, Volume 35, Issue 5, pp 575–589 | Cite as

The Potential Cost Effectiveness of Different Dengue Vaccination Programmes in Malaysia: A Value-Based Pricing Assessment Using Dynamic Transmission Mathematical Modelling

  • Asrul Akmal ShafieEmail author
  • Hui Yee Yeo
  • Laurent Coudeville
  • Lucas Steinberg
  • Balvinder Singh Gill
  • Rohani Jahis
  • Amar-Singh HSS
Original Research Article



Dengue disease poses a great economic burden in Malaysia.


This study evaluated the cost effectiveness and impact of dengue vaccination in Malaysia from both provider and societal perspectives using a dynamic transmission mathematical model. The model incorporated sensitivity analyses, Malaysia-specific data, evidence from recent phase III studies and pooled efficacy and long-term safety data to refine the estimates from previous published studies. Unit costs were valued in $US, year 2013 values.


Six vaccination programmes employing a three-dose schedule were identified as the most likely programmes to be implemented. In all programmes, vaccination produced positive benefits expressed as reductions in dengue cases, dengue-related deaths, life-years lost, disability-adjusted life-years and dengue treatment costs. Instead of incremental cost-effectiveness ratios (ICERs), we evaluated the cost effectiveness of the programmes by calculating the threshold prices for a highly cost-effective strategy [ICER <1 × gross domestic product (GDP) per capita] and a cost-effective strategy (ICER between 1 and 3 × GDP per capita). We found that vaccination may be cost effective up to a price of $US32.39 for programme 6 (highly cost effective up to $US14.15) and up to a price of $US100.59 for programme 1 (highly cost effective up to $US47.96) from the provider perspective. The cost-effectiveness analysis is sensitive to under-reporting, vaccine protection duration and model time horizon.


Routine vaccination for a population aged 13 years with a catch-up cohort aged 14–30 years in targeted hotspot areas appears to be the best-value strategy among those investigated. Dengue vaccination is a potentially good investment if the purchaser can negotiate a price at or below the cost-effective threshold price.



The authors thank the Director General of Health Malaysia for his permission to publish this article. We also acknowledge the technical input and constructive suggestions from the following experts: Dr. Chee Kheong Chong and Dr. Rose Nani Mudin from Disease Control Division, MOH Malaysia. We acknowledge Nicola Truss, inScience Communications, Springer Healthcare, who provided proofreading assistance. This assistance was funded by Sanofi Pasteur.

Author contributions

AAS and HYY designed the study. LC constructed the model. BSG, RJ and A-SHSS advised on the parameterization of the model construction. LS made substantial contribution in the acquisition of data. AAS and HYY assembled the data and did the statistical analysis. HYY wrote the first draft and all authors contributed to further drafts and approved the final manuscript.

Compliance with ethical standards


This study was supported by an agreement between Sanofi-Aventis Singapore and Universiti Sains Malaysia.

Conflict of interest

HYY and AAS have received research grants from Sanofi-Aventis Singapore Ptd. Lte. LC and LS are employees of Sanofi-Pasteur. BSG and RJ have no conflicts of interest. A-SHSS has received consultation honorarium from Sanofi-Aventis Singapore Ptd. Lte.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

40273_2017_487_MOESM1_ESM.docx (327 kb)
Supplementary material 1 (DOCX 326 kb)
40273_2017_487_MOESM2_ESM.docx (40 kb)
Supplementary material 2 (DOCX 39 kb)


  1. 1.
    Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013;496(7446):504–7. doi: 10.1038/nature12060.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    World Health Organization. Dengue Situation Updates. Accessed 11 Oct 2016.
  3. 3.
    Shepard DS, Undurraga EA, Lees RS, Halasa Y, Lum LC, Ng CW. Use of multiple data sources to estimate the economic cost of dengue illness in Malaysia. Am J Trop Med Hyg. 2012;87(5):796–805. doi: 10.4269/ajtmh.2012.12-0019.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Undurraga EA, Halasa YA, Shepard DS. Use of expansion factors to estimate the burden of dengue in southeast Asia: a systematic analysis. PLoS Negl Trop Dis. 2013;7(2):e2056. doi: 10.1371/journal.pntd.0002056.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Horstick O, Runge-Ranzinger S, Nathan MB, Kroeger A. Dengue vector-control services: how do they work? A systematic literature review and country case studies. Trans R Soc Trop Med Hyg. 2010;104(6):379–86. doi: 10.1016/j.trstmh.2009.07.027.CrossRefGoogle Scholar
  6. 6.
    Beatty ME, Beutels P, Meltzer MI, Shepard DS, Hombach J, Hutubessy R, et al. Health economics of dengue: a systematic literature review and expert panel’s assessment. Am J Trop Med Hyg. 2011;84(3):473–88. doi: 10.4269/ajtmh.2011.10-0521.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Shepard DS, Suaya JA, Halstead SB, Nathan MB, Gubler DJ, Mahoney RT, et al. Cost-effectiveness of a pediatric dengue vaccine. Vaccine. 2004;22(9):1275–80.CrossRefGoogle Scholar
  8. 8.
    Lee BY, Connor DL, Kitchen SB, Bacon KM, Shah M, Brown ST, et al. Economic value of dengue vaccine in Thailand. Am J Trop Med Hyg. 2011;84(5):764–72. doi: 10.4269/ajtmh.2011.10-0624.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Carrasco LR, Lee LK, Lee VJ, Ooi EE, Shepard DS, Thein TL, et al. Economic impact of dengue illness and the cost-effectiveness of future vaccination programs in Singapore. PLoS Negl Trop Dis. 2011;5(12):e1426. doi: 10.1371/journal.pntd.0001426.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Durham DP, Ndeffo Mbah ML, Medlock J, Luz PM, Meyers LA, Paltiel AD, et al. Dengue dynamics and vaccine cost-effectiveness in Brazil. Vaccine. 2013;31(37):3957–61. doi: 10.1016/j.vaccine.2013.06.036.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Shim E. Dengue dynamics and vaccine cost-effectiveness analysis in the Philippines. Am J Trop Med Hyg. 2016;16:0194.Google Scholar
  12. 12.
    Coudeville L, Garnett GP. Transmission dynamics of the four dengue serotypes in southern Vietnam and the potential impact of vaccination. PLoS One. 2012;7(12):e51244. doi: 10.1371/journal.pone.0051244.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Amar-Singh HSS, Koh M-T, Tan KK, Chan LG, Zhou L, Bouckenooghe A, et al. Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2–11 years in Malaysia: a randomized, placebo-controlled, phase III study. Vaccine. 2013;31(49):5814–21. doi: 10.1016/j.vaccine.2013.10.013.CrossRefGoogle Scholar
  14. 14.
    Villar L, Dayan GH, Arredondo-Garcia JL, Rivera DM, Cunha R, Deseda C, et al. Efficacy of a tetravalent dengue vaccine in children in Latin America. N Engl J Med. 2015;372(2):113–23. doi: 10.1056/NEJMoa1411037.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Capeding MR, Tran NH, Hadinegoro SRS, Ismail HIHJM, Chotpitayasunondh T, Chua MN, et al. 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. 2014;384(9951):1358–65. doi: 10.1016/S0140-6736(14)61060-6.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Hadinegoro SR, Arredondo-García JL, Capeding MR, Deseda C, Chotpitayasunondh T, Dietze R, et al. Efficacy and long-term safety of a dengue vaccine in regions of endemic disease. N Engl J Med. 2015;373(13):1195–206. doi: 10.1056/NEJMoa1506223.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    World Health Organization. Summary of the April 2016 meeting of the Strategic Advisory Group of Experts on immunization (SAGE). Geneva: WHO; 2016. p. 02016.Google Scholar
  18. 18.
    World Health Organization. Comparative modelling of dengue vaccine public health impact (CMDVI). Geneva: WHO; 2016.Google Scholar
  19. 19.
    Mohd-Zaki AH, Brett J, Ismail E, L’Azou M. Epidemiology of dengue disease in Malaysia (2000–2012): a systematic literature review. PLoS Negl Trop Dis. 2014;8(11):e3159. doi: 10.1371/journal.pntd.0003159.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    UNICEF. State of the world’s children 2015 country statistical information. New York: UNICEF; 2013. Accessed 30 July 2015.
  21. 21.
    World Health Organization. Managing vaccine wastage at country level: guidelines for programme managers. Geneva: WHO; 2003.Google Scholar
  22. 22.
    Suaya JA, Shepard DS, Siqueira JB, Martelli CT, Lum LC, Tan LH, et al. Cost of dengue cases in eight countries in the Americas and Asia: a prospective study. Am J Trop Med Hyg. 2009;80(5):846–55.CrossRefGoogle Scholar
  23. 23.
    Shepard DS, Undurraga EA, Halasa YA. Economic and disease burden of dengue in southeast Asia. PLoS Negl Trop Dis. 2013;7(2):e2055. doi: 10.1371/journal.pntd.0002055.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    International Monetary Fund. World Economic Outlook Database. Accessed 15 Dec 2014.
  25. 25.
    Malaysia Ministry of Health. Pharmacoeconomic guideline for Malaysia. Putrajaya: MoH; 2012.Google Scholar
  26. 26.
    Commission on Macroeconomics and Health. Macroeconomics and health: investing in health for economic development. Report of the Commission on Macroeconomics and Health. Geneva: World Health Organization; 2001.Google Scholar
  27. 27.
    Malaysia Ministry of Health. Age-specific annual dengue incidence in Selangor 2003–2013. Putrajaya: MoH; 2014.Google Scholar
  28. 28.
    Rodriguez-Barraquer I, Mier-y-Teran-Romero L, Schwartz IB, Burke DS, Cummings DA. Potential opportunities and perils of imperfect dengue vaccines. Vaccine. 2014;32(4):514–20.CrossRefGoogle Scholar
  29. 29.
    Halloran ME, Haber M, Longini IM, Struchiner CJ. Direct and indirect effects in vaccine efficacy and effectiveness. Am J Epidemiol. 1991;133(4):323–31.CrossRefGoogle Scholar
  30. 30.
    World Health Organization. Global strategy for dengue prevention and control, 2012–2020 Report no. WHO/HTM/NTD/VEM/2012.5. Geneva: WHO; 2012.Google Scholar
  31. 31.
    Aljunid S, Zafar A, Saperi S, Amrizal M. Burden of disease associated with cervical cancer in Malaysia and potential costs and consequences of HPV vaccination. Asian Pac J Cancer Prev. 2010;11(6):1551–9.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Pitman R, Fisman D, Zaric GS, Postma M, Kretzschmar M, Edmunds J, et al. Dynamic transmission modeling: a report of the ISPOR-SMDM modeling good research practices task force-5. Value Health. 2012;15(6):828–34.CrossRefGoogle Scholar
  33. 33.
    Tu HA, Woerdenbag HJ, Kane S, Rozenbaum MH, Li SC, Postma MJ. Economic evaluations of rotavirus immunization for developing countries: a review of the literature. Expert Rev Vaccines. 2011;10(7):1037–51. doi: 10.1586/erv.11.65.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Fesenfeld M, Hutubessy R, Jit M. Cost-effectiveness of human papillomavirus vaccination in low and middle income countries: a systematic review. Vaccine. 2013;31(37):3786–804. doi: 10.1016/j.vaccine.2013.06.060.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Walker DG, Hutubessy R, Beutels P. WHO guide for standardisation of economic evaluations of immunization programmes. Vaccine. 2010;28(11):2356–9.CrossRefGoogle Scholar
  36. 36.
    Shafie AA, Lim YW, Chua GN, Hassali MAA. Exploring the willingness to pay for a quality-adjusted life-year in the state of Penang, Malaysia. Clinicoecon Outcomes Res. 2014;6:473–81. doi: 10.2147/CEOR.S67375.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Lim YW, Shafie AA, Chua GN, Hassali M. Determination of cost-effectiveness threshold for Malaysia. George Town: Universiti Sains Malaysia; 2015.Google Scholar
  38. 38.
    Department of Statistics Malaysia. Population distribution and basic demographic characteristic report 2010. Putrajaya: DoS; 2011.Google Scholar
  39. 39.
    Salomon JA, Wang H, Freeman MK, Vos T, Flaxman AD, Lopez AD, et al. Healthy life expectancy for 187 countries, 1990–2010: a systematic analysis for the Global Burden Disease Study 2010. Lancet. 2013;380(9859):2144–62.CrossRefGoogle Scholar
  40. 40.
    World Health Organization. Choosing interventions that are cost effective (WHO-CHOICE). Geneva: WHO; 2011.
  41. 41.
    Guidelines on the Implementation of the Minimum Wages Order 2012. In: Putrajaya, editor. Ministry of Human Resources. National Wages Consultative Council; 2012.Google Scholar
  42. 42.
    Ministry of Health Malaysia. Handbook of National Immunization Programme for Babies and Children (for Nurses). Putrajaya: Family Health Promotion Division; 2008.Google Scholar
  43. 43.
    Coudeville L, Baurin N, Vergu E. Estimation of parameters related to vaccine efficacy and dengue transmission from two large phase III studies. Vaccine. 2015. doi: 10.1016/j.vaccine.2015.11.023.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Nealon JTA, Capeding MR, Tran NH, Hadinegoro SR, Chotpitayasunondh T, et al. Symptomatic dengue burden in 5 countries in Asia-Pacific: epidemiological evidence from a dengue vaccine trial. In: 5th Asian vaccine conference, Hanoi; 2015.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Asrul Akmal Shafie
    • 1
    Email author
  • Hui Yee Yeo
    • 1
  • Laurent Coudeville
    • 2
  • Lucas Steinberg
    • 3
  • Balvinder Singh Gill
    • 4
  • Rohani Jahis
    • 4
  • Amar-Singh HSS
    • 5
  1. 1.Discipline of Social and Administrative Pharmacy, School of Pharmaceutical SciencesUniversiti Sains Malaysia (USM)George TownMalaysia
  2. 2.Sanofi Pasteur SALyon Cedex 07France
  3. 3.Sanofi Pasteur MalaysiaPetaling JayaMalaysia
  4. 4.Disease Control DivisionMinistry of Health MalaysiaPutrajayaMalaysia
  5. 5.Pediatric Department and Clinical Research CenterHospital Raja Permaisuri Bainun Ipoh, Jalan HospitalIpohMalaysia

Personalised recommendations