Search

Since the introduction of Haemophilus Influenzae type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important. In Europe, currently three different hexavalent combination vaccines containing Hib conjugates are marketed. In this phase IV, single-blind, randomized, controlled, multi-country study (NCT04535037), we aimed to compare, in a 2 + 1 vaccination schedule, the immunogenicity and safety and show non-inferiority, as well as superiority, of DTPa-HBV-IPV/Hib (Ih group) versus DTaP5-HB-IPV-Hib (Va group) in terms of anti-polyribosylribitol phosphate (PRP) antibody geometric mean concentrations (GMCs) and proportion of participants reaching anti-PRP antibody concentrations greater than or equal to a threshold of 5 µg/mL. One month after the booster vaccination, the anti-PRP antibody GMC ratio (Ih group/Va group) was 0.917 (95% CI: 0.710-1.185), meeting the non-inferiority criteria. The difference in percentage of participants (Ih group - Va group) reaching GMCs ≥5 µg/mL was -6.3% (95% CI: -14.1% to 1.5%), not reaching the predefined non-inferiority threshold. Interestingly, a slightly higher post-booster antibody avidity was observed in the Ih group versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. This study illustrates the different kinetics of the anti-PRP antibody response post-primary and post-booster using the two vaccines containing different Hib conjugates and indicates a potential differential impact of concomitant vaccinations on the anti-PRP responses. The clinical implications of these differences should be further studied.

Ancient DNA research in the past decade has revealed that European population structure changed dramatically in the prehistoric period (14,000-3000 years before present, YBP), reflecting the widespread introduction of Neolithic farmer and Bronze Age Steppe ancestries. However, little is known about how population structure changed from the historical period onward (3000 YBP - present). To address this, we collected whole genomes from 204 individuals from Europe and the Mediterranean, many of which are the first historical period genomes from their region (e.g. Armenia and France). We found that most regions show remarkable inter-individual heterogeneity. At least 7% of historical individuals carry ancestry uncommon in the region where they were sampled, some indicating cross-Mediterranean contacts. Despite this high level of mobility, overall population structure across western Eurasia is relatively stable through the historical period up to the present, mirroring geography. We show that, under standard population genetics models with local panmixia, the observed level of dispersal would lead to a collapse of population structure. Persistent population structure thus suggests a lower effective migration rate than indicated by the observed dispersal. We hypothesize that this phenomenon can be explained by extensive transient dispersal arising from drastically improved transportation networks and the Roman Empire's mobilization of people for trade, labor, and military. This work highlights the utility of ancient DNA in elucidating finer scale human population dynamics in recent history., Competing Interests: MA, CW, SS, VO, HM, JS, OC, BZ, EP, KÖ, LD, PG, DF, ML, TA, SA, PA, CB, ŽB, AB, LB, PB, EB, DB, FC, MC, DD, ID, KE, MF, AG, GG, FG, SG, ZH, RJ, KV, GJ, IK, KK, HK, AK, SK, MK, VK, MK, DK, FL, ML, SL, TL, TL, WL, AS, VM, YC, NM, IM, NM, BM, LN, MN, AN, CN, JN, AO, JP, LP, DP, KP, SP, MR, MS, AS, AS, TS, MT, IT, DT, JT, DV, TW, DW, MŽ, MF, MČ, MŠ, DB, MN, AC, RP, JP No competing interests declared, ZG Reviewing editor, eLife, MB Affiliated with Palisada Ltd. The author has no financial interests to declare, JB, DL Affiliated with Kaducej Ltd. The author has no financial interests to declare, RM Affiliated with Skupina STIK. The author has no financial interests to declare, (© 2024, Antonio, Weiß, Gao et al.)

Background: Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination., Methods: In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 27 0/7 -36 6/7 weeks' gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11-18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively., Results: 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4-1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related)., Conclusions: As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation., Clinical Trial Registration: ClinicalTrials.gov: NCT02853929., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BAN reports grants from the GSK group of companies (GSK) and support from other vaccine manufacturers. BC, MAC, NMes, NMey and SOK are employees of GSK, and BC, MAC and NMes own GSK restricted shares. FMT, JGS, SAH, TN and KPP’s institutions received grants from GSK during the conduct of the study. FMT’s institution received financial and non-financial support from Ablynx, Astra Zeneca, GSK, Jansen, MedImmune, MSD, Novavax, Pfizer, Regeneron, Roche, Sanofi Pasteur and Seqirus outside the submitted work. SAH received honoraria for participation in ad-hoc advisory committees for GSK and Sanofi Pasteur. TN received personal fees from GSK for serving as chair of advisory committees outside the submitted work. BT’s institution received grants from GSK during the conduct of the study; research grants for clinical trials were also given to his institution by Pfizer, MSD and Sanofi Pasteur. KPP received a fellowship from National Health and Medical Research Council for conducting the present work, and her institution received financial support from DBV Technologies, Medlmmune, Novavax and Pfizer for conducting trials outside the submitted work. ISC has received grants and/or honoraria as a consultant/advisor or to attend conferences and practical courses from GSK, Sanofi Pasteur, MSD and Pfizer outside the submitted work. JMMA reports receiving fees and non-financial support from GSK, as well as fees from Pfizer and MSD outside the submitted work. LK is working as consultant for GSK. MB, JB, MJCO, EEP, JJ, MMV, PK, PGM, JTRA, SR, ZS, MV, OGV and GVZ declare no conflicts of interest., (Copyright © 2021 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.)

Background: Although sensitizer-induced occupational asthma (OA) accounts for an appreciable fraction of adult asthma, the severity of OA has received little attention., Objective: The aim of this study was to characterize the burden and determinants of severe OA in a large multicenter cohort of subjects with OA., Methods: This retrospective study included 997 subjects with OA ascertained by a positive specific inhalation challenge completed in 20 tertiary centers in 11 European countries during the period 2006 to 2015. Severe asthma was defined by a high level of treatment and any 1 of the following criteria: (1) daily need for a reliever medication, (2) 2 or more severe exacerbations in the previous year, or (3) airflow obstruction., Results: Overall, 162 (16.2%; 95% CI, 14.0%-18.7%) subjects were classified as having severe OA. Multivariable logistic regression analysis revealed that severe OA was associated with persistent (vs reduced) exposure to the causal agent at work (odds ratio [OR], 2.78; 95% CI, 1.50-5.60); a longer duration of the disease (OR, 1.04; 95% CI, 1.00-1.07); a low level of education (OR, 2.69; 95% CI, 1.73-4.18); childhood asthma (OR, 2.92; 95% CI, 1.13-7.36); and sputum production (OR, 2.86; 95% CI, 1.87-4.38). In subjects removed from exposure, severe OA was associated only with sputum production (OR, 3.68; 95% CI, 1.87-7.40); a low education level (OR, 3.41; 95% CI, 1.72-6.80); and obesity (OR, 1.98; 95% CI, 0.97-3.97)., Conclusions: This study indicates that a substantial proportion of subjects with OA experience severe asthma and identifies potentially modifiable risk factors for severe OA that should be targeted to reduce the adverse impacts of the disease., (Copyright © 2019. Published by Elsevier Inc.)

This observational, prospective study was undertaken to estimate the burden of rotavirus (RV) gastroenteritis (GE) leading to general practitioner (GP)/family paediatrician (FP) visits among children aged <5 years in Czech Republic, Germany, Italy, Poland, Spain and the UK. Children aged <5 years presenting with acute GE provided stool samples for rapid RV testing. RV+ samples were confirmed and typed by RT-PCR. Demographic and clinical data were collected for all RVGE episodes. Transmission patterns among other household children aged <5 years were also assessed. From November 2005 to May 2007, excluding data from the UK, 497/3,813 (13.0%) children aged <5 years presenting with acute GE to GP/FP and tested were RV+ by PCR. Most RVGE cases (69.1%) occurred in children aged <2 years, occurred between December and May (93.1%) and were moderate or severe by Vesikari score (92.9%). RV strain distribution varied between countries: G9P[8] was the most common type in Poland (54/76) and Spain (172/196), G1P[8] was predominant in the Czech Republic (56/64) and Italy (46/107), and G4P[8] and G1P[8] both prevailed in Germany (17/54 and 13/54, respectively). A total of 24/122 (19.7%) children aged <5 years resident in the same household as a PCR+ study participant also developed RVGE. Conclusion. This multinational epidemiological study in Europe shows that RV is easily transmitted among household children, with RVGE burden highest among children aged <2 years accessing primary healthcare for acute GE.

Sporadic and endemic forms of pemphigus foliaceus exist. Incidences of the various forms of pemphigus vary from country to country: pemphigus vulgaris is most common in Europe and the USA, whereas pemphigus foliaceus is more prevalent in Northern Africa, Turkey and Southern America. Endemic pemphigus foliaceus (also known as fogo selvagem and Brazilian pemphigus foliaceus) is a variant of the disease that is frequently diagnosed in some areas of Brazil and other underdeveloped areas of the world, including Tunisia and Colombia. Both genetic and environmental factors have been associated with the occurrence of auto-immune pemphigus and endemic pemphigus is very interesting from this point of view. Most of the patients with auto-immune pemphigus are aged 40-60 years at the onset of the disease. The incidence and prevalence of pemphigus are low. The demonstration of association of pemphigus vulgaris with HLA class II alleles is supported by various studies., (2009 Elsevier B.V. All rights reserved.)