Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Vaccination prevented secondary hepatitis A virus infection in household contacts

ACP J Club. 1999 Sept-Oct;131:45. doi:10.7326/ACPJC-1999-131-2-045


Source Citation

Sagliocca L, Amoroso P, Stroffolini T, et al. Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: a randomised trial. Lancet. 1999 Apr 3;353:1136-9. [PubMed ID: 99224683]


Abstract

Question

Can hepatitis A vaccination prevent secondary hepatitis A virus (HAV) infection in household contacts who have been exposed to a family member with acute HAV infection?

Design

Randomized controlled trial with 45-day follow-up.

Setting

A hospital and its catchment area in Naples, Italy.

Patients

380 adults hospitalized with HAV infection were screened, and 146 were studied (62% men). Inclusion criteria were primary HAV infection, positivity for HAV IgM, serum alanine aminotransferase levels ≥ twice the normal value, and hospitalization within 1 week of symptom onset. All members of the patient's household who were 1 to 40 years of age were studied as a household unit.

Intervention

Household units were randomly allocated by week of study to receive vaccination (n = 71 households and 197 persons) or not to receive vaccination (n = 75 households and 207 persons). Vaccinations were a single intramuscular injection in the deltoid. 1440 enzyme-linked immunosorbent assay (ELISA) units were used in persons ≥ 11 years of age, and 720 ELISA units were used in children < 11 years of age. Household contacts were categorized as being co-primary cases, immune, or susceptible. Only household contacts who were negative for anti-HAV IgM were followed (110 in the vaccination group and 102 in the control group). Final data were available for 97% of participants and 100% of households.

Main outcome measure

Secondary HAV infection ascertained by a positive test result for anti-HAV IgM at least 2 weeks after vaccination.

Main results

Fewer households and household contacts in the vaccination group had secondary infections than did households { P = 0.01}* or contacts { P = 0.004}* in the control group (Table).

Conclusion

Vaccination of household contacts after primary hepatitis A virus infection in a family member reduced the rate of secondary hepatitis A virus infection in households and in household contacts.

Source of funding: Viral Hepatitis Project and Blood Project, Istituto Superiore di Sanità.

For correspondence: Dr. A. Mele, Laboratory of Epidemiology, ISS, Viale Regina Elena 299, 00161 Rome, Italy. FAX 39-064938 7173.

*Numbers calculated from data in article.


Table. Laboratory-confirmed secondary cases of hepatitis A virus infection in household contacts for vaccination vs no vaccination at 45-day follow-up†

Unit of analysis Vaccination No vaccination RRR (95% CI) NNT (CI)
Households (n = 146) 2.8% 13.3% 79% (18 to 95) 10 (5 to 54)
Household contacts (n = 404) 1.0% 5.8% 82% (31 to 96) 21 (11 to 70)

†Abbreviations defined in Glossary. RRR, CI, and NNT calculated from data in article.


Commentary

Postexposure prophylaxis for HAV infection has relied on intramuscular im-munoglobulin for > 50 years. When administered within 2 weeks of an exposure to HAV, immunoglobulin protects against clinical HAV infection in at least 70% to 90% of patients, and the U.S. Centers for Disease Control and Prevention (CDC) recommends its use without concurrent vaccination for postexposure prophylaxis (1, 2). A standard dose, however, confers protection for < 3 months.

HAV vaccines are efficacious for interrupting outbreaks and provide long-term immunity (2), but their role in postexposure prophylaxis is unknown. During outbreaks, HAV vaccination has resulted in a substantial decrease in rates of acute hepatitis, to < 2% in vaccinated persons (3, 4). Sagliocca and colleagues compared persons who received HAV vaccine and untreated persons among household members of patients hospitalized for acute HAV infection. The study did not include a group that received immunoglobulin. The vaccine reduced clinical, biochemical, and serologic hepatitis to a degree similar to that expected with immunoglobulin. This study supports further investigation into the role of HAV vaccine for postexposure prophylaxis, but the CDC guidelines based on immunoglobulin should not yet be amended.

Paul D. King, MD
University of Missouri School of MedicineColumbia, Missouri, USA


References

1. Koff RS. Preventing hepatitis A infections in travelers to endemic areas. Am J Trop Med Hyg. 1995;53:586-90.

2. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 1996;45:1-30.

3. 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.

4. McMahon BJ, Beller M, Williams J, et al. A program to control an outbreak of hepatitis A in Alaska by using an inactivated hepatitis A vaccine. Arch Pediatr Adolesc Med. 1996;50:733-9.