Post-Exposure Prophylactic Vaccination against Rabies: A Systematic Review
Background: Post-exposure prophylaxis (PEP) is an effective method for preventing rabies, a highly fatal infection in exposed persons. Malaysia is currently using the purified Vero cell rabies vaccine (PVRV). Nonetheless, there are other commercially available vaccine types and regimens. This systematic review aimed at comparing the effectiveness of the different PEP vaccines, regimens and routes of administration among Asian populations.
Methods: We systematically reviewed the PubMed and Web of Science databases for articles reporting on the effectiveness of PEP vaccination against rabies among Asian populations between 2015 and 2019.
Results: Our search identified 11 relevant studies. Majority of study either used PCECV or PVRV type of vaccine, with different regimes and method. All are non-inferior to the other. Most of the studies recorded adequate response by Day 14 of vaccination. Nonetheless, the intradermal (ID) vaccination used minimal volume of vaccine used in all settings, thus cost less and the concurrent administration of RIG to the wound(s) doesn’t affect the RVNA GMT response.
Conclusion: PCECV, using either the Essen or Zagreb regimen, might be a useful alternative for the healthy population in the context of PVRV shortage, especially during an outbreak. Use of the Zagreb or Thai Red Cross (TRC) regimens can be considered (either PVRV or PCECV), as both demonstrate good immunogenic outcomes in Asian populations.
2. World Health Organization (2020) Rabies: Factsheet.World Health Organization. Available from: https://www.who.int/news-room/fact-sheets/detail/rabies
3. Audu SW, Mshelbwala PP, Jahun BM, et al (2019). Two fatal cases of rabies in hu-mans who did not receive rabies postex-posure prophylaxis in Nigeria. Clin Case Rep, 7(4):749–752.
4. Peng J, Lu S, Zhu Z, et al (2016). Safety comparison of four types of rabies vac-cines in patients with WHO category II animal exposure An observation based on different age groups. Medicine (Balti-more), 95(47):e5049.
5. World Health Organization (1992). WHO Expert Committee on Rabies: Eighth Report (WHO technical report series: 824). Geneva, pp.:13-14.
6. Salahuddin N, Gohar MA, Baig-Ansari N (2016). Reducing Cost of Rabies Post Exposure Prophylaxis: Experience of a Tertiary Care Hospital in Pakistan. PLoS Negl Trop Dis, 10(2):e0004448.
7. Warrell MJ (2012). Current rabies vaccines and prophylaxis schedules: Preventing rabies before and after exposure. Travel Med Infect Dis, 10(1):1–15.
8. Rahimi P, Vahabpour RA, Aghasadeghi MR, et al (2015). Neutralizing antibody re-sponse after intramuscular purified Vero cell rabies vaccination (PVRV) in Iranian patients with specific medical conditions. PLoS One, 10(10):e0139171.
9. Shi N, Zhang Y, Zheng H, et al (2017). Im-munogenicity, safety and antibody persis-tence of a purified vero cell cultured ra-bies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects. Hum Vaccines Im-munother, 13(6):1-8.
10. Narayana A, Manoharan A, Narayan MS, et al (2015). Comparison of safety and im-munogenicity of 2 WHO prequalified ra-bies vaccines administered by one week, 4 site intra dermal regimen (4-4-4-0-0) in animal bite cases. Hum Vaccines Immunother, 11 (7):1748–53.
11. Hampson K, Coudeville L, Lembo T, et al (2015). Estimating the Global Burden of Endemic Canine Rabies. PLoS Negl Trop Dis, 9 (5):e0003709.
12. Buchy P, Preiss S, Singh V, Mukherjee P (2017). Heterogeneity of rabies vaccina-tion recommendations across Asia. Trop Med Infect Dis, 2 (3):23.
13. Vickneshwaran Muthu (2018). Rabies Malay-sia. 1st Inaugural ARACON Meeting. Glob Alliance Rabies Control, Thailand. Available from: https://rabiesalliance.org/resource/lessons-learned-malaysia
14. Anwar Z (2017). Claims on shortage of ra-bies vaccines in Sarawak untrue: Health Ministry. New Straits Times online, Ma-laysia. Available from: https://api.nst.com.my/news/nation/2017/07/259694/claims-shortage-rabies-vaccines-sarawak-untrue-health-ministry
15. Disease Control Division (2018). Interim Guideline for Human Rabies Prevention & Con-trol in Malaysia. Ministry of Health Malay-sia, Putrajaya, pp: 6-7.
16. Moher D, Liberati A, Tetzlaff J, Altman DG, the PG (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLOS Med 6(7):e1000097.
17. Hong QN, Fàbregues S, Bartlett G, et al (2018). The Mixed Methods Appraisal Tool (MMAT) version 2018 for infor-mation professionals and researchers. Educ Inf, 34 (4):285–291.
18. Bose A, Munshi R, Tripathy RM, et al (2016). A randomized non-inferiority clinical study to assess post-exposure prophylaxis by a new purified vero cell rabies vaccine (Rabivax-S) administered by intramuscular and intradermal routes. Vaccine, 34 (40):4820–6.
19. Li RC, Li YP, Wen SQ, et al (2015). Immu-nogenicity and safety of purified chickembryo cell rabies vaccine under za-greb 2-1-1 or 5-dose essen regimen in chinese children 6 to 17 years old and adults over 50 years: A randomized open-label study. Hum Vaccines Immunother, 11 (2):435–42.
20. Mahendra BJ, Ashwath Narayana DH, Agarkhedkar S, et al (2015). Comparative study on the immunogenicity and safety of a purified chick embryo cell rabies vac-cine (Pcecv) administered according to two different simulated post exposure in-tramuscular regimens (zagreb versus es-sen). Hum Vaccines Immunother, 11 (2):428–34.
21. Kalimuddin S, Wijaya L, Chan YFZ, et al (2017). A phase II randomized study to determine the safety and immunogenicity of the novel PIKA rabies vaccine con-taining the PIKA adjuvant using an accel-erated regimen. Vaccine, 35 (51):7127–7132.
22. Wijaya L, Tham CYL, Chan YFZ, et al (2017). An accelerated rabies vaccine schedule based on toll-like receptor 3 (TLR3) agonist PIKA adjuvant augments rabies virus specific antibody and T cell response in healthy adult volunteers. Vac-cine, 35 (8):1175–1183.
23. Sirikun J, Suputtamongkol Y, Rattanachina-korn P, et al (2018). Immunogenic re-sponse in obese patients undergoing ra-bies post-exposure prophylaxis with combined equine rabies immunoglobulin and rabies vaccination. Vaccine, 36 (2):285–291.
24. Quiambao BP, Ambas C, Diego S, et al (2019). Intradermal post-exposure rabies vaccination with purified Vero cell rabies vaccine: Comparison of a one-week, 4-site regimen versus updated Thai Red Cross regimen in a randomized non-inferiority trial in the Philippines. Vaccine, 37 (16):2268–2277.
25. Kerdpanich P, Chanthavanich P, De Los Reyes MR, et al (2018). Shortening intra-dermal rabies post-exposure prophylaxis regimens to 1 week: Results from a phase III clinical trial in children, adolescents and adults. PLoS Negl Trop Dis, 12(6):e0006340.
26. Montagnon B, Fanget B (1996). Purified Vero cell vaccine for humans. In: Meslin FX, Kaplan MM, Koprowski H (eds) Lab. Tech. rabies, 4th ed. World Health Or-ganization, Geneva, pp 285–289
27. Branche R (1996) .Vaccines for Humans Prepared in Human Diploid Cells. In: Meslin FX, Kaplan MM, Koprowski H (eds) Lab. Tech. rabies, 4th ed. World Health Organization, Geneva, pp: 280–284.
28. WHO/ Department of Control of Neglect-ed Tropical Diseases (2018). WHO | Ra-bies vaccines: WHO position paper – April 2018. World Health Organization, Geneva. pp:1-19.
29. Preiss S, Chanthavanich P, Chen LH, et al (2018). Post-exposure prophylaxis (PEP) for rabies with purified chick embryo cell vaccine: a systematic literature review and meta-analysis. Expert Rev Vaccines, 17 (6):525–545.
30. WHO (2017). WHO | The Immunological Basis for Immunization Series: Module 17: Rabies (2017 update). In: WHO (ed) WHO, 2017 Update. World Health Or-ganization, Geneva, pp.: 1–49.
31. Tarantola A, Tejiokem MC, Briggs DJ (2019). Evaluating new rabies post-exposure prophylaxis (PEP) regimens or vaccines. Vaccine, 1:A88-A93.
32. WHO Expert Consultation on Rabies, third report (2018). (WHO Technical Report Series, No. 1012) Geneva: World Health Organization.
33. WHO Strategic Advisory Group of Experts (2018). Rabies vaccines: WHO position paper. World Health Organization, Ge-neva. pp.:
34. Kessels JA, Recuenco S, Navarro-Vela AM, et al (2017). Pre-exposure rabies prophy-laxis: a systematic review. Bull World Health Organ, 95 (3):210-219C.
35. Hampson K, Abela-Ridder B, Bharti O, et al (2019). Modelling to inform prophylaxis regimens to prevent human rabies. Vac-cine, A166–A173.
36. Garg S, Thongcharoen P, Praphasiri P, et al (2016). Randomized Controlled Trial to Compare Immunogenicity of Standard-dose Intramuscular versus Intradermal Trivalent Inactivated In. Clin Infect Dis, 62 (3):383–391.
37. Both L, Banyard AC, van Dolleweerd C, et al (2012). Passive immunity in the preven-tion of rabies. Lancet Infect Dis, 12 (5):397–407.
38. Wilde H, Lumlertdacha B, Meslin FX, et al (2016). Worldwide rabies deaths preven-tion—A focus on the current inadequa-cies in postexposure prophylaxis of ani-mal bite victims. Vaccine, 34 (2):187–189.
|Issue||Vol 51 No 5 (2022)|
|Rabies Post-exposure prophylaxis Human Vaccine|
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