Hepatitis A Virus (HAV) is hepatotropic which causes an acute self limiting infection of the liver. Transmission of the virus is typically by feco-oral route usually through contaminated food and water. Though there are several genotypes of HAV, a single serotype exists. Thus vaccine produced using any of the strains would be useful anywhere.

Epidemiology
Outbreak of Hepatitis A infection may occur both in endemic and epidemic form. In developing countries with poor sanitation most children are seropositive by the age of 5 years. At this age children are mostly asymptomatic or have mild symptoms and as such prevalence of HAV infection is difficult to measure (1) With improvement in living conditions, and good sanitation an epidemiological shift occurs i.e. shifts of age of infection from young age to older group children and adults when the disease is more severe. This phenomenon was noticed in Spain, Greece , Israel , Japan and several SE Asian countries with outbreaks in adults. On the basis seropositivity rate by cut off years countries are now being leveled as high, intermediate and low endemic (80% are seropositive by 10, 20 and 50 years respectively).

India is considered as hyper endemic for hepatitis A but several studies suggest an epidemiological shift in different regions India. Based on population-based serosurveys conducted in urban and rural areas of Pune, western India, during 1982, 1992 and 19987, it has been shown that 69 per cent (6-10 yr), 53 per cent (11-15 yr) and 15 per cent (16-25 yr) of the population belonging to higher socio-economic status was anti- HAV negative in 1998. In contrast, 94-100 per cent of those belonging to lower socio-economic status were exposed to HAV in the same age groups respectively. Based on these results, possibility of epidemics of HAV in high socio-economic status population was predicted (2). In Mumbai, a hospital based survey showed a significant lower exposure of higher socio-economic group (64.5%) compared with lower socio-economic group (85%)(3). One study from Delhi has also observed that cord blood antibody levels are low (60%) indicating a decrease in exposure in adult populations (4). Another Delhi-based study(5) reported a significantly lower anti-HAV positivity in subjects <35 yr (57%) than > 35 yr (92.1%). Surprisingly, no difference with respect to socio-economic status was noted. The same group recorded that 37.4 per cent of the first year medical students were anti-HAV negative(6). In a prospective study, at six centers in five cities (Calcutta, Cochin, Indore, Jaipur and Patna) the overall seroprevalence rate was 65.9%, varying from 26.2% to 85.3% ; Seropositivity increased with age from 52.2% in the 1-5 year age group to 80.8% in those aged 16 years or more. Seroprevalence rates were significantly lower in those aged 1-5 years compared with other age groups (p<0.0001)(7). One small study from Hyderabad has shown that 69% children below 10 yr and 25% children below 15 year are anti HAV negative. Almost all children from low socioeconomic group are exposed to HAV and presently do not qualify for immunization with HAV vaccine. But recent studies indicate that a substantial susceptible pool is generated in India in some regions and higher socioeconomic group and outbreak of hepatitis A is distinct possibility as was recently reported from medical college area in Kottyam, Kerala (8). A large scale outbreak of viral hepatitis involving over 100 children with HAV as etiology has also been reported(9).

Hepatitis A vaccination
Hepatitis A vaccine has been licensed for use in India but is not included in the national immunization schedule. WHO recommends vaccination programs in children as a supplement to health education and improved sanitation in countries with intermediate endemicity. In regions of low endemicity, vaccination against hepatitis A is indicated for individuals with increased risk of contracting the infection. So far, Israel is the only country adopting the policy of universal immunization(10).

IAP recommends HAV as an additional vaccine on one to one “ named child” basis in children from higher socioeconomic strata; adolescents who have not had viral hepatitis earlier or are known to be HAV IgG negative may also be vaccinated.

Vaccine is indicated in all patients with chronic liver disease, liver and kidney transplant recipients, Hep B and C carriers and immunocompromized children to minimize the risk of developing liver failure. Children in day care centers may receive the vaccination as outbreaks of hepatitis A have been reported from such centers several countries including India(11).Travelers from low to high endemic regions will also benefit from vaccination.

Currently inactivated Hepatitis A vaccine is being used in most countries. These vaccines are prepared by purification of a virus propagated in cell culture followed by formalin inactivation and addition of adjuvant aluminium hydroxide. The vaccine does not contain thiomersol a mercury containing preservative and uses phenoxy xenthol as preservative. The vaccine should be given by intramuscular route; however, in patients with bleeding diathesis the vaccine has been found to be safe and immunogenic administered by subcutaneous route. At present the vaccine is licensed for children aged over 1 year (except USA where it is licensed for children over 2 years). Vaccination below 1 year is futile as most mothers are usually anti-HAV positive and maternal interfere with uptake till 9-10 months(12). The vaccine is highly potent with more than 95% of the vaccinees seroconverted (defined as an anti-HAV antibody level of >20 mIU/mL) and they develop very high titers of the antibody. Protection given by the vaccine is at least for 15 years and may be lifelong. The vaccine is given in a 2-dose schedule 6 mo apart after 1 year. GMT obtained in vaccines given the dose after 2 years is higher than when it is given between 1 to 2 years but clinical efficacy does not differ in both the groups. From logistical point of view the first dose may be given at 18 mo along with DPT 1st booster and 2nd dose at 2 years along with typhoid vaccine. Adult dose is generally twice that of pediatric dose and should be used after the recommended cut off age which varies from 15 to 18 years depending on instruction of manufacturers.

Products available in India are: Havrix (GSK) – 720 EU (0.5ml) for 1-18 yrs and 1440 EU for >18 yrs; Avaxim (Sanofi Pasteur) 80 AU (0.5ml) for 1-15 yrs and – 160 AU for >15 years. Havpur (Chiron Panacea) is a recent addition which is aluminium-free hepatitis A vaccine based on the virosome technology.

A live attenuated HAV based on H2 strain of hepatitis A virus is also available. The strain was attenuated after a serial passage in human diploid cell (KMB 17 cell line) in different temperature. China has successfully controlled the epidemic of HA infection with mass use of this vaccine. The dose is 1 ml SC in children aged 1-15 years. Seroconversion has been found to be >98% 2 mo after single dose vaccination. Ten years follow up with single dose has shown 100% efficacy, seropositivity rates of 80%, GM 145 IU/ml(13). At KEM hospital, Pune, a 96% seroconversion was noted between the ages of 1-12 years single dose vaccination(14). Though one dose appears sufficient especially for mass vaccination program, at individual level some experts believe that 2 dose schedule may ensure better longterm efficacy.

A combined Hepatitis A and B vaccine is also available (Twinrix-GSK) and has shown high seroconversion rate with no significant side effects. Children between 1-15 years are given the vaccine (0.5 ml IM) in a 3 dose schedule of 0, 1 and 6 months. Two dose schedule of the vaccine for better compliance is being explored with encouraging results(15). Children who have missed Hep B vacc in infancy can op for his vaccine.

All HAV vaccine has an excellent safety profile. Adverse events are mostly minor in nature like local pain, redness, induration and headache. The inactivated HAV vaccine can be give concurrently with other vaccines though it is recommended that the injection be given at different sites. The vaccine can also be given with immunoglobulin at different sites.

Post exposure prophylaxis
For household contacts of patients with HA virus infection vaccine should be given within 10 days; however it may not be effective if the contact has the same source of infection as the index patient. Simultaneous use of immunoglobulin would improve the protection. In outbreak situation one small study has shown a protective efficacy of 79% when given within 8 days of onset of symptoms of the index case while other studies have shown that vaccine alone may not be sufficient(16).

REFERENCES
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