Caitlin M. Rivers

Modeling the Impact of Interventions on an Epidemic of Ebola in Sierra Leone and Liberia

Background: An Ebola outbreak of unparalleled size is currently affecting several countries in West Africa, and international efforts to control the outbreak are underway. However, the efficacy of these interventions, and their likely impact on an Ebola epidemic of this size, is unknown. Forecasting and simulation of these interventions may inform public health efforts. Methods: We use existing data from Liberia and Sierra Leone to parameterize a mathematical model of Ebola and use this model to forecast the progression of the epidemic, as well as the efficacy of several interventions, including increased contact tracing, improved infection control practices, the use of a hypothetical pharmaceutical intervention to improve survival in hospitalized patients. Findings: Model forecasts until Dec. 31, 2014 show an increasingly severe epidemic with no sign of having reached a peak. Modeling results suggest that increased contact tracing, improved infection control, or a combination of the two can have a substantial impact on the number of Ebola cases, but these interventions are not sufficient to halt the progress of the epidemic. The hypothetical pharmaceutical intervention, while impacting mortality, had a smaller effect on the forecasted trajectory of the epidemic. Interpretation: Near-term, practical interventions to address the ongoing Ebola epidemic may have a beneficial impact on public health, but they will not result in the immediate halting, or even obvious slowing of the epidemic. A long-term commitment of resources and support will be necessary to address the outbreak.

What Factors Might Have Led to the Emergence of Ebola in West Africa

An Ebola outbreak of unprecedented scope emerged in West Africa in December 2013 and presently continues unabated in the countries of Guinea, Sierra Leone, and Liberia. Ebola is not new to Africa, and outbreaks have been confirmed as far back as 1976. The current West African Ebola outbreak is the largest ever recorded and differs dramatically from prior outbreaks in its duration, number of people affected, and geographic extent. The emergence of this deadly disease in West Africa invites many questions, foremost among these: why now, and why in West Africa? Here, we review the sociological, ecological, and environmental drivers that might have influenced the emergence of Ebola in this region of Africa and its spread throughout the region. Containment of the West African Ebola outbreak is the most pressing, immediate need. A comprehensive assessment of the drivers of Ebola emergence and sustained human-to-human transmission is also needed in order to prepare other countries for importation or emergence of this disease. Such assessment includes identification of country-level protocols and interagency policies for outbreak detection and rapid response, increased understanding of cultural and traditional risk factors within and between nations, delivery of culturally embedded public health education, and regional coordination and collaboration, particularly with governments and health ministries throughout Africa. Public health education is also urgently needed in countries outside of Africa in order to ensure that risk is properly understood and public concerns do not escalate unnecessarily. To prevent future outbreaks, coordinated, multiscale, early warning systems should be developed that make full use of these integrated assessments, partner with local communities in high-risk areas, and provide clearly defined response recommendations specific to the needs of each community.

Estimation of MERS-Coronavirus Reproductive Number and Case Fatality Rate for the Spring 2014 Saudi Arabia Outbreak: Insights from Publicly Available Data

Background: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was initially recognized as a source of severe respiratory illness and renal failure in 2012. Prior to 2014, MERS-CoV was mostly associated with sporadic cases of human illness, of presumed zoonotic origin, though chains of person-to-person transmission in the healthcare setting were reported. In spring 2014, large healthcare-associated outbreaks of MERS-CoV infection occurred in Jeddah and Riyadh, Kingdom of Saudi Arabia. To date the epidemiological information published by public health investigators in affected jurisdictions has been relatively limited. However, it is important that the global public health community have access to information on the basic epidemiological features of the outbreak to date, including the basic reproduction number (R0) and best estimates of case-fatality rates (CFR). We sought to address these gaps using a publicly available line listing of MERS-CoV cases. Methods: R0 was estimated using the incidence decay with exponential adjustment (“IDEA”) method, while period-specific case fatality rates that incorporated non-attributed death data were estimated using Monte Carlo simulation. Results: 707 cases were available for evaluation. 52% of cases were identified as primary, with the rest being secondary. IDEA model fits suggested a higher R0 in Jeddah (3.5-6.7) than in Riyadh (2.0-2.8); control parameters suggested more rapid reduction in transmission in the former city than the latter. The model accurately projected final size and end date of the Riyadh outbreak based on information available prior to the outbreak peak; for Jeddah, these projections were possible once the outbreak peaked. Overall case-fatality was 40%; depending on the timing of 171 deaths unlinked to case data, outbreak CFR could be higher, lower, or equivalent to pre-outbreak CFR. Conclusions: Notwithstanding imperfect data, inferences about MERS-CoV epidemiology important for public health preparedness are possible using publicly available data sources. The R0 estimated in Riyadh appears similar to that seen for SARS-CoV, but CFR appears higher, and indirect evidence suggests control activities ended these outbreaks. These data suggest this disease should be regarded with equal or greater concern than the related SARS-CoV.

Opinion: Mathematical models: A key tool for outbreak response

The 2014 outbreak of Ebola in West Africa is unprecedented in its size and geographic range, and demands swift, effective action from the international community. Understanding the dynamics and spread of Ebola is critical for directing interventions and extinguishing the epidemic; however, observational studies of local conditions have been incomplete and limited by the urgent need to direct resources to patient care.

Ebola: models do more than forecast

This corrects the article DOI: 10.1038/514S60a

Accuracy of epidemiological inferences based on publicly available information: retrospective comparative analysis of line lists of human cases infected with influenza A(H7N9) in China

BackgroundAppropriate public health responses to infectious disease threats should be based on best-available evidence, which requires timely reliable data for appropriate analysis. During the early stages of epidemics, analysis of ‘line lists’ with detailed information on laboratory-confirmed cases can provide important insights into the epidemiology of a specific disease. The objective of the present study was to investigate the extent to which reliable epidemiologic inferences could be made from publicly-available epidemiologic data of human infection with influenza A(H7N9) virus.MethodsWe collated and compared six different line lists of laboratory-confirmed human cases of influenza A(H7N9) virus infection in the 2013 outbreak in China, including the official line list constructed by the Chinese Center for Disease Control and Prevention plus five other line lists by HealthMap, Virginia Tech, Bloomberg News, the University of Hong Kong and FluTrackers, based on publicly-available information. We characterized clinical severity and transmissibility of the outbreak, using line lists available at specific dates to estimate epidemiologic parameters, to replicate real-time inferences on the hospitalization fatality risk, and the impact of live poultry market closure.ResultsDemographic information was mostly complete (less than 10% missing for all variables) in different line lists, but there were more missing data on dates of hospitalization, discharge and health status (more than 10% missing for each variable). The estimated onset to hospitalization distributions were similar (median ranged from 4.6 to 5.6 days) for all line lists. Hospital fatality risk was consistently around 20% in the early phase of the epidemic for all line lists and approached the final estimate of 35% afterwards for the official line list only. Most of the line lists estimated >90% reduction in incidence rates after live poultry market closures in Shanghai, Nanjing and Hangzhou.ConclusionsWe demonstrated that analysis of publicly-available data on H7N9 permitted reliable assessment of transmissibility and geographical dispersion, while assessment of clinical severity was less straightforward. Our results highlight the potential value in constructing a minimum dataset with standardized format and definition, and regular updates of patient status. Such an approach could be particularly useful for diseases that spread across multiple countries.

Risks of Death and Severe Disease in Patients With Middle East Respiratory Syndrome Coronavirus, 2012–2015

Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen, first recognized in 2012, with a high case fatality risk, no vaccine, and no treatment beyond supportive care. We estimated the relative risks of death and severe disease among MERS-CoV patients in the Middle East between 2012 and 2015 for several risk factors, using Poisson regression with robust variance and a bootstrap-based expectation maximization algorithm to handle extensive missing data. Increased age and underlying comorbidity were risk factors for both death and severe disease, while cases arising in Saudi Arabia were more likely to be severe. Cases occurring later in the emergence of MERS-CoV and among health-care workers were less serious. This study represents an attempt to estimate risk factors for an emerging infectious disease using open data and to address some of the uncertainty surrounding MERS-CoV epidemiology.

Estimating human cases of avian influenza A(H7N9) from poultry exposure

In March 2013 an outbreak of avian influenza A(H7N9) was first recognized in China. To date there have been 130 cases in human, 47% of which are in men over the age of 55.The influenza strain is a novel subtype not seen before in humans; little is known about zoonotic transmission of the virus, but it is hypothesized that contact with poultry in live bird markets may be a source of exposure. The purpose of this study is to estimate the transmissibility of the virus from poultry to humans by estimating the amount of time shoppers, farmers, and live bird market retailers spend exposed to poultry each day. Results suggest that increased risk among older men is not due to greater exposure time at live bird markets.

Planning and response in the aftermath of a large crisis: an agent-based informatics framework

We present a synthetic information and modeling environment that can allow policy makers to study various counter-factual experiments in the event of a large human-initiated crisis. The specific scenario we consider is a ground detonation caused by an improvised nuclear device in a large urban region. In contrast to earlier work in this area that focuses largely on the prompt effects on human health and injury, we focus on co-evolution of individual and collective behavior and its interaction with the differentially damaged infrastructure. This allows us to study short term secondary and tertiary effects. The present environment is suitable for studying the dynamical outcomes over a two week period after the initial blast. A novel computing and data processing architecture is described; the architecture allows us to represent multiple co-evolving infrastructures and social networks at a highly resolved temporal, spatial, and individual scale. The representation allows us to study the emergent behavior of individuals as well as specific strategies to reduce casualties and injuries that exploit the spatial and temporal nature of the secondary and tertiary effects. A number of important conclusions are obtained using the modeling environment. For example, the studies decisively show that deploying ad hoc communication networks to reach individuals in the affected area is likely to have a significant impact on the overall casualties and injuries.

Make Data Sharing Routine to Prepare for Public Health Emergencies.

Jean-Paul Chretien and colleagues argue that recent Ebola and Zika virus outbreaks highlight the importance of data sharing in scientific research.