Frequently asked questions on Hepatitis B vaccination in China

18 August 2014

A. General information about Hepatitis B and its prevention

1. What is hepatitis B?

Hepatitis B is a serious and potentially life-threatening liver infection caused by the hepatitis B virus. Hepatitis B is a major global health problem, and is the leading cause of cirrhosis of the liver and liver cancer in China and the world.

Hepatitis B infection can lead to a chronic, life-long infection in which the virus is constantly in the blood and other body fluids of an infected person. This is called chronic hepatitis B virus infection.

2. How is hepatitis B transmitted to others?

Hepatitis B is transmitted through contact with blood or other body fluids of a person with chronic hepatitis B infection. Hepatitis B virus is only spread person-to-person; it is not spread by air, food, or water. However, the hepatitis B virus is highly infectious: 50 to 100 times more infectious than HIV.

One of the most common and important ways that the virus infects a person is through childbirth, when a baby is born to a mother who has chronic hepatitis B infection. In this situation, the baby becomes exposed to hepatitis B virus from the mother’s blood and body fluids. This exposure usually leads to infection of the newborn baby, unless the baby is vaccinated within 24 hours of birth and twice subsequently within the first 12 months (see below). When a newborn baby is infected during childbirth, he or she has a 90% chance of becoming chronically infected. The newly infected baby often shows no symptoms, and can remain without symptoms for decades but is able to spread the infection to people who are not immune to hepatitis B.

3. How can hepatitis B be prevented?

Vaccination with hepatitis B vaccine is the safest and most effective way to prevent hepatitis B infection and its complications. Hepatitis B vaccine was invented over 20 years ago and has been in global use since that time. Many hundreds of millions of individuals have received hepatitis B vaccine. This vaccine prevents more than 95% of infections.

The vaccine consists of protein parts of the hepatitis B virus that are able to cause the body’s immune system to recognize and respond to any potential infection with hepatitis B virus in the future. The vaccine does not contain hepatitis B virus, and so cannot itself cause infection. Immunization with three doses of hepatitis B vaccine is believed to result in lifelong immunity from hepatitis B virus infection.

If a susceptible person is exposed to hepatitis B virus, for example via a needle stick of a healthcare worker, it is possible to prevent infection with post-exposure prophylaxis using hepatitis B immunoglobulin with hepatitis B vaccination. Similarly, if an infant is exposed to hepatitis B virus during childbirth, infection can almost always be prevented by vaccination with hepatitis B vaccine on the day of birth, followed by 2 more doses during infancy.

4. What does WHO recommend for the prevention of hepatitis B?

WHO recognizes that the safest and most effective way to prevent hepatitis B virus infection is through timely vaccination with hepatitis B vaccine. WHO recommends vaccination of all newborn infants.

WHO recommends that the first dose of hepatitis B vaccine be given within 24 hours of birth, to all newborn infants. This birth dose should be followed by 2 more doses of hepatitis B vaccine during infancy.

5. Does WHO recommend a routine booster dose of hepatitis B vaccine after the 3-dose primary series of hepatitis B vaccine?

No. WHO does not recommend a routine booster dose of hepatitis B vaccine. Current scientific studies indicate that successful immunization with 3 doses of hepatitis B vaccine results in long-lasting immunity, probably lifelong. Since the modern hepatitis B vaccine was first licensed 28 years ago, the duration of protection will continue to be studied.

6. Does WHO recommend testing for antibodies against hepatitis B virus?

WHO does not recommend testing of everyone vaccinated with hepatitis B vaccine for antibodies. However, there are individuals at high risk of infection with hepatitis B virus and whose clinical management depends on knowledge of their immune status. WHO does recommend that these individuals be tested for antibodies. They are: (1) infants born to mothers with chronic hepatitis B infection; (2) people at risk of occupationally acquired infection; (3) chronic hemodialysis patients, people infected with HIV and other immunocompromised people; and (4) sex partners or needle-sharing partners of people who have chronic hepatitis B infection. In these situations, testing should be performed 1–2 months after administration of the last dose of the vaccine series using a method that allows for determination of a protective concentration of anti-HBs antibodies (≥10 mIU/ml). If someone is recommended for antibody testing and they are found to have a level less than 10 mIU/ml, they may need to be revaccinated and retested. If you fall into one of these categories and are not sure of your vaccination or immunity status, we recommend you speak with your doctor or health care provider.

B. Vaccinating newborns with a timely birth dose of hepatitis B vaccine

7. Why does hepatitis B need to be given to a newborn baby within 24 hours of birth?

During the process of childbirth from a woman with chronic hepatitis B infection, the baby becomes exposed to active hepatitis B virus from the mother’s blood and body fluids. This exposure to the virus places the newborn baby at extremely high risk of infection. When newborn babies become infected with hepatitis B virus, they have a 90% chance of becoming chronically infected. Thus, birth to a woman with chronic hepatitis B infection is an urgent, dangerous situation for the newborn baby.

Hepatitis B vaccine, when given within 24 hours of the exposure to hepatitis B virus during childbirth, can prevent infection of the newborn baby 95% of the time. However, if the vaccine is given after 24 hours of birth, its effectiveness decreases markedly. This is because the hepatitis B virus is able to start the process of infection during birth that late vaccination will not be able to stop. Therefore, administering the timely birth dose of hepatitis B vaccine to a baby born to a mother with chronic hepatitis B infection is a medical emergency requiring urgent vaccination.

8. Does a timely birth dose of hepatitis B vaccine need to be given to every newborn infant?

WHO recommends a timely birth dose for all newborn infants. Vaccination of newborn infants is safe and effective. If a baby is born to a mother who has chronic hepatitis B infection, the timely birth dose is lifesaving, as it prevents infection that would likely occur if no vaccine is given. If the hepatitis B status of the mother is unknown, the timely birth dose will protect the baby in case the mother has chronic hepatitis B infection. If the mother has a laboratory screening test showing that she does not have chronic hepatitis B infection, the timely birth dose can protect the baby in case the mother is really infected but there was a laboratory error or miscommunication of laboratory results. In this situation, the timely birth dose serves as a safety net for the baby. It also protects the baby from developing Hepatitis B infection from other sources of exposure later in life.

9. Is it safe to vaccinate newborn babies with hepatitis B vaccine?

Yes. Hundreds of millions of newborn babies around the world have been vaccinated with hepatitis B vaccine on the day of their birth. Population-based studies have shown that hepatitis B vaccine is not associated with any serious adverse event following immunization, except for very rare cases of allergic shock. This is a very rare risk with all vaccines. Allergic shock is an immediate event that is treatable, once recognized. Population studies have specifically looked for any relation between infant vaccines, including hepatitis B vaccine, and Sudden Infant Death Syndrome, and no relationship has ever been found.

10. What is China’s experience with the timely birth dose of hepatitis B vaccine?

As of 2012, over 95% of newborn babies receive the timely birth dose of hepatitis B vaccine. Hepatitis B vaccination of infants was introduced in 1992, and was fully integrated into the routine immunization program with the vaccine being made free of charge to all babies in 2002. Hepatitis B vaccine coverage (3 doses) increased from 30.0% for children born in 1992 to 99.7% for children born in 2012. Receipt of a timely birth dose increased from 22.2% to 95.7% for children born during this interval.

As a result of the timely birth dose and infant immunization, the prevalence of chronic hepatitis B infection has been reduced markedly in China. In the pre-vaccine era, over 9% of young children were chronically infected. That was reduced to less than 1% by 2006, as shown in a serological survey. Thus, through vaccination starting with the timely birth dose, China reduced the prevalence of chronic hepatitis B infection by 90% - a remarkable public health achievement.

11. How many babies are born to mothers with chronic hepatitis B infection in China?

Most women who are now of childbearing age in China were born before hepatitis B vaccination was fully integrated into the immunization program system in 2002, and most were born before the vaccine was readily available in China. Thus, many women who are currently of childbearing age were infected with hepatitis B virus during their birth. The prevalence of chronic heaptitis B infection among women of childbearing age is approximately 6%. Approximately 50,000 babies are born every day in China, and so nearly 3,000 babies are born every day to women with chronic hepatitis B infection – about one million babies every year.

12. How many countries recommend a timely birth dose of hepatitis B vaccine?

As of July 2011, 93 countries have introduced the hepatitis B birth dose. A total of 179 WHO Member States vaccinate infants against hepatitis B as part of their routine vaccination schedules. This is a major increase compared with 31 countries in 1992, the year that the World Health Assembly passed a resolution to recommend global vaccination against hepatitis B.

C. Safety of hepatitis B vaccine and infant deaths following vaccination

13. How safe are hepatitis B vaccines?

Hepatitis B vaccines are known to be safe and effective. The safety of hepatitis B vaccines has been regularly studied since they were first used over 20 years ago. There are common, minor side effects of the vaccine, such as local pain at the injection site and fever lasting less than one day.

It is possible to have an allergic reaction to any component of the hepatitis B vaccine. A serious allergic reaction, called allergic shock or anaphylaxis, happens rarely – estimated at 1 time per 1.1 million doses administered. Allergic shock, once recognized, is treatable. There is no evidence of long-lasting, serious adverse events being caused by hepatitis B vaccination. Sudden Infant Death Syndrome has been shown not to be related to any infant vaccines, including hepatitis B vaccine.

14. What is done to assure the safety of vaccines?

Only licensed vaccines are used in China. Prior to licensure, vaccines are evaluated for safety and efficacy in controlled clinical trials. Licensing of vaccines is accomplished by national regulatory authorities that evaluate the clinical study data for safety and efficacy. In addition to evaluation of clinical studies, the regulatory authorities inspect the manufacturing facilities and processes to assure that the current good manufacturing practices are followed. Once a vaccine is licensed and has market authorization, the manufacturer is allowed to sell the vaccine for use in accordance with the licensed indications. Each lot (batch) of vaccine is individually tested by the China regulatory authorities prior to being released for use.

Vaccines are monitored for safety in China as they are used. Adverse events following immunization are reported to a national monitoring system. Serious adverse events following immunization are individually evaluated to determine whether the vaccine caused the adverse event or whether the adverse event was coincidental with the vaccine but not caused by the vaccine.

The National Regulatory Authority (NRA) of China for vaccines – the China Food and Drug Administration and its affiliated institutions – has been evaluated by WHO and passed the evaluation, initially in 2010, and again in 2014. WHO has therefore verified that the regulation of vaccines in China is at the level of WHO/international standards. Vaccine regulation in China ensures that the vaccines licensed and used in China are of high quality and purity, and are safe and effective.

15. Please explain the circumstances of the infant deaths that followed hepatitis B vaccination in late 2013.

In December 2013, there were widespread media and social media reports of infant deaths following vaccination with hepatitis B vaccine. Within 2 days, use of the manufacturer’s hepatitis B vaccine was suspended and an investigation was launched jointly by the China Food and Drug Administration and the National Health and Family Planning Commission. To make sure that babies could still get lifesaving hepatitis B vaccine, hospitals and clinics were provided with hepatitis B vaccine from other manufacturers during the investigation.

The clinical investigation showed that all of the infant deaths were due to causes other than vaccination. These causes included pneumonia, kidney failure, congenital heart disease, and other medical conditions. The vaccine did not cause or contribute to any of the deaths. Chemical and biological tests of the vaccine showed that it was pure and uncontaminated, and was within the agreed-upon specifications. Investigation of the manufacturing facilities and processes showed that they were within the approved specifications for producing safe, effective, and high-quality hepatitis B vaccine.

Following the investigation, WHO experts were invited to study the investigation data and results. The WHO experts agreed that the investigations were professionally done and provided reliable information. The WHO experts agreed with the conclusion that the vaccine did not contribute to the deaths of the infants and that the vaccine and its manufacturing complied with the relevant international standards. Following the conclusions of the investigation, the China Food and Drug Administration allowed resumption of the use of this manufacturer’s vaccines on January 17, approximately one month after the initial media reports of infant deaths.

Since that time, WHO has reaffirmed its confidence in China’s national regulatory oversight of vaccines more generally, with WHO Director-General Dr Margaret Chan announcing the successful results of WHO’s re-assessment of China’s National Regulatory Authority (NRA) for vaccines during her visit to China in July 2014.

16. How it is that an infant can die following vaccination, but that the vaccine did not cause the deaths?

In China, as in the rest of the world, some infants sadly do not survive to their first birthday. The official neonatal mortality rate is 1.2% in China, and most of these deaths happen in the first month of life. The United Nations estimates that in China in 2012, over 150,000 live-born babies die within one month of their birth. There are many causes of these infant deaths, including prematurity, congenital heart defects, pneumonia, and other medical conditions. Some infants die suddenly, without showing any symptoms of illness.

Infancy is also a time when babies are susceptible to infectious diseases and their medical complications. Some of these infectious diseases are preventable by immunization, and that is why vaccination of infants is so important. In general, vaccine preventable diseases are more severe when they happen during infancy than when they happen after infancy, and therefore, early protection is important.

During the first month of life, 2 doses of hepatitis B vaccine are recommended – one dose on the first day of life, and a second dose at one month of age. Hepatitis B vaccine is the only vaccine with 2 doses recommended in the first month of life.

Because infancy is a time that some babies die from a variety of causes, and is also a time when vaccinations need to be given, some infants who are vaccinated will die of these other, unrelated causes following a vaccination. This coincidence in time can give the appearance that a death might be caused by the vaccine, even though that is almost never the case. In other words, the infant would have died even if the vaccine was not given.

When a death or other unexpected serious adverse event follows vaccination, a clinical investigation is necessary to understand the circumstances of the death and to determine whether the vaccine was related to the adverse event. In the case of the hepatitis B event in China in December 2013, the investigation was conducted by China FDA and NHFPC in a timely manner, and the investigation showed that the deaths were not caused by vaccinations.

No parent should be hesitant to have their baby protected with hepatitis B vaccine. Hepatitis B vaccine is, and has always been, safe and effective. Vaccination is the safest way to protect children from vaccine preventable diseases like hepatitis B.

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