Disease Introduction Is Associated With a Phase Transition in Bighorn Sheep Demographics

Ecological theory suggests that pathogens are capable of regulating or limiting host population dynamics, and this relationship has been empirically established in several settings. However, although studies of childhood diseases were integral to the development of disease ecology, few studies show population limitation by a disease affecting juveniles. Here, we present empirical evidence that disease in lambs constrains population growth in bighorn sheep (Ovis canadensis) based on 45 years of population‐level and 18 years of individual‐level monitoring across 12 populations. While populations generally increased (λ = 1.11) prior to disease introduction, most of these same populations experienced an abrupt change in trajectory at the time of disease invasion, usually followed by stagnant‐to‐declining growth rates (λ = 0.98) over the next 20 years. Disease‐induced juvenile mortality imposed strong constraints on population growth that were not observed prior to disease introduction, even as adult survival returned to pre‐invasion levels. Simulations suggested that models including persistent disease‐induced mortality in juveniles qualitatively matched observed population trajectories, whereas models that only incorporated all‐age disease events did not. We use these results to argue that pathogen persistence may pose a lasting, but under‐recognized, threat to host populations, particularly in cases where clinical disease manifests primarily in juveniles

Contact Networks and Mortality Patterns Suggest Pneumonia-Causing Pathogens may Persist in Wild Bighorn Sheep

Efficacy of disease control efforts is often contingent on whether the disease persists locally in the host population or is repeatedly introduced from an alternative host species. Local persistence is partially determined by the interaction between host contact structure and disease transmission rates: relatively isolated host groups facilitate pathogen persistence by slowing the rate at which highly transmissible pathogens access new susceptibles; alternatively, isolated host groups impede persistence for pathogens with low transmission rates by limiting the number of available hosts and forcing premature fade-out. Here, we use long-term data from the Hells Canyon region to investigate whether variable host contact patterns are associated with survival outcomes for 46 cohorts of bighorn sheep (Ovis canadensis) lambs subject to recurrent pneumonia outbreaks. We build social contact networks for each lamb cohort, and quantify variation in lamb mortality attributable to populations, years, and groups. We then refine estimates of chronic carriage rates in ewes, and disease-induced mortality rates in lambs, by finding parameters for the disease process that produce lamb morality rates similar to those observed when simulated on the observed host contact networks. Our results suggest that summer lamb hazards are spatially structured at the subpopulation level: 92.5 percent of the variation in lamb hazards during pneumonia outbreak years was attributable to sub-population-level groups, whereas 1.7 percent and 5.6 percent were attributable to year and population, respectively.  Additionally, the posterior distribution generated by our disease transmission model suggests that pneumonia-causing pathogens may persist locally in bighorn sheep populations, even during apparently healthy years

Epidemic growth rates and host movement patterns shape management performance for pathogen spillover at the wildlife–livestock interface

Managing pathogen spillover at the wildlife–livestock interface is a key step towards improving global animal health, food security and wildlife conservation. However, predicting the effectiveness of management actions across host–pathogen systems with different life histories is an on-going challenge since data on intervention effectiveness are expensive to collect and results are system-specific.We developed a simulation model to explore how the efficacies of different management strategies vary according to host movement patterns and epidemic growth rates. The model suggested that fast-growing, fast-moving epidemics like avian influenza were best-managed with actions like biosecurity or containment, which limited and localized overall spillover risk. For fast-growing, slower-moving diseases like foot-and-mouth disease, depopulation or prophylactic vaccination were competitive management options. Many actions performed competitively when epidemics grew slowly and host movements were limited, and how management efficacy related to epidemic growth rate or host movement propensity depended on what objectivewas used to evaluatemanagement performance. This framework offers one means of classifying and prioritizing responses to novel pathogen spillover threats, and evaluating current management actions for pathogens emerging at the wildlife–livestock interface. This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’

Pneumonia in Bighorn Sheep: Testing the Super-Spreader Hypothesis

Following introduction of pneumonia, disease can persist in bighorn sheep (Ovis canadensis) populations for decades as annual or sporadic pneumonia epidemics in lambs.  Recurring years of depressed recruitment due to high rates of pneumonia-induced mortality in juveniles is a major obstacle to population recovery.  Management strategies for resolving this problem have so far been elusive. We are investigating the feasibility of removing individual “super-spreaders” to improve lamb survival.  Individual variation in infection and transmission is well documented in human diseases (e.g. “Typhoid Mary”).  We are testing the hypothesis that pneumonia epidemics in lambs are initiated by transmission of pathogens from a few “chronic-shedder” ewes. We have completed the first year of a 5-year project in the Hells Canyon region of Idaho, Oregon, and Washington, and in a captive population at South Dakota State University. Through repeated testing of free-ranging individuals in Hells Canyon, we have identified individual differences in shedding of Mycoplasma ovipneumoniae, a primary pathogen in the bighorn sheep respiratory disease complex.  We also found that when penned separately in captivity, lambs of ewes that consistently tested positive (chronic shedders) were infected and died of pneumonia, whereas lambs born to ewes from an infected population that tested negative (non-shedders), were not infected and survived.  Over the next 4 years we plan to 1) continue and expand testing of free-ranging and captive animals, 2) determine whether removal of chronic-shedder ewes improves lamb survival in free-ranging populations, 3) expand and replicate chronic-shedder commingling experiments in captivity, and 4) establish and monitor a new population founded with non-shedders from an infected population

Prediction and analysis of protein structure

This thesis, which contains an introduction and four manuscripts, summarises my efforts during my the past four years to understand proteins, their structure and dynamics. The first manuscript presents a protocol that refines models as part of a protein structure prediction pipeline. To achieve this, we used spatial information from determined structures and sequence information from multiple alignments. The protocol was used to improve the quality of rough models containing only one point per residue. In the second manuscript we investigated protein fold space. We compared models with known fold to determined structures and found that out models contained many folds that were not seen in the present pool of structures in the PDB. Comparison of structural features revealed no reason why the model folds could not exist. We investigated how well geometric comparison methods distinguished fold in the third manuscript. We presented a novel measure of topological similarity and showed that geometric methods have trouble distinguishing fold differences between both models and PDB structures. In the last manuscript we showed that the architecture is the most important factor for dynamics as measured by normal modes. Protein fold has some effect and cannot be discarded completely, but larger differences in fold does not necessarily correspond to larger differences in flexibility if the architecture is the same

Evidence for Strain-Specific Immunity to Pneumonia in Bighorn Sheep

Transmission of pathogens commonly carried by domestic sheep and goats poses a serious threat to bighorn sheep (Ovis canadensis) populations. All‐age pneumonia die‐offs usually ensue, followed by asymptomatic carriage of Mycoplasma ovipneumoniae by some of the survivors. Lambs born into these chronically infected populations often succumb to pneumonia, but adults are usually healthy. Surprisingly, we found that introduction of a new genotype (strain) of M. ovipneumoniae into a chronically infected bighorn sheep population in the Hells Canyon region of Washington and Oregon was accompanied by adult morbidity (100%) and pneumonia‐induced mortality (33%) similar to that reported in epizootics following exposure of naïve bighorn sheep. This suggests an immune mismatch occurred that led to ineffective cross‐strain protection. To understand the broader context surrounding this event, we conducted a retrospective analysis of M. ovipneumoniae strains detected in 14 interconnected populations in Hells Canyon over nearly 3 decades. We used multi‐locus sequence typing of DNA extracts from 123 upper respiratory tract and fresh, frozen, and formalin‐fixed lung samples to identify 5 distinct strains of M. ovipneumoniae associated with all‐age disease outbreaks between 1986 and 2014, a pattern consistent with repeated transmission events (spillover) from reservoir hosts. Phylogenetic analysis showed that the strain associated with the outbreak observed in this study was likely of domestic goat origin, whereas strains from other recent disease outbreaks probably originated in domestic sheep. Some strains persisted and spread across populations, whereas others faded out or were replaced. Lack of cross‐strain immunity in the face of recurrent spillovers from reservoir hosts may account for a significant proportion of the disease outbreaks in bighorn sheep that continue to happen regularly despite a century of exposure to domestic sheep and goats. Strain‐specific immunity could also complicate efforts to develop vaccines. The results of our study support existing management direction to prevent contacts that could lead to pathogen transmission from domestic small ruminants to wild sheep, even if the wild sheep have previously been exposed. Our data also show that under current management, spillover is continuing to occur, suggesting that enhanced efforts are indicated to avoid introducing new strains of M. ovipneumoniae into wild sheep populations. We recommend looking for new management approaches, such as clearing M. ovipneumoniae infection from domestic animal reservoirs in bighorn sheep range, and placing greater emphasis on existing strategies to elicit more active cooperation by the public and to increase vigilance on the part of resource managers. © 2016 The Wildlife Society

Genetic Structure of Mycoplasma Ovipneumoniae Informs Pathogen Spillover Dynamics Between Domestic and Wild Caprinae in the Western United States

Spillover diseases have significant consequences for human and animal health, as well as wildlife conservation. We examined spillover and transmission of the pneumonia-associated bacterium Mycoplasma ovipneumoniae in domestic sheep, domestic goats, bighorn sheep, and mountain goats across the western United States using 594 isolates, collected from 1984 to 2017. Our results indicate high genetic diversity of M. ovipneumoniae strains within domestic sheep, whereas only one or a few strains tend to circulate in most populations of bighorn sheep or mountain goats. These data suggest domestic sheep are a reservoir, while the few spillovers to bighorn sheep and mountain goats can persist for extended periods. Domestic goat strains form a distinct clade from those in domestic sheep, and strains from both clades are found in bighorn sheep. The genetic structure of domestic sheep strains could not be explained by geography, whereas some strains are spatially clustered and shared among proximate bighorn sheep populations, supporting pathogen establishment and spread following spillover. These data suggest that the ability to predict M. ovipneumoniae spillover into wildlife populations may remain a challenge given the high strain diversity in domestic sheep and need for more comprehensive pathogen surveillance

Epidemic growth rates and host movement patterns shape management performance for pathogen spillover at the wildlife–livestock interface

Managing pathogen spillover at the wildlife–livestock interface is a key step towards improving global animal health, food security and wildlife conservation. However, predicting the effectiveness of management actions across host–pathogen systems with different life histories is an on-going challenge since data on intervention effectiveness are expensive to collect and results are system-specific.We developed a simulation model to explore how the efficacies of different management strategies vary according to host movement patterns and epidemic growth rates. The model suggested that fast-growing, fast-moving epidemics like avian influenza were best-managed with actions like biosecurity or containment, which limited and localized overall spillover risk. For fast-growing, slower-moving diseases like foot-and-mouth disease, depopulation or prophylactic vaccination were competitive management options. Many actions performed competitively when epidemics grew slowly and host movements were limited, and how management efficacy related to epidemic growth rate or host movement propensity depended on what objectivewas used to evaluatemanagement performance. This framework offers one means of classifying and prioritizing responses to novel pathogen spillover threats, and evaluating current management actions for pathogens emerging at the wildlife–livestock interface. This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’

Spatio-Temporal Dynamics of Pneumonia in Bighorn Sheep

1. Bighorn sheep mortality related to pneumonia is a primary factor limiting population recovery across western North America, but management has been constrained by an incomplete understanding of the disease. We analysed patterns of pneumonia-caused mortality over 14 years in 16 interconnected bighorn sheep populations to gain insights into underlying disease processes. 2. We observed four age-structured classes of annual pneumonia mortality patterns: all-age, lamb-only, secondary all-age and adult-only. Although there was considerable variability within classes, overall they differed in persistence within and impact on populations. Years with pneumonia-induced mortality occurring simultaneously across age classes (i.e. all-age) appeared to be a consequence of pathogen invasion into a na€ıve population and resulted in immediate population declines. Subsequently, low recruitment due to frequent high mortality outbreaks in lambs, probably due to association with chronically infected ewes, posed a significant obstacle to population recovery. Secondary all-age events occurred in previously exposed populations when outbreaks in lambs were followed by lower rates of pneumoniainduced mortality in adults. Infrequent pneumonia events restricted to adults were usually of short duration with low mortality. 3. Acute pneumonia-induced mortality in adults was concentrated in fall and early winter around the breeding season when rams are more mobile and the sexes commingle. In contrast, mortality restricted to lambs peaked in summer when ewes and lambs were concentrated in nursery groups. 4. We detected weak synchrony in adult pneumonia between adjacent populations, but found no evidence for landscape-scale extrinsic variables as drivers of disease. 5. We demonstrate that there was a \u3e60% probability of a disease event each year following pneumonia invasion into bighorn sheep populations. Healthy years also occurred periodically, and understanding the factors driving these apparent fade-out events may be the key to managing this disease. Our data and modelling indicate that pneumonia can have greater impacts on bighorn sheep populations than previously reported, and we present hypotheses about processes involved for testing in future investigations and management