Universal Mass Vaccination Against Hepatitis A

  • F. E. André
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 304)


When first introduced in 1992 the hepatitis A vaccine was recommended for individuals at high risk of exposure. This policy was not expected to have a significant impact on disease incidence at population level in view of the epidemiology of the hepatitis A virus (HAV).More recently two countries, Israel and Bahrain, and regions or subpopulations in others (Australia, China, Byelorussia, Italy, Spain, US) have embarked upon more ambitious vaccination programmes that aim to immunize whole birth cohorts. After a brief survey of the virology and epidemiology of HAV, the disease burden it inflicts and a short history of the development of HAV vaccines — both live (in China) and killed vaccines are available — the vaccination programmes introduced in the countries mentioned above are described. The results have been spectacular: disease incidence, not only in the vaccinated cohorts but also in the whole population, have plummeted within a few years of the start of mass vaccination. There is now convincing evidence that the vaccine confers herd immunity if the main spreaders of the virus are targeted for immunization. This finding should encourage other countries to start mass vaccination programmes against HAV, particularly as pharmacoeconomic studies are beginning to show that such a strategy could be a cost-effective way of controlling the disease. It is now even conceivable to eradicate HAV. In fact, this should be easier to achieve than polio eradication as HAV vaccines confer more durable immunity than polio vaccines. However, the global disease burden of HAV is generally thought not to be high enough to justify such an undertaking in the foreseeable future.


Disease Incidence Vaccination Programme Herd Immunity Mass Vaccination Indigenous Child 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Deinhardt F (1992) Prevention of hepatitis A: past, present and future. Vaccine 10(Suppl.1):S10–S14PubMedCrossRefGoogle Scholar
  2. 2.
    Hilleman MR (1993) Hepatitis and hepatitis A vaccine: a glimpse of history. J Hepatol 18(Suppl. 2):S5–S10PubMedCrossRefGoogle Scholar
  3. 3.
    Hollinger FB, André FE, Melnick J (eds) (1992) Proceedings of International Symposiumon active immunization against hepatitis A. Vaccine 10(Suppl.1):S1–S176Google Scholar
  4. 4.
    André FE (1997) Hepatitis A vaccine: current status and future use. In:Proceedings of IX Triennial International Symposium on Viral Hepatis and Liver Disease. Rizetto M, Purcell RH, Gerin JL, Verne G (eds.). Minerva Medica, Rome, Italy, pp 624–626Google Scholar
  5. 5.
    André FE (2002) Randomised, cross-over controlled comparison of two inactivated hepatitis A vaccines. Vaccine 20:292–293CrossRefGoogle Scholar
  6. 6.
    Mao JS, Dong DX, Zhang HY, et al. (1989) Primary study of attenuated live hepatitis A vaccine (H2 strain) in humans. J Infect Dis 159:621–624PubMedGoogle Scholar
  7. 7.
    André FE (1995) Approaches to a vaccine against hepatitis A: development and manufacture of an inactivated vaccine. J Infect Dis 171(Suppl.1):S33–S39PubMedGoogle Scholar
  8. 8.
    Margolis HS, Shapiro CN (1992) Who should receive hepatitis A vaccine? Considerations for the development of an immunization strategy. Vaccine 10(Suppl.1):S85–S87PubMedCrossRefGoogle Scholar
  9. 9.
    Committee for Safety of Medicines (1994) Hepatitis A vaccination (Havrix). Curr Prob Pharmacovigilance 20:16Google Scholar
  10. 10.
    Niu MT, Salive M, Krueger C, Ellenberg SS (1998) Two-year review of hepatitis Avaccine safety: data from the Vaccine Adverse Event Reporting System(VAERS). Clin Infect Dis 26:1475–1476PubMedGoogle Scholar
  11. 11.
    André FE, Van Damme P, Safary A, Banatvala J (2002) Inactivated hepatitis A vaccine: immunogenicity, efficacy, safety and review of official recommendations for use. Exp Rev Vaccines 1(1):9–23CrossRefGoogle Scholar
  12. 12.
    Jacobs RJ, Margolis HS, Coleman PJ (2000) The cost-effectiveness of adolescent hepatitis A vaccination in states with the highest disease rates. Arch Pediatr Adolesc Med 154(8):763–770PubMedGoogle Scholar
  13. 13.
    Ginsberg GM, Slater PE, Shouval D (2001) Cost-benefit of a nationwide infant immunization programme against hepatitis A in an area of intermediate endemicity. J Hepatol 34:92–99CrossRefGoogle Scholar
  14. 14.
    Chabot I, Goetghebeur MM, Grégoire J-P (2004) The societal value of childhood immunization. Vaccine 22:1992–2005PubMedCrossRefGoogle Scholar
  15. 15.
    Melnick JL (1992) Properties and classification of hepatitis A virus. Vaccine 10(Suppl.1):S24–S26PubMedCrossRefGoogle Scholar
  16. 16.
    Balayan MS (1992) Natural hosts of hepatitis Avirus. Vaccine 10(Suppl.1):S27–S31PubMedCrossRefGoogle Scholar
  17. 17.
    Garin D, Biziagos E, Crance JM et al. (1996) Survival of infectious hepatitis A virus in mineral water and seawater. In: Proceedings of the International Symposium on enterically-transmitted hepatitis viruses. Buisson Y, Coursaget P, Kane M (eds). La Simarre, Tours, France pp 48–49Google Scholar
  18. 18.
    Halliday ML, Kang LY, Zhou TK, et al. (1991) An epidemic of hepatitis A attributable to the ingestion of raw clams in Shanghai, China. J Infect Dis 164:852–859PubMedGoogle Scholar
  19. 19.
    Favero MS, Bond WW (1998) Disinfection and sterilization. In:Zuckerman AJ, Thomas HC (eds) Viral Hepatitis: Scientific Basis and Clinical Management. New York, Alan R. Liss, pp 565–575Google Scholar
  20. 20.
    McCaustland GL, Bond WW, Bradley DW, et al. (1982) Survival of hepatitis A in feces after drying and storage for 1 month. J Clin Microbiol 16:957–958PubMedGoogle Scholar
  21. 21.
    Lemon SM, Jansen RW, Brown EA (1992) Genetic, antigenic and biological differences between strains of hepatitis A virus. Vaccine 10(Suppl.1):S40–S44PubMedCrossRefGoogle Scholar
  22. 22.
    Lemon SM (1994) The natural history of hepatitis A: the potential for transmission by transfusion of blood and blood products. Vox Sang 67(Suppl.4):19–23PubMedGoogle Scholar
  23. 23.
    Tassapoulos NC, Papaevangelou GL, Ticehurst JR, et al. (1986) Fecal excretion of Greek strains of hepatitis A virus in patients with hepatitis A and in experimentally infected chimpanzees. J Infect Dis 154:231–237Google Scholar
  24. 24.
    Zuckerman AJ (1983) The history of viral hepatitis from antiquity to the present. In: Deinhardt F, Deinhardt J (eds.). Viral Hepatitis: Laboratory and Clinical Science. Marcel Decker, New York, pp 2–32Google Scholar
  25. 25.
    Gust G (1992) Epidemiological patterns of hepatitis A in different parts of the world. Vaccine 10(Suppl.1):S56–S58PubMedCrossRefGoogle Scholar
  26. 26.
    Banatvala J (1996) Epidemiology of hepatitis A (HAV) in Europe and its relationship to immunisation. In: Proceedings of the International Symposium on enterically-transmitted hepatitis viruses. Buisson Y, Coursaget P, Kane M (eds), La Simarre, Tours, France pp 72–77Google Scholar
  27. 27.
    Steffen R, Kane MA, Shapiro CN, et al. (1994) Epidemiology and prevention of hepatitis A in travelers. JAMA 272:885–889PubMedCrossRefGoogle Scholar
  28. 28.
    Friedman MS, Blake PA, Koehler JE et al. (2000) Factors influencing a communitywide campaign to administer hepatitis A vaccine to men who have sex with men. Am J Public Health 90:1942–1946PubMedGoogle Scholar
  29. 29.
    Harkness J, Gildon B, Istre GR (1989) Outbreaks of hepatitis A among illicit drug users, Oklahoma, 1984–1987. Am J Public Health 79:463–466Google Scholar
  30. 30.
    Jacobson KH, Koopman JS. (2004) Declining hepatitis A seroprevalence: a global review and analysis. Epidemiol Infect 132:1005–1022CrossRefGoogle Scholar
  31. 31.
    Jacobs RJ, Greenberg DP, Koff RS, Saab S, Meyerhoff AS (2003) Regional variation in the cost-effectiveness of chilhood hepatitis A immunization. Pediatr Infect Dis J 22:904–914PubMedCrossRefGoogle Scholar
  32. 32.
    WHO (2000) Weekly Epidemiol Rec 75:38–44Google Scholar
  33. 33.
    Armstrong GL, Bell BP (2002) Hepatitis A virus infection in the United States: model-based estimates and implications for childhood immunization. Pediatrics 209:839–845CrossRefGoogle Scholar
  34. 34.
    CDC (2000) Hepatitis Surveillance Report No.57 38:1–31Google Scholar
  35. 35.
    Yao G (1991) Clinical spectrum and natural history of viral hepatitis A in a 1988 Shanghai epidemic. In:Hollinger FB, Lemon SM, Margolis HS (eds). Viral Hepatitis and Liver Disease. Williams & Wilkins, Baltimore, pp 76–78Google Scholar
  36. 36.
    Ciocca M (2000) Clinical course and consequences of hepatitis A infection. Vaccine 18(Suppl.1):S71–S74PubMedCrossRefGoogle Scholar
  37. 37.
    Reverbel da Silveira T, Ciocca M, Moreira-Silva SF et al. (2002) Hepatitis A as an etiological agent of acute liver failure in six Latin American countries. Presentation at 3rd World Congress of Pediatric Infectious Diseases, Santiogo, Chile, November 19–23, 2002Google Scholar
  38. 38.
    CDC (1999) MMWR 48:1–37Google Scholar
  39. 39.
    Kremastinou L, Kalapothaki V, Trichopoulos D (1984) the changing epidemiology of hepatitis A in urban Greece. Am J Epidemiol 120:703–706PubMedGoogle Scholar
  40. 40.
    André FE, D’Hondt E, Delem A, Safary A (1992) Clinical assessment of the safety and efficacy of an inactivated vaccine: rationale and summary of findings. Vaccine 10(Suppl.1):S160–S168PubMedCrossRefGoogle Scholar
  41. 41.
    Van Herck K, Beutels P, Van Damme P et al. (2000) Mathematical models for assessment of long-term persistence of antibodies after vaccination with two inactivated hepatitis A vaccines. J Med Virol 60(1):1–7PubMedCrossRefGoogle Scholar
  42. 42.
    Van Damme P, Banatvala J, Fay O et al. (2003) Hepatitis A booster vaccination: is there a need? Lancet 362:1065–1071PubMedCrossRefGoogle Scholar
  43. 43.
    Leentvaar-Kuijpers A, Coutinho RA, Brulein V, Safary A (1992) Simultaneous passive and active immunization against hepatitis A. Vaccine 10(Suppl.1):S138–S141PubMedCrossRefGoogle Scholar
  44. 44.
    Piazza M, Safary A, Vengente A et al. (1999) Safety and immunogenicity of hepatitis A vaccine in infants: a candidate for inclusion in the childhood vaccination programme. Vaccine 17:585–588PubMedCrossRefGoogle Scholar
  45. 45.
    Dagan R, Amir J, Mijalovsky A et al. (2000) Immunization against hepatitis A in the first year of life: priming despite the presence of maternal antibodies. Pediatr infect Dis J 19:1045–1052PubMedGoogle Scholar
  46. 46.
    Anderson RM, May RM (1985) Age-related changes in the rate of disease transmission: implications for the design of vaccination programme. J Hyg (Camb) 94:365–436CrossRefGoogle Scholar
  47. 47.
    Fine PEM (2004) Community immunity. In: Vaccines, 4th ed. Plotkin SA, Orenstein WA (eds.) Elsevier, Philadelphia, pp 1443–1461Google Scholar
  48. 48.
    Miller M, Hinman AR (2004) Economic analyses of vaccine policies. In: Vaccines, 4th ed. Plotkin SA, Orenstein WA (eds.) Elsevier Inc., pp 1463–1490Google Scholar
  49. 49.
    Shapiro CN, Coleman PJ, McQuillan GM, Alter MJ, Margolis HS (1992) Epidemiology of hepatitis A: seroepidemiology and risk groups in the USA. Vaccine 10(Suppl.1) S59–S62PubMedCrossRefGoogle Scholar
  50. 50.
    Bell BP, Shapiro CN, Alter MJ et al. (1998) The diverse patterns of hepatitis A in the United States-implications for vaccination strategies. J Infect Dis 178:1579–1584PubMedCrossRefGoogle Scholar
  51. 51.
    World Health Organization (1992) Expanded Programme on Immunization global advisory group. Weekly Epidemiol Rec 3:11–16Google Scholar
  52. 52.
    Smith PF, Grabau JC, Wertzberger A, et al. (1997) The role of young children in a community-wide outbreak of hepatitis A. Epidemiol Infect 118:243–252PubMedCrossRefGoogle Scholar
  53. 53.
    Gorkum J, Leenvaar-Kuijpers A, Kool JL, Coutinho RA (1998) Association between the yearly hepatitis A epidemic and travel behavior of children of immigrants in the four major cities of The Netherlands. Ned Tijdschr Geneesk 34: 1919–1923Google Scholar
  54. 54.
    Fine PEM (1993) Herd immunity: history, theory, practice. Epidemiol Rev 15:265–302PubMedGoogle Scholar
  55. 55.
    Wertzberger A, Mench B, Kuter B et al. (1992) A controlled trial of a formalin-inactivated hepatitis A vaccine in healthy children. N Eng J Med 327:453–457CrossRefGoogle Scholar
  56. 56.
    Innis BL, Snitbhan R, Kunasol P et al. (1994) Protection against hepatitis A by an inactivated vaccine. JAMA 271:28–34CrossRefGoogle Scholar
  57. 57.
    Prikazsky V, Olear A, Cernoch A, Safary A, André FE. (1994) Interruption of an outbreak of hepatitis A in two villages by vaccination. J Med Virol 44:457–459PubMedGoogle Scholar
  58. 58.
    McMahon BJ, Beller M, Williams J et al. (1996) A program to control an outbreak of hepatitis A by using an inactivated hepatitis A vaccine. Arch Pediatr Adolesc Med 150:733–739PubMedGoogle Scholar
  59. 59.
    Averhoff F, Shapiro C Hyams I et al. (1996) The use of inactivated hepatitis A vaccine to interrupt a communitywide hepatitis A outbreak. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Washington DC: American Society for Microbiogy 176: [Abstract H73].Google Scholar
  60. 60.
    Craig AS, Sockwell DC, Schaffner W et al. (1998) Use of hepatitis A vaccine in a communitywide outbreak of hepatitis A. Clin Infect Dis 27:531–535PubMedGoogle Scholar
  61. 61.
    Mele A, Stroffolini T, Palumbo F et al. (1997) Incidence of and risk for hepatitis A in Italy: Public health indications from a 10-year surveillance. J Hepatol 26:743–747PubMedCrossRefGoogle Scholar
  62. 62.
    Lucioni C, Cipriani V, Mazzi S, Panunzio M (1998) Cost of an outbreak of hepatitis A in Puglia, Italy. Pharmacoeconomics 13:257–266PubMedCrossRefGoogle Scholar
  63. 63.
    Mele A, Stroffolini T, Sagliocca L et al. (1997) Control of hepatitis B in Italy. In: Proceedings of IX Triennial International Symposium on Viral Hepatitis and Liver Disease. Rizetto M, Purcell RH, Gerin JL, Verne G (eds.). Minerva Medica, Rome, Italy pp 675–677Google Scholar
  64. 64.
    Lopalco PL, Salleras L, Barbuti S et al. (2001) Hepatitis A and B in children and adolescents — what can we learn from Puglia (Italy) and Catalonia (Spain)? Vaccine 19:470–474CrossRefGoogle Scholar
  65. 65.
    Boccia D (2004) Community outbreak of hepatitis A in southern Italy-Campania, January–May 2004. Eurosurveillance Weekly 8(23): http://www.eurosurveillance.org/ew/2004/040603.aspGoogle Scholar
  66. 66.
    de la Torre J, Esteban R (1995) Implementing universal vaccination programmes: Spain. Vaccine 13(Suppl.1):S72–S74PubMedCrossRefGoogle Scholar
  67. 67.
    Salleras L, Brugera M, Buti M, Dominguez A (2000) Prospects for vaccination against hepatitis A and B in Catalonia (Spain). Vaccine 18(Suppl.1):S80–S82PubMedCrossRefGoogle Scholar
  68. 68.
    Dominguez A, Salleras L, Carmona G, Batalla J (2003) Effectiveness of a mass hepatitis A vaccination program in preadolescents. Vaccine 21:698–701PubMedCrossRefGoogle Scholar
  69. 69.
    Navas E, Salleras l, Gisbert R, Dominguez A, Prat A (2004) Economic evaluation of the incorporation of the hepatitis A vaccine as a combined A+B vaccine to the universal hepatitis B vaccination programme of preadolescents in schools. Fourth World Congress on Vaccines and Immunization in Tokyo, Japan, September 30–October 3 2004 [Abstract S1–S10]Google Scholar
  70. 70.
    Hanna JN, Hills SL, Humphreys JL (2004) Impact of hepatitis A vaccination of Indigenous Children on notifications of hepatitis A in North Queensland. Med J Aus 181:482–485Google Scholar
  71. 71.
    Merritt A, Symons D, Griffiths M (1999) The epidemiology of acute hepatitis A in North Queensland, 1996–1997. Commun Dis Intell 23:120–124PubMedGoogle Scholar
  72. 72.
    Hanna JN, Warnock TH, Shepherd RW, Selvey LA (2000) Fulminant hepatitis A in Indigenous children in North Queensland. Med J Aus 172:19–21Google Scholar
  73. 73.
    Zamir C, Rishpon D, Zamir D, Leventhal A, Rimon N, Ben-Porath E (2001) Control of a community-wide outbreak of hepatitis A by mass vaccination with inactivated hepatitis A vaccine. Eur J Clin Microbiol Infect Dis 20:185–187PubMedCrossRefGoogle Scholar
  74. 74.
    Dagan R, Leventhal A, Anis E, Slater P, Shouval D (2002) National hepatitis Avirus (HAV) immunization program aimed exclusively at toddlers in an endemic country resulting in >90% reduction in morbidity rate in all ages. 40th Annual Meeting of Infectious Diseases Society of America [Abstract 825]Google Scholar
  75. 75.
    Shouval D (2004) Universal immunization against hepatitis A to toddlers in Israel is leading to disappearance of HAV infection — The Jerusalem experience. Proceedings Biennial Scientific Meeting of International Association for Study of the Liver, Bahia, Brazil 4;4–5Google Scholar
  76. 76.
    Dagan R, Leventhal A, Anis E, Slater P, Ashur Y, Shouval D (2005) Incidence of hepatitis A in Israel following universal immunization of toddlers. JAMA 294:202–210PubMedCrossRefGoogle Scholar
  77. 77.
    CDC (1996) Prevention of hepatitis A through active or passive immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 45(RR-15):1–30Google Scholar
  78. 78.
    CDC (1999) Prevention of hepatitis A through active or passive immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 48(RR-12):1–37Google Scholar
  79. 79.
    Bialek SR, Thoroughman DA, Hu D et al. (2004) Hepatitis A incidence and hepatitis A vaccination among American Indians and Alaska Natives, 1990–2001. Am J Public Health 94:996–1001PubMedCrossRefGoogle Scholar
  80. 80.
    Samandari T, Bell BP, Armstrong GL (2004) Quantifying the impact of hepatitis A immunization in the United States, 1995–2001. Vaccine 22:4342–4350PubMedCrossRefGoogle Scholar
  81. 81.
    Van Effelterre T, Zink TK, Rosenthal P (2005) A model of hepatitis A transmission in the US. Poster 19 at Conference of American College of Preventive Medicine held on February, 16–20, Washington DCGoogle Scholar
  82. 82.
    Jacobs RJ, Zink T, Meyerhoff AS (2004) Hepatitis A immunization strategies: universal versus targeted approaches. Proceedings annual Meeting of Pediatric Academic Societies, San Francisco, May 1–4Google Scholar
  83. 83.
    CDC (2005) Hepatitis A vaccination coverage among children aged 24–35 months, United States, 2003. MMWR 54:141–144Google Scholar
  84. 84.
    CDC hepatitis A slide set. (http://www.cdc.gov)Google Scholar
  85. 85.
    Wasley A, Samandari T, Bell BP (2005) Incidence of hepatitis A in the United States in the era of vaccination. JAMA 294:194–201PubMedCrossRefGoogle Scholar
  86. 86.
    Samoilovich EO (2005) Personal communication. March 2nd 2005Google Scholar
  87. 87.
    Anonymous (1992) Prospects for control of hepatitis A: panel discussion. In: Hollinger FB, André FE, Melnick J (eds). Proceedings of International Symposium on active immunization against hepatitis A. Vaccine 10(Suppl.1):S170–S174Google Scholar
  88. 88.
    Bell BP, Feinstone SM(2004) Hepatitis A vaccine. In: Vaccines, 4th ed. Plotkin SA, Orenstein WA (eds.) Elsevier Inc., pp 269–297Google Scholar
  89. 89.
    Scheifele DW (2005) Hepatitis A vaccines: the growing case for universal immunization of children. Expert Opin Pharmacother 6:157–164PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • F. E. André
    • 1
  1. 1.RixensartBelgium

Personalised recommendations