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NEW THIS FRIDAY: EFFECTIVENESS OF HBV VACCINATION IN INFANTS AND PREDICTION OF HBV PREVALENCE TREND UNDER NEW VACCINATION PLAN: FINDINGS OF A LARGE-SCALE INVESTIGATION

Wednesday, 31st of July 2013

• EFFECTIVENESS OF HBV VACCINATION IN INFANTS AND PREDICTION OF HBV PREVALENCE TREND UNDER NEW VACCINATION PLAN: FINDINGS OF A LARGE-SCALE INVESTIGATION

PLoS One. 2012

Published online 2012 October 19.

Shi-gui Yang,¹ Bing Wang,¹ Ping Chen,¹ Cheng-bo Yu,¹ Min Deng,¹ Jun Yao,² Chun-xia Zhu,¹ Jing-jing Ren,¹ Wei Wu,¹ Bin Ju,³ Jian-feng Shen,³ Yu Chen,¹ Ming D. Li,^1,* Bing Ruan,^1,* and Lanjuan Li^1,*

Suryaprakash Sambhara, Editor

¹The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, the Key Laboratory of Infectious Diseases, Zhejiang Province, Hangzhou, China

²Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China copie montre france

³Zhejiang Province Health Bureau Center of Information, Hangzhou, China

Centers for Disease Control and Prevention, United States of America

* E-mail: ml2km@zju.edu.cn (MDL); Email: hzruanbing@163.com (BR); Email: ljli@zju.edu.cn (LL)

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: LjL S-gY MDL BR. Performed the experiments: BR BW PC C-bY MD JY C-xZ J-jR WW YC. Analyzed the data: S-gY BW PC C-bY. Contributed reagents/materials/analysis tools: LjL S-gY BJ J-fS. Wrote the paper: LjL S-gY MDL.

Received May 30, 2012; Accepted September 17, 2012.

Copyright notice

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

This article has been cited by other articles in PMC.

Background

Hepatitis B virus (HBV) infection remains a severe public health problem. Investigating its prevalence and trends is essential to prevention.

Methods

To evaluate the effectiveness of HBV vaccination under the 1992 Intervention Program for infants and predicted HBV prevalence trends under the 2011 Program for all ages. We conducted a community-based investigation of 761,544 residents of 12 counties in Zhejiang Province selected according to their location, population density, and economic development. The HBV prevalence trends were predicted by a time-shifting approach. HBV surface antigen (HBsAg) and alanine amino transferase (ALT) were determined.

Results

Of the 761,544 persons screened for HBsAg, 54,132 were positive (adjusted carrier rate 6.13%); 9,455 had both elevated ALT and a positive HBsAg test (standardized rate 1.18%). The standardized HBsAg carrier rate for persons aged ≤20 years was 1.51%. Key factors influencing HBV infection were sex, age, family history, drinking, smoking, employment as a migrant worker, and occupation. With the vaccination program implemented in 2011, we predict that by 2020, the HBsAg carrier rate will be 5.27% and that for individuals aged ≤34 years will reach the 2% upper limit of low prevalence according to the WHO criteria, with a standardized rate of 1.86%.

Conclusions

The national HBV vaccination program for infants implemented in 1992 has greatly reduced the prevalence of HBV infection. The 2011 program is likely to reduce HBV infection in Zhejiang Province to a low moderate prevalence, and perinatal transmission is expected to be controlled by 2020.

. . .  

Hepatitis B virus infection is endemic worldwide, but its prevalence differs greatly among regions[19], [20]. The last two surveys in China showed that the national prevalence of HBsAg was 8.75% in 1979[7] and 9.75% in 1992[8], making China a high endemic region. With the infant immunization beginning 1992, the prevalence of HBsAg was reduced to 7.18% in 2006[9]. However, this is still much higher than in Western countries, and a comprehensive prevention strategy is required[21]. An expanded population-based test for HBV infection is thus recommended [22].

By stratified analysis of community-based epidemiologic data, we identified several factors impacting the prevalence of HBV: male sex, being an adult aged ≥20 years, a family history of hepatitis B, drinking, smoking, being a migrant worker, and/or having some specific occupations (fishermen, construction worker, and long-distance truck driver). Chronic nicotine treatment increases the incidence of infection with several viruses, such as influenza[23], HIV-1[24], and HSV-1[25]. Although a high prevalence of HBsAg in long-distance truck drivers has never been reported before, a high incidence of HIV infection has been reported[26], which provides further support for our finding, as these viruses have similar infection modes[27].

Participants <20 years old had a significantly lower HBsAg carrier rate than other age groups. Most participants in this group were born after 1992, when the national HBV vaccination program for infants was implemented. National vaccination programs significantly decrease not only the HBV carrier rate but also HBV-associated complications[28], [29]. Although other factors, such as differences in population growth rate and increased investment and improved medical care structure, might affect the HBsAg rate, the reduction we observed provides supporting evidence for the effectiveness of the national vaccination program, which brought the HBsAg carrier rate to 1.51% by 2010. This is a highly significant reduction, as the rate was approximately 9%–12% for a similar age group prior to 1992[8] and equals a reduction of an estimated 1,577,391 HBsAg carriers and a savings of US$17.8 billion for treatment of HBV infections in Zhejiang Province. Likely reasons for the continued 1.51% HBsAg prevalence rate in young individuals are different vaccine coverage rates during early implementation and vaccine failure in some individuals.

To reduce the HBV infection rate in the older population, we implemented a comprehensive program for both infants and adults in 2011. Although immunization of targeted high-risk populations has been less successful in the US [2], it is too early to confirm the impact of the 2011 Program on HBV infection in China. However, considering the factors associated with the cost to a patient and different degrees of government involvement in the US and China, we expect the outcome in China would be very different. We predict that the 2011 Program will lead to a reduction of 468,071 HBV carriers and bring the HBsAg carrier rate among individuals under 34 years old to the low epidemic level of 2% or less by 2020. In contrast, with the 1992 Program, there would be a reduction of 59,870 HBV carriers and a change in the HBsAg carrier rate among individuals <28 years old to the low epidemic level by 2020. Thus, the 2011 Program would cause a 7.82-fold reduction in the number of carriers and expand the age range of those protected from 28 to 34 years. This is highly significant because this group is in their primary reproductive period[30], and a low HBsAg carrier rate (<2%), especially among prospective parents under 34 years old, implies fewer infants infected with HBV and parental transmission can be effectively controlled.

It appears that the new HBV vaccination program not only strengthened neonatal vaccination but also controlled HBV infection among women of childbearing age. Further, the 2011 Program would be expected to save US$5.27 billion for treating hepatitis B within the next 10 years, a benefit: cost ratio of 38.51, under the same assumptions and approaches used in a previous study [17].

There are a few limitations of this study. First, anti-HBc and HBV DNA status were unavailable, there is significant fibrosis and inflammation in a small proportion of HBV-infected patients with persistently normal ALT, and an immune tolerance phase with a normal ALT and high HBV DNA often is found in the period of active reproduction in young women, which leads to much of the perinatal transmission[31]. Thus, the benefits of HBV vaccination could have been under estimated. Second, despite the safety and effectiveness of the hepatitis B vaccine and the benefits of government-oriented free programs, some potential barriers, included scheduling conflicts and forgetfulness, may influence the 2011 program, which may overestimate the effectiveness of the program[2], [32]. Third, we did not consider inflation and exchange rate differences between Chinese and US currency in our cost and benefit analyses, as we have no way to predict what could happen during this long period of time.

In conclusion, by analyzing large-scale epidemiologic data on hepatitis B in Zhejiang Province of China, we identified several factors impacting HBV infection. The 1992 Program has contributed greatly to a reduced HBsAg carrier rate in the young. Further, our modelling suggested that the 2011 Program not only reduced the costs associated with hepatitis B treatment, but also brought the HBsAg carrier rate among people under the age of 34 years to 2%, expanding the age of protection from 28 years under the 1992 Program to 34 years under the 2011 Program. This is highly significant, as this age group is highly active reproductively, and a reduced HBV infection rate would mean a reduction of parental transmission. It is our hope that the findings from this study can be used to support application of the new HBV vaccination program to other high and middle endemic regions of China and other countries fighting hepatitis B.