Contact among healthcare workers in the hospital setting: developing the evidence base for innovative approaches to infection control.

BACKGROUND: Nosocomial, or healthcare-associated infections (HAI), exact a high medical and financial toll on patients, healthcare workers, caretakers, and the health system. Interpersonal contact patterns play a large role in infectious disease spread, but little is known about the relationship between health care workers' (HCW) movements and contact patterns within a heath care facility and HAI. Quantitatively capturing these patterns will aid in understanding the dynamics of HAI and may lead to more targeted and effective control strategies in the hospital setting. METHODS: Staff at 3 urban university-based tertiary care hospitals in Canada completed a detailed questionnaire on demographics, interpersonal contacts, in-hospital movement, and infection prevention and control practices. Staff were divided into categories of administrative/support, nurses, physicians, and "Other HCWs" - a fourth distinct category, which excludes physicians and nurses. Using quantitative network modeling tools, we constructed the resulting HCW "co-location network" to illustrate contacts among different occupations and with locations in hospital settings. RESULTS: Among 3048 respondents (response rate 38%) an average of 3.79, 3.69 and 3.88 floors were visited by each HCW each week in the 3 hospitals, with a standard deviation of 2.63, 1.74 and 2.08, respectively. Physicians reported the highest rate of direct patient contacts (> 20 patients/day) but the lowest rate of contacts with other HCWs; nurses had the most extended (> 20 min) periods of direct patient contact. "Other HCWs" had the most direct daily contact with all other HCWs. Physicians also reported significantly more locations visited per week than nurses, other HCW, or administrators; nurses visited the fewest. Public spaces such as the cafeteria had the most staff visits per week, but the least mean hours spent per visit. Inpatient settings had significantly more HCW interactions per week than outpatient settings. CONCLUSIONS: HCW contact patterns and spatial movement demonstrate significant heterogeneity by occupation. Control strategies that address this diversity among health care workers may be more effective than "one-strategy-fits-all" HAI prevention and control programs.

Increasing health policy and systems research capacity in low- and middle-income countries: results from a bibliometric analysis.

BACKGROUND: For 20 years, substantial effort has been devoted to catalyse health policy and systems research (HPSR) to support vulnerable populations and resource-constrained regions through increased funding, institutional capacity-building and knowledge production; yet, participation from low- and middle-income countries (LMICs) is underrepresented in HPSR knowledge production. METHODS: A bibliometric analysis of HPSR literature was conducted using a high-level keyword search. Health policy and/or health systems literature with a topic relevant to LMICs and whose lead author's affiliation is in an LMIC were included for analysis. The trends in knowledge production from 1990 to 2015 were examined to understand how investment in HPSR benefits those it means to serve. RESULTS: The total number of papers published in PubMed increases each year. HPSR publications represent approximately 10% of these publications, but this percentage is increasing at a greater rate than PubMed publications overall and the discipline is holding this momentum. HPSR publications with topics relevant to LMICs and an LMIC-affiliated lead authors (specifically from low-income countries) are increasing at a greater rate than any other category within the scope of this analysis. CONCLUSIONS: While the absolute number of publications remains low, lead authors from an LMIC have participated exponentially in the life and biomedical sciences (PubMed) since the early 2000s. HPSR publications with a topic relevant to LMICs and an LMIC lead author continue to increase at a greater rate than the life and biomedical science topics in general. This correlation is likely due to increased capacity for research within LMICs and the support for publications surrounding large HPSR initiatives. These findings provide strong evidence that continued support is key to the longevity and enhancement of HPSR toward its mandate.

Health policy and systems research collaboration pathways: lessons from a network science analysis.

BACKGROUND: The 2004 Mexico Declaration, and subsequent World Health Assembly resolutions, proposed a concerted support for the global development of health policy and systems research (HPSR). This included coordination across partners and advocates for the field of HPSR to monitor the development of the field, while promoting decision-making power and implementing responsibilities in low- and middle-income countries (LMICs). METHODS: We used a network science approach to examine the structural properties of the HPSR co-authorship network across country economic groups in the PubMed citation database from 1990 to 2015. This analysis summarises the evolution of the publication, co-authorship and citation networks within HPSR. RESULTS: This method allows identification of several features otherwise not apparent. The co-authorship network has evolved steadily from 1990 to 2015 in terms of number of publications, but more importantly, in terms of co-authorship network connectedness. Our analysis suggests that, despite growth in the contribution from low-income countries to HPSR literature, co-authorship remains highly localised. Lower middle-income countries have made progress toward global connectivity through diversified collaboration with various institutions and regions. Global connectivity of the upper middle-income countries (UpperMICs) are almost on par with high-income countries (HICs), indicating the transition of this group of countries toward becoming major contributors to the field. CONCLUSIONS: Network analysis allows examination of the connectedness among the HSPR community. Initially (early 1990s), research groups operated almost exclusively independently and, despite the topic being specifically on health policy in LMICs, HICs provided lead authorship. Since the early 1990s, the network has evolved significantly. In the full set analysis (1990-2015), for the first time in HPSR history, more than half of the authors are connected and lead authorship from UpperMICs is on par with that of HICs. This demonstrates the shift in participation and influence toward regions which HPSR primarily serves. Understanding these interactions can highlight the current strengths and future opportunities for identifying new strategies to enhance collaboration and support capacity-building efforts for HPSR.

Human mobility patterns predict divergent epidemic dynamics among cities.

The epidemic dynamics of infectious diseases vary among cities, but it is unclear how this is caused by patterns of infectious contact among individuals. Here, we ask whether systematic differences in human mobility patterns are sufficient to cause inter-city variation in epidemic dynamics for infectious diseases spread by casual contact between hosts. We analyse census data on the mobility patterns of every full-time worker in 48 Canadian cities, finding a power-law relationship between population size and the level of organization in mobility patterns, where in larger cities, a greater fraction of workers travel to work in a few focal locations. Similarly sized cities also vary in the level of organization in their mobility patterns, equivalent on average to the variation expected from a 2.64-fold change in population size. Systematic variation in mobility patterns is sufficient to cause significant differences among cities in infectious disease dynamics-even among cities of the same size-according to an individual-based model of airborne pathogen transmission parametrized with the mobility data. This suggests that differences among cities in host contact patterns are sufficient to drive differences in infectious disease dynamics and provides a framework for testing the effects of host mobility patterns in city-level disease data.

Vaccination against 2009 pandemic H1N1 in a population dynamical model of Vancouver, Canada: timing is everything.

BACKGROUND: Much remains unknown about the effect of timing and prioritization of vaccination against pandemic (pH1N1) 2009 virus on health outcomes. We adapted a city-level contact network model to study different campaigns on influenza morbidity and mortality. METHODS: We modeled different distribution strategies initiated between July and November 2009 using a compartmental epidemic model that includes age structure and transmission network dynamics. The model represents the Greater Vancouver Regional District, a major North American city and surrounding suburbs with a population of 2 million, and is parameterized using data from the British Columbia Ministry of Health, published studies, and expert opinion. Outcomes are expressed as the number of infections and deaths averted due to vaccination. RESULTS: The model output was consistent with provincial surveillance data. Assuming a basic reproduction number = 1.4, an 8-week vaccination campaign initiated 2 weeks before the epidemic onset reduced morbidity and mortality by 79-91% and 80-87%, respectively, compared to no vaccination. Prioritizing children and parents for vaccination may have reduced transmission compared to actual practice, but the mortality benefit of this strategy appears highly sensitive to campaign timing. Modeling the actual late October start date resulted in modest reductions in morbidity and mortality (13-25% and 16-20%, respectively) with little variation by prioritization scheme. CONCLUSION: Delays in vaccine production due to technological or logistical barriers may reduce potential benefits of vaccination for pandemic influenza, and these temporal effects can outweigh any additional theoretical benefits from population targeting. Careful modeling may provide decision makers with estimates of these effects before the epidemic peak to guide production goals and inform policy. Integration of real-time surveillance data with mathematical models holds the promise of enabling public health planners to optimize the community benefits from proposed interventions before the pandemic peak.

Epidemics with general generation interval distributions.

We study the spread of susceptible-infected-recovered (SIR) infectious diseases where an individual's infectiousness and probability of recovery depend on his/her "age" of infection. We focus first on early outbreak stages when stochastic effects dominate and show that epidemics tend to happen faster than deterministic calculations predict. If an outbreak is sufficiently large, stochastic effects are negligible and we modify the standard ordinary differential equation (ODE) model to accommodate age-of-infection effects. We avoid the use of partial differential equations which typically appear in related models. We introduce a "memoryless" ODE system which approximates the true solutions. Finally, we analyze the transition from the stochastic to the deterministic phase.

Estimated epidemiologic parameters and morbidity associated with pandemic H1N1 influenza.

BACKGROUND: In the face of an influenza pandemic, accurate estimates of epidemiologic parameters are required to help guide decision-making. We sought to estimate epidemiologic parameters for pandemic H1N1 influenza using data from initial reports of laboratory-confirmed cases. METHODS: We obtained data on laboratory-confirmed cases of pandemic H1N1 influenza reported in the province of Ontario, Canada, with dates of symptom onset between Apr. 13 and June 20, 2009. Incubation periods and duration of symptoms were estimated and fit to parametric distributions. We used competing-risk models to estimate risk of hospital admission and case-fatality rates. We used a Markov Chain Monte Carlo model to simulate disease transmission. RESULTS: The median incubation period was 4 days and the duration of symptoms was 7 days. Recovery was faster among patients less than 18 years old than among older patients (hazard ratio 1.23, 95% confidence interval 1.06-1.44). The risk of hospital admission was 4.5% (95% CI 3.8%-5.2%) and the case-fatality rate was 0.3% (95% CI 0.1%-0.5%). The risk of hospital admission was highest among patients less than 1 year old and those 65 years or older. Adults more than 50 years old comprised 7% of cases but accounted for 7 of 10 initial deaths (odds ratio 28.6, 95% confidence interval 7.3-111.2). From the simulation models, we estimated the following values (and 95% credible intervals): a mean basic reproductive number (R0, the number of new cases created by a single primary case in a susceptible population) of 1.31 (1.25-1.38), a mean latent period of 2.62 (2.28-3.12) days and a mean duration of infectiousness of 3.38 (2.06-4.69) days. From these values we estimated a serial interval (the average time from onset of infectiousness in a case to the onset of infectiousness in a person infected by that case) of 4-5 days. INTERPRETATION: The low estimates for R0 indicate that effective mitigation strategies may reduce the final epidemic impact of pandemic H1N1 influenza.

Heterogeneous bond percolation on multitype networks with an application to epidemic dynamics.

Considerable attention has been paid, in recent years, to the use of networks in modeling complex real-world systems. Among the many dynamical processes involving networks, propagation processes-in which the final state can be obtained by studying the underlying network percolation properties-have raised formidable interest. In this paper, we present a bond percolation model of multitype networks with an arbitrary joint degree distribution that allows heterogeneity in the edge occupation probability. As previously demonstrated, the multitype approach allows many nontrivial mixing patterns such as assortativity and clustering between nodes. We derive a number of useful statistical properties of multitype networks as well as a general phase transition criterion. We also demonstrate that a number of previous models based on probability generating functions are special cases of the proposed formalism. We further show that the multitype approach, by naturally allowing heterogeneity in the bond occupation probability, overcomes some of the correlation issues encountered by previous models. We illustrate this point in the context of contact network epidemiology.

Time evolution of epidemic disease on finite and infinite networks.

Mathematical models of infectious diseases, which are in principle analytically tractable, use two general approaches. The first approach, generally known as compartmental modeling, addresses the time evolution of disease propagation at the expense of simplifying the pattern of transmission. The second approach uses network theory to incorporate detailed information pertaining to the underlying contact structure among individuals while disregarding the progression of time during outbreaks. So far, the only alternative that enables the integration of both aspects of disease propagation simultaneously while preserving the variety of outcomes has been to abandon the analytical approach and rely on computer simulations. We offer an analytical framework, that incorporates both the complexity of contact network structure and the time progression of disease spread. Furthermore, we demonstrate that this framework is equally effective on finite- and "infinite"-size networks. This formalism can be equally applied to similar percolation phenomena on networks in other areas of science and technology.

A comparative analysis of influenza vaccination programs.

BACKGROUND: The threat of avian influenza and the 2004-2005 influenza vaccine supply shortage in the United States have sparked a debate about optimal vaccination strategies to reduce the burden of morbidity and mortality caused by the influenza virus. METHODS AND FINDINGS: We present a comparative analysis of two classes of suggested vaccination strategies: mortality-based strategies that target high-risk populations and morbidity-based strategies that target high-prevalence populations. Applying the methods of contact network epidemiology to a model of disease transmission in a large urban population, we assume that vaccine supplies are limited and then 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. CONCLUSIONS: 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.

Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example.

Emerging and re-emerging infections such as SARS (2003) and pandemic H1N1 (2009) have caused concern for public health researchers and policy makers due to the increased burden of these diseases on health care systems. This concern has prompted the use of mathematical models to evaluate strategies to control disease spread, making these models invaluable tools to identify optimal intervention strategies. A particularly important quantity in infectious disease epidemiology is the basic reproduction number, R0. Estimation of this quantity is crucial for effective control responses in the early phase of an epidemic. In our previous study, an approach for estimating the basic reproduction number in real time was developed. This approach uses case notification data and the structure of potential transmission contacts to accurately estimate R0 from the limited amount of information available at the early stage of an outbreak. Based on this approach, we extend the existing methodology; the most recent method features intra- and inter-age groups contact heterogeneity. Given the number of newly reported cases at the early stage of the outbreak, with parsimony assumptions on removal distribution and infectivity profile of the diseases, experiments to estimate real time R0 under different levels of intra- and inter-group contact heterogeneity using two age groups are presented. We show that the new method converges more quickly to the actual value of R0 than the previous one, in particular when there is high-level intra-group and inter-group contact heterogeneity. With the age specific contact patterns, number of newly reported cases, removal distribution, and information about the natural history of the 2009 pandemic influenza in Hong Kong, we also use the extended model to estimate R0 and age-specific R0.

Epidemic progression on networks based on disease generation time.

We investigate the time evolution of disease spread on a network and present an analytical framework using the concept of disease generation time. Assuming a susceptible-infected-recovered epidemic process, this network-based framework enables us to calculate in detail the number of links (edges) within the network that are capable of producing new infectious nodes (individuals), the number of links that are not transmitting the infection further (non-transmitting links), as well as the number of contacts that individuals have with their neighbours (also known as degree distribution) within each epidemiological class, for each generation period. Using several examples, we demonstrate very good agreement between our analytical calculations and the results of computer simulations.

H3N2v and other influenza epidemic risk based on age-specific estimates of sero-protection and contact network interactions.

Cases of a novel swine-origin influenza A(H3N2) variant (H3N2v) have recently been identified in the US, primarily among children. We estimated potential epidemic attack rates (ARs) based on age-specific estimates of sero-susceptibility and social interactions. A contact network model previously established for the Greater Vancouver Area (GVA), Canada was used to estimate average epidemic (infection) ARs for the emerging H3N2v and comparator viruses (H1N1pdm09 and an extinguished H3N2 seasonal strain) based on typical influenza characteristics, basic reproduction number (R(0)), and effective contacts taking into account age-specific sero-protection rates (SPRs). SPRs were assessed in sera collected from the GVA in 2009 or earlier (pre-H1N1pdm09) and fall 2010 (post-H1N1pdm09, seasonal A/Brisbane/10/2007(H3N2), and H3N2v) by hemagglutination inhibition (HI) assay. SPR was assigned per convention based on proportion with HI antibody titre ≥40 (SPR40). Recognizing that the HI titre ≥40 was established as the 50%sero-protective threshold we also explored for ½SPR40, SPR80 and a blended gradient defined as: »SPR20, ½SPR40, ¾SPR80, SPR160. Base case analysis assumed R(0) = 1.40, but we also explored R(0) as high as 1.80. With R(0) = 1.40 and SPR40, simulated ARs were well aligned with field observations for H1N1pdm09 incidence (AR: 32%), sporadic detections without a third epidemic wave post-H1N1pdm09 (negligible AR<0.1%) as well as A/Brisbane/10/2007(H3N2) seasonal strain extinction and antigenic drift replacement (negligible AR<0.1%). Simulated AR for the novel swine-origin H3N2v was 6%, highest in children 6-11years (16%). However, with modification to SPR thresholds per above, H3N2v AR ≥20% became possible. At SPR40, H3N2v AR ≥10%, ≥15% or ≥30%, occur if R(0)≥1.48, ≥1.56 or ≥1.86, respectively. Based on conventional assumptions, the novel swine-origin H3N2v does not currently pose a substantial pandemic threat. If H3N2v epidemics do occur, overall community ARs are unlikely to exceed typical seasonal influenza experience. However risk assessment may change with time and depends crucially upon the validation of epidemiological features of influenza, notably the serologic correlate of protection and R(0).

Optimizing tactics for use of the U.S. antiviral strategic national stockpile for pandemic influenza.

In 2009, public health agencies across the globe worked to mitigate the impact of the swine-origin influenza A (pH1N1) virus. These efforts included intensified surveillance, social distancing, hygiene measures, and the targeted use of antiviral medications to prevent infection (prophylaxis). In addition, aggressive antiviral treatment was recommended for certain patient subgroups to reduce the severity and duration of symptoms. To assist States and other localities meet these needs, the U.S. Government distributed a quarter of the antiviral medications in the Strategic National Stockpile within weeks of the pandemic's start. However, there are no quantitative models guiding the geo-temporal distribution of the remainder of the Stockpile in relation to pandemic spread or severity. We present a tactical optimization model for distributing this stockpile for treatment of infected cases during the early stages of a pandemic like 2009 pH1N1, prior to the wide availability of a strain-specific vaccine. Our optimization method efficiently searches large sets of intervention strategies applied to a stochastic network model of pandemic influenza transmission within and among U.S. cities. The resulting optimized strategies depend on the transmissability of the virus and postulated rates of antiviral uptake and wastage (through misallocation or loss). Our results suggest that an aggressive community-based antiviral treatment strategy involving early, widespread, pro-rata distribution of antivirals to States can contribute to slowing the transmission of mildly transmissible strains, like pH1N1. For more highly transmissible strains, outcomes of antiviral use are more heavily impacted by choice of distribution intervals, quantities per shipment, and timing of shipments in relation to pandemic spread. This study supports previous modeling results suggesting that appropriate antiviral treatment may be an effective mitigation strategy during the early stages of future influenza pandemics, increasing the need for systematic efforts to optimize distribution strategies and provide tactical guidance for public health policy-makers.

The dynamic nature of contact networks in infectious disease epidemiology.

Although contact network models have yielded important insights into infectious disease transmission and control throughout the last decade, researchers have just begun to explore the dynamic nature of contact patterns and their epidemiological significance. Most network models have assumed that contacts are static through time. Developing more realistic models of the social interactions that underlie the spread of infectious diseases thus remains an important challenge for both data gatherers and modelers. In this article, we review some recent data-driven and process-driven approaches that capture the dynamics of human contact, and discuss future challenges for the field.

The shifting demographic landscape of pandemic influenza.

BACKGROUND: As Pandemic (H1N1) 2009 influenza spreads around the globe, it strikes school-age children more often than adults. Although there is some evidence of pre-existing immunity among older adults, this alone may not explain the significant gap in age-specific infection rates. METHODS AND FINDINGS: Based on a retrospective analysis of pandemic strains of influenza from the last century, we show that school-age children typically experience the highest attack rates in primarily naive populations, with the burden shifting to adults during the subsequent season. Using a parsimonious network-based mathematical model which incorporates the changing distribution of contacts in the susceptible population, we demonstrate that new pandemic strains of influenza are expected to shift the epidemiological landscape in exactly this way. CONCLUSIONS: Our analysis provides a simple demographic explanation for the age bias observed for H1N1/09 attack rates, and suggests that this bias may shift in coming months. These results have significant implications for the allocation of public health resources for H1N1/09 and future influenza pandemics.

Optimizing tactics for use of the U.S. Antiviral Strategic National Stockpile for Pandemic (H1N1) Influenza, 2009.

Public health agencies across the globe are working to mitigate the impact of the 2009 pandemic caused by swine-origin influenza A (H1N1) virus. Prior to the large-scale distribution of an effective vaccine, the primary modes of control have included careful surveillance, social distancing and hygiene measures, strategic school closures, other community measures, and the prudent use of antiviral medications to prevent infection (prophylaxis) or reduce the severity and duration of symptoms (treatment). Here, we use mathematical models to determine the optimal geo-temporal tactics for distributing the U.S. strategic national stockpile of antivirals for treatment of infected cases during the early stages of a pandemic, prior to the wide availability of vaccines.We present a versatile optimization method for efficiently searching large sets of public health intervention strategies, and apply it to evaluating tactics for distributing antiviral medications from the U.S. Strategic National Stockpile (SNS). We implemented the algorithm on a network model of H1N1 transmission within and among U.S. cities to project the epidemiological impacts of antiviral stockpile distribution schedules and priorities. The resulting optimized strategies critically depend on the rates of antiviral uptake and wastage (through misallocation or loss). And while a surprisingly simple pro rata distribution schedule is competitive with the optimized strategies across a wide range of uptake and wastage, other equally simple policies perform poorly.Even as vaccination campaigns get underway worldwide, antiviral medications continue to play a critical in reducing H1N1-associated morbidity and mortality. If efforts are made to increase the fraction of cases treated promptly with antivirals above current levels, our model suggests that optimal use of the antiviral component of the Strategic National Stockpile may appreciably slow the transmission of H1N1 during fall 2009, thereby improving the impact of targeted vaccination. A more aggressive optimized antiviral strategy of this type may prove critical to mitigating future flu pandemics, but may increase the risk of antiviral resistance.

The shifting demographic landscape of influenza.

BACKGROUND: As Pandemic (H1N1) 2009 influenza spreads around the globe, it strikes school-age children more often than adults. Although there is some evidence of pre-existing immunity among older adults, this alone may not explain the significant gap in age-specific infection rates. METHODS & FINDINGS: Based on a retrospective analysis of pandemic strains of influenza from the last century, we show that school-age children typically experience the highest attack rates in primarily naive populations, with the burden shifting to adults during the subsequent season. Using a parsimonious network-based mathematical model which incorporates the changing distribution of contacts in the susceptible population, we demonstrate that new pandemic strains of influenza are expected to shift the epidemiological landscape in exactly this way. CONCLUSIONS: Our results provide a simple demographic explanation for the age bias observed for H1N1/09 attack rates, and a prediction that this bias will shift in coming months. These results also have significant implications for the allocation of public health resources including vaccine distribution policies.

Initial human transmission dynamics of the pandemic (H1N1) 2009 virus in North America.

BACKGROUND: Between 5 and 25 April 2009, pandemic (H1N1) 2009 caused a substantial, severe outbreak in Mexico, and subsequently developed into the first global pandemic in 41 years. We determined the reproduction number of pandemic (H1N1) 2009 by analyzing the dynamics of the complete case series in Mexico City during this early period. METHODS: We analyzed three mutually exclusive datasets from Mexico City Distrito Federal which constituted all suspect cases from 15 March to 25 April: confirmed pandemic (H1N1) 2009 infections, non-pandemic influenza A infections and patients who tested negative for influenza. We estimated the initial reproduction number from 497 suspect cases identified prior to 20 April, using a novel contact network methodology incorporating dates of symptom onset and hospitalization, variation in contact rates, extrinsic sociological factors, and uncertainties in underreporting and disease progression. We tested the robustness of this estimate using both the subset of laboratory-confirmed pandemic (H1N1) 2009 infections and an extended case series through 25 April, adjusted for suspected ascertainment bias. RESULTS: The initial reproduction number (95% confidence interval range) for this novel virus is 1.51 (1.32-1.71) based on suspected cases and 1.43 (1.29-1.57) based on confirmed cases before 20 April. The longer time series (through 25 April) yielded a higher estimate of 2.04 (1.84-2.25), which reduced to 1.44 (1.38-1.51) after correction for ascertainment bias. CONCLUSIONS: The estimated transmission characteristics of pandemic (H1N1) 2009 suggest that pharmaceutical and non-pharmaceutical mitigation measures may appreciably limit its spread prior the development of an effective vaccine.