August 2007

Hepatitis A

• Introduction
• Epidemiology
• Risk for travellers
• Transmission
• Signs and symptoms
• Treatment
• Prevention
• Vaccination information
• References
• Links

Introduction

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

Epidemiology

Global epidemiology

Figure 1: Geographic distribution of the prevalence of hepatitis A virus [1].

Hepatitis A occurs worldwide; it is estimated that around 1.5 million cases of clinical hepatitis A occur per year [2]. 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]. 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 India, Pakistan, Bangladesh and Nepal), Sub-Saharan and North Africa, and parts of the Far East (not Japan), South and Central America, and the Middle East (Figure 1). 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 those in Western and Northern Europe, North America, and Australia, New Zealand, and Japan 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 as children and adults.

In some countries in Eastern Europe and in parts of Asia and the Americas there has been a recent reduction in endemicity. 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 (and therefore not acquired any immunity) to the virus as a child [1]. 

Hepatitis A in travellers from England, Wales, and Northern Ireland

Figure 2: Laboratory reports of hepatitis A by travel history, England, Wales, and Northern Ireland: 1996-2005

Figure 2 shows the laboratory reports of hepatitis A to the Health Protection Agency, Centre for Infections between 1996 and 2005 [3]. There has been a decline in reported hepatitis A cases seen (in total) in England, Wales, and Northern Ireland since the mid-1990s. The majority of laboratory reports do not have a travel history so it is not possible to say where most of the cases were acquired. There has been a steady decline in travel history reporting since the mid-1990s with only 6.5% of case reports in 2005 having any information regarding recent travel.

Between 2003 and 2005, there were 68 reported cases of hepatitis A with a recent history of foreign travel (table 1). Of those, 30 (44%) had travelled to the Indian sub-continent (20 to Pakistan, 10 to India), 13 had travelled to various European countries, six to African countries and 14 to other countries; five cases had no country of travel stated. The Indian sub-continent remained the most reported region of travel for travel-associated hepatitis A between 2003 and 2005, which is consistent with previous years [3].

Table.1 Laboratory reports of hepatitis A by country of travel England, Wales, and Northern Ireland: 2003 - 2005

Country of travel	2003	2004	2005	Totals
Bulgaria	-	-	1	1
Cyprus	1	-	-	1
Dominican Republic	-	-	2	2
Eastern Europe	-	-	1	1
Europe/Mediterranean	1	-	-	1
Egypt	1	1	1	3
Eritrea	-	1	-	1
Finland	1	-	-	1
Greece	1	1	-	2
India	2	6	2	10
Kenya	1	-	-	1
Nigeria	1	-	-	1
Pakistan	7	9	4	20
Russia	-	1	-	1
South Africa	-	-	1	1
South east Asia	-	1	-	1
Spain	3	1	-	4
Switzerland	1	-	-	1
Tanzania	-	-	1	1
Thailand	-	1	1	2
Tibet	-	-	1	1
Turkey	1	-	-	1
Tunisia	-	-	2	2
USA	1	-	1	2
Zambia	-	-	1	1
Country not stated	1	1	3	5
Total	23	23	22	68

Risk for travellers

The risk of acquiring hepatitis A in high-income countries is low.  Non-immune travellers to countries of high or intermediate endemicity are at risk of contracting the disease as they have had no previous exposure to the virus. The risk of acquiring hepatitis A in low-income regions depends on several factors including living conditions, length of stay and standards of food and water hygiene. Those at higher risk include travellers visiting friends and relatives, long-stay travellers, and those visiting areas of poor sanitation. However, cases have occasionally occurred in tourists staying in good quality hotel accommodation.

Hepatitis A remains one of the most common of the travel-related vaccine preventable diseases. However, the incidence in travellers is declining. A study published in 2006 found the incidence of hepatitis A amongst non-immune travellers varied between six and 30 cases per 100,000 travellers per month [4]. The highest rates were found in travellers to Africa, south-central Asia, particularly the Indian sub-continent and Latin America.

Transmission

Hepatitis A in travellers is usually acquired through food or water contaminated by human faeces. As examples, foods that grow close to the ground such as strawberries and lettuce may be a risk. Crustaceans which feed at the bottom of the ocean such as oysters and clams, may 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 proper hygiene.

Personal contact in conditions of poor faecal hygiene is also a risk factor. This mode of transmission may occur between children or in adults during certain sexual practices [5].

                                                                     

Virus shedding in the faeces occurs during the incubation period, 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 & 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 [6].

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 include fulminant hepatitis.

Following infection with hepatitis A, patients acquire life long 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 common sense guidelines on food and water hygiene and by ensuring good personal hygiene.

Several highly effective and well-tolerated hepatitis A vaccines are available for travellers intending to visit endemic areas. However, the vaccine should not be an alternative 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 travellers visiting friends and relatives, long stay 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. An increase in hepatitis A has been noted in men who have sex with men [5];
• Vaccination should also be given to those with haemophilia, injecting drug users and those at occupational risk;
• Further information on indications for vaccination can be found in Immunisation against Infectious Disease ‘the Green Book’.

Availability of vaccine

There are several vaccines licensed for use in the UK, all of which are inactivated.

Details of these can be found in the summary table below.

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

Vaccine schedules [7-11]

Vaccine	Manufacturer/distributor	Schedule	Length of Protection*	Age range
Avaxim	Sanofi Pasteur MSD	2 doses, given 6-12 months apart	10 years following 2nd dose*	Adults from 16 years
Epaxal	Berna Biotech/MASTALtd	2 doses, given 6-12 months apart	20 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*	Adults from 16 years
Havrix Junior Monodose	GlaxoSmithKline	2 doses, given 6-12 months apart	Up to 25 years following 2nd dose*	Children from 1 to 15 years
Vaqta Paediatric	Sanofi Pasteur MSD	2 doses, given 6-12 months apart	At least 9 years following 2nd dose*	Children form 1 to 17 years

* There is no evidence that further reinforcing doses of hepatitis A vaccine are needed in immunocompetent individuals following completion of the primary course [12]. The duration of protection from a completed course of vaccine can be expected to be at least 20 years and probably indefinite. The Joint Committee on Vaccination and Immunisation (JCVI) has accepted a 20 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 [13,- 15], 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.

The SPC for Epaxal states that the second dose can be delayed for up to 4 years. Good protective antibody levels are achieved even if the booster dose of Epaxal is given up to 56 months after the primary dose [8].

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. 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. Second doses delayed beyond the recommended interval are not covered by the Product Licence. However, research suggests that second doses of Havrix Monodose and Junior Monodose given up to 66 months after the first dose will still boost the primary dose [16].

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

Thus, based on evidence from available studies, there is no 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 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. Bell BP. Global epidemiology of hepatitis A: implications for control strategies. 10th International symposium on viral hepatitis A and liver disease.

2. World Health Organization.  Hepatitis A vaccines: WHO position paper.  Weekly Epidemiological Record 2000; 5: 38-44.  Available at: http://www.who.int/wer/pdf/2000/wer7505.pdf

3. Health Protection Agency. Foreign travel-associated illness in England, Wales and Northern Ireland: 2007 report. London, Health Protection Agency; 2007. Available at http://www.hpa.org.uk/webw/HPAweb&

HPAwebStandard/HPAweb_C/1204186178825?p=1158945066450

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

5. Centers for Disease Control and Prevention. Hepatitis A amongst homosexual men. MMWR 1992;41:161-4.

6. Steffen R. Changing travel-related global epidemiology of hepatitis A. Am J Med 2005; 118: 46S-49S.

7. Sanofi Pasteur MSD Ltd. Summary of Product Characteristics - Avaxim. Updated 20 September 2006. [accessed 8 January 2007] Available at http://emc.medicines.org.uk/

8. Masta Ltd. Summary of Product Characteristics – Epaxal. Updated 12 January 2005. [accessed 8 January 2007] Available at: http://emc.medicines.org.uk/

9. GlaxoSmithKline UK. Summary of Product Characteristics – Havrix Monodose. Updated 5 April 2006 [accessed 8 January 2007]. Available at: http://emc.medicines.org.uk/

10. GlaxoSmithKline UK. Summary of Product Characteristics – Havrix Junior Monodose. Updated 5 April 2006 [accessed 8 January 2007]. Available at: http://emc.medicines.org.uk/

11. Sanofi Pasteur MSD Ltd. Summary of Product Characteristics – Vaqta Paediatric. Updated 11 November 2005 [accessed 8 January 2007] Available at: http://emc.medicines.org.uk/

12. Zuckerman JN, Kirkpatrick CT, Huang M. Immunogenicity and reactogenicity of Avaxim (160 AU) as compared with Havrix (1440 EL.U) as a booster following primary immunization with Havrix (1440 EL.U) against hepatitis A. J Travel Med 1998;5:18-22.

13. 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 2001;19:4429-33.

14. 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. Journal of Travel Medicine 2004;11:201-207.

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

16. 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 2003;37:e126-8.

Links

Health Protection Agency

http://www.hpa.org.uk/infections/topics_az/hepatitis_a/menu.htm

Immunisation against infectious disease ‘The Green Book’

http://www.dh.gov.uk/en/Policyandguidance/Healthandsocial

caretopics/Greenbook/DH_4097254