Michele Tizzoni

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.

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.

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

BackgroundMathematical 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.MethodsWe 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.ResultsReal-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.ConclusionsOur 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.

Heterogeneous length of stay of hosts’ movements and spatial epidemic spread

Infectious diseases outbreaks are often characterized by a spatial component induced by hosts’ distribution, mobility, and interactions. Spatial models that incorporate hosts’ movements are being used to describe these processes, to investigate the conditions for propagation, and to predict the spatial spread. Several assumptions are being considered to model hosts’ movements, ranging from permanent movements to daily commuting, where the time spent at destination is either infinite or assumes a homogeneous fixed value, respectively. Prompted by empirical evidence, here we introduce a general metapopulation approach to model the disease dynamics in a spatially structured population where the mobility process is characterized by a heterogeneous length of stay. We show that large fluctuations of the length of stay, as observed in reality, can have a significant impact on the threshold conditions for the global epidemic invasion, thus altering model predictions based on simple assumptions, and displaying important public health implications.

Human mobility and time spent at destination: Impact on spatial epidemic spreading

Host mobility plays a fundamental role in the spatial spread of infectious diseases. Previous theoretical works based on the integration of network theory into the metapopulation framework have shown that the heterogeneities that characterize real mobility networks favor the propagation of epidemics. Nevertheless, the studies conducted so far assumed the mobility process to be either Markovian (in which the memory of the origin of each traveler is lost) or non-Markovian with a fixed traveling time scale (in which individuals travel to a destination and come back at a constant rate). Available statistics however show that the time spent by travelers at destination is characterized by wide fluctuations, ranging from a single day up to several months. Such varying length of stay crucially affects the chance and duration of mixing events among hosts and may therefore have a strong impact on the spread of an emerging disease. Here, we present an analytical and a computational study of epidemic processes on a complex subpopulation network where travelers have memory of their origin and spend a heterogeneously distributed time interval at their destination. Through analytical calculations and numerical simulations we show that the heterogeneity of the length of stay alters the expression of the threshold between local outbreak and global invasion, and, moreover, it changes the epidemic behavior of the system in case of a global outbreak. Additionally, our theoretical framework allows us to study the effect of changes in the traveling behavior in response to the infection, by considering a scenario in which sick individuals do not leave their home location. Finally, we compare the results of our non-Markovian framework with those obtained with a classic Markovian approach and find relevant differences between the two, in the estimate of the epidemic invasion potential, as well as of the timing and the pattern of its spatial spread. These results highlight the importance of properly accounting for host trip duration in epidemic models and open the path to the inclusion of such an additional layer of complexity to the existing modeling approaches.

Modeling vaccination campaigns and the Fall/Winter 2009 activity of the new A(H1N1) influenza in the Northern Hemisphere

The unfolding of pandemic influenza A(H1N1) for Fall 2009 in the Northern Hemisphere is still uncertain. Plans for vaccination campaigns and vaccine trials are underway, with the first batches expected to be available early October. Several studies point to the possibility of an anticipated pandemic peak that could undermine the effectiveness of vaccination strategies. Here, we use a structured global epidemic and mobility metapopulation model to assess the effectiveness of massive vaccination campaigns for the Fall/Winter 2009. Mitigation effects are explored depending on the interplay between the predicted pandemic evolution and the expected delivery of vaccines. The model is calibrated using recent estimates on the transmissibility of the new A(H1N1) influenza. Results show that if additional intervention strategies were not used to delay the time of pandemic peak, vaccination may not be able to considerably reduce the cumulative number of cases, even when the mass vaccination campaign is started as early as mid-October. Prioritized vaccination would be crucial in slowing down the pandemic evolution and reducing its burden.

Predicting human mobility through the assimilation of social media traces into mobility models

Predicting human mobility flows at different spatial scales is challenged by the heterogeneity of individual trajectories and the multi-scale nature of transportation networks. As vast amounts of digital traces of human behaviour become available, an opportunity arises to improve mobility models by integrating into them proxy data on mobility collected by a variety of digital platforms and location-aware services. Here we propose a hybrid model of human mobility that integrates a large-scale publicly available dataset from a popular photo-sharing system with the classical gravity model, under a stacked regression procedure. We validate the performance and generalizability of our approach using two ground-truth datasets on air travel and daily commuting in the United States: using two different cross-validation schemes we show that the hybrid model affords enhanced mobility prediction at both spatial scales.

Quantifying social contacts in a household setting of rural Kenya using wearable proximity sensors

Close proximity interactions between individuals influence how infections spread. Quantifying close contacts in developing world settings, where such data is sparse yet disease burden is high, can provide insights into the design of intervention strategies such as vaccination. Recent technological advances have enabled collection of time-resolved face-to-face human contact data using radio frequency proximity sensors. The acceptability and practicalities of using proximity devices within the developing country setting have not been investigated.We present and analyse data arising from a prospective study of 5 households in rural Kenya, followed through 3 consecutive days. Pre-study focus group discussions with key community groups were held. All residents of selected households carried wearable proximity sensors to collect data on their close (<1.5 metres) interactions. Data collection for residents of three of the 5 households was contemporaneous. Contact matrices and temporal networks for 75 individuals are defined and mixing patterns by age and time of day in household contacts determined. Our study demonstrates the stability of numbers and durations of contacts across days. The contact durations followed a broad distribution consistent with data from other settings. Contacts within households occur mainly among children and between children and adults, and are characterised by daily regular peaks in the morning, midday and evening. Inter-household contacts are between adults and more sporadic when measured over several days. Community feedback indicated privacy as a major concern especially regarding perceptions of non-participants, and that community acceptability required thorough explanation of study tools and procedures.Our results show for a low resource setting how wearable proximity sensors can be used to objectively collect high-resolution temporal data without direct supervision. The methodology appears acceptable in this population following adequate community engagement on study procedures. A target for future investigation is to determine the difference in contact networks within versus between households. We suggest that the results from this study may be used in the design of future studies using similar electronic devices targeting communities, including households and schools, in the developing world context.

Unveiling patterns of international communities in a global city using mobile phone data

We analyse a large mobile phone activity dataset provided by Telecom Italia for the Telecom Big Data Challenge contest. The dataset reports the international country codes of every call/SMS made and received by mobile phone users in Milan, Italy, between November and December 2013, with a spatial resolution of about 200 meters. We first show that the observed spatial distribution of international codes well matches the distribution of international communities reported by official statistics, confirming the value of mobile phone data for demographic research. Next, we define an entropy function to measure the heterogeneity of the international phone activity in space and time. By comparing the entropy function to empirical data, we show that it can be used to identify the city’s hotspots, defined by the presence of points of interests. Eventually, we use the entropy function to characterize the spatial distribution of international communities in the city. Adopting a topological data analysis approach, we find that international mobile phone users exhibit some robust clustering patterns that correlate with basic socio-economic variables. Our results suggest that mobile phone records can be used in conjunction with topological data analysis tools to study the geography of migrant communities in a global city.

Social Data Mining and Seasonal Influenza Forecasts: The FluOutlook Platform

FluOutlook is an online platform where multiple data sources are integrated to initialize and train a portfolio of epidemic models for influenza forecast. During the 2014/15 season, the system has been used to provide real-time forecasts for 7 countries in North America and Europe.