Hepatitis A and B Vaccination in Elderly Travellers
Monovalent Hepatitis A Virus Vaccines In a study evaluating the effect of age and weight on the response to HAV vaccine (Vaqta™ Adult; Sanofi Pasteur MSD Ltd, Lyon, France), seroconversion rates and antibody levels were lower in individuals >40 years of age (70%, GMT 14.3mIU/ml) compared with individuals <40 years of age (91%; GMT 29.0mIU/ml) one month after a single vaccine dose.95 The seroresponse improved following a second dose at two weeks, so that there was no longer any difference between individuals >40 years of age (96%, GMT 106.1mIU/ml) and individuals <40 years of age (95%, GMT 123.9mIU/ml) at 24 weeks. Thus, adults >40 years of age respond less favourably to a single dose of the vaccine than younger individuals but respond equally well following two doses of the vaccine.
Low seroprotection rates in older subjects were similarly observed in a study with Epaxal™.112
The younger subjects (18–45 years of age)
had 1.7-fold higher antibody titres compared with the subjects aged ≥50 years of age after the initial vaccination. Whereas all the younger subjects had seroprotective antibody titres (considered in this study to be ≥20mIU/ml) one month after the initial vaccination, only 70% of subjects aged 50–60 years of age and 60% of those >60 years of age had seroprotective antibody titres. However, the older subjects produced a robust immune response to a second dose at 12 months, as seen by the similar proportional increase in antibody titres in both older and younger subjects. In the 30 subjects older than 50 years of age, all except one were seroprotected by one month after the second dose.
The above studies might suggest that elderly travellers should be given two doses of HAV vaccine, at least two weeks apart, prior to departure to increase the likelihood of protection. They should be vaccinated well in advance of undertaking their journey113
as they
experience a slower development of the immune response compared with younger subjects.95,114
Monovalent Hepatitis B Virus Vaccines Age was shown to influence the efficacy of HBV vaccine (Engerix-B™; GlaxoSmithKline Biologicals, Rixensart, Belgium) in a prospective study in healthcare workers and their relatives. The seroprotection rate was found to be age dependent after a three-dose schedule at 0, one and six months (p=0.01) but was still close to 95% in vaccinees who were 40–59 years of age.115
Increasing age was also significantly
associated with lower antibody GMTs (p<0.001). Another study demonstrated that the occurrence of inadequate levels of HBV antibody (<10mIU/ml) following vaccination with Recombivax HB™ (Merck & Co., West Point, PA, US) increased significantly with age, from 2.8% in subjects <30 years of age to 42.1% in those >60 years of age (p<0.0001).98
A third study in subjects ≥39 years of age (mean
age 48) showed that immunisation with a 20µg dose of recombinant HBV vaccine (Engerix-B™) produced higher anti-HBs titres than immunisation with a 10µg dose (Recombivax-HB™); among male subjects the higher dose also appeared to give a more rapid development of seroprotective anti-HBs levels.94
A meta-analysis of
studies (using the vaccines Engerix B™, Recombivax HB™ or both) on the HBV vaccine response among older individuals showed that an increased risk of non-response is seen from as young as 30 years of age.116
The reduced levels of anti-HBs (and development of anti-HAV) generated in elderly vaccinees may suggest the need for a shorter
EUROPEAN GASTROENTEROLOGY & HEPATOLOGY REVIEW
interval between the primary vaccine series and the booster vaccination.96,97,112,114,116
Combination Hepatitis A Virus/Hepatitis B Virus Vaccine The efficacy and safety of the combined hepatitis A and B vaccine (Twinrix™; GlaxoSmithKline Biologicals, Rixensart, Belgium) and co-administered monovalent vaccines (Engerix-B™ + Havrix™ or HB VAX PRO™ [Sanofi Pasteur MSD Ltd, Lyon, France] + Vaqta™) were compared in a population >40 years of age.110
Anti-HAV seropositivity
rates (% ≥15mIU/ml) in subjects receiving Twinrix™ (97%) were non-inferior to those receiving Engerix-B™ + Havrix™ (99%) or HB VAX PRO™ + Vaqta (99%). The anti-HBs seroprotection rates (% ≥10mIU/ml) one month after the full three-dose primary vaccination series were higher in subjects given Twinrix™ (92%) compared with Engerix-B™ + Havrix™ (80%) or HB VAX PRO™ + Vaqta™ (71%). Anti-HBs antibody levels were also highest with Twinrix™. Thus, Twinrix™ was the most immunogenic of the three vaccines against HBV, most significantly in subjects >60 years of age, with similar anti- HAV responses. A follow-up study to assess persistence of the immune response showed that after four years the anti-HAV responses had been sustained with either regimen, while the anti-HBs seroprotection rates and antibody titres remained higher in subjects given the combined HAV/HBV vaccine (76.9%, GMT 42.3 mIU/ml) compared with the monovalent vaccine groups (61.9%, GMT 23.6 mIU/ml in the Engerix-B™ + Havrix™ group; 51.6%, GMT 13.7 mIU/ml in the HB VAX PRO™ + Vaqta group).117
A booster dose of the
corresponding vaccines produced a greater response in the combined vaccine group than in subjects administered the monovalent vaccines. The primary anti-HBs response was consistent with the results of a previous study evaluating Twinrix™ against the monovalent HBV vaccines Engerix-B™ and Gen-HB-Vax™ (Merck & Co., West Point, PA, US), where Twinrix™ showed the highest seroprotection rates (92.3 versus 87.7% for Engerix-B™ and 79.3% for Gen-HB-Vax™), particularly in the elderly.118
Less encouraging results on the immunogenicity of Twinrix™ were obtained in a study by Wolters and co-workers, where only 65% of vaccinees >40 years of age gained protection against HAV and only 29% gained protection against HBV.119
These low results are not
consistent with other data on the combined and monovalent vaccines.106,120–123
A number of factors are thought to have influenced the outcome from the Wolters study, such as the extended time interval between the last vaccine dose and blood sampling (mean 16.8 months), rather than the recommended time frame of one to three months for determining anti-HBs titres.124
A critical analysis of
pooled data from five clinical trials carried out exclusively on subjects >40 years of age (mean age = 49 years) concluded that Twinrix™ is highly immunogenic in this age group.121
Insight into the performance of the combined vaccine under real-life conditions was obtained through a retrospective study conducted in subjects >40 years of age who had received Twinrix™ in a zero, one and six months schedule at five vaccination centres, and were tested for anti-HAV and anti-HBs at a mean time interval of 3.1 months after schedule completion (range 0–28 months).125
This revealed that
97.9% of subjects were seropositive for anti-HAV, and that the seroprotection rate for the anti-HBs response was 96.3%. The authors concluded that hepatitis A and B vaccination is of benefit in older people at risk of HAV or HBV infection, such as those travelling to endemic areas.
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