Heidi Theeten

Cytomegalovirus-associated accumulation of late-differentiated CD4 T-cells correlates with poor humoral response to influenza vaccination

Influenza vaccination is less effective in the elderly compared to the young. Studies that have attempted to identify immune parameters correlating with satisfactory vaccine responses have yielded inconclusive results. Here, we correlate the distribution of different circulating CD4+ and CD8+ T-cell phenotypes with the humoral response to vaccination with Intanza, an intradermal seasonal vaccine, in 54 individuals of different ages. Subjects were stratified according to age (below or over 60) and presence of a latent infection with Cytomegalovirus (CMV). CMV-seropositivity was significantly associated with a lower response rate to the vaccine in people over but not below 60 yr of age. Unlike reported data, late-differentiated (CD45RA+CCR7-CD27-CD28-) CD4+, but not CD8+ T-cells associated with a poorer vaccine response. Thus, latent CMV infection has a deleterious effect on influenza antibody responses in the elderly, which might be mediated through CD4 T-cells lacking CCR7, CD27 and CD28 and re-expressing CD45RA.

Comparison of rubella seroepidemiology in 17 countries: progress towards international disease control targets

OBJECTIVE To standardize serological surveillance to compare rubella susceptibility in Australia and 16 European countries, and measure progress towards international disease-control targets. METHODS Between 1996 and 2004, representative serum banks were established in 17 countries by collecting residual sera or community sampling. Serum banks were tested in each country and assay results were standardized. With a questionnaire, we collected information on current and past rubella vaccination programmes in each country. The percentage of seronegative (< 4 IU/ml) children (2-14 years of age) was used to evaluate rubella susceptibility, and countries were classified by seronegativity as group I (< 5%), group II (5-10%) or group III (> 10%). The proportion of women of childbearing age without rubella protection (< or = 10 IU/ml) was calculated and compared with WHO targets of < 5%. FINDINGS Only Romania had no rubella immunization programme at the time of the survey; the remaining countries had a two-dose childhood schedule using the measles, mumps and rubella (MMR) vaccine. The percentage of susceptible children defined five countries as group I, seven as group II and four as group III. Women of childbearing age without rubella protection were < 5% in only five countries. CONCLUSION Despite the low reported incidence in many countries, strengthening the coverage of the routine two-dose of MMR vaccine among children is needed, especially in group III countries. Catch-up campaigns in older age groups and selective targeting of older females are needed in many countries to ensure necessary levels of protective immunity among women of childbearing age.

Towards elimination : measles susceptibility in Australia and 17 European countries

OBJECTIVE To evaluate age-specific measles susceptibility in Australia and 17 European countries. METHODS As part of the European Sero-Epidemiology Network 2 (ESEN2), 18 countries collected large national serum banks between 1996 and 2004. These banks were tested for measles IgG and the results converted to a common unitage to enable valid intercountry comparisons. Historical vaccination and disease incidence data were also collected. Age-stratified population susceptibility levels were compared to WHO European Region targets for measles elimination of < 15% in those aged 2-4 years, < 10% in 5-9-year-olds and < 5% in older age groups. FINDINGS Seven countries (Czech Republic, Hungary, Luxembourg, Spain, Slovakia, Slovenia and Sweden) met or came very close to the elimination targets. Four countries (Australia, Israel, Lithuania and Malta) had susceptibility levels above WHO targets in some older age groups indicating possible gaps in protection. Seven countries (Belgium, Bulgaria, Cyprus, England and Wales, Ireland, Latvia and Romania) were deemed to be at risk of epidemics as a result of high susceptibility in children and also, in some cases, adults. CONCLUSION Although all countries now implement a two-dose measles vaccination schedule, if the WHO European Region target of measles elimination by 2010 is to be achieved higher routine coverage as well as vaccination campaigns in some older age cohorts are needed in some countries. Without these improvements, continued measles transmission and outbreaks are expected in Europe.

Vaccination coverage in 14-year-old adolescents: documentation, timeliness, and sociodemographic determinants.

OBJECTIVE. The objective of this study was to measure the coverage and influencing determinants of hepatitis B virus, measles-mumps-rubella, and Meningococcus serogroup C vaccination in 14-year-old adolescents in Flanders, Belgium, in 2005. METHODS. A total of 1500 adolescents who were born in 1991 and were living in Flanders were selected with a 2-stage cluster sampling technique. Home visits to copy vaccination documents and complete a questionnaire on sociodemographic and other related factors were conducted by trained interviewers. Only documented vaccination dates were accepted. Missing data were, when possible, retrieved through medical charts of the School Health System. RESULTS. For 1344 (89.6%) adolescents, a home visit was performed. Vaccination coverage was 75.7% for the third dose of hepatitis B virus, 80.6% for the first dose and 83.6% for the second dose of measles-mumps-rubella, and 79.8% for Meningococcus serogroup C. Only 74.6% of the adolescents had proof of 2 measles-mumps-rubella vaccines. Although 1006 (74.8%) adolescents had vaccination data available at home at the time of the interview, only 427 (31.8%) were able to show written proof of all studied vaccines. The probably underestimated coverage rates are well below World Health Organization recommendations, but timeliness of vaccinations was respected. Univariate logistic regression showed that unemployment of the father as proxy measure of socioeconomic status was detrimental for vaccination status, in contrast to partial employment of the mother, which was a favorable factor. Previously unreported determinants of lower coverage rates inferred from this study are single divorced parents, larger families (≥4 children), lower adolescent educational level, enrollment in special education, and repeating a grade. CONCLUSIONS. Insufficient documentation is a major barrier in this vaccination coverage study. More attention should go to those with the lowest coverage rates, such as adolescents from large families, with separated parents, and with a lower socioeconomic background.

A comparison of hepatitis B seroepidemiology in ten European countries

To inform current and future vaccination strategies, we describe the seroepidemiology of hepatitis B virus (HBV) infection in ten representative European countries using standardized serology that allowed international comparisons. Between 1996 and 2003, national serum banks were compiled by collecting residual sera or by community sampling; sera were then tested by each country using its preferred enzyme immunoassays and testing algorithm, and assay results were standardized. Information on current and past HBV vaccination programmes in each country was also collected. Of the ten countries, six reported low levels (<3%) of antibodies against HBV core antigen (anti-HBc). Of the eight countries testing for HBV surface antigen (HBsAg), the highest prevalence was reported in Romania (5.6%) and in the remaining seven countries prevalence was <1%. Universal HBV vaccination programmes had been established in seven countries as recommended by the World Health Organization, but the seroprevalence of antibodies against HBsAg (anti-HBs) was lower than the reported vaccine coverage in three countries. Regular serological surveys to ascertain HBV status within a population, such as reported here, provide important data to assess the need for and to evaluate universal HBV vaccination programmes.

Seroepidemiology of mumps in Europe (1996–2008): why do outbreaks occur in highly vaccinated populations?

Mumps outbreaks have recently been recorded in a number of highly vaccinated populations. We related seroprevalence, epidemiological and vaccination data from 18 European countries participating in The European Sero-Epidemiology Network (ESEN) to their risk of mumps outbreaks in order to inform vaccination strategies. Samples from national population serum banks were collected, tested for mumps IgG antibodies and standardized for international comparisons. A comparative analysis between countries was undertaken using age-specific mumps seroprevalence data and information on reported mumps incidence, vaccine strains, vaccination programmes and vaccine coverage 5-12 years after sera collection. Mean geometric mumps antibody titres were lower in mumps outbreak countries [odds ratio (OR) 0·09, 95% confidence interval (CI) 0·01-0·71)]. MMR1 vaccine coverage ⩾95% remained protective in a multivariable model (P < 0·001), as did an interval of 4-8 years between doses (OR 0·08, 95% CI 0·01-0·85). Preventing outbreaks and controlling mumps probably requires several elements, including high-coverage vaccination programmes with MMR vaccine with 4-8 years between doses.

Are we hitting immunity targets? The 2006 age-specific seroprevalence of measles, mumps, rubella, diphtheria and tetanus in Belgium

Susceptibility to vaccine-preventable diseases in Belgium in 2006 was estimated from a serum survey. Immunoglobulins against measles, mumps, rubella (MMR) and diphtheria at all available ages (1-65 years), and against tetanus in >40-year-olds, were measured by ELISA. Age-standardized overall seronegativity for MMR was low (3·9%, 8·0%, 10·4%, respectively). However, the World Health Organizations targets for measles elimination were not met in 5- to 24-year-olds and about 1 in 7 women at childbearing age (15-39 years) were seronegative for rubella. In adults >40 years, tetanus immunity (87·2%, >0·16 IU/ml) largely exceeded diphtheria immunity (20-45%, >0·1 IU/ml). Despite free universal vaccination against MMR for more than 20 years and against diphtheria and tetanus for almost 60 years, our study revealed specific age groups remaining at risk for infection with these pathogens.

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.

Like mother, like daughter? Mother's history of cervical cancer screening and daughter's Human Papillomavirus vaccine uptake in Flanders (Belgium)

OBJECTIVE We investigated whether and to what extent the uptake of the Human Papillomavirus (HPV) vaccine by girls aged 12-18 was related to the cervical cancer screening history of age-appropriate older female household members (assumed to be their mothers) in Flanders (Belgium). METHODS We studied administrative records on 127,854 female members of the National Alliance of Christian Mutualities, which is the largest health insurance fund in Flanders. Reimbursement data for HPV vaccination of girls for the period 2007-2009 were linked with reimbursement data for cervical cancer screening of their mothers in the three preceding years. A multilevel logit model was used to study associations between both preventive behaviors. In the model we controlled for both the girls and the mothers age, the province of residence and the socio-economic background of the family. RESULTS A clear association between a mothers history of participation in cervical cancer screening and her daughters HPV vaccination initiation was found. The conditional odds of HPV vaccination initiation were more than 4 times higher for girls whose mother had one Pap test than for girls whose mother had none (odds ratio [OR]=4.5; 95% confidence interval [CI]=3.5-5.9). For girls whose mother had three or more Pap tests, the conditional odds were 16 times higher than for girls whose mother did not have any pap tests ([OR]=16.0; 95% [CI]=12.1-21.2). The effect of screening (having received 1 pap smear as compared to none) was larger for girls living in neighborhoods with the lowest median income ([OR]=6.0, 95% [CI]=3.6-10.1). CONCLUSION In a situation where both cervical cancer screening and HPV vaccination are opportunistic, we found evidence that these preventive behaviors cluster within families.

Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines

ABSTRACT Objective: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa‑IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults ≥ 40 years of age without diphtheria or tetanus vaccination for 20 years or with an unknown vaccination history. Research design and methods: Double-blind, randomized, controlled clinical trial. Primary vaccination with either three doses of dTpa, one dose of dTpa‑IPV followed by two doses of Td, or three doses of Td vaccine (control) administered in a 0‑1‑6-month schedule. Main outcome measures: Blood samples were collected before commencement and 1 month after each dose. Local and general symptoms were solicited for 15 days after each dose. Results: A total of 460 adults were enrolled, of whom over 48% did not have protective antibody concentrations against diphtheria and tetanus. One month after dose 3 > 99% had seroprotective anti-diphtheria and tetanus antibodies. Three doses were required to maximize anti-diphtheria seroprotection rates. A vaccine response to pertussis antigens was observed in > 92% of dTpa and dTpa‑IPV recipients after dose 1. One month after dTpa‑IPV, > 98.4% had seroprotective anti-polio titres. No statistically significant differences in local or general symptoms between groups were observed. Conclusions: dTpa and dTpa‑IPV can provide primary vaccination of adults. Combinations of dTpa or dTpa‑IPV can be used to replace Td and provide booster vaccination against pertussis and polio simultaneously with diphtheria and tetanus, even in situations where the primary vaccination history is unknown.