The synthetic bacterial lipopeptide Pam3CSK4 modulates respiratory syncytial virus infection independent of TLR activation

Respiratory syncytial virus (RSV) is an important cause of acute respiratory disease in infants, immunocompromised subjects and the elderly. However, it is unclear why most primary RSV infections are associated with relatively mild symptoms, whereas some result in severe lower respiratory tract infections and bronchiolitis. Since RSV hospitalization has been associated with respiratory bacterial co-infections, we have tested if bacterial Toll-like receptor (TLR) agonists influence RSVA2- GFP infection in human primary cells or cell lines. The synthetic bacterial lipopeptide Pam3-Cys-Ser-Lys4 (Pam3CSK4), the prototype ligand for the heterodimeric TLR1/TLR2 complex, enhanced RSV infection in primary epithelial, myeloid and lymphoid cells. Surprisingly, enhancement was optimal when lipopeptides and virus were added simultaneously, whereas addition of Pam3CSK4 immediately after infection had no effect. We have identified two structurally related lipopeptides without TLR-signaling capacity that also modulate RSV infection, whereas Pam3CSK4-reminiscent TLR1/2 agonists did not, and conclude that modulation of infection is independent of TLR activation. A similar TLR-independent enhancement of infection could also be demonstrated for wild-type RSV strains, and for HIV-1, measles virus and human metapneumovirus. We show that the effect of Pam3CSK4 is primarily mediated by enhanced binding of RSV to its target cells. The Npalmitoylated cystein

Airway response to respiratory syncytial virus has incidental antibacterial effects.

RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children. Here, we report that the airway abundance of Streptococcus was higher in samples collected at the time of RSV infection compared with samples collected one month later. RSV infection is associated with neutrophil influx into the airway and degranulation and is marked by overexpression of proteins with known antibacterial activity including BPI, EPX, MPO and AZU1. Airway secretions of children infected with RSV, have significantly greater antibacterial activity compared to RSV-negative controls. This RSV-associated, neutrophil-mediated antibacterial response in the airway appears to act as a regulatory mechanism that modulates bacterial growth in the airways of RSV-infected children

Variability of wavefront aberration measurements in small pupil sizes using a clinical Shack-Hartmann aberrometer

BACKGROUND: Recently, instruments for the measurement of wavefront aberration in the living human eye have been widely available for clinical applications. Despite the extensive background experience on wavefront sensing for research purposes, the information derived from such instrumentation in a clinical setting should not be considered a priori precise. We report on the variability of such an instrument at two different pupil sizes. METHODS: A clinical aberrometer (COAS Wavefront Scienses, Ltd) based on the Shack-Hartmann principle was employed in this study. Fifty consecutive measurements were perfomed on each right eye of four subjects. We compared the variance of individual Zernike expansion coefficients as determined by the aberrometer with the variance of coefficients calculated using a mathematical method for scaling the expansion coefficients to reconstruct wavefront aberration for a reduced-size pupil. RESULTS: Wavefront aberration exhibits a marked variance of the order of 0.45 microns near the edge of the pupil whereas the central part appears to be measured more consistently. Dispersion of Zernike expansion coefficients was lower when calculated by the scaling method for a pupil diameter of 3 mm as compared to the one introduced when only the central 3 mm of the Shack – Hartmann image was evaluated. Signal-to-noise ratio was lower for higher order aberrations than for low order coefficients corresponding to the sphero-cylindrical error. For each subject a number of Zernike expansion coefficients was below noise level and should not be considered trustworthy. CONCLUSION: Wavefront aberration data used in clinical care should not be extracted from a single measurement, which represents only a static snapshot of a dynamically changing aberration pattern. This observation must be taken into account in order to prevent ambiguous conclusions in clinical practice and especially in refractive surgery

Vaccination coverage and annual report of the National Immunisation Programme in the Netherlands, 2022

In Nederland krijgen kinderen vaccinaties tegen twaalf besmettelijke ziekten die ernstig kunnen verlopen. Het RIVM beschrijft elk jaar het percentage kinderen dat is gevaccineerd (vaccinatiegraad). Ook beschrijft het RIVM de ontwikkelingen binnen het Rijksvaccinatieprogramma (RVP(Rijksvaccinatie programma)). Vaccinatiegraad De vaccinatiegraad is lager dan vorig jaar. Het RIVM maakt zich zorgen om deze daling. Een hoge vaccinatiegraad is belangrijk om mensen tegen ernstige ziekten te kunnen blijven beschermen en om uitbraken van deze ziekten te voorkomen. Het RIVM vindt het daarom belangrijk dat alle betrokken partijen uitzoeken welke maatregelen mogelijk zijn om de vaccinatiegraad zo hoog mogelijk te krijgen. Het RIVM weet niet precies hoeveel lager de vaccinatiegraad is. Dat komt doordat het sinds 1 januari 2022 de gegevens van een deel van de vaccinaties anoniem ontvangt. Dat gebeurt als mensen geen toestemming geven om hun gegevens met het RIVM te delen. Anonieme vaccinaties kunnen niet worden meegeteld voor de vaccinatiegraad, waardoor deze lager wordt gerapporteerd dan hij daadwerkelijk is. Het aantal vaccinaties dat niet kan worden meegeteld, is nu nog vrij klein. Een groot deel van de kinderen heeft namelijk al vóór 2022 de RVP-vaccinaties gehad. Ontwikkelingen 2022 Door de coronamaatregelen kregen minder mensen een ziekte waartegen het RVP beschermt dan voor de coronapandemie. In 2022 is dat effect nog steeds te zien. Nieuw in het RVP is dat sinds 2022 ook jongens tegen HPV(humaan papillomavirus) worden gevaccineerd en dat de leeftijd voor de HPV-vaccinatie is verlaagd van 13 naar 10 jaar. Verder is er een HPV-inhaalcampagne gestart voor degenen die deze vaccinatie eerder niet kregen aangeboden of hebben gehaald. Op advies van de Gezondheidsraad krijgt iedereen die voor de HPV-vaccinatie in aanmerking komt vanaf september 2022 nog maar 2 in plaats van 3 vaccinaties. In het voorjaar van 2022 bleek dat minder tieners een vaccinatie halen, zoals voor BMR(bof, mazelen,rodehond) en HPV. Een peiling van het RIVM liet zien dat iets meer ouders van jonge kinderen in 2022 negatiever denken over vaccineren dan in 2013; de meesten zijn er nog steeds positief over.In the Netherlands, children receive vaccinations against 12 infectious diseases that can be serious. Each year, RIVM describes the percentage of children who have been vaccinated (vaccination coverage). RIVM also describes the developments within the National Immunisation Programme (NIP). Vaccination coverage The vaccination coverage is lower than last year. RIVM is concerned about this decrease. A high coverage is important to continue to protect people against serious diseases and to prevent outbreaks of these diseases. RIVM therefore considers it important that all parties involved find out which measures can be taken to get the coverage as high as possible. RIVM does not know exactly how much lower the vaccination coverage is. That is because data on some of the vaccinations are being anonymised with effect from 1 January 2022. This happens when people do not give permission to share their data with RIVM. Anonymous vaccinations cannot be counted towards the vaccination coverage, so the coverage is reported to be lower than it actually is. The number of vaccinations that cannot be counted is still quite small. A large proportion of the children have already had the NIP vaccinations before 2022. Developments in 2022 Due to the coronavirus measures, fewer people contracted a disease against which the NIP protects than before the coronavirus pandemic. That effect persisted into 2022. New developments in the NIP as of 2022 are that boys will also be vaccinated against HPV and that the age for the HPV vaccination has been lowered from 13 to 10. Furthermore, an HPV catch-up campaign has been launched for those who have not previously been invited for this vaccination or who missed out. On the advice of the Health Council of the Netherlands, everyone who is eligible for HPV vaccination will receive only two instead of three vaccinations from September 2022. In the spring of 2022, it turned out that fewer teenagers got vaccinated against for example MMR and HPV. A survey by RIVM showed that slightly more parents of young children think more negatively about vaccination in 2022 than in 2013. Most are still positive about it