K. van Herck

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

Summary.  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.

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 ≥ 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 ≥ 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. J. Med. Virol. 60:1–7, 2000.

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 ⩾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.

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. Fishers 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.

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.

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.

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. J. Med. Virol. 84:11–17, 2011.

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 ones 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 ones children) and mental health problems (depressive symptoms and vital exhaustion).

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.

Chronic hepatitis and other liver disease

PART 1 - THE SCOPE OF PUBLIC HEALTH 1. The development of the discipline of public health 2. Determinants of health and disease 3. Public health policies 4. Law, ethics, and challenges PART 2 - THE METHODS OF PUBLIC HEALTH 5. Information systems and sources of intelligence 6. Epidemiologic and biostatistical approaches 7. Social Science techniques 8. Environmental and occupational health sciences PART 3 - THE PRACTICE OF PUBLIC HEALTH 9. Major health problems 10. Prevention and control of public health hazards 11. Intervention for special populations 12. Public health functions