Tinne Lernout

Pediatric Pneumococcal Serotypes in 4 European Countries

After heptavalent pneumococcal conjugate vaccine (PCV7) was marketed in France, Spain, Belgium, and England and Wales (United Kingdom), invasive disease from non-PCV7 serotypes (NVT) increased. Adjusted serotype-specific incidences among children <15 years of age were compared between 1999-2002 (prevaccine) and 2005-2006 (postmarketing). Vaccine coverage increased to approximately 32%-48% in France, Spain, and Belgium but remained <1% in England and Wales. Serotype 1 incidence rose in all age groups and countries (incidence rate ratio [IRR] 1.3-4.2; p<0.004), independently of PCV7 use, but incidence of serotypes 7F and 19A increased most in France, Spain, and Belgium (IRR 1.9-16.9 in children <5 years; p<0.001), where PCV7 coverage was greater. Vaccine-induced replacement of PCV7 serotypes possibly contributed to NVT increases, as did secular trends. New vaccines targeting these serotypes are available, but serotype dynamics needs further exploration that accounts for underreporting and prevaccine trends.

Impact of conjugate 7-valent vaccination in Belgium: Addressing methodological challenges

In Belgium, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the national schedule in 2007. The early impact of PCV7 vaccination on paediatric invasive disease was estimated by comparing pre- and post-vaccination incidence from national surveillance. In children <2 year-olds, vaccine-serotype incidence declined by 96% but non-vaccine-types increased 2-3-fold. Overall invasive disease decreased by 23-46%, depending on adjustment for under-reporting and pre-vaccine trends. Non-vaccine-types 1 and 19A had increased before PCV7 use, suggesting the contribution of other factors. Estimation of PCV7 impact comparing pre- and post-vaccination data should adjust for pre-vaccine trends, and serotype dynamics need further exploration.

Timeliness of infant vaccination and factors related with delay in Flanders, Belgium

Achieving high vaccination coverage is a necessary, but not a sufficient indicator of the quality of a vaccination programme, in terms of control and prevention of childhood infectious diseases. For optimal protection of infants, timeliness of vaccination is increasingly recognized as another important target. The aim of this study was to assess the timeliness of measles-mumps-rubella (MMR) and diphtheria-tetanus-pertussis (DTP) vaccination in infants in Flanders (Belgium), and to identify predictors of vaccination delay. The timeliness was assessed using the Kaplan-Meier estimator in three consecutive vaccination coverage surveys among children aged 18-24 months, conducted in 2005, 2008 and 2012, respectively. Factors associated with delayed administration of the vaccines were identified using Cox regression analysis. Over the time period, vaccination coverage for the first dose of MMR ranged from 94.0 to 96.6% and for the third dose of DTP from 97.9 to 98.7%. However, up to 32% (for MMR1) and 95% (for DTP3) of infants received vaccine doses delayed according to the recommended schedule. Although some improvement was achieved over the last decade, further efforts are needed to reach risk groups with delays, more specifically children vaccinated outside the baby well clinics, born from a mother originating from outside the European Union, children with a higher ranking or in families with a lower income.

Rotavirus vaccination coverage and adherence to recommended age among infants in Flanders (Belgium) in 2012

In Belgium, rotavirus vaccination has been recommended and partially reimbursed since October 2006. Through a retrospective survey in 2012, we estimated the coverage rate of the rotavirus vaccination in Flanders among infants born in 2010. Using a standardised questionnaire, 874 families were interviewed at home, collecting information on demographic characteristics, socio-economic background and documented vaccination history (updated from medical files and vaccination database, if needed). Adherence to the recommended age for vaccination (8, 12 and 16 weeks) was also assessed. The coverage rate for two doses of rotavirus vaccination was 92.2% (95% confidence interval: 90.2-93.8). Respectively 31.7% and 10.1% of the children received their first and second dose at the recommended age. Incomplete vaccination was often a deliberate choice of the parents. Only eight children (1%) were vaccinated after the maximum age of 26 weeks. Factors identified by multiple logistic regression as related to incomplete vaccination were: living in the province of Antwerp, unemployed mother, and three or more older siblings in the household. Four years after introduction, the coverage rates were surprisingly high for a vaccine that is not fully reimbursed and not readily available in the vaccinators fridge, which is the case for the other recommended infant vaccines.

Incentives and barriers regarding immunization against influenza and hepatitis of health care workers.

A meeting of the Viral Hepatitis Prevention Board in Barcelona in November 2012 brought together health care professionals concerned with viral hepatitis and those concerned with other vaccine-preventable diseases (especially influenza) in order to share experiences and find ways to increase the protection of health care workers through vaccination. Despite the existence of numerous intergovernmental and national resolutions, recommendations or published guidelines, vaccine uptake rates in health care workers are often shockingly low and campaigns to increase those rates have been generally unsuccessful. Participants reviewed the numerous incentives and barriers to vaccine uptake. Reasons for low uptake range from lack of commitment by senior management of health facilities and unclear policies to lack of knowledge, and denial of risk. Positive factors included leadership, involvement of all concerned parties, reminders and peer pressure. Innovative approaches, including the use of social media, are needed. It was concluded that strategies should be modified appropriately to reach specific health care worker populations at risk and that policies for preventing infection of health care workers could include obligatory health checks to determine vaccination status or immunity. Further, mandatory vaccination of health care workers may be the only effective means in order to achieve high vaccination coverage rates. Suggested possible future activities included: refurbishment of the image of the occupation health profession; resolving the logistical problems of administering vaccine; elaborating policy on managing health care workers who have been vaccinated against hepatitis B at birth or in early childhood and who are now starting to work in the health professions; and embedding and applying policies on vaccination against vaccine-preventable diseases in all health care facilities and training institutions. Above all, national action plans need to be written, with the involvement of health care workers in their design and implementation.

Assessing the risk of measles resurgence in a highly vaccinated population: Belgium anno 2013

Despite long-standing two-dose measles-mumps-rubella (MMR) vaccination, measles outbreaks still occur in highly vaccinated European populations. For instance, large measles outbreaks occurred in France (2008–13), the United Kingdom (2012–13) and the Netherlands (2012). Based on a multicohort model approach, using spatial serological survey data, MMR vaccination coverage data and data on social contacts, we found effective reproduction numbers significantly higher than 1 for measles in Belgium. This indicates that at one of the expected re-introductions, a measles outbreak is likely to spread, especially when it occurs during school term. The predicted average effective reproduction number increased over a 30-year time span from 1.3 to 2.2 and from 1.9 to 3.2 for basic reproduction numbers of 12 and 18, respectively. The expected relative measles incidence was highest in infants under one year of age, in adolescents and young adults. In conclusion, gradually increasing proportions of susceptible adolescents and young adults provide through their highly active social life an avenue for measles to resurge in large outbreaks upon re-introduction in Belgium, especially during school terms. Infants form an important vulnerable group during future measles outbreaks.

Assessing vaccination coverage in infants, survey studies versus the Flemish immunisation register: achieving the best of both worlds

Infant immunisation coverage in Flanders, Belgium, is monitored through repeated coverage surveys. With the increased use of Vaccinnet, the web-based ordering system for vaccines in Flanders set up in 2004 and linked to an immunisation register, this database could become an alternative to quickly estimate vaccination coverage. To evaluate its current accuracy, coverage estimates generated from Vaccinnet alone were compared with estimates from the most recent survey (2012) that combined interview data with data from Vaccinnet and medical files. Coverage rates from registrations in Vaccinnet were systematically lower than the corresponding estimates obtained through the survey (mean difference 7.7%). This difference increased by dose number for vaccines that require multiple doses. Differences in administration date between the two sources were observed for 3.8-8.2% of registered doses. Underparticipation in Vaccinnet thus significantly impacts on the register-based immunisation coverage estimates, amplified by underregistration of administered doses among vaccinators using Vaccinnet. Therefore, survey studies, despite being labour-intensive and expensive, currently provide more complete and reliable results than register-based estimates alone in Flanders. However, further improvement of Vaccinnets completeness will likely allow more accurate estimates in the nearby future.

A cohesive European policy for hepatitis B vaccination, are we there yet?

Despite the availability of safe and effective hepatitis B virus (HBV) vaccines for more than 30 years, the burden of hepatitis B disease is still substantial. In 1992, the WHO recommended the inclusion of HBV vaccination in all national vaccination programmes. As of 2012, 47 of the 53 European countries (89%) had implemented a universal hepatitis B vaccination programme. The most recent countries to follow the recommendation were Ireland (in 2008) and the Netherlands (in 2011). Still, six countries (Denmark, Finland, Iceland, Norway, Sweden and the UK) adopt risk-group-targeted vaccination only, instead of adding a universal vaccination programme. However, changing demography, increasing immigration and the current vaccine costs make the cost–benefit ratios in these remaining low endemicity countries strongly in favour of universal HBV vaccination. Global efforts, including a cohesive European vaccination policy, are essential to control and prevent hepatitis B.

Prevalence of HBV and HCV among outpatients in the plovdiv region of Bulgaria, 2010–2011

Viral hepatitis, particularly hepatitis B and C, are diseases with worldwide distribution that present a significant public health problem. Seroprevalence studies allow assessment of the extent of the disease burden, the identification of populations at risk and the monitoring trends over time. A multi‐center seroprevalence study, carried out in Bulgaria (covering the five largest cities – Sofia, Plovdiv, Varna, Pleven, and Stara Zagora) in 1999–2000 estimated a crude seroprevalence rate of 3.9% for HBsAg and 1.3% for anti‐HCV. A decade later, comparable rates were observed in a study including 865 outpatients consulting a clinical laboratory in Plovdiv, the second largest administrative region in Bulgaria. The crude seroprevalence rate measured for hepatitis B (HBsAg) was 3.9%. The HBsAg prevalence rate in individuals ≤19 years of age (targeted by vaccination) was significantly lower compared to the rate in adults ≥20 years of age –1% versus 4.8%. The lack of dynamics in the overall level of HBsAg carriers is likely related to the excessively low hepatitis B vaccine coverage in individuals, born before the introduction of the universal vaccination of newborns in August 1991. Anti‐HCV antibodies were detected in 0.7% of the subjects. J. Med. Virol. 87:401–406, 2015.

Prevalence of rotavirus antibodies in breast milk and inhibitory effects to rotavirus vaccines

Rotavirus (RV) is the most common cause of childhood diarrhea worldwide, and several vaccines have been successfully developed to reduce the burden of disease. However, lower vaccine immunogenicity and efficacy in developing countries might be related to the virus-neutralizing activity of breast milk. We examined possible differences in breast milk antibody levels (total IgA antibody, RV-specific antibodies, and RV-neutralizing antibodies) between healthy mothers living in a rural area (n = 145) and mothers living in an urban area (n = 147) of Vietnam. Total IgA concentration was significantly higher in samples from mothers in the rural region than in samples from mothers in the urban region, whereas urban mothers had significantly higher RV-specific IgA antibody titers than did rural mothers. Neutralizing antibodies against RV strain G1P[8] were undetected in nearly one-half of the breast milk samples (45–48%), whereas the majority of the remaining samples had low antibody titers (2–16). Despite these low titers, the breast milk still reduced vaccine strain titers (2 × 106 plaque forming units/mL) up to 80% or more, even at a milk-to-virus ratio of 1:8. An increase in neutralizing anti-G1P[8] antibody titers (P < 0.05) in rural infants over time suggests a continuous exposure to circulating RV. These results contribute to the understanding of the potential interference of breast milk with RV vaccine efficacy and immunogenicity in Vietnamese infants.