Summary
Hepatitis A virus (HAV) infection, once endemic in children in most continents and usually asymptomatic, is now declining. As a result, more and more adult populations worldwide are becoming susceptible to HAV infection, which is frequently symptomatic and disabling in those above 12 to 15 years of age.
Traditionally, serum immunoglobulins containing high-titre antibodies to HAV (anti-HAV) have been used effectively during the past 50 years for post- or pre-exposure prophylaxis. However, decreasing prevalence of individuals with anti-HAV has led to a worldwide decline in anti-HAV titres in blood donors and, as a result, to a shortage of immunoglobulin. Meanwhile, several excellent vaccines have been developed from attenuated HAV propagated in tissue culture and inactivated by formaldehyde. These vaccines are highly efficacious and immunogenic, and so far have an excellent record of safety and tolerability.
Currently, a single dose of these HAV vaccines will prime the immune system in children and young adults, affording rapid protection against clinical HAV-induced disease within 3 to 5 weeks of administration and lasting for more than 6 months. Booster doses will prolong protection for several years.
To date, some federal health agencies believe that cost-benefit analysis still favours immunoglobulin administration over active immunisation for hepatitis A prophylaxis. However, once the cost of the new vaccines drops, immunisation is expected to gain worldwide acceptance by national healthcare authorities.
Available data already suggest that 2 to 3 doses of the new vaccines will provide long term immunity against HAV, thus reducing the discomfort and unknown long term risks associated with immunoglobulin injection. Thus, regardless of economic considerations, travel medicine experts and primary care physicians in most Western countries recommend active immunisation against HAV for individuals at risk if they can afford to cover the cost.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Siegl G, Frösner GG. Characterization and classification of virus particles associated with hepatitis A. I and II. J Virol 1978; 26: 40–53
Robertson BH, Khanna B, Nainan OV, et al. Epidemiologic patterns of wild-type hepatitis A virus determined by genetic variation. J Infect Dis 1990; 163: 286–92
Ticehurst JR, Racianello VR, Baroudy BM, et al. Molecular cloning and characterization of hepatitis A virus cDNA. Proc Natl Acad Sci USA 1983; 80: 5885–9
Brown EA, Ticehurst J, Lemon SM. Immunopathology of hepatitis A and hepatitis E virus infections. In: Thomas HC, Waters J, editors. Immunology of liver disease. Dordrecht: Kluwer, 1994: 11–37
Shapiro CN, Margolis HS. Worldwide epidemiology of hepatitis A virus infection. J Hepatol 1993; 18 Suppl. 2: 11S–4S
Robertson BH, Friedberg D, Normann A, et al. Sequence variability of hepatitis A virus and factor VIII associated hepatitis A infections in hemophilia patients in Europe. Vox Sang 1994; 67 Suppl. 1: 39–46
Hadler SC. Global impact of hepatitis A infection changing patterns. In: Hollinger FB, Lemon SM, Margolis HS, editors. Viral hepatitis and liver disease. Proceedings of the 1990 International Symposium on Viral Hepatitis and Liver Disease. Baltimore: Williams and Wilkins, 1990: 14–20
Tao GB. Clinical spectrum and natural history of viral hepatitis A in 1988 Shanghai epidemic. In: Hollinger FB, Lemon SM, Margolis HS, editors. Viral hepatitis and liver disease. Proceedings of the 1990 International Symposium on Viral Hepatitis and Liver Disease. Baltimore: Williams and Wilkins, 1990: 76–8
Koff RS. Difficult serologic diagnoses in viral hepatitis. In: Hollinger FB, Lemon SM, Margolis HS, editors. Viral hepatitis and liver disease. Proceedings of the 1990 International Symposium on Viral Hepatitis and Liver Disease. Baltimore: Williams and Wilkins, 1990: 790–1
Glikson M, Galun E, Oren R, et al. Relapsing hepatitis A: review of 14 cases and literature survey. Medicine 1992; 71: 14–23
Villarejos VM, Serra JC, Anderson-Visona K, et al. Hepatitis A virus infection in households. Am J Epidemiol 1982; 115: 577–86
Winokur PL, Stapleton JT. Immune globulin prophylaxis of hepatitis A. Clin Infect Dis 1992; 14: 580–6
Ellerbeck E, Lewis J, Midthun K, et al. Safety and immunogenicity of an inactivated hepatitis A virus vaccine. In: Hollinger FB, Lemon SM, Margolis HS, editors. Viral hepatitis and liver disease. Proceedings of the 1990 International Symposium on Viral Hepatitis and Liver Disease. Baltimore: Williams and Wilkins, 1990: 91–3
Ambrosch F, Wiedermann G, André FE, et al. Comparison of HAV antibodies induced by vaccination, passive immunization, and natural infection. In: Hollinger FB, Lemon SM, Margolis HS, editors. Viral hepatitis and liver disease. Proceedings of the 1990 International Symposium on Viral Hepatitis and Liver Disease. Baltimore: Williams and Wilkins, 1990: 98–100
Gerety RJ, Smallwood LA, Finlayson JS, et al. Standardization of the antibody to hepatitis A virus (anti-HAV) content of immunoglobulin. Dev Biol Stand 1983; 54: 411–6
Lemon SM. Immunologic approaches to assessing the response to inactivated hepatitis A vaccine. J Hepatol 1993; 18 Suppl. 2: 15S–9S
Margolis HS, Hadler SC, Shapiro CN, et al. Immunization strategies for the control of hepatitis A in the United States. In: Hollinger FB, Lemon SM, Margolis HS, editors. Viral hepatitis and liver disease. Proceedings of the 1990 International Symposium on Viral Hepatitis and Liver Disease. Baltimore: Williams and Wilkins, 1990: 724–6
Stokes Jr J, Neefe JR. The prevention and attenuation of infectious hepatitis by gamma globulin. JAMA 1945; 127: 144–5
Havens Jr WP, Jr Paul. Prevention of infectious hepatitis with gamma globulin. JAMA. 1945; 129: 270–2
Gellis SS, Stokes Jr J, Brother GM, et al. The use of human immune serum globulin (gamma globulin) in infectious (epidemic) hepatitis in the Mediterranean Theatre of Operations. I. Studies on prophylaxis in two epidemics of infectious hepatitis. JAMA 1945; 128: 1062–3
Woodson RD, Clinton JJ. Hepatitis prophylaxis abroad: effectiveness of immune serum globulin in protecting Peace Corps volunteers. JAMA 1969; 209: 1053–8
Kark JD, Witztum E, Mazkin H, et al. The three-year incidence of non-B viral hepatitis morbidity in a controlled trial of pre-exposure immune serum globulin prophylaxis. Infection 1984; 12: 251–5
Lednar WM, Lemon SM, Kirkpatrick JW, et al. Frequency of illness associated with epidemic hepatitis A virus infections in adults. Am J Epidemiol 1985; 122: 226–33
Conrad ME, Lemon SM. Prevention of endemic icteric viral hepatitis by administration of immune serum gamma globulin. J Infect Dis 1987; 156: 56–63
Stapleton JT. Passive immunization against hepatitis A. Vaccine 1992; 10 Suppl. 1: 45S–7S
Fujiyama S, Iino S, Odoh K, et al. Time course of hepatitis A virus antibody titer after active and passive immunization. Hepatology 1992; 15: 983–8
Behrens RH, Doherty JF. Severe hepatitis A despite passive immunization. Lancet 1993; 341: 972
Shouval D, Ashur Y, Adler R, et al. Single and booster dose responses to an inactivated hepatitis A virus vaccine: comparison with immune serum globulin prophylaxis. Vaccine 1993; 11 Suppl. 1: 9S–14S
Provost PJ, Ittensohn OL, Villarejos VM, et al. Etiological relationship of marmoset-propagated CR326 hepatitis A virus to hepatitis in man. Proc Soc Exp Biol Med 1973; 142: 1257–67
Sjogren MH, Hoke CH, Binn LN, et al. Immunogenicity of an inactivated hepatitis A vaccine. Ann Intern Med 1991; 114: 470–1
Just M, Berger R, Drechsler H, et al. A single vaccination with an inactivated hepatitis A liposome vaccine induces protective antibodies after only two weeks. Vaccine 1992; 10: 737–9
Flehmig B, Heinricy U, Pfisterer M. Immunogenicity of a killed hepatitis A vaccine in seronegative volunteers. Lancet 1989; I: 1039–41
Totsuka A, Moritsugu Y. Hepatitis A vaccine development in Japan. In: Nishioka K, Suzuki H, Mishiro S, et al., editors. Viral hepatitis and liver disease. Proceedings of the International Symposium on Viral Hepatitis and Liver Disease; 1993. Tokyo: Springer-Verlag, 1994: 509–13
Mao JS, Dong DX, Zhang HY, et al. Primary study of attenuated live hepatitis A vaccine (H2 strain) in humans. J Infect Dis 1989; 159: 621–4
Kusov YY, Elbert LB, Nelga IV, et al. Immunogenicity trial of inactivated hepatitis A virus vaccine in human volunteers. Vaccine 1991; 9: 540–1
Armstrong ME, Giesa PA, Davide JP, et al. Development of the formalin-inactivated hepatitis A vaccine, VAQTA™, from the live attenuated virus strain CR326F. J Hepatol 1993; 18 Suppl. 2: 20S–6S
Peetermens J. Production, quality control and characterization of an inactivated hepatitis A vaccine. Vaccine 1992; 10 Suppl. 1: 99S–101S
Midthun K, Ellerbeck E, Gersham K, et al. Safety and immunogenicity of a live attenuated hepatitis A virus vaccine in seronegative volunteers. J Infect Dis 1991; 163: 735–9
Sjogren MH, Purcell RH, McKee K, et al. Clinical and laboratory observations following oral or intramuscular administration of a live attenuated hepatitis A vaccine candidate. Vaccine 1992; 10 Suppl. 1: 135S–7S
Shouval D, editor. International Symposium on Hepatitis A Vaccine. J Hepatol 1993; 18 Suppl. 2: S1–71
Hollinger FB, Andre FE, Melnick J, editors. International Symposium on Active Immunization against Hepatitis A. Vaccine 1992; 10 Suppl. 1: S1–174
Werzberger A, Mensch B, Kuter B, et al. A controlled trial of a formalin-inactivated hepatitis A vaccine in healthy children. N Engl J Med 1992; 327: 453–7
Public health control of hepatitis A: memorandum from a WHO meeting. Bull World Health Organ 1995; 73(1): 15–20
Innis BL, Snitbhan R, Kunasol P, et al. Protection against hepatitis A by an inactivated vaccine. JAMA 1994; 271: 1328–34
Van Damme P, Matheì C, Thoelen S, et al. Single dose inactivated hepatitis A vaccine: rationale and clinical assessment of the safety and immunogenicity. J Med Virol 1994; 44: 435–41
Van Damme P, Thoelen S, Cramm M, et al. Inactivated hepatitis A vaccine: reactinogenicity, and long-term antibody persistence. J Med Virol 1994; 44: 446–51
Leentvaar-Kuijpers A, Coutinho RA, Brulein V, et al. Simultaneous passive and active immunization against hepatitis A. Vaccine 1992; 10 Suppl. 1: 138S–41S
Tormans G, Van Damme P, Van Doorslaer E. Cost-effectiveness analysis of hepatitis A prevention in travellers. Vaccine 1992; 10 Suppl. 1: 88S–92S
Zuckerman JN, Powell L. Hepatitis A antibodies in attenders of London travel clinics: cost-benefit of screening prior to hepatitis A immunisation. J Med Virol 1994; 44: 393–4
Steffen R, Gyurech D. Advances in hepatitis A prevention in travellers. J Med Virol 1994; 44: 460–2
Van Doorslaer E, Tormans G, Van Damme P. Cost-effectiveness analysis of vaccination against hepatitis A in travellers. J Med Virol 1994; 44: 463–9
Gray GC, Rodier GR. Prevaccination screening for citizens of the United States living abroad who are at risk for hepatitis A. Clin Infect Dis 1994; 19: 225–6
Steinninger P, Bader T. Declining prevalence of immunity of hepatitis A virus [abstract no. 311]. In: The American Association for the Study of Liver Diseases, postgraduate course & 46th annual meeting. 1995 Nov 3–7, Chicago. Hepatology 1995; 22: 184A
Behrens RH, Roberts JA. Is travel prophylaxis worthwhile? Economic appraisal of prophylactic measures against malaria, hepatitis A, and typhoid in travellers. BMJ 1994; 309: 918–22
Poovorawan Y, Theamboonlers A, Sanpavat S, et al. The immunogenicity and reactogenicity of combined tetravalent diphtheria, tetanus, pertussis, and hepatitis B vaccine in infants. In: Nishioka K, Suzuki H, Mishiro S, et al., editors. Viral hepatitis and liver disease. Proceedings of the International Symposium on Viral Hepatitis and Liver Disease, 1993 Tokyo: Springer-Verlag, 1994: 526–9
Ambrosch F, Wiedermann G, Andre FE, et al. Clinical and immunological investigation of a new combined hepatitis A and hepatitis B vaccine. J Med Virol 1994; 44: 452–6
Andre FE. Approaches to a vaccine against hepatitis A: development and manufacture of an inactivated vaccine. J Infect Dis 1995; 171 Suppl. 1: 33S–9S
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Adler, R., Shouval, D. Hepatitis A Prophylaxis. Clin. Immunother. 6, 261–272 (1996). https://doi.org/10.1007/BF03259088
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03259088