Review: hepatitis B immune globulin for prevention of hepatitis B infection.

Specific hepatitis B immune globulin (HBIG) contains a high titer of antibody to hepatitis B surface antigens and provides immediate passive protection against infection with hepatitis B virus, after acute exposure to infection. It is now generally combined with active immunization with hepatitis B vaccine. The principal indications for administration of HBIG are: a single acute percutaneous exposure to hepatitis B virus (HBV); mucocutaneous exposure; unprotected sexual exposure; mother-to-infant transmission; prevention of re-infection after liver transplantation; non-responders to hepatitis B vaccine and immunosuppressed patients.

Safety and immunogenicity profile of an experimental hepatitis B vaccine adjuvanted with AS04.

The reactogenicity and safety of an experimental hepatitis B (HB) vaccine containing adjuvant system (AS04) was compared with a licensed vaccine in a phase III, single-blind, randomised study in healthy volunteers >or=15 years of age. A total of 1303 subjects were enrolled to receive either two doses of HB-AS04 (0, 6 months) or three doses of the comparator vaccine (0, 1, 6 months). Two doses of HB-AS04 elicited seroprotection rates close to 100% and two-fold higher GMTs than the comparator vaccine. Results showed that both vaccines were well tolerated and the general safety profile of HB-AS04 was similar to that of the comparator vaccine.

Pre-travel preparation and outcome of HIV-infected travellers from a UK clinic.

Objectives. To review the pre-travel preparations and travel health outcomes of HIV-infected individuals. Methods. A prospective questionnaire-based study among English speaking adults with HIV infection attending an outpatient clinic from July to November 2000. Results. Baseline and follow-up questionnaire data were available for 34 individuals whose median CD4 count was 451 cells/mm(3). Eleven of these (32%) had sought travel advice before departure. Eight (23.5%) had been vaccinated or were planning vaccination against at least one condition and 17 (50%) listed travel-specific medications they planned to take with them. Those who were travelling to Africa were more likely to be vaccinated than those who were not travelling to Africa (3/4 vs 5/30, respectively, P=0.03). Those travelling to Europe were less likely to be vaccinated than those who were not (1/16 vs 7/18, P=0.04). The median duration of travel was 14 days (1-180). Fifteen subjects (44%) became ill while abroad. Those who became ill abroad were more likely to have visited Asia (P=0.003) and less likely to have visited the Americas (P=0.02) than those who did not become ill abroad. In addition, they tended to have stayed abroad for longer periods (P=0.07) and had visited more countries (P=0.04) than those who did not become ill abroad. Sixteen individuals (47%) reported illness on their return to the UK. Conclusions. HIV-infected travellers have an increased susceptibility to opportunistic and other travel-related infections and the need for appropriate advice, vaccination and prophylactic therapy is important. Health care provision in this field is in need of uniform guidelines to coordinate travel health management for this particular high risk group.

A new accelerated vaccination schedule for rapid protection against hepatitis A and B.

BACKGROUND: Increasing travel stresses the requirement for rapid protection against infections such as hepatitis A and B. METHODS: This randomised, multicentre study investigated an accelerated vaccination schedule using a combined hepatitis A and B vaccine (Twinrix, Smithkline Beecham Biologicals) compared with simultaneous administration of the two corresponding monovalent vaccines. The combined vaccine was administered on days 0, 7 and 21, whereas the comparison group received hepatitis A vaccine on day 0 and hepatitis B vaccine on days 0, 7 and 21. All subjects received booster vaccination at month 12. RESULTS: At month 1, 100% of subjects in the combined group and 99% of the controls were seropositive for anti-HAV antibodies. The corresponding seroprotection rates for anti-HBs antibodies were 82.0 and 83.9%, respectively. Examination of the 95% confidence intervals (CIs) for the treatment differences showed the two vaccines to be equivalent in terms of immunogenicity 1 week after the initial vaccination course. Just prior to the booster, the seropositivity rate for anti-HAV was 96.2% in the combined group and 95% in the control group. For anti-HBs, this was 94 and 91.6%, respectively. All subjects were seropositive for anti-HAV and seroprotected against hepatitis B at month 13. The anti-HAV GMCs were 9571mIU/ml with the combined vaccine and 5206mIU/ml in control subjects. The anti-HBs titre was 26002 and 29,196mIU/ml, respectively. Both groups had a similar reactogenicity profile. CONCLUSIONS: The accelerated schedule of the combined vaccine provides a good immune response against hepatitis A and B antigens and is suitable for last minute immunisation.

Evaluation of a new hepatitis B triple-antigen vaccine in inadequate responders to current vaccines.

In this double-blind, randomized, controlled study, healthcare professionals with a history of inadequate response to currently available single-antigen hepatitis B vaccines confirmed by measuring hepatitis B surface antibody titer before entry to the study were revaccinated with a 20-microg dose either of a novel triple-antigen (S, pre-S1, and pre-S2) recombinant vaccine or of a present single-antigen (S only) vaccine. Hepatitis B surface antibody titers were measured 8 weeks' post revaccination. A total of 925 individuals were randomized and vaccinated, of whom 915 (98.9%) completed the study and were included in the efficacy analysis. A single dose of the new triple-antigen hepatitis B vaccine (Hepacare) produced a successful response in over three quarters of these subjects who had not mounted an adequate response to current vaccines. The antibody response was statistically significantly superior (P =.002) to that after a single dose of current vaccines. An evaluation of the overall response showed that only the triple-antigen vaccine was able to raise the average antibody response (geometric mean titer [GMT]) to over 100 IU/L. The superior effect of the new vaccine was most pronounced in subjects who were previously complete nonresponders to currently available hepatitis B vaccines. Both vaccines were well tolerated and had similar safety profiles. This study demonstrated that in healthcare workers who had responded inadequately to at least a full course of immunization (median, 5 doses), a single 20-microg dose of a new triple-antigen vaccine induced protective antibody level in more vaccinees (P =.002) and increased the average antibody titer (GMT) in those protected successfully to a greater degree (P <.001) than a further attempt with a current vaccine (Engerix-B).

Management of hepatitis B virus infections in two gibbons and a western lowland gorilla in a zoological collection.

Since 1996, three primates newly arrived at London Zoo have been found to be infected with hepatitis B virus. The species involved were white-cheeked gibbons (Hylobates leucogenys leucogenys and Hylobates leucogenys siki) and a western lowland gorilla (Gorilla gorilla gorilla). The protocols for the practical management of these cases, including the immunisation of susceptible non-human primates and the staff with recombinant hepatitis B vaccine are described, and the origin and evolution of hepatitis B infection in primates are discussed.

Inadequate protection against yellow fever of children visiting endemic areas.

The guidelines of the World Health Organization call for immunization against yellow fever at least 10 days before travel to endemic areas. The goal of this study was to determine whether these guidelines have been applied in 2 travel clinic settings in teaching hospitals in Israel and the United Kingdom specifically for children traveling to endemic areas. Two groups of children aged 9 months to 15 years (n = 98), who were planning to travel to yellow fever-endemic areas, were evaluated regarding characteristics related to the administration of yellow fever vaccine before travel. Overall, 19 children in both clinics (19.4%; 95% confidence interval, 12.1-28.6) had received their yellow fever vaccination < 10 days before departure (no interclinic difference). Eleven of these children received the vaccine < 7 days before departure. We found that the World Health Organization guidelines for yellow fever vaccination are frequently not followed. An initiative to explain to the public the importance of vaccination well before travel to endemic areas should be undertaken.

Current topics in hepatitis B.

Over two billion people around the world have been infected with hepatitis B virus, of whom over 350 million are chronic carriers. Some 25% of carriers develop progressive liver disease. The annual mortality from hepatitis B infection and its sequelae is 1-2 million people worldwide.The following current topics are reviewed: immunization strategies against hepatitis B and the kinetics and antibody response; the controversy on screening blood donors for anti-core antibodies; mutations of hepatitis B surface antigen, including evidence that not all such mutants are detectable by current laboratory tests and, finally, the introduction of second generation nucleoside analogues for treatment of chronic hepatitis B infection, including treatment of patients with decompensated liver disease and liver transplantation.

A study of the incidence of accidents occurring during an Arctic expedition: another important aspect of travel medicine?

The number of expeditioners and independent adventure travelers to remote and physically demanding areas is increasing. Recent evidence suggests that trauma and accidents (resulting mainly from road traffic accidents and drowning) are the primary cause of mortality in travelers rather than infectious diseases.1,2 The risks and potential hazards faced on an expedition are likely to be different from those encountered by other travelers. An extensive literature search revealed little data concerning the incidence and nature of accidents on expeditions, or concerning the young adventure traveler. The objective of this study was to determine the frequency and type of accidents that occurred on a 6-week summer arctic expedition, undertaken by "young explorers" and their leaders. This information will be valuable in order to identify potential risks as part of the pretravel risk assessment, and consequently improve the medical briefing and training of expeditioners and adventure travelers.

Risks of hepatitis B in travelers as compared to immunization status.

BACKGROUND: Our objective was to determine the risks of infection with hepatitis B among European travelers and to compare this with the immunization status in various risk groups. METHODS: A cross-sectional telephone questionnaire survey of randomly selected subjects, in nine European study populations was used. A total of 9, 008 individuals were involved, with approximately 1,000 interviews conducted in each country in the native languages. Situations with a high risk of hepatitis B infection, such as invasive medical procedures, attending to a bleeding person, and skin perforating cosmetic practices, particularly when performed in countries with medium/high transmission risk, and vaccination status of travelers, were the main outcome measures. RESULTS: Depending upon the destination, 6.6-11.2% of travelers were classified as at high risk of hepatitis B, with 24.4% vaccinated; between 60.8-75.8% of travelers at potential risk, with 19.2% vaccinated; and 33.4% of travelers where no hepatitis B risk was identified. Significantly more travelers who only visited medium/high endemicity regions exposed themselves to a high risk of contracting hepatitis B, (40, 10.5%) compared to travelers who only visited low endemicity regions (225, 6.6%; p <.01). CONCLUSIONS: A significant proportion of travelers surveyed unwittingly exposed themselves to the risk of hepatitis B infection while at medium/high risk destinations. The majority of at-risk travelers had not been vaccinated, regardless of their destination. Improved advice and clear recommendations to avoid transmission are needed.

Imported tropical respiratory tract infections.

As the trends in travel continue to rise, travelers are exposed increasingly to a variety of infectious diseases, either by virtue of their chosen geographic destination or as a result of underlying immunosuppressive disease. Little has been published regarding imported tropical respiratory diseases. This article, however, reviews the incidence of respiratory disease both by destination and by travel-related risk groups and factors.

The influence of host factors and immunogenetics on lymphocyte responses to Hepagene vaccination.

We have shown that both demographic and immunogenetic factors are involved in the immune responses of Hepagene vaccinated individuals who were persistent nonresponders to 'S' containing hepatitis B vaccines. The HLA-DRB1 0701; DQB1 0202 genotype was found to be associated with a decline of anti-HBs antibodies (anti-HBs) and were frequent in those individuals who remained nonresponders following booster vaccination. Contrary to previously published 'S' vaccination data, Hepagene stimulated T-cell responses showed a lack of correlation with the humoral responses. Limiting dilution analysis demonstrated that the cellular immune response is associated with the kinetics of exposure to Hepagene rather than magnitude of the anti-HBs response. It remains that despite the inclusion of the pre-S proteins 74% nonresponder vaccinated individuals failed to produce > 100 IU/l of anti-HBs. However, these were persistent nonresponders and it was therefore encouraging that two doses of Hepagene did seroconvert (> 10 IU/L) 61% of this difficult group.

Human leukocyte antigens influence the immune response to a pre-S/S hepatitis B vaccine.

In this study we investigated the effects of a single pre-S/S (Hepagene) revaccination in a large population of multiple 'S' vaccinated anti-HBs antibody nonresponder individuals (< 3 IU/l). We investigate the influence of vaccine dose (5, 10, 20 and 40 micrograms/ml), number of previous 'S' containing vaccinations and the individuals HLA genotype on both B- and T-cell responses. We show that 76% of persistently nonresponder individuals produce anti-HBs antibody (> 3 IU/l) following a single revaccination with Hepagene. This anti-HBs antibody response was dose dependent. The group that received 5 micrograms/ml of Hepagene vaccine produced significantly less anti-HBs antibody than those receiving 10, 20 and 40 micrograms/ml doses (p < 0.05 in all cases). Individuals homozygous for HLA-DRB1*0701; DQB1*0202 failed to produce > 100 IU/l of anti-HBs antibody, whereas, heterozygous individuals required > 10 micrograms/ml Hepagene vaccine. The T-cell responses to Hepagene were exclusive of the dose and magnitude of anti-HBs antibody responses. There was a trend towards increased stimulation indices in those individuals who received repeated 'S' containing vaccines. We have clearly shown that the immune response to Hepagene is influenced by the HLA genotype of the individual. However, further investigation is required to determine the specific role of these molecules in hepatitis B vaccine nonresponse. Hepagene is a registered trademark of Hedeva Pharma Ltd.

Hepatitis B third-generation vaccines: improved response and conventional vaccine non-response--evidence for genetic basis in humans.

The lack of response to hepatitis B vaccination remains a problem for those individuals directly at risk of hepatitis B infection, particularly those who work in the health care industry. The factors associated with non-response to hepatitis B vaccination have been investigated in 86 non-responder health care workers who had received multiple 'S' vaccinations without sustained production of anti-HBs. This group received a recently developed hepatitis B vaccine, Hepagene, which included proteins derived from the envelope region of HBV, not present in currently licensed vaccines. The pre-S1 and pre-S2 proteins were included in Hepagene in order to circumvent anti-HBs non-responsiveness which had previously been demonstrated in the inbred mouse model. The inclusion of these additional proteins in Hepagene enabled some seroconverion, from non-responder to responder; however, a proportion of the vaccinees remained non-responders and the reasons for this have been investigated here, with reference to HLA alleles and the demographic predisposition. Here the mechanisms that underlie hepatitis B vaccine non-response have considered the distribution of HLA alleles, age, sex, height and weight in addition to the T-cell responses to Hepagene derived antigens.

Hepatitis B third-generation vaccines: improved response and conventional vaccine non-response--third generation pre-S/S vaccines overcome non-response.

A new triple-S containing recombinant hepatitis B vaccine was evaluated in terms of immunogenicity and reactogenicity in a cohort of healthy healthcare professionals who were persistent non-responders to the currently licensed hepatitis B vaccines. One hundred subjects were allocated randomly to receive two doses of 5, 10, 20 or 40 micrograms of a new hepatitis B vaccine 2 months apart. The overall seroconversion rate was 70% with a single dose of 20 micrograms of the vaccine being as effective as two doses of either 20 micrograms or 40 micrograms of the vaccine formulation in terms of seroconversion, seroprotection and geometric mean titres.