The new Italian guidelines for the use of hepatitis A vaccine

1. The new Italian guidelines for the use of hepatitis A vaccine Elisabetta Franco Dept. of Public Health University of Rome Tor Vergata - Italy

2. Consequences of the change in epidemiology (improved socio-economic/hygiene conditions) Exposure in early life Proportion of susceptibles among older children & adults Risk for clinically significant OUTBREAKS + Proportion of symptomatic disease with age

3. WHO RECOMMENDATIONS In highly endemic countries most persons are asymptomatically infected with HAV in childhood, which effectively prevents clinical hepatitis A in adolescents and adults. In these countries large scale programs are not recommended. In countries of intermediate endemicity where much of the population is susceptible and hepatitis A represents a health burden, large scale vaccination may be considered as a supplement to education and sanitation.

4. WHO RECOMMENDATIONS In regions of low endemicity, vaccination against HAV is recommended for individuals with increased risk of infection. Epidemiological and cost benefit studies should be considered before deciding on national policies concerning immunization. Wkly Epidemiol Rev 2000 5:38-44

5. Documento di indirizzo: L'uso del vaccino anti epatite A in Italia • Sicurezza, efficacia, indicazioni d'impiego nei gruppi a rischio e in caso di epidemia Maggio 2002

6. WHY? The paper contains the evidence available in literature and the expert opinions on the possible use of the vaccine, in the attempt to assist public health doctors and clinicians in controlling HAV infection and in counselling of patients and contacts.

7. METHODS • Individuation of a multidisciplinary team of experts toaddress clinic and organization questions • Research of scientific evidences from literature in database as Medline, Embase, The Cochrane Controlled Trial Register • Evaluation of papers obtained from literature search • Selection and evaluation of pertinent evidences • Synthesis of conclusive data • Conversion of evidences into recommendations

8. CONTENTS The Guidelines include: • Epidemiology of HAV infection in Italy • A systematic review of the effectiveness and safety of vaccine • An economic evaluation for the use of the vaccine • A systematic review of risk groups • A systematic review of measures in course of outbreaks • A systematic review of post-exposure prophylaxis • A synthesis of the main evidences

9. EFFECTIVENESS AND SAFETY OF VACCINE Seven papers have been obtained by systematic review. The effectiveness of vaccine was 86% in pre exposure and 82% in post exposure prophylaxis. No important adverse reactions have been reported.

10. ECONOMIC EVALUATION From the economic point of view mass vaccination is convenient only in course of outbreaks, while the vaccination of the contacts of acute hepatitis A cases should be used as a routine measure.

11. Travelers Military Personnel Health Care Workers Sewage Workers Food Handlers Day Care Centers Institutions Transfusion Hemophilia Drug Addicts Homosexual Prisoners HIV Transplantation RISK GROUPS for Hepatitis A virus infection

12. TRAVELERS Evidences about the risk of acquiring hepatitis A essentially date back to studies performed in the eighties and early nineties; however, despite the improvement of socio-economic level, travels are still considered a risk factor, with a gradation dependent on the endemicity of visited areas and on the observance of hygiene preventive measures

13. HEALTH CARE WORKERS On the basis of the documented effectiveness of the universal precaution measures in protecting against HAV occupational exposure a group, in which there is no evidence of higher antibody seroprevalence than in the general population, there is no evidence that health care workers constitute a risk group for HAV infection.

14. SEWAGE WORKERS There is evidence that sewage workers are exposed to a higher personal risk related to the profession, even observing adequate hygienic precautions. However they do not represent a risk for the community and no epidemics are reported where they represented the infection source.

15. FOOD HANDLERS Food handlers can contract HAV from contaminated food, and, once infected, they may be the source of infection. There are, however, no evidences to consider food handlers as a risk group and the contamination of food by infected food handlers or the infection by contaminated food manipulation are easily avoidable by observing the most common and basic hygienic norms.

16. DAY CARE PERSONNEL In day care centre not only children, but also family members and personnel are at risk for HAV infection. For both groups the risk is related to close contact with children and is greater within the family as in personnel it can be easily avoided observing the generally adopted standard hygienic measures. There are therefore no strong evidences for considering personnel of day care centres as a risk group for HAV.

17. INSTITUTIONALIZED PERSONS Outbreaks of hepatitis A in institutions for subjects with physical and, above all, mental handicaps have been described in which the age of residents and the length of stay were related to the risk of acquiring HAV and a higher antibody prevalence was detected among patients. There is evidence of risk of contracting hepatitis A among institutionalised subjects while staff members may easily protect themselves from exposure to HAV.

18. HAEMOPHILIA PATIENTS Hepatitis A outbreaks among haemophiliacs treated with S/D inactivated factors VIII/IX concentrates have been described in the past, but in the last years no more cases of HAV infection have been reported, due to the improved inactivation methods and the use of products obtained through genetic recombination techniques. Seroprevalence and case-control studies do not show an increased risk of hepatitis A among haemophiliacs.

19. DRUG ADDICTS Epidemics that happen regularly among drug addicts and homosexual men have been described and it is pointed out that these groups may become important sources of hepatitis A, even if drug addicts are not recognised as sources of epidemics in the general population. Hepatitis A prevalence is slightly higher in drug addicts than in various control populations; the transmission is connected to socio-economic factors, sexual promiscuity, syringe exchange and contamination of instruments used to prepare drug.

20. SEXUAL PROMISCUITY The hypothesis of considering homosexuals as a potential group at risk of acquiring HAV dates back to the early Nineties and arises from the demonstration of a peak incidence of hepatitis A in males aged 20 – 39 and the description of many outbreaks among homosexuals. The risk of acquiring HAV infection is linked to oro–anal sexual practices and sexual promiscuity. Prevalence studies do not show significant differences in anti-HAV prevalence between homosexuals and control groups.

21. PATIENTS WITH CHRONIC LIVER DISEASE Even if not all the examined papers are of high quality, from the systematic review it results that these patients show a greater risk of complications. The vaccination is recommended to patients with an advanced chronic liver disease.

22. OUTBREAKS In closed communities, like day care centers, where most subjects are susceptible and the risk for person to person transmission is high, vaccine is recommended for family members, school mates and personnel after a single case. In older age groups, vaccination is recommended if a secondary case is demonstrated.

23. OUTBREAKS In small open communities, like small towns (less than 5.000 inhabitants), vaccination is recommended to more susceptible age groups like children and adolescents. This intervention is effective if coverage is more than 80% of the target population.

24. OUTBREAKS In large communities with high interepidemic incidence and periodic outbreaks mass vaccination cannot be offered due to the difficulty of reaching high coverage in a short time. Vaccine should be offered to contacts of acute cases, combined with the improvement of sanitation.

25. POST-EXPOSURE PROPHYLAXIS There is only a recent trial about the effectiveness of vaccine as post-exposure prophylaxis (82%). The vaccine administered not later than 8 days since the exposure is preferred to the use of gamma-globulins.

26. IN CONCLUSION Although the proposed recommendations are meant for the Italian epidemiological context, the evidence and the discussion presented in the Guide Lines are useful materials for implementing vaccination against hepatitis A in other western countries.