Hepatitis A Vaccine

Clinical & Epidemiological Background

Hepatitis A virus (HAV) is the most common cause of viral hepatitis worldwide. In resource-limited countries, most people are infected during the first decade of life, but the incidence of disease attributable to HAV has declined significantly since the hepatitis A vaccine was first licensed in Europe in 1991 and the United States in 1995.

Almost always childhood infection is anicteric and asymptomatic, resulting in lifelong protective immunity. In contrast, infections acquired during adolescence and adult are symptomatic and typically lasts several weeks, with jaundice occurring in 70% or more; although 10% to 15% of symptomatic people have prolonged or relapsing disease lasting as long as 6 months. A member of the Picornaviridae family, HAV has only one serotype. Chronic infection does not occur. Fulminant hepatitis is rare but is more common in people with underlying liver disease.

Unlike hepatitis B (HBV) and C (HCV) viruses, HAV is spread primarily through the fecal-oral route, carried via the bloodstream to its primary target, the hepatocyte, where it replicates robustly but without causing much damage to the cells. A newly-made virus is released via the bile ducts secreted into the intestines and stool. Being mostly asymptomatic and having longer fecal shedding of virus, both Infants and children have remained the primary reservoir of HAV and are a source of infection for vulnerable adults.

HAV infection is more likely to result in significant liver disease in individuals coinfected with HBV or HCV or HEV, patients waiting for or having undergone liver transplantation, pregnant women, and people infected with HIV infection. HAV has been identified as the most common cause of acute hepatitis and the disease may be prolonged for months and has a particularly high mortality rate in the presence of chronic liver disease. For these high-risk populations, not only is the acute infection more severe, but the immune response to HAV vaccination is relatively poor. Hence, it is imperative to vaccinate patients at special risk early, before they have suffered significant hepatic damage from their underlying disease.

The Major Methods of Prevention of HAV Infections

• Personal hand hygiene,

• Improved sanitation (eg, in food preparation and of water sources)

• Immunization with hepatitis A vaccine.

• Standard Immune globulin (IGIM) are recommended for post-exposure prophylaxis for unimmunized patients

Hepatitis A Vaccines (hepa Vaccines)

Commercially available HepA vaccines are Havrix (GlaxoSmithKline, USA), Vaqta (Merck & Co Inc., USA), and Avaxim (Sanofi Pasteur; France, Canada). The vaccines are prepared from cell culture-adapted HAV, which is propagated in human fibroblasts, purified from cell lysates, formalin-inactivated, and adsorbed to an aluminum hydroxide adjuvant. The pediatric doses contain half the amount of viral antigen and aluminum. Inactivated whole-virus vaccines require a booster at least 6 months after the initial dose.

Routine Vaccination

• The IAP and the Advisory Committee on Immunization Practices (ACIP) USA, recommends routine vaccination against HAV of all children, starting at 12 to 23 months of age.

• Initiate the 2-dose inactivated HepA vaccine series at 12 months of age, with a booster dose 6 to 18 months later and catch-up for older children.

• The adult formulations are recommended for people 19 years and older.

• Completion of the immunization regimen with the same product is preferable; immunization with other inactivated product is acceptable.

• May be administered simultaneously with other childhood vaccines. Vaccines should be given in a separate syringe and at a separate injection site .

• Recommended doses and schedules for the Pediatrics & adults are given in the Table.1

Table: Recommended Doses and Schedules for Hepatitis A Virus (Hep A) Vaccines

Immunogenicity

Available inactivated vaccines are highly immunogenic when given in their respective recommended schedules and doses. At least 95% of healthy children, adolescents, and adults have protective antibody concentrations when measured 1 month after receipt of the first dose of vaccine. One month after a second dose, more than 99% of healthy children, adolescents, and adults have protective antibody concentrations.

• Vaccine-induced protective immunity appears to be long term, with kinetics-based estimates indicating at least 20 years or longer.

• Protective efficacy in preventing clinical HAV infection is 94% to 100%

• The immune response in immunocompromised people, including people with HIV, may be suboptimal

• The vaccines are safe, are interchangeable, and can be administered at the same time as other vaccines. Adverse events are uncommon

• Inactivated vaccines are classified in pregnancy category C.

• There also is a combined HAV-HBV vaccine approved for patients 18 years and older

Combinations Vaccines are Available for Adults Use

• Twinrix [a combination of HepB (Engerix-B, 20 µg) and Hep A (Havrix, 720 ELU)] for adults. 18 years and older.

• Viatim (combined typhoid Vi/HA vaccine) for adults with a booster dose after 3 years significantly increased antibody levels with some evidence of relative hypo responsiveness of the typhoid response.

Live Attenuated H2 Hav Strain Vaccine (Chinese Vaccine)

Both WHO and IMA recommend a single dose subcutaneous injection at 12 months of age. Long term follows up data on immunogenicity, efficacy, and safety of a single dose attenuated vaccine are limited. This vaccine is not FDA approved.

People at Increased Risk of Hav Infection Should Be Immunized Routinely

• All susceptible people traveling to or working in countries that have high or intermediate hep A endemicity should be immunized or receive Intramuscular standard immunoglobulin before departure. One dose of single-antigen vaccine administered at any time before departure can provide adequate protection for most healthy people

• Susceptible people with chronic liver disease or those who are awaiting or have received liver transplants should be immunized because they are at increased risk of fulminant hepatitis

• Household and sexual contacts. All previously unimmunized people with close personal contact with a person with serologically confirmed HAV infection, such as household and sexual contacts, should receive the HepA vaccine or IGIM within 2 weeks after the most recent exposure. Serologic testing of contacts is not recommended, because testing adds unnecessary cost and may delay the administration of post-exposure prophylaxis.

• Newborn infants of HAV-infected mothers. Perinatal transmission of HAV is rare. Some experts advise giving IGIM (0.02 mL/kg) to an infant if the mother’s symptoms began between 2 weeks before and 1 week after delivery. Severe disease in healthy infants is rare.

Post and Pre-exposure Prophylaxis for Unimmunized Patients

• Post-exposure prophylaxis for unimmunized patients includes either a single-dose of HAV single-antigen vaccine or immune globulin (IGIM) as soon as possible, and within 14 days after exposure. No information exists regarding the efficacy of IGIM or vaccine if administered >2 weeks after exposure

• Pre-exposure prophylaxis; HepA vaccine is preferred in all populations unless contraindicated and should be administered at least 2 weeks before expected exposure. Completion of the vaccine series according to the licensed schedule is necessary for long -term protection.

Hepatitis A Vaccine - Conclusion

Even though we have effective vaccines against HAV, we should not forget the importance of cleanliness. The virus, excreted in feces, often is spread through contaminated waters, but food in restaurant and child care center, kitchens handled by infected workers who have not washed properly also is a common source of outbreaks. Fruits and vegetables, salads, cold cuts and sandwiches, milk, and juices all have been implicated in HAV infection. Hand washing really is cost-effective!