Paediatric pneumococcal disease in Central Europe.

Streptococcus pneumoniae causes considerable global paediatric morbidity and mortality, despite the availability of safe and effective pneumococcal conjugate vaccines (PCVs). To justify the introduction of PCVs, accurate information on the burden of disease is required. Here, we present an appraisal of the pneumococcal epidemiological situation in 11 Central European countries. The data are based on study findings presented at the 12th Central European Vaccine Advisory Group (CEVAG) meeting, held on 21-22 May 2010 in Sofia, Bulgaria, and a literature review of the PubMed database using the search terms 'pneumococcal' or 'Streptococcus pneumoniae', in combination with 'otitis media', 'pneumonia', 'meningitis' or 'bacteraemia/sepsis', and '[Central European country name]'. The incidence of pneumococcal disease appears to be lower in Central Europe than previously reported for Europe as a whole, with the highest risk in infants aged 0-2 years. The fatality rates in the under fives from invasive infections are up to 40%. A paucity of comprehensive country-specific data on pneumococcal disease burden arises from the lack of homogenous surveillance programmes. Standardised, active surveillance systems are required for the accurate evaluation of the pneumococcal disease burden in the region. Only then can the need for vaccination be addressed.

Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study.

BACKGROUND: We aimed to assess the efficacy of the oral live attenuated human rotavirus vaccine Rotarix (RIX4414) for prevention of rotavirus gastroenteritis in European infants during their first 2 years of life. METHODS: 3994 study participants were enrolled from six countries and were randomly assigned two oral doses of either RIX4414 (n=2646) or placebo (n=1348), which were coadministered with the first two doses of specific childhood vaccinations. Follow-up for gastroenteritis episodes was undertaken from 2 weeks post-dose two through the two consecutive rotavirus seasons following vaccinations (combined efficacy follow-up period; mean duration 17 months [SD 1.6]). Our primary endpoint was vaccine efficacy against rotavirus gastroenteritis of any severity during the first efficacy follow-up period (2 weeks post-dose two to the end of the first rotavirus season). Stool specimens obtained during gastroenteritis episodes were tested for rotavirus by ELISA and typed by RT-PCR. Episodes scoring 11 or greater on the 20-point Vesikari scale were classified as severe. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140686 (eTrack102247). FINDINGS: 120 infants were excluded from the according-to-protocol analysis. During the first efficacy follow-up period (mean duration 5.7 months [SD 1.2]), 24 of 2572 infants allocated RIX4414 versus 94 of 1302 given placebo had rotavirus gastroenteritis episodes of any severity, resulting in a vaccine efficacy of 87.1% (95% CI 79.6-92.1; p<0.0001). For the combined efficacy follow-up period, vaccine efficacy against severe rotavirus gastroenteritis was 90.4% (85.1-94.1; p<0.0001), for admission owing to rotavirus gastroenteritis 96.0% (83.8-99.5; p<0.0001), and for rotavirus-related medical attention 83.8% (76.8-88.9; p<0.0001), and significant protection against severe rotavirus gastroenteritis by circulating G1, G2, G3, G4, and G9 rotavirus types was shown. INTERPRETATION: In a European setting, two doses of RIX4414 coadministered with childhood vaccines provided high protection against any and severe rotavirus gastroenteritis, with an overall reduction of admissions for gastroenteritis over two consecutive rotavirus epidemic seasons.

[Immunogenicity of vaccines against viral hepatitis A and B in the population above 40 years of age -- impact of risk factors]. / Imunogenita vakcín proti virovým hepatitidám A a B u osob starsích 40 let -- vliv rizikových faktoru.

UNLABELLED: The immune reaction following vaccination against viral hepatitis A (HAV) and viral hepatitis B (HBV) can be influenced by a variety of factors. Among the most important are age, gender and body weight. STUDY OBJECTIVE: This prospective randomized study compared immunogenicity of available vaccines against HAV and HBV infections in the population above 40 years of age and the impact of risk factors. MATERIAL AND METHODS: The vaccinated subjects were divided into 3 groups based on the vaccine used. Within each group, the subjects were equally distributed by age, gender and body weight. The vaccine was always applied intramuscularly in the deltoid. Group 1 was given the combined vaccine Twinrix (GSK) against HAV and HBV infections in the left deltoid; group 2 was vaccinated with the Havrix vaccine against HAV (GSK) in the right deltoid and with the Engerix-B vaccine against HBV (GSK) in the left deltoid; group 3 received the Vaqta vaccine against HAV (Sanofi Pasteur) in the right deltoid and the HB VAX PRO against HBV (Sanofi-Pasteur) in the left deltoid. RESULTS: The following anti-HBs seroprotectivity rates: 92%, 80% and 71%, and anti-HAV seropositivity rates: 97%, 99% and 99%, were observed at 1 month after the end of the complete vaccination in groups 1, 2 and 3, respectively. The anti-HBs seroprotectivity rate was statistically significantly higher in group 1. The anti-HAV seropositivity rates were comparable (did not significantly differ) in all three study groups. CONCLUSION: The impact of age was revealed: the immune response decreases with increasing age. The lowest immunogenicity of the vaccines against HAV and HBV infections was observed in subjects above 60 years of age. Males achieved lower geometric mean titres (GMT) of antibodies and lower seroprotectivity rates compared to females. The impact of body weight was also observed, with the obese subjects showing the lowest immune response. The anti-HBs reactivity was significantly influenced by the vaccine used. The combined vaccine against HAV and HBV infections (Twinrix) induced higher anti-HBs seroprotectivity and comparable anti-HAV seropositivity when compared with the other monovalent study vaccines in the population above 40 years of age.

[Seroprevalence of antibodies against hepatitis A virus and hepatitis B virus in nonvaccinated adult population over 40 years of age]. / Séroprevalence protilátek proti viru hepatitidy A, viru hepatitidy B u nevakcinované dospelé populace starsí 40 let.

STUDY OBJECTIVE: To determine prevalence rates of antibodies against hepatitis A virus (HAV) and hepatitis B virus (HBV) in the general adult male and female population over 40 years of age with no history of viral hepatitis A (VHA) and viral hepatitis B (VHB) who have never been vaccinated against hepatitis and to assess the cost-effectiveness of the pre-vaccination serological screening. MATERIAL AND METHODS: In 2003-2004, a total of 972 persons of three age categories: 41-50 years, 51-60 years, 61 and more years, were screened. Persons with a history of VHA and/or VHB and those who had been vaccinated against hepatitis were not included in the study. The following four indicators were determined from a 5 ml specimen of whole venous blood by electrochemiluminiscence assay: total anti-HAV antibodies, total anti-HBc antibodies, anti-HBs antibodies and HBsAg, as the most suitable markers of experienced hepatitis or previous vaccination. RESULTS: The prevalence rates of anti-HAV antibodies were lower in females compared to males for all of the three age categories. These antibodies were detected in 16.8%, 52.9% and 77.5% of 41-50-year-olds, 51-60-year-olds and > or = 61-year-olds, respectively. The total prevalence rate for the three age groups was 61.6%. The anti-HBc antibody seroprevalence rates were 1.9%, 5.3% and 6.1%, respectively. CONCLUSION: The results show high prevalence of VHA in higher age groups. Such a high seroprevalence of antibodies in nonvaccinated persons with no history of viral hepatitis is suggestive of a very frequent incidence of asymptomatic infection. For this reason, the prevaccination screening of anti-HAV antibodies is cost-effective in the population over 50 years of age but is not justified in persons under 40 years of age. Prevaccination screening for anti-HBc antibodies appears not to be cost-effective regardless of age in view of their low prevalence in the Czech population.

Alternatives to HIST for acellular pertussis vaccines: progress and challenges in replacement.

The 'International Workshop on Alternatives to the Murine Histamine Sensitization Test for Acellular Pertussis Vaccines: Progress and Challenges in the Replacement of HIST' was held on 24 August 2014, in Prague, Czech Republic, as a satellite meeting to the 9th World Congress on Alternatives and Animal Use in the Life Sciences. Participants discussed the progress and challenges associated with the development, validation, and implementation of in vitro assays as replacements for the histamine sensitisation test (HIST) for acellular pertussis vaccines. Discussions focused on the consistency approach, the necessary framework for regulatory acceptance of a harmonised method, and recent international efforts towards the development of in vitro assays to replace the HIST. Workshop participants agreed that acceptable alternatives to the HIST should be based on ADP ribosylation-mediated cell intoxication and therefore that the CHO cell clustering assay, which measures cell intoxication, should be further pursued and developed as a possible replacement for the HIST. Participants also agreed to continue ongoing multinational discussions involving national and international standardisation authorities to reach consensus and to organise collaborative studies in this context for assay characterisation and calibration of reference materials.

Concomitant vaccination against hepatitis A and typhoid fever.

BACKGROUND: The purpose of this study was to evaluate the reactogenicity and immunogenicity of a hepatitis A vaccine (Havrix-1440TM) when administered simultaneously with a Vi polysaccharide typhoid vaccine. METHODS: Two open, randomized studies were conducted using 2 and 4 treatment groups respectively, at the Clinique Notre-Dame de Grâce, Belgium (Study 1) and University Hospital of Hradec Kralové, Czech Republic (Study 2). SUBJECTS: Healthy adults aged 18-50 years were administered either both vaccines concomitantly in separate arms or a single injection of the two vaccines mixed extemporaneously (Study 1), or one injection of each vaccine alone, or the combined vaccine, or both vaccines concomitantly in separate arms (Study 2). The study measured solicited and unsolicited signs and symptoms until 28 days post-vaccination. Anti-hepatitis A and anti-Vi titers were determined in pre- and post-vaccination sera. RESULTS: The vast majority of local and general symptoms were mild to moderate and all resolved without sequelae. No serious adverse events were reported in either study. In study 1, geometric mean antibody titers (GMTs) were similar after extemporaneous syringe mixing of both vaccines (anti-Vi = 1159 EL.U/mL; anti-HAV = 302 EL.U/mL) and after concomitant vaccination (anti-Vi = 1331 EL.U/mL; anti-HAV = 367 EL. U/mL). In study 2, GMTs following vaccination with either vaccine alone, both vaccines administered concomitantly or as a combined vaccine (anti-Vi: 1307, 1247 and 942 EL.U/mL, respectively; anti-HAV: 462, 517 and 432 EL.U/mL, respectively) were not significantly different (p = .45 for anti-HAV, p = .18 for anti-Vi). Seroconversion rates were > 94.4% in all cases. CONCLUSIONS: The inactivated hepatitis A and Vi polysaccharide typhoid vaccines are safe and well tolerated when administered simultaneously (mixed or concomitant) and as a combined vaccine. Subjects seroconverted to both antigens to the same extent as the monovalent vaccines and there was no cross-interference in the immune profiles of the vaccines.

Comparison of Streptococcus pneumoniae serotypes causing acute otitis media & invasive disease in young children in the Czech Republic.

BACKGROUND & OBJECTIVES: The availability of a type-specific pneumococcal vaccine for children is a worldwide problem. It is necessary to study the serotypes prevalent in a country before introducing a type-specific vaccine. The objective of the present study was to analyse the prevalence of Streptococcus pneumoniae serotypes in children suffering from acute otitis media or invasive pneumococcal disease and to compare a coverage of serotypes by individual pneumococcal vaccines. METHODS: Children suffering from acute otitis media and invasive pneumococcal disease were analysed in the Czech Republic from October 1999 to November 2000. Serotyping was performed by the quellung technique using antisera from Statens Serum Institute (Denmark). RESULTS: The most frequent serotypes in patients with acute otitis media were 3, 19F, 23F, 14, 9V, 1, 6B, 11A and 28F. Vaccine coverage for the identified serotypes in acute otitis media patients was 52.1 per cent for the 7-valent vaccine, 57.8 per cent for the 9-valent vaccine and 75.7 per cent for the 11-valent form of the vaccine. In 108 patients with invasive pneumococcal disease, the most frequent serotypes were 6B, 9V, 14, 19F, 3 and 23F. Vaccine coverage for the identified serotypes in patients with invasive pneumococcal disease was 62 per cent for the 7-valent vaccine, 66.4 per cent for the 9-valent vaccine and 77.5 per cent for the 11-valent form of the vaccine. INTERPRETATION & CONCLUSION: Vaccine coverage for the identified serotypes for the 11-valent pneumococcal vaccine was better than the other two vaccines.

[Analysis of prevention of an epidemic of viral hepatitis A in the Czech army 1970-1989]. / Analýza protiepidemických opatrení u virové hepatitidy typu A v cs. armáde v období 1970-1989.

Viral hepatitis is a serious medical and economic problem. By far the most frequent viral hepatitis occurring in Czechoslovak army is viral hepatitis A. Although the trends of the global incidence of hepatitis A in the Czech Army are identical with the trends in the civilian sector and thus descending, the great danger for the military sector arises specially from specific conditions of organized life. Screening and postexposure gammaglobulin prophylaxis with 70% protection are proved most effective. The protection is lower than the values published by authors abroad, but this is connected with the time of gammaglobulin administration. Norga prophylaxis is quite justified, in indicated cases, i.e. in contacts and in time.

[Epidemiology of noninfectious diseases--principles and methodology]. / Epidemiologie neinfekcních onemocnení--principy a metodologie.

Contemporary epidemiology as a science extends considerably its object of research interest. Originally it was interested in the prevalence of communicable diseases in the population and investigated all the factors, which affected this distribution. In the last few decades, epidemiology passed from following-up of communicable diseases to the description and the analysis of all diseases, which occur on our planet. Because of interest in the diseases, which endanger civilization as a result of its development, is the epidemiology with this target is called sometimes the epidemiology of non-communicable diseases. Traditional and the historical experience of communicable diseases epidemiology, methods of the classic statistics and the epidemiological working method are its basic principles. Adequate design of epidemiological studies and modern indicators for evaluation of the health status are used. Epidemiology does not investigate the disease and the risk factor separately, but they are analyzed mutually at three levels as a relation, association and causality. Emphasis is laid on minimalization or complete elimination of confounding and bias.

[Seroprevalence of anti-hepatitis A antibodies in Czech soldiers serving in U.N. forces--suggestions for a hepatitis A vaccination schedule]. / Séroprevalence anti-HAV protilátek u ceských vojáku U.N. jednotek--Návrh vakcinacního schématu proti VHA.

Viral hepatitis A is a frequent disease particularly in developing countries. All workers and UN forces (UNO) are vaccinated against VHA with Havrix vaccine. The Czech units which were and are engaged on the territory of former Jugoslavia are not yet vaccinated against this contagious disease. The main purpose of the present study was to assess the immunity rate of VHA among Czech soldiers of the UN forces before their departure to the site of action. Another objective was to assess a suitable vaccination procedure. Sera were examined by the MEIA method (Microparticle Enzyme Immunoassay) in a fully automated IMx system in the Military Health Institute, Ceské Budejovice. For investigation HAVAB kits of Abbott Co. were used. A total of 667 serum samples were assembled, 19 had to be discarded because of small amounts (less than 50 microliters or because of haemolysis. The positive titre of "total" antibodies was set at 35 mIU anti-HAV; thus a total of 648 specimens were examined in 1991 - 1994 (1991 - 65, 1992 - 296, 1993 - 265, 1994 - 22). Of these 249 (38.4%) were positive and 399 (61.6%) were negative. The examined subjects were divided into four age groups (20 - 29, 30 - 39, 40 - 49, 50 - 59), the approximate distribution being 23%, 50%, 25%, 2%. The ratio of negative and positive specimens in different age groups was 1:0.3, 1:0.6, 1:1, 1:2.7. The seroprevalence of anti-HAV antibody increases from 25.3% in the first age group, in the second one it is 37.9%, in the third one 49.5% and 72.7% in the last age group, i.e. in the age bracket of 50 - 59 years. The results indicate a very low immunity rate in the lower age brackets and the necessity to vaccinate them before they depart. It is beyond doubt that it pays to examine the soldiers for the presence of total anti-HAV and immunize only subjects with a negative antibody titre. The vaccination approach Havrix 2 x 720 EU was recommended.

Hepatitis A vaccination by Havrix in the Czech U.N. Troops according to data of seroprevalence in 1991-1995.

Viral hepatitis A is a common disease, particularly in developing countries. All staff and troops of the U.N. (United Nations) are vaccinated by the Havrix vaccine. Till 1995 we did not vaccinate Czech troops which have operated in the area of former Yugoslavia. The main goal of this study was to obtain data about the seroprevalence of hepatitis A antibody among the Czech U.N. troops before their departure to the conflict area and to optimize the vaccination approach. The serum samples were examined by the MEIA (Microparticle Enzyme Immunoassay) method in the fully automated system for immunoassays IMx in the Military Institute of Health in Ceské Budejovice. We used HAVAB kits of Abbott Company. 692 serum samples (military staff of the Czech U.N. troops in Yugoslavia) were examined in 1991-1995. In the laboratory 19 samples were eliminated due to small amounts (less than 50 microliters) or haemolysis. 673 (1991 - 65, 1992 - 296, 1993 - 265, 1994 - 35, 1995 - 12) were investigated. The staff was divided into four age cohorts by decades (20-29, 30-39, 40-49, 50-59); 26.0%, 47.4%, 24.9% and 1.7%, respectively. There were 253 (37.4%) positive samples and 420 (62.6%) negatives ones, ratio 1:1.7. The ratio of the positive and negative samples--immunity rate and seroprevalence--were 1:0.4 (26.2%), 1:0.6 (37.9%); 1:0.9 (46.4%) and 1:2.7 (72.7%), respectively in the age cohorts. The results show a relatively low seroprevalence of the anti-HAV antibody in all the age cohorts and necessity to vaccinate the Czech U.N. troops by the special basic schedule--Havrix 2 x 720 E.U. at the same time. This regimen will be used in the new units that will be stationed in Bosnia. So far 200 persons have been vaccinated in this way.

Evaluation of reactogenicity and immunogenicity of two influenza vaccines (vaxigrip and fluarix) in the season 1996-1997.

Influenza is a very serious disease, which causes thousands of deaths all over the world every year. As there is so far no sufficiently effective causal therapy of influenza the main function of vaccination lies in prevention. Influenza is a major problem especially in collective facilities. Therefore, great emphasis is laid in the Czech Republic Army on the vaccination of military groups and on the evaluation of reactogenicity and immunogenicity of the vaccines used. The specific aim of the clinical trial was to evaluate the reactogenicity and immunogenicity of two inactivated split influenza vaccines Fluarix and Vaxigrip in healthy adult volunteers aged 18-60 years with stress on military groups. The study was designed as an open clinical trial with 2 groups each of 100 volunteers in one centre. Randomisation was not conducted so that each group received only the vaccine specified beforehand. Both the inactivated split vaccines evaluated, Vaxigrip and Fluarix are highly immunogenic both against declared and other antigenic variants of influenza. The study has demonstrated a favourable trend in the preparation of influenza vaccines towards a marked reduction of general solicited symptoms as compared with previous years. Despite minute differences in immunogenicity and reactogenicity, the vaccines are generally speaking comparable, and in healthy individuals aged 18-60 years they induce a sufficient protection against the onset and development of influenza. The results of our open clinical trial (without randomisation) have again proved that both manufacturers produce vaccines of a high European standard.

The seroprevalence of the "total" anti-HAV antibody in the Czech UNPRO Forces (1991-1995).

Viral hepatitis A is a common disease particularly in developing countries. That disease is endemic and it is always associated with poor standards of sanitation. All staff and troops in the U.N. (United Nations) are vaccinated by the Havrix vaccine. Till 1995 we did not vaccinate the Czech troops which have operated in the area of the former Yugoslavia. The main goal of this study was to obtain data about the seroprevalence of hepatitis A antibody among the Czech U.N. troops before their departure to the conflict area. The serum samples were investigated by the MEIA (Microparticle Enzyme Immunoassay) method in the fully automated system for immunoassays IMx in the Military Institute of Health in Ceské Budejovice. We use the HAVAB investigation kits of the Abbott company. We obtained 884 serum samples (military staff of the Czech U.N. troops in Yugoslavia) in the years 1991-1995. In the laboratory we excluded 19 of the samples due to the small amount (less than 50 ul) or hemolysis. We investigated 865 of them (1991--65, 1992--296, 1993--265, 1994--35, 1995--204). The staff was divided into four age cohorts by ten years (20-29, 30-39, 40-49, 50-59), where the distribution of percentage was 32.6%, 43.6%, 22.5%, and 1.3% respectively. The positive samples were 287 (average seroprevalence was 33.2%, CI 30.1%-36.3%), the negative ones were 578 (66.8%). The seroprevalence 18.1% (CI 13.6%-22.6%), 36.1% (CI 31.3%-40.9%), 47.1% (CI 40.1%-54.1%), 72.7% (CI 46.4%-99.0%) in the age cohorts. The results show relatively low seroprevalence of the anti-HAV antibody in all the age cohorts and necessity to vaccinate the Czech UNPROFOR or IFOR units by Havrix before their departure to conflict area.

Online survey: knowledge about risks, prevention and consequences of infections with HBV among travellers from four European countries.

OBJECTIVE: To evaluate knowledge about risks, prevention and consequences of infection with hepatitis B virus (HBV) among travellers from four low HBV risk, European countries. METHODS: Individuals from an internet panel and based in the Czech Republic, the Netherlands, Spain and Sweden were invited to take part in an online survey. A total of 4203 respondents met the inclusion criteria and completed the survey. RESULTS: The majority (62.3%) of respondents did not know the main travel destinations with moderate or high prevalence for HBV. Also, 20.1% were somewhat or very unaware of the ways in which HBV can be caught and travellers aged 18-35 years were significantly more likely (p < 0.01) to have participated in at least one risky activity abroad. Three-quarters (74.9%) thought they were somewhat or very aware of the health implications of contracting HBV, but only 11.8% of participants selected more than three out of the six correct answers relating to conditions caused by HBV. Only 39.3% of those who knew their vaccination status had received vaccination against HBV within the previous 5 years, although some patients may have been vaccinated prior to this period. CONCLUSIONS: As country-specific variables were not analysed in this study, the results do not allow interpretation by country. A high proportion of the respondents were at an elevated risk of HBV infection while visiting moderate or high prevalence countries. They were unlikely to be immunised or take appropriate precautions; participation in risk activities abroad was high, and knowledge of HBV was limited. These findings indicate there is a need for healthcare professionals and the travel industry to educate travellers on the risks of HBV infections while abroad and the importance of preventing infection through vaccination.