TBE Vaccination Breakthrough Cases-Does Age Matter?

Tick-borne encephalitis (TBE) vaccines are highly effective in preventing TBE and vaccine failures (VF) are rare events. In this study, we compared the age distribution of TBE cases and TBE VF in three endemic countries: Sweden, Southern Germany, and Latvia. While the age distribution of TBE cases was similar for those <50 years versus those ≥50 years in all three countries, in Sweden, a higher proportion of VF cases was ≥50 years, whereas most VF cases in Latvia were <50 years of age and more evenly distributed between those <50 years versus those ≥50 in Southern Germany. Here, theoretical explanations were provided, including differences in diagnostic practices, vaccine uptake between age groups, behavioral patterns and underlying medical conditions, as to why VF were generally older in Sweden than the other countries. There is no scientific rationale to give an extra priming dose of TBE vaccine to subjects ≥50 years of age.

How to optimise the coverage rate of infant and adult immunisations in Europe.

BACKGROUND: Although vaccination has been proved to be a safe, efficacious, and cost-effective intervention, immunisation rates remain suboptimal in many European countries, resulting in poor control of many vaccine-preventable diseases. DISCUSSION: The Summit of Independent European Vaccination Experts focused on the perception of vaccines and vaccination by the general public and healthcare professionals and discussed ways to improve vaccine uptake in Europe. Despite the substantial impact and importance of the media, healthcare professionals were identified as the main advocates for vaccination and the most important source of information about vaccines for the general public. Healthcare professionals should receive more support for their own education on vaccinology, have rapid access to up-to-date information on vaccines, and have easy access to consultation with experts regarding vaccination-related problems. Vaccine information systems should be set up to facilitate promotion of vaccination. SUMMARY: Every opportunity to administer vaccines should be used, and active reminder systems should be set up. A European vaccine awareness week should be established.

Human toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy.

Toll-like receptor 4 (TLR4) is required for efficient recognition of bacterial infections. We investigated an association between 2 TLR4 mutations (Asp(299)Gly and Thr(399)Ile) and meningococcal disease in 197 patients and 214 healthy controls by allele-specific real time polymerase chain reaction and direct sequencing. Although the allele frequency was not higher in the overall patient population, a significantly higher frequency in the 40 patients younger than 12 months of age (P = 0.007) was observed. We conclude that TLR4 mutations represent a risk factor for meningococcal disease in this age group.

Child vaccination policies in Europe: a report from the Summits of Independent European Vaccination Experts.

Despite the proven safety and efficacy of vaccines, common vaccine-preventable diseases such as measles are not yet controlled in all European countries. This is largely due to three factors. First, vaccination systems differ widely throughout Europe and they vary between highly centralised and totally decentralised systems. Both have advantages and disadvantages, but without doubt they can all work locally. "Harmonisation" in this field is neither a prerequisite nor a guarantee for success. Second, perception of vaccination--and this includes education of the public--is most crucial. In this field the media play an important part, but their ability or will to communicate complicated scientific matters in an appropriate way to the public is often insufficient. Third, political will may be the single most important factor for success in vaccination. Only if the European Union comes up with and implements common vaccination goals with firm deadlines can the best health through vaccination of all Europeans be accomplished. The system as well as the schedule used would then be of minor importance.

Prediction of the potential benefit of different pneumococcal conjugate vaccines on invasive pneumococcal disease in German children.

BACKGROUND: In the US a pneumococcal conjugate vaccination program with a 7-valent conjugate vaccine was successfully implemented in 2000. How much invasive pneumococcal disease can potentially be prevented by the 7-valent (or 11-valent) vaccine in Europe? METHODS: Prospective, active surveillance of invasive pneumococcal disease in German children age <16 years was performed between 1997 and 2000. Age- and disease-specific coverage and incidence rates were assessed in children old enough to benefit from complete vaccination to estimate the annual number of cases potentially preventable. RESULTS: A total of 1,743 cases were reported; 667 isolates were serotyped. Coverage of 7-valent (11-valent) conjugate vaccines in children age 6 months and older was age- and diagnosis-dependent, ranging from 10.5% (15.8%) to 78.3% (82.6%) for meningitis and from 13.6% (68.2%) to 75.0% (89.3%) for nonmeningitis invasive pneumococcal disease cases. Of an estimated annual number of 176 children with pneumococcal meningitis age 6 months or older, 112 (122) cases had serotypes included in the 7-valent (11-valent) conjugate vaccine compared with 181 (254) of 324 nonmeningitis invasive pneumococcal disease cases, with 37 of the 73 cases covered by the 11-valent vaccine only in children older than 5 years. Regarding meningitis in this age group the potential benefit was equally poor for both the 7-valent (12 of 37 cases) and the 11-valent vaccine (15 of 37 cases). CONCLUSION: Coverage of the 7- and 11-valent conjugate vaccines depends markedly on age and disease. The additional potential benefit of the 11-valent compared with the 7-valent vaccine for pneumococcal meningitis was marginal.

Tolerability of the Biken acellular pertussis vaccine in adults with or without previous vaccination against pertussis in childhood.

PURPOSE: The objective of this study was to assess the local and systemic tolerability of two batches of the Biken acellular pertussis (Pa) vaccine following administration of a single vaccine dose to adults with or without a history of prior pertussis immunization. The results from this study were compared to data from published literature. PATIENTS AND METHODS: In a controlled, open-labeled double-blind trial, 518 healthy male and female adults with or without primary pertussis immunization were enrolled at three centers. All study participants had received one single dose (0.5 ml) of the Biken two-component (23.4 mg PT; 23.4 mg FHA) Pa vaccine deeply intramuscularly. Local and systemic adverse events were solicited for 4 days using diary cards. On two occasions, between day 4-7 and between day 12-16 postvaccination, vaccinees were reexamined. At the end of the observation period (day 28) vaccinees had to send a preprinted letter to the study center indicating their state of health. RESULTS: One serious adverse event (acute appendicitis) occurred and was considered not to be related to the study vaccine. At the injection site, redness > 20 mm was observed in one subject (0.2%), and swelling > 20 mm was seen in ten subjects (1.98%). Edematous swelling occurred in three subjects (0.59%). In 27 subjects (5.34%) a "late-onset muscle mass swelling" could be palpated, usually occurring on day 6-12 postvaccination. 429 subjects (84.78%) experienced none or only slight tenderness on pressure during the. rst 4 days postvaccination, moderate tenderness on pressure was reported by 60 subjects (11.86%) and severe tenderness by 16 vaccinees (3.16%). Systemic side effects were rare: no fever > 38.5 degrees C was observed, and only seven subjects (1.39%) took antipyretics. Five patients (0.99%) experienced exhaustion or nausea. The vast majority of the participants (97.43%) would opt for the vaccination again. CONCLUSION: The study vaccine was safe and induced only infrequently and mostly mild, local or general symptoms that all resolved spontaneously. It was well tolerated and accepted in adults.

Pediatric disease burden and vaccination recommendations: understanding local differences.

BACKGROUND: Diphtheria (D), tetanus (T), pertussis (P), hepatitis B (HepB), invasive Haemophilus influenzae type b (Hib) disease, and measles cause substantial global morbidity and mortality. METHODS: This unique review highlights geographic differences in disease burden across certain countries in the African, Americas, Mediterranean, South-East Asian, and Western Pacific World Health Organization (WHO) regions, and relates this to vaccination coverage and local vaccine recommendations using the authors' countries as illustrations. RESULTS: Substantial differences were observed in the incidence of these diseases and in vaccination coverage between the countries studied. Disease incidence often reflected inadequate surveillance, but also variable or poor vaccination coverage. Vaccination coverage against HepB was particularly low in the African and South-East Asian WHO regions; vaccination coverage against invasive Hib disease was low in these regions and in the Eastern Mediterranean and Western Pacific WHO regions. Vaccination schedules within some countries in these regions do not include, or have only recently included, vaccinations against HepB and Hib disease. The use of DTwP-HepB-Hib (diphtheria, tetanus, whole-cell pertussis, HepB, Hib) combination vaccines has now been adopted by some countries to help increase vaccination coverage. CONCLUSIONS: Vaccination coverage and vaccination schedules vary markedly between the countries studied, often according to the resources available. DTwP-HepB-Hib combination vaccines represent a cost-effective option, with the potential to substantially reduce the burden associated with these diseases by increasing coverage and compliance.

Two versus three doses of a meningococcal C conjugate vaccine concomitantly administered with a hexavalent DTaP-IPV-HBV/Hib vaccine in healthy infants.

The immunogenicity and reactogenicity of a meningococcal serogroup C (MenC) conjugate vaccine given concomitantly with DTaP-IPV-HBV/Hib vaccine according to a two- or three-dose schedule in healthy infants was evaluated. At 1 month post-vaccination, 98% (two doses) and 100% (three doses) of subjects had serum bactericidal antibody using human complement assay (hSBA) titres > or =1:8; at 12 months of age > or =89% of subjects in each group remained seroprotected. Induction of immunological memory, as evaluated by administration of a meningococcal serogroup A/C polysaccharide vaccine challenge dose, was similar for both regimens and no interference was observed in the immune response to MenC or hepatitis B virus antigens. Reactogenicity was similar in each group. MenC conjugate vaccine given concomitantly with DTaP-IPV-HBV/Hib to healthy infants in the first year of life using a two-dose schedule is as safe and immunogenic as a three-dose regimen.

Immunogenicity, reactogenicity, and immune memory after primary vaccination with a novel Haemophilus influenzae-Neisseria meningitidis serogroup C conjugate vaccine.

We evaluated two formulations of a new combined Haemophilus influenzae type b (Hib)-meningococcal serogroup C (MenC)-tetanus toxoid (TT) conjugated vaccine and two formulations of a new MenC-TT vaccine (trials 711202/001 and 711202/008; clinical trial register numbers NCT00135486 and NCT00135564 [www.ClinicalTrials.gov]). A total of 520 healthy infants were randomized to receive primary vaccination (at 2, 3, and 4 months) with either MenC-TT plus diphtheria-tetanus-acellular pertussis (DTPa)-hepatitis B virus (HBV)-inactivated poliovirus (IPV)/Hib, Hib-MenC-TT plus DTPa-HBV-IPV, or MenC-CRM(197) plus DTPa-HBV-IPV/Hib (control). At 12 to 15 months, subjects received a polysaccharide challenge with meningococcal polysaccharide C plus a DTPa-HBV-IPV/Hib booster. Immune responses were assessed 1 month after dose 2, 1 month after dose 3, and prior to and 1 month after the booster. After primary vaccination, there was no difference between groups in seroprotection rates as measured by titers of serum bactericidal antibody (SBA) to MenC (> or = 1:8) or concentrations of anti-polyribosyl ribitol phosphate (PRP) antibody (> or = 0.15 microg/ml). Prior to the booster, there was no difference between groups in SBA seroprotection rates, whereas anti-PRP seroprotection rates were significantly higher after priming with Hib-MenC-TT. Booster doses induced large increases in SBA and anti-PRP antibodies in primed groups, indicating successful priming with induction of immune memory. Reactogenicity and safety were similar in all groups during the primary and booster phases. A novel combined Hib-MenC-TT conjugate vaccine induced MenC and Hib responses comparable to those induced by licensed monovalent vaccines. A Hib-MenC-TT conjugate vaccine provides vaccination against two major pathogens in a single injection and is a suitable candidate for use in primary or booster vaccination schedules.

Ten years' experience with year-round active surveillance of up to 19 respiratory pathogens in children.

INTRODUCTION: Surveillance systems for acute respiratory infections (ARI) in children currently are often limited in terms of the panel of pathogens and the age range investigated or are only syndromic and at times only active in the winter season. METHODS: Within PID-ARI.net, a research network for ARI in children in Germany, an active, year-round surveillance system was formed in three regions from north to south for population-based analysis. Children from birth to 16 years of age were included and up to 19 noncolonizing airway pathogens were tested for with multiplex RT-PCR. RESULTS: In the 10-year period from July 1996 to June 2006, a total of 18,899 samples were tested. The positive rate increased with the size of the test panel to up to 72.9%. Picornaviruses (35-39%), paramyxoviruses (23-28%) and orthomyxoviruses (5.8-12.5%) comprised the highest fraction. Reoviruses and Legionella pneumophila were not found at all and Chlamydia pneumoniae and Bordetella parapertussis only rarely. Respiratory syncytial virus and parainfluenza virus (PIV) type 3 were anticyclical in rhythmicity with metapneumovirus and PIV1 and PIV2. The age medians per pathogen depended predominantly upon the attack rate and interepidemic intervals. CONCLUSION: Active surveillance systems for ARI are superior to passive systems. They should be pathogen-specific and comprehensive for viruses and bacteria and age ranges. They should be population-based and multilevel to avoid bias. The impact of atypical bacteria in children was highly overestimated in earlier studies.

Population-based burden of pneumonia before school entry in Schleswig-Holstein, Germany.

UNLABELLED: Community-acquired pneumonia (CAP) is of predominant interest in analysing the burden of airway diseases. No population-based incidence data for children in Germany exist. In retrospective cohort studies from 1999 to 2001, parents of an entire age-class (28,000-30,000) of 5- to 7-year-old children at school entry medical examination (S1) in a complete federal state (Schleswig-Holstein, population 2.77 million) were interviewed by the Children and Adolescent Service of the Public Health Service. CAP was defined as pneumonia diagnosed by a physician at the time it occurred. The proportion of children investigated (participation rate) was 82.0-86.1%. The CAP-positive rate was 6.7-7.4%, 6.9-8.2% of whom had recurrent CAP. The mean age at first CAP was 36.4-39.4 months (median 42 months). This resulted in a population-based incidence for the age groups 0-1 year and 0-5 years (under 5) of 1,664-1,932 and 1,369-1,690 per 100,000, respectively; 93.7-95.9% received antibiotics. For each percent of CAP, 458 days (1999), 312 days (2000) and 319 days (2001) of at least one parent's work were lost, respectively. CONCLUSIONS: Despite a relatively weak case definition, the population-based incidence of CAP before school entry was the same as recently reported form California and about 30-50% of that reported 20 to 40 years ago in the USA and Finland.

Pneumococcal conjugate vaccines: proceedings from an interactive symposium at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy.

Globally, Streptococcus pneumoniae is a leading cause of invasive and noninvasive disease in infants and young children. The emergence of antibiotic-resistant strains has increased interest in prevention through immunization. Currently, the only available conjugate pneumococcal vaccine is a seven-valent formulation, PNCRM7. This paper presents excerpts from a symposium that provided an update of ongoing surveillance data and clinical trials evaluating pneumococcal conjugate vaccines. The topics addressed included: (1) PNCRM7 postmarketing safety data; (2) the impact of PNCRM7 in premature infants; (3) the direct and indirect effect of pneumococcal conjugate vaccines on colonization; (4) the effect of pneumococcal conjugate vaccines on replacement disease and the rate of resistance among replacement serotypes; (5) the current recommendations for the use of PNCRM7; and (6) the potential impact of conjugate vaccines in Europe and the Asia-Pacific region.

A global perspective on vaccine safety and public health: the Global Advisory Committee on Vaccine Safety.

Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established, its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles-mumps-rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines.