Kezia Manlove

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 naïve 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 pneumonia-induced 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 >60% 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.

Female elk contacts are neither frequency nor density dependent

Identifying drivers of contact rates among individuals is critical to understanding disease dynamics and implementing targeted control measures. We studied the interaction patterns of 149 female elk (Cervus canadensis) distributed across five different regions of western Wyoming over three years, defining a contact as an approach within one body length (-2 min). Using hierarchical models that account for correlations within individuals, pairs, and groups, we found that pairwise contact rates within a group declined by a factor of three as group sizes increased 33-fold. Per capita contact rates, however, increased with group size according to a power function, such that female elk contact rates fell in between the predictions of density- or frequency-dependent disease models. We found similar patterns for the duration of contacts. Our results suggest that larger elk groups are likely to play a disproportionate role in the disease dynamics of directly transmitted infections in elk. Supplemental feeding of elk had a limited impact on pairwise interaction rates and durations, but per capita rates were more than two times higher on feeding grounds. Our statistical approach decomposes the variation in contact rate into individual, dyadic, and environmental effects, and provides insight into factors that may be targeted by disease control programs. In particular, female elk contact patterns were driven more by environmental factors such as group size than by either individual or dyad effects.

“One Health” or Three? Publication Silos Among the One Health Disciplines

The One Health initiative is a global effort fostering interdisciplinary collaborations to address challenges in human, animal, and environmental health. While One Health has received considerable press, its benefits remain unclear because its effects have not been quantitatively described. We systematically surveyed the published literature and used social network analysis to measure interdisciplinarity in One Health studies constructing dynamic pathogen transmission models. The number of publications fulfilling our search criteria increased by 14.6% per year, which is faster than growth rates for life sciences as a whole and for most biology subdisciplines. Surveyed publications clustered into three communities: one used by ecologists, one used by veterinarians, and a third diverse-authorship community used by population biologists, mathematicians, epidemiologists, and experts in human health. Overlap between these communities increased through time in terms of author number, diversity of co-author affiliations, and diversity of citations. However, communities continue to differ in the systems studied, questions asked, and methods employed. While the infectious disease research community has made significant progress toward integrating its participating disciplines, some segregation—especially along the veterinary/ecological research interface—remains.

Costs and benefits of group living with disease: a case study of pneumonia in bighorn lambs (Ovis canadensis)

Group living facilitates pathogen transmission among social hosts, yet temporally stable host social organizations can actually limit transmission of some pathogens. When there are few between-subpopulation contacts for the duration of a disease event, transmission becomes localized to subpopulations. The number of per capita infectious contacts approaches the subpopulation size as pathogen infectiousness increases. Here, we illustrate that this is the case during epidemics of highly infectious pneumonia in bighorn lambs (Ovis canadensis). We classified individually marked bighorn ewes into disjoint seasonal subpopulations, and decomposed the variance in lamb survival to weaning into components associated with individual ewes, subpopulations, populations and years. During epidemics, lamb survival varied substantially more between ewe-subpopulations than across populations or years, suggesting localized pathogen transmission. This pattern of lamb survival was not observed during years when disease was absent. Additionally, group sizes in ewe-subpopulations were independent of population size, but the number of ewe-subpopulations increased with population size. Consequently, although one might reasonably assume that force of infection for this highly communicable disease scales with population size, in fact, host social behaviour modulates transmission such that disease is frequency-dependent within populations, and some groups remain protected during epidemic events.

Use of exposure history to identify patterns of immunity to pneumonia in bighorn sheep (Ovis canadensis).

Individual host immune responses to infectious agents drive epidemic behavior and are therefore central to understanding and controlling infectious diseases. However, important features of individual immune responses, such as the strength and longevity of immunity, can be challenging to characterize, particularly if they cannot be replicated or controlled in captive environments. Our research on bighorn sheep pneumonia elucidates how individual bighorn sheep respond to infection with pneumonia pathogens by examining the relationship between exposure history and survival in situ. Pneumonia is a poorly understood disease that has impeded the recovery of bighorn sheep (Ovis canadensis) following their widespread extirpation in the 1900s. We analyzed the effects of pneumonia-exposure history on survival of 388 radio-collared adults and 753 ewe-lamb pairs. Results from Cox proportional hazards models suggested that surviving ewes develop protective immunity after exposure, but previous exposure in ewes does not protect their lambs during pneumonia outbreaks. Paradoxically, multiple exposures of ewes to pneumonia were associated with diminished survival of their offspring during pneumonia outbreaks. Although there was support for waning and boosting immunity in ewes, models with consistent immunizing exposure were similarly supported. Translocated animals that had not previously been exposed were more likely to die of pneumonia than residents. These results suggest that pneumonia in bighorn sheep can lead to aging populations of immune adults with limited recruitment. Recovery is unlikely to be enhanced by translocating naïve healthy animals into or near populations infected with pneumonia pathogens.

Age-specific infectious period shapes dynamics of pneumonia in bighorn sheep

Superspreading, the phenomenon where a small proportion of individuals contribute disproportionately to new infections, has profound effects on disease dynamics. Superspreading can arise through variation in contacts, infectiousness or infectious periods. The latter has received little attention, yet it drives the dynamics of many diseases of critical public health, livestock health and conservation concern. Here, we present rare evidence of variation in infectious periods underlying a superspreading phenomenon in a free-ranging wildlife system. We detected persistent infections of Mycoplasma ovipneumoniae, the primary causative agent of pneumonia in bighorn sheep (Ovis canadensis), in a small number of older individuals that were homozygous at an immunologically relevant genetic locus. Interactions among age-structure, genetic composition and infectious periods may drive feedbacks in disease dynamics that determine the magnitude of population response to infection. Accordingly, variation in initial conditions may explain divergent population responses to infection that range from recovery to catastrophic decline and extirpation.

Contact and contagion: Probability of transmission given contact varies with demographic state in bighorn sheep

Understanding both contact and probability of transmission given contact are key to managing wildlife disease. However, wildlife disease research tends to focus on contact heterogeneity, in part because the probability of transmission given contact is notoriously difficult to measure. Here, we present a first step towards empirically investigating the probability of transmission given contact in free-ranging wildlife. We used measured contact networks to test whether bighorn sheep demographic states vary systematically in infectiousness or susceptibility to Mycoplasma ovipneumoniae, an agent responsible for bighorn sheep pneumonia. We built covariates using contact network metrics, demographic information and infection status, and used logistic regression to relate those covariates to lamb survival. The covariate set contained degree, a classic network metric describing node centrality, but also included covariates breaking the network metrics into subsets that differentiated between contacts with yearlings, ewes with lambs, and ewes without lambs, and animals with and without active infections. Yearlings, ewes with lambs, and ewes without lambs showed similar group membership patterns, but direct interactions involving touch occurred at a rate two orders of magnitude higher between lambs and reproductive ewes than between any classes of adults or yearlings, and one order of magnitude higher than direct interactions between multiple lambs. Although yearlings and non-reproductive bighorn ewes regularly carried M. ovipneumoniae, our models suggest that a contact with an infected reproductive ewe had approximately five times the odds of producing a lamb mortality event of an identical contact with an infected dry ewe or yearling. Consequently, management actions targeting infected animals might lead to unnecessary removal of young animals that carry pathogens but rarely transmit. This analysis demonstrates a simple logistic regression approach for testing a priori hypotheses about variation in the odds of transmission given contact for free-ranging hosts, and may be broadly applicable for investigations in wildlife disease ecology.

Heterologous Vaccination and Checkpoint Blockade Synergize To Induce Antileukemia Immunity

Checkpoint blockade-based immunotherapies are effective in cancers with high numbers of nonsynonymous mutations. In contrast, current paradigms suggest that such approaches will be ineffective in cancers with few nonsynonymous mutations. To examine this issue, we made use of a murine model of BCR-ABL+ B-lineage acute lymphoblastic leukemia. Using a principal component analysis, we found that robust MHC class II expression, coupled with appropriate costimulation, correlated with lower leukemic burden. We next assessed whether checkpoint blockade or therapeutic vaccination could improve survival in mice with pre-established leukemia. Consistent with the low mutation load in our leukemia model, we found that checkpoint blockade alone had only modest effects on survival. In contrast, robust heterologous vaccination with a peptide derived from the BCR-ABL fusion (BAp), a key driver mutation, generated a small population of mice that survived long-term. Checkpoint blockade strongly synergized with heterologous vaccination to enhance overall survival in mice with leukemia. Enhanced survival did not correlate with numbers of BAp:I-Ab–specific T cells, but rather with increased expression of IL-10, IL-17, and granzyme B and decreased expression of programmed death 1 on these cells. Our findings demonstrate that vaccination to key driver mutations cooperates with checkpoint blockade and allows for immune control of cancers with low nonsynonymous mutation loads.

Within the fortress: A specialized parasite of ants is not evicted

Every level of biological organization from cells to societies require that composing units come together to form parts of a bigger unit (1). Our knowledge of how behavioral manipulating parasites change social interactions between social hosts is limited. Here we use an endoparasite to observe changes in social interactions between infected and healthy ants, using trophallaxis (liquid food exchange) and spatial data as proxies for food sharing and social segregation. We found no change in trophallaxis (p-value = 0.5156). By using K-function and nearest neighbor analyses we did see a significant difference in spatial segregation on day 3 (less than 8 millimeters; p-value < 0.05). These results suggest healthy individuals are unable to detect the parasite within the host.

The ecology of movement and behaviour: a saturated tripartite network for describing animal contacts

Ecologists regularly use animal contact networks to describe interactions underlying pathogen transmission, gene flow, and information transfer. However, empirical descriptions of contact often overlook some features of individual movement, and decisions about what kind of network to use in a particular setting are commonly ad hoc. Here, we relate individual movement trajectories to contact networks through a tripartite network model of individual, space, and time nodes. Most networks used in animal contact studies (e.g. individual association networks, home range overlap networks, and spatial networks) are simplifications of this tripartite model. The tripartite structure can incorporate a broad suite of alternative ecological metrics like home range sizes and patch occupancy patterns into inferences about contact network metrics such as modularity and degree distribution. We demonstrate the models utility with two simulation studies using alternative forms of ecological data to constrain the tripartite networks structure and inform expectations about the harder-to-measure metrics related to contact.