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Hepatitis A

Introduction

Hepatitis A virus is a small, unenveloped RNA virus within the genus Hepatovirus, a member of the family Picornaviridae.  It causes acute inflammation of the liver.

 

Epidemiology

Global Epidemiology

Figure 1: Hepatitis A antibody prevalence

map of heaptitis A antibody prevalence

View a large version (opens in new window)

Map from: Health Information for Overseas Travel, 2010 [1]

 

The incidence of hepatitis A is closely related to socio-economic conditions, and sero-epidemiological studies show that prevalence of anti-hepatitis A antibodies varies from 15% to close to 100% in different parts of the world [2]. An estimated 1.5 million clinical cases of hepatitis A occur worldwide each year. The disease is endemic in many low-income countries where food and water hygiene may be of a low standard.

Regions where hepatitis A is highly endemic include the Indian sub-continent (particularly Bangladesh, India, Nepal and Pakistan), Sub-Saharan and North Africa, parts of the Far East (except Japan), South and Central America and the Middle East. Clinical cases of hepatitis A in adults are uncommon in highly endemic countries, as most people have been exposed to the virus at a young age and have acquired life-long immunity.

Most high-income countries such as Australia, Japan and New Zealand, and those in North America and Northern Europe are of low endemicity for hepatitis A. The majority of the population in these countries will have no immunity to hepatitis A and are therefore susceptible to the infection.

In some countries of the Americas, Asia and the Middle East,there has been a reduction in endemicity [3]. These countries are now in transition from high to

intermediate and low endemicity, such that hepatitis A is more common in young adults and teenagers who may not have had previous exposure to the virus as a child (and therefore not acquired any immunity) [2].

 

Hepatitis A in travellers from England and Wales

Hepatitis A is now relatively uncommon in the UK and is more often associated with specific risk groups (such as injecting drug users) or those individuals who travel to an endemic country [4, 5]. Since the mid-1990s there has been a decline in laboratory-confirmed cases of hepatitis A reported in England and Wales [4, 6]. However, travel history or other risk factor information is seldom reported, so it is difficult to say whether the decline is due to a change in travel patterns or to other factors.

Between 1998 and 2009 there were 527 reported cases of hepatitis A with a known recent history of foreign travel (6% of the total) [4]. The majority of cases, where the area of travel was known, were associated with travel to: Pakistan (98), India (47), Spain (24) and Egypt (22). Note that all but one of the cases acquired in Spain occurred before and during 2003.

 

Risk for travellers

The risk of acquiring hepatitis A in high-income countries is low. Non-immune travellers are at risk of contracting the disease during visits to countries of high or intermediate endemicity. The risk during travel depends on living conditions, length of stay and standards of food and water hygiene. Those at higher risk include travellers visiting friends and relatives (VFRs) [7], long-term travellers, and those visiting areas of poor sanitation. However, cases have occurred in tourists staying in good quality hotel accommodation [8, 9].

Hepatitis A remains one of the most common travel-related vaccine preventable diseases. However, the incidence in travellers is declining. The incidence of hepatitis A amongst non-immune travellers has been between estimated between six and 30 cases per 100,000 travellers per month [9].

 

Transmission

Hepatitis A is usually acquired through food or water contaminated by human faeces; foods that grow close to the ground such as strawberries and lettuce can be a risk. Crustaceans that feed at the bottom of the ocean such as oysters and clams can concentrate the virus and be a risk if ingested under-cooked or raw. Food handlers excreting hepatitis A virus can contaminate foods if they do not observe good personal hygiene.

Person to person transmission in conditions of poor faecal hygiene is also a risk factor. This mode of transmission can occur during certain sexual practices (e.g. oral/anal sexual contact), through unhygienic injection drug use, and between children [1].

Virus shedding in the faeces occurs during the incubation period of hepatitis A, and continues for a few days after the onset of jaundice. It is at this stage that patients are most infectious. Virus shedding can be prolonged in immunocompromised persons.

 

Signs and symptoms

Hepatitis A is usually a sub-clinical illness in young children. However, the disease becomes more serious with advancing age, with approximately 2% mortality rate in those over 50 years of age [10].

After an average incubation period of 28 days (range of 15-50 days), patients can experience a prodrome of malaise, anorexia, nausea and fever before developing jaundice [2]. Recovery takes about a month in young people, but some patients are ill for many weeks. Complications are more likely in those with pre-existing chronic liver disease, and can include fulminant hepatitis.

Following clearance of hepatitis A infection patients acquire lifelong immunity.

 

Treatment

There is no specific anti-viral treatment for hepatitis A, but rather supportive intervention.

Prevention

Hepatitis A is transmitted via the faecal-oral route; therefore the most common mode of infection for travellers is through eating contaminated food, or drinking contaminated water. The risk of acquiring hepatitis A can be reduced by following guidelines on food and water hygiene and by ensuring good personal hygiene.

Several effective and well-tolerated hepatitis A vaccines are available for travellers intending to visit endemic areas. The vaccine is a complement to food and water hygiene precautions.

 

Hepatitis A Vaccine Information

 

Indications for use of vaccine

  • Hepatitis A vaccine is recommended for:
  • Travellers visiting areas of hepatitis A risk, particularly those visiting friends and relatives, long-term travellers and those visiting areas of poor sanitation
  • Persons with chronic liver disease. Although not at greater risk of hepatitis A infection, the disease can produce a more serious illness in this group
  • Persons whose sexual behaviour is likely to put them at an increased risk. There is an increase in hepatitis A in men who have sex with men
  • Vaccination should be given to injecting drug users and those with chronic liver disease, haemophilia, or at occupational risk.
 

Further information on indications for vaccination can be found in Immunisation against Infectious Disease known as the ‘Green Book’.

Country-specific information on the risk of hepatitis A can be found in the NaTHNaC Country Information Pages.

 

Availability of vaccine

Several vaccines are licensed for use in the UK, all of which are inactivated.  Details of these can be found in the summary table below. The Summary of Product Characteristics (SmPC) should be consulted prior to the administration of any vaccine [11-21].

Combined hepatitis A and B vaccines, and combined hepatitis A and typhoid vaccines are available.

 

Vaccine schedules (listed alphabetically)

Vaccine

Manufacturer/distributor

Schedule

Length of protection against hepatitis A*

Age range

Ambirix

Combined hepatitis A and B

GlaxoSmithKline

2 doses, given 6-12 months apart

Hepatitis A*: 10 years following 2nd dose.

See also hepatitis B information sheet

1 to 15 years

Avaxim

Sanofi Pasteur MSD

2 doses, given 6-12 months apart

10 years following 2nd dose*

≥ 16 years

Epaxal

Crucell UK Ltd

2 doses, given 6-12 months apart

Up to 30 years following 2nd dose*

Adults & children from ≥1 year

 

Havrix Monodose

GlaxoSmithKline

2 doses, given 6-12 months apart

Up to 25 years following 2nd dose*

≥ 16 years

Havrix Junior Monodose

GlaxoSmithKline

2 doses, given 6-12 months apart

Up to 25 years following 2nd dose*

1 to 15 years

Hepatyrix

Combined hepatitis A and typhoid

GlaxoSmithKline

1 dose followed by a single antigen hepatitis A vaccine 6-12 months later

Hepatitis A*: up to 25 years following 2nd dose.

See also typhoid information sheet

≥15 years

Twinrix Adult

Combined hepatitis A and B

GlaxoSmithKline

3 doses, 0, 1, and 6 months

Hepatitis A*: up to 25 years following 3rd dose.

See also hepatitis B information sheet

≥16 years

4 doses, days 0, 7 and 21, 4th dose at 12 months.

Hepatitis A*: up to 25 years following 4th dose. See also hepatitis B information sheet

≥18 years

Twinrix Paediatric

Combined hepatitis A and B

GlaxoSmithKline

3 doses, 0, 1 and 6 months

Hepatitis A: up to 25 years following 3rd dose*

See also hepatitis B information sheet

1 to 15 years

Vaqta Adult Sanofi Pasteur MSD 2 doses, given 6-12 months apart At least 6 years following the 2nd dose* ≥18 years

Vaqta Paediatric

Sanofi Pasteur MSD

2 doses, given 6-18 months apart

At least 10 years following 2nd dose*

1 to 17 years

ViaTIM

Combined hepatitis A and typhoid

Sanofi Pasteur MSD

1 dose followed by a single antigen hepatitis A vaccine 6-12 months later

At least 10 years following 2nd dose*

See also typhoid information sheet

≥16 years

* There is no evidence that further reinforcing doses of hepatitis A vaccine are needed in immunocompetent individuals following completion of the primary course [22]. The duration of protection from a completed course of vaccine can be expected to be at least 25 years and probably indefinite. The Joint Committee on Vaccination and Immunisation (JCVI) has accepted a 25 year interval for a booster dose of vaccine for those at ongoing risk. However, specific advice should be sought for individuals with altered immune responses.

It is good practice to continue a course of hepatitis A with the same brand of vaccine. However, evidence suggests that hepatitis A vaccines are likely to be compatible with each other [22-24], and if necessary a different preparation of hepatitis A vaccine could be given.

 

Interrupted courses

The Summary of Product Characteristics (SPC) for Avaxim states that the second dose may be administered up to 36 months after the primary dose [12].

The SPC for Epaxal states that the second dose can be delayed for up to 10 years [14].

The SPC for Havrix Monodose states that a second dose that is delayed for up to 5 years can be expected to induce similar antibody levels as a booster given within the recommended 6-12 months [15]. For Havrix Junior Monodose, a booster that is delayed for up to 3 years can be expected to induce similar antibodies as a second dose given within the recommended 6-12 months [16].

Vaqta Paediatric second doses can be administered up to 18 months following the primary dose [20].

Although booster doses delayed beyond the recommended intervals described above are not covered by the product licence, research indicates that a second dose given at long intervals will still result in a boosting immune response [24-28].

Thus, based on evidence from available studies, there is no maximum interval which would require restarting a course of hepatitis A vaccine.

 

Contraindications

  • Current febrile illness
  • Individuals who develop hypersensitivity reactions after vaccination should not receive further doses

Specifically relating to Epaxal

  • Hypersensitivity to eggs and chicken protein

Adverse events

Adverse reactions following hepatitis A vaccine tend to be mild and transient. They include tenderness, redness and swelling at the injection site. Less commonly, fever, headaches, dizziness and malaise have been reported.

 

References

1. Field VK, Ford L, Hill DR (eds). Health Information for Overseas Travel. National Travel Health Network and Centre, London, 2010.

2. World Health Organization. The global prevalence of hepatitis A virus infection and susceptibility: A systematic review. WHO/IVB/10.01, 2010. [Accessed 20 September 2013]. Available at: http://whqlibdoc.who.int/hq/2010/WHO_IVB_10.01_eng.pdf

3. Jacobsen KH, Koopman JS. The effects of socioeconomic development on worldwide hepatitis A virus seroprevalence patterns. Int J Epidemiology. 34:600-9, 2005.

4. Public Health England. Hepatitis A laboratory reports by travel history, England and Wales, 1998-2009. [Accessed 20 September 2013]. Available at: http://www.hpa.org.uk/web/HPAweb&HPAwebStandard/HPAweb

_C/1195733816731

5. Kumbang J, Ejide S, Tedder RS et al. Outbreak of hepatitis A in an extended family after importation by non-immune travellers. Epidemiol Infect. 2012 Oct;140(10):1813-20.

6. Public Health England. Hepatitis A. Last reviewed 25 November 2011 [Accessed 20 September 2013]. Available at: http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/

TravelHealth/EpidemiologicalData/GastrointestinalInfections/

travHepatitisA/

7. Public Health England. Foreign travel-associated illness – a focus on those visiting friends and relatives 2008 report. London, Health Protection Agency; 2008. [Accessed 20 September 2013]. Available at: http://www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPA

web_C/1231419801008?p=1158945066450

8. MacDonald E, Steens A, Stene-Johansen K et al.  Increase in Hepatitis A in tourists from Denmark, England, Germany, the Netherlands, Norway and Sweden returning from Egypt, November 2012 to March 2013. [Accessed 20 September 2013]. Available at: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20468

9. Mütsch M, Spicher VM, Gut C, Steffen R. Hepatitis A virus infections in travelers, 1988-2004. Clin Infect Dis. 42:490-7, 2006.

10. Sharapov UA. Hepatitis A. In: Centers for Disease Control and Prevention. CDC Health Information for International Travel 2012. New York: Oxford University Press, 2012.

11. GlaxoSmithKline UK. Summary of Product Characteristics Ambirix. Updated 22 August 2012. [Accessed 20 September 2013]. Available at: http://www.medicines.org.uk/emc/medicine/20491/SPC/

Ambirix+suspension+for+injection/

12. Sanofi Pasteur MSD Ltd. Summary of Product Characteristics Avaxim. Updated 1 September 2011. [Accessed 20 September 2013]. Available at: http://emc.medicines.org.uk/medicine/6206/SPC/AVAXIM/

13. Crucell UK Ltd. Summary of Product Characteristics Epaxal. Updated 1 April 2012. [Accessed 20 September 2013]. Available at: http://emc.medicines.org.uk/medicine/12742/SPC/Epaxal/

14. GlaxoSmithKline UK. Summary of Product Characteristics Havrix Monodose. Updated 22 July 2013 [Accessed 20 September 2013]. Available at:

http://www.medicines.org.uk/emc/medicine/2041/SPC/

Havrix+Monodose+Vaccine/

15. GlaxoSmithKline UK. Summary of Product Characteristics Havrix Junior Monodose. Updated 22 July 2013. [Accessed 20 September 2013]. Available at: http://www.medicines.org.uk/emc/medicine/2040/SPC/

Havrix+Junior+Monodose+Vaccine/

16. GlaxoSmithKline UK. Summary of Product Characteristics Hepatyrix. Updated 25 January 2012. [Accessed 20 September 2013]. Available at: http://emc.medicines.org.uk/medicine/2537/SPC/Hepatyrix/

17. GlaxoSmithKline UK. Summary of Product Characteristics Twinrix Adult. Updated 19 January 2012. [Accessed 20 September 2013]. Available at: http://www.medicines.org.uk/emc/medicine/2061/SPC/Twinrix+

Adult+Vaccine%2c+suspension+for+injection+in+

prefilled+syringe/

18. GlaxoSmithKline UK. Summary of Product Characteristics Twinrix Paediatric. Updated 31 January 2012 . [Accessed 20 September 2013]. Available at: http://www.medicines.org.uk/emc/medicine/2062/SPC/Twinrix+

Paediatric+Vaccine+suspension+for+injection+in+pre-filled+syringe/

19. Sanofi Pasteur MSD Ltd. Summary of Product Characteristics Vaqta Adult. Updated 12 February 2013. [Accessed 20 September 2013]. Available at: http://www.medicines.org.uk/emc/medicine/6210/SPC/

VAQTA+Adult/

20. Sanofi Pasteur MSD Ltd. Summary of Product Characteristics  Vaqta Paediatric. Updated 17 July 2012. [Accessed 20 September 2013]. Available at: http://www.medicines.org.uk/emc/medicine/6211/SPC/VAQTA+

Paediatric/

21. Sanofi Pasteur MSD Ltd. Summary of Product Characteristics  ViATIM. Updated. [Accessed 20 September 2013]. Available at: http://emc.medicines.org.uk/medicine/7684/SPC/ViATIM/

22. Ott JJ, Irving G, Wiersma ST. Long-term protective effects of hepatitis A vaccines. A systematic review. Vaccine 31; 3–11, 2012.

23. Clarke P, Kitchin N, Souverbie F. A randomised comparison of two inactivated hepatitis A vaccines, Avaxim and Vaqta, given as a booster to subjects primed with Avaxim. Vaccine 19:4429-33, 2001.

24. Beck BR, Hatz CFR, Loutan L, Steffen R. Immunogenicity of booster vaccination with a virosomal hepatitis A vaccine after primary immunization with an aluminum-adsorbed hepatitis A vaccine. J Travel Med. 11:201-7, 2004.

25. Van Damme P, Banatvala J, Fay O et al. Hepatitis A booster vaccination: is there a need? Lancet 362:1065-71, 2003.

26. Beck BR, Hatz C, Bronnimann R, Herzog C. Successful booster antibody response up to 54 months after single primary vaccination with virosome-formulated, aluminum-free hepatitis A vaccine. Clin Infect Dis. 37:e126-8, 2003.

27. Landry P, Tremblay S, Darioli R, Genton B. Inactivated hepatitis A vaccine booster given ≥ 24 months after primary dose. Vaccine 19: 399-402, 2001.

28. Iwarson S, Lindh M and Widerstrom L. Excellent booster response 4 to 8 years after a single primary dose of an inactivated hepatitis A vaccine. J Travel Med. 11:120-1, 2004.

 

Links

 

Updated September 2013