Vaccination Research

Open journal

ISSN 2771-750X

Herd Immunity Conferred By Hepatitis B Vaccination Increases the Protection Efficacy against Hepatitis B Virus Infection

Yuting Wang, Ling-Ling Lu, Dongmei Wang and Chunfeng Qu*

Chunfeng Qu, MD, PhD

Professor, Department of Immunology, State Key Lab of Molecular Oncology, National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021, China; Tel. 86 10 8778 3103; E-mail: quchf@cicams.ac.cn

INTRODUCTION

Hepatitis B Virus (HBV) infection is one of the leading cause of illness and death in China.1 Primary Liver Cancer (PLC) and liver cirrhosis are the long-term major adverse outcomes of chronic HBV infection.2 In the Chinese population, most of the chronic infections are acquired in perinatal period or in early life. In 1992 before the national HBV vaccination program, seropositive rate of HBV surface antigen (HBsAg), that reflect the status of chronic HBV infection, in the 1-4 age group was 9.67%, as high as in the general population (9.75%).3 In response to the recommendation from a WHO scientific group about the prevention of chronic HBV infection and PLC,4 China implemented the universal immunization to newborns by integrating the HBV vaccination into the Expended Program of Immunization (EPI), beginning in January, 1992 with 3 doses of vaccines paid by the family.5 From January 1, 2002 the HBV vaccination was integrated into the national EPI program with the vaccine provided entirely by the government. Here we reported the effect of herd immunity after HBV vaccination on HBV infection among children.

METHODS

Study Population

The children aged 5-6 years who were born in different years and resided in Qidong county, Jiangsu Province of China were recruited for the study. Serum samples were collected in the following years, respectively. In 1985 just before the Hepatitis B vaccine was introduced into China, a total of 433 blood samples from the children born in 1979-1980 were collected.

In 1991 before the Expended Program of Immunization (EPI), a total of 3002 children, who were born in 1985-1986 and had the record of not receiving the vaccine, donated the blood samples. In addition, 674 children, who were born in 1985-1986 and had the record of receiving 3 dose of the plasma-derived hepatitis B vaccination after birth, donated the blood samples. In 2008 a total of 823 children born in 2002-2003 when all the neonates received obligatory hepatitis B vaccination after birth donated blood samples.

Serological analysis for HBV infection

Upon receiving a written consent from the children’s parents, 2 ml peripheral blood was collected from each of children. All HBV serological markers were determined within 12 hours after blood sampling. Individuals with serum HBsAg-positivity were retested in six months. All the serum HBsAg was detected using the reagents from Abbott Laboratories, North Chicago, IL, USA.

Statistical analysis

Chi-square test and Fisher’s exact test were conducted to compare HBsAg seropositive rates. Vaccine protection efficacy is calculated based on the HBsAg seropositivity determined among the children born in 1979-80 (as the reference group) by the form: HBsAg(+) rate in reference group -HBsAg(+) rate in intervention group)/ HBsAg(+) rate in reference group.

RESULTS

HBsAg Seroprevalene among the Children in Different Period

We conducted HBV serosurveys among the children aged 5-6 years in different period. The using of disposable medical materials and having the baby delivered in hospital began from 1980s in Qidong, one of the rural areas with HBV high prevalence. The seropositive rate of HBsAg was 13.39% among the children born in 1979-1980 and was 11.86% among those born in 1985-1986 when no vaccination was given after birth (Table 1). Chi-square test showed no difference among the children born in these two different years (p=0.3587).

Table 1: HBsAg seroprevalence in the children aged 5-7 years living in Qidong in different years.

Group

Year Born Year Sampled Age Determined Total Num HBsAg(+) Number Rate (%) P value

Protection Efficacy

No vaccination

1979-80

1985 5-6 years 433 58 13.39 0.3587a

Reference

No vaccination

1985-86

1991 5-6 years 3002 356 11.86

11.43%

vaccination

1985-86

1991 5-6 years 674 14 2.08 0.0006b

84.47%

vaccination

2002-03

2008 6-7 years 823 2

0.24

98.21%

aChi-square test
bFisher’s exact test

Protection Efficacy of HBV Vaccination on the Children in Different Period

The Expended Program of Immunization (EPI) began in January, 1992. Some of the children born in 1985-1986 received the hepatitis B vaccination after birth. It was found that the HBsAg sero-positive rate (2.08%) decreased dramatically in the vaccinated children compared to those children without vaccination (11.86%) who were born in the same year. The protection efficacy of HBV vaccination was 84.47%. With increased vaccination coverage among the population the HBsAg seropositive rate (0.24%) further decreased, with 98.21% protection efficacy.

DISCUSSION

With the using of disposable medical materials and having the baby delivered in hospital the HBsAg-seroprevalence decreased in the HBV highly prevalence area. However, the most important strategy to protect the children from HBV infection was proven to be the neonatal HBV vaccination. Vertical transmission is a major route for HBV infection in Asian countries and endemic areas, which accounts for about 40-50% of HBsAg carriers in Taiwan and in mainland China.3,6 However, horizontal transmission through close contact among children and family members is also a critical route for HBV infection.6 Our results showed that HBsAg-seropositive rate was further reduced among the population when all the neonates received obligatory hepatitis B vaccination after birth. Thus herd immunity by vaccination is critical to protect population from HBV infection.

The nationwide HBV sero-survey among the mainland of China conducted in 2006 showed that the HBsAg-seroprevalence was 0.96% in the population aged 1-4 years, 2.32% aged 5-14 years, 5.4% aged 15-19 years, and more than 8.0% aged 20-59 years.7 In 2014, the HBsAg-seroprevalence decreased to 0.32% in the 1~4 age group, to 0.94% in the 5~14 age group and 4.38% in those aged 15~29 years.8 These data highlighted the importance of national wide neonatal HBV vaccination in reducing the HBV infection in child and adults.

ACKNOWLEDGMENTS

This work was support by the State Key Projects Specialized on Infectious Diseases (2012ZX10002008-001) to and National Natural Science Foundation of China (81571620) to CQ.

CONFLICTS OF INTEREST:

None.

1. Chen J, Peto R, Pan WH, Liu BQ, Campbell TC. Mortality, biochenmistry, diet and lifestyle in rural China. Oxford, Britain; Oxford University Press 2006.

2. McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology. 2009; 49(5 Suppl): S45-S55. doi: 10.1002/hep.22898

3. Xia GL, Liu CB, Cao HL, Bi SL, Zhan MY, Su CA, et al. Prevalence of hepatitis B and C virus infections in the general Chinese population: results from a nationwide cross-sectional seroepidemiologic study of hepatitis A, B,C, D and E virus infections in China, 1992. Int Hepatol Commun. 1996; 5(1): 62- 73. doi: 10.1016/S0928-4346(96)82012-3

4. Zuckerman AJ, Sun TT, Linsell A, Stjernsward J. Prevention of Primary Liver Cancer-Report on a Meeting of a W.H.O. Scientific Group. Lancet. 1983; 1(8322): 463-465. doi: 10.1016/ S0140-6736(83)91454-X

5. Sun Z, Ming L, Zhu X, Lu J. Prevention and control of hepatitis B in China. J Med Virol. 2002; 67(3): 447-450. doi: 10.1002/ jmv.10094

6. Chang MH. Hepatitis B virus infection. Semin Fetal Neonatal Med. 2007; 12(3): 160-167. doi: 10.1016/j.siny.2007.01.013

7. Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, et al. Epidemiological serosurvey of hepatitis B in China–declining HBV prevalence due to hepatitis B vaccination. Vaccine. 2009; 27(47): 6550-6557. doi: 10.1016/j.vaccine.2009.08.048

8. Chinese Society of Hepatology, Chinese Medical Association. Guidelines for prevention of chronic hepatitis-Chronic Hepatitis B. 2015.

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