Active surveillance study of adverse events following immunisation of children in the Czech Republic.

BACKGROUND: Despite the undisputed public health benefits of routine vaccination, adverse events following immunisation (AEFI) remain a concern. As most adverse events are mild, they may be under-reported; this may underlie the wide range of AEFI rates reported in the literature. We investigated the rates of AEFI related to routine vaccination of children 0-10 years old in the Czech Republic. METHODS: The study reviewed patients' records in a sample of 49 paediatric GP practices covering all 12 administrative regions of the Czech Republic between 2011 and 2013. Adverse events following routine immunisation of children aged 0-10 years were identified and recorded. RESULTS: The overall rate of AEFI was 209/100,000 doses; this was 6 times higher than the rate reported to the Czech State Institute for Drug Control (34/100,000 doses). Over two fifths (44%) of all AEFI occurred after the booster dose of the combined diphteria, tetanus and pertussis vaccine in 5-year old children. The vast majority of AEFI were non-serious local events (e.g. redness) and fever. Most AEFI occurred the second day after the immunisation, lasted 4 days on average, and were treated by cold therapy, antipyretics and analgesics. CONCLUSIONS: The rate of AEFI identified in this study was considerably higher than the officially reported rate. Although the vast majority of AEFI were non-serious, health care providers and the public should be educated and encouraged to report AEFI to address the issue of underreporting, to increase the safety profile of vaccines, and to improve public confidence in immunisation programmes.

Vaccine Ingredients: Components that Influence Vaccine Efficacy.

Vaccination is defined as the administration of an antigenic material in order to stimulate the immune system, leading to the development of adaptive immunity to a pathogen. Vaccines can prevent or reduce morbidity from a vast number of infections. This manuscript presents an analysis of vaccine types and vaccine substances, concentrating on individual components including the active ingredient, adjuvants, preservatives, stabilizers, inactivators, antibiotics, diluents and other substances. While many papers have been published on individual vaccine components, this review provides detail on a wide range of the most commonly-used vaccine ingredients and components that have been tested in clinical trials.

Factors Associated with Parental Refusal of Routine Vaccination in the Czech Republic.

AIM: Routine vaccination is one of the most important preventive methods which is responsible for the decreasing trend of morbidity and mortality of vaccine preventable infectious diseases, their complications and sequelae. The impact of vaccination on declining trend of these diseases is well known and confirmed by a large number of epidemiological studies. In the Czech Republic, there is high vaccination coverage in regards to most vaccine preventable diseases. However, during the last decade proportion of parents refusing routine vaccination of their children due to different factors is increasing. The presented study evaluates current situation in the Czech Republic and describes the most significant factors in parents decision making. METHODS: The study was conducted between 1 July 2013 and 31 March 2014 as a questionnaire based survey (cross-sectional study). The questionnaire was created with multiple choice answers. Questions were addressed to parents or legal representatives of children aged 0-18 years. Types of questions were divided into several subgroups. The study was performed in the Czech Republic in two different districts of Prague and Zlín. RESULTS: In the sample size (n=480) we detected 11 parents who refused vaccination of 11 children (2.29%). The most often refused vaccines in the prevalence study were hexavaccine (1st dose) and measles, mumps and rubella vaccine (1st dose). The hexavaccine includes tetanic anatoxin, diphtheric anatoxin, acellular pertussis vaccine, conjugate vaccine against Haemophilus influenzae b, inactivated polio vaccine, and recombinant vaccine against viral hepatitis B. The measles, mumps, rubella vaccine contains live attenuated viruses of measles, mumps, rubella. CONCLUSION: We observed increasing trend of routine vaccination refusal in children during the last ten years (compared to situation in the year 2004, p<0.001). The most important factors associated with this progression were distrust to vaccination, fear of some vaccine components and fear of adverse reactions.

Bordetella adenylate cyclase toxin differentially modulates toll-like receptor-stimulated activation, migration and T cell stimulatory capacity of dendritic cells.

Adenylate cyclase toxin (CyaA) is a key virulence factor of the whooping cough agent Bordetella pertussis. The toxin targets CD11b-expressing phagocytes and delivers into their cytosol an adenylyl cyclase (AC) enzyme that subverts cellular signaling by increasing cAMP levels. In the present study, we analyzed the modulatory effects of CyaA on adhesive, migratory and antigen presenting properties of Toll-like receptor (TLR)-activated murine and human dendritic cells (DCs). cAMP signaling of CyaA enhanced TLR-induced dissolution of cell adhesive contacts and migration of DCs towards the lymph node-homing chemokines CCL19 and CCL21 in vitro. Moreover, we examined in detail the capacity of toxin-treated DCs to induce CD4(+) and CD8(+) T cell responses. Exposure to CyaA decreased the capacity of LPS-stimulated DCs to present soluble protein antigen to CD4+ T cells independently of modulation of co-stimulatory molecules and cytokine production, and enhanced their capacity to promote CD4(+)CD25(+)Foxp3(+) T regulatory cells in vitro. In addition, CyaA decreased the capacity of LPS-stimulated DCs to induce CD8(+) T cell proliferation and limited the induction of IFN-γ producing CD8(+) T cells while enhancing IL-10 and IL-17-production. These results indicate that through activation of cAMP signaling, the CyaA may be mobilizing DCs impaired in T cell stimulatory capacity and arrival of such DCs into draining lymph nodes may than contribute to delay and subversion of host immune responses during B. pertussis infection.

2'-O-Lysylaminohexyl oligonucleotides: modifications for antisense and siRNA.

A novel type of oligonucleotide has been developed, characterized by the attachment of a lysyl moiety to a 2'-O-aminohexyl linker. A protected lysine building block was tethered to 2'-O-aminohexyluridine, and the product was converted into the corresponding phosphoramidite. Up to six modified nucleosides were incorporated in dodecamer DNA and RNA oligonucleotides using standard phosphoramidite chemistry. Each of the building blocks contributes one positive charge to the oligonucleotide instead of the negative charge of a wild-type nucleotide. Thermal denaturation profiles indicated a stabilizing effect of 2'-O-lysylaminohexyl chains that was more pronounced in RNA duplexes. Incubation of the oligonucleotides with 5'-exonuclease revealed an exceptionally high stability against enzymatic degradation. Incorporation of up to three modifications into functional antisense and siRNA oligonucleotides targeted at ICAM-1 showed that the gene-silencing activity was higher with an increasing number of lysylaminohexyl nucleotides. Compared with wild-type antisense or siRNA, compounds with three modifications led to equal or higher ICAM-1 downregulation.