Epidemiology and prevention of hepatitis A in travelers.

BACKGROUND: Hepatitis A is the second most common vaccine-preventable travel-associated infectious disease and hepatitis A virus (HAV) is the most common cause of viral hepatitis. The incidence of infection is closely related to sanitary conditions and the level of economic development. METHODS: We evaluated HAV incidence, infection-related risk factors, and HAV vaccination rates in international travelers through retrospective analyses using major databases, such as CENTRAL, MEDLINE, EMBASE, and the current literature describing epidemiological data for HAV infection in recent years. RESULTS AND CONCLUSIONS: We found that the incidence of HAV infection in developed countries is very low. As international travel increases, the incidence of hepatitis A among travelers remains high and likely leads to regional outbreaks. Travelers should visit the Centers for Disease Control and Prevention website or Infectious Disease Prevention Center of their countries to learn about the incidence of infectious diseases associated with their destination before going abroad to determine if they should be vaccinated.

Hepatitis A en niños / Hepatitis A in children

La Hepatitis A (HVA), también llamada hepatitis infecciosa, transmitida por alimentos, epidémica,ictericia catarral o epidémica, entre otros, es una enfermedad producida por un agente viral que se trasmite por vía fecal oral y generalmente su curso es autolimitado, aunque, puede progresar ahepatitis fulminante ocasionando la muerte a una proporción pequeña de los infectados. Pertenece al géner o Hepatovir us de la Familia Picornaviridae. La HVA, tiene una distribución universal, aunque con grandes diferencias geográficas en cuanto a su prevalencia, ocurre en forma esporádica y epidémica en todo el mundo, con una tendencia a presentarse en ciclos. La HVA, tiene un periodo de incubación prolongado, entre 15 a 50 días, con un promedio de 29 días, lo que hace difícil relacionar los síntomas con algún alimento o bebida ingerida. El diagnostico de la HVA, se basa en la detección de anticuerpos contra el VHA tipo IgM e IgG. El tratamiento básicamente es de soporte, sintomático y en casos de falla hepática, el trasplante es la única opción. La inmunoglobulina confiere inmunidad pasiva a corto plazo mientras la vacuna provee una protección activa a largo plazo.

Hepatitis A (HVA), also called infectious hepatitis, foodborne, epidemic, or epidemic or catarrhaljaundice, among others, is a disease caused by a viral agent that spreads through fecal-oral routeand usually self-limited course, although fulminant hepatitis can progress to causing death to a small proportion of those infected. Is a Hepatovirus genus of the Picornaviridae Family. The HVA, has a worldwide distribution, but with large geographical differences in its prevalence, occurs in sporadic and epidemic worldwide, with a tendency to occur in cycles. The HVA, has a long incubation period between 15 to 50 days, with an average of 29 days, making it difficult to correlate symptoms with food or drink intake. The diagnosis of HVA was based on the detection of antibodies against HAV IgM and IgG.

Virosomal hepatitis a vaccine: comparing intradermal and subcutaneous with intramuscular administration.

BACKGROUND: Vaccination against hepatitis A virus (HAV) is unaffordable to many developing countries. Substantial reductions in cost occur when vaccines are administered intradermally at low doses. Aluminum-free HAV vaccines are considered more suitable for intradermal use than traditional vaccines which can cause long-lasting local reactions. Thus, we compared the immunogenicity and safety of an aluminum-free virosomal HAV vaccine (Epaxal) administered by different routes: intradermal (i.d.), subcutaneous (s.c.), and intramuscular (i.m.). METHODS: Two open pilot studies were conducted as sub-studies of a large lot consistency trial. Healthy subjects aged 18 to 45 were enrolled. Study 1 compared two i.d. regimens of a lower dose of Epaxal [0.1 mL (4.8 IU), one or two injection sites] with i.m. administration of the standard dose [0.5 mL (24 IU)]. Study 2 compared the s.c. with the i.m. administration of the standard dose. At month 12, subjects in study 1 received a booster dose of 0.1 mL i.d. or 0.5 mL i.m.; subjects in study 2 received 0.5 mL via the respective route (s.c. or i.m.). Serum was tested for antibodies at baseline, 2 weeks (study 1), and 1 and 6 months after the primary vaccination as well as prior and 1 month after the booster dose. Incidences of solicited and unsolicited adverse events were recorded. RESULTS: Seroprotection rates (anti-HAV geometric mean concentration of > or =20 mIU/mL) after 1 month ranged from 93.2% to 100% in all groups and remained high until month 12 (range 85.2&-90.2%). Complete (100%) seroprotection was achieved by all subjects in all groups after booster vaccination. All routes of administration were well tolerated. Local reactions were more common in subjects vaccinated i.d. and s.c. than i.m. CONCLUSIONS: The aluminum-free virosomal HAV vaccine Epaxal is highly immunogenic and well tolerated when administered either via i.d., s.c., or i.m. Vaccination via the i.d. route may confer significant cost savings over the conventional i.m. route.

Seroepidemiology of hepatitis A virus in Kuwait.

AIM: To find the current seroepidemiology of hepatitis A virus (HAV) in Kuwait. METHODS: A total of 2851 Kuwaitis applying for new jobs were screened. RESULTS: HAV-positive cases were 28.8%; 59% were males and 41% were females. The highest prevalence was in the Ahmadi area. High prevalence was among the group of non-educated rather than educated parents. This is the first study in Kuwait demonstrating the shifting epidemiology of HAV. CONCLUSION: This study reflects the need of the Kuwaiti population for an HAV vaccine.

Vaccines and changes in coagulation parameters in adults on chronic warfarin therapy: a cohort study.

PURPOSE: Warfarin is commonly used among patients who receive influenza, pneumococcal, and tetanus and diphtheria toxoid vaccines, and persons on warfarin therapy may also receive Hepatitis A vaccine. There has been concern that vaccinations could potentially alter coagulation parameters in patients on warfarin therapy. We sought to determine whether vaccinations are associated with changes in International Normalized Ratio (INR) in persons on long-term warfarin therapy. METHODS: We conducted a retrospective cohort study of 5167 members of Group Health, a health maintenance organization (HMO) in western Washington State, who were aged 18 years and older and who were on stable long-term warfarin therapy between 1 January 1992 and 31 December 2003. We made within-person comparisons between mean INR values in the 28 days after receipt of influenza, pneumococcal, tetanus, or hepatitis A vaccine versus mean INR values during other times. RESULTS: Receipt of influenza vaccine was not associated with a change in INR value (mean change, 0.01; 95% confidence interval (CI) -0.01 to 0.03); similar results were observed for pneumococcal (mean change 0.01; 95%CI -0.07 to 0.09), tetanus (mean change 0.03; 95%CI -0.03 to 0.10), and hepatitis A vaccines (mean change 0.03; 95%CI -0.10 to 0.14). CONCLUSIONS: Our results do not suggest that vaccinations lead to clinically significant alterations in coagulation measures among adults on chronic warfarin therapy.

Immunogenicity of a chimeric hepatitis A virus (HAV) carrying the HIV gp41 epitope 2F5.

Its stable particle structure combined with its high immunogenicity makes the hepatitis A virus (HAV) a perfect carrier to expose foreign epitopes to the host immune system. In an earlier report [Beneduce, F., Kusov, Y., Klinger, M., Gauss-Müller, V., Morace, G., 2002. Chimeric hepatitis A virus particles presenting a foreign epitope (HIV gp41) at their surface. Antiviral Res. 55, 369-377] chimeric virus-like particles (HAV-gp41) were described that carried at their surface the dominant gp41 epitope 2F5 (2F5e) of the human immunodeficiency virus HIV-1. Extending this work, we now report that chimeric virus HAV-gp41 replicates in HAV-susceptible cells as well as in non-human primates. Infected marmosets developed both an anti-HAV and anti-2F5 epitope immune response. Furthermore, an HIV-neutralizing antibody response was elicited in guinea pigs immunized with HAV-gp41 chimeric particles. The results demonstrate that the replication-competent chimeric HAV-gp41 can serve as either a live or a subunit vaccine for eliciting of antibodies directed against a foreign antigenic epitope.

Hepatitis A vaccine in the last-minute traveler.

Current recommendations state that travelers should receive hepatitis A vaccine 2 to 4 weeks before departure. Such recommendations, however, may dissuade last-minute travelers from receiving the vaccine. A preponderance of evidence exists to support hepatitis A vaccination of the imminent-departure traveler and therefore suggests that these guidelines merit reconsideration. In examining this issue, one of the most important elements to determine is the amount of time required for seroconversion following vaccination. Clinical trials of hepatitis A vaccines measured antibody response at 2 and 4 weeks after vaccination. However, studies investigating early seroconversion found that the vast majority of vaccinees develop antibodies within 2 weeks of vaccination, some as early as 12 days after vaccination. This is relevant information, given that the hepatitis A virus has an average incubation period of 28 days. Seroconversion is predicated on achieving a "protective" antibody level. However, levels of antibody considered protective remain debatable. Evidence suggests that clinical disease does not occur at antibody levels lower than those currently accepted as protective. Furthermore, hepatitis A vaccine has been proved effective in controlling outbreaks worldwide. Research data show that a single dose of vaccine can halt outbreaks if an adequate number of susceptible individuals are vaccinated. Information from rapid-outbreak control studies and those assessing postexposure administration of hepatitis A vaccine suggest that late vaccination provides a significant degree of protection. For these reasons, hepatitis A vaccine may be administered at any time before departure because it will still provide travelers with protection.

Public health perspective on vaccine-preventable hepatitis: integrating hepatitis A and B vaccines into public health settings.

Hepatitis A and B vaccinations can and should be integrated into public health settings that serve adults at high risk for infection (e.g., sexually transmitted disease and/or human immunodeficiency virus clinics, criminal justice settings), and a policy of universal immunization may be the best way to accomplish this goal in these settings. Although hepatitis vaccines should be given to all susceptible persons at risk, many opportunities to vaccinate adults at high risk are missed, and there are several barriers and challenges to vaccination of adults. These challenges and barriers can be overcome. Successful integration of hepatitis vaccination for adults into existing public health services and clinics has been accomplished across the United States at both state and local levels. Additional funds must be provided for the infrastructure and purchase of vaccines for adults in these settings.

Vaccination against hepatitis A during outbreaks starting in schools: what can we learn from experiences in central Italy?

Two outbreaks of hepatitis A started almost simultaneously in a maternal school and in a day care centre located at opposite sides of Florence, Italy, at the end of 2002. Both of them originated from immigrant children, and in both cases, hepatitis A was initially not recognised due to aspecific symptoms. While vaccination of contacts started with delay in the first outbreak, the same intervention was organised and performed in 3 days in the other. The outbreak starting in the maternal school caused 30 notified cases, plus 7 cases diagnosed retrospectively. Nine of them were in a secondary school, where vaccination (in accordance with the Italian national guidelines on hepatitis A (HA) vaccination) had been started only after a secondary case occurred. Only three cases occurred overall in the other outbreak starting in the day care centre, where >80% of infants, children and personnel were immunised. Although few asymptomatic infections probably occurred, no source of contagion existed any longer 2 months after immunisation. A rapid vaccination of school and family contacts of hepatitis A cases after the first case (irrespective of school grade) seems to play an important role to shorten outbreak duration.

Production of interferon-gamma and interleukin-10 after inactivated hepatitis A immunization.

STUDY OBJECTIVE: To assess helper T cell function by measuring cytokine production over time after hepatitis A immunization. DESIGN: Open-label, single-dose study. SETTING: General clinical research center of a university hospital. SUBJECTS: Twenty-five healthy adults. INTERVENTION: Each subject was immunized with inactivated hepatitis A vaccine; blood was drawn on day 0 (the day of immunization) and days 2, 5, 7, 10, and 28 after immunization. MEASUREMENTS AND MAIN RESULTS: Production of interferon (IFN)-gamma and interleukin (IL)-10 by peripheral blood mononuclear cells stimulated in culture with hepatitis A virus was measured by enzyme-linked immunosorbent assay. Concentrations of hepatitis A antibody were measured on day 28. Both IFN-gamma and IL-10 production peaked on day 10 after immunization (IFN-gamma day 0 median = 7.35 pg/ml, interquartile ratio [IQR] = 20.8 vs day 10 median = 22.35 pg/ml, IQR = 42.4, p < 0.05; IL-10 day 0 median = 1.00, IQR = 7.4 vs day 10 median = 11.75 pg/ml, IQR = 92.3, p < 0.02, Wilcoxon signed rank test). The IL-10:IFN-gamma ratio on day 10 correlated with antibody production (Pearson product moment correlation 0.46, p < 0.05). This ratio was used as a measure of helper T cell phenotype. CONCLUSION: Both IFN-gamma and IL-10 are produced in response to hepatitis A vaccine. The parallel production after immunization may contribute to the high efficacy of these vaccine preparations in inducing both cell-mediated immune response and a protective antibody response.

Vaccination against hepatitis viruses in Poland.

At present, two etiologic varieties of viral hepatitis (VH) can be directly vaccine-preventable: VH type A and VH type B. In addition, VH type D can be prevented indirectly through vaccination against VH-B. The first commercially available vaccine against VH-B appeared in 1981 and was human plasma-derived. After several years, it has generally been replaced by a recombinant type of vaccines. The obvious benefits of vaccination against VH-B prompted its introduction into the national immunization program in Poland in 1989. At that time, vaccination was offered free of charge to high-risk groups: newborns of HBsAg-carrier mothers, health-care workers, students: at medical schools, nursing schools, medical technology schools, and caretakers at institutions for mentally retarded persons. However, similarly to the experiences of other countries, observations in Poland indicated that such a targeted strategy fails to induce major epidemiological changes. In 1989 and in 1993, the incidence of VH-B per 100000 was 40.3 and 34.6, respectively. In addition, during these years, the incidence of V-B per 100000 children aged 0-4 years was 20.0 and 38.4, respectively. It has been decided that vaccination against VH-B will be obligatory for all newborns beginning from 1993. Due to financial constraints, it has been introduced in three phases, and since 1996, all newborns in Poland have been vaccinated. Already in 1993, three additional risk groups have been offered vaccination: patients with chronic diseases, patients awaiting planned surgery, and persons coming into close contact with acute VH-B or chronically HBV-infected individuals. In 1999, the incidence of VH-B per 100000 was 9.1/100000, and it may be assumed that vaccination helped to decrease the incidence of VH-B in Poland. The country experience with vaccination against VH-A is still limited. At present, it is recommended for children and adolescents and people dealing with food distribution, as well as for several other groups of people, such as travellers or long-term visitors (soldiers, missionaries, diplomats) to the endemic regions of the world. It has also been recommended in connection with natural disasters such as floods occurring in a large area of Poland in 1997.

Vaccination policy against hepatitis A in Italy.

In Italy, improved sanitation and living conditions have led to a decline in the rate of hepatitis A infection among children generating an increasing proportion of adults susceptible to this virus. Shellfish consumption is a major source of infection while person to person transmission is important in the spread of infection and in the maintenance of outbreaks. Thus prevention of secondary HAV infection is a crucial point. A randomised controlled trial of hepatitis A vaccine in household contacts of people with sporadic HAV infection in Italy has shown a protective efficacy of 82% (CI 20-96%). The two secondary infections in the vaccine group were symptomless, suggesting that the disease expression may be weaker in vaccinated subjects.

Randomized, cross-over, controlled comparison of two inactivated hepatitis A vaccines.

The immunogenicity, tolerability and interchangeability of two hepatitis A vaccines, Vaqta (Merck and Co.) and Havrix (SmithKline) were studied in a randomized, crossover, controlled clinical trial. Vaccine was administered to 201 volunteers at 0 and 26 weeks in one of four vaccine regimens: Havrix-Havrix; Havrix-Vaqta; Vaqta-Havrix or Vaqta-Vaqta. Seroconversion rates (>/=10 mIU/ml) for those whose first dose was Vaqta or Havrix, respectively, were: 41/96 (43%) versus 30/95 (32%) (P=0.15) at 2 weeks and 91/98 (93%) versus 84/97 (87%) (P=0.43) at 4 weeks, and 100% at 26 weeks. Geometric mean concentrations (GMC) of total antibody to hepatitis A virus (anti-HAV) for Vaqta and Havrix were 189 and 114 mIU/ml (P=0.011) at 4 weeks and 234 and 136 mIU/ml (P<0.001) at 26 weeks. At 30 weeks, the GMC after two doses of Havrix was 2612 mIU/ml compared with 5497 after two doses of Vaqta (P<0.001). The GMC in the Havrix-Vaqta group was 5672 mIU/ml compared with 3077 mIU/ml in the Vaqta-Havrix group (P<0.001). Less than half of vaccine recipients reported tenderness or pain. In this study, seroconversion rates of the two vaccines were similar. Vaqta produces significantly higher anti-HAV antibody than Havrix. Crossover immunization is well tolerated and results in high antibody concentrations, especially when Vaqta is the booster dose. The significance of higher anti-HAV antibody concentrations in terms of long-term protection is unknown.

Prevalence of hepatitis A virus infection in sewage plant workers of Central Italy: is indication for vaccination justified?

Prevalence of antibodies to hepatitis A virus (HAV) was studied in a group of 65 sewage plant workers living in Tuscany, Central Italy. In order to evaluate the effect of several confounders (age, place of birth, income, educational degree, sea-food consumption, etc.), subjects under study were matched with 160 other workers residing in the same area. Anti-HAV was detected in about 51% of sewage workers and 44% of other employees. The difference was not statistically significant. Both univariate and multivariate analysis showed that the main variables related to previous HAV infection were increasing age (P<0.001), birth in Southern Italy (P<0.01) and lower educational degree (P<0.001). Although other studies in Northern and Central Europe showed a slightly higher risk of infection in sewage workers versus general population, lack of evidence of occupational risk in Italy might be explained by the relative importance of a higher degree of viral circulation in the past. The changing epidemiology of HAV infection in Italy with increasing numbers of susceptibles in adults and the potential occupational risk suggest that the present indication to immunize sewage plant workers against hepatitis A should be maintained.

Hepatitis A and B in children and adolescents--what can we learn from Puglia (Italy) and Catalonia (Spain)?

Viral hepatitis remains a major contributor to the global disease burden. Mass immunisation strategies against hepatitis B have been adopted by more than 90 developing and industrialised countries. Countries with low hepatitis A endemicity are experiencing cyclical outbreaks and an epidemiological shift, with larger numbers of individuals at risk of infection at an older age, resulting in increased morbidity. The high cost of outbreaks in these countries has made immunisation strategies cost-effective. The development of a vaccine against hepatitis A and a combined vaccine against hepatitis A and hepatitis B offers potentially exciting opportunities for a preventative approach in areas of both low and high endemicity. Existing mass immunisation programmes against hepatitis B will facilitate the adoption of joint strategies illustrated by the examples of Puglia (Italy) and Catalonia (Spain).