TIPICO IX: report of the 9th interactive infectious disease workshop on infectious diseases and vaccines.

The Ninth Interactive Infectious Disease workshop TIPICO was held on November 22-23, 2018, in Santiago de Compostela, Spain. This 2-day academic experience addressed current and topical issues in the field of infectious diseases and vaccination. Summary findings of the meeting include: cervical cancer elimination will be possible in the future, thanks to the implementation of global vaccination action plans in combination with appropriate screening interventions. The introduction of appropriate immunization programs is key to maintain the success of current effective vaccines such as those against meningococcal disease or rotavirus infection. Additionally, reduced dose schedules might improve the efficiency of some vaccines (i.e., PCV13). New vaccines to improve current preventive alternatives are under development (e.g., against tuberculosis or influenza virus), while others to protect against infectious diseases with no current available vaccines (e.g., enterovirus, parechovirus and flaviviruses) need to be developed. Vaccinomics will be fundamental in this process, while infectomics will allow the application of precision medicine. Further research is also required to understand the impact of heterologous vaccine effects. Finally, vaccination requires education at all levels (individuals, community, healthcare professionals) to ensure its success by helping to overcome major barriers such as vaccine hesitancy and false contraindications

Effectiveness of Meningococcal B Vaccine against Endemic Hypervirulent Neisseria meningitidis W Strain, England

Serum samples from children immunized with a meningococcal serogroup B vaccine demonstrated potent serum bactericidal antibody activity against the hypervirulent Neisseria meningitidis serogroup W strain circulating in England. The recent introduction of this vaccine into the United Kingdom national immunization program should also help protect infants against this endemic strain

Correlation of Group C Meningococcal Conjugate Vaccine Response with B- and T-Lymphocyte Activity

Despite the success of conjugate vaccination against meningococcal group C (MenC) disease, post-vaccination, some individuals still exhibit rapid waning of initially protective bactericidal antibody levels. The mechanism of this relative loss of humoral protection remains undetermined. In this report we have investigated the relationship between T- and B-cell activation and co-stimulation and the loss of protective antibody titers. We have found that healthy volunteers who lose protective MenC antibody levels one year after receipt of glycoconjugate vaccine exhibit no detectable cellular defect in polyclonal B- or T-cell activation, proliferation or the B-memory pool. This suggests that the processes underlying the more rapid loss of antibody levels are independent of defects in either initial T- or B-cell activation

Multilaboratory comparison of pneumococcal multiplex immunoassays used in immunosurveillance of streptococcus pneumoniae across Europe

Surveillance studies are required to estimate the impact of pneumococcal vaccination in both children and the elderly across Europe. The World Health Organization (WHO) recommends use of enzyme immunoassays (EIAs) as standard methods for immune surveillance of pneumococcal antibodies. However, as levels of antibodies to multiple serotypes are monitored in thousands of samples, a need for a less laborious and more flexible method has evolved. Fluorescent-bead-based multiplex immunoassays (MIAs) are suitable for this purpose. An increasing number of public health and diagnostic laboratories use MIAs, although the method is not standardized and no international quality assessment scheme exists. The EU Pneumo Multiplex Assay Consortium was initiated in 2013 to advance harmonization of MIAs and to create an international quality assessment scheme. In a multilaboratory comparison organized by the consortium, agreement among nine laboratories that used their own optimized MIA was assessed on a panel of 15 reference sera for 13 pneumococcal serotypes with the new WHO standard 007sp. Agreement was assessed in terms of assay accuracy, reproducibility, repeatability, precision, and bias. The results indicate that the evaluated MIAs are robust and reproducible for measurement of vaccine-induced antibody responses. However, some serotype-specific variability in the results was observed in comparisons of polysaccharides from different sources and of different conjugation methods, especially for serotype 4. On the basis of the results, the consortium has contributed to the harmonization of MIA protocols to improve reliability of immune surveillance of Streptococcus pneumoniae. IMPORTANCE Serology of Streptococcus pneumoniae is challenging due to existence of multiple clinically relevant serotypes and the introduction of multivalent vaccines in national immunization programs. Multiplex immunoassays (MIAs) are applied as high-throughput cost-effective methods for serosurveillance, and yet laboratories use their own protocols. The aims of this study were to assess the agreement of results generated by MIAs in different laboratories within the EU Pneumo Multiplex Assay Consortium, to analyze factors contributing to differences in outcome, and to create a harmonized protocol. The study demonstrated good agreement of results of MIAs performed by laboratories using controlled assays for determination of levels of vaccine-induced pneumococcal antibodies. The EU Pneumo Multiplex Assay Consortium is open to everyone working in public health services, and it aims to facilitate efforts by participants to run and maintain a cost-effective, reproducible, high-quality MIA platform.publishedVersio

Restructuring and repositioning of private accomodation in Primorsko-Goranska county: problems and solutions

The paper presents the results of a research conducted on private accommodation as most common form of accommodation within the tourism offer of Primorsko-Goranska County. The study was conducted in 2008, and the obtained results of the research are analysed in the paper, conclusions made, key problems identified and appropriate measures proposed, with the aim of enhancing the quality of this segment of the tourism industry. The goal of the above mentioned measures’ implementation are quality improvement, repositioning and restructuring of private accommodation and its transformation into small family hotels, boarding houses or apart-hotels

The global meningitis genome partnership.

Genomic surveillance of bacterial meningitis pathogens is essential for effective disease control globally, enabling identification of emerging and expanding strains and consequent public health interventions. While there has been a rise in the use of whole genome sequencing, this has been driven predominately by a subset of countries with adequate capacity and resources. Global capacity to participate in surveillance needs to be expanded, particularly in low and middle-income countries with high disease burdens. In light of this, the WHO-led collaboration, Defeating Meningitis by 2030 Global Roadmap, has called for the establishment of a Global Meningitis Genome Partnership that links resources for: N. meningitidis (Nm), S. pneumoniae (Sp), H. influenzae (Hi) and S. agalactiae (Sa) to improve worldwide co-ordination of strain identification and tracking. Existing platforms containing relevant genomes include: PubMLST: Nm (31,622), Sp (15,132), Hi (1935), Sa (9026); The Wellcome Sanger Institute: Nm (13,711), Sp (> 24,000), Sa (6200), Hi (1738); and BMGAP: Nm (8785), Hi (2030). A steering group is being established to coordinate the initiative and encourage high-quality data curation. Next steps include: developing guidelines on open-access sharing of genomic data; defining a core set of metadata; and facilitating development of user-friendly interfaces that represent publicly available data

Multilaboratory Comparison of Pneumococcal Multiplex Immunoassays Used in lmmunosurveillance of Streptococcus pneumoniae across Europe

Surveillance studies are required to estimate the impact of pneumococcal vaccination in both children and the elderly across Europe. The World Health Organization (WHO) recommends use of enzyme immunoassays (EIAs) as standard methods for immune surveillance of pneumococcal antibodies. However, as levels of antibodies to multiple serotypes are monitored in thousands of samples, a need for a less laborious and more flexible method has evolved. Fluorescent-bead-based multiplex immunoassays (MIAs) are suitable for this purpose. An increasing number of public health and diagnostic laboratories use MIAs, although the method is not standardized and no international quality assessment scheme exists. The EU Pneumo Multiplex Assay Consortium was initiated in 2013 to advance harmonization of MIAs and to create an international quality assessment scheme. In a multilaboratory comparison organized by the consortium, agreement among nine laboratories that used their own optimized MIA was assessed on a panel of 15 reference sera for 13 pneumococcal serotypes with the new WHO standard 007sp. Agreement was assessed in terms of assay accuracy, reproducibility, repeatability, precision, and bias. The results indicate that the evaluated MIAs are robust and reproducible for measurement of vaccine-induced antibody responses. However, some serotype-specific variability in the results was observed in comparisons of polysaccharides from different sources and of different conjugation methods, especially for serotype 4. On the basis of the results, the consortium has contributed to the harmonization of MIA protocols to improve reliability of immune surveillance of Streptococcus pneumoniae

Persistence of antibodies in laboratory staff immunized with quadrivalent meningococcal polysaccharide vaccine

Background Occupational exposure to live meningococci can potentially cause invasive meningococcal disease in laboratory staff. While, until recently, immunization with quadrivalent polysaccharide vaccine represented one cornerstone of protection, data on long-term persistence of antibodies in adults remain scarce. Methods We analyzed the relationship of antibody levels and time following quadrivalent polysaccharide vaccination (Mencevax® ACWY, GlaxoSmithKline) in a cross-sectional sample of 20 laboratory workers vaccinated at ages between 16.4 to 40.7 years from Germany. Sera were obtained 0.4 to 158.5 (median 35.3) months after vaccination. At the time of sampling, laboratory workers had been regularly exposed to meningococci for periods between 3.2 to 163.8 (median 41.2) months. Serum bactericidal assay (SBA) with rabbit complement and a microsphere-based flow analysis method were used to determine bactericidal titers and concentrations of IgG, respectively, against serogroups A, C, W135, and Y. Decay of antibodies was modeled using linear regression. Protective levels were defined as SBA titers ≥ 8. Results Half-lives of SBA titers against serogroups A, C, W135, and Y were estimated at 27.4, 21.9, 18.8, and 28.0 months, respectively. Average durations of protection were estimated at 183.9, 182.0, 114.6, and 216.4 months, respectively. Inter-individual variation was high; using lower margins of 95% prediction intervals, minimal durations of protection against serogroups A, C, W135 and Y were estimated at 33.5, 24.6, 0.0, and 55.1 months, respectively. The proportion of staff with protective SBA titers against W135 (65.0%) was significantly lower than proportions protected against A (95.0%), C (94.7%), and Y (95.0%). Consistently, geometric mean titer (97.0) and geometric mean concentration of IgG (2.1 μg/ml) was lowest against serogroup W135. SBA titers in a subset of individuals with incomplete protection rose to ≥ 128 (≥ 8 fold) after reimmunization with a quadrivalent glycoconjugate vaccine. Conclusions The average duration of protection following immunization with a quadrivalent polysaccharide vaccine in adults was ≥ 115 months regardless of serogroup. A substantial proportion (approximately 23% according to our decay model) of adult vaccinees may not retain protection against serogroup W135 for five years, the time suggested for reimmunization

Immunogenicity and safety of meningococcal group A, C, W and Y tetanus toxoid conjugate vaccine: review of clinical and real-world evidence

Protection by meningococcal group A, C, W and Y (MenACWY) vaccines against four meningococcal disease-causing serogroups is increasingly important because of changing epidemiologic patterns of meningococcal disease, including recent meningococcal serogroup W outbreaks/disease clusters. The MenACWY vaccine conjugated to tetanus toxoid (MenACWY-TT) has been extensively evaluated across the age spectrum (age ≥6 weeks) in randomized Phase II and III and in postmarketing studies. Results support the robust immunogenicity of MenACWY-TT across ages and coadministration with other vaccines. The safety profile is similar regardless of age, primary versus booster vaccination, or concomitant administration; local (swelling, pain, redness) and systemic (fever, fatigue, headache, drowsiness, loss of appetite, irritability) reactogenicity events are most common. These data support use of MenACWY-TT to protect against MenACWY disease. </jats:p