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Background: The currently licensed quadrivalent MenACWY-CRM conjugate vaccine presentation consists of two vials (lyophilised MenA and liquid MenCWY) to be reconstituted before injection. A new fully liquid formulation in a single vial has been developed to further improve the vaccine presentation. Since the MenA structure is subject to hydrolytic degradation, this study was conducted to compare the immunogenicity and safety of the investigational MenACWY-CRM liquid vaccine with the licensed vaccine. Methods: In this multicentre, randomised, controlled, observer-blind, phase 2b study, 979 healthy adults were administered a single dose of MenACWY-CRM liquid presentation or the currently licensed MenACWY-CRM vaccine. MenA free saccharide generation was accelerated to approximately 30% in the liquid presentation and MenA polysaccharide O-acetylation was reduced to approximately 40%, according to a controlled procedure. Immunological non-inferiority of the MenACWY-CRM liquid to the licensed vaccine, as measured by human serum bactericidal assay (hSBA) geometric mean titres (GMTs) against MenA 1 month post-vaccination, was the primary study objective. Safety assessment was among the secondary objectives. Results: Immune responses against each serogroup were similar between the two vaccine groups and was non-inferior for MenA. Adjusted hSBA GMTs for MenA were 185.16 and 211.33 for the MenACWY-CRM liquid presentation and currently licensed vaccine presentation, respectively. The between-group ratio of hSBA GMTs for MenA was 0.88, with a two-sided 95% confidence interval lower limit of 0.64, greater than the prespecified non-inferiority margin of 0.5, thus meeting the primary study objective. Both vaccines were well tolerated. No serious adverse events were considered related to vaccination. Conclusions: The levels of MenA free saccharide and polysaccharide O-acetylation did not affect the immunogenicity of the fully liquid presentation, which was demonstrated to be non-inferior to the immunogenicity of the currently licensed MenACWY-CRM vaccine against MenA. The immunogenicity, reactogenicity and safety profiles of the two vaccine presentations were similar. (c) 2021 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background: The availability of accurate and rapid diagnostic tools for COVID-19 is essential for tackling the ongoing pandemic. Our study aimed to quantify the performance of available antigen-detecting rapid diagnostic tests (Ag-RDTs) in a real-world hospital setting. Methods: In this retrospective analysis, the diagnostic performance of 7 Ag-RDTs was compared with real-time reverse transcription quantitative polymerase chain reaction assay in terms of sensitivity, specificity and expected predictive values. Results: A total of 321 matched Ag-RDTreal-time reverse transcription quantitative polymerase chain reaction samples were analyzed retrospectively. The overall sensitivity and specificity of the Ag-RDTs was 78.7% and 100%, respectively. However, a wide range of sensitivity estimates by brand (66.0%–93.8%) and cycle threshold (Ct) cut-off values (Ct

This systematic review and meta-analysis aimed at summarizing available data on the impact of PCV10 and PCV13 in reducing the incidence of CAP hospitalizations in children aged5years.A systematic search of the literature was conducted. We included time-series analyses and before-after studies, reporting the incidence of hospitalization for pneumonia in the periods before and after the introduction of PCV10 or PCV13 into the immunization program. Pooled estimates of Incidence Rate Ratio (IRR) were calculated by using a random-effects meta-analytic model. Results were stratified according to age-groups (24months and 24-59months) and case definitions of pneumonia (clinically and radiologically confirmed pneumonia).A total of 1533 potentially relevant articles were identified. Of these, 12 articles were included in the analysis. In children aged24months, the meta-analysis showed a reduction of 17% (95%CI: 11-22%, p-value0.001) an of 31% (95%CI: 26-35%, p-value0.001) in the hospitalization rates respectively for clinically and radiologically confirmed pneumonia, respectively, after the introduction of the novel PCVs. In children aged 24-59months, the meta-analysis showed a reduction of 9% (95%CI: 5-14%, p-value0.001) and of 24% (95%CI: 12-33%, p-value0.001) in the hospitalization rates for clinically and radiologically confirmed pneumonia, respectively, after the introduction of the novel PCVs. High heterogeneity was detected among studies evaluating the hospitalization rate for clinically and radiologically confirmed pneumonia.The results of this study revealed a significant impact of PCV10 and PCV13 in reducing the hospitalizations for pneumonia, particularly in children aged24months and for radiologically confirmed disease. Further appropriately designed studies, comparing the impact of PCV10 and PCV13, are needed in order to obtain solid data on which to establish future immunization strategies.

Systemic lupus erythematosus (SLE) is a chronic immune-mediated inflammatory multisystem disease. The onset of viral and bacterial infections may favor the exacerbation of the disease, amplify autoimmune processes and contribute to mortality and morbidity. The prevention of influenza and Streptococcus pneumoniae infections with vaccination should receive particular attention in SLE patients considering their elevated incidence, their high attack rate in epidemic periods, their potentially severe complications as well as the immunocompromised state of the host. The use of non-adjuvanted vaccine preparations should be preferred in order to avoid the onset of the "Autoimmune (auto-inflammatory) Syndrome Induced by Adjuvants" or "ASIA". In this review, we report that influenza and pneumococcal vaccinations in SLE patients are: 1) recommended to reduce the risk of development of these infections; 2) strongly suggested in elderly subjects and in those receiving high dose immunosuppressive treatments; 3) efficacious, even if specific immune responses may be lower than in the general population, as generally the humoral response fulfills the criteria for vaccine immunogenicity; and 4) safe in inactive disease although may favor a transient increase in autoantibody levels and rarely disease flares.

The aim of the present study was to explore the ability of Intanza(®) 15 μg, the intradermal (ID) trivalent inactivated split-virion influenza vaccine containing 15 μg hemagglutinin per strain, to enhance the antibody responses against heterologous circulating H3N2 strains in adults 60 years and older. During the 2006-2007 influenza season, subjects aged 60 years or older were randomly assigned to receive one dose of ID or an intramuscular (IM, Vaxigrip(®)) influenza vaccine, which contained the reassortant A/Wisconsin/67/05(H3N2) strain as the H3N2 component. Antibody responses were assessed against the homologous vaccine strain, against the A/Brisbane/10/07(H3N2) reassortant strain and against four heterologous H3N2 field isolates (A/Genoa/62/05(H3N2), A/Genoa/3/07(H3N2), A/Genoa/2/07(H3N2), A/Genoa/3/06(H3N2)). The viruses tested belonged to three different clades that were closely related antigenically to A/California/7/04(H3N2), A/Nepal/921/06(H3N2) and A/Brisbane/10/07(H3N2). Antibody responses to these viruses were measured in 25 subjects per group using both haemagglutination inhibition (HI) and neutralization (NT) assays. At least one Committee for Medicinal Products for Human Use (CHMP) immunogenicity criteria for vaccine approval in the elderly was reached by both vaccines against all the viruses used in the study. All three CHMP criteria were reached against A/California/7/04(H3N2)-like, A/Nepal/921/06(H3N2)-like and A/Brisbane/10/07(H3N2)-like viruses by Intanza(®) 15 μg ID vaccine, while IM vaccination did not meet seroprotection criteria against circulating A/Nepal/921/06(H3N2)-like and A/Brisbane/10/07(H3N2)-like viruses or seroconversion criteria against A/Brisbane/10/07(H3N2)-like viruses. Post-vaccination HI titer, seroconversion, and seroprotection rates were higher against all viruses in subjects who received Intanza(®) 15 μg. The superiority of the seroprotection rate against the A/Nepal/921/06(H3N2)-like strain attained statistical significance despite the small sample size. Upon Beyer correction for pre-vaccination status, post-immunization HI titers against A/California/7/04(H3N2)-like and A/Brisbane/10/07(H3N2)-like strains and NT post-immunization titers against A/Wisconsin/67/05(H3N2), A/California/7/04(H3N2)-like, A/Brisbane/10/07(H3N2)-like strains were significantly higher in subjects immunized with Intanza(®) 15 μg than in individuals receiving IM vaccine. This study, although limited in the size of study population, demonstrated the broader immune response elicited by an ID influenza vaccine vs. a standard IM influenza vaccine against heterologous viruses including field isolates.

A laboratory-based surveillance study was conducted from January 2007 to May 2010 in San Martino Tertiary Referral Hospital in Genoa, Italy in which the molecular epidemiology of multidrug-resistant Acinetobacter baumannii was investigated in the five intensive care units (ICUs). A total of 53 A. baumannii strains were isolated from patients admitted to ICUs (69.8%) and to other epidemiologically linked hospital wards (30.2%) and were genotyped by repetitive extragenic palindromic polymerase chain reaction (REP-PCR), multilocus sequence typing (MLST) and adeB sequence typing. REP-PCR fingerprinting analysis, MLST and adeB typing results were well correlated and allowed us to classify strains causing epidemic events into three major epidemic clones: A (REP-I/ST4, adeB-STII genotype) isolated for the first time in May 2007, B (REP-IV/ST95, adeB-STI genotype) from November 2007 to May 2009 and C (REP-VII/ST118, adeB-STII genotype) from July 2008 to May 2010. MLST results demonstrated that epidemic clones A and C were related as they were members of the widespread clonal complex CC92. The genetic determinants of carbapenem resistance were investigated and resistance associated with the presence of the bla(OxA-58-like) gene with ISAba2 and ISAba3 elements flanking it in clone A, and with the bla(OxA-23-like) gene flanked by ISAba1 in clones B and C. A molecular approach allowed the prompt introduction of infection control measures and the evaluation of data in a global epidemiological context.

A series of case reports and anecdotal references describe the adverse effects on human health ascribed to the marine toxin palytoxin (PLTX) after different exposure routes. They include poisonings after oral intake of contaminated seafood, but also inhalation and cutaneous/systemic exposures after direct contact with aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing cnidarian zoanthids. The symptoms commonly recorded during PLTX intoxication are general malaise and weakness, associated with myalgia, respiratory effects, impairment of the neuromuscular apparatus and abnormalities in cardiac function. Systemic symptoms are often recorded together with local damages whose intensity varies according to the route and length of exposure. Gastrointestinal malaise or respiratory distress is common for oral and inhalational exposure, respectively. In addition, irritant properties of PLTX probably account for the inflammatory reactions typical of cutaneous and inhalational contact. Unfortunately, the toxin identification and/or quantification are often incomplete or missing and cases of poisoning are indirectly ascribed to PLTXs, according only to symptoms, anamnesis and environmental/epidemiological investigations (i.e. zoanthid handling or ingestion of particular seafood). Based on the available literature, we suggest a “case definition of PLTX poisonings” according to the main exposure routes, and, we propose the main symptoms to be checked, as well as, hemato-clinical analysis to be carried out. We also suggest the performance of specific analyses both on biological specimens of patients, as well as, on the contaminated materials responsible for the poisoning. A standardized protocol for data collection could provide a more rapid and reliable diagnosis of palytoxin-poisoning, but also the collection of necessary data for the risk assessment for this family of toxins.

This study evaluated the immunogenicity of a double dose of the seasonal virosomal-adjuvanted influenza vaccine (Inflexal V, Crucell, The Netherlands) in 65 previously unvaccinated children aged less than 3 years: 43 received double doses (two doses of 0.50 mL 4 weeks apart) and 22 standard doses (two doses of 0.25 mL 4 weeks apart). Both treatments evoked a response that satisfied the EMEA criteria for adequate immunogenicity for all three vaccine strains, but the double dose had a significantly greater effect on all of the studied parameters of humoral and cell-mediated immune response (p0.05). This result was achieved without any increase in the incidence of local and systemic adverse events. This means that doubling the dose of the virosomal-adjuvanted influenza vaccine (i.e. administering the same dose as that usually given to older children) effectively and safely increases the immune response to inactivated influenza vaccine in unprimed children aged less than 3 years.

In a 3-year, randomized, controlled, open-label phase III trial enrolling 3707 adults aged ≥60 years we evaluated whether the immunogenicity of an intradermal trivalent inactivated seasonal influenza vaccine, containing 15 μg of haemagglutinin per strain per 0.1 ml dose, is superior to that of a conventional intramuscular vaccine. Intradermal vaccine was given using an intradermal microinjection system. After the first vaccination, both vaccines satisfied the immunogenicity criteria for influenza vaccines for older adults set out in European regulatory guidelines, and geometric mean haemagglutination inhibition antibody titers and seroprotection rates were higher (statistically superior) with intradermal vaccination. Higher immune responses with intradermal vaccine were also observed after the 2nd and 3rd annual vaccinations. Both vaccines were well tolerated with similar systemic reactogenicity profiles. This intradermal influenza vaccine for older adults is a beneficial option for influenza protection, consistently enhancing antibody responses without compromising safety.

Vaccination is considered the most effective means of reducing influenza burden, providing substantial benefits in terms of reduction of morbidity, complications, hospitalizations and deaths, even if vaccines have been associated with a reduced immune response and lower effectiveness in older adults, in particular when a mismatch between the vaccine and the circulating virus strains occurred. Several strategies have been proposed to enhance vaccine protection against drifted strains, including the use of adjuvants. Among oil-emulsion adjuvants, MF-59 was approved for human use more than a decade ago and it is largely used for adjuvantation of influenza vaccine. Recent studies have demonstrated that addition of the MF-59 to subunit influenza vaccine can lead to higher haemagglutination-inhibiting seroprotection rates and to higher neutralization antibody titers against drifted strains not included in the vaccine respect to non-adjuvanted vaccine. Promising results were obtained using a new generation of oil-in-water emulsion adjuvants, named AS, offering cross-protection against heterologous challenge in ferrets.

The total burden of acute respiratory diseases in children is still not completely understood. Clinical and epidemiological surveillance of influenza (FLU) and other Acute Respiratory Infections (ARI) are currently a major objective of Public Health in order to approach “ad hoc” prevention strategies in pediatric population. The principal aim of our study was to describe the epidemiology of these diseases using an appropriate surveillance system. During 2000–2001 and 2001–2002 seasons, respectively 49 and 55 sentinel paediatricians monitored 10 Italian Regions (Liguria, Lombardy, Friuli Venezia Giulia, Tuscany, Umbria, Marche, Abbruzzo, Puglia, Calabria and Sicily) weekly notifying FLU, monitored as Influenza Like Illness (ILI), and ARI clinical cases. We calculated cumulative weekly morbidity rate×1000 subjects between 0 and 14 years during winter season (44th to 17th week). The FLU vaccinal status and the number of hospitalisations were also looked into.

A clinical trial with four groups receiving either 0.6, 3.5, 10 or 20 micro g of purified non-adsorbed hepatitis B surface antigen (HBsAg) was performed to study the kinetics as well as the capacity of the immune memory to respond following exposure to HBsAg in responders to a complete course of hepatitis B vaccine, in whom anti-HBs titres had declined below the seroprotective level. The study population included 64 healthy individuals. All response parameters seropositivity, seroprotection rates, booster response rates and geometric mean titres (GMTs), consistently showed that the immune response was highly satisfactory and dose-dependent. A remarkable immune response was obtained even with a trace amount of HBsAg. This study further supports recent indication that booster hepatitis B vaccine doses may be unnecessary in healthy adult responders to a full course of hepatitis B vaccination.

The aim of this study was to create a model that forecasted the stay in the intensive care unit in post–liver transplantation. Methods Twenty-three consecutive patients who underwent liver transplantation provided samples for serum sodium, serum creatinine, total bilirubin, cholesterol, aspartate and alanine aminotransferase, alkaline phosphatase (ALP), albumin, and platelet count for correlation together with age at transplantation in a Pearson correlation model with intensive care unit stay. Multivariate analysis used a regression model to evaluate the relationship between the dependent variable “intensive care unit stay” and the predictor variables that were correlated by a Pearson correlation test. To test the acceptability and strength of the model, analyses of variance was performed and a multiple correlation coefficient R was calculated for the model. Results Pearson correlation test showed a strong correlation between intensive care unit stay and creatinine (correlation coefficient = 0.34, P = .03), serum sodium (correlation coefficient = −0.42, P P = .06). Other variables showed no significant correlation, namely correlation coefficients P > .1). The final model to evaluate the relationship between the dependent variable “intensive care unit stay” and laboratory parameters included ALP, serum creatinine, serum sodium, and total bilirubin as well as a correction for age. Conclusions The most significant parameters were total bilirubin, serum creatinine, and serum sodium. The proposal model significantly correlated with the variable “intensive care unit stay.” Such data are particularly important since increased intensive care unit stay correlates with a significant reduction in 1-year survival rate.

An analytical and laboratory evaluation of a newly-developed fully-automated third generation ELISA for the detection of anti-HCV (Cobas Core Anti-HCV EIA, Roche) was undertaken. Coefficients of variation (CVs) calculated on positive control and serum samples ranged from 5.9 to 9.8% in the intra-assay precision test and from 3.9 to 11.3% in the inter-assay evaluation. With regard to the study of clinical laboratory performance, five groups of sera pre-screened with two third generation ELISA (Ortho HCV 3.0 ELISA; Innotest HCV Ab III) were assayed: anti-HCV negative samples (n = 932); anti-HCV positive samples (n = 449); difficult sera of different origin (n = 113); sera with discrepant results in the two ELISAs (n = 50); sera with an indeterminate result in one or more confirmatory test (n = 34). The overall concordance between the Roche anti-HCV EIA and the two reference assays was 97.5 and 97.8% for the Ortho and for the Innogenetics assays, respectively. Although it is not possible to provide absolute figures for clinical sensitivity and specificity, the results of the study on discrepant samples show that the Cobas Core Anti-HCV gives a number of negative results with positive or indeterminate confirmatory anti-HCV tests, which is intermediate between the Ortho and the Innogenetics assay. In contrast, only 5% Cobas Core Anti-HCV reactive sera are not positive or clear-cut single band reactive by supplemental assays. The results show that the new fully-automated third generation anti-HCV test is a valid alternative to other commercially available assays for screening of antibodies to the hepatitis C virus.

Background and aim: To evaluate the feasibility, safety and efficacy of single-step balloon-occluded-RFA followed by TACE in patients with “complex” unresectable HCC, previously not suitable to RFA alone due to their localization. Material and methods: 63 consecutive patients with at least one HCC lesion (mean diameter 4.35±1.8cm), adjacent to the diaphragm/glisson’s capsule (33 lesions), proximal to the hepatic or portal vein (19), cholecistis (6) and/or located on the intra-abdominal free surface (5), considered as “complex” for their unfavourable location, and not suitable for RFA alone, were enrolled in our single-center multidisciplinary pilot study. The treatment was composed by RFA (single 2-cm or 3-cm monopolar needle insertion) during occlusion of the feeding artery followed by superselective TACE (conventional-TACE or with DC-BEAD). Adverse events and intra/periprocedural complications were clinically assessed. Tumor response was evaluated on 1-month and 6 months follow-up multiphasic CT based on mRECIST criteria. Results: Technical success was achievied in all patients. 7 patients (11,2%) experienced intra and periprocedural self-limiting complications: fistulae (2), bleeding (3), cholecistitis (1) and ascites (1). A mean total treated diameter (necrotic diameter plus circonferential peripheral lipiodol uptake for conventional TACE; mean necrotic diameter for TACE with DC-Bead) of 4.96±2,37 was obtained. Based on mRECIST criteria, on 1and 3-months follow up CT, a radiologic response was obtained in all patients, with a complete response achieved in 31 out of 63 pts (49,2%), a partial response in 38,1% (24 pts: residual tumor 30%- 50% in 4 pts), and no response in 3 pts, without any progressive disease. 5 pts were lost to follow up. 18 out of 27 pts (66,6%) that underwent a CT-scan on 6-months follow up maintained a complete response. Conclusions: Balloon-occluded-RFA plus TACE seems to be a safe and effective therapy for the treatment of “complex“ HCC, allowing to obtain a high complete local response rate, without complications, also in patients not suitable to RFA alone.

28% (1360/4890); 45% (520/1154) in meningitis and 22% (840/3736) in other IPD cases (p < 0.001). Of patients tested for HIV, HIV-seroprevalence was 512/664 (77%) amongst meningitis cases and 2062/2346 (88%) amongst other IPD (p < 0.001). On multivariable analysis of meningitis cases, HIV-coinfection was associated with increased odds of death when controlling for age group, severity of illness [Pitt bacteraemia score], prior antibiotic use and province (odds ratio 2.2, 95% confidence interval 1.3—3.6). HIV-coinfection was not an independent risk factor for death in other IPD cases. Conclusions: Pneumococcal meningitis has a high mortality in South Africa, and HIV-infected patients are at increased risk of death. Access to antiretroviral therapy for HIV-positive patients and introduction of the pneumococcal conjugate vaccine for routine immunization should be prioritized.