Journal of Medical Virology 34:96-99 (1991)
Seroprevalence of Hepatitis B Virus Infection in Children in Taipei, 1989: Five Years After a Mass Hepatitis B Vaccination Program Yee-Jeng Tsen, Mei-Hwei Chang, Hong-Yuan Hsu, Chin-Yun Lee, Juei-Low Sung, and DingShinn Chen Departments of Pediatrics (Y.J.T., M.H.C., H.Y.H., C.Y.L.) and Internal Medicine (J.L.S., D.S.C.), and Hepatitis Research Center (J.L.S., D.S.C.), National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Republic of China A nationwide hepatitis B vaccination program was launched in Taiwan in 1984. To study the impact of this ongoing program on hepatitis B virus (HBV) infection, a follow-up seroepidemiologic study was carried out in 1989 in a Taipei district where pre-vaccination seroepidemiology had been studied. HBV markers were studied in 1134 apparently healthy children (619 boys and 515 girls) under 13 years of age between March and July 1989. The prevalence of hepatitis B surface antigen (HBsAg) in children under 5 years of age decreased from 9.3% in 1984 to approximately 2% in 1989. A significant decrrease in HBsAg prevalence and hepatitis B core antibody in 5- to 8-year-old children who were not immunized against HBV showed that horizontal infection among the older children had also decreased. Thus, this program not only protected vaccinated subjects; the reduction in numbers of highly infectious young HBV carriers also contributed to a lower prevalence of hepatitis B infection and carrier rates in some older children. This study demonstrates that hepatitis B vaccination is effective in protecting the majority of children in hyperendemic areas from HBV infection and from becoming chronic carriers.
KEY WORDS: hepatitis B vaccine, vaccination program, hepatitis
B virus
INTRODUCTION Taiwan is a hyperendemic area for hepatitis B virus infection, a virus which plays an important role in development of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma [Shiraki et al., 1977; Beasley et al., 1981; Beasley, 1.9821. The carrier rate in the Taiwanese general population is 15 to 20%, and periQ 1991 WILEY-LISS, LNC.
natal HBV transmission accounts for 40%-50% of the carrier pool [Stevens et al., 19751. Perinatal transmission and horizontal transmission of HBV occur relatively early in life in Taiwan [Stevens et al., 1975; Beasley et al., 1982; Chen et al., 19781. To combat this early HBV infection, a mass HBV vaccination program was launched in Taiwan since July 1984, starting from newborns of hepatitis B surface antigen (HBsAg)carrier mothers. In July 1986, the program was extended to all newborns; and in 1987, preschool children were also included [Chen et al., 19871. A baseline seroepidemiologic study of HBV infection in children in Taipei was carried out in 1984,just before the mass vaccination program [Hsu et al., 19861. In 1989, 5 years after the beginning of that program, another study was conducted on children in the same area of Taipei to study the seroepidemiologic changes. The results by the same investigators are reported and compared with the data obtained before the vaccination program began.
SUBJECTS AND METHODS Serum samples were collected in March through June 1989 from 1134 apparently healthy children under 13 years of age in Taipei. There were 619 boys and 515 girls, who included 1) children attending 2 well-baby clinics, 2) children from 2 local kindergartens, and 3) children from a primary school. These subjects lived in the Cheng-Chung District of Taipei City, the same site of the baseline seroepidemiologic study carried out in 1984 [Hsu et al., 19861. Informed consent was obtained from all parents. The vaccination history in children below 3 years of age was obtained mainly by reviewing their vaccination records, while in Accepted for publication January 22, 1991. Address reprint requests to Professor M.H. Chang, National Taiwan University Hospital, 1 Chang-Te Street, Taipei, Taiwan 10016, Republic of China.
HBV Seroepidemiology in Taiwan After Vaccination
97
children over 3 years of age it was obtained by a written TABLE I. Vaccination Historv questionnaire for their parents and based mainly on No. of vaccinations per person No. Age parental recall. 1 2 3 4 3 + 4a (vears) studied 0 Hepatitis B surface antigen (HBsAg), and its anti9 63 (95.5) < I 66 2 0 1 54 body (anti-HBs), hepatitis B core antibody (anti-HBc), 1-2 1 0 22 166 188 (91.3) 206 17 and hepatitis B e antigen (HBeAg) and antibody (anti3-4 139 3 42 (22.7) 1 12 30 185 HBe) were tested by radioimmunoassay (RIA) using 193 2 3 19 5-6 12 31 (13.5) 229 Ausria 11, Ausab, Corab, and Abbott-HBe (Abbott 21 (12.2) 7-8 172 134 10 7 8 13 5 9-10 103 8 6 1 123 Laboratories, North Chicago, IL), respectively. HBeAgl 6 (4.9) 3 7 5 2 136 153 5 (3.3) anti-HBe detection was limited to HBsAg-positive sub- 11-12 1134 724 31 23 118 238 356 (31.4) jects only. Chi square test with Yates’s correction was Total used for statistical analysis. A P value of < 0.05 was “3 + 4 denotes the sum of the numbers of persons who received 3 judged to reflect a significant difference; a P value doses and 4 doses. between 0.05 and 0.1 was judged to reflect a trend.
RESULTS Vaccination History Among these 1134 children, 356 (31.4%)received 3 or more doses of hepatitis B vaccine, while 724 (63.8%) children had received none. The vaccine coverage was highest in those < 2 years old (92.3%),and much lower in those > 2 years of age (Table I). Seroprevalence 1989 The prevalence rate of HBsAg was 3.0%in infancy, 1.5%at 1-2 years of age, and 4.7%at 7-8 years of age. It became 9.8%at 9-10 years of age, remaining about the same at 11-12 years of age (Table 11).The overall prevalence rate of HBsAg was 4.8%.High positive rates of anti-HBs were observed in infancy and children from 1 to 2 years of age, 83.3%and 84.5%,respectively. The anti-HBs positive rate then decreased to about 20% after 3 years of age (Table 111).The prevalence rate of anti-HBc was 19.7%in infancy, decreased to 4.9%and 5.9% in children 1-2 and 3-4 years of age, then increased to around 13% in children 5-8 years of age and was up to around 30%in children 9-12 years old (Table IV). Of the 54 HBsAg-positive children, 39 (72.2%)were HBeAg positive, 10 (18.5%)were anti-HBe positive, 5 (9.3%)were both HBeAg and anti-HBe negative, and none were positive for both. Among the 1134 children, statistically significant difference was not found in seroprevalence by sex [274 (44.3%)of 619 boys vs. 198 (38.4%)of 515 girls (P > 0.1)l.Among the seropositives, the frequency of HBsAg was slightly higher in males: 35 (12.8%)of 274 boys vs. 19 (9.5%)of 200 girls. The difference was not statistically significant (P > 0.1). Comparison Between 1989 and 1984 Compared with the 1984 results, a significant decrease of HBsAg prevalence rate was observed in children aged from 1 to 6 years old and a trend of decrease in children from 7 to 8 years of age (P = 0.09). The overall HBsAg prevalence rate also showed a significant decrease (Table 11).A significant increase of anti-HBs positive rate was observed in infants and children between 1 and 4 years of age, and the overall positive rate for anti-HBs also showed a significant increase. In the mean time, a significant decrease of
anti-HBs positivity was observed in children 11-12 years of age (Table (111). A significant decrease of anti-HBc prevalence rate was observed in children 1-8 years of age and a trend of decrease in children 11-12 years of age (P = 0.07). The overall anti-HBc prevalence rate also showed a significant decrease (Table IV). If the anti-HBc positive rates of the vaccinated group (those who had received three or more HBV vaccines) and non-vaccinated group (those did not receive any vaccine) were compared separately with that of 1984, a significant decrease of anti-HBc positivity could be observed in children 3-8 years of age of the nonvaccinated group and children 1-2 years of age of the vaccinated group (Table V). The overall anti-HBc prevalence rate in both groups also showed a significant decrease. DISCUSSION A nationwide mass hepatitis B vaccination program was launched in Taiwan on July 1, 1984, starting from infants of HBsAg-carrier mothers. The coverage rate of the hepatitis B immune globulin was 77% in infants born to highly infectious mothers, and that of the first, second, third, and the fourth doses of vaccine was 88%, 86%,84%,and 71%,respectively [Chen et al., 19871. In infants who had highly infectious mothers and who received hepatitis B immune globulin and vaccine on schedule, the protective efficacy was about 85%.Overall, the response rate was 81% [Hsu et al., 19881. The vaccination program was further extended to all newborns from July 1986 and to preschool children from July 1987 [Chen et al., 19871. Therefore, in this study, most of the children below three years of age and most children between three and four years of age born to carrier mothers were immunized against hepatitis B after birth. In the meantime, as shown in Table I, 12-13.5% of the children 4-7 years of age had received personally-paid-for HBV vaccination after their infancy, when the vaccination program was extended to kindergarten between July 1987 and June 1988. Compared with the 1984 results, a significant decrease in HBsAg and anti-HBc prevalence rate was observed in children aged from 1 to 6 years. HBV vaccination protected most children below 6 years of
Tsen et al.
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TABLE 11. Comparison of Prevalence of HBsAg Between Year 1984 and Year 1989 1984a 1989 No. HBsAg(+) No. HBsAg(+) Age % studied No. % P No. (years) studied NSb 2 3.0 3 5.1 66 59
Seroprevalence of Hepatitis B Virus Infection in Children in Taipei, 1989: Five Years After a Mass Hepatitis B Vaccination Program Yee-Jeng Tsen, Mei-Hwei Chang, Hong-Yuan Hsu, Chin-Yun Lee, Juei-Low Sung, and DingShinn Chen Departments of Pediatrics (Y.J.T., M.H.C., H.Y.H., C.Y.L.) and Internal Medicine (J.L.S., D.S.C.), and Hepatitis Research Center (J.L.S., D.S.C.), National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Republic of China A nationwide hepatitis B vaccination program was launched in Taiwan in 1984. To study the impact of this ongoing program on hepatitis B virus (HBV) infection, a follow-up seroepidemiologic study was carried out in 1989 in a Taipei district where pre-vaccination seroepidemiology had been studied. HBV markers were studied in 1134 apparently healthy children (619 boys and 515 girls) under 13 years of age between March and July 1989. The prevalence of hepatitis B surface antigen (HBsAg) in children under 5 years of age decreased from 9.3% in 1984 to approximately 2% in 1989. A significant decrrease in HBsAg prevalence and hepatitis B core antibody in 5- to 8-year-old children who were not immunized against HBV showed that horizontal infection among the older children had also decreased. Thus, this program not only protected vaccinated subjects; the reduction in numbers of highly infectious young HBV carriers also contributed to a lower prevalence of hepatitis B infection and carrier rates in some older children. This study demonstrates that hepatitis B vaccination is effective in protecting the majority of children in hyperendemic areas from HBV infection and from becoming chronic carriers.
KEY WORDS: hepatitis B vaccine, vaccination program, hepatitis
B virus
INTRODUCTION Taiwan is a hyperendemic area for hepatitis B virus infection, a virus which plays an important role in development of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma [Shiraki et al., 1977; Beasley et al., 1981; Beasley, 1.9821. The carrier rate in the Taiwanese general population is 15 to 20%, and periQ 1991 WILEY-LISS, LNC.
natal HBV transmission accounts for 40%-50% of the carrier pool [Stevens et al., 19751. Perinatal transmission and horizontal transmission of HBV occur relatively early in life in Taiwan [Stevens et al., 1975; Beasley et al., 1982; Chen et al., 19781. To combat this early HBV infection, a mass HBV vaccination program was launched in Taiwan since July 1984, starting from newborns of hepatitis B surface antigen (HBsAg)carrier mothers. In July 1986, the program was extended to all newborns; and in 1987, preschool children were also included [Chen et al., 19871. A baseline seroepidemiologic study of HBV infection in children in Taipei was carried out in 1984,just before the mass vaccination program [Hsu et al., 19861. In 1989, 5 years after the beginning of that program, another study was conducted on children in the same area of Taipei to study the seroepidemiologic changes. The results by the same investigators are reported and compared with the data obtained before the vaccination program began.
SUBJECTS AND METHODS Serum samples were collected in March through June 1989 from 1134 apparently healthy children under 13 years of age in Taipei. There were 619 boys and 515 girls, who included 1) children attending 2 well-baby clinics, 2) children from 2 local kindergartens, and 3) children from a primary school. These subjects lived in the Cheng-Chung District of Taipei City, the same site of the baseline seroepidemiologic study carried out in 1984 [Hsu et al., 19861. Informed consent was obtained from all parents. The vaccination history in children below 3 years of age was obtained mainly by reviewing their vaccination records, while in Accepted for publication January 22, 1991. Address reprint requests to Professor M.H. Chang, National Taiwan University Hospital, 1 Chang-Te Street, Taipei, Taiwan 10016, Republic of China.
HBV Seroepidemiology in Taiwan After Vaccination
97
children over 3 years of age it was obtained by a written TABLE I. Vaccination Historv questionnaire for their parents and based mainly on No. of vaccinations per person No. Age parental recall. 1 2 3 4 3 + 4a (vears) studied 0 Hepatitis B surface antigen (HBsAg), and its anti9 63 (95.5) < I 66 2 0 1 54 body (anti-HBs), hepatitis B core antibody (anti-HBc), 1-2 1 0 22 166 188 (91.3) 206 17 and hepatitis B e antigen (HBeAg) and antibody (anti3-4 139 3 42 (22.7) 1 12 30 185 HBe) were tested by radioimmunoassay (RIA) using 193 2 3 19 5-6 12 31 (13.5) 229 Ausria 11, Ausab, Corab, and Abbott-HBe (Abbott 21 (12.2) 7-8 172 134 10 7 8 13 5 9-10 103 8 6 1 123 Laboratories, North Chicago, IL), respectively. HBeAgl 6 (4.9) 3 7 5 2 136 153 5 (3.3) anti-HBe detection was limited to HBsAg-positive sub- 11-12 1134 724 31 23 118 238 356 (31.4) jects only. Chi square test with Yates’s correction was Total used for statistical analysis. A P value of < 0.05 was “3 + 4 denotes the sum of the numbers of persons who received 3 judged to reflect a significant difference; a P value doses and 4 doses. between 0.05 and 0.1 was judged to reflect a trend.
RESULTS Vaccination History Among these 1134 children, 356 (31.4%)received 3 or more doses of hepatitis B vaccine, while 724 (63.8%) children had received none. The vaccine coverage was highest in those < 2 years old (92.3%),and much lower in those > 2 years of age (Table I). Seroprevalence 1989 The prevalence rate of HBsAg was 3.0%in infancy, 1.5%at 1-2 years of age, and 4.7%at 7-8 years of age. It became 9.8%at 9-10 years of age, remaining about the same at 11-12 years of age (Table 11).The overall prevalence rate of HBsAg was 4.8%.High positive rates of anti-HBs were observed in infancy and children from 1 to 2 years of age, 83.3%and 84.5%,respectively. The anti-HBs positive rate then decreased to about 20% after 3 years of age (Table 111).The prevalence rate of anti-HBc was 19.7%in infancy, decreased to 4.9%and 5.9% in children 1-2 and 3-4 years of age, then increased to around 13% in children 5-8 years of age and was up to around 30%in children 9-12 years old (Table IV). Of the 54 HBsAg-positive children, 39 (72.2%)were HBeAg positive, 10 (18.5%)were anti-HBe positive, 5 (9.3%)were both HBeAg and anti-HBe negative, and none were positive for both. Among the 1134 children, statistically significant difference was not found in seroprevalence by sex [274 (44.3%)of 619 boys vs. 198 (38.4%)of 515 girls (P > 0.1)l.Among the seropositives, the frequency of HBsAg was slightly higher in males: 35 (12.8%)of 274 boys vs. 19 (9.5%)of 200 girls. The difference was not statistically significant (P > 0.1). Comparison Between 1989 and 1984 Compared with the 1984 results, a significant decrease of HBsAg prevalence rate was observed in children aged from 1 to 6 years old and a trend of decrease in children from 7 to 8 years of age (P = 0.09). The overall HBsAg prevalence rate also showed a significant decrease (Table 11).A significant increase of anti-HBs positive rate was observed in infants and children between 1 and 4 years of age, and the overall positive rate for anti-HBs also showed a significant increase. In the mean time, a significant decrease of
anti-HBs positivity was observed in children 11-12 years of age (Table (111). A significant decrease of anti-HBc prevalence rate was observed in children 1-8 years of age and a trend of decrease in children 11-12 years of age (P = 0.07). The overall anti-HBc prevalence rate also showed a significant decrease (Table IV). If the anti-HBc positive rates of the vaccinated group (those who had received three or more HBV vaccines) and non-vaccinated group (those did not receive any vaccine) were compared separately with that of 1984, a significant decrease of anti-HBc positivity could be observed in children 3-8 years of age of the nonvaccinated group and children 1-2 years of age of the vaccinated group (Table V). The overall anti-HBc prevalence rate in both groups also showed a significant decrease. DISCUSSION A nationwide mass hepatitis B vaccination program was launched in Taiwan on July 1, 1984, starting from infants of HBsAg-carrier mothers. The coverage rate of the hepatitis B immune globulin was 77% in infants born to highly infectious mothers, and that of the first, second, third, and the fourth doses of vaccine was 88%, 86%,84%,and 71%,respectively [Chen et al., 19871. In infants who had highly infectious mothers and who received hepatitis B immune globulin and vaccine on schedule, the protective efficacy was about 85%.Overall, the response rate was 81% [Hsu et al., 19881. The vaccination program was further extended to all newborns from July 1986 and to preschool children from July 1987 [Chen et al., 19871. Therefore, in this study, most of the children below three years of age and most children between three and four years of age born to carrier mothers were immunized against hepatitis B after birth. In the meantime, as shown in Table I, 12-13.5% of the children 4-7 years of age had received personally-paid-for HBV vaccination after their infancy, when the vaccination program was extended to kindergarten between July 1987 and June 1988. Compared with the 1984 results, a significant decrease in HBsAg and anti-HBc prevalence rate was observed in children aged from 1 to 6 years. HBV vaccination protected most children below 6 years of
Tsen et al.
98
TABLE 11. Comparison of Prevalence of HBsAg Between Year 1984 and Year 1989 1984a 1989 No. HBsAg(+) No. HBsAg(+) Age % studied No. % P No. (years) studied NSb 2 3.0 3 5.1 66 59
