Herpes Zoster Burden in Canadian Provinces: A Narrative Review and Comparison with Quebec Provincial Data.

BACKGROUND: The main aim of this review was to assess incidence rates and trends of medically attended and death cases of herpes zoster in Canada. METHODS: The search was conducted in five databases (PubMed, Cochrane, Embase, PsycNET, and Web of Science). Data on herpes zoster-related consultations and hospitalisations and deaths were also extracted from three Quebec provincial administrative databases (RAMQ, MED-ECHO, and ISQ). RESULTS: The electronic search yielded 587 publications. Seventeen publications satisfied inclusion criteria. These publications reported data from eleven studies. Ten studies used provincial databases, and one study used the Canadian Primary Care Sentinel Surveillance Network electronic database. Seven studies evaluated overall rates of medically attended cases (consultations and hospitalisations). Four of these studies reported an increase in rates of medically attended cases during the study period; one study reported stable rates, and two studies reported only an average rate. The rates varied from 316 to 450/100,000 p.y. The Quebec analysis shows similar rates with a slight decreasing trend (from 369 to 350/100,000 p.y.). Incidence rates of consultations were reported separately in three studies. Two studies reported an increase in rates (from 258 to 348/100,000 p.y. and from 324 to 366/100,000 p.y.), and the third study reported a decrease (from 525 to 479/100,000 p.y.). Hospitalization rates were reported separately in two studies, both reporting a decrease (from 12 to 8 cases/100,000 p.y. and from 9 to 4 cases/100,000 p.y.). Quebec data also showed a decrease, from 9 to 6 cases/100,000 p.y. One study reported herpes zoster-related deaths. In this study, the reported death rate was 0.7/1,000,000 p.y. in the overall population and 5.5/1,000,000 p.y. in those aged ≥65 years. Quebec analysis showed a death rate of 1.2/1,000,000 p.y. in the overall population and 8.6/1,000,000 p.y. in those aged ≥65 years. CONCLUSIONS: The results of the reviewed studies and our analysis of Quebec provincial data indicate important variations in the reported overall incidence rates of medically attended herpes zoster cases in Canada. The trends in time are heterogeneous in studies in which hospitalisations and medical consultations were pooled together. We observed a decrease in hospitalization rates and a slight increase in consultation rates in studies reporting hospitalisations and consultations separately. These results consolidate the understanding of the herpes zoster burden in Canada and might be used as a tool in decision-making regarding future preventive interventions.

Long-term persistence of immunity after vaccination of pre-adolescents with low doses of a recombinant hepatitis B vaccine.

BACKGROUND AND AIMS: Recent studies have shown no detectable antibodies and no response to a challenge dose of vaccine 10-20 y after receiving low doses (2.5-5 µg) of recombinant hepatitis B vaccine during first months of life. Little information is available on long-term persistence of immunity after vaccinating pre-adolescents with low doses of hepatitis B vaccine. RESULTS: The results of 560 subjects were included in this analysis. All subjects had a seroprotective antibody titer (≥10 IU/L) one month post-primary vaccination; 5, 10 and 15 y post-vaccination 95%, 95% and 87% had detectable antibodies, and 82%, 86%, and 68% had a seroprotective antibody titer; GMTs were 73 IU/L, 89 IU/L, and 28 IU/L, respectively. More than 99.4% of subjects had an anamnestic response to a challenge dose of vaccine given 5, 10, or 15 y post-vaccination. Five and ten years post-booster dose 97% and 95% of subjects still have a seroprotective anti-HBs titer with GMTs 16-18-fold higher when compared with those observed 5-10 y post-primary vaccination. MATERIALS AND METHODS: This randomized trial was initiated in 1996 with the main objective to assess the persistence of antibodies and immune memory 5, 10 and 15 y after vaccinating 8-10 y-old children with three doses of Recombivax 2.5 µg, as well as the short and long-term effect of a booster dose given at different intervals. CONCLUSIONS: Virtually all children vaccinated at the age of 8-10 y with low doses of hepatitis B vaccine still have an excellent immune memory up to age of 25 y. The results of this study do not support the use of booster doses.

Antibody persistence and the effect of a booster dose given 5, 10 or 15 years after vaccinating preadolescents with a recombinant hepatitis B vaccine.

The persistence of antibody obtained post-vaccination of preadolescents with three doses of Engerix-B and the effect of a booster administered 5, 10 or 15 years later were monitored in 663 vaccinees. Five, 10 and 15 years post-vaccination >94% of subjects had detectable antibodies and 88.2%, 86.4% and 76.7% had a titre ≥10 IU/L; GMTs were 269 IU/L, 169 IU/L and 51 IU/L, respectively; 99.1-100% vaccinees reached a titre ≥10 IU/l post-booster. GMTs were 118012 IU/L, 32477 IU/L, and 13946 IU/L when the booster was administered 5, 10 or 15 years post-vaccination, respectively. We conclude that vaccination induces immunity in the great majority of vaccinees for at least 15 years. The response to a booster dose suggests persistence of immune memory in almost all vaccinees. Although a booster dose increases substantially anti-HBs titres, the clinical relevance of such an increase remains unknown. These results do not support the need of a booster for at least 15 years when vaccinating preadolescents with Engerix-B.

Antibody and immune memory persistence after vaccination of preadolescents with low doses of recombinant hepatitis B vaccine.

Little is known about the impact of low-dose hepatitis B vaccine on the persistence of anti-HBs and immune memory in school-age children. Recombivax-HB 2.5 µg (RB) has been widely used in school-age children. RB induces high seroprotectionrates, but relatively low anti-HBs titers. The main objectives of this phase of the study were to assess anti-HBs persistence and the presence of immune memory 10 years post-vaccination of 8-10 year-old children with 3 doses of RB and the persistence of anti-HBs post-booster dose administration 5 (Group A; n=250) or 10 years (Group B; n=263) post-vaccination. No significant difference was observed between GMTs and the proportion of subjects with anti-HBs titers ≥ 10 mIU/mL 5 or 10 years post-vaccination. In both groups, a 56-fold decrease of anti-HBs GMTs was observed. One month post-booster, all but two subjects in Group A had an anti-HBs titer ≥ 10 mIU/mL. A 4.9- and 11.4-fold decrease in anti-HBs GMTs were observed during the first year post-booster in Group A and B, respectively. One year post-booster, the two groups were equivalent: ≥ 98.8% of subjects had an anti-HBs ≥ 10 mIU/mL. In group A, five years post-booster, 96.8% had a titer ≥ 10 mIU/mL; the GMT was 17-fold higher than the GMT 5 years post-vaccination (p<0.0001). In both groups, there was a strong positive correlation (p<0.0001) between anti-HBs titers observed post-primary vaccination and at following study time points (r=0.70-0.90). Three doses of RB administered at the age of 8-10 years induce a 10 years long-lasting immunity in virtually all vaccinees. The booster does not appear necessary on a 10 years perspective.

Antibody kinetics among 8-10 years old respondents to hepatitis B vaccination in a low endemic country and the effect of a booster dose given 5 or 10 years later.

Few data are available concerning the persistence of anti-HBs and the effect of booster doses given several years post-vaccination against hepatitis B during preadolescence. The objective of this open-labelled clinical trial was to evaluate the persistence of antibodies after vaccination with three paediatric doses of Engerix-B at the age of 8-10 years and the effect of a booster dose given 5 (Group Y5) or 10 (Group Y10) years later. Anti-HBs were measured before and one month post-primary vaccination, then 5 and 10 years later, before the booster dose, as well as one month and 1 year post-booster. The anamnestic response was defined as a >or=fourfold increase of anti-HBs post-booster (>or=10 IU/L) when compared to pre-booster. Ten years post-primary vaccination, 559 of the 652 initially randomized subjects (86%) were eligible for analysis. Group Y5, 5 years post-booster results: 99% of subjects had detectable levels of antibodies and 96% a titer >or=10 IU/L. The anti-HBs GMTs decreased from 114,489 IU/L one month post-booster to 3354 IU/L 5 years later. Group Y10 results: 10 years post-primary vaccination 96% of subjects had a detectable level of anti-HBs and 85% were above the threshold of 10 IU/L. The GMTs one month post-booster were 31,030 IU/L. The challenge with a booster demonstrated an anamnestic response in 99% of subjects in group Y5 and 100% of subjects in group Y10. All subjects were anti-HBc negative. The booster doses were well tolerated. The excellent anamnestic response observed after the booster dose demonstrates the persistence of immunity in virtually all young adults vaccinated at the age of 8-10 with three paediatric doses of Engerix-B.

Comparative long term immunogenicity of two recombinant hepatitis B vaccines and the effect of a booster dose given after five years in a low endemicity country.

BACKGROUND: Few data are available concerning the long term immunogenicity of the pediatric doses of hepatitis B vaccines given to preteenagers. The long term effect of the booster dose in teenagers is unknown. We evaluated the immunogenicity of 2 pediatric hepatitis vaccines after primary vaccination and after a booster dose. METHODS: A prospective 15-year follow-up study of the immunogenicity of 2 hepatitis B vaccines was initiated in 1995 in Quebec City, Canada. One year apart, 1129 children 8-10 years old received Engerix-B 10 microg (EB), and 1126 received Recombivax-HB 2.5 microg (RB) vaccine after a 0-, 1-, 6-month schedule. After 5 years, one-third of the 2 cohorts were randomly selected. A booster dose of EB 10 microg or RB 5 microg was administered according to the vaccine used in the primary immunization. Antibodies were measured before, 1 month after and 1 year after the booster injection. RESULTS: Before the booster dose, anti-HB surface antibody (HBs) was detected in 94.7% of the EB subjects and in 95.2% of the RB subjects (P = 0.85). The geometric mean titer (GMT) was higher in the EB than in the RB group (252 mIU/mL versus 66 mIU/mL, P < 0.0001). One month after the booster, 99.7% of subjects in the EB group and 99.6% in the RB group had a detectable anti-HBs, and 99.0 and 99.3%, respectively, had anti-HBs > or =10 mIU/mL. The anti-HBs GMT was 113,201 mIU/mL in the EB and 16,623 mIU/mL in the RB groups (P < 0.0001). One year after the booster, 99.3% of subjects in the EB group and 100% in the RB group had detectable anti-HBs, and 97.9 and 98.5% respectively, had anti-HBs > or =10 mIU/mL. The anti-HBs GMT was 14,028 mIU/mL in the EB and 3437 mIU/mL in the RB group (P < 0.0001). CONCLUSIONS: The immunity persists for at least 5 years after the primary vaccination with both pediatric vaccines in 99% of children vaccinated at the age of 8-10 years. It confirms that no booster is needed at that point.

Preadolescent non- and hyporesponders following three doses of hepatitis B vaccine need only one more dose.

A small proportion of healthy children fail to develop antibodies against hepatitis B after three doses of vaccine. Few data are available regarding the optimal re-immunization strategy. We measured the immune response 1 month after a single supplementary dose of recombinant hepatitis B vaccines in 18 young preadolescents who were non- or hyporesponsive after a regular primary course of three doses of recombinant hepatitis B vaccines. Among them, 100% seroconverted and 89% reached the seroprotective titer of 10 milli-International Units (mIU)/ml. Most healthy children, particularly if they are hyporesponders, will have reached the seroprotective level after one dose and will not need further injections.