1. Hepatitis A Vaccination Offers Long-Term Immunity

3. The Hepatitis A Virus

4. The HAV Replication Cycle

7. Hepatitis A – Transmission is typically by the faecal-oral route: Contamination of food or water Close person-to-person contact Sexual oral-anal contact Less typically, hepatitis A may be transmitted in body fluids such as blood and saliva.

8. Symptomatic Ratio in Day - Care Children

9. “ Clinical illness is rare in children infected in the first year of life, occurs in about one - fourth of those under the age of 15, and is almost universal in adults. Gust &Feinstone 1990

10. Symptoms of Hepatitis A in Children & Adults

15. Complications of Hepatitis A Cholestatic Joundice Relapsing Hepatitis Fulminant Hepatitis

17. Hepatitis A: Clinical Characteristics of Patients by Age Group Clinical Characteristics <1-14yrs 15-39yrs 40+yrs (n=1692) (n=4918) (n=1386) Jaundice 81.7% 86.8% 70.3% Hospitalised for Hepatitis 17.1% 32.2% 70.3% Death as a result of Hepatitis 0.1% 0.3% 2.1%

18. “As there is no specific treatment for hepatitis A, management is basically Supportive…” Dr lan D Gust & Dr Sptephen M Feinstone

29. Highly developed countries, such as japan, Australia, and most parts of North America and Europe, are largely low endemicity regions for hepatitis A Many residents of these areas have no natyral immunity against hepatitis A virus

35. Morbidity & Mortality per 100,000 Unprotected Travellers to Developing Countries per Month of Stay Abroad INFECTIONMorbidityCase Fatality rate(%) Mortality _______________________________________________________________ _______ Malaria,West Africa 2400 2(for p. falciparum) 40 Malaria,South America 50 2(for p. falciparum) 0.15 Hepatitis A: generally 300(-600) 0.1 0.3(-0.6) Hepatitis A:backpackers 2000 0.1 2 Hepatitis B:expatriates 80(-240) 2 1.6(-4.8) Typhoid fever : usual destination 3 1 0.03 Typhoid : India, N-,W-Africa 30 1 0.3 Ppliomyelitis : symptomatic 0.120 0.02 Poliomyelitis: Symptomatic 0.1 20 0.02 Poliomyelitis: asymptomatic2(-100) - (contacts) Cholera 0.3 2 0.006

36. Travellers at Risk of HAV Infection Tourists Business travellers Foreign aid workers Airline Personnel Missionaries Professionals working abroad

37. “Symptomatic hepatitis A is the most frequently occurring immunisable infection in travellers” “The incidence rate of symptomatic hepatitis A for a one month journey from an industrialised country to a developing country is 3/1000 for the usual non-immune traveller” “This applies also to tourists staying in renowned hotels”

38. Uk Travellers Abroad Protection is advised for non-immune Travellers from the UK visiting all countries Outside of Northern Europe, North America, New Zealand and Australia

39. “ In unprotected travellers, hepatitis A occurs 40 times more frequently than typhoid fever and 800 times more frequently than cholera” Steffen 1991

40. This availabillity of an effective hepatitis A vaccine will make it possible, at last, to provide protection against one of the oldest disease threats to the healthy soldier Col WH Bancroft MD Walter Reed Army Institute,washington DC

41. This enhanced risk of hepatitis Ainfection for the nursing profession … prompts us to demand that (this type of disease) should also of professional diseases Windorfer et al 1989

42. Hepatitis A in both employees and household contacts is strongly related to contact with children whoo attend day-care centre Hadler et al 1980

43. Protection is advised for close contacts of all ages in order to control outbreaks of hepatitis A in households and in institutions Joint Committee on Vaccination and Immunisation

44. Prevention of Hepatitis A Improvement in water Supply, sanitation and hygiene Isolation of infected individuals Passive immunisation (IG) Active immunisation ( vaccination)

45. Passive Immunisation Short –term protection- requires frequent renewal No stimulation of antibody production in recipient Plasma- derived product Large injection volumes

46. Active Vaccination Long –term immunity from active vaccination Stimulates antibody production in the recipient Non plasma-derived product Small IM injection volumes administered via deltoid

47. Recombinant Vaccines HAV epitope is complex Current technology has not been able to reproduce the epitope in isolation The development of a recombinant vaccine against hepatitis A will be very difficult

48. Live, Attenuated Vaccines Difficult to develop Under-attenuation may lead to active infection Over-attenuation may lead to vaccine failure Re-emergence infection in both recipient and close contacts

49. Inactivated Vaccine Killed virus – incapable of causing active infection Killed Virus – possesses the antigens which stimulate the production of anti-HAV Can be developed using proven technology (polio, salk)

52. ‘Havrix’ Hepatitis A Vaccine Seroconversion Rates Injections given at months o ad 1 with a booster dose at 6 months Blood Sample Taken M O N T H 1 2 7 % Seroconversion 95.6 99.9 100 (987/1032) (1035/1036) (592/592)

54. Hepatitis A Vaccination Offers Long- Term Immunity

55. Havrix Hepatitis A Vaccine Prescribing Information and References available at this meeting SB Smithkline Beecham Pharmaceuticals ‘Havrix’ is a trade mark 1992 smithkline Beecham Pharmaceuticals