Immunogenicity of booster vaccination with a virosomal hepatitis A vaccine after primary immunization with an aluminum-adsorbed hepatitis A vaccine

BACKGROUND: Increasing numbers of individuals are traveling to areas of high hepatitis A endemicity and require immunization against the hepatitis A virus (HAV). The option of using a virosomal, aluminum-free, HAV vaccine (Epaxal) for booster immunization following primary vaccination with an aluminum-adsorbed vaccine has been assessed. METHODS: In total, 142 healthy subjects, 79 men and 63 women, aged 12 to 72 years, were injected intramuscularly with a booster dose of Epaxal (0.5 mL containing < or =500 RIA units of HAV antigen) 6 to 24 months after primary vaccination with Havrix (0.5 or 1.0 mL containing 720 or 1440 ELISA units of HAV antigen, respectively, adsorbed onto aluminum hydroxide). Anti-HAV antibody titers were measured on days 0 and 28 by an enzyme immunoassay. Adverse events were recorded for 1 month postinjection. RESULTS: Overall, 98/118 subjects (83%) with no serologic evidence of past HAV infection were still seroprotected at enrolment (anti-HAV antibody titer < or = 20 mIU/mL). The seroprotection rate was 87% in those primed with Havrix 1440 6 to 12 months earlier (n=93) and 60% in those primed < or =12 months before enrolment (n=20, mean 16 months). The geometric mean anti-HAV antibody titer increased from 65 mIU/mL at day 0 to 1,722 mIU/mL at day 28 after a single booster dose with Epaxal in evaluable subjects who were primarily vaccinated with either a single dose of Havrix 1440 (n=111) or two separate doses of Havrix 720 (n=4). All subjects were seroprotected at day 28, and 98% showed at least a four-fold increase in anti-HAV antibody titer. Epaxal was well tolerated and no serious adverse events were reported. At day 28, the tolerability of the vaccination was judged as either "very good" or "good" by 96% of vaccinees and by all investigators. CONCLUSION: Epaxal can be successfully used to boost immunization following primary vaccination with an aluminum-adsorbed vaccine, and is well tolerated.     

Immunogenicity and Reactogenicity of Avaxim (160 AU) as Compared with Havrix (1440 EL.U) as a Booster Following Primary Immunization with Havrix (1440 EL.U) against Hepatitis A

Background: Hepatitis A vaccination is recommended for travelers from the UK to areas of moderate or high endemicity. Two licensed hepatitis A vaccines are now available in the UK, and this trial was undertaken to determine whether Avaxim can be used as a booster following a primary course of Havrix.
Methods: One hundred and eighty-five subjects were randomized to receive a booster dose of either Avaxim (n=92) or Havrix (n=93), 6 to 7 months after a primary dose of Havrix. Subjects were observed for 30 minutes for immediate reactions and subsequently completed a diary card for a further 2 weeks. Serology samples for HAV antibody titers were taken at 28 ± 7 days later.
Results: One month following the booster dose, all subjects in both treatment groups achieved HAV antibody titers ± 20 mlU/mL. In the Avaxim group, geometric mean liter (GMT) values increased from 642 mlU/mL (97.5% Cl 330–1250 mlU/mL) to 6669 mlU/mL (4566–9740 mlU/mL), compared with 739 mlU/mL (379–1443 mlU/mL) at baseline to 4460 mlU/mL (2880–6908 mlU/mL) following the administration of Havrix. The increase in GMT following the administration of Avaxim was significantly greater than that following Havrix (p=.02). Eight percent of subjects reported pain at the injection site following a booster dose of Havrix, compared with none following Avaxim. This difference in reactogenicity was statistically significant (p=.01). In all other respects, both preparations were safe and equally well tolerated.
Conclusion: Either Avaxim or Havrix may be given as a booster dose of hepatitis A vaccine when Havrix has been administered as the primary dose.     

Response to Hepatitis A Vaccine in Children after a Single Dose with a Booster Administration 6 Months Later

Background: Children are of an age group susceptible to infection by the hepatitis A virus (HAV). Active immunization of children against HAV became reality in 1993, when the first pediatric hepatitis A vaccine was licensed. This initial vaccine required two injections to induce a full immune response in recipients. The purpose of this study was to assess the feasibility of a single dose primary vaccine plus a booster after 6 months against hepatitis A in children.
Methods: A total of 60 healthy and seronegative children between 2 and 13 years of age were administered inactivated hepatitis A vaccine, containing 720 enzyme-linked immunosorbent assay (ELISA) units (EL.U) of hepatitis A antigen, intramuscularly in the deltoid region at months 0 and 6. Symptoms were recorded by parents or guardians on individual diary cards. Antibodies against HAV (antiHAV) were measured using an ELISA inhibition assay, and a seropositive titer was defined as being ≥20 mIU/mL.
Results: Fifteen days after the single primary dose, 96% of the vaccinees were seropositive with a geometric mean titer (GMT) of 351 mIU/mL The seropositivity rate reached 100% 1 month after the first dose, with a GMT of 305 mIU/mL Prior to the second dose at month 6, 93% remained seropositive, and the GMT was 153 mIU/mL. By month 7, 1 month after the second vaccination, the seropositivity rate recovered to 100% with a rise in GMTs to 3644 mIU/mL. Local symptoms were reported after 23.9% of doses, and general symptoms after 19.7% of doses. All symptoms were of short duration and resolved spontaneously.
Conclusions :This inactivated vaccine against hepatitis A is safe, well-tolerated, and excellently immunogenic when administered to children following a single dose plus booster course at months 0 and 6.     

Tolerance and immunogenicity of the simultaneous administration of virosome hepatitis A and yellow fever vaccines

BACKGROUND: The purpose of this study was to evaluate the tolerance and immunogenicity of a hepatitis A vaccine using immunopotentiating reconstituted influenza virosomes (IRIV) as adjuvant when administered simultaneously with a yellow fever vaccine (YFV). METHOD: An open prospective trial with two parallel groups was conducted with 105 volunteers to study the effect of these vaccinations on the anti-hepatitis A virus (HAV) antibody response. Half of the volunteers (53) received one dose of IRIV-HAV vaccine (Epaxal) and one dose of live attenuated YFV (Stamaril) on the same day at two different sites. Fifty-six volunteers were given a single injection of IRIV-HAV as a control group. Anti-HAV titers were measured at days 14, 28, months 3, 12, 13, and 24 using a standardized test (Enzymun test Anti-HAV). Neutralizing yellow fever antibodies were measured at days 14 and 28 for the YFV recipients. Regarding vaccine tolerance, the volunteers were asked to record all their adverse reactions on a standard report sheet for the 6 days following the immunization. RESULTS: Seroconversion rates for HAV were 88% after 14 days and 100% after 4 weeks. There was no statistically significant difference between the two groups every time the titers were checked (IRIV-HAV vs HAV only: D14: 81 vs 101; D28: 275 vs 368; M3: 153 vs 169; M12: 117 vs 226; geometrical mean titers (GMT) in mIU/mL). However, lower titers were found among male volunteers, and were not attributable to YFV administration. The seroconversion rates for YFV were 90% after 14 days and 96% after 4 weeks. No serious general side-effects and only mild local reactions were reported. The administration of a booster of IRIV-HAV at 12 months resulted in a 24-fold increase in GMT. CONCLUSION: When needed, the simultaneous administration of the IRIV-HAV and YFV is immunogenic, safe and well-tolerated, as volunteers seroconverted to both antigens, with no cross-interference.     

Safety and Immunogenicity of a High–Potency Inactivated Hepatitis A Vaccine

Background: In recent years, several hepatitis A vaccines have been developed. We wished to evaluate the safety, reactogenicity, and immunogenicity of an inactivated hepatitis A vaccine, containing 1440 EI.U., and to monitor the kinetics of the antibodies monthly for the first year after administration of a single dose of vaccine.
Methods: We conducted an open clinical trial, started in March 1992 and completed in July 1993, at two general hospitals and one pediatric hospital in Antwerp, Belgium, with 194 healthy adult healthcare volunteers. Each volunteer received a single dose hepatitis A vaccine, given intramuscularly at month 0 and a booster at month 12. We undertook serologic follow-up of antihepatitis A virus (antiHAV) antibodies and liver enzymes at day 15 and at months 1, 6, 9, 12, and 13. For a random subgroup of participants, blood samples were taken monthly. In addition, all participants noted local and general symptoms following administration of the vaccine.
Results: This single dose vaccine was well-tolerated; 2 weeks after the vaccination, 80% of the participants had seroconverted (antiHAV antibodies ≥ 20 mlU/mL); after 1 month, seroconversion reached 99% (geometric mean titer (GMT): 383 mlU/mL). One year after the single dose of vaccine, 94% still had antiHAV antibodies above 20 mlU/mL (GMT: 176 mlU/mL). One month afterthe booster dose, seroconversion was 100%, and GMT increased from 176 mlU/mL at month 12 to 4775 mlU/mL at month 13.
Conclusions: The single dose hepatitis A vaccine is safe and highly immunogenic; it gives a rapid antibody production and a rapid increase of GMT. The persistence of protective antibodies until month 12 allows a booster at month 12. This schedule will easily fit into existing travel or occupational health vaccination schedules and will improve vaccination compliance.     

Vaccination Strategies Against Hepatitis A in Travelers Older Than 40 Years: An Economic Evaluation

Background.  In recent years, the number of travelers aged >40 years who acquire hepatitis A while traveling has increased. Therefore, there is a need to review hepatitis A vaccination protocols in travelers. The aims of the study were to assess immunity levels to hepatitis A virus (HAV) in international travelers >40 years and to determine the least costly immunization strategy.
Methods.  A serological examination of HAV antibodies in 427 international travelers aged >40 years traveling endemic zones was carried out. The prevalence of antibodies in each age group was assessed. The costs of two preventive strategies, direct vaccination of all subjects (independent of the immune status) or screening and subsequent vaccination of susceptible subjects were compared. The critical value of prevalence (CVP) (the value at which the costs for the two strategies are equal) was calculated.
Results.  Total prevalence of HAV antibodies was 78.9% [95% confidence interval (CI): 74.8–82.5] and was 80.0% (95% CI: 73.8–85.2) in men and 77.9% (95% CI: 71.9–83.2) in women. There was a positive association with age. In the 40 to 49, 50 to 59, 60 to 69, and 70 to 95 years age groups, the prevalence rates were 62.6 (95% CI: 53.8–71.5), 76.8 (95% CI: 70.0–82.7), 91.7 (95% CI: 85.2–95.6), and 97.5% (95% CI: 87.4–99.6), respectively. The CVP was 58.4% using two doses of vaccine.
Conclusions.  The CVP was lower than the prevalence rate found in our international travelers. Therefore, we recommend systematic screening for HAV antibodies before selective vaccination of international travelers aged >40 years traveling to hepatitis A endemic zones.     

Immunogenicity, reactogenicity and adherence with hepatitis A vaccination among drug users

Hepatitis A virus (HAV) vaccination is recommended in drug users (DUs) because this population has a very high prevalence of hepatitis C virus, and additional infection with HAV can lead to increased morbidity and mortality. The efficacy of hepatitis A vaccine (1440 ELISA units), in terms of immunogenicity, reactogenicity and compliance among 44 heroin DUs using a 0-6 month schedule was investigated. Three subjects (6.8%) experienced adverse reactions. After the first dose of hepatitis A vaccine, 37% of subjects seroconverted. Two months after the 6-month booster vaccination, all vaccinated patients became seropositive. The mean serum antibody concentration was 40 mIU/ml after 6 months and 558 mIU/ml after 8 months. Although all DUs proved seropositive after the booster vaccination, the seroconversion rate, at the 2 and 6 months time points was much lower than in healthy subjects. The lower geometric mean titre could affect the kinetics of decrease of antibody titres and the protection conferred by vaccination may be less durable in these patients. These findings indicate that the 0-12 months schedule could be reduced to a shorter 0-6 months schedule in order to shorten the unprotected period. Further studies among drug users are needed to explore the efficacy and immunogenicity of higher doses or alternative schedules of HAV vaccine.     

Inactivated hepatitis A vaccine in Chinese patients with chronic hepatitis B infection

BACKGROUND: Hepatitis B (HBV)-infected patients have a higher morbidity and mortality when super-infected by hepatitis A (HAV). AIM: To evaluate the immunogenicity and safety of a commercial inactivated HAV vaccine in Chinese patients with chronic HBV infection. METHODS: Sixty-five HBV-infected patients (30 carriers, 22 chronic hepatitis, 13 cirrhosis), who were seronegative for HAV, received a dose of 1440 ELISA units of HAV vaccine at weeks 0 and 24. Twenty-eight healthy individuals aged 18-57 years, who were seronegative for both HBV and HAV infection, also received the same vaccination regimen. Seroconversion was defined as an anti-HAV titre >/= 33 mIU/mL. RESULTS: The seroconversion rates for the HBV-infected patients at weeks 2, 4 and 24 were 72, 91 and 80%, respectively. The corresponding geometric mean titres (GMTs) were 103, 311 and 123 mIU/mL. In the healthy control group the seroconversion rates were 86, 93 and 89% at weeks 2, 4 and 24. The corresponding GMTs were 112, 158 and 250 mIU/mL. There was no difference in the seroconversion rates between the two groups, but healthy controls had a significantly higher GMT at week 24 (P=0.04). Side-effects were more common in HBV patients. CONCLUSION: The HAV vaccine is equally efficacious in patients with chronic HBV infection.     

Hepatitis B vaccine boosters: further studies in children

Two groups of children were given reduced dose boosters with Merck Sharp and Dohme (MSD) recombinant DNa, yeast derived hepatitis B vaccine (YDV), 30 and 34 months respectively after primary immunisation with MSD plasma derived vaccine (PDV). In the first group of unselected children the geometric mean titre (GMT) rose from 387 to 8346 IU/L, with all children protected. The second group were selected as the poorest responders to their primary course of vaccine. The booster raised the GMT from 14.6 to 325 IU/L, with 95% having protective levels of anti-HBs (greater than 10 IU/L). This study confirms that the vaccine used by the New Zealand Department of Health for the hepatitis B immunisation programme in preschoolers, will provide protection for the great majority of children for at least three years.     

Early rabies antibody response to intramuscular booster in previously intradermally immunized travelers using human diploid cell rabies vaccine

BACKGROUND: Postexposure treatment (PET) of travelers who may have had a potential rabies exposure is simpler, safer, and cheaper if the traveler is preimmunized. Preimmunization can be done with human diploid cell rabies vaccine (HDCV) administered intramuscularly or intradermally. Some authorities, however, are now advocating that travelers vaccinated by the intradermal (ID) route should be treated as if they are not immunized. A particular concern raised is that travelers who have received pre-exposure rabies vaccination intradermally, may have a delayed response to postexposure boosters. This study is designed to elucidate whether a single intramuscular (IM) HDCV booster will provoke an early (day 5) immune response in individuals given pre-exposure ID HDCV. METHODS: Twenty-nine travelers who had received a course of three 0.1 mL ID HDCV between 12 and 24 months previously were given a single 1.0 mL IM booster of HDCV. Rabies antibody levels were compared 5 days later to those before the booster. RESULTS: Twenty-five of the 29 subjects (86%) showed an adequate rise in virus neutralizing antibody (VNA) titer 5 days after booster. Nine of the 29 subjects (31%) had inadequate antibody levels prior to the simulated postexposure booster. Five days after the postexposure booster, 27 of 29 (93%) had adequate antibody levels. The other 2 travelers were subsequently shown to have adequate VNA levels when tested 4 and 6 weeks later, respectively. CONCLUSION: For travelers who were given pre-exposure ID HDCV vaccination within the last 2 years and received one IM postexposure booster dose of HDCV, most mounted an adequate early immune response. This data does not support a change in current recommendations for rabies PET in this group. Further research to ascertain the duration of protection of pre-exposure ID rabies immunization is required.     

Immune Response to Hepatitis A Vaccine Combined or Given Simultaneously with Typhoid Fever Vaccine

Background: Because both hepatitis A and typhoid vaccination are frequently indicated in the same traveler, a prospective, randomized controlled study was performed to evaluate the feasibility of simultaneous administration of hepatitis A and typhoid fever vaccines in adult volunteers.
Methods: Two groups of 25 subjects received either separate injections of hepatitis A (Havrix™, SmithKline Beecham Biologicals) and typhoid fever (Typhim Vi™, Pasteur-Mérieux) vaccines in opposite arms, or a syringe-mixed combination of both vaccines as a single injection. A booster dose of Havrix was given at 6 months.
Results: The immune response to hepatitis A tended to be higher in the mixed-injection group, but this difference was significant (p=.048) only following the booster dose. Adverse reactions were generally mild with no differences between the two groups.
Conclusion: A combined formulated vaccine against both typhoid fever and hepatitis A is feasible and offers more convenience without added adverse reactions to travelers who have appropriate indications for both vaccines.     

Safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Chilean children

The safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix?) were assessed in 240 healthy Chilean children randomized to receive 3 doses of PHiD-CV (PHiD-CV group) or hepatitis A vaccine (HAV control group) at 2-4-6 months of age. All were offered 1 HAV dose at 12 months (outside study). The PHiD-CV group received a second HAV dose at 18-21 months and PHiD-CV booster at 20-23 months. The HAV control group received 2 PHiD-CV catch-up doses at 18-21 and 20-23 months. Adverse events were recorded and pneumococcal antibody responses and opsonophagocytic activity (OPA) were measured. Both PHiD-CV vaccination schedules were well tolerated and immunogenic against the pneumococcal vaccine serotypes and protein D. The reactogenicity of PHiD-CV primary, booster and catch-up doses was in line with previous PHiD-CV studies, although generally higher than with HAV. For each vaccine serotype, the percentage of subjects with antibody concentrations ≥0.2 μg/ml (GSK's 22F-inhibition ELISA) was at least 93.2% following 3 PHiD-CV primary doses and at least 97.4% post-booster; percentages with OPA titers ≥8 were at least 91.7% post-booster. After 2-dose catch-up, at least 94.3% of children had antibody concentrations ≥0.2 μg/ml against each serotype except 6B (84.3%); at least 95.2% had OPA titers ≥8 except against serotypes 1, 5 and 6B. In conclusion, the safety profiles of 2 PHiD-CV vaccination schedules (3-dose primary plus booster and 2-dose catch-up) were in line with previous studies and PHiD-CV was immunogenic for all 10 vaccine serotypes and protein D.     

A single dose, combined vaccine against typhoid fever and hepatitis A: consistency, immunogenicity and reactogenicity

BACKGROUND: Vaccines against hepatitis A and typhoid fever are well established and have an excellent safety and immunogenicity profile. Yet these diseases, which share the same geographic distribution, remain an important cause of morbidity in travelers to endemic countries. Combined vaccination provides dual protection and improves compliance and coverage for travelers. METHODS: This multicenter study evaluated the consistency of three lots of combined hepatitis A and typhoid fever vaccine. A total of 462 healthy subjects, aged 15-50 years, were enrolled and randomly allocated to 3 groups. The single dose of vaccine contains 25 microg typhoid Vi polysaccharide and at least 1,440 ELISA units of inactivated hepatitis A in a 1 mL dose. RESULTS: Bioequivalence of all production lots was shown in terms of safety and immunogenicity. Pain at injection site was the most frequent reported local symptom, and headache was the most frequent reported general symptom. As early as 14 days after immunization >95% of the subjects were positive for anti-Vi antibodies and >86% were positive for anti-HAV antibodies. The GMTs and seropositivity rates were maintained during the 6 month follow-up. CONCLUSION: The first combined vaccine against typhoid fever and hepatitis A was safe and elicited a very good immune response, with the majority of subjects seropositive at 1 month for both antigens. This combined vaccine offered more convenience and rapid seroconversion to travelers.     

Hepatitis B vaccination in children: five year booster study.

AIM: to demonstrate that appropriate doses of hepatitis B vaccines would be protective for at least five years in children. This would be shown by administering booster doses and measuring the response. METHODS: 2 micrograms intramuscular (IM) doses of Merck Sharp and Dohme (MSD) recombinant DNA vaccine (rDNAV) were given to 318 children who had received age appropriate doses of MSD plasma derived vaccine (PDV) five years earlier. Sera were tested for hepatitis B virus (HBV) seromarkers pre- and postbooster. RESULTS: all children who had responsed to primary immunisation demonstrated an anamnestic response. The geometric mean titre (GMT) of antibody to hepatitis B surface antigen (antiHBs) rose from 89 to 4777 IU/L. AntiHBs was detected in 94% of vaccinees just prior to the five year booster, and 96.5% a mean of 10 days later. CONCLUSION: when initial vaccine seroconversion is satisfactory, protection of responders persists for at least five years, assuming that the response to vaccine boosters mimics the response to wild virus. Therefore, for population control of hepatitis B in children in endemic areas, booster doses are not required for at least five years.     

Intranasal immunization against influenza.

Nasalflu is a novel influenza subunit vaccine, which is administered by the intranasal route using a spray device. Nasalflu is based on the virosomal concept which is registered in the EU as Epaxal Berna, a vaccine against Hepatitis A, and Inflexal Berna V, a subunit influenza vaccine. The virosome is a carrier system which delivers antigens to cells and is able to induce both B- and T-cell immunity. When virosomal vaccines are given parenterally, an immune response is elicited fast and sufficiently.     

Immunologic non-inferiority of a newly licensed inactivated trivalent influenza vaccine versus an established vaccine: a randomized study in US adults

A trivalent inactivated influenza vaccine (Fluarix (?) , GlaxoSmithKline Biologicals) was licensed under US accelerated approval regulations. We performed a randomized, observer-blind, post-approval study to demonstrate its immunological non-inferiority versus an established US-licensed vaccine (primary endpoint). Adult (including elderly) subjects received a single injection of newly-licensed vaccine (n = 923) or established vaccine (n = 922). Serum hemagglutination-inhibition titers were determined pre-vaccination and 21-28 days after vaccination. Non-inferiority was assessed by post-vaccination geometric mean titer (GMT) ratio (upper 95% confidence interval [CI] ≤ 1.5) and difference in seroconversion rate (upper 95% CI ≤ 0.1) for all three vaccine strains. Safety was monitored for 6 months. The newly-licensed vaccine was non-inferior to the established vaccine in all subjects (≥ 18 years) and in elderly subjects (≥ 65 years). Adjusted GMT ratios (established/newly-licensed) against the H1N1, H3N2 and B strains were 0.65 (95% CI: 0.58, 0.73), 0.93 (0.83, 1.04) and 1.13 (1.03, 1.25) for all subjects and 0.75 (0.67, 0.85), 0.95 (0.82, 1.09) and 1.13 (1.00, 1.27) for elderly subjects. Corresponding values for the differences in seroconversion rate (established minus newly-licensed) were -0.12 (-0.16, -0.07), -0.02 (-0.06, 0.03) and 0.01 (-0.04, 0.06) for all subjects and -0.11 (-0.16, -0.05), -0.02 (-0.07, 0.04) and 0.02 (-0.04, 0.08) for elderly subjects. The most common adverse events with both vaccines were injection site pain, fatigue and headache, and no serious adverse events or deaths were considered related; there were no clinically relevant differences between the vaccines. In conclusion, the newly-licensed vaccine was well tolerated and immunologically non-inferior to the established vaccine for all three vaccine strains in the whole population and the elderly.     

Intradermal, low dose, short course hepatitis B vaccination

Seventy-five of 88 (85.2%) vaccinees seroconverted at three months after three 2 micrograms doses of a plasma-derived hepatitis B vaccine had been given intradermally one month apart. Vaccinees under 30 years of age had a significantly better seroconversion rate (88.8%) than older subjects (50%) as measured at three months. Forty-three of 47 (91%) vaccinees who were bled one year post vaccination had antibody levels in excess of 10 IU/1. This study indicates that short course, low dose, intradermal vaccination with plasma-derived hepatitis B vaccine may be a viable and cheap regimen for inducing immunity against hepatitis B in younger subjects.     

Combined typhoid fever and hepatitis A vaccine: comparison of immunogenicity and safety to concomitant monovalent vaccine over 3 years

BACKGROUND: The safety and immunogenicity of Viatim, a combined hepatitis A (HA) and typhoid fever (Vi) vaccine, were compared with the monovalent component vaccines up to and 1 month after a booster dose at 3 years. METHODS: Healthy, adult volunteers were randomized to receive Viatim (group A, n = 179) or separate HA and Vi vaccines (group B, n = 181); subgroups were boosted after 3 years with Viatim (groups C and D, n = 56 and 46, respectively). Local and systemic reactions were recorded for 28 days postvaccination. Seroconversion and seroprotection rates and geometric mean antibody concentrations were measured at 14 and 28 days, 1, 2, and 3 years postvaccination, and 28 days after the booster dose. RESULTS: Local and systemic safety profiles were equivalent between the two groups. Immediate local reactions were infrequent (1 in group A and 2 in group B). Local reactions, consisting mostly of mild or moderate pain, were least frequent with monovalent HA. Antibody concentrations to both antigens were similar in groups A and B, in which HA seroprotection rates (> or = 20 mIU/mL) were respectively, 98.7% and 100% at day 28, and 99.1% and 99.0% after 3 years, achieving 100% after the booster. Vi seroprotection rates (> or = 1 microg/mL) of 85.2% and 84.9% after 28 days fell to 32.1% and 35.6% after 3 years, increasing to 67.3% and 69.8% after the booster dose. CONCLUSIONS: The combined HA/Vi vaccine, Viatim, had equivalent tolerability and safety and was as rapidly immunogenic as its component monovalent vaccines when given concurrently. A booster dose after 3 years significantly increased antibody levels with some evidence of relative hyporesponsiveness of the typhoid response.     

Immunogenicity of two modern tissue culture rabies vaccines in pre-exposure prophylaxis

Pre-exposure prophylaxis was given to employees supposed to be involved in rabies vaccine production in India. Prior to availability of the manufacturer's own human diploid cell (HDC) vaccine (Rabivax), immunization was executed with a chick embryo cell (CEC) vaccine (Rabipur). This constellation gave an opportunity to compare retrospectively immunogenicity of these two vaccines. The data was collected by retrospective analysis over more than three years at the clinic of Serum Institute of India Ltd. As per the standard protocol, persons with negative rabies vaccination history receive a dose of 1 ml of rabies vaccine intramuscularly on day 0, 7 and 28, and the virus anti-glycoprotein antibodies are measured one month after the third dose. The antibody levels > or =0.5 IU/ml are considered protective. The CEC and HDC vaccines were used during the analysis period. In all, 43 individuals received the CEC vaccine, 106 the HDC vaccine. The mean age of recipients was 33 years five months (Rabipur) and 30 years three months (Rabivax). All subjects in both groups were males. Five commercial batches of the CEC vaccine (129 doses) and seven batches of the HDC vaccine (318 doses) were used. Ninety-nine percent of the HDC and 93% of the CEC vaccine recipients were protected after the standard three dose schedule. Geometric mean titre was significantly greater for the HDC than CEC vaccine, being 5.05 IU/ml and 2.90 IU/ml, respectively (p = 0.0002). The HDC vaccine showed a good lot-to-lot consistency with respect to GMT both by ANOVA test and Nonparametric ANOVA test. On the other hand, the CEC vaccine demonstrated a variation in titres, when the lots were compared. Three out of four low-responders accepted a booster vaccination, and regardless of whether Rabipur or Rabivax was used, all three responded well one month after the booster. The Indian HDC vaccine compares well with the CEC vaccine in terms of immunogenicity. With HDC vaccines, cost has been an issue. However, since the new HDC vaccine has a comparable cost to the CEC vaccine, it may be possible to use it in large-scale vaccinations.     

Malaria Prophylaxis in Different Age Groups

Background: There is a perceived increased health risk in senior visitors to malaria endemic countries.
Methods: The authors sought to compare effectiveness and tolerability of malaria chemoprophylaxis in senior travelers (≥60 years) with those in younger travelers (20–59 years). The "Malpro 2" database consists of more than 100,000 questionnaires completed by travelers on charter planes returning from East Africa to Europe during July 1988-December 1991. Among them, 9106 (9.1%) of the travelers were 60 years or older, and 84,562 (84.6%) of the travelers reported to be 20–59 years. Variables of demography, travel data, and the effectiveness and tolerability of chemoprophylaxis were compared in the two subgroups.
Results: Malaria in Africa was reported by 8 (1/1000) elderly travelers and by 189 (2.2/1000) travelers aged 20–59 years. Adjusting for age, sex, prophylaxis, and duration of stay in Africa in a logistic regression model, malaria was significantly more frequent in younger than in senior travelers (p<.05). Any travel-associated illness was reported by 7.0% in the senior age group and by 13.6% in the younger age group (p<.05). The rates of travelers who indicated they had "side effects" attributable to malaria prophylaxis varied between 9.7% in the elderly and 15.5% in the younger travelers (p<.05).
Conclusion: Senior travelers tolerate malaria chemoprophylaxis and visits to the tropics at least as well as younger travelers.