Acute hepatitis immunization program successful in Italy

April 2008

Acute hepatitis B incidence has decreased dramatically during the 14 years since universal vaccinations were introduced in Italy, but challenges remain to reach even lower rates.

Intermediate-level endemicity HBV infection peaked in Italy in the 1970s and 1990s. In 1992, Italy implemented a mandatory HBV vaccination program, making it the first European country to require universal HBV vaccination. Through the program, which aimed to immunize all newborns and children aged 12 years, more than 12 million children were vaccinated against HBV.

The researchers from several institutions located in different regions of Italy assessed trends in morbidity both before and after the implementation of the mandatory HBV vaccination program. Results and commentary on the study appeared in Clinical Infectious Diseases.

People aged 15 to 24 years reaped the most benefit from the targeted immunization program. Risks for acute HBV infection in that age group decreased 50 times in the years following mandatory vaccination. A decline in HBV cases in Italy began before the immunization program was implemented — incidence rates dropped from 10.4 cases per 100,000 people in 1987 to 5.4 cases per 100,000 people in 1990. The researchers attributed the decline to socioeconomic change in Italy.

The strongest associations with acute HBV infection after the implementation of mandatory immunizations were blood transfusions, living with an HBV carrier, intravenous drug use and unsafe sexual practices. Most infections occurred in people aged 25 years and older and were associated with these risk groups, skin treatments or exposure through medical treatment.

Vaccine coverage for high risk groups, infection control measures to reduce exposure risk during surgery and skin treatment, and additional HBV screening for blood transfusions should be improved to further curtail acute HBV infections in Italy, the researchers wrote.

Health policy prevention programs also should include targeting immigrant populations., they said

An estimated 2 billion people worldwide have HBV, 350 million people have chronic infection and 4 million new acute infections are diagnosed each year. More than half of all cases of hepatocellular carcinoma are caused by HBV, and roughly 600,000 deaths are attributed to HBV each year.

In early childhood, vertical and horizontal transmission play the greatest roles in creating HBV infection endemicity. Countries with high or intermediate HBV endemicity also report increased rates of other types of transmission, including high-risk sexual activity and unsafe injections.

In developing countries, an estimated 30% of new HBV infections are caused by reusing syringes in health care settings, the researchers wrote.

Incidence rates

Cases of acute HBV are reported to The National Surveillance System for Acute Viral Hepatitis (SEIEVA), coordinated by the Italian National Institute of Health, which covers an estimated 60% of Italy’s population.

Incidence rates of acute HBV infection were estimated from the inception of the mandatory vaccination program in 1991 to 2005 through a case-control study within population-based surveillance for acute viral hepatitis. Of the 9,160 patients with acute HBV infection surveyed during the 14-year period, approximately 75% were men, and 90% were aged 25 years or older.

The researchers also analyzed the association between acute HBV infection and risk factors from 2001 to 2005. During 2001 to 2005, 2,740 cases of acute HBV infection were reported and 12 of those patients died. Median age of patients was 66 years. HBV patients were compared with a control group of patients (n=4,893) who reported acute hepatitis A infections during the same period.

Risk groups identified

Incidence of acute HBV decreased progressively from 5.1 cases per 100,000 people in 1991 to 1.3 cases per 100,000 people in 2005.

Acute HBV incidence decreased markedly in two target age groups - patients aged 0 to 14 years and patients aged 15 to 24 years. Incidence rates decreased 50-fold in patients aged 0 to 14 years and 24-fold in patients aged 15 to 24 years. Overall, incidence rates in people aged 25 years and younger decreased by half.

The researchers identified multiple risk factors for acute HBV infection. Patients who had blood transfusions were more than eight times more likely to acquire acute HBV infection, and people living with HBV carriers were more than five times more likely to acquire acute HBV. Injection drug use increased the likelihood for acute HBV infection by more than three times, and unsafe sexual practice increased the likelihood for acute HBV infection by nearly three times.

Approximately 3% of the 9,160 acute HBV infection cases reported since 1992 occurred within the target age group and should have been covered by the mandatory vaccination program. Thirty of the patients with acute HBV infection had undergone vaccinations at various doses and 194 of these patients had not been vaccinated.

Missed opportunities for vaccination were reported for approximately half of the patients with acute HBV who lived with HBV carriers and for 70% of patients who reported intravenous drug use.

The researchers also analyzed cases of acute HBV infection among immigrants to Italy. Of the 948 patients with acute HBV infection, 129 were people who immigrated to Italy from Eastern Europe, Asia, or Africa. Of these immigrants, 17% lived with chronic HBV carriers and 8% reported high-risk sexual activity. In 2004 to 2005, immigrants accounted for 14% of acute HBV cases and for 57% of people who should have been vaccination targets.

Italian program lauded

“It appears that universal vaccination has indeed been a success, leading to a dramatic decrease in the incidence of acute HBV infection,” Anne Gervais and colleagues from the Service de Maladies Infectieuses et Tropicales, d’Hôpital Bichat in Paris, wrote in commentary in Clinical Infectious Diseases.

Experts also praised the vaccination program for economic benefit, but echoed the researchers’ emphasis on the need for public information programs about HBV infection risk in households with HBV carriers and among the medical community.

“The Italian experience shows that universal immunization must be combined with general and targeted improvement in education to stimulate access to vaccination among members of persistently high-risk groups,” Gervais and colleagues wrote.

International efforts for universal vaccinations should be made for developing countries with limited resources to further the WHO goal of eradicating HBV and to bolster HBV programs implemented in countries visited by unvaccinated immigrants, the experts wrote.

For more information:

• Mele A, Tosti ME, Mariano A, et al. Acute hepatitis B 14 years after the implementation of universal vaccination: Areas of improvement and emerging challenges. Clin Infect Dis. 2008;46:868-875.
• Gervais A, Longuet P, Leport C. A success story: universal vaccination in Italy – what has to be done to eradicate residual acute hepatitis B? Clin Infect Dis. 2008;46:876-877.