The question of whether influenza vaccine effectiveness (VE) wanes over the winter season is still open and some contradictory findings have been reported. This study investigated the possible ...decline in protection provided by the available influenza vaccines.
An individual-level pooled analysis of six test-negative case-control studies conducted in Italy between the 2018/2019 and 2022/2023 seasons was performed. Multivariable logistic regression analyses were performed to estimate weekly change in the odds of testing positive for influenza 14 days after vaccination.
Of 6490 patients included, 1633 tested positive for influenza. Each week that had elapsed since vaccination was associated with an increase in the odds of testing positive for any influenza (4.9%; 95% CI: 2.0-8.0%) and for A(H3N2) (6.5%; 95% CI: 2.9-10.3%). This decline in VE was, however, significant only in children and older adults. A similar increase in the odds of testing positive was seen when the dataset was restricted to vaccinees only. Conversely, VE waning was less evident for A(H1N1)pdm09 or B strains.
Significant waning of VE, especially against influenza A(H3N2), may be one of the factors associated with suboptimal end-of-season VE. Next-generation vaccines should provide more durable protection against A(H3N2).
•Both adjuvanted trivalent (aTIV) and unadjuvanted quadrivalent (QIVe) flu vaccines are used in older adults.•It is largely unknown if aTIV is more effective than QIVe against confirmed ...influenza.•aTIV was more effective than QIVe against severe laboratory-confirmed influenza.•The relative effectiveness of aTIV vs QIVe may be biased by confounding by indication.
In this study, we aimed to investigate the relative vaccine effectiveness (rVE) of the MF59-adjuvanted trivalent (aTIV) and non-adjuvanted quadrivalent (QIVe) egg-based standard-dose vaccines against severe laboratory-confirmed influenza.
This test-negative case-control study was conducted in a hospital setting during four recent Italian influenza seasons (from 2018/19 to 2021/22). The clinical outcome was severe acute respiratory infection (SARI) with laboratory confirmation diagnosed among subjects aged ≥65 years. rVE of aTIV versus QIVe was estimated through propensity score matching followed by logistic regression.
The influenza virus circulated to a significant extent only during the 2018/19 and 2019/20 seasons. The final population included 512 vaccinated older adults, of which 83 were cases and 429 were test-negative controls. aTIV and QIVe users differed substantially from the point of view of several baseline characteristics. The propensity score adjusted rVE of aTIV vs QIVe was 59.2% (95% CI: 14.6%, 80.5%), 54.7% (95% CI: -28.7%, 84.0%) and 56.9% (95% CI: -7.8%, 82.8%) against any influenza, A(H1N1)pdm09 and A(H3N2), respectively.
aTIV was more effective than QIVe in preventing laboratory-confirmed SARI. The benefits of aTIV may be obscured by confounding indication.
The integration of empirical data in computational frameworks designed to model the spread of infectious diseases poses a number of challenges that are becoming more pressing with the increasing ...availability of high-resolution information on human mobility and contacts. This deluge of data has the potential to revolutionize the computational efforts aimed at simulating scenarios, designing containment strategies, and evaluating outcomes. However, the integration of highly detailed data sources yields models that are less transparent and general in their applicability. Hence, given a specific disease model, it is crucial to assess which representations of the raw data work best to inform the model, striking a balance between simplicity and detail.
We consider high-resolution data on the face-to-face interactions of individuals in a pediatric hospital ward, obtained by using wearable proximity sensors. We simulate the spread of a disease in this community by using an SEIR model on top of different mathematical representations of the empirical contact patterns. At the most detailed level, we take into account all contacts between individuals and their exact timing and order. Then, we build a hierarchy of coarse-grained representations of the contact patterns that preserve only partially the temporal and structural information available in the data. We compare the dynamics of the SEIR model across these representations.
We show that a contact matrix that only contains average contact durations between role classes fails to reproduce the size of the epidemic obtained using the high-resolution contact data and also fails to identify the most at-risk classes. We introduce a contact matrix of probability distributions that takes into account the heterogeneity of contact durations between (and within) classes of individuals, and we show that, in the case study presented, this representation yields a good approximation of the epidemic spreading properties obtained by using the high-resolution data.
Our results mark a first step towards the definition of synopses of high-resolution dynamic contact networks, providing a compact representation of contact patterns that can correctly inform computational models designed to discover risk groups and evaluate containment policies. We show in a typical case of a structured population that this novel kind of representation can preserve in simulation quantitative features of the epidemics that are crucial for their study and management.
The present study aims to evaluate the cost-effectiveness of the newly introduced varicella and herpes zoster (HZ) vaccination programmes in Italy. The appropriateness of the introduction of the ...varicella vaccine is highly debated because of concerns about the consequences on HZ epidemiology and the expected increase in the number of severe cases in case of suboptimal coverage levels.
We performed a cost-utility analysis based on a stochastic individual-based model that considers realistic demographic processes and two different underlying mechanisms of exogenous boosting (temporary and progressive immunity). Routine varicella vaccination is given with a two-dose schedule (15 months, 5-6 years). The HZ vaccine is offered to the elderly (65 years), either alone or in combination with an initial catch-up campaign (66-75 years). The main outcome measures are averted cases and deaths, costs per quality-adjusted life years gained, incremental cost-effectiveness ratios, and net monetary benefits associated with the different vaccination policies.
Demographic processes have contributed to shaping varicella and HZ epidemiology over the years, decreasing varicella circulation and increasing the incidence of HZ. The recent introduction of varicella vaccination in Italy is expected to produce an enduring reduction in varicella incidence and, indirectly, a further increase of HZ incidence in the first decades, followed by a significant reduction in the long term. However, the concurrent introduction of routine HZ vaccination at 65 years of age is expected to mitigate this increase and, in the longer run, to reduce HZ burden to its minimum. From an economic perspective, all the considered policies are cost-effective, with the exception of varicella vaccination alone when considering a time horizon of 50 years. These results are robust to parameter uncertainties, to the two different hypotheses on the mechanism driving exogenous boosting, and to different demographic projection scenarios.
The recent introduction of a combined varicella and HZ vaccination programme in Italy will produce significant reductions in the burden of both diseases and is found to be a cost-effective policy. This programme will counterbalance the increasing trend of zoster incidence purely due to demographic processes.
Protection provided by seasonal influenza vaccination (SIV) may be measured against numerous outcomes, and their heterogeneity may hamper decision-making. The aim of this study was to explore ...outcomes used for estimation of SIV efficacy/effectiveness (VE) and obtain expert consensus on their importance.BACKGROUNDProtection provided by seasonal influenza vaccination (SIV) may be measured against numerous outcomes, and their heterogeneity may hamper decision-making. The aim of this study was to explore outcomes used for estimation of SIV efficacy/effectiveness (VE) and obtain expert consensus on their importance.An umbrella review was first conducted to collect and map outcomes considered in systematic reviews of SIV VE. A Delphi study was then performed to reach expert convergence on the importance of single outcomes, measured on a 9-point Likert scale, in principal target groups, namely children, working-age adults, older adults, subjects with co-morbidities and pregnant women.RESEARCH DESIGN AND METHODSAn umbrella review was first conducted to collect and map outcomes considered in systematic reviews of SIV VE. A Delphi study was then performed to reach expert convergence on the importance of single outcomes, measured on a 9-point Likert scale, in principal target groups, namely children, working-age adults, older adults, subjects with co-morbidities and pregnant women.The literature review identified 489 outcomes. Following data reduction, 20 outcomes were selected for the Delphi process. After two Delphi rounds and a final consensus meeting, convergence was reached. All 20 outcomes were judged to be important or critically important. More severe outcomes, such as influenza-related hospital encounters and mortality with or without laboratory confirmation, were generally top-ranked across all target groups (median scores ≥8 out of 9).RESULTSThe literature review identified 489 outcomes. Following data reduction, 20 outcomes were selected for the Delphi process. After two Delphi rounds and a final consensus meeting, convergence was reached. All 20 outcomes were judged to be important or critically important. More severe outcomes, such as influenza-related hospital encounters and mortality with or without laboratory confirmation, were generally top-ranked across all target groups (median scores ≥8 out of 9).Rather than focusing on laboratory-confirmed infection per se, experimental and observational VE studies should include more severe influenza-related outcomes because they are expected to exercise a greater impact on decision-making.CONCLUSIONSRather than focusing on laboratory-confirmed infection per se, experimental and observational VE studies should include more severe influenza-related outcomes because they are expected to exercise a greater impact on decision-making.
Italy has experienced severe consequences (ie, hospitalizations and deaths) during the COVID-19 pandemic. Online decision support systems (DSS) and self-triage applications have been used in several ...settings to supplement health authority recommendations to prevent and manage COVID-19. A digital Italian health tech startup, Paginemediche, developed a noncommercial, online DSS with a chat user interface to assist individuals in Italy manage their potential exposure to COVID-19 and interpret their symptoms since early in the pandemic.
This study aimed to compare the trend in online DSS sessions with that of COVID-19 cases reported by the national health surveillance system in Italy, from February 2020 to March 2021.
We compared the number of sessions by users with a COVID-19-positive contact and users with COVID-19-compatible symptoms with the number of cases reported by the national surveillance system. To calculate the distance between the time series, we used the dynamic time warping algorithm. We applied Symbolic Aggregate approXimation (SAX) encoding to the time series in 1-week periods. We calculated the Hamming distance between the SAX strings. We shifted time series of online DSS sessions 1 week ahead. We measured the improvement in Hamming distance to verify the hypothesis that online DSS sessions anticipate the trends in cases reported to the official surveillance system.
We analyzed 75,557 sessions in the online DSS; 65,207 were sessions by symptomatic users, while 19,062 were by contacts of individuals with COVID-19. The highest number of online DSS sessions was recorded early in the pandemic. Second and third peaks were observed in October 2020 and March 2021, respectively, preceding the surge in notified COVID-19 cases by approximately 1 week. The distance between sessions by users with COVID-19 contacts and reported cases calculated by dynamic time warping was 61.23; the distance between sessions by symptomatic users was 93.72. The time series of users with a COVID-19 contact was more consistent with the trend in confirmed cases. With the 1-week shift, the Hamming distance between the time series of sessions by users with a COVID-19 contact and reported cases improved from 0.49 to 0.46. We repeated the analysis, restricting the time window to between July 2020 and December 2020. The corresponding Hamming distance was 0.16 before and improved to 0.08 after the time shift.
Temporal trends in the number of online COVID-19 DSS sessions may precede the trend in reported COVID-19 cases through traditional surveillance. The trends in sessions by users with a contact with COVID-19 may better predict reported cases of COVID-19 than sessions by symptomatic users. Data from online DSS may represent a useful supplement to traditional surveillance and support the identification of early warning signals in the COVID-19 pandemic.
Since 1985, two antigenically distinct lineages of influenza B viruses (Victoria-like and Yamagata-like) have circulated globally. Trivalent seasonal influenza vaccines contain two circulating ...influenza A strains but a single B strain and thus provide limited immunity against circulating B strains of the lineage not included in the vaccine. In this study, we describe the characteristics of influenza B viruses that caused respiratory illness in the population in Italy over 13 consecutive seasons of virological surveillance, and the match between the predominant influenza B lineage and the vaccine B lineage, in each season.
From 2004 to 2017, 26,886 laboratory-confirmed influenza cases were registered in Italy, of which 18.7% were type B. Among them, the lineage of 2465 strains (49%) was retrieved or characterized in this study by a real-time RT-PCR assay and/or sequencing of the hemagglutinin (HA) gene.
Co-circulation of both B lineages was observed each season, although in different proportions every year. Overall, viruses of B/Victoria and B/Yamagata lineages caused 53.3 and 46.7% of influenza B infections, respectively. A higher proportion of infections with both lineages was detected in children, and there was a declining frequency of B/Victoria detections with age. A mismatch between the vaccine and the predominant influenza B lineage occurred in eight out of thirteen influenza seasons under study. Considering the seasons when B accounted for > 20% of all laboratory-confirmed influenza cases, a mismatch was observed in four out of six seasons. Phylogenetic analysis of the HA1 domain confirmed the co-circulation of both lineages and revealed a mixed circulation of distinct evolutionary viral variants, with different levels of match to the vaccine strains.
This study contributes to the understanding of the circulation of influenza B viruses in Italy. We found a continuous co-circulation of both B lineages in the period 2004-2017, and determined that children were particularly vulnerable to Victoria-lineage influenza B virus infections. An influenza B lineage mismatch with the trivalent vaccine occurred in about two-thirds of cases.
This comprehensive retrospective data-linkage study aimed at evaluating the impact of Direct-Acting Antivirals (DAAs) on Hepatitis C Virus (HCV) testing, treatment trends, and access to care in ...Tuscany over six years following their introduction. Utilizing administrative healthcare records, our work reveals a substantial increase in HCV tests in 2017, attributed to the decision to provide universal access to treatment. However, despite efforts to eradicate chronic HCV through a government-led plan, the target of treating 6,221 patients annually was not met, and services contracted after 2018, exacerbated by the COVID-19 pandemic. Key findings indicate a higher prevalence of HCV screening among females in the 33-53 age group, influenced by pregnancy-related recommendations, while diagnostic tests and treatment uptake were more common among males. Problematic substance users constituted a significant proportion of those tested and treated, emphasizing their priority in HCV screening. Our paper underscores the need for decentralized HCV models and alternative testing strategies, such as point-of-care assays, especially in populations accessing harm reduction services, communities, and prisons. The study acknowledges limitations in relying solely on administrative records, advocating for improved data access and timely linkages to accurately monitor HCV care cascades and inform regional plans. Despite challenges, the paper demonstrates the value of administrative record linkages in understanding the access to care pathway for hard-to-reach populations. The findings emphasize the importance of the national HCV elimination strategy and the need for enhanced data collection to assess progress accurately, providing insights for future regional and national interventions.
KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential ...diagnosis. We aimed to better characterize natural history of KBGS. In the context of a European collaborative study, we collected the largest cohort of KBGS patients (49). A combined array- based Comparative Genomic Hybridization and next generation sequencing (NGS) approach investigated both genomic Copy Number Variants and SNVs. Intellectual disability (ID) (82%) ranged from mild to moderate with severe ID identified in two patients. Epilepsy was present in 26.5%. Short stature was consistent over time, while occipitofrontal circumference (median value: -0.88 SD at birth) normalized over years. Cerebral anomalies, were identified in 56% of patients and thus represented the second most relevant clinical feature reinforcing clinical suspicion in the paediatric age when short stature and vertebral/dental anomalies are vague. Macrodontia, oligodontia and dental agenesis (53%) were almost as frequent as skeletal anomalies, such as brachydactyly, short fifth finger, fifth finger clinodactyly, pectus excavatum/carinatum, delayed bone age. In 28.5% of individuals, prenatal ultrasound anomalies were reported. Except for three splicing variants, leading to a premature termination, variants were almost all frameshift. Our results, broadening the spectrum of KBGS phenotype progression, provide useful tools to facilitate differential diagnosis and improve clinical management. We suggest to consider a wider range of dental anomalies before excluding diagnosis and to perform a careful odontoiatric/ear-nose-throat (ENT) evaluation in order to look for even submucosal palate cleft given the high percentage of palate abnormalities. NGS approaches, following evidence of antenatal ultrasound anomalies, should include ANKRD11.
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