Research Open Access
Like 0



The risk of contracting rabies is low for travellers. However, the number of Dutch travellers potentially exposed abroad following an animal-associated injury and needing post-exposure prophylaxis (PEP) has increased, resulting in increased costs.


Here, we evaluated the costs and the cost-effectiveness of different pre- and post-exposure interventions in the Netherlands, taking into account the 2018 World Health Organization (WHO) recommendations for the prevention of rabies.


A decision tree-based economic model was constructed. We calculated and compared the cost of different WHO pre-exposure prophylaxis (PrEP) recommendations, intramuscular vs intradermal vaccination and PEP subsequent to increased vaccination coverage in risk groups. We estimated cost-effectiveness, expressed as incremental costs per rabies immunoglobulin (RIG) administration averted, using a societal perspective. Statistical uncertainty regarding number of travellers and vaccination coverage was assessed.


Total costs at the national level were highest using previous WHO recommendations from 2012, estimated at EUR 15.4 million annually. Intradermal vaccinations in combination with the current recommendations led to the lowest costs, estimated at EUR 10.3 million. Higher vaccination uptake resulted in higher overall costs. The incremental costs per RIG administration averted varied from EUR 21,300-46,800.


The change in rabies PrEP and PEP recommendations in 2018 reduced total costs. Strategies with increased pre-travel vaccination uptake led to fewer RIG administrations and fewer vaccinations after exposure but also to higher total costs. Although larger scale intradermal administration of rabies vaccine can reduce total costs of PrEP and can positively influence vaccination uptake, it remains a costly intervention.


Article metrics loading...

Loading full text...

Full text loading...



  1. Hampson K, Coudeville L, Lembo T, Sambo M, Kieffer A, Attlan M, et al. Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis. 2015;9(4):e0003709.  https://doi.org/10.1371/journal.pntd.0003709  PMID: 25881058 
  2. SAGE working group. Background paper: proposed revision of the policy on rabies vaccines and rabies immunoglobulins. Geneva: World Health Organization; 2017. Available from: https://www.who.int/immunization/sage/meetings/2017/october/1_Background_paper_WG_RABIES_final.pdf?ua=1
  3. Crowcroft NS, Thampi N. The prevention and management of rabies. BMJ. 2015;350(jan14 26):g7827.  https://doi.org/10.1136/bmj.g7827  PMID: 25589091 
  4. Lankau EW, Cohen NJ, Jentes ES, Adams LE, Bell TR, Blanton JD, et al. Prevention and control of rabies in an age of global travel: a review of travel- and trade-associated rabies events--United States, 1986-2012. Zoonoses Public Health. 2014;61(5):305-16.  https://doi.org/10.1111/zph.12071  PMID: 23870674 
  5. World Health Organization. Rabies vaccines: WHO position paper, April 2018 - Recommendations. Vaccine. 2018;36(37):5500-3.  https://doi.org/10.1016/j.vaccine.2018.06.061  PMID: 30107991 
  6. Steffen R, Behrens RH, Hill DR, Greenaway C, Leder K. Vaccine-preventable travel health risks: what is the evidence--what are the gaps? J Travel Med. 2015;22(1):1-12.  https://doi.org/10.1111/jtm.12171  PMID: 25378212 
  7. Carrara P, Parola P, Brouqui P, Gautret P. Imported human rabies cases worldwide, 1990-2012. PLoS Negl Trop Dis. 2013;7(5):e2209.  https://doi.org/10.1371/journal.pntd.0002209  PMID: 23658853 
  8. Eurocross Assistance. Steeds meer reizigers maken melding van mogelijke besmetting met hondsdolheid. [More and more travellers report possible rabies infection]. Leiden: Eurocross Assistance; 2018. Dutch. Available from: https://www.eurocross.nl/nieuws/2018/steeds-meer-reizigers-maken-melding-van-mogelijke-besmetting-met-hondsdolheid/
  9. World Health Organization (WHO). WHO expert consultation on rabies: third report. Geneva: WHO; 2018. Available from: https://apps.who.int/iris/handle/10665/272364
  10. Rijksinstituut voor Volksgezondheid en Milieu (RIVM). Rabiës richtlijn. [Rabies guideline]. Bilthoven: RIVM. [Accessed: 18 Sep 2019]. Dutch. Available from: https://lci.rivm.nl/richtlijnen/rabies
  11. Bharti OK, Madhusudana SN, Gaunta PL, Belludi AY. Local infiltration of rabies immunoglobulins without systemic intramuscular administration: An alternative cost effective approach for passive immunization against rabies. Hum Vaccin Immunother. 2016;12(3):837-42.  https://doi.org/10.1080/21645515.2015.1085142  PMID: 26317441 
  12. Bharti OK, Madhusudana SN, Wilde H. Injecting rabies immunoglobulin (RIG) into wounds only: A significant saving of lives and costly RIG. Hum Vaccin Immunother. 2017;13(4):762-5.  https://doi.org/10.1080/21645515.2016.1255834  PMID: 28277089 
  13. Kong LY, Vincelette J, Laplante G, Duchesne JA, Libman M, Barkati S. Intradermal pre-exposure rabies vaccination in a Canadian travel clinic: 6-year retrospective observational study. CMAJ Open. 2018;6(2):E168-75.  https://doi.org/10.9778/cmajo.20170147  PMID: 29636332 
  14. Bantjes S, Haverkate M, Ruijs H, van den Hoogen G, Croughs M, Pijtak A, et al. Predictors of possible rabies exposure in travelers: a case-control study. Eur J Public Health. 2018;28(suppl_4).
  15. Wieten RW, Tawil S, van Vugt M, Goorhuis A, Grobusch MP. Risk of rabies exposure among travellers. Neth J Med. 2015;73(5):219-26. PMID: 26087801 
  16. van Dee L, Dimmendaal M, Bantjes S, Haverkate M, van Kessel R. Rabiëscasuïstiek in de GGD-regio Utrecht. [Rabies in the MHS region Utrecht]. Infectieziekten Bulletin. 2018;29(9). Dutch. Available from: https://magazines.rivm.nl/2018/11/infectieziekten-bulletin/rabi%C3%ABscasu%C3%AFstiek-de-ggd-regio-utrecht-0
  17. Hampson K, Abela-Ridder B, Bharti O, Knopf L, Léchenne M, Mindekem R, et al. Modelling to inform prophylaxis regimens to prevent human rabies. Vaccine. 2019;37(Suppl 1):A166-73.  https://doi.org/10.1016/j.vaccine.2018.11.010  PMID: 30528846 
  18. LeGuerrier P, Pilon PA, Deshaies D, Allard R. Pre-exposure rabies prophylaxis for the international traveller: a decision analysis. Vaccine. 1996;14(2):167-76.  https://doi.org/10.1016/0264-410X(95)00110-M  PMID: 8852415 
  19. Anothaisintawee T, Julienne Genuino A, Thavorncharoensap M, Youngkong S, Rattanavipapong W, Meeyai A, et al. Cost-effectiveness modelling studies of all preventive measures against rabies: A systematic review. Vaccine. 2019;37(Suppl 1):A146-53.  https://doi.org/10.1016/j.vaccine.2018.11.071  PMID: 30554795 
  20. Kessels JA, Recuenco S, Navarro-Vela AM, Deray R, Vigilato M, Ertl H, et al. Pre-exposure rabies prophylaxis: a systematic review. Bull World Health Organ. 2017;95(3):210-219C.  https://doi.org/10.2471/BLT.16.173039  PMID: 28250534 
  21. Leder K, Chen LH, Wilson ME. Aggregate travel vs. single trip assessment: arguments for cumulative risk analysis. Vaccine. 2012;30(15):2600-4.  https://doi.org/10.1016/j.vaccine.2011.12.133  PMID: 22234265 
  22. Lammert SM, Rao SR, Jentes ES, Fairley JK, Erskine S, Walker AT, et al. Refusal of recommended travel-related vaccines among U.S. international travellers in Global TravEpiNet. J Travel Med. 2016;24(1):taw075.  https://doi.org/10.1093/jtm/taw075  PMID: 27799502 
  23. Marano C, Moodley M, Melander E, De Moerlooze L, Nothdurft HD. Perceptions of rabies risk: a survey of travellers and travel clinics from Canada, Germany, Sweden and the UK. J Travel Med. 2019;26(Suppl 1):S3-9.  https://doi.org/10.1093/jtm/tay062  PMID: 30476212 
  24. Cleaveland S, Lankester F, Townsend S, Lembo T, Hampson K. Rabies control and elimination: a test case for One Health. Vet Rec. 2014;175(8):188-93.  https://doi.org/10.1136/vr.g4996  PMID: 25172649 
  25. Rysava K, Miranda ME, Zapatos R, Lapiz S, Rances P, Miranda LM, et al. On the path to rabies elimination: The need for risk assessments to improve administration of post-exposure prophylaxis. Vaccine. 2019;37(Suppl 1):A64-72.  https://doi.org/10.1016/j.vaccine.2018.11.066  PMID: 30573356 
  26. Fitzpatrick MC, Shah HA, Pandey A, Bilinski AM, Kakkar M, Clark AD, et al. One Health approach to cost-effective rabies control in India. Proc Natl Acad Sci USA. 2016;113(51):14574-81.  https://doi.org/10.1073/pnas.1604975113  PMID: 27994161 
  27. Lechenne M, Mindekem R, Madjadinan S, Oussiguéré A, Moto DD, Naissengar K, et al. The importance of a participatory and integrated one health approach for rabies control: the case of N’Djaména, Chad. Trop Med Infect Dis. 2017;2(3):43.  https://doi.org/10.3390/tropicalmed2030043  PMID: 30270900 
  28. Lankester F, Davis A, Kinung’hi S, Yoder J, Bunga C, Alkara S, et al. An integrated health delivery platform, targeting soil-transmitted helminths (STH) and canine mediated human rabies, results in cost savings and increased breadth of treatment for STH in remote communities in Tanzania. BMC Public Health. 2019;19(1):1398.  https://doi.org/10.1186/s12889-019-7737-6  PMID: 31660915 
  29. Jonker EFF, Visser LG. Single visit rabies pre-exposure priming induces a robust anamnestic antibody response after simulated post-exposure vaccination: results of a dose-finding study. J Travel Med. 2017;24(5).  https://doi.org/10.1093/jtm/tax033  PMID: 28931127 
  30. European Centre for Disease Prevention and Control (ECDC). Rabies – Annual epidemiological report for 2018. Stockholm: ECDC; 2019. Available from: https://www.ecdc.europa.eu/en/publications-data/rabies-annual-epidemiological-report-2018
  31. Zorginstituut Nederland. Rabiesvaccin merieux flacon 2,5IE+solvens 1ml. [Rabies vaccine merieux vial 2.5IE + solvens 1ML]. Diemen: Zorginstituut Nederland. [Accessed: 18 Sep 2019]. Dutch. Available from: https://www.medicijnkosten.nl/medicijn?artikel=RABIESVACCIN+MERIEUX+FLACON+2%2C5IE+%2B+SOLVENS+1ML&id=91558d973ee8763efce00192f24d314e
  32. Zorginstituut Nederland. Richtlijn voor het uitvoeren van economische evaluaties in de gezondheidszorg. [Guideline for conducting economic evaluations in healthcare]. Amsterdam: Zorginstituut Nederland; 2016. Dutch. Available from: https://www.zorginstituutnederland.nl/publicaties/publicatie/2016/02/29/richtlijn-voor-het-uitvoeren-van-economische-evaluaties-in-de-gezondheidszorg
  33. Gemeenschappelijke Gezondheidsdienst (GGD). Reisvaccinaties. Tarieven. [MHS tariffs]. [Accessed: 18 Sep 2019]. Dutch. Available from: https://www.ggdreisvaccinaties.nl/tarieven
  34. Vaccinatiecentrum. Prijzen vaccinaties en medicatie. [Tropical health advice and vaccination. Prices of vaccines and medications]. [Accessed: 18 Sep 2019]. Dutch. Available from: https://vaccinatiecentrum.nl/index.php/vaccinaties-en-medicatie/prijzen

Data & Media loading...

Supplementary data

Submit comment
Comment moderation successfully completed
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