Since the 1990s, many countries have implemented universal hepatitis B (HB) vaccination in infants.1–4 A few countries, including Canada, have decided to immunize schoolchildren. In the province of Quebec, routine vaccination for grade 4 students has been available since 1994. Three pediatric doses of Engerix-B or Recombivax-HB were used in the school-based program. During the first decade of the program, the vaccination coverage varied from 85 to 95% and >2.5 million doses of vaccine were distributed. The majority (>90%) of these vaccines were administered to people younger than 20 years. Quebec did not introduce routine HB vaccination in infants mainly because of low incidence in this age group, lower anti-HBs titers in vaccinated infants when compared with older groups, unknown duration of protection and an already crowded infant vaccination schedule.
To document the impact of school-based immunization coupled with selective vaccination of groups at risk, we evaluated trends in the rates of acute HB in different age groups between 1990 and 2003. To estimate potential case preventability with a hypothetical infant program and with the existing program, we assessed risk factors and HB vaccination status in cases younger than 20 years. Finally, using recent data on HB cases in children younger than 10 years, we estimated what would be the potential benefit of adding an infant program in Quebec.
All reported acute HB cases from 1990 to 2003 were retrieved from the Provincial Registry of Notifiable Diseases. Reporting of acute cases of HB by physicians and laboratories to the Registry has been mandatory since the 1980s. A standardized case definition of acute HB was used by clinicians and public health authorities throughout the analyzed period.5 Risk factors and vaccination status were extracted from regional public health unit records for cases younger than 10 years reported from 1994 to 2003 and for 10- to 19-year-old cases from 1999 to 2003. Data collection was performed by using a standardized questionnaire. In children younger than 10 years, a case was defined as unpreventable if the child was adequately vaccinated for his age. To determine whether cases in 10- to 19-year-olds could have been prevented by the existing vaccination program, we took into consideration the year of HB occurrence and the individual’s age at the onset of infection. A case was defined as unpreventable if the birth cohort he belonged to was not covered by routine vaccination or the case was fully vaccinated. For the assessment of disease trends, the ratios of incidence rates before and after the introduction of the program were calculated. Disease incidences were compared by using the χ2 test. Statistical significance was set a priori at α = 5%.
From 1990 to 2003, a total of 3715 cases of acute HB were reported. In the years before the introduction of routine vaccination (1990–1993), incidence was relatively stable, with 422–460 cases notified annually (6.0–6.5 cases/100,000) (Fig. 1). There has been no decrease of HB incidence in children less than 10 years since 1990. A consistent decline in the incidence of acute HB has been observed in older age groups. The incidence has decreased by 79% in the general population, by 91% in 10- to 19-year-olds, and by 77% in those 20 years and older. Average incidence was 2.4 times higher in male cases than in female cases (P < 0.0001).
Cases in 0- to 9-Year-Olds.
More than one-half (53.3%) of the cases 10 years or younger were in foreign-born children. Almost one-third (31.1%) of cases were born from hepatitis B surface antigen (HBsAg)-positive mothers. Blood transfusion or household contact with a HB case was present in 6.7 and 2.2% of cases, respectively. There was no known risk factor in 20% of cases. Thirty-six cases (80%) were in unvaccinated, vaccinated without proof or undervaccinated children and were considered as potentially preventable by a hypothetical immunization program at 2, 4 and 6 months of age. Nine cases (20%) were considered as nonpreventable. In 6 of these 9 cases, HB was diagnosed before the age of 6 months or during the first 6 months after arrival in Quebec for foreign-born children. Three other infants, all born from HBsAg-positive mothers, were younger than 1 year old and received HB immunoglobulin plus HB vaccine according to the recommended schedule but failed to be protected. Seven of 14 children born from HBsAg-positive mothers were not vaccinated against HB.
Cases in 10- to 19-Year-Olds.
Sexual transmission was reported in 11 cases (37.9%). Injection drug use or body piercing were reported in 3 cases (10.3%) each. A small proportion of cases (6.9%) was probably acquired outside Canada. Eight (27.6%) cases were in individuals belonging to birth cohorts covered by the routine vaccination program but had not been vaccinated. Seven cases (24.1%) were in those undervaccinated or with unknown immunization status. Fourteen cases (48.3%) were considered as unpreventable. All these cases were in teenagers belonging to birth cohorts not initially covered by vaccination program (born before 1984). One of these cases, a 19-year-old teenager, was vaccinated according to the schedule 0, 1, 6 months at the age of 13–14 years.
Since the introduction of the school-based vaccination, HB incidence has declined in the general population and nearly disappeared in vaccinated birth cohorts. More than 700,000 children were vaccinated, and only 1 HB case was reported in a fully vaccinated person during the first 10 years of vaccination. The partially vaccinated subjects (1–2 doses) were likely infected before vaccination. Symptoms of HB in these vaccinees appeared 1–4 months after immunization initiation. Absence of cases in those vaccinated in the regular school-based program and consistent decline of the HB rates in those older than 10 years along with immunogenicity field study data6 suggest high effectiveness of the program.
More than 4300 acute HB cases have been prevented between 1994 and 2003, if the incidence rate of the prevaccination era (1990–1993) is applied. Taking into consideration the number of vaccine doses distributed, we can estimate that in our low endemic area, for each group of 200 individuals immunized, 1 acute HB case was prevented during the first 10 years of the program. The implementation of a preadolescent immunization was an appropriate strategy for obtaining a rapid and important decrease in HB incidence. Similar results were obtained with combined infant-child vaccination in the United States7 and with a school-based program in British Columbia8 and Catalonia.9 However, in both the United States and Catalonia, the declining trend seems to have halted lately.7,9 In Quebec, we continue to see a consistent decreasing trend in incidence. However, since 1990, no significant change in the trend of HB in children younger than 10 has been observed.
It is difficult to evaluate the number of additional HB cases that would be prevented by an infant program because of the age-dependent proportion of clinically evident and declared cases,10 and because the cohorts routinely vaccinated are reaching child-bearing age. In 1999–2003, an average of 3.6 cases per year were declared in children younger than 10 years. During this period, one-third of cases were reported in foreign-born children who constitute ∼23% of those younger than 10 years in the Quebec population. With the same level of risk and 80% preventability of cases, we can expect a decrease of 3 acute cases notified per year. Taking into consideration the small proportion of clinical cases in this age group (10–20%), the real number of prevented cases could be estimated up to 15–30 cases. Assuming a conservative 90% vaccine efficacy and no cases prevented in foreign-born children, 9–18 cases would be prevented per year.
In 10- to 19-year-olds, 13 of 14 unpreventable cases were attributable to the initial phase of the vaccination program that did not cover children born before 1984. Since by 2004 all birth cohorts between 10 and 19 years of age have been offered vaccination, we can expect very few unpreventable cases in teenagers.
The present study has several limitations. First, data on HB cases were obtained from a passive surveillance system, and we may have underestimated the actual incidence and the number of HB cases that would have been prevented by an infant program. However, there was no important change in the practice of testing and reporting of suspected HB cases during the study period. Therefore, even if some cases were missed, the observed change in trend is most likely a reliable criterion of reduced risk and morbidity. Secondly, the available data on vaccination were incomplete. Vaccination status was unknown for 16.2% of cases, and vaccination was without proof in 5.4% of cases. However, almost all missing data were in subjects born outside Quebec who were not eligible for school-based vaccination. Thus it is unlikely the missing data contributed substantially to the underestimation of vaccine failures in the school-based program.
In summary, Quebec experienced a substantial decline in the rate of acute HB infections among vaccine-eligible cohorts and in the general population. To prevent the decrease in disease incidence from halting as observed in other countries,7,9,11 some new approaches might be needed. According to our data, an infant immunization program in Quebec could prevent several infections each year, and the availability of a diphtheria-tetanus-pertussis-hepatitis B-polio inactivated-Haemophilus influenzae type vaccine facilitates such a program.
1. National Advisory Committee on Immunization. Lignes directrices révisées relatives aux vaccins de rappel contre l’hépatite B. Union Med Canada
2. Organisation Mondiale de la Santé. Déclaration sur le vaccin contre l’hépatite B. Relevé Épidemiol Hebdomadaire
3. Centers for Disease Control and Prevention. Hepatitis B vaccination of adolescents: California, Louisiana, and Oregon, 1992–1994. JAMA
4. National Advisory Committee on Immunization. Canadian Immunization Guide
. 6th ed. Ottawa, Canada: Public Health Agency of Canada; 2002.
5. Manitoba Schools Science Symposium. Surveillance des MADO au Québec Définition Nosologique
6. Duval B, Boulianne N, De Serres G, et al. Comparative immunogenicity under field conditions of two recombinant hepatitis B vaccines in 8–10-year-old children. Vaccine
7. Incidence of acute hepatitis B: United States, 1990–2002. MMWR
8. Patrick DM, Bigham M, Ng H, White R, Tweed A, Skowronski DM. Elimination of acute hepatitis B among adolescents after one decade of an immunization program targeting grade 6 students. Pediatr Infect Dis J
9. Salleras L, Dominguez A, Bruguera M, et al. Dramatic decline in acute hepatitis B infection and disease incidence rates among adolescents and young people after 12 years of a mass hepatitis B vaccination programme of pre-adolescents in the schools of Catalonia (Spain). Vaccine
10. Shepard CW, Finelli L, Fiore AE, Bell BP. Epidemiology of hepatitis B and hepatitis B virus infection in United States children. Pediatr Infect Dis J
11. Giacchino R, Zancan L, Vajro P, et al. Hepatitis B virus infection in native versus immigrant or adopted children in Italy following the compulsory vaccination. Infection
. 2001;29: 188–191.