Coverage determinants of breast cancer screening in Flanders: an evaluation of the past decade.

BACKGROUND: Breast cancer (BC) is the most common cancer in women in the developed world. In order to find developing cancers in an early stage, BC screening is commonly used. In Flanders, screening is performed in and outside an organized breast cancer screening program (BCSP). However, the determinants of BC screening coverage for both screening strategies are yet unknown. OBJECTIVE: To assess the determinants of BC screening coverage in Flanders. METHODS: Reimbursement data were used to attribute a screening status to each woman in the target population for the years 2008-2016. Yearly coverage data were categorized as screening inside or outside BCSP or no screening. Data were clustered by municipality level. A generalized linear equation model was used to assess the determinants of screening type. RESULTS: Over all years and municipalities, the median screening coverage rate inside and outside BCSP was 48.40% (IQR: 41.50-54.40%) and 14.10% (IQR: 9.80-19.80%) respectively. A higher coverage rate outside BSCP was statistically significantly (P < 0.001) associated with more crowded households (OR: 3.797, 95% CI: 3.199-4.508), younger age, higher population densities (OR: 2.528, 95% CI: 2.455-2.606), a lower proportion of unemployed job seekers (OR: 0.641, 95% CI: 0.624-0.658) and lower use of dental care (OR: 0.969, 95% CI: 0.967-0.972). CONCLUSION: Coverage rate of BC screening is not optimal in Flanders. Women with low SES that are characterized by younger age, living in a high population density area, living in crowded households, or having low dental care are less likely to be screened for BC in Flanders. If screened, they are more likely to be screened outside the BCSP.

Regional differences in the validity of self-reported use of health care in Belgium: selection versus reporting bias.

BACKGROUND: The Health Care Module of the European Health Interview Survey (EHIS) is aimed to obtain comparable information on the use of inpatient and ambulatory care in all EU member states. In this study we assessed the validity of self-reported information on the use of health care, collected through this instrument, in the Belgian Health Interview Survey (BHIS), and explored the impact of selection and reporting bias on the validity of regional differences in health care use observed in the BHIS. METHODS: To assess reporting bias, self-reported BHIS 2008 data were linked with register-based data from the Belgian compulsory health insurance (BCHI). The latter were compared with similar estimates from a random sample of the BCHI to investigate the selection bias. Outcome indicators included the prevalence of a contact with a GP, specialist, dentist and a physiotherapist, as well as inpatient and day patient hospitalisation. The validity of the estimates and the regional differences were explored through measures of agreement and logistic regression analyses. RESULTS: Validity of self-reported health care use varies by type of health service and is more affected by reporting than by selection bias. Compared to health insurance estimates, self-reported results underestimate the percentage of people with a specialist contact in the past year (50.5 % versus 65.0 %) and a day patient hospitalisation (7.8 % versus 13.9 %). Inversely, survey results overestimated the percentage of people having visited a dentist in the past year: 58.3 % versus 48.6 %. The best concordance was obtained for an inpatient hospitalisation (kappa 0.75). Survey data overestimate the higher prevalence of a contact with a specialist [OR 1.51 (95 % CI 1.33-1.72) for self-report and 1.08 (95 % CI 1.05-1.15) for register] and underestimate the lower prevalence of a contact with a GP [ORs 0.59 (95 % CI 0.51-0.70) and 0.41 (95 % CI 0.39-0.42) respectively] in Brussels compared to Flanders. CONCLUSION: Cautiousness is needed to interpret self-reported use of health care, especially for ambulatory care. Regional differences in self-reported health care use may be influenced by regional differences in the validity of the self-reported information.

First results of the Flemish colorectal cancer screening program : start-up- period late 2013.

BACKGROUND AND AIMS: Investigation of the first participation rate and follow-up results of the Flemish colorectal cancer screening program. PATIENTS AND METHODS: In 2013 five age cohorts with an even age between 66 and 74 year old (n=243 335) were invited by mail to return a completed iFOBT. Participants who tested positive (≥75ng/ml) were referred to a follow-up colonoscopy. RESULTS: Participation rate was 48.4% (n=117 774). Overall positivity rate was 10.1%, and 78.1% of those tested positive underwent a colonoscopy. The positive predictive value of colonoscopy for CRC was 8.2%, for advanced adenoma 16.9% and for non-advanced adenoma 36.5%. CONCLUSIONS: Based on the EU-guidelines 35% was expected as participation for a first screening round, thus a participation rate of 48.4% is more than acceptable for a first screening year. The high positivity rate can partly be explained by including only the older ages in the start-up-period and by the first year of mass screening in Flanders. (Acta gastroenterol. belg., 2016, 79, 421-428).

Quantifying independent risk factors for failing to rescreen in a breast cancer screening program in Flanders, Belgium.

BACKGROUND: Mammographic screening may reduce breast cancer mortality by about 20%, provided participation is high and women screen regularly. We quantified independent risk factors for failing to rescreen and built a model to predict how rescreening rates change if these risk factors would be modified. METHODS: Multivariate analysis was used to analyze data from a prospective study which included a self-administered questionnaire and rescreening status 30months after a t0 mammogram, using a random sample of women 50-67years (Belgium 2010-2013). RESULTS: A false positive result at the most recent past mammogram (Odds Ratio=5.0, 95% Confidence Interval 3.6-6.8), an interval until new invitation greater than 25months (Odds Ratio=4.8 for >29months, 95% Confidence Interval 2.9-8.1), waiting times in the mammography unit >1h (Odds Ratio=2.1, 95% Confidence Interval 1.2-3.7) and difficulties in reaching the unit (Odds Ratio=2.5, 95% Confidence Interval 1.4-4.4) were the strongest independent predictors for failing to rescreen. The area under the curve of the receiver operating characteristic analysis was 0.705 for the model development stage and 0.717 for the validation stage and goodness-of-fit was good. CONCLUSIONS: Maintaining an invitation cycle of maximum 25months, limiting waiting time in the mammography unit and lowering the number of false positives could increase breast cancer screening compliance.

Epidemiology and outcome of invasive pneumococcal disease among adults in Belgium, 2009-2011.

This epidemiological study examined morbidity and case fatality of invasive pneumococcal disease (IPD) in adults in Belgium as well as distribution and antibiotic susceptibility of Streptococcus pneumoniae serotypes.Adults hospitalised with microbiologically proven IPD were prospectively enrolled. The study started in 2009 with patients aged ≥50 years, whereas in 2010 and 2011, patients aged ≥18 years were included. The clinical presentation, patient profile, treatment, outcome, and mortality were recorded during hospitalisation.Outcome was also assessed one month afterdischarge. Of the 1,875 patients with IPD identified, 1,332 were included in the analysis. Bacteraemic pneumonia, affecting 1,049 of the patients, was the most frequent IPD type (79%), and chronic obstructive pulmonary disease and cancer were the main comorbidities.One-third of patients required admission to intensive care unit. A total of 208 (16%) patients died during hospitalisation and an additional 21 (2%) within one month after discharge. Case fatality rates of ≥20%were observed in patients with chronic heart failure, hepatic disease, and renal insufficiency. Serotypes 7F, 1, 19A, and 3 were the most prevalent and together accounted for 47% (569/1,214) of all IPD cases and 42% (80/189) of mortality. Of the patient isolates, 21% (255/1,204) were resistant to erythromycin and 22% (264/1,204) to tetracycline. Penicillin non-susceptibility was mostly found in serotype 19A isolates. These baseline data are essential when assessing the impact of pneumococcal conjugate vaccination in adults in the future.

Higher proportion of G2P[4] rotaviruses in vaccinated hospitalized cases compared with unvaccinated hospitalized cases, despite high vaccine effectiveness against heterotypic G2P[4] rotaviruses.

The overall vaccine effectiveness of the monovalent rotavirus vaccine in an observational, prospective, multicentre, hospital-based case-control study in Belgium (RotaBel) was 90%. However, rotavirus genotype and co-infecting pathogens are important parameters to take into account when assessing vaccine effectiveness. In this study we specifically investigated the effect of rotavirus genotypes and co-infecting pathogens on vaccine effectiveness of the monovalent vaccine. In addition, we also investigated the effect of co-infecting pathogens on disease severity. From February 2008 to June 2010 stool samples of rotavirus gastroenteritis cases of a random sample of 39 Belgian hospitals were collected and subsequently genotyped. Fisher's exact tests were performed to investigate the relationships between rotavirus genotype, co-infecting pathogens and disease severity. The vaccine effectiveness of a full series of the monovalent rotavirus vaccine against hospitalized rotavirus gastroenteritis caused by G1P[8] rotavirus strains was 95% (95% CI 77.5-98.7). Against G2P[4], the vaccine effectiveness was 85% (95% CI: 63.7-93.8). G4P[8]- and G3P[8]-specific vaccine effectiveness was 90% (95% CI 19.2-98.7) and 87% (95% CI -5.2 to 98.4), respectively. A post-hoc analysis showed that the genotype distribution was significantly related to the vaccination status (p <0.001), whereby G2P[4] strains were proportionally more prevalent in vaccinated cases than in unvaccinated cases. No statistical associations were found between co-infection status and vaccination status, Vesikari severity score or rotavirus genotype. The high vaccine effectiveness against the individual genotypes implies robust protection of the monovalent rotavirus vaccine against hospitalized rotavirus gastroenteritis caused by the major human rotavirus genotypes. The prevalence of G2P[4] requires continued monitoring.

Behavioural and psychosocial correlates of nondipping blood pressure pattern among middle-aged men and women at work.

The underlying pathogenetic mechanisms of nondipping blood pressure (BP) pattern are not completely understood. Especially the role of psychosocial correlates remains unclear. The aim was to assess the association between nondipping BP pattern, behavioural and psychosocial factors in a sample of working men and women. The study sample included 167 working men and women aged 40-64 years from the BELSTRESS cohort. Socio-demographic, behavioural and psychosocial factors were assessed by self-administered questionnaires. Participants were medically examined and underwent an ambulatory BP monitoring during 24 h. Nondipping was defined when the average nocturnal decline in BP was <10%. The prevalence of nondipping for both systolic and diastolic BP was 7.8%. Nondipping was not significantly related to smoking, alcohol consumption and leisure time physical activity. A crude significant association was observed between nondipping and sleep problems. After adjusting for gender, education and body mass index, the risk for nondipping was associated with job strain, living alone, being unsatisfied about the contact with one's children, depressive symptoms and vital exhaustion. Nondipping BP pattern was consistently related to psychosocial factors in this study: positive associations were observed with measures of job strain, poor private life support (living alone and being unsatisfied about the contact with one's children) and mental health problems (depressive symptoms and vital exhaustion).

Antibody persistence and immune memory in adults, 15 years after a three-dose schedule of a combined hepatitis A and B vaccine.

A combined hepatitis A and B vaccine is available since 1996. Two separate open-label primary studies evaluated the immunogenicity and safety of this hepatitis A and B vaccine (720 EI.U of HAV and 20 µg of HBsAg) in 306 healthy subjects aged 17-43 years who received three doses of the vaccine following a 0, 1, and 6 months schedule. These subjects were followed up annually for the next 15 years to evaluate long-term persistence of anti-HAV and anti-HBs antibodies. The subjects whose antibody concentrations fell below the cut-offs between Year 11 and Year 15 (anti-HAV: <15 mIU/ml; anti-HBs: <10 mIU/ml) were offered an additional dose of the appropriate monovalent hepatitis A and/or B vaccine. In subjects who received the additional vaccine dose, a blood sample was collected 1 month after vaccination. At the Year 15 time point, all subjects in Study A and Study B were seropositive for anti-HAV antibodies and 89.3% and 92.9% of subjects in the respective studies had anti-HBs antibody concentrations ≥10 mIU/ml. Four subjects (two in each study) received an additional dose of monovalent hepatitis B vaccine and mounted anamnestic responses to vaccination. No vaccine-related serious adverse events were reported. This study confirms the long-term immunogenicity of the three-dose regimen of the combined hepatitis A and B vaccine, as eliciting long-term persistence of antibodies and immune memory against hepatitis A and B for up to at least 15 years after a primary vaccination.

Has the time come to control hepatitis A globally? Matching prevention to the changing epidemiology.

For the first time a global meeting on hepatitis A virus (HAV) infection as vaccine preventable disease was organized at the end of 2007. More than 200 experts from 46 countries gathered to investigate the changing global HAV epidemiology reflecting the increasing numbers of persons at risk for severe clinical disease and mortality from HAV infection. The benefits of childhood and adult hepatitis A (HepA) vaccination strategies and the data needed by individual countries and international health organizations to assess current HepA prevention strategies were discussed. New approaches in preventing HAV infection including universal HepA vaccination were considered. This introductory paper summarizes the major findings of the meeting and describes the changing epidemiology of HAV infections and the impact of HepA vaccination strategies in various countries. Implementation of HepA vaccination strategies should take into account the level of endemicity, the level of the socio-economic development and sanitation, and the risk of outbreaks. A stepwise strategy for introduction of HepA universal immunisation of children was recommended. This strategy should be based on accurate surveillance of cases and qualitative documentation of outbreaks and their control, secure political support on the basis of high-quality results, and comprehensive cost-effectiveness studies. The recognition of the need for increased global attention towards HepA prevention is an important outcome of this meeting.

Schedules for hepatitis B vaccination of risk groups: balancing immunogenicity and compliance.

INTRODUCTION: Vaccination is an important tool in hepatitis B prevention. However, several vaccine doses are required to induce long-term protection. Several at-risk groups have difficulties in adhering to the standard vaccination schedule. OBJECTIVES: This paper aims to review the use of accelerated hepatitis B vaccination schedules, in terms of immunogenicity and compliance. RESULTS: Accelerated schedules (0.1.2.12 months) or super-accelerated schedules (0.7.21.360 days) have been shown to result in higher proportions of healthy vaccinees reaching anti-HBs antibody levels >or=10 IU/l more rapidly. A fourth completing dose is required to lift antibody levels to an equal height, as does a standard (0.1.6 months) schedule. Accelerated schedules do also increase the uptake of hepatitis B vaccine, that is the proportion of vaccinees who receive three doses. However, completing the schedule with a fourth dose is usually more difficult than completing a standard 0.1.6-month schedule. Several additional tools can help to increase the compliance (eg, reminder systems, outreach services and incentive schemes). CONCLUSION: For rapid seroconversion and almost immediate protection in the short term, a (super)accelerated schedule could be used in at-risk groups. As long-term protection data with these (super) accelerated schedules have not been documented yet, a fourth dose at month 12 is still required. A shortened schedule (0.1.4 months) might be an alternative worth considering compared with the standard 0.1.6, as it convenes to internationally accepted minimum dose intervals and offers earlier protection. There is a clear need to study the long-term protection and effectiveness of the primary part of (super)accelerated schedules.

Ten-year antibody persistence induced by hepatitis A and B vaccine (Twinrix) in adults.

BACKGROUND: Hepatitis A and B infections are prevalent worldwide and cause significant morbidity and mortality. A combined vaccine providing dual protection against hepatitis A and B is available (Twinrix, GlaxoSmithKline Biologicals). METHOD: Two cohorts of adults aged 17-43 years were vaccinated with Twinrix according to a 0, 1, 6 months schedule and followed up for 10 years. RESULTS: One month after the primary vaccination course (Month 7), all subjects were seropositive for anti-HAV and all had anti-HBs> or = 10 mIU/ml. At month 120, 100% of subjects (N=34; N=29) in both cohorts were seropositive for anti-HAV; 94.1% and 86.2% of subjects had anti-HBs > or = 10 mIU/ml. The geometric mean concentrations (GMC; mIU/ml) were 373.9 and 674.6 in the two cohorts for anti-HAV, and 103.8 and 320.0, respectively, for anti-HBs. None of the serious adverse events reported throughout the follow-up period were considered by the investigator to be causally related to vaccination. CONCLUSIONS: Combined hepatitis A and B vaccine, Twinrix, is safe, well-tolerated and has demonstrated a highly immunogenic profile. Persistence of anti-HAV and anti-HBs antibodies in adults remains high for at least 10 years after primary vaccination.

Compliance and immunogenicity of two hepatitis B vaccination schedules in sex workers in Belgium.

OBJECTIVES: To compare the coverage for the third dose and the compliance to two hepatitis B vaccination schedules: 0,1,4 versus 0,1,6 months, in commercial sex workers (CSW) in Belgium; to compare the immunogenicity of the actually administered schedules. METHODS: In seven health centres in Belgium, hepatitis B vaccination was offered free of charge to CSW. In a randomised, prospective study a commercialised hepatitis B vaccine (Engerix-B 20mcgr) was offered according to one of both schedules. After complete vaccination, bleeding was performed to assess immunogenicity. RESULTS: Between June 2003 and September 2004, 615 non-immune CSW were enrolled, of whom 52% in the 0,1,4 month schedule (n=322). Coverage of the third dose was 57% overall, 59% (0,1,4) and 54% (0,1,6), respectively. Age, the health centre and drug use significantly influenced the compliance and the coverage of dose 3, whereas the planned vaccination did not. When comparing the immunogenicity results as a function of the actually administered vaccination schedule, immune responses did not significantly differ between CSW receiving the third dose 4-6 months and those receiving it at least 6 months after the first dose. In total, 19 persons (8%) were not protected after a full vaccination course (anti-HBs <10IU/L). Two health centres measured markedly lower anti-HBs levels. CONCLUSIONS: In this highly mobile at-risk population, a 0,1,4 month schedule is more easy to offer and confers equal protection within a shorter period of time. We therefore propose this 0,1,4 month schedule to vaccinate CSW in the future.

High-dose cefepime as an alternative treatment for infections caused by TEM-24 ESBL-producing Enterobacter aerogenes in severely-ill patients.

This study evaluated retrospectively the efficacy of treatment with cefepime vs. a carbapenem, in combination with amikacin or ciprofloxacin, for seriously-ill patients infected with ESBL-producing Enterobacter aerogenes who were admitted to an intensive care unit. Forty-four episodes of infection were investigated in 43 patients: 21 treated with cefepime; 23 with a carbapenem. The two treatment groups did not differ statistically in terms of age, APACHE II scores, and infection sites, but the average duration of antibiotic exposure was significantly shorter in the cefepime group (8.5 days vs. 11.4 days; p 0.04). Clinical improvement was seen in 62% of patients receiving cefepime vs. 70% of patients receiving a carbapenem (p 0.59). Bacteriological eradication was achieved in 14% of patients receiving cefepime vs. 22% of patients receiving a carbapenem (p 0.76). The 30-day mortality rates related to infection were 33% in the cefepime group and 26% in the carbapenem group (p 0.44). Thus, outcome parameters did not differ significantly between the two groups. Nevertheless, a statistically significant increase in failure to eradicate ESBL-producing E. aerogenes was observed as the MICs of cefepime rose (p 0.017). Pulsed-field gel electrophoresis revealed three distinct clones, but one predominant clone harbouring the bla(TEM-24) gene was associated with most (42/44) of the episodes of infection. It was concluded that cefepime may be an alternative agent for therapy of severe infections caused by TEM-24 ESBL-producing E. aerogenes, although further studies are required to confirm these observations.

Hepatitis A booster vaccination: is there a need?

Hepatitis A is one of the most common vaccine-preventable infectious diseases in the world. Effective vaccines against hepatitis A have been available since 1992, and they provide long-term immunity against the infection. However, there is no worldwide consensus on how long protection will last or whether there will be a need for hepatitis A virus (HAV) booster vaccinations in the future. In most countries, booster-vaccination policy is guided by manufacturers' recommendations, national authorities, or both. In June, 2002, a panel of international experts met to review the long-term immunogenicity and protection conferred by HAV vaccine in different population groups. Data have shown that after a full primary vaccination course, protective antibody amounts persist beyond 10 years in healthy individuals, and underlying immune memory provides protection far beyond the duration of anti-HAV antibodies. The group concluded that there is no evidence to lend support to HAV booster vaccination after a full primary vaccination course in a healthy individual. However, further investigations are needed before deciding if boosters can be omitted in special patient-groups.

Long-term persistence of antibodies induced by vaccination and safety follow-up, with the first combined vaccine against hepatitis A and B in children and adults.

It is important to monitor the long-term persistence of antibodies induced by vaccination. Four cohorts were followed for their long-term immunity after vaccination with a combined hepatitis A and B vaccine (Twinrix; SmithKline Beecham Biologicals, Rixsenart, Belgium). Two cohorts of adults (ages 17-60 years), one of 1-6-year-olds, and one of 6-15-year-olds were vaccinated following a 0, 1, and 6-month schedule. Follow-up data until month 72 (adults) and month 60 (children) are available. At month 72, antibody to hepatitis A virus (anti-HAV) seropositivity (S+) was 100% for both adult cohorts (n = 40 and n = 47) and 95% and 89% of the vaccinees were seroprotected against hepatitis B virus (HBV), respectively. The geometric mean titres (GMTs; mIU/ml) for anti-HAV were 977 and 542 and the GMTs for the antibody to hepatitis B surface antigen (anti-HBs) were 322 and 90. For 1-6-year-olds at month 60 (n = 39), anti-HAV S+ was 100% with a GMT of 479 and 97% were protected against HBV with a GMT of 195. At month 60 for the 6-15-year-olds (n = 42), anti-HAV S+ was 100% with a GMT of 990 and 95% were protected against HBV with a GMT of 263. There have been no safety issues during the follow-up. In the past 5 years, a postmarketing surveillance system was available. Using this system, all spontaneous adverse events are collected and archived. Although infrequent, the most commonly reported adverse events after more than 13 million doses were allergic-type reactions followed by fever and injection site reactions. The combined hepatitis A and B vaccine is safe and is well tolerated. Immunity provided by the vaccine remains high in adults and children with comparable results to those obtained with monovalent vaccines.

Inactivated hepatitis A vaccine-induced antibodies: follow-up and estimates of long-term persistence.

To estimate the long-term persistence of anti-HAV antibodies, 120 (schedule 0-6) and 194 (schedule 0-12) adults were vaccinated and followed-up annually for 6 years. Shortly after the last dose, anti-HAV levels fell sharply (annual decline rate delta > 65%). Thereafter, delta diminished to 10-15%. GMTs 5.5 years after the last dose were 522 mIU/ml (0-6 group) and 749 mIU/ml (0-12 group); all subjects except one maintained detectable antibodies. The average delta over the whole follow-up period was 15-20%, resulting in an estimated persistence of anti-HAV levels > or =20 mIU/ml for 20-25 years. These estimates were similar for both applied calculation methods (GMT or individual based) and both vaccination schedules. Because the individual antibody levels tended to stabilise between the last two measurements, the hypothesis of a slow, log-linear decrease and its matching calculation methods might be subject to reconsideration. With the current methodology, however, detectable antibodies are estimated to persist for 20-25 years.

Mathematical models for assessment of long-term persistence of antibodies after vaccination with two inactivated hepatitis A vaccines.

Very few studies with inactivated hepatitis A vaccines were designed for long-term follow-up of antibody persistence. Based on the serological data from these vaccine trials, mathematical models were developed to predict the decrease of anti-hepatitis A virus (anti-HAV) antibodies after vaccination. This study was designed to compare Avaxim (0-6 months) to Havrix 720 (0-1-6 months). In this paper, both groups of vaccinees are described considering the age, gender, and weight of the subjects at enrollment. For mathematical modelling, two different approaches were used: one starting the calculations from the geometric mean titres (GMTs) at each point in time, the other basing the calculations on individual anti-HAV titres. Both vaccines are very immunogenic, although Avaxim shows a higher GMT at each point in time. When these data are used in mathematical models to predict the persistence of anti-HAV antibodies, both vaccines (Avaxim and Havrix 720) show similar long-term antibody kinetics. Antibody levels > or = 20 mIU/ml are estimated to last on average for at least 10 years after completion of the full vaccination course. Ten years after the full course, approximately 53% of subjects are estimated to have antibody levels > or = 20 mIU/ml. At 15 years, these levels will be maintained by about 34% of vaccinees. Avaxim and Havrix 720 show a similar long-term profile of persistence of anti-HAV. A mathematical model based on GMTs appeared to give equivalent results to a model based on individual serological data. The GMT method is easier to apply than the individual based method. However, the advantage of the latter method is the possibility of calculating confidence limits for the predicted values and making estimates of the percentage of subjects having a certain level of antibody titres at a certain time.

Two-dose combined vaccination against hepatitis A and B in healthy subjects aged 11-18 years.

BACKGROUND: In this open, randomized trial the safety, reactogenicity, and immunogenicity profile of a high-dose combined hepatitis A and B candidate vaccine was compared with that of Twinrix Paediatric in healthy volunteers aged 11-18 years. METHODS: One hundred subjects were randomly allocated to either of two groups. One group received the high-dose vaccine (720 E1.U HAV antigen; 20 microg hepatitis B surface antigen (HBsAg) at months 0 and 6; the second group received Twinrix Paediatric (360 E1.U HAV antigen; 10 microg HBsAg), following a 0-1-6-month schedule. RESULTS: Injection site soreness and fatigue were the most frequently reported solicited symptoms. For hepatitis A all subjects had seroconverted at month 7, and geometric mean titres (GMT) were 8,151 mIU/ml in the high-dose group and 6,394 mIU/ml in the Twinrix Paediatric group. For hepatitis B the GMT for the Twinrix Paediatric group was significantly higher at month 2 and month 6. However, no difference in GMT between groups could be established at month 7. The seroprotection rate attained 100% in both groups, and GMT were 4,212 mIU/ml (high-dose group) and 6,330 mIU/ml (Twinrix Paediatric). CONCLUSIONS: The two vaccines showed similar safety and reactogenicity profiles. After completion of the vaccination schedule, no difference in immunogenicity was shown. This high-dose vaccine, administered following a two-dose schedule, can be considered an alternative regimen for the immunization of healthy adolescents against hepatitis A and hepatitis B infections, in a setting where vaccinees are not immediately at risk of exposure to hepatitis B.