Behavioral Changes Associated With COVID-19 Vaccination: Cross-National Online Survey.

BACKGROUND: During the initial phases of the vaccination campaign worldwide, nonpharmaceutical interventions (NPIs) remained pivotal in the fight against the COVID-19 pandemic. In this context, it is important to understand how the arrival of vaccines affected the adoption of NPIs. Indeed, some individuals might have seen the start of mass vaccination campaigns as the end of the emergency and, as a result, relaxed their COVID-safe behaviors, facilitating the spread of the virus in a delicate epidemic phase such as the initial rollout. OBJECTIVE: The aim of this study was to collect information about the possible relaxation of protective behaviors following key events of the vaccination campaign in four countries and to analyze possible associations of these behavioral tendencies with the sociodemographic characteristics of participants. METHODS: We developed an online survey named "COVID-19 Prevention and Behavior Survey" that was conducted between November 26 and December 22, 2021. Participants were recruited using targeted ads on Facebook in four different countries: Brazil, Italy, South Africa, and the United Kingdom. We measured the onset of relaxation of protective measures in response to key events of the vaccination campaign, namely personal vaccination and vaccination of the most vulnerable population. Through calculation of odds ratios (ORs) and regression analysis, we assessed the strength of association between compliance with NPIs and sociodemographic characteristics of participants. RESULTS: We received 2263 questionnaires from the four countries. Participants reported the most significant changes in social activities such as going to a restaurant or the cinema and visiting relatives and friends. This is in good agreement with validated psychological models of health-related behavioral change such as the Health Belief Model, according to which activities with higher costs and perceived barriers (eg, social activities) are more prone to early relaxation. Multivariate analysis using a generalized linear model showed that the two main determinants of the drop of social NPIs were (1) having previously tested positive for COVID-19 (after the second vaccine dose: OR 2.46, 95% CI 1.73-3.49) and (2) living with people at risk (after the second vaccine dose: OR 1.57, 95% CI 1.22-2.03). CONCLUSIONS: This work shows that particular caution has to be taken during vaccination campaigns. Indeed, people might relax their safe behaviors regardless of the dynamics of the epidemic. For this reason, it is crucial to maintain high compliance with NPIs to avoid hindering the beneficial effects of the vaccine.

Potential Impact of Environmental Pollution by Human Antivirals on Avian Influenza Virus Evolution.

Antiviral (AV) drugs are the main line of defense against pandemic influenza. However, different administration policies are applied in countries with different stocks of AV drugs. These policies lead to different occurrences of drug metabolites in the aquatic environment, altering animal behavior with evolutionary consequences on viruses. The aim of this study was to investigate the potential impact of environmental pollution by human antivirals, such as oseltamivir carboxylate (OC), on the evolutionary rate of avian influenza. We used NA, HA, NP, and MP viral segments from two groups of neighboring countries sharing migratory routes of wild birds and characterized by different AV stockpiles. BEAST analyses were performed using the uncorrelated lognormal clock evolutionary model and the Bayesian skyline tree prior model. The ratios between the rate of evolution of the NA gene and the HA, NP, and MP segments were considered. The two groups of countries were compared by analyzing the differences in the ratio distributions. Our analyses highlighted a possible different behavior in the evolution of H5N1 2.3 clade viral strains when OC environmental pollution is present. In conclusion, the widespread consumption of antivirals and their presence in wastewater could influence the selective pressure on viruses.

Interplay between mobility, multi-seeding and lockdowns shapes COVID-19 local impact.

Assessing the impact of mobility on epidemic spreading is of crucial importance for understanding the effect of policies like mass quarantines and selective re-openings. While many factors affect disease incidence at a local level, making it more or less homogeneous with respect to other areas, the importance of multi-seeding has often been overlooked. Multi-seeding occurs when several independent (non-clustered) infected individuals arrive at a susceptible population. This can lead to independent outbreaks that spark from distinct areas of the local contact (social) network. Such mechanism has the potential to boost incidence, making control efforts and contact tracing less effective. Here, through a modeling approach we show that the effect produced by the number of initial infections is non-linear on the incidence peak and peak time. When case importations are carried by mobility from an already infected area, this effect is further enhanced by the local demography and underlying mixing patterns: the impact of every seed is larger in smaller populations. Finally, both in the model simulations and the analysis, we show that a multi-seeding effect combined with mobility restrictions can explain the observed spatial heterogeneities in the first wave of COVID-19 incidence and mortality in five European countries. Our results allow us for identifying what we have called epidemic epicenter: an area that shapes incidence and mortality peaks in the entire country. The present work further clarifies the nonlinear effects that mobility can have on the evolution of an epidemic and highlight their relevance for epidemic control.

The importance of non-pharmaceutical interventions during the COVID-19 vaccine rollout.

The promise of efficacious vaccines against SARS-CoV-2 is fulfilled and vaccination campaigns have started worldwide. However, the fight against the pandemic is far from over. Here, we propose an age-structured compartmental model to study the interplay of disease transmission, vaccines rollout, and behavioural dynamics. We investigate, via in-silico simulations, individual and societal behavioural changes, possibly induced by the start of the vaccination campaigns, and manifested as a relaxation in the adoption of non-pharmaceutical interventions. We explore different vaccination rollout speeds, prioritization strategies, vaccine efficacy, as well as multiple behavioural responses. We apply our model to six countries worldwide (Egypt, Peru, Serbia, Ukraine, Canada, and Italy), selected to sample diverse socio-demographic and socio-economic contexts. To isolate the effects of age-structures and contacts patterns from the particular pandemic history of each location, we first study the model considering the same hypothetical initial epidemic scenario in all countries. We then calibrate the model using real epidemiological and mobility data for the different countries. Our findings suggest that early relaxation of safe behaviours can jeopardize the benefits brought by the vaccine in the short term: a fast vaccine distribution and policies aimed at keeping high compliance of individual safe behaviours are key to mitigate disease resurgence.

Socio-economic determinants of mobility responses during the first wave of COVID-19 in Italy: from provinces to neighbourhoods.

After more than 1 year into the COVID-19 pandemic, governments worldwide still face the challenge of adopting non-pharmaceutical interventions to mitigate the risks posed by the emergence of new SARS-CoV-2 variants and the lack of a worldwide equitable vaccine allocation. Thus, it becomes crucial to identify the drivers of mobility responses to mitigation efforts during different restriction regimes, for planning interventions that are both economically and socially sustainable while effective in controlling an outbreak. Here, using anonymous and privacy-enhanced cell phone data from Italy, we investigate the determinants of spatial variations of reductions in mobility and co-location in response to the adoption and the lift of restrictions, considering both provinces and city neighbourhoods. In large urban areas, our analysis uncovers the desertification of historic city centres, which persisted after the end of the lockdown. Such centre-periphery gradient was mainly associated with differences in educational attainment. At the province level, the local structure of the labour market mainly explained the variations in mobility responses, together with other demographic factors, such as the population's age and sex composition. In the future, targeted interventions should take into account how the ability to comply with restrictions varies across geographical areas and socio-demographic groups.

To trust or not to trust an explanation: using LEAF to evaluate local linear XAI methods.

The main objective of eXplainable Artificial Intelligence (XAI) is to provide effective explanations for black-box classifiers. The existing literature lists many desirable properties for explanations to be useful, but there is a scarce consensus on how to quantitatively evaluate explanations in practice. Moreover, explanations are typically used only to inspect black-box models, and the proactive use of explanations as a decision support is generally overlooked. Among the many approaches to XAI, a widely adopted paradigm is Local Linear Explanations-with LIME and SHAP emerging as state-of-the-art methods. We show that these methods are plagued by many defects including unstable explanations, divergence of actual implementations from the promised theoretical properties, and explanations for the wrong label. This highlights the need to have standard and unbiased evaluation procedures for Local Linear Explanations in the XAI field. In this paper we address the problem of identifying a clear and unambiguous set of metrics for the evaluation of Local Linear Explanations. This set includes both existing and novel metrics defined specifically for this class of explanations. All metrics have been included in an open Python framework, named LEAF. The purpose of LEAF is to provide a reference for end users to evaluate explanations in a standardised and unbiased way, and to guide researchers towards developing improved explainable techniques.

Patterns of Routes of Administration and Drug Tampering for Nonmedical Opioid Consumption: Data Mining and Content Analysis of Reddit Discussions.

BACKGROUND: The complex unfolding of the US opioid epidemic in the last 20 years has been the subject of a large body of medical and pharmacological research, and it has sparked a multidisciplinary discussion on how to implement interventions and policies to effectively control its impact on public health. OBJECTIVE: This study leverages Reddit, a social media platform, as the primary data source to investigate the opioid crisis. We aimed to find a large cohort of Reddit users interested in discussing the use of opioids, trace the temporal evolution of their interest, and extensively characterize patterns of the nonmedical consumption of opioids, with a focus on routes of administration and drug tampering. METHODS: We used a semiautomatic information retrieval algorithm to identify subreddits discussing nonmedical opioid consumption and developed a methodology based on word embedding to find alternative colloquial and nonmedical terms referring to opioid substances, routes of administration, and drug-tampering methods. We modeled the preferences of adoption of substances and routes of administration, estimating their prevalence and temporal unfolding. Ultimately, through the evaluation of odds ratios based on co-mentions, we measured the strength of association between opioid substances, routes of administration, and drug tampering. RESULTS: We identified 32 subreddits discussing nonmedical opioid usage from 2014 to 2018 and observed the evolution of interest among over 86,000 Reddit users potentially involved in firsthand opioid usage. We learned the language model of opioid consumption and provided alternative vocabularies for opioid substances, routes of administration, and drug tampering. A data-driven taxonomy of nonmedical routes of administration was proposed. We modeled the temporal evolution of interest in opioid consumption by ranking the popularity of the adoption of opioid substances and routes of administration, observing relevant trends, such as the surge in synthetic opioids like fentanyl and an increasing interest in rectal administration. In addition, we measured the strength of association between drug tampering, routes of administration, and substance consumption, finding evidence of understudied abusive behaviors, like chewing fentanyl patches and dissolving buprenorphine sublingually. CONCLUSIONS: This work investigated some important consumption-related aspects of the opioid epidemic using Reddit data. We believe that our approach may provide a novel perspective for a more comprehensive understanding of nonmedical abuse of opioids substances and inform the prevention, treatment, and control of the public health effects.

COVID-19 outbreak response, a dataset to assess mobility changes in Italy following national lockdown.

Italy has been severely affected by the COVID-19 pandemic, reporting the highest death toll in Europe as of April 2020. Following the identification of the first infections, on February 21, 2020, national authorities have put in place an increasing number of restrictions aimed at containing the outbreak and delaying the epidemic peak. On March 12, the government imposed a national lockdown. To aid the evaluation of the impact of interventions, we present daily time-series of three different aggregated mobility metrics: the origin-destination movements between Italian provinces, the radius of gyration, and the average degree of a spatial proximity network. All metrics were computed by processing a large-scale dataset of anonymously shared positions of about 170,000 de-identified smartphone users before and during the outbreak, at the sub-national scale. This dataset can help to monitor the impact of the lockdown on the epidemic trajectory and inform future public health decision making.

Spatial heterogeneity and socioeconomic determinants of opioid prescribing in England between 2015 and 2018.

BACKGROUND: Opioid overdoses have had a serious impact on the public health systems and socioeconomic welfare of several countries. Within this broader context, we focus our study on primary care opioid prescribing in England from 2015 to 2018, particularly the patterns of spatial variations at the community level and the socioeconomic and environmental factors that drive consumption. METHODS: Leveraging open data sources, we combine prescription records with aggregated data on patient provenance and build highly granular maps of Oral Morphine Equivalent (OME) prescribing rates for Lower Layer Super Output Areas (LSOA). We quantify the strength of spatial associations by means of the Empirical Bayes Index (EBI) that accounts for geographical variations in population density. We explore the interplay between socioeconomic and environmental determinants and prescribing rates by implementing a multivariate logistic regression model across different temporal snapshots and spatial scales. RESULTS: We observe, across time and geographical resolutions, a significant spatial association with the presence of localized hot and cold spots that group neighboring areas with homogeneous prescribing rates (e.g., EBI = 0.727 at LSOA level for 2018). Accounting for spatial dependency effects, we find that LSOA with both higher employment deprivation (OR = 62.6, CI 52.8-74.3) and a higher percentage of ethnically white (OR = 30.1, CI 25.4-35.7) inhabitants correspond to higher prescribing rates. Looking at educational attainment, we find LSOA with the prevalent degree of education being apprenticeship (OR = 2.33, CI 1.96-2.76) a risk factor and those with level 4+ (OR = 0.41, CI 0.35-0.48) a protective factor. Focusing on environmental determinants, housing (OR = 0.18, CI 0.15-0.21) and outdoor environment deprivation (OR = 0.62, CI 0.53-0.72) indices capture the bi-modal behavior observed in the literature concerning rural/urban areas. The results are consistent across time and spatial aggregations. CONCLUSIONS: Failing to account for local variations in opioid prescribing rates smooths out spatial dependency effects that result in underestimating/overestimating the impact on public health policies at the community level. Our study suggests a novel approach to inform more targeted interventions toward the most vulnerable population strata.

Assessing the use of mobile phone data to describe recurrent mobility patterns in spatial epidemic models.

The recent availability of large-scale call detail record data has substantially improved our ability of quantifying human travel patterns with broad applications in epidemiology. Notwithstanding a number of successful case studies, previous works have shown that using different mobility data sources, such as mobile phone data or census surveys, to parametrize infectious disease models can generate divergent outcomes. Thus, it remains unclear to what extent epidemic modelling results may vary when using different proxies for human movements. Here, we systematically compare 658 000 simulated outbreaks generated with a spatially structured epidemic model based on two different human mobility networks: a commuting network of France extracted from mobile phone data and another extracted from a census survey. We compare epidemic patterns originating from all the 329 possible outbreak seed locations and identify the structural network properties of the seeding nodes that best predict spatial and temporal epidemic patterns to be alike. We find that similarity of simulated epidemics is significantly correlated to connectivity, traffic and population size of the seeding nodes, suggesting that the adequacy of mobile phone data for infectious disease models becomes higher when epidemics spread between highly connected and heavily populated locations, such as large urban areas.

Association between recruitment methods and attrition in Internet-based studies.

Internet-based systems for epidemiological studies have advantages over traditional approaches as they can potentially recruit and monitor a wider range of individuals in a relatively inexpensive fashion. We studied the association between communication strategies used for recruitment (offline, online, face-to-face) and follow-up participation in nine Internet-based cohorts: the Influenzanet network of platforms for influenza surveillance which includes seven cohorts in seven different European countries, the Italian birth cohort Ninfea and the New Zealand birth cohort ELF. Follow-up participation varied from 43% to 89% depending on the cohort. Although there were heterogeneities among studies, participants who became aware of the study through an online communication campaign compared with those through traditional offline media seemed to have a lower follow-up participation in 8 out of 9 cohorts. There were no clear differences in participation between participants enrolled face-to-face and those enrolled through other offline strategies. An Internet-based campaign for Internet-based epidemiological studies seems to be less effective than an offline one in enrolling volunteers who keep participating in follow-up questionnaires. This suggests that even for Internet-based epidemiological studies an offline enrollment campaign would be helpful in order to achieve a higher participation proportion and limit the cohort attrition.

Pattern of tick aggregation on mice: larger than expected distribution tail enhances the spread of tick-borne pathogens.

The spread of tick-borne pathogens represents an important threat to human and animal health in many parts of Eurasia. Here, we analysed a 9-year time series of Ixodes ricinus ticks feeding on Apodemus flavicollis mice (main reservoir-competent host for tick-borne encephalitis, TBE) sampled in Trentino (Northern Italy). The tail of the distribution of the number of ticks per host was fitted by three theoretical distributions: Negative Binomial (NB), Poisson-LogNormal (PoiLN), and Power-Law (PL). The fit with theoretical distributions indicated that the tail of the tick infestation pattern on mice is better described by the PL distribution. Moreover, we found that the tail of the distribution significantly changes with seasonal variations in host abundance. In order to investigate the effect of different tails of tick distribution on the invasion of a non-systemically transmitted pathogen, we simulated the transmission of a TBE-like virus between susceptible and infective ticks using a stochastic model. Model simulations indicated different outcomes of disease spreading when considering different distribution laws of ticks among hosts. Specifically, we found that the epidemic threshold and the prevalence equilibria obtained in epidemiological simulations with PL distribution are a good approximation of those observed in simulations feed by the empirical distribution. Moreover, we also found that the epidemic threshold for disease invasion was lower when considering the seasonal variation of tick aggregation.

Interplay of network dynamics and heterogeneity of ties on spreading dynamics.

The structure of a network dramatically affects the spreading phenomena unfolding upon it. The contact distribution of the nodes has long been recognized as the key ingredient in influencing the outbreak events. However, limited knowledge is currently available on the role of the weight of the edges on the persistence of a pathogen. At the same time, recent works showed a strong influence of temporal network dynamics on disease spreading. In this work we provide an analytical understanding, corroborated by numerical simulations, about the conditions for infected stable state in weighted networks. In particular, we reveal the role of heterogeneity of edge weights and of the dynamic assignment of weights on the ties in the network in driving the spread of the epidemic. In this context we show that when weights are dynamically assigned to ties in the network, a heterogeneous distribution is able to hamper the diffusion of the disease, contrary to what happens when weights are fixed in time.

On the use of human mobility proxies for modeling epidemics.

Human mobility is a key component of large-scale spatial-transmission models of infectious diseases. Correctly modeling and quantifying human mobility is critical for improving epidemic control, but may be hindered by data incompleteness or unavailability. Here we explore the opportunity of using proxies for individual mobility to describe commuting flows and predict the diffusion of an influenza-like-illness epidemic. We consider three European countries and the corresponding commuting networks at different resolution scales, obtained from (i) official census surveys, (ii) proxy mobility data extracted from mobile phone call records, and (iii) the radiation model calibrated with census data. Metapopulation models defined on these countries and integrating the different mobility layers are compared in terms of epidemic observables. We show that commuting networks from mobile phone data capture the empirical commuting patterns well, accounting for more than 87% of the total fluxes. The distributions of commuting fluxes per link from mobile phones and census sources are similar and highly correlated, however a systematic overestimation of commuting traffic in the mobile phone data is observed. This leads to epidemics that spread faster than on census commuting networks, once the mobile phone commuting network is considered in the epidemic model, however preserving to a high degree the order of infection of newly affected locations. Proxies' calibration affects the arrival times' agreement across different models, and the observed topological and traffic discrepancies among mobility sources alter the resulting epidemic invasion patterns. Results also suggest that proxies perform differently in approximating commuting patterns for disease spread at different resolution scales, with the radiation model showing higher accuracy than mobile phone data when the seed is central in the network, the opposite being observed for peripheral locations. Proxies should therefore be chosen in light of the desired accuracy for the epidemic situation under study.

Determinants of follow-up participation in the Internet-based European influenza surveillance platform Influenzanet.

BACKGROUND: "Influenzanet" is a network of Internet-based platforms aimed at collecting real-time data for influenza surveillance in several European countries. More than 30,000 European volunteers participate every year in the study, representing one of the largest existing Internet-based multicenter cohorts. Each week during the influenza season, participants are asked to report their symptoms (if any) along with a set of additional questions. OBJECTIVE: Focusing on the first influenza season of 2011-12, when the Influenzanet system was completely harmonized within a common framework in Sweden, the United Kingdom, the Netherlands, Belgium, France, Italy, and Portugal, we investigated the propensity of users to regularly come back to the platform to provide information about their health status. Our purpose was to investigate demographic and behavioral factors associated with participation in follow-up. METHODS: By means of a multilevel analysis, we evaluated the association between regular participation during the season and sociodemographic and behavioral characteristics as measured by a background questionnaire completed by participants on registration. RESULTS: We found that lower participation in follow-up was associated with lower educational status (odds ratio [OR] 0.80, 95% CI 0.75-0.85), smoking (OR 0.64, 95% CI 0.59-0.70), younger age (OR ranging from 0.30, 95% CI 0.26-0.33 to 0.70, 95% CI 0.64-0.77), not being vaccinated against seasonal influenza (OR 0.77, 95% CI 0.72-0.84), and living in a household with children (OR 0.69, 95% CI 0.65-0.74). Most of these results hold when single countries are analyzed separately. CONCLUSIONS: Given the opportunistic enrollment of self-selected volunteers in the Influenzanet study, we have investigated how sociodemographic and behavioral characteristics may be associated with follow-up participation in the Influenzanet cohort. The study described in this paper shows that, overall, the most important determinants of participation are related to education and lifestyle: smoking, lower education level, younger age, people living with children, and people who have not been vaccinated against seasonal influenza tend to have a lower participation in follow-up. Despite the cross-country variation, the main findings are similar in the different national cohorts, and indeed the results are found to be valid also when performing a single-country analysis. Differences between countries do not seem to play a crucial role in determining the factors associated with participation in follow-up.

Real-time numerical forecast of global epidemic spreading: case study of 2009 A/H1N1pdm.

BACKGROUND: Mathematical and computational models for infectious diseases are increasingly used to support public-health decisions; however, their reliability is currently under debate. Real-time forecasts of epidemic spread using data-driven models have been hindered by the technical challenges posed by parameter estimation and validation. Data gathered for the 2009 H1N1 influenza crisis represent an unprecedented opportunity to validate real-time model predictions and define the main success criteria for different approaches. METHODS: We used the Global Epidemic and Mobility Model to generate stochastic simulations of epidemic spread worldwide, yielding (among other measures) the incidence and seeding events at a daily resolution for 3,362 subpopulations in 220 countries. Using a Monte Carlo Maximum Likelihood analysis, the model provided an estimate of the seasonal transmission potential during the early phase of the H1N1 pandemic and generated ensemble forecasts for the activity peaks in the northern hemisphere in the fall/winter wave. These results were validated against the real-life surveillance data collected in 48 countries, and their robustness assessed by focusing on 1) the peak timing of the pandemic; 2) the level of spatial resolution allowed by the model; and 3) the clinical attack rate and the effectiveness of the vaccine. In addition, we studied the effect of data incompleteness on the prediction reliability. RESULTS: Real-time predictions of the peak timing are found to be in good agreement with the empirical data, showing strong robustness to data that may not be accessible in real time (such as pre-exposure immunity and adherence to vaccination campaigns), but that affect the predictions for the attack rates. The timing and spatial unfolding of the pandemic are critically sensitive to the level of mobility data integrated into the model. CONCLUSIONS: Our results show that large-scale models can be used to provide valuable real-time forecasts of influenza spreading, but they require high-performance computing. The quality of the forecast depends on the level of data integration, thus stressing the need for high-quality data in population-based models, and of progressive updates of validated available empirical knowledge to inform these models.

Optimizing surveillance for livestock disease spreading through animal movements.

The spatial propagation of many livestock infectious diseases critically depends on the animal movements among premises; so the knowledge of movement data may help us to detect, manage and control an outbreak. The identification of robust spreading features of the system is however hampered by the temporal dimension characterizing population interactions through movements. Traditional centrality measures do not provide relevant information as results strongly fluctuate in time and outbreak properties heavily depend on geotemporal initial conditions. By focusing on the case study of cattle displacements in Italy, we aim at characterizing livestock epidemics in terms of robust features useful for planning and control, to deal with temporal fluctuations, sensitivity to initial conditions and missing information during an outbreak. Through spatial disease simulations, we detect spreading paths that are stable across different initial conditions, allowing the clustering of the seeds and reducing the epidemic variability. Paths also allow us to identify premises, called sentinels, having a large probability of being infected and providing critical information on the outbreak origin, as encoded in the clusters. This novel procedure provides a general framework that can be applied to specific diseases, for aiding risk assessment analysis and informing the design of optimal surveillance systems.

Dynamical patterns of cattle trade movements.

Despite their importance for the spread of zoonotic diseases, our understanding of the dynamical aspects characterizing the movements of farmed animal populations remains limited as these systems are traditionally studied as static objects and through simplified approximations. By leveraging on the network science approach, here we are able for the first time to fully analyze the longitudinal dataset of Italian cattle movements that reports the mobility of individual animals among farms on a daily basis. The complexity and inter-relations between topology, function and dynamical nature of the system are characterized at different spatial and time resolutions, in order to uncover patterns and vulnerabilities fundamental for the definition of targeted prevention and control measures for zoonotic diseases. Results show how the stationarity of statistical distributions coexists with a strong and non-trivial evolutionary dynamics at the node and link levels, on all timescales. Traditional static views of the displacement network hide important patterns of structural changes affecting nodes' centrality and farms' spreading potential, thus limiting the efficiency of interventions based on partial longitudinal information. By fully taking into account the longitudinal dimension, we propose a novel definition of dynamical motifs that is able to uncover the presence of a temporal arrow describing the evolution of the system and the causality patterns of its displacements, shedding light on mechanisms that may play a crucial role in the definition of preventive actions.

Human mobility networks, travel restrictions, and the global spread of 2009 H1N1 pandemic.

After the emergence of the H1N1 influenza in 2009, some countries responded with travel-related controls during the early stage of the outbreak in an attempt to contain or slow down its international spread. These controls along with self-imposed travel limitations contributed to a decline of about 40% in international air traffic to/from Mexico following the international alert. However, no containment was achieved by such restrictions and the virus was able to reach pandemic proportions in a short time. When gauging the value and efficacy of mobility and travel restrictions it is crucial to rely on epidemic models that integrate the wide range of features characterizing human mobility and the many options available to public health organizations for responding to a pandemic. Here we present a comprehensive computational and theoretical study of the role of travel restrictions in halting and delaying pandemics by using a model that explicitly integrates air travel and short-range mobility data with high-resolution demographic data across the world and that is validated by the accumulation of data from the 2009 H1N1 pandemic. We explore alternative scenarios for the 2009 H1N1 pandemic by assessing the potential impact of mobility restrictions that vary with respect to their magnitude and their position in the pandemic timeline. We provide a quantitative discussion of the delay obtained by different mobility restrictions and the likelihood of containing outbreaks of infectious diseases at their source, confirming the limited value and feasibility of international travel restrictions. These results are rationalized in the theoretical framework characterizing the invasion dynamics of the epidemics at the metapopulation level.

Estimate of Novel Influenza A/H1N1 cases in Mexico at the early stage of the pandemic with a spatially structured epidemic model.

Determining the number of cases in an epidemic is fundamental to properly evaluate several disease features of high relevance for public health policies such as mortality, morbidity or hospitalization rates. Surveillance efforts are however incomplete especially at the early stage of an outbreak due to the ongoing learning process about the disease characteristics. An example of this is represented by the number of H1N1 influenza cases in Mexico during the first months of the current pandemic. Several estimates using backtrack calculation based on imported cases from Mexico in other countries point out that the actual number of cases was likely orders of magnitude larger than the number of confirmed cases. Realistic computational models fed with the best available estimates of the basic disease parameters can provide an ab-initio calculation of the number of cases in Mexico as other countries. Here we use the Global Epidemic and Mobility (GLEaM) model to obtain estimates of the size of the epidemic in Mexico as well as of imported cases at the end of April and beginning of May. We find that the reference range for the number of cases in Mexico on April 30th is 121,000 to 1,394,000 in good agreement with the recent estimates by Lipsitch et al. [M. Lipsitch, PloS One 4:e6895 (2009)]. The number of imported cases from Mexico in several countries is found to be in good agreement with the surveillance data.