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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).

Abstract 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 ( $$\le 10 km)$$ ≤ 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.

Abstract 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.

BackgroundThe 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.MethodsIn 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.ResultsNowcasting 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.ConclusionsNowcasting augments epidemic awareness, empowering better informed public health responses.

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.

Abstract 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.

BackgroundEmerging arboviral diseases in Europe pose a challenge due to difficulties in detecting and diagnosing cases during the initial circulation of the pathogen. Early outbreak detection enables public health authorities to take effective actions to reduce disease transmission. Quantification of the reporting delays of cases is vital to plan and assess surveillance and control strategies. Here, we provide estimates of reporting delays during an emerging arboviral outbreak and indications on how delays may have impacted onward transmission.Methodology/principal findingsUsing descriptive statistics and Kaplan-Meyer curves we analyzed case reporting delays (the period between the date of symptom onset and the date of notification to the public health authorities) during the 2017 Italian chikungunya outbreak. We further investigated the effect of outbreak detection on reporting delays by means of a Cox proportional hazard model. We estimated that the overall median reporting delay was 15.5 days, but this was reduced to 8 days after the notification of the first case. Cases with symptom onset after outbreak detection had about a 3.5 times higher reporting rate, however only 3.6% were notified within 24h from symptom onset. Remarkably, we found that 45.9% of identified cases developed symptoms before the detection of the outbreak.Conclusions/significanceThese results suggest that efforts should be undertaken to improve the early detection and identification of arboviral cases, as well as the management of vector species to mitigate the impact of long reporting delays.

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%.

Natural disasters and epidemics are unfortunate recurring events that lead to huge societal and economic loss. Recent advances in supercomputing can facilitate simulations of such scenarios in (or even ahead of) real-time, therefore supporting the design of adequate responses by public authorities. By incorporating high-velocity data from sensors and modern high-performance computing systems, ensembles of simulations and advanced analysis enable urgent decision-makers to better monitor the disaster and to employ necessary actions (e.g., to evacuate populated areas) for mitigating these events. Unfortunately, frameworks to support such versatile and complex workflows for urgent decision-making are only rarely available and often lack in functionalities. This paper gives an overview of the VESTEC project and framework, which unifies orchestration, simulation, in-situ data analysis, and visualization of natural disasters that can be driven by external sensor data or interactive intervention by the user. We show how different components interact and work together in VESTEC and describe implementation details. To disseminate our experience three different types of disasters are evaluated: a Wildfire in La Jonquera (Spain), a Mosquito-Borne disease in two regions of Italy, and the magnetic reconnection in the Earth magnetosphere.

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).

BackgroundOutbreaks of Aedes-borne diseases in temperate areas are not frequent, and limited in number of cases. We investigate the associations between habitat factors and temperature on individuals' risk of chikungunya (CHIKV) in a non-endemic area by spatially analyzing the data from the 2017 Italian outbreak.Methodology/principal findingsWe adopted a case-control study design to analyze the association between land-cover variables, temperature, and human population density with CHIKV cases. The observational unit was the area, at different scales, surrounding the residence of each CHIKV notified case. The statistical analysis was conducted considering the whole dataset and separately for the resort town of Anzio and the metropolitan city of Rome, which were the two main foci of the outbreak. In Rome, a higher probability for the occurrence of CHIKV cases is associated with lower temperature (OR = 0.72; 95% CI: 0.61-0.85) and with cells with higher vegetation coverage and human population density (OR = 1.03; 95% CI: 1.00-1.05). In Anzio, CHIKV case occurrence was positively associated with human population density (OR = 1.03; 95% CI: 1.00-1.06) but not with habitat factors or temperature.Conclusion/significanceUsing temperature, human population density and vegetation coverage data as drives for CHIKV transmission, our estimates could be instrumental in assessing spatial heterogeneity in the risk of experiencing arboviral diseases in non-endemic temperate areas.

Reactive school class closures have been widely implemented to mitigate COVID-19 outbreaks. Here, the authors show that, compared to symptom-prompted PCR testing, screening for cases in schools with antigen tests leads to greater reductions in infection rates in both students and the wider community.

Vaccination campaigns against COVID-19 are allowing the progressive release of physical distancing restrictions in many countries. Here, the authors assess the impact of the vaccination program in Italy and evaluate possible prospects for reopening the society while at the same time keeping COVID-19 under control.

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.

Italy introduced a system of tiered SARS-CoV-2 control measures in November 2020. Here, the authors quantify the effect of these measures on SARS-CoV-2 transmissibility and hospitalisation, and find reductions across all tiers with the greatest impacts associated with the most restrictive level.

Summary: 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.

Abstract 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.

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.

Abstract Background The spatial spread of many mosquito-borne diseases occurs by focal spread at the scale of a few hundred meters and over longer distances due to human mobility. The relative contributions of different spatial scales for transmission of chikungunya virus require definition to improve outbreak vector control recommendations. Methods We analyzed data from a large chikungunya outbreak mediated by the mosquito Aedes albopictus in the Lazio region, Italy, consisting of 414 reported human cases between June and November 2017. Using dates of symptom onset, geographic coordinates of residence, and information from epidemiological questionnaires, we reconstructed transmission chains related to that outbreak. Results Focal spread (within 1 km) accounted for 54.9% of all cases, 15.8% were transmitted at a local scale (1–15 km) and the remaining 29.3% were exported from the main areas of chikungunya circulation in Lazio to longer distances such as Rome and other geographical areas. Seventy percent of focal infections (corresponding to 38% of the total 414 cases) were transmitted within a distance of 200 m (the buffer distance adopted by the national guidelines for insecticide spraying). Two main epidemic clusters were identified, with a radius expanding at a rate of 300–600 m per month. The majority of exported cases resulted in either sporadic or no further transmission in the region. Conclusions Evidence suggest that human mobility contributes to seeding a relevant number of secondary cases and new foci of transmission over several kilometers. Reactive vector control based on current guidelines might allow a significant number of secondary clusters in untreated areas, especially if the outbreak is not detected early. Existing policies and guidelines for control during outbreaks should recommend the prioritization of preventive measures in neighboring territories with known mobility flows to the main areas of transmission.

During the COVID-19 pandemic, several countries have resorted to self-adaptive mechanisms that tailor non-pharmaceutical interventions to local epidemiological and health care indicators. These mechanisms reinforce the mutual influence between containment measures and the evolution of the epidemic. To account for such interplay, we develop an epidemiological model that embeds an algorithm mimicking the self-adaptive policy mechanism effective in Italy between November 2020 and March 2022. This extension is key to tracking the historical evolution of health outcomes and restrictions in Italy. Focusing on the epidemic wave that started in mid-2021 after the diffusion of Delta, we compare the functioning of alternative mechanisms to show how the policy framework may affect the trade-off between health outcomes and the restrictiveness of mitigation measures. Mechanisms based on the reproduction number are generally highly responsive to early signs of a surging wave but entail severe restrictions. The emerging trade-off varies considerably depending on specific conditions (e.g., vaccination coverage), with less-reactive mechanisms (e.g., those based on occupancy rates) becoming more appealing in favorable contexts.

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.

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.

Abstract Background Aedes koreicus was detected in northern Italy for the first time in 2011, and it is now well established in several areas as a new invasive mosquito species. Data regarding the influence of temperature on mosquito survival and development are not available yet for this species. Methods We experimentally investigated the influence of different constant rearing temperatures (between 4 and 33 °C) on the survival rates and developmental times of different life stages of Ae. koreicus under laboratory conditions. The resulting data were subsequently used to inform a mathematical model reproducing the Ae. koreicus life-cycle calibrated to counts of adult females captured in the field in the autonomous province of Trento (northern Italy) between 2016 and 2018. Results We found that temperatures above 28 °C are not optimal for the survival of pupae and adults, whereas temperate conditions of 23–28 °C seem to be very favorable, explaining the recent success of Ae. koreicus at establishing into new specific areas. Our results indicate that Ae. koreicus is less adapted to local climatic conditions compared to Ae. albopictus, another invasive species which has been invading the area for the last three decades. Warmer seasons, which are more likely to occur in the future because of climate change, might extend the breeding time and therefore increase the abundance of Ae. koreicus in the study region. Conclusions Our findings provide, to our knowledge, the first evidence on how temperature influences the bionomics and dynamics of Ae. koreicus and highlight the need for further studies on the phenology of this species in temperate areas of Europe.

Key resultsBoth outbreaks started in small towns, but cases were also detected in nearby larger cities where transmission was limited to small clusters. The time spans between the first and the last symptom onsets were similar between the 2 outbreaks, and the delay from the symptom onset of the index case and the first case notified was considerable. Comparable infection and transmission rates were observed in laboratory. The basic reproductive number (R0) was estimated in the range of 1.8-6 (2007) and 1.5-2.6 (2017). Clinical characteristics were similar between outbreaks, and no acute complications were reported, though a higher frequency of ocular symptoms, myalgia, and rash was observed in 2017. Very little is known about the immune mediator profile of CHIKV-infected patients during the 2 outbreaks. Regarding public health responses, after the 2007 outbreak, the Italian Ministry of Health developed national guidelines to implement surveillance and good practices to prevent and control autochthonous transmission. However, only a few regional authorities implemented it, and the perception of outbreak risk and knowledge of clinical symptoms and transmission dynamics by general practitioners remained low.Major conclusionsEfforts should be devoted to developing suitable procedures for early detection of virus circulation in the population, possibly through the analysis of medical records in near real time. Increasing the awareness of CHIKV of general practitioners and public health officials through tailored education may be effective, especially in small coastal towns where the outbreak risk may be higher. A key element is also the shift of citizen awareness from considering Aedes mosquitoes not only as a nuisance problem but also as a public health one. We advocate the need of strengthening the surveillance and of promoting the active participation of the communities to prevent and contain future outbreaks.

There is increasing urgency to understand the spatiotemporal dynamics of dengue in non-endemic regions. Here, the authors reconstruct likely dengue transmission chains in the city of Porto Alegre based on geo-located cases only, and find that most transmission events occur over short-distances.

Management of vector population is a commonly used method for mitigating transmission of mosquito-borne infections, but quantitative information on its practical public health impact is scarce. We study the effectiveness of Ultra-Low Volume (ULV) insecticide spraying in public spaces for preventing secondary dengue virus (DENV) cases in Porto Alegre, a non-endemic metropolitan area in Brazil. We developed a stochastic transmission model based on detailed entomological, epidemiological and population data, accounting for the geographical distribution of mosquitoes and humans in the study area and spatial transmission dynamics. The model was calibrated against the distribution of DENV cluster sizes previously estimated from the same geographical setting. We estimated a ULV-induced mortality of 40% for mosquitoes and found that the implemented control protocol avoided about 24% of symptomatic cases occurred in the area throughout the 2015-2016 epidemic season. Increasing the radius of treatment or the mortality of mosquitoes by treating gardens and/or indoor premises would greatly improve the result of control, but trade-offs with respect to increased efforts need to be carefully analyzed. We found a moderate effectiveness for ULV-spraying in public areas, mainly due to the limited ability of this strategy in effectively controlling the vector population. These results can be used to support the design of control strategies in low-incidence, non-endemic settings.

In the last decades, several European countries where arboviral infections are not endemic have faced outbreaks of diseases such as chikungunya and dengue, initially introduced by infectious travellers from tropical endemic areas and then spread locally via mosquito bites. To keep in check the epidemiological risk, interventions targeted to control vector abundance can be implemented by local authorities. We assessed the epidemiological effectiveness and economic costs and benefits of routine larviciding in European towns with temperate climate, using a mathematical model of Aedes albopictus populations and viral transmission, calibrated on entomological surveillance data collected from ten municipalities in Northern Italy during 2014 and 2015.We found that routine larviciding of public catch basins can limit both the risk of autochthonous transmission and the size of potential epidemics. Ideal larvicide interventions should be timed in such a way to cover the month of July. Optimally timed larviciding can reduce locally transmitted cases of chikungunya by 20% - 33% for a single application (dengue: 18-22%) and up to 43% - 65% if treatment is repeated four times throughout the season (dengue: 31-51%). In larger municipalities (>35,000 inhabitants), the cost of comprehensive larviciding over the whole urban area overcomes potential health benefits related to preventing cases of disease, suggesting the adoption of more localized interventions. Small/medium sized towns with high mosquito abundance will likely have a positive cost-benefit balance. Involvement of private citizens in routine larviciding activities further reduces transmission risks but with disproportionate costs of intervention. International travels and the incidence of mosquito-borne diseases are increasing worldwide, exposing a growing number of European citizens to higher risks of potential outbreaks. Results from this study may support the planning and timing of interventions aimed to reduce the probability of autochthonous transmission as well as the nuisance for local populations living in temperate areas of Europe.

We use age-structured models for VZV transmission and reactivation to reconstruct the natural history of VZV in Norway based on available pre-vaccination serological data, contact matrices, and herpes zoster incidence data. Depending on the hypotheses on contact and transmission patterns, the basic reproduction number of varicella in Norway ranges between 3.7 and 5.0, implying a vaccine coverage between 73 and 80% to effectively interrupt transmission with a 100% vaccine efficacy against infection. The varicella force of infection peaks during early childhood (3-5 yrs) and shows a prolonged phase of higher risk during the childbearing period, though quantitative variations can occur depending on contact patterns. By expressing the magnitude of exogenous boosting as a proportion of the force of infection, it is shown that reactivation is well described by a progressive immunity mechanism sustained by a large, though possibly below 100%, degree of exogenous boosting, in agreement with findings from other Nordic countries, implying large reproduction numbers of boosting. Moreover, magnitudes of exogenous boosting below 40% are robustly disconfirmed by data. These results bring further insight on the magnitude of immunity boosting and its relationship with reactivation.

Background: Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination. Methods: We searched MEDLINE and Embase for transmission-dynamic modelling studies published between Jan 1, 2009, and April 28, 2015, that predicted the population-level impact of vaccination on HPV 6, 11, 16, and 18 infections in high-income countries. We contacted authors to determine whether they were willing to produce new predictions for standardised scenarios. Strategies investigated were girls-only vaccination and girls and boys vaccination at age 12 years. Base-case vaccine characteristics were 100% efficacy and lifetime protection. We did sensitivity analyses by varying vaccination coverage, vaccine efficacy, and duration of protection. For all scenarios we pooled model predictions of relative reductions in HPV prevalence (RRprev) over time after vaccination and summarised results using the median and 10th and 90th percentiles (80% uncertainty intervals [UI]). Findings: 16 of 19 eligible models from ten high-income countries provided predictions. Under base-case assumptions, 40% vaccination coverage and girls-only vaccination, the RRprev of HPV 16 among women and men was 0·53 (80% UI 0·46–0·68) and 0·36 (0·28–0·61), respectively, after 70 years. With 80% girls-only vaccination coverage, the RRprev of HPV 16 among women and men was 0·93 (0·90–1·00) and 0·83 (0·75–1·00), respectively. Vaccinating boys in addition to girls increased the RRprev of HPV 16 among women and men by 0·18 (0·13–0·32) and 0·35 (0·27–0·39) for 40% coverage, and 0·07 (0·00–0·10) and 0·16 (0·01–0·25) for 80% coverage, respectively. The RRprev were greater for HPV 6, 11, and 18 than for HPV 16 for all scenarios investigated. Finally at 80% coverage, most models predicted that girls and boys vaccination would eliminate HPV 6, 11, 16, and 18, with a median RRprev of 1·00 for women and men for all four HPV types. Variability in pooled findings was low, but increased with lower vaccination coverage and shorter vaccine protection (from lifetime to 20 years). Interpretation: Although HPV models differ in structure, data used for calibration, and settings, our population-level predictions were generally concordant and suggest that strong herd effects are expected from vaccinating girls only, even with coverage as low as 20%. Elimination of HPV 16, 18, 6, and 11 is possible if 80% coverage in girls and boys is reached and if high vaccine efficacy is maintained over time. Funding: Canadian Institutes of Health Research.

The rapid invasion and spread of Aedes albopictus (Skuse, 1894) within new continents and climatic ranges has created favorable conditions for the emergence of tropical arboviral diseases in the invaded areas. We used mosquito abundance data from 2014 collected across ten sites in northern Italy to calibrate a population model for Aedes albopictus and estimate the potential of imported human cases of chikungunya or dengue to generate the condition for their autochthonous transmission in the absence of control interventions. The model captured intra-year seasonality and heterogeneity across sites in mosquito abundance, based on local temperature patterns and the estimated site-specific mosquito habitat suitability. A robust negative correlation was found between the latter and local late spring precipitations, indicating a possible washout effect on larval breeding sites. The model predicts a significant risk of chikungunya outbreaks in most sites if a case is imported between the beginning of summer and up to mid-November, with an average outbreak probability between 4.9% and 25%, depending on the site. A lower risk is predicted for dengue, with an average probability between 4.2% and 10.8% for cases imported between mid-July and mid-September. This study shows the importance of an integrated entomological and medical surveillance for the evaluation of arboviral disease risk, which is a precondition for designing cost-effective vector control programs.

Jockers' recent book describes a host of digital techniques that can be applied to literary studies. The main focus is the idea of Macro-Analysis, developed during his work at Stanford Literary Lab, in collaboration with Franco Moretti. Le récent ouvrage de Jocker décrit de nombreuses techniques numériques qui peuvent être appliquées aux études littéraires. Le principal objectif est l’idée de la macroanalyse, mise au point dans le cadre de son travail au laboratoire littéraire de Stanford, en collaboration avec Franco Moretti.

The Human Papillomavirus (HPV) is a sexually transmitted virus that causes cervical cancer. Since 2008 a vaccination program targeting 12-year-old girls has been initiated in Italy, backing up the cervical screening program already active since 1996. We propose a mathematical model of HPV transmission dynamics with the aim of evaluating the impact of these prevention strategies. The model considers heterosexual transmission of HPV types 16 and 18, structured by sex, age and sexual activity level, where transition to sexual activity is explicitly modeled from recent survey data. The epidemiological structure is a hybrid SIS/SIR, where a fraction of individuals recovering from infection develops permanent immunity against reinfection. Infections may progress to cervical lesions and cancer and heal spontaneously or upon treatment. Women undergoing hysterectomy (either after treatment of HPV lesions or by other causes) also transmit HPV infection. The model fits well both the age-specific prevalence of HPV infections and the incidence of cervical cancers in Italy, and accurately reproduces the decreasing trend in cancer incidence due to the introduction of the screening program. The model predicts that if the screening coverage is maintained at current levels, even in the absence of vaccination, such trend will continue in the next few decades, eventually plateauing at 25% below the current level. The additional initiation of routine vaccination targeting 12-year-old girls will further reduce cervical cancer incidence by two thirds at equilibrium, under realistic assumptions of 70% coverage and a duration of protective immunity of 50 years. If catch-up immunization of 25-year-old women at first cervical screening is also introduced, about 3,000 cervical cancer cases overall can be averted, corresponding to 9.6% of all cases expected in the scenario without catch-up. We conclude that HPV vaccination in addition to cervical screening will significantly reduce the burden of cervical cancer in Italy.

Finding more effective vaccines against tuberculosis (TB) and improved preventive treatments against endogenous reactivation of latent TB is strategic to block transmission and reach the WHO goal of eliminating TB by 2050. Key related open questions in TB research include: i) what are the determinants of a strong memory response upon primary infection? ii) what is the role of cytokines towards protective memory response against a secondary infection? iii) what are the mechanisms responsible for the increased risk of reactivation in elderly individuals? To address these questions, we explored a computational model of the immune response to Mycobacterium tuberculosis including a mathematical description of immunosenescence and the generation and maintenance of immune memory. Sensitivity analysis techniques, together with extensive model characterization and in silico experiments, were applied to identify key mechanisms controlling TB reactivation and immunological memory. Key findings of this study are summarized by the following model predictions: i) increased strength and duration of memory protection is associated with higher levels of Tumor Necrosis Factor-[Formula: see text] (TNF) during primary infection; ii) production of TNF, but not of interferon-[Formula: see text], by memory T cells during secondary infection is a major determinant of effective protection; iii) impaired recruitment of CD4+ T cells may promote reactivation of latent TB infections in aging hosts. This study is a first attempt to consider the immune dynamics of a persistent infection throughout the lifetime of the host, taking into account immunosenescence and memory. While the model is TB specific, the results are applicable to other persistent bacterial infections and can aid in the development, evaluation and refinement of TB treatment and/or vaccine protocols.

The introduction of mass vaccination against Varicella-Zoster-Virus (VZV) is being delayed in many European countries because of, among other factors, the possibility of a large increase in Herpes Zoster (HZ) incidence in the first decades after the initiation of vaccination, due to the expected decline of the boosting of Cell Mediated Immunity caused by the reduced varicella circulation. A multi-country model of VZV transmission and reactivation, is used to evaluate the possible impact of varicella vaccination on HZ epidemiology in Italy, Finland and the UK. Despite the large uncertainty surrounding HZ and vaccine-related parameters, surprisingly robust medium-term predictions are provided, indicating that an increase in HZ incidence is likely to occur in countries where the incidence rate is lower in absence of immunization, possibly due to a higher force of boosting (e.g. Finland), whereas increases in HZ incidence might be minor where the force of boosting is milder (e.g. the UK). Moreover, a convergence of HZ post vaccination incidence levels in the examined countries is predicted despite different initial degrees of success of immunization policies. Unlike previous model-based evaluations, our investigation shows that after varicella immunization an increase of HZ incidence is not a certain fact, rather depends on the presence or absence of factors promoting a strong boosting intensity and which might or not be heavily affected by changes in varicella circulation due to mass immunization. These findings might explain the opposed empirical evidences observed about the increases of HZ in sites where mass varicella vaccination is ongoing.