Fast Variance Prediction for Iteratively Reconstructed CT Images With Locally Quadratic Regularization.

Predicting noise properties of iteratively reconstructed CT images is useful for analyzing reconstruction methods; for example, local noise power spectrum (NPS) predictions may be used to quantify the detectability of an image feature, to design regularization methods, or to determine dynamic tube current adjustment during a CT scan. This paper presents a method for fast prediction of reconstructed image variance and local NPS for statistical reconstruction methods using quadratic or locally quadratic regularization. Previous methods either require impractical computation times to generate an approximate map of the variance of each reconstructed voxel, or are restricted to specific CT geometries. Our method can produce a variance map of the entire image, for locally shift-invariant CT geometries with sufficiently fine angular sampling, using a computation time comparable to a single back-projection. The method requires only the projection data to be used in the reconstruction, not a reconstruction itself, and is reasonably accurate except near image edges where edge-preserving regularization behaves highly nonlinearly. We evaluate the accuracy of our method using reconstructions of both simulated CT data and real CT scans of a thorax phantom.

Management of on-farm risk to livestock from bovine tuberculosis in Michigan, USA, white-tailed deer: Predictions from a spatially-explicit stochastic model.

The eradication of bovine tuberculosis (bTB), caused by Mycobacterium bovis, from cattle in many locations worldwide is complicated by endemic foci of the disease in free-ranging wildlife. Recent simulation modeling of the bTB outbreak in white-tailed deer (WTD) in Michigan, USA, suggests current management is unlikely to eradicate bTB from the core outbreak area (DMU 452) within the next three decades. However, some level of control short of eradication might sufficiently reduce transmission from deer to cattle to a point at which the negative effects of bTB on the cattle industry could be reduced or eliminated, while minimizing the negative consequences of reducing deer numbers. We extended our existing spatially-explicit, individual-based stochastic simulation model of bTB transmission in WTD to incorporate transmission to cattle, to characterize the effects of vaccination and increased harvest of WTD on cattle herd breakdown rates, to examine the effects of localized culling or vaccination of WTD in the vicinity of cattle farms, to assess the effects of concurrent deer baiting, and to determine the effect of progressive restriction of deer/cattle contact on herd breakdowns. A spatially-explicit "cattle layer" was constructed describing the spatial locations, farm size and cattle density of all farms within and directly adjacent to DMU452. Increased hunter harvest or vaccination of deer, or a combination, would likely decrease the number of cattle herd breakdowns to <1 per year in less than 15 years. Concurrent deer baiting variably increased the time necessary to achieve zero breakdowns. The prevalence of bTB in deer needed to fall below ∼0.5% before ≤1 herd breakdown per year could be expected, and below 0.1% before zero breakdowns were likely. Locally applied post-harvest deer culling or vaccination also rapidly reduced herd breakdowns. On farm biosecurity measures needed to reduce deer to cattle contact by >95% in order to reliably reduce herd breakdowns, and did not achieve zero breakdowns in the absence of other deer controls.

Rapid detection of serum antibody by dual-path platform VetTB assay in white-tailed deer infected with Mycobacterium bovis.

Bovine tuberculosis (TB) in cervids remains a significant problem affecting farmed herds and wild populations. Traditional skin testing has serious limitations in certain species, whereas emerging serological assays showed promising diagnostic performance. The recently developed immunochromatographic dual-path platform (DPP) VetTB assay has two antigen bands, T1 (MPB83 protein) and T2 (CFP10/ESAT-6 fusion protein), for antibody detection. We evaluated the diagnostic accuracy of this test by using serum samples collected from groups of white-tailed deer experimentally inoculated with Mycobacterium bovis, M. avium subsp. paratuberculosis, or M. bovis BCG Pasteur. In addition, we used serum samples from farmed white-tailed deer in herds with no history of TB, as well as from free-ranging white-tailed deer culled during field surveillance studies performed in Michigan known to have bovine TB in the wild deer population. The DPP VetTB assay detected antibody responses in 58.1% of experimentally infected animals within 8 to 16 weeks postinoculation and in 71.9% of naturally infected deer, resulting in an estimated test sensitivity of 65.1% and a specificity of 97.8%. The higher seroreactivity found in deer with naturally acquired M. bovis infection was associated with an increased frequency of antibody responses to the ESAT-6 and CFP10 proteins, resulting in a greater contribution of these antigens, in addition to MPB83, to the detection of seropositive animals, compared with experimental M. bovis infection. Deer experimentally inoculated with either M. avium subsp. paratuberculosis or M. bovis BCG Pasteur did not produce cross-reactive antibodies that could be detected by the DPP VetTB assay. The present findings demonstrate the relatively high diagnostic accuracy of the DPP VetTB test for white-tailed deer, especially in the detection of naturally infected animals.

Recent advances in the management of bovine tuberculosis in free-ranging wildlife.

Established foci of Mycobacterium bovis (the causative agent of bovine tuberculosis [bTB]) in free-ranging wildlife are currently under various stages of management on three continents (Africa, Europe and North America) and in New Zealand. Other, as yet undiagnosed, foci seem likely to exist elsewhere. The complex roles that these wildlife foci play in the ecology of bTB remain among the greatest challenges facing bTB control globally. Conceptually, management of bTB in free-ranging wildlife can be thought of as progressing from the discovery of an outbreak through frequently overlapping stages of epidemiological characterization, initial control, simulation and forecasting, focused control, and verification of eradication. Surveillance in its various forms remains a critical component of assessment throughout. Since the Fourth International M. bovis Conference in 2005, research on management of bTB in free-ranging wildlife has encompassed such areas as the human dimensions of wildlife management, mitigation of bTB risks from wildlife on cattle farms, vaccine biology, and epidemiology, with a major contribution from simulation modeling. In order to advance the actual field management of bTB, however, research must be sufficiently grounded to aid development of practical, affordable and politically defensible management interventions which stand a reasonable chance of being implemented. The current management of two wildlife reservoirs of bTB, brushtail possums (Trichosurus vulpecula) in New Zealand, and white-tailed deer (Odocoileus virginianus) in Michigan, USA, serve as contrasting examples of different wildlife management strategies aimed at achieving a common goal. In New Zealand, the importance of agricultural export markets and the status of the possum as a non-native pest have facilitated direct, aggressive management of the disease reservoir, resulting in considerable progress towards bTB freedom since 1994. In Michigan, the relative importance of the hunting economy and of whitetails as a game animal have made such aggressive culling politically untenable. This has forced reliance upon publicly supported, and implemented, management tools, and so provided impetus to better understand social support for wildlife management policy, its limitations, and ways to employ it in disease control policy development.

Management of bovine tuberculosis in Michigan wildlife: current status and near term prospects.

Surveillance and control activities for bovine tuberculosis (bTB) in free-ranging Michigan white-tailed deer (Odocoileus virginianus) have now been underway for over a decade. Significant progress has been made, lowering apparent prevalence in deer in the core area by >60%, primarily via reduction of deer densities through hunting, and restrictions on public feeding and baiting of deer. These broad strategies of the Michigan Department of Natural Resources (MDNR), implemented with the cooperation of Michigan deer hunters, halved the deer population in the bTB endemic area. However, as hunters see fewer deer, their willingness to sustain aggressive harvests has waned, and public resentment of control measures has grown. During the past four years, apparent prevalence in core area deer has held approximately steady just below 2%. After bottoming out in 2004 at an estimated 10-12 deer/km(2), deer numbers have since rebounded by ∼ 30%. Public compliance with baiting and feeding restrictions has been variable. In general, hunters in the core area do not perceive bTB as a problem, in spite of 13 years of MDNR outreach. To date, MDNR has expended more than US$23 million on TB-related activities. Of late, a substantial portion of that funding has been diverted to support other programs which have suffered from budget shortfalls. Livestock herd breakdowns continue to occur sporadically, averaging 3-4 per year 2005 to present. In total, 46 cattle and 4 captive deer herds have been diagnosed bTB positive statewide, the majority yielding only 1 positive animal. Five cattle herds were twice infected, one thrice. Michigan Department of Agriculture (MDA) policy emphasis has shifted towards obtaining producer support for wildlife risk mitigation and farm biosecurity. Funding has proven a limiting factor, with the majority of the US$63 million spent to date devoted to whole herd testing. Nevertheless, some initiatives justify cautious optimism. Promising research to support eventual vaccination of wild deer continues. Some hunters and landowners have begun to recognize the costs of high deer densities and supplemental feeding. A peninsula-wide ban on baiting and feeding was enacted. Some cattle producers, recognizing their precarious circumstances, have begun work to change long-held prevailing opinions among their peers about farm biosecurity. Yet formidable challenges remain, and evidence suggests that eradication of bTB, if it can be achieved, will take decades, and will require greater public and political resolve than has been demonstrated thus far.

Public acceptance as a determinant of management strategies for bovine tuberculosis in free-ranging U.S. wildlife.

When bovine tuberculosis (bTB) is detected in free-ranging wildlife populations, preventing geographic spread and the establishment of a wildlife reservoir requires rapid, often aggressive response. Public tolerance can exert a significant effect on potential control measures available to managers, and thus on the success of disease management efforts. Separate outbreaks of bTB in free-ranging white-tailed deer (Odocoileus virginianus) in two midwestern states provide a case study. In Minnesota, bTB was first discovered in cattle in 2005 and subsequently in deer. To date, 12 beef cattle farms and 26 white-tailed deer have been found infected with the disease. From 2005 to 2008, disease prevalence in deer has decreased from 0.4% (SE=0.2%) to <0.1% and remained confined to a small (<425 km(2)) geographic area. Deer population reduction through liberalized hunting and targeted culling by ground sharpshooting and aerial gunning, combined with a prohibition on baiting and recreational feeding, have likely been major drivers preventing disease spread thus far. Without support from cattle producers, deer hunters and the general public, as well as politicians, implementation of these aggressive strategies by state and federal authorities would not have been possible. In contrast, Michigan first discovered bovine bTB in free-ranging deer in 1975, and disease management efforts were not instituted until 1995. The first infected cattle herd was diagnosed in 1998. Since 1995, disease prevalence in free-ranging deer has decreased from 4.9% to 1.8% in the ∼ 1500 km(2) core outbreak area. Culture positive deer have been found as far as 188 km from the core area. Liberalized harvest and restrictions on baiting and feeding have facilitated substantial reductions in prevalence. However, there has been little support on the part of hunters, farmers or the general public for more aggressive population reduction measures such as culling, and compliance with baiting and feeding restrictions has been variable and often problematic. We compare and contrast the Minnesota and Michigan outbreaks with respect to temporal, social, economic, and logistical factors that shape public attitudes toward aggressive disease control strategies, the limitations these factors place on management, and the implications for bTB eradication from wildlife reservoirs in the U.S.

Evaluation of blood assays for detection of Mycobacterium bovis in white-tailed deer (Odocoileus virginianus) in Michigan.

Surveillance and control activities related to bovine tuberculosis (TB) in free-ranging, Michigan white-tailed deer (Odocoileus virginianus) have been underway for over a decade, with significant progress. However, foci of higher TB prevalence on private lands and limited agency ability to eliminate them using broad control strategies have led to development and trial of new control strategies, such as live trapping, testing, and culling or release. Such strategies require a prompt, accurate live animal test, which has thus far been lacking. We report here the ability of seven candidate blood assays to determine the TB infection status of Michigan deer. Our aims were twofold: to characterize the accuracy of the tests using field-collected samples and to evaluate the feasibility of the tests for use in a test-and-cull strategy. Samples were collected from 760 deer obtained via five different surveys conducted between 2004 and 2007. Blood samples were subjected to one or more of the candidate blood assays and evaluated against the results of mycobacterial culture of the cranial lymph nodes. Sensitivities of the tests ranged from 46% to 68%, whereas specificities and negative predictive values were all >92%. Positive predictive values were highly variable. An exploratory analysis of associations among several host and sampling-related factors and the agreement between blood assay and culture results suggested these assays were minimally affected. This study demonstrated the capabilities and limitations of several available blood tests for Mycobacterium bovis on specimens obtained through a variety of field surveillance methods. Although these blood assays cannot replace mass culling, information on their performance may prove useful as wildlife disease managers develop innovative methods of detecting infected animals where mass culling is publicly unacceptable and cannot be used as a control strategy.

Serum 25-hydroxyvitamin D concentrations in captive and free-ranging, white-tailed deer (Odocoileus virginianus).

Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were determined for free-ranging and captive white-tailed deer (WTD). Effects of gender, season, and age on 25(OH)D concentrations were determined as well as comparisons to concentrations in serum from captive reindeer and elk. Seasonal variations in 25(OH)D concentrations were detected for both captive and free-ranging WTD with greatest concentrations detected in August/September (approximately 25 ng/mL) and lowest concentrations in February (approximately 5 - 10 ng/mL). Free-ranging WTD < 1 year of age had lower 25(OH)D concentrations (approximately 6 ng/mL) than did free-ranging WTD > 1 year of age (approximately12 ng/mL). For captive WTD fawns, 25(OH)D concentrations increased from 1 to 9 days of age (exceeding 100 ng/mL) and then steadily declined to approximately 10 ng/mL by 3 months of age. In general, differences in 25(OH)D concentrations based on gender were not detected. 25(OH)D concentrations in captive WTD did not differ from that of captive reindeer; yet, 25(OH)D concentrations were lower in WTD than in captive elk. Additional research is necessary to determine if low serum 25(OH)D concentrations during the winter or pre-weaning period are associated with increased rates of infectious and metabolic disease.

Estimating the true prevalence of Mycobacterium bovis in free-ranging elk in Michigan.

Although relatively small, Michigan's elk (Cervus elaphus nelsoni) herd is highly valued by both hunters and the general public. Elk and red deer (Cervus elaphus elaphus) are highly susceptible to infection with Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), and outbreaks have been documented worldwide. The Michigan elk range lies entirely within counties where TB is known to be enzootic in white-tailed deer (Odocoileus virginianus). Consequently, a project was undertaken to estimate the true prevalence of TB in Michigan's free-ranging elk herd. All elk harvested by licensed hunters during 2002-2004, and all nonharvest elk mortalities examined by the Michigan Department of Natural Resources Wildlife Disease Laboratory from November 2002-May 2005, were screened for gross lesions of TB with samples of cranial lymph nodes and palatine tonsils collected for histopathology and mycobacterial culture. In all, 334 elk were included in the study. Twenty-three elk with gross lesions were considered TB suspects; all were culture-negative for M. bovis. However, M. bovis was cultured from two elk without gross lesions. The sensitivity, specificity, and negative predictive value of the current TB surveillance protocol were 0%, 100%, and 99.4%, respectively, while the apparent prevalence and true prevalence calculated directly from the sample were 0% and 0.6%, respectively. The positive predictive value and the estimated true prevalence of the population were undefined. The poor sensitivity of current surveillance was likely an artifact of its application to a relatively small sample, in order to detect a disease present at very low prevalence. The low prevalence of TB in Michigan elk, and the early stage of pathogenesis of the few infected animals, does not suggest elk are maintenance hosts at the present time.

An outbreak of Eastern equine encephalitis virus in free-ranging white-tailed deer in Michigan.

Eastern equine encephalitis (EEE) virus has been recognized as affecting horses and humans in the eastern United States for 70 yr. Evidence of exposure with EEE virus has been reported in a variety of free-ranging wild birds and mammals but cases of clinical disease are much less commonly reported. In Michigan, reports of outbreaks of EEE virus in equine species extend back more than a half century. We report diagnosis of EEE virus infection of multiple free-ranging white-tailed deer (Odocoileus virginianus) from three Michigan counties during late summer of 2005. Infection was confirmed in seven of 30 deer collected based on reported neurologic signs and results from immunohistochemistry, polymerase chain reaction, and/or virus isolation. One of the deer also was infected with West Nile virus and an eighth deer had microscopic lesions in the cerebrum consistent with those reported for EEE. To our knowledge, this is the first report of multiple cases of EEE in free-ranging white-tailed deer, and highlights several issues of significance to wildlife managers and public health officials.

Spatial analysis of Mycobacterium bovis infection in white-tailed deer (Odocoileus virginianus) in Michigan, USA.

The wild white-tailed deer (Odocoileus virginianus) population in Michigan, USA, has endemic Mycobacterium bovis. We determined whether there were spatial clusters of retrospective TB cases in white-tailed deer in northeastern Michigan and identified specific factors associated with the spatial clusters. Data from hunter-harvested deer (age, gender, TB status, and geographic section) were collected by the Michigan Department of Natural Resources (MDNR) during TB surveillance from 1995 to 2002. Land cover (vegetation, land-use) and land type (soil types and drainage characteristics, landforms) described potential deer habitats. Specific locations of large-scale supplemental feeding sites were collected from the MDNR aerial surveillance program from 1997 to 2002. Analyses were conducted using principal components derived from environmental data (and other risk factors) on spatial clusters of disease (identified by the spatial scan statistic). Spatial effects were incorporated into the multivariable analyses by using a neighborhood approach. A total of 420 deer with M. bovis infection were identified from 1995 to 2002, out of 39,451 harvested deer from 3216 TRS units, and spatial clusters of cases were identified. A total of seven principal components of environmental data were generated. Clusters were associated with the presence of large expanses of deciduous forests on moraine ridges separated by low areas of forested wetlands, and the presence of many small lakes. Factors that promoted congregation of deer for extended periods of time (natural cover, access to water, and less human contact) appeared to be associated with increased odds of TB positivity. This suggests that there are specific areas where interventions can be implemented to reduce congregation of animals and disrupt the cycle of infection transmission.

Managing the wildlife reservoir of Mycobacterium bovis: the Michigan, USA, experience.

Historical, social and economic factors combined to provide a focus where bovine tuberculosis has become established in free-ranging wildlife in northeastern lower Michigan. White-tailed deer, the primary reservoir and maintenance host of tuberculosis, are highly valued by the public, and particularly hunters, for cultural and economic reasons. Since 1995, significant progress has been made in defining and reducing the reservoir of tuberculosis in deer. As yet, no other wildlife species has been shown to play an epidemiologically important role in the disease cycle. The importance of deer and deer hunting to Michigan has uniquely shaped tuberculosis control policies, and poses ongoing challenges as wildlife managers strive to maintain momentum for broad control strategies, and develop focused strategies that are publicly acceptable. Even if momentum and funding can be maintained, tuberculosis will likely continue to be present for a decade or longer. Thus, cattle producers waiting for tuberculosis to be eradicated from wildlife to eliminate risks to their herds and markets face disappointment for the foreseeable future. Such unrealistic expectations also place Michigan's federal tuberculosis accreditation status at perpetual risk. Accredited free status is unlikely to be regained without accompanying changes in cattle management. In Michigan, management of tuberculosis has clearly demonstrated that social issues and public approval are likely to be the critical limiting factors in control.

Mortality of Rocky Mountain elk in Michigan due to meningeal worm.

Mortality from cerebrospinal parelaphostrongylosis caused by the meningeal worm (Parelaphostrongylus tenuis) has been hypothesized to limit elk (Cervus elaphus nelsoni) populations in areas where elk are conspecific with white-tailed deer (Odocoileus virginianus). Elk were reintroduced into Michigan (USA) in the early 1900s and subsequently greatly increased population size and distribution despite sympatric high-density (>or=12/km2) white-tailed deer populations. We monitored 100 radio-collared elk of all age and sex classes from 1981-94, during which time we documented 76 mortalities. Meningeal worm was a minor mortality factor for elk in Michigan and accounted for only 3% of mortalities, fewer than legal harvest (58%), illegal kills (22%), other diseases (7%), and malnutrition (4%). Across years, annual cause-specific mortality rates due to cerebrospinal parelaphostrongylosis were 0.033 (SE=0.006), 0.029 (SE=0.005), 0.000 (SE=0.000), and 0.000 (SE=0.000) for calves, 1-yr-old, 2-yr-old, and >or=3-yr-old, respectively. The overall population-level mortality rate due to cerebrospinal parelaphostrongylosis was 0.009 (SE=0.001). Thus, meningeal worm had little impact on elk in Michigan during our study despite greater than normal precipitation (favoring gastropods) and record (>or=14 km2) deer densities. Further, elk in Michigan have shown sustained population rates-of-increase of >or=18%/yr and among the highest levels of juvenile production and survival recorded for elk in North America, indicating that elk can persist in areas with meningeal worm at high levels of population productivity. It is likely that local ecologic characteristics among elk, white-tailed deer, and gastropods, and degree of exposure, age of elk, individual and population experience with meningeal worm, overall population vigor, and moisture determine the effects of meningeal worm on elk populations.

Estimating the true prevalence of Mycobacterium bovis in hunter-harvested white-tailed deer in Michigan.

Apparent prevalence, although useful as a consistent index, may underestimate the true prevalence of disease. In Michigan, the ability to estimate the true prevalence of bovine tuberculosis (TB; caused by Mycobacterium bovis) in free-ranging white-tailed deer (Odocoileus virginianus) will become increasingly important to accurately assess progress towards eradication. Our objectives were threefold: to estimate the true prevalence of M. bovis in free-ranging deer in Michigan, to evaluate the effectiveness of existing TB surveillance methods, and to indirectly assess whether TB epidemiologic data from captive cervid herds can be meaningfully extrapolated to free-ranging populations. The study population consisted of all free-ranging deer submitted for TB testing in 2001 from six townships in northeastern Lower Michigan. Tissue samples of tonsil and cranial lymph nodes were collected bilaterally from all deer eligible for the study that did not have gross lesions suggestive of TB (n = 701). Samples were subjected to histopathologic, acid-fast (AF) staining, mycobacterial culture, and polymerase chain reaction (PCR) testing. Seven deer cultured positive for M. bovis that would not have been detected by current surveillance, yielding apparent and true prevalence estimates (95% confidence limits) of 2.7% (1.6, 3.8) and 3.6% (2.3, 4.9), respectively. The sensitivity, specificity, and positive and negative predictive values of the current surveillance protocol were 75, 100, 100, and 99%, respectively. Histologic lesions were present only in tonsils, and ranged from simple necrosis to caseation, suppuration, and granuloma formation. Acid-fast staining and PCR detected M. bovis in only one of the seven culture-positive deer. Our study provides the first estimate of the true prevalence of M. bovis in Michigan's free-ranging deer population and suggests modest underestimation of that prevalence by current surveillance. This study also suggests that caution is warranted when extrapolating epidemiologic data on TB in captive cervids to free-ranging populations and confirms the pivotal role of the tonsil in early infections.

Prevalence of Mycobacterium bovis infection in cervids on privately owned ranches.

OBJECTIVE: To determine prevalence of tuberculosis caused by infection with Mycobacterium bovis in cervids on privately owned ranches in northeastern lower Michigan. DESIGN: Epidemiologic survey. ANIMALS: Cervids on 96 privately owned ranches. PROCEDURES: A combination of slaughter and skin tuberculin testing was used to collect data. Infection with M. bovis was confirmed by use of standard necropsy and bacteriologic culture techniques. RESULTS: Cervids with tuberculosis were detected on 1 of the 96 ranches. The apparent prevalence of tuberculosis in cervids from the 96 ranches was 1.1 cases/100 cervids (21 cases/1,867 cervids tested). For the ranch with infected cervids, prevalence of infection with M. bovis was 12.1 cases/100 cervids (21 cases/174 cervids tested). No obvious gross lesions were seen in 8 of 21 white-tailed deer and 1 coyote with culture-confirmed M. bovis infection. CONCLUSIONS AND CLINICAL RELEVANCE: The lack of visible lesions in a substantial proportion of infected animals should be taken into consideration in studies involving detection and prevalence of tuberculosis.

Bovine tuberculosis in Michigan wildlife and livestock.

Since 1994, the state of Michigan has recognized a problem with bovine tuberculosis (TB), caused by Mycobacterium bovis, in wild white-tailed deer from a 12-county area in northeastern Lower Michigan. A total of 65,000 free-ranging deer have been tested, and 340 have been found to be positive for M. bovis. The disease has been found in other wildlife species, and, in 1998, in domestic cattle, where to date 13 beef cattle and 2 dairy cattle herds have been diagnosed with bovine TB. Unfortunately, the situation is unique in that there have never been reports of self-sustaining bovine TB in a wild, free-ranging cervid population in North America. Scientists, biologists, epidemiologists, and veterinarians who have studied this situation have concluded that the most logical theory is that high deer densities and the focal concentration caused by baiting (the practice of hunting deer over feed) and feeding are the factors most likely responsible for the establishment of self-sustaining TB in free-ranging Michigan deer. Baiting and feeding have been banned since 1998 in counties where the disease has been found. In addition, the deer herd has been reduced by 50% in the endemic area with the use of unlimited antlerless permits. The measures of apparent TB prevalence have been decreased by half since 1997, providing hopeful preliminary evidence that eradication strategies are succeeding.