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Adaptive management and the value of information: learning via intervention in epidemiology

Optimal intervention for disease outbreaks is often impeded by severe scientific uncertainty. Adaptive management (AM), long-used in natural resource management, is a structured decision-making approach to solving dynamic problems that accounts for the value of resolving uncertainty via real-time evaluation of alternative models. We propose an AM approach to design and evaluate intervention strategies in epidemiology, using real-time surveillance to resolve model uncertainty as management proceeds, with foot-and-mouth disease (FMD) culling and measles vaccination as case studies. We use simulations of alternative intervention strategies under competing models to quantify the effect of model uncertainty on decision making, in terms of the value of information, and quantify the benefit of adaptive versus static intervention strategies. Culling decisions during the 2001 UK FMD outbreak were contentious due to uncertainty about the spatial scale of transmission. The expected benefit of resolving this uncertainty prior to a new outbreak on a UK-like landscape would be £45–£60 million relative to the strategy that minimizes livestock losses averaged over alternate transmission models. AM during the outbreak would be expected to recover up to £20.1 million of this expected benefit. AM would also recommend a more conservative initial approach (culling of infected premises and dangerous contact farms) than would a fixed strategy (which would additionally require culling of contiguous premises). For optimal targeting of measles vaccination, based on an outbreak in Malawi in 2010, AM allows better distribution of resources across the affected region; its utility depends on uncertainty about both the at-risk population and logistical capacity. When daily vaccination rates are highly constrained, the optimal initial strategy is to conduct a small, quick campaign; a reduction in expected burden of approximately 10,000 cases could result if campaign targets can be updated on the basis of the true susceptible population. Formal incorporation of a policy to update future management actions in response to information gained in the course of an outbreak can change the optimal initial response and result in significant cost savings. AM provides a framework for using multiple models to facilitate public-health decision making and an objective basis for updating management actions in response to improved scientific understanding.

PLoS Biology↗

Fish Rhabdoviruses

Many important viral pathogens of fish are members of the family Rhabdoviridae . The viruses in this large group cause significant losses in populations of wild fish as well as among fish reared in aquaculture. Fish rhabdoviruses often have a wide host and geographic range, and infect aquatic animals in both freshwater and seawater. The fish rhabdoviruses comprise a diverse collection of isolates that can be placed in one of two quite different groups: isolates that are members of the established genus Novirhabdovirus , and those that are most similar to members of the genus Vesiculovirus . Because the diseases caused by fish rhabdoviruses are important to aquaculture, diagnostic methods for their detection and identification are well established. In addition to regulations designed to reduce the spread of fish viruses, a significant body of research has addressed methods for the control or prevention of diseases caused by fish rhabdoviruses, including vaccination. The number of reported fish rhabdoviruses continues to grow as a result of the expansion of aquaculture, the increase in global trade, the development of improved diagnostic methods, and heightened surveillance activities. Fish rhabdoviruses serve as useful components of model systems to study vertebrate virus disease, epidemiology, and immunology.

Book chapter↗

Feathers and flu: Identifying data gaps in avian influenza host dynamics to prioritize wildlife conservation

Highly pathogenic avian influenza viruses (HPAIV) have had disastrous, worldwide effects on wild birds and domestic poultry since the emergence of the A/goose/Guangdong/1/1996 (Gs/GD/96) lineage. The currently circulating H5N1 clade 2.3.4.4b has an expanded set of susceptible hosts, including many migratory wild birds, and is associated with higher transmission rates, increased susceptibility among wild bird hosts, and a greater number of wildlife reservoirs. Certain wild bird life-history strategies and behaviors have been suggested to explain avian hosts’ susceptibility and exposure to HPAIV. These biological traits include gregariousness, such as colonial nesting and mixed flock foraging, predation or scavenging on wild birds, and association with aquatic habitats. Variation in host infection responses (e.g., infectability, shedding rates and duration, mortality rate, antibody development) informs the overall infection risk across avian species, yet the specific role of biological traits is often inconsistent and unclear across taxa. Moreover, the interactions and potential compounding effects among these biological traits remain largely unknown. To develop a more holistic understanding of cumulative risk across bird species, we integrate existing information on infection risk factors (i.e., susceptibility, immunological response, and behavioral traits) into a qualitative multivariate analysis. This approach enabled us to examine how infection risk factors relate to biological traits (e.g., phylogeny, physiology, behavior, species range) and to begin disentangling their complex interactions. We quantified and summarized these risk factors across host species and qualitatively ranked species by their viral responses along a proposed HPAIV response continuum, guided by expectations of traits and metrics associated with competence or vulnerability to HPAIV. In doing so, we aimed to better understand how viral responses and biological traits synergistically interact to influence cumulative risk across wild bird species. This work broadly expands on the previous avian influenza literature, which has focused on Anseriformes and Charadriiformes as primary viral reservoirs. We tie our findings to effective disease management responses with links to risk components, including descriptions of potential surveillance strategies applied to research and One Health goals, as well as a fuller understanding of how resources may be better deployed for rapid response when spillovers do inevitably occur. Additionally, we identified numerous areas where vital epidemiological information is lacking to best characterize the spread of these viruses. Ultimately, this improved understanding will help identify and inform disease management needs and decision making.

Wildlife Monographs↗

Retrospective analysis of the epidemiologic literature, 1990–2015, on wildlife-associated diseases from the Republic of Korea

To assess the status of research on wildlife diseases in the Republic of Korea (ROK) and to identify trends, knowledge gaps, and directions for future research, we reviewed epidemiologic publications on wildlife-associated diseases in the ROK. We identified a relatively small but rapidly increasing body of literature. The majority of publications were focused on public or livestock health and relatively few addressed wildlife health. Most studies that focused on human and livestock health were cross-sectional whereas wildlife health studies were mostly case reports. Fifteen diseases notifiable to the World Organisation for Animal Health were identified and 21 diseases were identified as notifiable to either the Korean Ministry of Health, Welfare, and Family Affairs or the Korean Ministry of Agriculture. Two diseases were reported as occurring as epidemics; highly pathogenic avian influenza (HPAI) and virulent Newcastle disease. Six diseases or disease agents were described in the literature as emerging including HPAI, rabies, Babesia microti , avian coronaviruses, scrub typhus, and severe fever thrombocytopenia syndrome virus. The diseases for which there were the largest number of publications were HPAI and rabies. The majority of wildlife-associated zoonotic disease publications focused on food-borne parasitic infections or rodent-associated diseases. Several publications focused on the potential of wildlife as reservoirs of livestock diseases; in particular, water deer ( Hydropotes inermis ) and wild boar ( Sus scrofa ). In contrast, there were few publications on diseases of concern for wildlife populations or research to understand the impacts of these diseases for wildlife management. Increased focus on prospective studies would enhance understanding of disease dynamics in wildlife populations. For the high-consequence diseases that impact multiple sectors, a One Health approach, with coordination among the public health, agricultural, and environmental sectors, would be important. This type of review can provide useful information for countries or regions planning or implementing national wildlife health programs.

Journal of Wildlife Diseases↗

Fatal interactions: Pneumonia in bighorn lambs following experimental exposure to carriers of Mycoplasma ovipneumoniae

We hypothesized that bighorn sheep ewes with chronic nasal Mycoplasma ovipneumoniae carriage are the source of infection that results in fatal lamb pneumonia. We tested this hypothesis in captive bighorn ewes at two study facilities over a 5-year period, by identifying carrier ewes and then comparing lamb fates in groups that did (exposed pens) or did not (non-exposed pens) include one or more carrier ewes. Most (23 of 30) lambs born in exposed pens, but none of 11 lambs born in non-exposed pens, contracted fatal pneumonia. In addition, surviving lambs in exposed pens showed obvious signs of respiratory disease while lambs in non-exposed pens did not. In crossover experiments, individual non-carrier ewes had lambs that experienced fatal pneumonia in years when housed in exposed pens, but not in years when housed in non-exposed pens. The results of these studies clearly associate lamb pneumonia to exposure to M. ovipneumoniae carrier ewes, consistent with a necessary role for this agent in epizootic pneumonia of bighorn sheep. These data specifically highlight the role of chronic M. ovipneumoniae carriage by some bighorn ewes in the epidemiology of this population-limiting wildlife disease.

Idaho, Montana, Nevada, Oregon, South Dakota, Wash↗

Recovering individual-level spatial inference from aggregated binary data

Binary regression models are commonly used in disciplines such as epidemiology and ecology to determine how spatial covariates influence individuals. In many studies, binary data are shared in a spatially aggregated form to protect privacy. For example, rather than reporting the location and result for each individual that was tested for a disease, researchers may report that a disease was detected or not detected within geopolitical units. Often, the spatial aggregation process obscures the values of response variables, spatial covariates, and locations of each individual, which makes recovering individual-level inference difficult. We show that applying a series of transformations, including a change of support, to a bivariate point process model allows researchers to recover individual-level inference for spatial covariates from spatially aggregated binary data. The series of transformations preserves the convenient interpretation of desirable binary regression models that are commonly applied to individual-level data. Using a simulation experiment, we compare the performance of our proposed method under varying types of spatial aggregation against the performance of standard approaches using the original individual-level data. We illustrate our method by modeling individual-level probability of infection using a data set that has been aggregated to protect an at-risk and endangered species of bats. Our simulation experiment and data illustration demonstrate the utility of the proposed method when access to original non-aggregated data is impractical or prohibited.

Northeast and Midwest United States↗

Transmission risk of Lyme disease and implications for tick management

Transmission risk of Lyme disease at a site can be estimated using the probability of exposure ( P 1 = probability of being bitten by at least one infected tick); P 1 =1 - (1 - k t ) n , where n = number of tick bites per person and k t = spirochete prevalence in questing ticks. This probability is more directly related to the likelihood of acquiring Lyme disease than the standard measure of transmission risk (the number of infected ticks per sample) and allows for direct consideration of the level of tick/human contact (by varying n ) in assessing exposure risk and designing management strategies. Projections predict that interventions that lower tick abundance or spirochete prevalence do not necessarily result in equivalent declines in human exposure risk. Management interventions are predicted to have greatest success at lowering disease incidence in humans when tick abundance and/or pathogen prevalence in questing ticks are initially low (e.g., for ticks in residential lawns or for low-prevalence diseases). These techniques are predicted to be less effective at lowering disease incidence in people engaged in high-risk activities at sites with high tick abundance and pathogen prevalence, such as wooded sites in highly endemic areas.

American Journal of Epidemiology↗

Sero-epidemiology of Highly Pathogenic Avian Influenza viruses among wild birds in subarctic intercontinental transition zones

Background: The geographic expansion and evolution of A/Goose/Guangdong/1/1996(H5N1) (Gs/GD) lineage H5Nx highly pathogenic avian influenza (HPAI) viruses since 1996 have raised awareness of enzootic circulation among migratory birds and the potential for intercontinental transport and spread. Recent Pacific- and Atlantic-route introductions of HPAI to North America were facilitated by avian migration through subarctic zones, specifically Alaska and Iceland. This study aimed to identify recent historical patterns of exposure to HPAI viruses among birds within and migrating through both regions and evaluate how geographic, demographic, and taxonomic differences contribute to exposure risk at two intercontinental staging locations. Methods: During 2010-2019, blood samples were obtained from captured wild migratory seabirds and waterfowl in Alaska and Iceland. All live birds were released following completion of sampling. Sampling date, species, sampling location, and age class was documented for each bird, and sex was documented when possible. Lentiviral pseudoviruses that express the influenza hemagglutinin surface glycoprotein for H5Nx HPAI and H5 low-pathogenicity avian influenza (LPAI) were constructed for use in serological assays to screen for and quantify titers of antibodies against the latter viruses. Data were analyzed to compare (a) categorical baseline ecological traits between Iceland and Alaska, and (b) ecological traits between birds identified to be seropositive and suggestive/seronegative/fully cross-reactive birds to H5Nx HPAI in Iceland and Alaska. Factors associated with seroreactivity to H5Nx HPAI and H5 LPAI were assessed. Results: The seroprevalence of HPAI among birds in both locations was 7.3% (112/1526). Findings reveal variability in seroprevalence by year, higher rates of exposure to H5 LPAI than H5Nx HPAI overall, and significantly more seropositive and suggestive exposure of birds to H5Nx HPAI in Alaska as compared to Iceland. Geographic, demographic, and taxonomic differences contribute to exposure risk between Alaska and Iceland. Most tested birds were immuno-naïve to HPAI in both locations, which indicates many migratory birds in the subarctic are susceptible to HPAI infection, demonstrating substantial risk for intercontinental transmission between Asia, Europe, and North America. Conclusions: Our findings provide further justification for increased viral and serosurveillance in Alaska and Iceland to monitor subarctic movements of migratory birds and intercontinental transmission dynamics of currently circulating and new strains of HPAI globally.

Research Square↗

Isolation and characterization of the fall Chinook aquareovirus

Background Salmon are paramount to the economy, ecology, and history of the Pacific Northwest. Viruses constitute one of the major threats to salmon health and well-being, with more than twenty known virus species that infect salmon. Here, we describe the isolation and characterization of the fall Chinook aquareovirus, a divergent member of the species Aquareovirus B within the family Reoviridae . Methods The virus was first found in 2014 as part of a routine adult broodstock screening program in which kidney and spleen tissue samples from healthy-appearing, adult fall Chinook salmon ( Oncorhynchus tshawytscha ) returning to a hatchery in Washington State produced cytopathic effects when inoculated onto a Chinook salmon embryo cell line (CHSE-214). The virus was not able to be confirmed by an RT-PCR assay using existing aquareovirus pan-species primers, and instead was identified by metagenomic next-generation sequencing. Metagenomic next-generation sequencing was used to recover the full genome and completed using 3′ RACE. Results The genome of the fall Chinook aquareovirus contains 11 segments of double-stranded RNA totaling 23.3 kb, with each segment flanked by the canonical sequence termini found in the aquareoviruses. Sequence comparisons and a phylogenetic analysis revealed a nucleotide identity of 63.2% in the VP7 gene with the Green River Chinook virus, placing the new isolate in the species Aquareovirus B . A qRT-PCR assay was developed targeting the VP2, which showed rapid growth of the isolate during the initial 5 days in culture using CHSE-214 cells. Conclusions This sequence represents the first complete genome of an Aquareovirus B species. Future studies will be required to understand the potential pathogenicity and epidemiology of the fall Chinook aquareovirus.

Virology Journal↗

Host vs. pathogen evolutionary arms race: Effects of exposure history on individual response to a genetically diverse pathogen

Introduction: Throughout their range, bighorn sheep ( Ovis canadensis ) populations have seen significant disease-associated declines. Unfortunately, understanding of the underlying epidemiological processes driving the disease dynamics in this species has hindered conservation efforts aimed at improving the health and long-term viability of these populations. Individual response to pathogen exposure emerges from dynamic interactions between competing evolutionary processes within the host and pathogen. The host’s adaptive immune system recognizes pathogens and mounts a defensive response. Pathogens have evolved strategies to overcome adaptive immune defenses including maintaining high genetic diversity through rapid evolution. The outcomes of this evolutionary warfare determine the success of pathogen invasion of the host and ultimately the success of conservation efforts. Methods: During an epizootic dominated by a single strain, we explore these host-pathogen dynamics by examining the variation in effects of pathogen invasion on captive bighorn sheep with differing histories of exposure to genetically diverse strains of Mycoplasma ovipneumoniae (Movi). We monitored clinical signs of disease and sampled animals and their environment to detect spread of Movi among 37 bighorn sheep separated into nine pens based on known exposure Results: We documented Movi transmission within and across pens and we detected Movi DNA in air, water, and invertebrate samples. Higher levels of antibody to Movi prior to the epizootic were associated with a lower likelihood of presenting clinical signs of pneumonia. Nonetheless, higher antibody levels in symptomatic individuals were associated with more severe progressive disease, increased probability and speed of pneumonia-induced mortality, and reduced likelihood of returning to a healthy state. Bighorn sheep with previous exposure to a strain other than the predominant epizootic strain were more likely to recover. Discussion: Our results indicate that Movi-strain variability was sufficient to overwhelm the adaptive host immunological defenses. This outcome indicates, in free-ranging herds, past exposure is likely insufficient to protect bighorn sheep from infection by new Movi strains, although it influences the progression of disease and recovery within the herd. Therefore, given Movi-strain variability and the lack of immunological protection from past exposure, focusing management efforts on minimizing the introduction of Movi into bighorn herds, through separation of domestic and bighorn sheep and avoidance of management activities that create commingling of bighorn sheep carrying differing Movi strains, will likely be the most effective approach for reducing the effects of disease and achieving bighorn sheep conservation goals.

Idaho, Oregon, South Dakota, Washington↗