Andrew W. Park

Ebola cases and health system demand in Liberia.

The authors develop a multi-type branching process model of the 2014 Liberian Ebola outbreak that incorporates the impacts of changes in behavior on potential transmission scenarios, thereby informing the path to containment of the epidemic.

The macroecology of infectious diseases: a new perspective on global-scale drivers of pathogen distributions and impacts

Identifying drivers of infectious disease patterns and impacts at the broadest scales of organisation is one of the most crucial challenges for modern science, yet answers to many fundamental questions remain elusive. These include what factors commonly facilitate transmission of pathogens to novel host species, what drives variation in immune investment among host species, and more generally what drives global patterns of parasite diversity and distribution? Here we consider how the perspectives and tools of macroecology, a field that investigates patterns and processes at broad spatial, temporal and taxonomic scales, are expanding scientific understanding of global infectious disease ecology. In particular, emerging approaches are providing new insights about scaling properties across all living taxa, and new strategies for mapping pathogen biodiversity and infection risk. Ultimately, macroecology is establishing a framework to more accurately predict global patterns of infectious disease distribution and emergence.

Spatial spread of the West Africa Ebola epidemic

Controlling Ebola outbreaks and planning an effective response to future emerging diseases are enhanced by understanding the role of geography in transmission. Here we show how epidemic expansion may be predicted by evaluating the relative probability of alternative epidemic paths. We compared multiple candidate models to characterize the spatial network over which the 2013–2015 West Africa epidemic of Ebola virus spread and estimate the effects of geographical covariates on transmission during peak spread. The best model was a generalized gravity model where the probability of transmission between locations depended on distance, population density and international border closures between Guinea, Liberia and Sierra Leone and neighbouring countries. This model out-performed alternative models based on diffusive spread, the force of infection, mobility estimated from cell phone records and other hypothesized patterns of spread. These findings highlight the importance of integrated geography to epidemic expansion and may contribute to identifying both the most vulnerable unaffected areas and locations of maximum intervention value.

Shifting white pox aetiologies affecting Acropora palmata in the Florida Keys, 1994–2014

We propose ‘the moving target hypothesis’ to describe the aetiology of a contemporary coral disease that differs from that of its historical disease state. Hitting the target with coral disease aetiology is a complex pursuit that requires understanding of host and environment, and may lack a single pathogen solution. White pox disease (WPX) affects the Caribbean coral Acropora palmata. Acroporid serratiosis is a form of WPX for which the bacterial pathogen (Serratia marcescens) has been established. We used long-term (1994–2014) photographic monitoring to evaluate historical and contemporary epizootiology and aetiology of WPX affecting A. palmata at eight reefs in the Florida Keys. Ranges of WPX prevalence over time (0–71.4%) were comparable for the duration of the 20-year study. Whole colony mortality and disease severity were high in historical (1994–2004), and low in contemporary (2008–2014), outbreaks of WPX. Acroporid serratiosis was diagnosed for some historical (1999, 2003) and contemporary (2012, 2013) outbreaks, but this form of WPX was not confirmed for all WPX cases. Our results serve as a context for considering aetiology as a moving target for WPX and other coral diseases for which pathogens are established and/or candidate pathogens are identified. Coral aetiology investigations completed to date suggest that changes in pathogen, host and/or environment alter the disease state and complicate diagnosis.

When More Transmission Equals Less Disease: Reconciling the Disconnect between Disease Hotspots and Parasite Transmission

The assumed straightforward connection between transmission intensity and disease occurrence impacts surveillance and control efforts along with statistical methodology, including parameter inference and niche modeling. Many infectious disease systems have the potential for this connection to be more complicated–although demonstrating this in any given disease system has remained elusive. Hemorrhagic disease (HD) is one of the most important diseases of white-tailed deer and is caused by viruses in the Orbivirus genus. Like many infectious diseases, the probability or severity of disease increases with age (after loss of maternal antibodies) and the probability of disease is lower upon re-infection compared to first infection (based on cross-immunity between virus strains). These broad criteria generate a prediction that disease occurrence is maximized at intermediate levels of transmission intensity. Using published US field data, we first fit a statistical model to predict disease occurrence as a function of seroprevalence (a proxy for transmission intensity), demonstrating that states with intermediate seroprevalence have the highest level of case reporting. We subsequently introduce an independently parameterized mechanistic model supporting the theory that high case reporting should come from areas with intermediate levels of transmission. This is the first rigorous demonstration of this phenomenon and illustrates that variation in transmission rate (e.g. along an ecologically-controlled transmission gradient) can create cryptic refuges for infectious diseases.

Infectious disease in animal metapopulations: the importance of environmental transmission.

Motivated by an array of infectious diseases that threaten wildlife populations, a simple metapopulation model (subpopulations connected by animal movement) is developed, which allows for both movement-based and environmental transmission. The model demonstrates that for a range of plausible parameterizations of environmental transmission, increased movement rate of animals between discrete habitats can lead to a decrease in the overall proportion of sites that are occupied. This can limit the ability of the rescue effect to ensure locally extinct populations become recolonized and can drive metapopulations down in size so that extinction by mechanisms other than disease may become more likely. It further highlights that, in the context of environmental transmission, the environmental persistence time of pathogens and the probability of acquiring infection by environmental transmission can affect host metapopulations both qualitatively and quantitatively. Additional spillover sources of infection from alternate reservoir hosts are also included in the model and a synthesis of all three types of transmission, acting alone or in combination, is performed revealing that movement-based transmission is the only necessary condition for a decline in the proportion of occupied sites with increasing movement rate, but that the presence of other types of transmission can reverse this qualitative result. By including the previously neglected role of environmental transmission, this work contributes to the general discussion of when dispersal by wild animals is beneficial or detrimental to populations experiencing infectious disease.

Waiting time to infectious disease emergence

Emerging diseases must make a transition from stuttering chains of transmission to sustained chains of transmission, but this critical transition need not coincide with the system becoming supercritical. That is, the introduction of infection to a supercritical system results in a significant fraction of the population becoming infected only with a certain probability. Understanding the waiting time to the first major outbreak of an emerging disease is then more complicated than determining when the system becomes supercritical. We treat emergence as a dynamic bifurcation, and use the concept of bifurcation delay to understand the time to emergence after a system becomes supercritical. Specifically, we consider an SIR model with a time-varying transmission term and random infections originating from outside the population. We derive an analytic density function for the delay times and find it to be, in general, in agreement with stochastic simulations. We find the key parameters to be the rate of introduction of infection and the rate of change of the basic reproductive ratio. These findings aid our understanding of real emergence events, and can be incorporated into early-warning systems aimed at forecasting disease risk.

Refugia and the evolutionary epidemiology of drug resistance

Drug resistance is a long-standing economic, veterinary and human health concern in human and animal populations. Efficacy of prophylactic drug treatments targeting a particular pathogen is often short-lived, as drug-resistant pathogens evolve and reach high frequency in a treated population. Methods to combat drug resistance are usually costly, including use of multiple drugs that are applied jointly or sequentially, or development of novel classes of drugs. Alternatively, there is growing interest in exploiting untreated host populations, refugia, for the management of drug resistance. Refugia do not experience selection for resistance, and serve as a reservoir for native, drug-susceptible pathogens. The force of infection from refugia may dilute the frequency of resistant pathogens in the treated population, potentially at an acceptable cost in terms of overall disease burden. We examine this concept using a simple mathematical model that captures the core mechanisms of transmission and selection common to many host–pathogen systems. We identify the roles of selection and gene flow in determining the utility of refugia.

The potential for sexual transmission to compromise control of Ebola virus outbreaks

Recent evidence suggests that sexual contact may give rise to transmission of Ebola virus long after infection has been cleared from blood. We develop a simple mathematical model that incorporates contact transmission and sexual transmission parametrized from data relating to the 2013–2015 West African Ebola epidemic. The model explores scenarios where contact transmission is reduced following infection events, capturing behaviour change, and quantifies how these actions reducing transmission may be compromised by sexual transmission in terms of increasing likelihood, size and duration of outbreaks. We characterize the extent to which sexual transmission operates in terms of the probability of initial infection resolving to sexual infectiousness and the sexual transmission rate, and relate these parameters to the overall case burden. We find that sexual transmission can have large effects on epidemic dynamics (increasing attack ratios from 25% in scenarios without sexual transmission but with contact-transmission-reducing behaviour, up to 80% in equivalent scenarios with sexual transmission).

APPARENT INCREASE OF REPORTED HEMORRHAGIC DISEASE IN THE MIDWESTERN AND NORTHEASTERN USA

Abstract We investigated temporal and spatial trends in reporting of hemorrhagic disease (HD) in the midwestern and northeastern US using a 33-yr (1980–2012) questionnaire-based data set. This data set was supported by an additional 19 yr (1994–2012) of bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) isolation results from clinically affected white-tailed deer (Odocoileus virginianus) in these regions. Both the number of counties that were reported positive for HD and the northern latitudinal range of reported HD increased with time. A similar increase was observed with both the number of states annually reporting HD and the number of counties where HD was reported. Large-scale outbreaks occurred in 1988, 1996, 2007, and 2012, and the scale of these individual outbreaks also increased with time. The predominant virus isolated from these regions was EHDV-2, but the prevalence of EHDV-6, which was first detected in 2006, appears to be increasing. Temporally, the extent of regional HD reporting was correlated with regional drought conditions. The significance of increases in reported HD and the incursions and establishment of new BTV and EHDV in the US currently are unknown.