wales. Vaccine 30: 67666776.[Crossref] [Google Scholar]
  56. World Health Organization, 2002. The World Health Report 2002: Reducing Risks, Promoting Healthy Life. Geneva, Switzerland: World Health Organization. [Google Scholar]
  57. Lee BY, Connor DL, Kitchen SB, Bacon KM, Shah M, Brown ST, Bailey RR, Laosiritaworn Y, Burke DS, Cummings DA, , 2011. Economic value of dengue vaccine in Thailand. Am J Trop Med Hyg 84: 764772.[Crossref] [Google Scholar]
  58. Orellano PW, Reynoso JI, Stahl HC, Salomon OD, , 2016. Cost-utility analysis of dengue vaccination in a country with heterogeneous risk of dengue transmission. Vaccine 34: 616621.[Crossref] [Google Scholar]
  59. Halstead SB, , 2006. Dengue in the Americas and southeast Asia: do they differ? Rev Panam Salud Publica 20: 407415.[Crossref] [Google Scholar]
  60. Shepard DS, Undurraga EA, Betancourt-Cravioto M, Guzman MG, Halstead SB, Harris E, Mudin RN, Murray KO, Tapia-Conyer R, Gubler DJ, , 2014. Approaches to refining estimates of global burden and economics of dengue. PLoS Negl Trop Dis 8: e3306.[Crossref] [Google Scholar]
  61. WHO-VMI Dengue Vaccine Modeling Group Beatty M, Boni MF, Brown S, Buathong R, Burke D, Coudeville L, Cummings DA, Edelman R, Farrar J, Focks DA, Gomes MG, Guignard A, Halstead S, Hombach J, Knerer G, Koelle K, Lam FC, Lang J, Longini I, Medlock J, Namgyal P, Powell M, Recker M, Rohani P, Standaert B, Struchiner C, Teyssou R, Wearing H, , , 2012. Assessing the potential of a candidate dengue vaccine with mathematical modeling. PLoS Negl Trop Dis 6: e1450.[Crossref] [Google Scholar]
  62. Barnighausen T, Bloom DE, Cafiero ET, O'Brien JC, , 2013. Valuing the broader benefits of dengue vaccination, with a preliminary application to Brazil. Semin Immunol 25: 104113.[Crossref] [Google Scholar]
  63. Murray NE, Quam MB, Wilder-Smith A, , 2013. Epidemiology of dengue: past, present and future prospects. Clin Epidemiol 5: 299309. [Google Scholar]

Data & Media loading...

  • Received : 10 Mar 2016
  • Accepted : 01 Aug 2016
  • Published online : 02 Nov 2016

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error