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We used published data from outbreak investigations of monkeypox virus clade I in the Democratic Republic of the Congo to estimate the distributions of critical epidemiological parameters. We estimated a mean incubation period of 9.9 days (95% credible interval [CrI] 8.5-11.5 days) and a mean generation time of 17.2 days (95% CrI 14.1-20.9 days) or 11.3 days (95% CrI 9.4-14.0 days), depending on the considered dataset. Presymptomatic transmission was limited. Those estimates suggest generally slower transmission dynamics in clade I than in clade IIb. The time-varying reproduction number for clade I in the Democratic Republic of the Congo was estimated to be below the epidemic threshold in the first half of 2024. However, in the South Kivu Province, where the newly identified subclade Ib has been associated with sustained human-to-human transmission, we estimated an effective reproduction number above the epidemic threshold (95% CrI 0.96-1.27).

Background: The time-varying reproduction number R is a critical variable for situational awareness during infectious disease outbreaks; however, delays between infection and reporting of cases hinder its accurate estimation in real-time. A number of nowcasting methods, leveraging available information on data consolidation delays, have been proposed to mitigate this problem., Methods: In this work, we retrospectively validate the use of a nowcasting algorithm during 18 months of the COVID-19 pandemic in Italy by quantitatively assessing its performance against standard methods for the estimation of R., Results: Nowcasting significantly reduced the median lag in the estimation of R from 13 to 8 days, while concurrently enhancing accuracy. Furthermore, it allowed the detection of periods of epidemic growth with a lead of between 6 and 23 days., Conclusions: Nowcasting augments epidemic awareness, empowering better informed public health responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bizzotto, Guzzetta, Marziano, Del Manso, Mateo Urdiales, Petrone, Cannone, Sacco, Poletti, Manica, Zardini, Trentini, Fabiani, Bella, Riccardo, Pezzotti, Ajelli and Merler.)

Quantifying the potential spatial spread of an infectious pathogen is key to defining effective containment and control strategies. The aim of this study is to estimate the risk of SARS-CoV-2 transmission at different distances in Italy before the first regional lockdown was imposed, identifying important sources of national spreading. To do this, we leverage on a probabilistic model applied to daily symptomatic cases retrospectively ascertained in each Italian municipality with symptom onset between January 28 and March 7, 2020. Results are validated using a multi-patch dynamic transmission model reproducing the spatiotemporal distribution of identified cases. Our results show that the contribution of short-distance ( ≤ 10 k m ) transmission increased from less than 40% in the last week of January to more than 80% in the first week of March 2020. On March 7, 2020, that is the day before the first regional lockdown was imposed, more than 200 local transmission foci were contributing to the spread of SARS-CoV-2 in Italy. At the time, isolation measures imposed only on municipalities with at least ten ascertained cases would have left uncontrolled more than 75% of spillover transmission from the already affected municipalities. In early March, national-wide restrictions were required to curb short-distance transmission of SARS-CoV-2 in Italy., (© 2024. The Author(s).)

Background: Surveillance data and vaccination registries are widely used to provide real-time vaccine effectiveness (VE) estimates, which can be biased due to underreported (i.e. under-ascertained and under-notified) infections. Here, we investigate how the magnitude and direction of this source of bias in retrospective cohort studies vary under different circumstances, including different levels of underreporting, heterogeneities in underreporting across vaccinated and unvaccinated, and different levels of pathogen circulation., Methods: We developed a stochastic individual-based model simulating the transmission dynamics of a respiratory virus and a large-scale vaccination campaign. Considering a baseline scenario with 22.5% yearly attack rate and 30% reporting ratio, we explored fourteen alternative scenarios, each modifying one or more baseline assumptions. Using synthetic individual-level surveillance data and vaccination registries produced by the model, we estimated the VE against documented infection taking as reference either unvaccinated or recently vaccinated individuals (within 14 days post-administration). Bias was quantified by comparing estimates to the known VE assumed in the model., Results: VE estimates were accurate when assuming homogeneous reporting ratios, even at low levels (10%), and moderate attack rates (<50%). A substantial downward bias in the estimation arose with homogeneous reporting and attack rates exceeding 50%. Mild heterogeneities in reporting ratios between vaccinated and unvaccinated strongly biased VE estimates, downward if cases in vaccinated were more likely to be reported and upward otherwise, particularly when taking as reference unvaccinated individuals., Conclusions: In observational studies, high attack rates or differences in underreporting between vaccinated and unvaccinated may result in biased VE estimates. This study underscores the critical importance of monitoring data quality and understanding biases in observational studies, to more adequately inform public health decisions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)

The "Investigating and translating genomic evidence for public health response to SARS-CoV-2 (INSIDE SARS-CoV-2)" project is part of the initiative "Joint science and technology cooperation call for joint project proposals for the years 2021-2023" promoted by the Italian Ministry of Foreign Affairs and International Cooperation (MAECI) and the Republic of India. To start the project activities, the pandemic response and the epidemiological situation in Italy and in India, together with the genomic surveillance strategies for SARS-CoV-2 virus in the two countries, are here described.

In 2022, a global outbreak of mpox occurred, predominantly impacting men who have sex with men (MSM). The rapid decline of this epidemic is yet to be fully understood. We investigated the Italian outbreak by means of an individual-based mathematical model calibrated to surveillance data. The model accounts for transmission within the MSM sexual contact network, in recreational and sex clubs attended by MSM, and in households. We indicate a strong spontaneous reduction in sexual transmission (61-87%) in affected MSM communities as the possible driving factor for the rapid decline in cases. The MSM sexual contact network was the main responsible for transmission (about 80%), with clubs and households contributing residually. Contact tracing prevented about half of the potential cases, and a higher success rate in tracing contacts could significantly amplify its effectiveness. Notably, immunizing the 23% of MSM with the highest sexual activity (10 or more partners per year) could completely prevent new mpox resurgences. This research underscores the importance of augmenting contact tracing, targeted immunization campaigns of high-risk groups, and fostering reactive behavioral changes as key strategies to manage and prevent the spread of emerging sexually transmitted pathogens like mpox within the MSM community., (© 2024. The Author(s).)

Background: Estimates of the spatiotemporal distribution of different mosquito vector species and the associated risk of transmission of arboviruses are key to design adequate policies for preventing local outbreaks and reducing the number of human infections in endemic areas. In this study, we quantified the abundance of Aedes albopictus and Aedes aegypti and the local transmission potential for three arboviral infections at an unprecedented spatiotemporal resolution in areas where no entomological surveillance is available., Methods: We developed a computational model to quantify the daily abundance of Aedes mosquitoes, leveraging temperature and precipitation records. The model was calibrated on mosquito surveillance data collected in 115 locations in Europe and the Americas between 2007 and 2018. Model estimates were used to quantify the reproduction number of dengue virus, Zika virus, and chikungunya in Europe and the Americas, at a high spatial resolution., Findings: In areas colonised by both Aedes species, A aegypti was estimated to be the main vector for the transmission of dengue virus, Zika virus, and chikungunya, being associated with a higher estimate of R 0 when compared with A albopictus. Our estimates highlighted that these arboviruses were endemic in tropical and subtropical countries, with the highest risks of transmission found in central America, Venezuela, Colombia, and central-east Brazil. A non-negligible potential risk of transmission was also estimated for Florida, Texas, and Arizona (USA). The broader ecological niche of A albopictus could contribute to the emergence of chikungunya outbreaks and clusters of dengue autochthonous cases in temperate areas of the Americas, as well as in mediterranean Europe (in particular, in Italy, southern France, and Spain)., Interpretation: Our results provide a comprehensive overview of the transmission potential of arboviral diseases in Europe and the Americas, highlighting areas where surveillance and mosquito control capacities should be prioritised., Funding: EU and Ministero dell'Università e della Ricerca, Italy (Piano Nazionale di Ripresa e Resilienza Extended Partnership initiative on Emerging Infectious Diseases); EU (Horizon 2020); Ministero dell'Università e della Ricerca, Italy (Progetti di ricerca di Rilevante Interesse Nazionale programme); Brazilian National Council of Science, Technology and Innovation; Ministry of Health, Brazil; and Foundation of Research for Minas Gerais, Brazil., Competing Interests: Declaration of interests MA has received research funding from Seqirus. The funding is related to influenza vaccination in Italy and thus not related to this manuscript. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Different monitoring and control policies have been implemented in schools to minimize the spread of SARS-CoV-2. Transmission in schools has been hard to quantify due to the large proportion of asymptomatic carriers in young individuals. We applied a Bayesian approach to reconstruct the transmission chains between 284 SARS-CoV-2 infections ascertained during 87 school outbreak investigations conducted between March and April 2021 in Italy. Under the policy of reactive quarantines, we found that 42.5% (95%CrI: 29.5-54.3%) of infections among school attendees were caused by school contacts. The mean number of secondary cases infected at school by a positive individual during in-person education was estimated to be 0.33 (95%CrI: 0.23-0.43), with marked heterogeneity across individuals. Specifically, we estimated that only 26.0% (95%CrI: 17.6-34.1%) of students and school personnel who tested positive during in-person education caused at least one secondary infection at school. Positive individuals who attended school for at least 6 days before being isolated or quarantined infected on average 0.49 (95%CrI: 0.14-0.83) secondary cases. Our findings provide quantitative insights on the contribution of school transmission to the spread of SARS-CoV-2 in young individuals. Identifying positive cases within 5 days after exposure to their infector could reduce onward transmission at school by at least 30%., Competing Interests: Declaration of Competing Interest MA has received research funding from Seqirus. The funding is not related to COVID-19. All other authors declare no competing interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The difficulty in identifying SARS-CoV-2 infections has not only been the major obstacle to control the COVID-19 pandemic but also to quantify changes in the proportion of infections resulting in hospitalization, intensive care unit (ICU) admission, or death., Methods: We developed a model of SARS-CoV-2 transmission and vaccination informed by official estimates of the time-varying reproduction number to estimate infections that occurred in Italy between February 2020 and 2022. Model outcomes were compared with the Italian National surveillance data to estimate changes in the SARS-CoV-2 infection ascertainment ratio (IAR), infection hospitalization ratio (IHR), infection ICU ratio (IIR), and infection fatality ratio (IFR) in five different sub-periods associated with the dominance of the ancestral lineages and Alpha, Delta, and Omicron BA.1 variants., Results: We estimate that, over the first 2 years of pandemic, the IAR ranged between 15% and 40% (range of 95%CI: 11%-61%), with a peak value in the second half of 2020. The IHR, IIR, and IFR consistently decreased throughout the pandemic with 22-44-fold reductions between the initial phase and the Omicron period. At the end of the study period, we estimate an IHR of 0.24% (95%CI: 0.17-0.36), IIR of 0.015% (95%CI: 0.011-0.023), and IFR of 0.05% (95%CI: 0.04-0.08)., Conclusions: Since 2021, changes in the dominant SARS-CoV-2 variant, vaccination rollout, and the shift of infection to younger ages have reduced SARS-CoV-2 infection ascertainment. The same factors, combined with the improvement of patient management and care, contributed to a massive reduction in the severity and fatality of COVID-19., Competing Interests: MA has received research funding from Seqirus. The funding is not related to COVID‐19. PS has received funding from GSK, not related to this project. All other authors declare no conflicts of interest., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

We estimated the mean serial interval for Sudan virus in Uganda to be 11.7 days (95 CI% 8.2-15.8 days). Estimates for the 2022 outbreak indicate a mean basic reproduction number of 2.4-2.7 (95% CI 1.7-3.5). Estimated net reproduction numbers across districts suggest a marked spatial heterogeneity.

Importance: Estimates of the rate of waning of vaccine effectiveness (VE) against COVID-19 are key to assess population levels of protection and future needs for booster doses to face the resurgence of epidemic waves., Objective: To quantify the progressive waning of VE associated with the Delta and Omicron variants of SARS-CoV-2 by number of received doses., Data Sources: PubMed and Web of Science were searched from the databases' inception to October 19, 2022, as well as reference lists of eligible articles. Preprints were included., Study Selection: Selected studies for this systematic review and meta-analysis were original articles reporting estimates of VE over time against laboratory-confirmed SARS-CoV-2 infection and symptomatic disease., Data Extraction and Synthesis: Estimates of VE at different time points from vaccination were retrieved from original studies. A secondary data analysis was performed to project VE at any time from last dose administration, improving the comparability across different studies and between the 2 considered variants. Pooled estimates were obtained from random-effects meta-analysis., Main Outcomes and Measures: Outcomes were VE against laboratory-confirmed Omicron or Delta infection and symptomatic disease and half-life and waning rate associated with vaccine-induced protection., Results: A total of 799 original articles and 149 reviews published in peer-reviewed journals and 35 preprints were identified. Of these, 40 studies were included in the analysis. Pooled estimates of VE of a primary vaccination cycle against laboratory-confirmed Omicron infection and symptomatic disease were both lower than 20% at 6 months from last dose administration. Booster doses restored VE to levels comparable to those acquired soon after the administration of the primary cycle. However, 9 months after booster administration, VE against Omicron was lower than 30% against laboratory-confirmed infection and symptomatic disease. The half-life of VE against symptomatic infection was estimated to be 87 days (95% CI, 67-129 days) for Omicron compared with 316 days (95% CI, 240-470 days) for Delta. Similar waning rates of VE were found for different age segments of the population., Conclusions and Relevance: These findings suggest that the effectiveness of COVID-19 vaccines against laboratory-confirmed Omicron or Delta infection and symptomatic disease rapidly wanes over time after the primary vaccination cycle and booster dose. These results can inform the design of appropriate targets and timing for future vaccination programs.

The worldwide inequitable access to vaccination claims for a re-assessment of policies that could minimize the COVID-19 burden in low-income countries. Nine months after the launch of the national vaccination program in March 2021, only 3.4% of the Ethiopian population received two doses of COVID-19 vaccine. We used a SARS-CoV-2 transmission model to estimate the level of immunity accrued before the launch of vaccination in the Southwest Shewa Zone (SWSZ) and to evaluate the impact of alternative age priority vaccination targets in a context of limited vaccine supply. The model was informed with available epidemiological evidence and detailed contact data collected across different geographical settings (urban, rural, or remote). We found that, during the first year of the pandemic, the mean proportion of critical cases occurred in SWSZ attributable to infectors under 30 years of age would range between 24.9 and 48.0%, depending on the geographical setting. During the Delta wave, the contribution of this age group in causing critical cases was estimated to increase on average to 66.7-70.6%. Our findings suggest that, when considering the vaccine product available at the time (ChAdOx1 nCoV-19; 65% efficacy against infection after 2 doses), prioritizing the elderly for vaccination remained the best strategy to minimize the disease burden caused by Delta, irrespectively of the number of available doses. Vaccination of all individuals aged ≥ 50 years would have averted 40 (95%PI: 18-60), 90 (95%PI: 61-111), and 62 (95%PI: 21-108) critical cases per 100,000 residents in urban, rural, and remote areas, respectively. Vaccination of all individuals aged ≥ 30 years would have averted an average of 86-152 critical cases per 100,000 individuals, depending on the setting considered. Despite infections among children and young adults likely caused 70% of critical cases during the Delta wave in SWSZ, most vulnerable ages should remain a key priority target for vaccination against COVID-19., (© 2023. The Author(s).)

Background: School closures and distance learning have been extensively adopted to counter the COVID-19 pandemic. However, the contribution of school transmission to the spread of SARS-CoV-2 remains poorly quantified., Methods: We analyzed transmission patterns associated with 976 SARS-CoV-2 exposure events, involving 460 positive individuals, as identified in early 2021 through routine surveillance and an extensive screening conducted on students, school personnel, and their household members in a small Italian municipality. In addition to population screenings and contact-tracing operations, reactive closures of class and schools were implemented., Results: From the analysis of 152 clear infection episodes and 584 exposure events identified by epidemiological investigations, we estimated that approximately 50%, 21%, and 29% of SARS-CoV-2 transmission was associated with household, school, and community contacts, respectively. We found substantial transmission heterogeneities, with 20% positive individuals causing 75% to 80% of ascertained infection episodes. A higher proportion of infected individuals causing onward transmission was found among students (46.2% vs. 25%, on average), who also caused a markedly higher number of secondary cases (mean: 1.03 vs. 0.35). By reconstructing likely transmission chains from the entire set of exposures identified during contact-tracing operations, we found that clusters originated from students or school personnel were associated with a larger average cluster size (3.32 vs. 1.15) and a larger average number of generations in the transmission chain (1.56 vs. 1.17)., Conclusions: Uncontrolled SARS-CoV-2 transmission at school could disrupt the regular conduct of teaching activities, likely seeding the transmission into other settings, and increasing the burden on contact-tracing operations., (© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Quantitative information on epidemiological quantities such as the incubation period and generation time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is scarce. We analysed a dataset collected during contact tracing activities in the province of Reggio Emilia, Italy, throughout 2021. We determined the distributions of the incubation period for the Alpha and Delta variants using information on negative polymerase chain reaction tests and the date of last exposure from 282 symptomatic cases. We estimated the distributions of the intrinsic generation time using a Bayesian inference approach applied to 9724 SARS-CoV-2 cases clustered in 3545 households where at least one secondary case was recorded. We estimated a mean incubation period of 4.9 days (95% credible intervals, CrI, 4.4-5.4) for Alpha and 4.5 days (95% CrI 4.0-5.0) for Delta. The intrinsic generation time was estimated to have a mean of 7.12 days (95% CrI 6.27-8.44) for Alpha and of 6.52 days (95% CrI 5.54-8.43) for Delta. The household serial interval was 2.43 days (95% CrI 2.29-2.58) for Alpha and 2.74 days (95% CrI 2.62-2.88) for Delta, and the estimated proportion of pre-symptomatic transmission was 48-51% for both variants. These results indicate limited differences in the incubation period and intrinsic generation time of SARS-CoV-2 variants Alpha and Delta compared to ancestral lineages.

We analyzed the first 255 PCR-confirmed cases of monkeypox in Italy in 2022. Preliminary estimates indicate mean incubation period of 9.1 (95% CI 6.5-10.9) days, mean generation time of 12.5 (95% CI 7.5-17.3) days, and reproduction number among men who have sex with men of 2.43 (95% CI 1.82-3.26).

Background: After a rapid upsurge of COVID-19 cases in Italy during the fall of 2020, the government introduced a three-tiered restriction system aimed at increasing physical distancing. The Ministry of Health, after periodic epidemiological risk assessments, assigned a tier to each of the 21 Italian regions and autonomous provinces. It is still unclear to what extent these different sets of measures altered the number of daily interactions and the social mixing patterns., Methods and Findings: We conducted a survey between July 2020 and March 2021 to monitor changes in social contact patterns among individuals in the metropolitan city of Milan, Italy, which was hardly hit by the second wave of the COVID-19 pandemic. The number of daily contacts during periods characterized by different levels of restrictions was analyzed through negative binomial regression models and age-specific contact matrices were estimated under the different tiers of restrictions. By relying on the empirically estimated mixing patterns, we quantified relative changes in SARS-CoV-2 transmission potential associated with the different tiers. As tighter restrictions were implemented during the fall of 2020, a progressive reduction in the mean number of daily contacts recorded by study participants was observed: from 15.9 % under mild restrictions (yellow tier), to 41.8 % under strong restrictions (red tier). Higher restrictions levels were also found to increase the relative contribution of contacts occurring within the household. The SARS-CoV-2 reproduction number was estimated to decrease by 17.1 % (95 %CI: 1.5-30.1), 25.1 % (95 %CI: 13.0-36.0) and 44.7 % (95 %CI: 33.9-53.0) under the yellow, orange, and red tiers, respectively., Conclusions: Our results give an important quantification of the expected contribution of different restriction levels in shaping social contacts and decreasing the transmission potential of SARS-CoV-2. These estimates can find an operational use in anticipating the effect that the implementation of these tiered restriction can have on SARS-CoV-2 reproduction number under an evolving epidemiological situation., Competing Interests: Competing interests M.A. has received research funding from Seqirus. The funding is not related to COVID-19 and to this study. The contents of this publication are the sole responsibility of the authors and don't necessarily reflect the views of the funders. All other authors declare no competing interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Starting from the final months of 2021, the SARS-CoV-2 Omicron variant expanded globally, swiftly replacing Delta, the variant that was dominant at the time. Many uncertainties remain about the epidemiology of Omicron; here, we aim to estimate its generation time., Methods: We used a Bayesian approach to analyze 23,122 SARS-CoV-2 infected individuals clustered in 8903 households as determined from contact tracing operations in Reggio Emilia, Italy, throughout January 2022. We estimated the distribution of the intrinsic generation time (the time between the infection dates of an infector and its secondary cases in a fully susceptible population), realized household generation time, realized serial interval (time between symptom onset of an infector and its secondary cases), and contribution of pre-symptomatic transmission., Findings: We estimated a mean intrinsic generation time of 6.84 days (95% credible intervals, CrI, 5.72-8.60), and a mean realized household generation time of 3.59 days (95%CrI: 3.55-3.60). The household serial interval was 2.38 days (95%CrI 2.30-2.47) with about 51% (95%CrI 45-56%) of infections caused by symptomatic individuals being generated before symptom onset., Interpretation: These results indicate that the intrinsic generation time of the SARS-CoV-2 Omicron variant might not have shortened as compared to previous estimates on ancestral lineages, Alpha and Delta, in the same geographic setting. Like for previous lineages, pre-symptomatic transmission appears to play a key role for Omicron transmission. Estimates in this study may be useful to design quarantine, isolation and contact tracing protocols and to support surveillance (e.g., for the accurate computation of reproduction numbers)., Funding: The study was partially funded by EU grant 874850 MOOD., Competing Interests: MA has received research funding from Seqirus. The funding is not related to COVID-19. All other authors declare no conflicts of interest., (© 2022 The Author(s).)

We analyzed 221 coronavirus disease 2019 cases identified between June 2020 and January 2021 in 6074 individuals screened for immunoglobulin G antibodies in May 2020, representing 77% of residents of 5 Italian municipalities. The relative risk of developing symptomatic infection in seropositive participants was 0.055 (95% confidence interval, .014-.220)., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

BackgroundSeveral SARS-CoV-2 variants of concern (VOC) have emerged through 2020 and 2021. There is need for tools to estimate the relative transmissibility of emerging variants of SARS-CoV-2 with respect to circulating strains.AimWe aimed to assess the prevalence of co-circulating VOC in Italy and estimate their relative transmissibility.MethodsWe conducted two genomic surveillance surveys on 18 February and 18 March 2021 across the whole Italian territory covering 3,243 clinical samples and developed a mathematical model that describes the dynamics of co-circulating strains.ResultsThe Alpha variant was already dominant on 18 February in a majority of regions/autonomous provinces (national prevalence: 54%) and almost completely replaced historical lineages by 18 March (dominant across Italy, national prevalence: 86%). We found a substantial proportion of the Gamma variant on 18 February, almost exclusively in central Italy (prevalence: 19%), which remained similar on 18 March. Nationally, the mean relative transmissibility of Alpha ranged at 1.55-1.57 times the level of historical lineages (95% CrI: 1.45-1.66). The relative transmissibility of Gamma varied according to the assumed degree of cross-protection from infection with other lineages and ranged from 1.12 (95% CrI: 1.03-1.23) with complete immune evasion to 1.39 (95% CrI: 1.26-1.56) for complete cross-protection.ConclusionWe assessed the relative advantage of competing viral strains, using a mathematical model assuming different degrees of cross-protection. We found substantial co-circulation of Alpha and Gamma in Italy. Gamma was not able to outcompete Alpha, probably because of its lower transmissibility.

There are contrasting results concerning the effect of reactive school closure on SARS-CoV-2 transmission. To shed light on this controversy, we developed a data-driven computational model of SARS-CoV-2 transmission. We found that by reactively closing classes based on syndromic surveillance, SARS-CoV-2 infections are reduced by no more than 17.3% (95%CI: 8.0-26.8%), due to the low probability of timely identification of infections in the young population. We thus investigated an alternative triggering mechanism based on repeated screening of students using antigen tests. Depending on the contribution of schools to transmission, this strategy can greatly reduce COVID-19 burden even when school contribution to transmission and immunity in the population is low. Moving forward, the adoption of antigen-based screenings in schools could be instrumental to limit COVID-19 burden while vaccines continue to be rolled out., (© 2022. The Author(s).)

During the spring of 2020, the coronavirus disease 2019 (COVID-19) epidemic caused an unprecedented demand for intensive-care resources in the Lombardy region of Italy. Using data on 43,538 hospitalized patients admitted between February 21 and July 12, 2020, we evaluated variations in intensive care unit (ICU) admissions and mortality over the course of 3 periods: the early phase of the pandemic (February 21-March 13), the period of highest pressure on the health-care system (March 14-April 25, when numbers of COVID-19 patients exceeded prepandemic ICU bed capacity), and the declining phase (April 26-July 12). Compared with the early phase, patients aged 70 years or more were less often admitted to an ICU during the period of highest pressure on the health-care system (odds ratio (OR) = 0.47, 95% confidence interval (CI): 0.41, 0.54), with longer ICU delays (incidence rate ratio = 1.82, 95% CI: 1.52, 2.18) and lower chances of dying in the ICU (OR = 0.47, 95% CI: 0.34, 0.64). Patients under 56 years of age had more limited changes in the probability of (OR = 0.65, 95% CI: 0.56, 0.76) and delay to (incidence rate ratio = 1.16, 95% CI: 0.95, 1.42) ICU admission and increased mortality (OR = 1.43, 95% CI: 1.00, 2.07). In the declining phase, all quantities decreased for all age groups. These patterns may suggest that limited health-care resources during the peak phase of the epidemic in Lombardy forced a shift in ICU admission criteria to prioritize patients with higher chances of survival., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

COVID-19 vaccination is allowing a progressive release of restrictions worldwide. Using a mathematical model, we assess the impact of vaccination in Italy since December 27, 2020 and evaluate prospects for societal reopening after emergence of the Delta variant. We estimate that by June 30, 2021, COVID-19 vaccination allowed the resumption of about half of pre-pandemic social contacts. In absence of vaccination, the same number of cases is obtained by resuming only about one third of pre-pandemic contacts, with about 12,100 (95% CI: 6,600-21,000) extra deaths (+27%; 95% CI: 15-47%). Vaccination offset the effect of the Delta variant in summer 2021. The future epidemic trend is surrounded by substantial uncertainty. Should a pediatric vaccine (for ages 5 and older) be licensed and a coverage >90% be achieved in all age classes, a return to pre-pandemic society could be envisioned. Increasing vaccination coverage will allow further reopening even in absence of a pediatric vaccine., (© 2021. The Author(s).)

Background: In the night of February 20, 2020, the first epidemic of the novel coronavirus disease (COVID-19) outside Asia was uncovered by the identification of its first patient in Lombardy region, Italy. In the following weeks, Lombardy experienced a sudden increase in the number of ascertained infections and strict measures were imposed to contain the epidemic spread., Methods: We analyzed official records of cases occurred in Lombardy to characterize the epidemiology of SARS-CoV-2 during the early phase of the outbreak. A line list of laboratory-confirmed cases was set up and later retrospectively consolidated, using standardized interviews to ascertained cases and their close contacts. We provide estimates of the serial interval, of the basic reproduction number, and of the temporal variation of the net reproduction number of SARS-CoV-2., Results: Epidemiological investigations detected over 500 cases (median age: 69, IQR: 57-78) before the first COVID-19 diagnosed patient (February 20, 2020), and suggested that SARS-CoV-2 was already circulating in at least 222 out of 1506 (14.7%) municipalities with sustained transmission across all the Lombardy provinces. We estimated the mean serial interval to be 6.6 days (95% CrI, 0.7-19). Our estimates of the basic reproduction number range from 2.6 in Pavia (95% CI, 2.1-3.2) to 3.3 in Milan (95% CI, 2.9-3.8). A decreasing trend in the net reproduction number was observed following the detection of the first case., Conclusions: At the time of first case notification, COVID-19 was already widespread in the entire Lombardy region. This may explain the large number of critical cases experienced by this region in a very short timeframe. The slight decrease of the reproduction number observed in the early days after February 20, 2020 might be due to increased population awareness and early interventions implemented before the regional lockdown imposed on March 8, 2020., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Solid estimates describing the clinical course of SARS-CoV-2 infections are still lacking due to under-ascertainment of asymptomatic and mild-disease cases. In this work, we quantify age-specific probabilities of transitions between stages defining the natural history of SARS-CoV-2 infection from 1965 SARS-CoV-2 positive individuals identified in Italy between March and April 2020 among contacts of confirmed cases. Infected contacts of cases were confirmed via RT-PCR tests as part of contact tracing activities or retrospectively via IgG serological tests and followed-up for symptoms and clinical outcomes. In addition, we provide estimates of time intervals between key events defining the clinical progression of cases as obtained from a larger sample, consisting of 95,371 infections ascertained between February and July 2020. We found that being older than 60 years of age was associated with a 39.9% (95%CI: 36.2-43.6%) likelihood of developing respiratory symptoms or fever ≥ 37.5 °C after SARS-CoV-2 infection; the 22.3% (95%CI: 19.3-25.6%) of the infections in this age group required hospital care and the 1% (95%CI: 0.4-2.1%) were admitted to an intensive care unit (ICU). The corresponding proportions in individuals younger than 60 years were estimated at 27.9% (95%CI: 25.4-30.4%), 8.8% (95%CI: 7.3-10.5%) and 0.4% (95%CI: 0.1-0.9%), respectively. The infection fatality ratio (IFR) ranged from 0.2% (95%CI: 0.0-0.6%) in individuals younger than 60 years to 12.3% (95%CI: 6.9-19.7%) for those aged 80 years or more; the case fatality ratio (CFR) in these two age classes was 0.6% (95%CI: 0.1-2%) and 19.2% (95%CI: 10.9-30.1%), respectively. The median length of stay in hospital was 10 (IQR: 3-21) days; the length of stay in ICU was 11 (IQR: 6-19) days. The obtained estimates provide insights into the epidemiology of COVID-19 and could be instrumental to refine mathematical modeling work supporting public health decisions., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

COVID-19 vaccination is being conducted in over 200 countries and regions to control SARS-CoV-2 transmission and return to a pre-pandemic lifestyle. However, understanding when non-pharmaceutical interventions (NPIs) can be lifted as immunity builds up remains a key question for policy makers. To address this, we built a data-driven model of SARS-CoV-2 transmission for China. We estimated that, to prevent the escalation of local outbreaks to widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs alone be capable of keeping the reproduction number (R t ) around 1.3, the synergetic effect of NPIs and vaccination could reduce the COVID-19 burden by up to 99% and bring R t below the epidemic threshold in about 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed to the population, especially in large populations with little natural immunity., (© 2021. The Author(s).)

To counter the second COVID-19 wave in autumn 2020, the Italian government introduced a system of physical distancing measures organized in progressively restrictive tiers (coded as yellow, orange, and red) imposed on a regional basis according to real-time epidemiological risk assessments. We leverage the data from the Italian COVID-19 integrated surveillance system and publicly available mobility data to evaluate the impact of the three-tiered regional restriction system on human activities, SARS-CoV-2 transmissibility and hospitalization burden in Italy. The individuals' attendance to locations outside the residential settings was progressively reduced with tiers, but less than during the national lockdown against the first COVID-19 wave in the spring. The reproduction number R(t) decreased below the epidemic threshold in 85 out of 107 provinces after the introduction of the tier system, reaching average values of about 0.95-1.02 in the yellow tier, 0.80-0.93 in the orange tier and 0.74-0.83 in the red tier. We estimate that the reduced transmissibility resulted in averting about 36% of the hospitalizations between November 6 and November 25, 2020. These results are instrumental to inform public health efforts aimed at preventing future resurgence of cases., (© 2021. The Author(s).)

Importance: Identifying health care settings and professionals at increased risk of SARS-CoV-2 infection is crucial to defining appropriate strategies, resource allocation, and protocols to protect health care workers (HCWs) and patients. Moreover, such information is crucial to decrease the risk that HCWs and health care facilities become amplifiers for SARS-CoV-2 transmission in the community., Objective: To assess the association of different health care professional categories and operational units, including in-hospital wards, outpatient facilities, and territorial care departments, with seroprevalence and odds of SARS-CoV-2 infection., Design, Setting, and Participants: This cross-sectional study was conducted using IgG serological tests collected from April 1 through May 26, 2020, in the Lombardy region in Italy. Voluntary serological screening was offered to all clinical and nonclinical staff providing any health care services or support to health care services in the region. Data were analyzed from June 2020 through April 2021., Exposures: Employment in the health care sector., Main Outcomes and Measures: Seroprevalence of positive IgG antibody tests for SARS-CoV-2 was collected, and odds ratios of experiencing infection were calculated., Results: A total of 140 782 professionals employed in the health sector were invited to participate in IgG serological screening, among whom 82 961 individuals (59.0% response rate) were tested for SARS-CoV-2 antibodies, with median (interquartile range [IQR]; range) age, 50 (40-56; 19-83) years and 59 839 (72.1%) women. Among these individuals, 10 115 HCWs (12.2%; 95% CI, 12.0%-12.4%) had positive results (median [IQR; range] age, 50 [39-55; 20-80] years; 7298 [72.2%] women). Statistically significantly higher odds of infection were found among health assistants (adjusted odds ratio [aOR], 1.48; 95% CI, 1.33-1.65) and nurses (aOR, 1.28; 95% CI, 1.17-1.41) compared with administrative staff and among workers employed in internal medicine (aOR, 2.24; 95% CI, 1.87-2.68), palliative care (aOR, 1.84; 95% CI, 1.38-2.44), rehabilitation (aOR, 1.59; 95% CI, 1.33-1.91), and emergency departments (aOR, 1.56; 95% CI, 1.29-1.89) compared with those working as telephone operators. Statistically significantly lower odds of infection were found among individuals working in forensic medicine (aOR, 0.40; 95% CI, 0.19-0.88), histology and anatomical pathology (aOR, 0.71; 95% CI, 0.52-0.97), and medical device sterilization (aOR, 0.54; 95% CI, 0.35-0.84) compared with those working as telephone operators. The odds of infection for physicians and laboratory personnel were not statistically significantly different from those found among administrative staff. The odds of infection for workers employed in intensive care units and infectious disease wards were not statistically significantly different from those of telephone operators., Conclusions and Relevance: These findings suggest that professionals partially accustomed to managing infectious diseases had higher odds of SARS-CoV-2 infection. The findings further suggest that adequate organization of clinical wards and personnel, appropriate personal protective equipment supply, and training of all workers directly and repeatedly exposed to patients with clinical or subclinical COVID-19 should be prioritized to decrease the risk of infection in health care settings.

Background: COVID-19 spread may have a dramatic impact in countries with vulnerable economies and limited availability of, and access to, healthcare resources and infrastructures. However, in sub-Saharan Africa, a low prevalence and mortality have been observed so far., Methods: We collected data on individuals' social contacts in the South West Shewa Zone (SWSZ) of Ethiopia across geographical contexts characterized by heterogeneous population density, work and travel opportunities, and access to primary care. We assessed how socio-demographic factors and observed mixing patterns can influence the COVID-19 disease burden, by simulating SARS-CoV-2 transmission in remote settlements, rural villages, and urban neighborhoods, under school closure mandate., Results: From national surveillance data, we estimated a net reproduction number of 1.62 (95% CI 1.55-1.70). We found that, at the end of an epidemic mitigated by school closure alone, 10-15% of the population residing in the SWSZ would have been symptomatic and 0.3-0.4% of the population would require mechanical ventilation and/or possibly result in a fatal outcome. Higher infection attack rates are expected in more urbanized areas, but the highest incidence of critical disease is expected in remote subsistence farming settlements. School closure contributed to reduce the reproduction number by 49% and the attack rate of infections by 28-34%., Conclusions: Our results suggest that the relatively low burden of COVID-19 in Ethiopia observed so far may depend on social mixing patterns, underlying demography, and the enacted school closures. Our findings highlight that socio-demographic factors can also determine marked heterogeneities across different geographical contexts within the same region, and they contribute to understand why sub-Saharan Africa is experiencing a relatively lower attack rate of severe cases compared to high-income countries.

Importance: Solid estimates of the risk of developing symptoms and of progressing to critical disease in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are key to interpreting coronavirus disease 2019 (COVID-19) dynamics, identifying the settings and the segments of the population where transmission is more likely to remain undetected, and defining effective control strategies., Objective: To estimate the association of age with the likelihood of developing symptoms and the association of age with the likelihood of progressing to critical illness after SARS-CoV-2 infection., Design, Setting, and Participants: This cohort study analyzed quarantined case contacts, identified between February 20 and April 16, 2020, in the Lombardy region of Italy. Contacts were monitored daily for symptoms and tested for SARS-CoV-2 infection, by either real-time reverse transcriptase-polymerase chain reaction using nasopharyngeal swabs or retrospectively via IgG serological assays. Close contacts of individuals with laboratory-confirmed COVID-19 were selected as those belonging to clusters (ie, groups of contacts associated with an index case) where all individuals were followed up for symptoms and tested for SARS-CoV-2 infection. Data were analyzed from February to June 2020., Exposure: Close contact with individuals with confirmed COVID-19 cases as identified by contact tracing operations., Main Outcomes and Measures: Age-specific estimates of the risk of developing respiratory symptoms or fever greater than or equal to 37.5 °C and of experiencing critical disease (defined as requiring intensive care or resulting in death) in SARS-CoV-2-infected case contacts., Results: In total, 5484 case contacts (median [interquartile range] age, 50 [30-61] years; 3086 female contacts [56.3%]) were analyzed, 2824 of whom (51.5%) tested positive for SARS-CoV-2 (median [interquartile range] age, 53 [34-64] years; 1604 female contacts [56.8%]). The proportion of infected persons who developed symptoms ranged from 18.1% (95% CI, 13.9%-22.9%) among participants younger than 20 years to 64.6% (95% CI, 56.6%-72.0%) for those aged 80 years or older. Most infected contacts (1948 of 2824 individuals [69.0%]) did not develop respiratory symptoms or fever greater than or equal to 37.5 °C. Only 26.1% (95% CI, 24.1%-28.2%) of infected individuals younger than 60 years developed respiratory symptoms or fever greater than or equal to 37.5 °C; among infected participants older than 60 years, 6.6% (95% CI, 5.1%-8.3%) developed critical disease. Female patients were 52.7% (95% CI, 24.4%-70.7%) less likely than male patients to develop critical disease after SARS-CoV-2 infection., Conclusions and Relevance: In this Italian cohort study of close contacts of patients with confirmed SARS-CoV-2 infection, more than one-half of individuals tested positive for the virus. However, most infected individuals did not develop respiratory symptoms or fever. The low proportion of children and young adults who developed symptoms highlights the possible challenges in readily identifying SARS-CoV-2 infections.

After the national lockdown imposed on March 11, 2020, the Italian government has gradually resumed the suspended economic and social activities since May 4, while maintaining the closure of schools until September 14. We use a model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission to estimate the health impact of different exit strategies. The strategy adopted in Italy kept the reproduction number R t at values close to one until the end of September, with marginal regional differences. Based on the estimated postlockdown transmissibility, reopening of workplaces in selected industrial activities might have had a minor impact on the transmissibility. Reopening educational levels in May up to secondary schools might have influenced SARS-CoV-2 transmissibility only marginally; however, including high schools might have resulted in a marked increase of the disease burden. Earlier reopening would have resulted in disproportionately higher hospitalization incidence. Given community contacts in September, we project a large second wave associated with school reopening in the fall., Competing Interests: Competing interest statement: M.A. has received research funding from Seqirus. The funding is not related to COVID-19. All other authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

On March 11, 2020, Italy imposed a national lockdown to curtail the spread of severe acute respiratory syndrome coronavirus 2. We estimate that, 14 days after lockdown, the net reproduction number had dropped below 1 and remained stable at »0.76 (95% CI 0.67-0.85) in all regions for >3 of the following weeks.

BackgroundOn 20 February 2020, a locally acquired coronavirus disease (COVID-19) case was detected in Lombardy, Italy. This was the first signal of ongoing transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the country. The number of cases in Italy increased rapidly and the country became the first in Europe to experience a SARS-CoV-2 outbreak.AimOur aim was to describe the epidemiology and transmission dynamics of the first COVID-19 cases in Italy amid ongoing control measures.MethodsWe analysed all RT-PCR-confirmed COVID-19 cases reported to the national integrated surveillance system until 31 March 2020. We provide a descriptive epidemiological summary and estimate the basic and net reproductive numbers by region.ResultsOf the 98,716 cases of COVID-19 analysed, 9,512 were healthcare workers. Of the 10,943 reported COVID-19-associated deaths (crude case fatality ratio: 11.1%) 49.5% occurred in cases older than 80 years. Male sex and age were independent risk factors for COVID-19 death. Estimates of R 0 varied between 2.50 (95% confidence interval (CI): 2.18-2.83) in Tuscany and 3.00 (95% CI: 2.68-3.33) in Lazio. The net reproduction number R t in northern regions started decreasing immediately after the first detection.ConclusionThe COVID-19 outbreak in Italy showed a clustering onset similar to the one in Wuhan, China. R 0 at 2.96 in Lombardy combined with delayed detection explains the high case load and rapid geographical spread. Overall, R t in Italian regions showed early signs of decrease, with large diversity in incidence, supporting the importance of combined non-pharmacological control measures.

We analysed 5,484 close contacts of coronavirus disease (COVID-19) cases in Italy, all tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection fatality ratio was 0.43% (95% confidence interval (CI): 0.21-0.79) for individuals younger than 70 years and 10.5% (95% CI: 8.0-13.6) for older individuals. Risk of death after infection was 62% lower (95% CI: 31-80) in clusters identified after 16 March 2020 and 1.8-fold higher for males (95% CI: 1.03-3.16).

Sustained coronavirus disease (COVID-19) transmission is ongoing in Italy, with 7,375 reported cases and 366 deaths by 8 March 2020. We provide a model-based evaluation of patient records from Lombardy, predicting the impact of an uncontrolled epidemic on the healthcare system. It has the potential to cause more than 250,039 (95% credible interval (CrI): 147,717-459,890) cases within 3 weeks, including 37,194 (95% CrI: 22,250-67,632) patients requiring intensive care. Aggressive containment strategies are required.

High-income countries are experiencing measles reemergence as the result of suboptimal vaccine uptake and marked immunity gaps among adults. In 2017, the Italian Government introduced mandatory vaccination at school entry for ten infectious diseases, including measles. However, sustainable and effective vaccination strategies targeting adults are still lacking. We use a data-driven model of household demography to estimate the potential impact on future measles epidemiology of a novel immunization strategy, to be implemented on top of the 2017 regulation, which consists of offering measles vaccine to the parents of children who get vaccinated. Model simulations suggest that the current vaccination efforts in Italy would not be sufficient to interrupt measles transmission before 2045 because of the frequency of susceptible individuals between 17 and 44 years of age. The integration of the current policy with parental vaccination has the potential to reduce susceptible adults by 17-35%, increasing the chance of measles elimination before 2045 up to 78.9-96.5%., Competing Interests: VM, PP, FT, AM, MA, SM No competing interests declared, (© 2019, Marziano et al.)

Annual incidence rates of varicella infection in the general population in France have been rather stable since 1991 when clinical surveillance started. Rates however show a statistically significant increase over time in children aged 0-3 years, and a decline in older individuals. A significant increase in day-care enrolment and structures' capacity in France was also observed in the last decade. In this work we investigate the potential interplay between an increase of contacts of young children possibly caused by earlier socialization in the community and varicella transmission dynamics. To this aim, we develop an age-structured mathematical model, informed with historical demographic data and contact matrix estimates in the country, accounting for longitudinal linear increase of early childhood contacts. While the reported overall varicella incidence is well reproduced independently of mixing variations, age-specific empirical trends are better captured by accounting for an increase in contacts among pre-school children in the last decades. We found that the varicella data are consistent with a 30% increase in the number of contacts at day-care facilities, which would imply a 50% growth in the contribution of 0-3y old children to overall yearly infections in 1991-2015. Our findings suggest that an earlier exposure to pathogens due to changes in day-care contact patterns, represents a plausible explanation for the epidemiological patterns observed in France. Obtained results suggest that considering temporal changes in social factors in addition to demographic ones is critical to correctly interpret varicella transmission dynamics., Competing Interests: I have read the journal's policy and the authors of this manuscript have no competing interests in relation to this work. Outside of this work, PP declares personal fees from Merck & Co. Inc. for consultancy activity.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

The spread of the 2009 H1N1 influenza pandemic in England was characterized by two major waves of infections: the first one was highly spatially localized (mainly in the London area), while the second one spread homogeneously through the entire country. The reasons behind this complex spatiotemporal dynamics have yet to be clarified. In this study, we perform a Bayesian analysis of five models entailing different hypotheses on the possible determinants of the observed pattern. We find a consensus among all models in showing a surprisingly low transmission distance (defined as the geographic distance between the place of residence of the infectors and her/his infectees) during the first wave: about 1.5 km (2.2 km if infections linked to household and school transmission are excluded). The best-fitting model entails a change in human activity regarding contacts not related to household and school. By using this model we estimate that the transmission distance sharply increased to 5.3 km (10 km when excluding infections linked to household and school transmission) during the second wave. Our study reveals a possible explanation for the observed pattern and highlights the need of better understanding human mobility and activity patterns under the pressure posed by a pandemic threat.

Varicella zoster virus (VZV) causes varicella upon first exposure and may reactivate later in life into herpes zoster (HZ), with a risk that is thought to be reduced by re-exposures to VZV. Given the decades-long time scales of reactivation and its dependence on the accumulation of re-exposure episodes, adopting a long-term perspective may be useful to correctly interpret current epidemiological trends of VZV. In this study, we investigate the possible impact of demographic changes on varicella and HZ in Spain, using an age-structured mathematical model informed with historical demographic data and calibrated against age-specific profiles of varicella seroprevalence and HZ incidence data. The model qualitatively reproduces the remarkable growth of HZ incidence observed in Spain between 1997 and 2004, before the introduction of varicella vaccination programmes. We demonstrate that this growth may be partially ascribed to the reduction of varicella circulation that followed the overall decline of the birth rate in the twentieth century. Model predictions further suggest that, even under the most optimistic projections, HZ incidence will continue its rise until at least 2040. Considering the effect of demographic changes can help interpreting variations in epidemiological trends of HZ, contributing to a more accurate evaluation of vaccination programmes against VZV., (© 2015 The Author(s) Published by the Royal Society. All rights reserved.)