Introduction of universal infant hepatitis B immunisation in the UK– paving the way to elimination

ABSTRACT

In May 2016, the World Health Assembly ratified the first ever Global Health Sector Strategy (GHSS) on Viral Hepatitis to eliminate viral hepatitis as a public health threat by 2030. In pursuit of this elimination goal and recognising that hepatitis control through immunisation is an essential foundation of a hepatitis B prevention programme, the World Health Organization set out vaccine coverage targets for both universal and selective childhood immunisation programmes, focusing on preventing mother to child transmission.

In August 2017 the UK introduced a hexavalent (DTaP/IPV/Hib/HepB) combination vaccine into the routine childhood immunisation programme, replacing the pentavalent vaccine given to all infants at 8, 12 and 16 weeks. With the addition of the 6th component to protect against hepatitis B the UK finally introduced universal hepatitis B immunisation. Prior to that, the UK had a selective immunisation policy targeting high risk groups for hepatitis B – including infants born to hepatitis B infected mothers. We tell the story of hepatitis B vaccination in the UK, and how we have evolved from selective to a universal infant immunisation programme, the factors considered in hepatitis B vaccine policy decision-making, and the progress towards elimination of viral hepatitis as a public health threat.

Introduction

In May 2016, 194 member states of the World Health Assembly – including the UK – signed up to the first ever Global Health Sector Strategy (GHSS) on Viral Hepatitis to eliminate viral hepatitis as a public health threat by 2030. This strategy set global targets for viral hepatitis, with a goal of a 90% reduction in incident hepatitis B (and C) chronic cases and 65% reduction in mortality by 2030. In pursuit of this ultimate elimination goal and recognising that hepatitis control through immunisation is an essential foundation of a hepatitis B prevention programme, the World Health Organization set out vaccine coverage targets for both universal childhood immunisation and selective immunisation to prevent mother to child transmission.

In August 2017 the UK took a big step forward in the fight against viral hepatitis -specifically hepatitis B – with the incorporation of the hexavalent (DTaP/IPV/Hib/HepB) combination vaccine into the routine childhood immunisation programme. This vaccine is now offered to all infants at 8, 12 and 16 weeks, replacing the pentavalent vaccine which protected against diphtheria, tetanus, pertussis, polio and haemophilus influenzae type B. With the addition of the 6th component, infants are now protected against hepatitis B.

In this article, we tell the story of hepatitis B vaccination in the UK, and how we have evolved from selective to a universal infant immunisation programme, the factors considered in hepatitis B vaccine policy decision-making, and the progress towards elimination of viral hepatitis as a public health threat.

Epidemiology of hepatitis B

Worldwide, an estimated 257 million people are living with hepatitis B infection, resulting in almost 900,000 deaths.¹ Despite this clear burden, public and professional awareness of hepatitis B remains low compared to HIV and other infections. Dubbed the ‘Silent Killer’, many of those who are chronically infected do not know they have the virus until cirrhosis or hepatocellular carcinoma has already occurred.

The hepatitis B virus (HBV), a double-stranded DNA hepadnavirus, is 50–100 times more infectious than HIV, and transmitted through percutaneous, mucocutaneous and vertical route.² Acute infection is often not clinically recognisable; less than 10% of infants and 30–50% of adults show non-specific symptoms.³ In a very small number of acute cases (0.1–0.5%), the infection may lead to fulminant hepatic failure which can be fatal. Whilst most adults are able to clear the virus and make a full recovery, a small proportion (5–10%) will progress to chronic, persistent infection. Younger individuals are less likely to clear the infection, with up to 50% of children and 90% of infants progressing to chronic disease.

In most developed countries, the seroprevalence of HBV infection is less than 2%. In these areas, most new cases occur among young adults through sexual intercourse or sharing of needles among people who inject drugs. In countries, such as those in Sub-Saharan Africa, South Asia and the Pacific Islands where the prevalence is high (>8%), vertical transmission from mother to child is the predominant route of transmission. In the UK, an estimated 0.4% of the population have chronic hepatitis B with the bulk of disease burden in migrants who have acquired the infection overseas in endemic countries prior to arrival in the UK. Overall, the UK is classified as a low incidence and prevalence country.

Selective versus universal immunisation against hepatitis B

Since safe and effective hepatitis B vaccines became available in the late 1980s the UK has had a selective immunisation policy recommending vaccination of those at increased risk of hepatitis B exposure e.g. healthcare workers, renal dialysis patients, people who inject drugs, prisoners and people travelling long-term or living in endemic countries. Additionally, vaccination is recommended for those at increased risk of complications from hepatitis B. e.g. people with other chronic liver conditions, people living with HIV, and also for those who have had a significant exposure to a known or unknown hepatitis B infected individual (post exposure vaccination).

Universal antenatal screening has been in place since 2000, and identifies around 3,000 hepatitis B positive pregnant women each year so that selective vaccination of the at-risk infant can be given. This selective hepatitis B immunisation programme provides post exposure vaccination starting from birth for neonates, the group at highest individual risk of infection, as they have already been exposed to infected blood during birth. Without intervention, up to 90% of hepatitis B infected women will transmit infection to their infant perinatally, leading to chronic infection.⁴ With post-exposure vaccination of the infant starting immediately at birth and continuing at 4 weeks, 8 weeks and with a booster at one year, however, this risk is dramatically reduced to below 10%.⁵

Infants born to mothers at particularly high risk of HBV transmission (e.g. viral load >10⁶ IU/ml at any time in the pregnancy, hepatitis B e antigen positive, or hepatitis B e antibody negative, acute hepatitis B in pregnancy) are also given hepatitis B immunoglobulin at birth which provides marginal additional protection beyond vaccine. In addition pregnant women with a high viral load are also recommended to receive antiviral treatment in the third trimester. All children born to infected mothers are recommended to have a blood test for the presence of hepatitis B surface antigen (HBsAg) at one year of age (for convenience, at the same time as routine vaccinations) to confirm or exclude chronic infection and allow early specialist referral, if infected. Without testing, infected children may be missed as they are unlikely to show any symptoms or signs to prompt testing. With over 95% uptake of vaccine at birth and around 80% uptake for subsequent doses, this programme has been successful in preventing maternal to child transmission and is known to be highly cost-effective.

In 1992, the World Health Assembly called for every country to adopt a universal hepatitis B immunisation programme by 1997. By 2008, 177 countries had incorporated hepatitis B into their primary infant routine immunisation programmes. At the time, because of the low prevalence and incidence in the UK, it was not cost-effective to implement a universal programme using the available monovalent hepatitis B vaccines.

UK considerations for introduction of universal hepatitis B vaccination

In England, the Department of Health and Social Care (DHSC) makes vaccine policy on the basis of recommendations from an expert independent scientific committee, the Joint Committee on Vaccination and Immunisation (JCVI).The JCVI reviews data on safety, immunogenicity (including that of other antigens in combination vaccines and concomitantly administered vaccines), efficacy, cost effectiveness and vaccine uptake for immunisation programmes. The NHS Constitution mandates that JCVI can only recommend a new vaccine programme if it meets the cost-effectiveness criteria: a cost per quality life adjusted year (QALY) of equal or less than £20,000.⁶

In 2009, the Secretary of State for Health requested a recommendation from the JCVI on universal hepatitis B vaccination. The JCVI were unable to recommend universal vaccination as the evidence indicated that a stand-alone (monovalent) hepatitis B vaccine was highly unlikely to be cost-effective.⁷ The model was based on the estimated incidence of acute infection, as most chronic hepatitis B in the UK is imported in adults and not preventable by a UK infant vaccination programme. Economic models did suggest, however, that the use of a combination infant vaccine containing hepatitis B could make a universal infant programme cost effective. However, there were concerns that the available infant hepatitis B-containing combination vaccines (those including 2- or 3-component acellular-pertussis antigens) could produce inferior Hib responses. The UK had just recovered from a resurgence of Hib disease in 2000 to 2002 when a 3-component acellular pertussis pentavalent infant vaccine was temporarily used during a period of vaccine shortage.

After a Hib booster at around one year of age was added to the schedule in 2006, the UK was able to use a pentavalent vaccine containing 3-component acellular-pertussis and had several years of sustained control of Hib. Therefore, in 2014, the JCVI re-evaluated their earlier advice and recommended that a universal hepatitis B infant programme would not be a risk to the control of Hib and was highly likely to be cost-effective.⁸ A suitable combination vaccine (Infanrix hexa®) was procured to commence routine infant immunisation from late 2017.

While Infanrix hexa® is new to the UK, it has been licensed in Europe since 2000 with worldwide successful implementation into routine programmes. It is licensed in and at least 97 other countries including Canada, Australia and New Zealand and an estimated 150 million doses have been given to infants worldwide to-date, with no safety concerns. Following three doses of the vaccine at 8, 12 and 16 weeks, clinical trials have shown nearly all children develop protective antibody titres against diphtheria (100%), tetanus (100%), pertussis (100%), hepatitis B (99.5%), polio (98–100%) and Hib (96%).⁹

Integrating universal and selective hepatitis B immunisation schedules

As the hexavalent vaccine is not given until eight weeks, JCVI also considered the best way to protect children born to hepatitis B positive mothers. They recommended that the babies still need to have the birth and 4 weeks doses (with monovalent vaccine) as these post exposure doses are critical to prevent maternal to child transmission at birth. These infants should then continue with hexavalent vaccine as part of the routine schedule at 8, 12, and 16 weeks and have a final monovalent hepatitis B vaccine dose at 1 year old, alongside the test to exclude chronic infection (see Figure 1). While this amounts to six doses of hepatitis B vaccine by the age of one, it was considered the safest option to ensure that protection was not compromised – for example if infants receive their routine doses late.¹⁰ The pre-school booster dose of hepatitis B vaccine was removed.

Figure 1.

UK hepatitis B vaccine schedules for the routine childhood and selective neonatal immunisation programmes.

Progress towards the elimination goal

With the well-established selective neonatal immunisation programme, the UK has already exceeded the WHO GHSS 2030 90% birth dose target (to prevent maternal to child transmission) in at-risk infants. With the introduction of universal childhood immunisation the 90% coverage third dose target should be easily attainable in UK as the pentavalent vaccine coverage has exceeded 90% for the last ten years. Based on market research into parents’ attitudes, we expect coverage of the new hexavalent vaccine to be equivalent to that achieved for pentavalent vaccine.

The recognition of viral hepatitis as a global major health burden and the united call for action to tackle it is a huge step forward in reducing the worldwide burden of this disease. By incorporating hepatitis B vaccine into the childhood immunisation programme, the UK has shown renewed commitment to this goal.

Funding Statement

none

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.