Vittoria Colizza

The role of the airline transportation network in the prediction and predictability of global epidemics

The systematic study of large-scale networks has unveiled the ubiquitous presence of connectivity patterns characterized by large scale hetero geneities and unbounded statistical fluctuations. These features affect dramatically the be havior of the diffusion processes occurring on networks, determining the ensuing statistical properties of their evolution pattern and dynamics. In this paper, we investigate the role of the large scale properties of the airline transportation network in determining the global evolution of emerging disease. We present a stochastic computational framework for the forecast of global epidemics that considers the complete world-wide air travel infrastructure complemented with census population data. We address two basic issues in global epidemic modeling: i) We study the role of the large scale properties of the airline transportation network in determining the global diffusion pattern of emerging diseases; ii) We evaluate the reliability of forecasts and outbreak scenarios with respect to the intrinsic stochasticit y of disease transmission and traffic flows. In order to address these issues we define a set of novel q uantitative measures able to characterize the level of heterogeneity and predictabil ity of the epidemic pattern. These

Multiscale mobility networks and the spatial spreading of infectious diseases

Among the realistic ingredients to be considered in the computational modeling of infectious diseases, human mobility represents a crucial challenge both on the theoretical side and in view of the limited availability of empirical data. To study the interplay between short-scale commuting flows and long-range airline traffic in shaping the spatiotemporal pattern of a global epidemic we (i) analyze mobility data from 29 countries around the world and find a gravity model able to provide a global description of commuting patterns up to 300 kms and (ii) integrate in a worldwide-structured metapopulation epidemic model a timescale-separation technique for evaluating the force of infection due to multiscale mobility processes in the disease dynamics. Commuting flows are found, on average, to be one order of magnitude larger than airline flows. However, their introduction into the worldwide model shows that the large-scale pattern of the simulated epidemic exhibits only small variations with respect to the baseline case where only airline traffic is considered. The presence of short-range mobility increases, however, the synchronization of subpopulations in close proximity and affects the epidemic behavior at the periphery of the airline transportation infrastructure. The present approach outlines the possibility for the definition of layered computational approaches where different modeling assumptions and granularities can be used consistently in a unifying multiscale framework.

Modeling the Worldwide Spread of Pandemic Influenza: Baseline Case and Containment Interventions

Background The highly pathogenic H5N1 avian influenza virus, which is now widespread in Southeast Asia and which diffused recently in some areas of the Balkans region and Western Europe, has raised a public alert toward the potential occurrence of a new severe influenza pandemic. Here we study the worldwide spread of a pandemic and its possible containment at a global level taking into account all available information on air travel. Methods and Findings We studied a metapopulation stochastic epidemic model on a global scale that considers airline travel flow data among urban areas. We provided a temporal and spatial evolution of the pandemic with a sensitivity analysis of different levels of infectiousness of the virus and initial outbreak conditions (both geographical and seasonal). For each spreading scenario we provided the timeline and the geographical impact of the pandemic in 3,100 urban areas, located in 220 different countries. We compared the baseline cases with different containment strategies, including travel restrictions and the therapeutic use of antiviral (AV) drugs. We investigated the effect of the use of AV drugs in the event that therapeutic protocols can be carried out with maximal coverage for the populations in all countries. In view of the wide diversity of AV stockpiles in different regions of the world, we also studied scenarios in which only a limited number of countries are prepared (i.e., have considerable AV supplies). In particular, we compared different plans in which, on the one hand, only prepared and wealthy countries benefit from large AV resources, with, on the other hand, cooperative containment scenarios in which countries with large AV stockpiles make a small portion of their supplies available worldwide. Conclusions We show that the inclusion of air transportation is crucial in the assessment of the occurrence probability of global outbreaks. The large-scale therapeutic usage of AV drugs in all hit countries would be able to mitigate a pandemic effect with a reproductive rate as high as 1.9 during the first year; with AV supply use sufficient to treat approximately 2% to 6% of the population, in conjunction with efficient case detection and timely drug distribution. For highly contagious viruses (i.e., a reproductive rate as high as 2.3), even the unrealistic use of supplies corresponding to the treatment of approximately 20% of the population leaves 30%–50% of the population infected. In the case of limited AV supplies and pandemics with a reproductive rate as high as 1.9, we demonstrate that the more cooperative the strategy, the more effective are the containment results in all regions of the world, including those countries that made part of their resources available for global use.

Detecting rich-club ordering in complex networks

Uncovering the hidden regularities and organizational principles of networks arising in physical systems ranging from the molecular level to the scale of large communication infrastructures is the key issue in understanding their fabric and dynamical properties1,2,3,4,5. The ‘rich-club’ phenomenon refers to the tendency of nodes with high centrality, the dominant elements of the system, to form tightly interconnected communities, and it is one of the crucial properties accounting for the formation of dominant communities in both computer and social sciences4,5,6,7,8. Here, we provide the analytical expression and the correct null models that allow for a quantitative discussion of the rich-club phenomenon. The presented analysis enables the measurement of the rich-club ordering and its relation with the function and dynamics of networks in examples drawn from the biological, social and technological domains.

Dynamics of person-to-person interactions from distributed RFID sensor networks.

Background Digital networks, mobile devices, and the possibility of mining the ever-increasing amount of digital traces that we leave behind in our daily activities are changing the way we can approach the study of human and social interactions. Large-scale datasets, however, are mostly available for collective and statistical behaviors, at coarse granularities, while high-resolution data on person-to-person interactions are generally limited to relatively small groups of individuals. Here we present a scalable experimental framework for gathering real-time data resolving face-to-face social interactions with tunable spatial and temporal granularities. Methods and Findings We use active Radio Frequency Identification (RFID) devices that assess mutual proximity in a distributed fashion by exchanging low-power radio packets. We analyze the dynamics of person-to-person interaction networks obtained in three high-resolution experiments carried out at different orders of magnitude in community size. The data sets exhibit common statistical properties and lack of a characteristic time scale from 20 seconds to several hours. The association between the number of connections and their duration shows an interesting super-linear behavior, which indicates the possibility of defining super-connectors both in the number and intensity of connections. Conclusions Taking advantage of scalability and resolution, this experimental framework allows the monitoring of social interactions, uncovering similarities in the way individuals interact in different contexts, and identifying patterns of super-connector behavior in the community. These results could impact our understanding of all phenomena driven by face-to-face interactions, such as the spreading of transmissible infectious diseases and information.

Seasonal transmission potential and activity peaks of the new influenza A(H1N1): a Monte Carlo likelihood analysis based on human mobility

BackgroundOn 11 June the World Health Organization officially raised the phase of pandemic alert (with regard to the new H1N1 influenza strain) to level 6. As of 19 July, 137,232 cases of the H1N1 influenza strain have been officially confirmed in 142 different countries, and the pandemic unfolding in the Southern hemisphere is now under scrutiny to gain insights about the next winter wave in the Northern hemisphere. A major challenge is pre-empted by the need to estimate the transmission potential of the virus and to assess its dependence on seasonality aspects in order to be able to use numerical models capable of projecting the spatiotemporal pattern of the pandemic.MethodsIn the present work, we use a global structured metapopulation model integrating mobility and transportation data worldwide. The model considers data on 3,362 subpopulations in 220 different countries and individual mobility across them. The model generates stochastic realizations of the epidemic evolution worldwide considering 6 billion individuals, from which we can gather information such as prevalence, morbidity, number of secondary cases and number and date of imported cases for each subpopulation, all with a time resolution of 1 day. In order to estimate the transmission potential and the relevant model parameters we used the data on the chronology of the 2009 novel influenza A(H1N1). The method is based on the maximum likelihood analysis of the arrival time distribution generated by the model in 12 countries seeded by Mexico by using 1 million computationally simulated epidemics. An extended chronology including 93 countries worldwide seeded before 18 June was used to ascertain the seasonality effects.ResultsWe found the best estimate R0 = 1.75 (95% confidence interval (CI) 1.64 to 1.88) for the basic reproductive number. Correlation analysis allows the selection of the most probable seasonal behavior based on the observed pattern, leading to the identification of plausible scenarios for the future unfolding of the pandemic and the estimate of pandemic activity peaks in the different hemispheres. We provide estimates for the number of hospitalizations and the attack rate for the next wave as well as an extensive sensitivity analysis on the disease parameter values. We also studied the effect of systematic therapeutic use of antiviral drugs on the epidemic timeline.ConclusionThe analysis shows the potential for an early epidemic peak occurring in October/November in the Northern hemisphere, likely before large-scale vaccination campaigns could be carried out. The baseline results refer to a worst-case scenario in which additional mitigation policies are not considered. We suggest that the planning of additional mitigation policies such as systematic antiviral treatments might be the key to delay the activity peak in order to restore the effectiveness of the vaccination programs.

Epidemic modeling in metapopulation systems with heterogeneous coupling pattern: theory and simulations.

The spatial structure of populations is a key element in the understanding of the large-scale spreading of epidemics. Motivated by the recent empirical evidence on the heterogeneous properties of transportation and commuting patterns among urban areas, we present a thorough analysis of the behavior of infectious diseases in metapopulation models characterized by heterogeneous connectivity and mobility patterns. We derive the basic reaction-diffusion equations describing the metapopulation system at the mechanistic level and derive an early stage dynamics approximation for the subpopulation invasion dynamics. The analytical description uses a homogeneous assumption on degree block variables that allows us to take into account arbitrary degree distribution of the metapopulation network. We show that along with the usual single population epidemic threshold the metapopulation network exhibits a global threshold for the subpopulation invasion. We find an explicit analytic expression for the invasion threshold that determines the minimum number of individuals traveling among subpopulations in order to have the infection of a macroscopic number of subpopulations. The invasion threshold is a function of factors such as the basic reproductive number, the infectious period and the mobility process and it is found to decrease for increasing network heterogeneity. We provide extensive mechanistic numerical Monte Carlo simulations that recover the analytical finding in a wide range of metapopulation network connectivity patterns. The results can be useful in the understanding of recent data driven computational approaches to disease spreading in large transportation networks and the effect of containment measures such as travel restrictions.

Simulation of an SEIR infectious disease model on the dynamic contact network of conference attendees

BackgroundThe spread of infectious diseases crucially depends on the pattern of contacts between individuals. Knowledge of these patterns is thus essential to inform models and computational efforts. However, there are few empirical studies available that provide estimates of the number and duration of contacts between social groups. Moreover, their space and time resolutions are limited, so that data are not explicit at the person-to-person level, and the dynamic nature of the contacts is disregarded. In this study, we aimed to assess the role of data-driven dynamic contact patterns between individuals, and in particular of their temporal aspects, in shaping the spread of a simulated epidemic in the population.MethodsWe considered high-resolution data about face-to-face interactions between the attendees at a conference, obtained from the deployment of an infrastructure based on radiofrequency identification (RFID) devices that assessed mutual face-to-face proximity. The spread of epidemics along these interactions was simulated using an SEIR (Susceptible, Exposed, Infectious, Recovered) model, using both the dynamic network of contacts defined by the collected data, and two aggregated versions of such networks, to assess the role of the data temporal aspects.ResultsWe show that, on the timescales considered, an aggregated network taking into account the daily duration of contacts is a good approximation to the full resolution network, whereas a homogeneous representation that retains only the topology of the contact network fails to reproduce the size of the epidemic.ConclusionsThese results have important implications for understanding the level of detail needed to correctly inform computational models for the study and management of real epidemics.Please see related article BMC Medicine, 2011, 9:88

Invasion threshold in heterogeneous metapopulation networks

We study the dynamics of epidemic and reaction-diffusion processes in metapopulation models with heterogeneous connectivity patterns. In susceptible-infected-removed-like processes, along with the standard local epidemic threshold, the system exhibits a global invasion threshold. We provide an explicit expression of the threshold that sets a critical value of the diffusion/mobility rate below, which the epidemic is not able to spread to a macroscopic fraction of subpopulations. The invasion threshold is found to be affected by the topological fluctuations of the metapopulation network. The results presented provide a general framework for the understanding of the effect of travel restrictions in epidemic containment.

Close Encounters in a Pediatric Ward: Measuring Face-to-Face Proximity and Mixing Patterns with Wearable Sensors

Background Nosocomial infections place a substantial burden on health care systems and represent one of the major issues in current public health, requiring notable efforts for its prevention. Understanding the dynamics of infection transmission in a hospital setting is essential for tailoring interventions and predicting the spread among individuals. Mathematical models need to be informed with accurate data on contacts among individuals. Methods and Findings We used wearable active Radio-Frequency Identification Devices (RFID) to detect face-to-face contacts among individuals with a spatial resolution of about 1.5 meters, and a time resolution of 20 seconds. The study was conducted in a general pediatrics hospital ward, during a one-week period, and included 119 participants, with 51 health care workers, 37 patients, and 31 caregivers. Nearly 16,000 contacts were recorded during the study period, with a median of approximately 20 contacts per participants per day. Overall, 25% of the contacts involved a ward assistant, 23% a nurse, 22% a patient, 22% a caregiver, and 8% a physician. The majority of contacts were of brief duration, but long and frequent contacts especially between patients and caregivers were also found. In the setting under study, caregivers do not represent a significant potential for infection spread to a large number of individuals, as their interactions mainly involve the corresponding patient. Nurses would deserve priority in prevention strategies due to their central role in the potential propagation paths of infections. Conclusions Our study shows the feasibility of accurate and reproducible measures of the pattern of contacts in a hospital setting. The obtained results are particularly useful for the study of the spread of respiratory infections, for monitoring critical patterns, and for setting up tailored prevention strategies. Proximity-sensing technology should be considered as a valuable tool for measuring such patterns and evaluating nosocomial prevention strategies in specific settings.