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

We present a study of the worldwide spread of a pandemic influenza and its possible containment at a global level taking into account all available information on air travel. 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 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.Comment: 16 page

The effectiveness of policies to control a human influenza pandemic : a literature review

The studies reviewed in this paper indicate that with adequate preparedness planning and execution it is possible to contain pandemic influenza outbreaks where they occur, for viral strains of moderate infectiousness. For viral strains of higher infectiousness, containment may be difficult, but it may be possible to mitigate the effects of the spread of pandemic influenza within a country and/or internationally with a combination of policies suited to the origins and nature of the initial outbreak. These results indicate the likelihood of containment success in'frontline risk'countries, given specific resource availability and level of infectiousness; as well as mitigation success in'secondary'risk countries, given the assumption of inevitable international transmission through air travel networks. However, from the analysis of the modeling results on interventions in the U.S. and U.K. after a global pandemic starts, there is a basis for arguing that the emphasis in the secondary risk countries could shift from mitigation towards containment. This follows since a mitigation-focused strategy in such developed countries presupposes that initial outbreak containment in these countries will necessarily fail. This is paradoxical if containment success at similar infectiousness of the virus is likely in developing countries with lower public health resources, based on results using similar modeling methodologies. Such a shift in emphasis could have major implications for global risk management for diseases of international concern such as pandemic influenza or a SARS-like disease.Avian Flu,Disease Control&Prevention,Health Monitoring&Evaluation,Population Policies,HIV AIDS

A Comparative Analysis of Influenza Vaccination Programs

The threat of avian influenza and the 2004-2005 influenza vaccine supply shortage in the United States has sparked a debate about optimal vaccination strategies to reduce the burden of morbidity and mortality caused by the influenza virus. We present a comparative analysis of two classes of suggested vaccination strategies: mortality-based strategies that target high risk populations and morbidity-based that target high prevalence populations. Applying the methods of contact network epidemiology to a model of disease transmission in a large urban population, we evaluate the efficacy of these strategies across a wide range of viral transmission rates and for two different age-specific mortality distributions. We find that the optimal strategy depends critically on the viral transmission level (reproductive rate) of the virus: morbidity-based strategies outperform mortality-based strategies for moderately transmissible strains, while the reverse is true for highly transmissible strains. These results hold for a range of mortality rates reported for prior influenza epidemics and pandemics. Furthermore, we show that vaccination delays and multiple introductions of disease into the community have a more detrimental impact on morbidity-based strategies than mortality-based strategies. If public health officials have reasonable estimates of the viral transmission rate and the frequency of new introductions into the community prior to an outbreak, then these methods can guide the design of optimal vaccination priorities. When such information is unreliable or not available, as is often the case, this study recommends mortality-based vaccination priorities

Characterising two-pathogen competition in spatially structured environments

Different pathogens spreading in the same host population often generate complex co-circulation dynamics because of the many possible interactions between the pathogens and the host immune system, the host life cycle, and the space structure of the population. Here we focus on the competition between two acute infections and we address the role of host mobility and cross-immunity in shaping possible dominance/co-dominance regimes. Host mobility is modelled as a network of traveling flows connecting nodes of a metapopulation, and the two-pathogen dynamics is simulated with a stochastic mechanistic approach. Results depict a complex scenario where, according to the relation among the epidemiological parameters of the two pathogens, mobility can either be non-influential for the competition dynamics or play a critical role in selecting the dominant pathogen. The characterisation of the parameter space can be explained in terms of the trade-off between pathogen's spreading velocity and its ability to diffuse in a sparse environment. Variations in the cross-immunity level induce a transition between presence and absence of competition. The present study disentangles the role of the relevant biological and ecological factors in the competition dynamics, and provides relevant insights into the spatial ecology of infectious diseases.Comment: 30 pages, 6 figures, 1 table. Final version accepted for publication in Scientific Report

Modeling highly pathogenic avian influenza transmission in wild birds and poultry in West Bengal, India.

Wild birds are suspected to have played a role in highly pathogenic avian influenza (HPAI) H5N1 outbreaks in West Bengal. Cluster analysis showed that H5N1 was introduced in West Bengal at least 3 times between 2008 and 2010. We simulated the introduction of H5N1 by wild birds and their contact with poultry through a stochastic continuous-time mathematical model. Results showed that reducing contact between wild birds and domestic poultry, and increasing the culling rate of infected domestic poultry communities will reduce the probability of outbreaks. Poultry communities that shared habitat with wild birds or those indistricts with previous outbreaks were more likely to suffer an outbreak. These results indicate that wild birds can introduce HPAI to domestic poultry and that limiting their contact at shared habitats together with swift culling of infected domestic poultry can greatly reduce the likelihood of HPAI outbreaks

Using epidemic prevalence data to jointly estimate reproduction and removal

This study proposes a nonhomogeneous birth--death model which captures the dynamics of a directly transmitted infectious disease. Our model accounts for an important aspect of observed epidemic data in which only symptomatic infecteds are observed. The nonhomogeneous birth--death process depends on survival distributions of reproduction and removal, which jointly yield an estimate of the effective reproduction number $R(t)$ as a function of epidemic time. We employ the Burr distribution family for the survival functions and, as special cases, proportional rate and accelerated event-time models are also employed for the parameter estimation procedure. As an example, our model is applied to an outbreak of avian influenza (H7N7) in the Netherlands, 2003, confirming that the conditional estimate of $R(t)$ declined below unity for the first time on day 23 since the detection of the index case.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS270 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

International chicken trade and increased risk for introducing or reintroducing highly pathogenic avian influenza A (H5N1) to uninfected countries.

Every year billions of chickens are shipped thousands of miles around the globe in order to meet the ever increasing demands for this cheap and nutritious protein source. Unfortunately, transporting chickens internationally can also increase the chance for introducing zoonotic viruses, such as highly pathogenic avian influenza A (H5N1) to new countries. Our study used a retrospective analysis of poultry trading data from 2003 through 2011 to assess the risk of H5N1 poultry infection in an importing country. We found that the risk of infection in an importing country increased by a factor of 1.3 (95% CI: 1.1-1.5) for every 10-fold increase in live chickens imported from countries experiencing at least one H5N1 poultry case during that year. These results suggest that the risk in a particular country can be significantly reduced if imports from countries experiencing an outbreak are decreased during the year of infection or if biosecurity measures such as screening, vaccination, and infection control practices are increased. These findings show that limiting trade of live chickens or increasing infection control practices during contagious periods may be an important step in reducing the spread of H5N1 and other emerging avian influenza viruses

Analysis of CDC social control measures using an agent-based simulation of an influenza epidemic in a city

Background: the transmission of infectious disease amongst the human population is a complex process which requires advanced, often individual-based, models to capture the space-time details observed in reality.Methods: an Individual Space-Time Activity-based Model (ISTAM) was applied to simulate the effectiveness of non-pharmaceutical control measures including: (1) refraining from social activities, (2) school closure and (3) household quarantine, for a hypothetical influenza outbreak in an urban area.Results: amongst the set of control measures tested, refraining from social activities with various compliance levels was relatively ineffective. Household quarantine was very effective, especially for the peak number of cases and total number of cases, with large differences between compliance levels. Household quarantine resulted in a decrease in the peak number of cases from more than 300 to around 158 for a 100% compliance level, a decrease of about 48.7%. The delay in the outbreak peak was about 3 to 17 days. The total number of cases decreased to a range of 3635-5403, that is, 63.7%-94.7% of the baseline value.When coupling control measures, household quarantine together with school closure was the most effective strategy. The resulting space-time distribution of infection in different classes of activity bundles (AB) suggests that the epidemic outbreak is strengthened amongst children and then spread to adults. By sensitivity analysis, this study demonstrated that earlier implementation of control measures leads to greater efficacy. Also, for infectious diseases with larger basic reproduction number, the effectiveness of non-pharmaceutical measures was shown to be limited.Conclusions: simulated results showed that household quarantine was the most effective control measure, while school closure and household quarantine implemented together achieved the greatest benefit. Agent-based models should be applied in the future to evaluate the efficacy of control measures for a range of disease outbreaks in a range of settings given sufficient information about the given case and knowledge about the transmission processes at a fine scal

The impact of surveillance and control on highly pathogenic avian influenza outbreaks in poultry in Dhaka division, Bangladesh

In Bangladesh, the poultry industry is an economically and socially important sector, but it is persistently threatened by the effects of H5N1 highly pathogenic avian influenza. Thus, identifying the optimal control policy in response to an emerging disease outbreak is a key challenge for policy-makers. To inform this aim, a common approach is to carry out simulation studies comparing plausible strategies, while accounting for known capacity restrictions. In this study we perform simulations of a previously developed H5N1 influenza transmission model framework, fitted to two separate historical outbreaks, to assess specific control objectives related to the burden or duration of H5N1 outbreaks among poultry farms in the Dhaka division of Bangladesh. In particular, we explore the optimal implementation of ring culling, ring vaccination and active surveillance measures when presuming disease transmission predominately occurs from premises-to-premises, versus a setting requiring the inclusion of external factors. Additionally, we determine the sensitivity of the management actions under consideration to differing levels of capacity constraints and outbreaks with disparate transmission dynamics. While we find that reactive culling and vaccination policies should pay close attention to these factors to ensure intervention targeting is optimised, across multiple settings the top performing control action amongst those under consideration were targeted proactive surveillance schemes. Our findings may advise the type of control measure, plus its intensity, that could potentially be applied in the event of a developing outbreak of H5N1 amongst originally H5N1 virus-free commercially-reared poultry in the Dhaka division of Bangladesh