Inactivated Hepatitis A Virus Vaccine Research Articles

Hepatitis A vaccine immunogenicity among seronegative liver transplanted children.

The hepatitis A virus (HAV) vaccine is highly immunogenic in general, yet data on its use in liver-transplanted (LT) children is limited. This study aimed to determine the seroimmunity to HAV in all LT children, and the immunogenicity of an inactivated HAV vaccine in seronegative LT children at King Chulalongkorn Memorial Hospital. Seronegative LT children received the inactivated HAV vaccine at 0 and 6-8months with adverse events monitored for 3days post-immunization. The result reviewed that among 105 LT children, vaccination records were available for 81%, of which 7.1% and 16.5% with one and two doses of HAV vaccine were immunized before transplantation, respectively. Post-transplantation, 20.1% were seropositive for HAV, with 9.5% due to pre-transplant immunization. Eighty-three seronegative LT children (aged 7.25 ± 4.40years; 48.6% male) received two vaccine doses. The seropositive rate increased following the first and second doses and reached to 51.5%, and 92.9%, respectively (p < 0.001), with no serious adverse events reported. Age at vaccination and the interval from transplantation to vaccination were risk factors for non-responsiveness (p < 0.001). The study highlighted inadequate HAV vaccination coverage, leaving most LT children susceptible to infection. HAV vaccine proved highly immunogenic and safe, emphasizing the need for improved vaccination strategies before and after liver transplantation.Trial registration TCTR20220110001.

Inactivated TZ84 strain hepatitis A vaccine and its impact: A narrative review

Hepatitis A (HepA) represents a significant global public health challenge. At present, there is no definitive treatment available for managing HepA. Before the availability of HepA vaccines, hepatitis A virus (HAV) infection had emerged as a leading cause of fulminant hepatic failure and a significant indication for liver transplantation in children living in Argentina, Brazil, the Republic of Korea, and India. Inactivated HAV vaccines have demonstrated a high level of immunogenicity. In addition, there is evidence supporting the use of inactivated HepA vaccines in immunocompromised individuals and as post-exposure prophylaxis. Recently, the inactivated TZ84 strain hepatitis A vaccine, which has shown superior immunogenicity for up to 30 years and fewer adverse reactions when compared with other inactivated HepA vaccines, has become available in India. Moreover, the TZ84 strain of the inactivated HAV vaccine has the potential to control community-wide outbreaks. This narrative review offers an overview of the existing evidence concerning immunization against HepA in India, with a particular emphasis on the TZ84 strain of the inactivated HAV vaccine.

Inactivated TZ84 strain hepatitis A vaccine and its impact: A narrative review

Hepatitis A (HepA) represents a significant global public health challenge. At present, there is no definitive treatment available for managing HepA. Before the availability of HepA vaccines, hepatitis A virus (HAV) infection had emerged as a leading cause of fulminant hepatic failure and a significant indication for liver transplantation in children living in Argentina, Brazil, the Republic of Korea, and India. Inactivated HAV vaccines have demonstrated a high level of immunogenicity. In addition, there is evidence supporting the use of inactivated HepA vaccines in immunocompromised individuals and as post-exposure prophylaxis. Recently, the inactivated TZ84 strain hepatitis A vaccine, which has shown superior immunogenicity for up to 30 years and fewer adverse reactions when compared with other inactivated HepA vaccines, has become available in India. Moreover, the TZ84 strain of the inactivated HAV vaccine has the potential to control community-wide outbreaks. This narrative review offers an overview of the existing evidence concerning immunization against HepA in India, with a particular emphasis on the TZ84 strain of the inactivated HAV vaccine.

Hepatitis A vaccination and its immunological and epidemiological long-term effects – a review of the evidence

ABSTRACT Hepatitis A virus (HAV) infections continue to represent a significant disease burden causing approximately 200 million infections, 30 million symptomatic illnesses and 30,000 deaths each year. Effective and safe hepatitis A vaccines have been available since the early 1990s. Initially developed for individual prophylaxis, HAV vaccines are now increasingly used to control hepatitis A in endemic areas. The human enteral HAV is eradicable in principle, however, HAV eradication is currently not being pursued. Inactivated HAV vaccines are safe and, after two doses, elicit seroprotection in healthy children, adolescents, and young adults for an estimated 30–40 years, if not lifelong, with no need for a later second booster. The long-term effects of the single-dose live-attenuated HAV vaccines are less well documented but available data suggest they are safe and provide long-lasting immunity and protection. A universal mass vaccination strategy (UMV) based on two doses of inactivated vaccine is commonly implemented in endemic countries and eliminates clinical hepatitis A disease in toddlers within a few years. Consequently, older age groups also benefit due to the herd protection effects. Single-dose UMV programs have shown promising outcomes but need to be monitored for many more years in order to document an effective immune memory persistence. In non-endemic countries, prevention efforts need to focus on ‘new’ risk groups, such as men having sex with men, prisoners, the homeless, and families visiting friends and relatives in endemic countries. This narrative review presents the current evidence regarding the immunological and epidemiological long-term effects of the hepatitis A vaccination and finally discusses emerging issues and areas for research.

Poor response to hepatitis A vaccination in hematopoietic stem cell transplant recipients.

Hepatitis A virus (HAV) infection is highly prevalent in developing countries. In countries experiencing a shift from intermediate/high endemicity to low endemicity, the World Health Organization recommends the incorporation of HAV vaccine into the national vaccination calendar for children aged ≥1year. Since HAV antibodies wane over time, most HSCT revaccination guidelines advise vaccination as optional, following the country recommendation. However, no study has evaluated the serological response to HAV vaccine in allogeneic HSCT recipients. We conducted a prospective study in 46 HSCT recipients who received two doses of inactivated HAV vaccine. Blood samples were taken before vaccination to determine HAV prevalence rates, and before and 4-6weeks after the second dose. Specific anti-HAV antibodies were detected by a competitive commercial enzyme immune assay. Patients received the first dose of vaccine at a median of 332.5 (120-4134) days after HSCT. Median absolute lymphocyte count at vaccination was 1947 (696-12500)/mm3 . The seroprevalence rate was 93.5% at inclusion. Although safe and well tolerated, the serological response to HAV vaccine in susceptible patients was poor (33%), and no boost effect was observed in seropositive patients. In areas with intermediate/high seroprevalence of HAV, serology should be recommended prior to referral to vaccination. The mechanisms of antibody interference and how to overcome T-cell function deficiency need to be better understood in transplant populations receiving HAV vaccine. Alternative schedules of HAV vaccination should be evaluated in prospective trials.

Immunogenicity and side-effects of the inactivated hepatitis A vaccine in periodic fever, aphthous stomatitis, pharyngitis, and adenitis patients.

The aim of this study was to compare the immunogenicity and side-effects of hepatitis A virus (HAV) vaccination between periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) patients and healthy controls who have not been previously exposed to HAV. A prospective observational study was carried out of 28 PFAPA patients and 76 controls who received two doses of the vaccine. Immunogenicity was expressed as seroconversion and seroprotection rates; mean HAV-immunoglobulin G concentration was measured at 0, 1, 7 and 18months. Side-effects were defined as incidence of adverse events and the effect of vaccination on PFAPA symptoms. All participants were seronegative and seroconverted at 1month. One month after primary vaccination, 92.9% of PFAPA patients and 77.6% of the controls attained seroprotection, while the rates increased to 100% and 96.1%, respectively, 1month after the second dose. Seroprotection rates remained adequate 1year after completion of vaccination. In conclusion, two doses of the inactivated HAV vaccine are well-tolerated and effective in children with PFAPA.

Hepatitis A: epidemiology in resource-poor countries.

Transmission of hepatitis A virus (HAV) infection is primarily fecal-oral. Symptomatic hepatitis, severe disease, and death are more likely to occur when infection occurs at an older age. Improvements in socioeconomic and hygienic conditions have led to a change in its epidemiology worldwide. In the last two decades, improved hygiene in several resource-poor countries has led to reduced transmission of HAV, an increase in average age at infection, and, consequently, a paradoxical increase in morbidity and mortality because of hepatitis A. In Argentina, introduction of one dose (instead of the conventional two doses, to reduce costs) of inactivated HAV vaccine at 12-month age in a universal childhood immunization program during such 'epidemiologic transition' has markedly reduced the incidence of symptomatic hepatitis A, and of fulminant hepatitis and liver transplantation caused by HAV infection. The monetary value of medical and nonmedical benefits of this strategy outweighed the expenditure on vaccination. These excellent results were possibly contingent upon a high vaccination coverage. Resource-poor countries should closely monitor the epidemiology of HAV infection and periodically undertake cost-effectiveness analyses of HAV immunization strategies. This should allow timely identification of epidemiologic transition and introduction of preventive strategies before HAV infection becomes a public health problem.

Development, Production, and Postmarketing Surveillance of Hepatitis A Vaccines in China

China has long experience using live attenuated and inactivated vaccines against hepatitis A virus (HAV) infection. We summarize this experience and provide recent data on adverse events after immunization (AEFIs) with hepatitis A vaccines in China. We reviewed the published literature (in Chinese and English) and the published Chinese regulatory documents on hepatitis A vaccine development, production, and postmarketing surveillance of AEFI. We described the safety, immunogenicity, and efficacy of hepatitis A vaccines and horizontal transmission of live HAV vaccine in China. In clinical trials, live HAV vaccine was associated with fever (0.4%–5% of vaccinees), rash (0%–1.1%), and elevated alanine aminotransferase (0.015%). Inactivated HAV vaccine was associated with fever (1%–8%), but no serious AEFIs were reported. Live HAV vaccine had seroconversion rates of 83% to 91%, while inactivated HAV vaccine had seroconversion rates of 95% to 100%. Community trials showed efficacy rates of 90% to 95% for live HAV and 95% to 100% for inactivated HAV vaccine. Postmarketing surveillance showed that HAV vaccination resulted in an AEFI incidence rate of 34 per million vaccinees, which accounted for 0.7% of adverse events reported to the China AEFI monitoring system. There was no difference in AEFI rates between live and inactivated HAV vaccines. Live and inactivated HAV vaccines manufactured in China were immunogenic, effective, and safe. Live HAV vaccine had substantial horizontal transmission due to vaccine virus shedding; thus, further monitoring of the safety of virus shedding is warranted.

Hepatitis A immunisation in persons not previously exposed to hepatitis A.

In many parts of the world, hepatitis A infection represents a significant cause of morbidity and socio-economic loss. Whilst hepatitis A vaccines have the potential to prevent disease, the degree of protection afforded against clinical outcomes and within different populations remains uncertain. There are two types of hepatitis A virus (HAV) vaccine, inactivated and live attenuated. It is important to determine the efficacy and safety for both vaccine types. To determine the clinical protective efficacy, sero-protective efficacy, and safety and harms of hepatitis A vaccination in persons not previously exposed to hepatitis A. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and China National Knowledge Infrastructure (CNKI) up to November 2011. Randomised clinical trials comparing HAV vaccine with placebo, no intervention, or appropriate control vaccines in participants of all ages. Data extraction and risk of bias assessment were undertaken by two authors and verified by a third author. Where required, authors contacted investigators to obtain missing data. The primary outcome was the occurrence of clinically apparent hepatitis A (infectious hepatitis). The secondary outcomes were lack of sero-protective anti-HAV immunoglobulin G (IgG), and number and types of adverse events. Results were presented as relative risks (RR) with 95% confidence intervals (CI). Dichotomous outcomes were reported as risk ratio (RR) with 95% confidence interval (CI), using intention-to-treat analysis. We conducted assessment of risk of bias to evaluate the risk of systematic errors (bias) and trial sequential analyses to estimate the risk of random errors (the play of chance). We included a total of 11 clinical studies, of which only three were considered to have low risk of bias; two were quasi-randomised studies in which we only addressed harms. Nine randomised trials with 732,380 participants addressed the primary outcome of clinically confirmed hepatitis A. Of these, four trials assessed the inactivated hepatitis A vaccine (41,690 participants) and five trials assessed the live attenuated hepatitis A vaccine (690,690 participants). In the three randomised trials with low risk of bias (all assessing inactivated vaccine), clinically apparent hepatitis A occurred in 9/20,684 (0.04%) versus 92/20,746 (0.44%) participants in the HAV vaccine and control groups respectively (RR 0.09, 95% CI 0.03 to 0.30). In all nine randomised trials, clinically apparent hepatitis A occurred in 31/375,726 (0.01%) versus 505/356,654 (0.18%) participants in the HAV vaccine and control groups respectively (RR 0.09, 95% CI 0.05 to 0.17). These results were supported by trial sequential analyses. Subgroup analyses confirmed the clinical effectiveness of both inactivated hepatitis A vaccines (RR 0.09, 95% CI 0.03 to 0.30) and live attenuated hepatitis A vaccines (RR 0.07, 95% CI 0.03 to 0.17) on clinically confirmed hepatitis A. Inactivated hepatitis A vaccines had a significant effect on reducing the lack of sero-protection (less than 20 mIU/L) (RR 0.01, 95% CI 0.00 to 0.03). No trial reported on a sero-protective threshold less than 10 mIU/L. The risk of both non-serious local and systemic adverse events was comparable to placebo for the inactivated HAV vaccines. There were insufficient data to draw conclusions on adverse events for the live attenuated HAV vaccine. Hepatitis A vaccines are effective for pre-exposure prophylaxis of hepatitis A in susceptible individuals. This review demonstrated significant protection for at least two years with the inactivated HAV vaccine and at least five years with the live attenuated HAV vaccine. There was evidence to support the safety of the inactivated hepatitis A vaccine. More high quality evidence is required to determine the safety of live attenuated vaccines.

Immunogenicity of Hepatitis A Vaccine in Children With Celiac Disease

The response to hepatitis A vaccine has not been studied in children with celiac disease (CD). The aim of the present study was to evaluate the immunogenicity of an inactivated hepatitis A virus (HAV) vaccine and the effect of the human leukocyte antigen (HLA) type on immunogenicity in children with CD. Thirty-three patients with CD and 62 healthy controls were enrolled in the study. Inactivated HAV vaccine (Havrix; GlaxoSmithKline Biologicals, Rixensart, Belgium) containing 720 enzyme-linked immunosorbent assay units of alum-adsorbed hepatitis A antigen was administered intramuscularly in a 2-dose schedule at 0 and 6 months. Seroconversion rates and antibody titers of HAV were measured at 1 and 7 months. At 1 month, seroconversion rates were 78.8% and 77.4% and geometric mean titers were 50.7 and 49.9 mIU/mL in the CD and control groups, respectively (P > 0.05). At 7 months, seroconversion rates were 97% and 98.4% and geometric mean titers were 138.5 and 133 mIU/mL in the CD and control groups, respectively (P > 0.05). The most frequent HLA types were HLA-DQ2, -DR3, and -DR7 alleles in patients with CD and HLA-DQ3, -DQ6, -DR11, and -DR14 in the controls. There was no association between HLA alleles and antibody titers of hepatitis A vaccine. Children with CD have a good immune response to hepatitis A vaccine, similar to healthy controls.

Antibody persistence and immune memory in healthy adults following vaccination with a two‐dose inactivated hepatitis A vaccine: Long‐term follow‐up at 15 years

Long-term persistence of vaccine-induced immune response in adults was assessed annually for 15 years following primary immunization with a two-dose inactivated hepatitis A vaccine. In 1992, 119 and 194 subjects aged 17-40 years and naïve for hepatitis A virus (HAV) were enrolled in two studies to receive 1,440 ELISA units (El.U) of inactivated hepatitis A vaccine (Havrix™, GlaxoSmithKline Biologicals, Belgium) according to a standard 0, 6 or an extended 0, 12 months schedule, respectively. Serum samples were taken 1 month after the second vaccine dose and every consecutive year up to 15 years after primary vaccination for measurement of anti-HAV antibody concentrations (NCT00291876 and NCT00289757). At year 15, 100% (48/48) and 97.3% (108/111) of subjects vaccinated at 0, 6 or 0, 12 months remained seropositive for anti-HAV antibodies, with geometric mean concentrations (GMCs) of 289.2 and 367.4 mIU/ml, respectively. An additional dose of HAV vaccine (1,440 El.U) was administered to the six subjects who had become seronegative for anti-HAV antibodies since year 11. All subjects mounted a humoral immune response to the additional HAV challenge dose, although post-challenge anti-HAV antibody levels remained low in one subject. These studies represent the longest annual follow-up of hepatitis A vaccine in healthy adults. The immune response induced by two doses of this inactivated HAV vaccine was shown to persist for at least 15 years. No difference in long-term antibody persistence was observed between the two primary vaccination schedules, reinforcing the potential for flexibility in the timing of the second primary vaccine dose.

VHA et VHE, une épidémiologie en évolution, une prophylaxie à adapter

Hepatitis A virus (HAV) and hepatitis B virus (HBV) are two non-enveloped RNA viruses, which cause acute hepatitis with no progression to chronic liver disease and no chronic carriage. This is why, for their survival, these two viruses have a particularly efficient transmission mechanism: the faecal-oral route. Despite this similarity, there are significant differences between HAV and HEV with respect to their viral characteristics, their epidemiology and their treatment. HAV is a member of the Picornaviridae, while HEV belongs to the small Hepeviridae family. Although several genotypes have been identified for these two viruses, only one serotype is recognized for each. For HAV, humans are the only reservoir. The infection is associated with poor sanitation. Socioeconomic improvements and better hygiene standards have reduced the transmission of HAV in developed countries. The mean age of exposure has increased, resulting in large numbers of teenagers and adults becoming susceptible to the virus. Unlike HAV, HEV is zoonotic. The virus is found in the faeces of many animals although pigs seem to be the main reservoir. Hepatitis E occurs predominantly in developing countries, resulting in large water-born epidemics. Person-to-person transmission is less frequent. In developed countries, most HEV infections are thought to be imported. In the last few years, increasing numbers of sporadic cases have been described in indigenous patients, while the seroprevalence ranges from 1 to 5%. This suggests that HEV may be more prevalent than previously considered in industrialized countries. Immunization with inactivated HAV vaccine results in highly effective, rapid and long-lasting immunity. The changing epidemiology of HAV infections in many countries should lead to a review of vaccination strategies. Several vaccines against HEV are currently undergoing evaluation in clinical trials.

The first experimental study on a candidate combined vaccine against hepatitis A and hepatitis E

To test the possibility of developing a combined vaccine against hepatitis A and E, groups of mice were immunized with different formulations containing different dosages of a commercially inactivated hepatitis A vaccine and a candidate recombinant hepatitis E vaccine. Monovalent vaccine components were used as controls. The experimental results showed that the combined vaccine could induce neutralizing antibodies against both hepatitis A virus (HAV) and hepatitis E virus (HEV) effectively in mice. Moreover, the inactivated hepatitis A vaccine could increase the immunogenicity of the recombinant HEV protein, and the recombinant HEV protein had no adverse effects on the immunogenicity of the inactivated HAV vaccine. Thus, the present study demonstrates an important first step for the further development of a combined hepatitis A and E vaccine.

Predictors of immunity after hepatitis A vaccination in HIV‐infected persons

Hepatitis A virus (HAV) infection remains a health risk for human immunodeficiency virus (HIV)-infected persons. While the inactivated HAV vaccine affords protection to immunocompetent persons >95% of the time, rates of developing protective antibody (anti-HAV) in HIV+ persons are considerably lower. Although low CD4+ T-cell counts have previously been reported to be correlated with this poor response, the effect of HIV viraemia on HAV vaccine response has not previously been reported. The medical records of HIV-infected patients who had received at least one dose of HAV vaccine (Havrix, 1440 EIU) were reviewed for factors associated with the development of a protective anti-HAV response. Serological data with regard to anti-HAV status after vaccination were available in 238 patients with 133 individuals (49.6%) developing immunity after vaccination. In a logistic regression model, the only factors associated with a protective antibody response were an HIV plasma RNA level <1000 copies/mL at the time of vaccination (P = 0.011) and male gender (P = 0.016). Neither nadir CD4+ T cell count nor CD4+ T-cell count at time of vaccination were predictive of the development of anti-HAV. Suppression of HIV replication at time of vaccination is associated with a protective antibody response to HAV vaccination in HIV-infected adults. The low rate of response warrants further research in alternative strategies for HAV vaccination among HIV-infected persons.

Rate, intensity, and duration of local reactions to a virosome-adjuvanted vs. an aluminium-adsorbed hepatitis A vaccine in UK travellers

Travellers increasingly require hepatitis A virus (HAV) vaccine for overseas travel to highly endemic areas. While the inactivated HAV vaccines currently in use are all highly immunogenic, studies have shown the aluminium-free, virosome-adjuvanted vaccine Epaxal to possess a superior local tolerability profile. The objective of this study was to analyse the pattern of local reactions caused by the aluminium-free Epaxal compared with an aluminium-adjuvanted HAV vaccine. Subjects recruited from travel health centres were randomised in a 4:1 ratio to receive a single dose of either Epaxal or Havrix vaccine. Vaccinees noted adverse reactions on a 7-day diary card that was returned by mail to the centre. 529 adults (> or =16 years) were vaccinated, and 413 (78.1%) subjects returned diary cards, 338 (76.5%) in the Epaxal group and 75 (86.2%) in the Havrix group. Subjects reported fewer local adverse reactions for Epaxal (23.4% vs. 57.3%; p<0.0001). Injection site pain categorised as Grade 2 (painful on movement) or Grade 3 (spontaneously painful) (4.7% vs. 22.7%, p=0.0001) was less frequent in the Epaxal group and resolved more quickly (> or =3 days of pain, 8.6% vs. 22.7%, p=0.0001). The lower reactogenicity of the virosome-adjuvanted vaccine is an important feature for travellers.

Acute and chronic hepatitis: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Acute and chronic hepatitis: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Immunization of seronegative infants with hepatitis A vaccine (HAVRIX ®; SKB): a comparative study of two dosing schedules

Hepatitis A virus (HAV) infection is of public health significance among infants and diapered children. Although two licensed HAV vaccines are available, they have not been assessed widely in children under the age of 2 years and are not currently licensed for this age group. The purpose of this study was to evaluate the immunogenicity and reactogenicity of HAV vaccine in seronegative infants. Fifty-three healthy infants were immunized with 360 ELISA Units (EL.U.) of an inactivated HAV vaccine at 2, 4, and 6 (Group 1) or 2, 4, and 15 months of age (Group 2). These injections were not received on the same day that participants received their routine childhood immunizations. HAV serum antibodies were detected using a modified radioimmunoassay procedure and concentrations were calculated using a World Health Organization serum anti-HAV reference standard. No serious systemic or local reactions were noted among the immunized infants. Three months following the third immunization, seroconversion rates were 100% and 93% in groups 1 and 2, respectively. No significant differences were observed in the geometric mean anti-HAV concentrations between the two groups at comparable time points, i.e. 2 months after the second dose, 3 months after the third dose, and 19 months after the first dose. Three infants, not included in the data presented above, had preexisting maternal antibodies; one never responded to the vaccine and the other two did not respond until maternal antibody levels had become reduced. The results indicate that the inactivated HAV vaccine is highly immunogenic in seronegative infants and could be included in the routine harmonized infant immunization schedule.

The effect of immunization with inactivated hepatitis A vaccine on the clinical course of HIV-1 infection: 1-year follow-up.

To determine the long-term safety of inactivated hepatitis A virus (HAV) vaccine in men infected with HIV-1. A 1-year prospective case-control study. Targeted primary care and sexually transmitted diseases clinics. Ninety HIV-1-positive patients who participated in an earlier efficacy study of HAV vaccination. Ninety HIV-1-positive men, matched for CD4+ lymphocyte percentage at baseline, who did not receive HAV vaccine. All cases were assigned to receive two intramuscular doses of 1440 enzyme-linked immunosorbent assay units of inactivated HAV vaccine (Havrix) either 1 or 6 months apart. Development of AIDS, survival, and T-cell subsets after 1 year of follow-up. No significant differences were seen between cases and control for the development of AIDS (10.1 versus 10.7%), deaths (7.3 versus 7.6%) nor for mean decline in circulating CD4+ lymphocyte count (125 versus 123 x 10(6)/1) after 1 year. Vaccination against HAV appears to be safe in the longer term for HIV-1-infected men.

Epidemiology and Prevention of Hepatitis A in Travelers

Objective. —To assess the risk of hepatitis A in international travelers and to recommend preventive measures. Data Sources. — Index Medicus , 1974 through 1983; MEDLINE, 1984 through 1993; and unpublished data of the Centers for Disease Control and Prevention. Study Selection. —Review of all retrospective and cohort studies on hepatitis A and other vaccine-preventable diseases in travelers, of seroepidemiologic surveys of hepatitis A virus (HAV) antibodies in travelers, of data on the various hepatitis A vaccines, of economic analyses, and of recommendations of recognized organizations. Data Extraction. —Independent analysis by multiple observers. Data Synthesis. —The incidence rate for unprotected travelers, including those staying in luxury hotels, is estimated to be three per 1000 travelers per month of stay in a developing country. Persons eating and drinking under poor hygienic conditions have a rate of 20/1000 per month. This makes hepatitis A the most frequent infection in travelers that may be prevented by immunization. In many industrialized countries persons born after 1945 have an HAV antibody seroprevalence (immunity) of less than 20%. New inactivated HAV vaccines induce protective antibodies in more than 95% of recipients and offer protection estimated to last for 10 years or more, whereas protection by immune globulin lasts only 3 to 5 months. Conclusions. —Hepatitis A vaccine, or immune globulin where HAV vaccine is not available, is recommended for all nonimmune travelers visiting developing countries. Prescreening for antibodies to HAV in travelers living in countries with low prevalence is usually not necessary in persons born after 1945. ( JAMA . 1994;272:885-889)

Antigenicity of hepatitis A virus after ultra-violet inactivation

Ultra-violet (UV) treatment has been shown to inactivate hepatitis A virus (HAV) in wastewater and polluted drinking water. Whether this method could be used to inactivate virus preparations made for vaccine purposes is not known since the effect of UV on the antigenicity of HAV has not been studied. HAV vaccine preparations have been treated effectively with formaldehyde. However, this method is time-consuming, since treatment times of up to 15 days have been published as necessary for a complete and safe inactivation. We used a cell-culture-derived HAV preparation with a TCID 50 of 10 9 for a UV irradiation experiment. The antigenicity (assessed by a panel of anti-HAV antibodies), viral genome titre (quantitated by polymerase chain reaction) and HAV infectivity were compared after treatment with UV doses of 0, 184, 368, 552, 736 and 920 J m −2. Our results showed the antigenicity of HAV was almost unaltered even when infectious viral particles were no longer detectable. This technique shows potential as a simple and low-cost method for an inactivated HAV vaccine.