Prion forensics: a multidisciplinary approach to investigate CWD at an illegal deer carcass disposal site.

Infectious prions are resistant to degradation and remain infectious in the environment for several years. Chronic wasting disease (CWD) has been detected in cervids inhabiting North America, the Nordic countries, and South Korea. CWD-prion spread is partially attributed to carcass transport and disposal. We employed a forensic approach to investigate an illegal carcass dump site connected with a CWD-positive herd. We integrated anatomic, genetic, and prion amplification methods to discover CWD-positive remains from six white-tailed deer (Odocoileus virginianus) and, using microsatellite markers, confirmed a portion originated from the CWD-infected herd. This approach provides a foundation for future studies of carcass prion transmission risk.

Herd-level risk factors associated with chronic wasting disease-positive herd status in Minnesota, Pennsylvania, and Wisconsin cervid herds.

The objective of this study was to evaluate risks related to introduction of Chronic Wasting Disease (CWD) to farmed cervid herds in Minnesota (MN), Pennsylvania (PA), and Wisconsin (WI). This was the first study to evaluate risk factors related to multiple pathways of CWD transmission to farmed cervid herds. Participating herds in this case-control study included 22 case and 49 control herds identified through participation in the respective mandatory State CWD herd program. Data was voluntarily collected from white-tailed deer (WTD) study herds using a questionnaire and state animal health agency databases. Univariable analyses identified associations between CWD-positive herds and variables representing different transmission pathways, including direct contact with infected farmed cervids (imported from a herd that later tested positive for CWD) odds ratio (OR):7.16, 95 % confidence intervals (CI):1.64-31.21 and indirect contact with infected wild cervids (access of domestic cats to pens or feed storage area) OR:4.07, 95 % CI:1.35-12.26, observed evidence of mammalian scavengers inside or outside of fenceline in the previous 12 months OR:6.55, 95 % CI:1.37-31.32, ≤ 5 km distance to nearest detected CWD-positive wild cervid OR:3.08, 95 % CI:1.01-9.39, forested area crosses the perimeter fenceline OR:3.54, 95 % CI:1.13-11.11, ≤ 0.3 m distance of water source to fenceline OR:4.71, 95 % CI:1.60-13.83, and water source shared with wild cervids (running or standing water) OR:4.17, 95 % CI:1.34-12.92. Three variables from univariable analyses that represented different biological transmission pathways were placed in a Firth's penalized maximum likelihood multivariable logistic regression to evaluate associations between transmission pathway and CWD herd infection status. For the issue of low sample size and overfitting, 95 % CIs for estimated coefficients for the three variables were computed via bootstrapping of 10,000 independent bootstrap samples. The three biological variables were significantly associated with herd CWD infection status: imported cervids from a herd that later tested positive for CWD (OR:5.63; 95 % CI:1.1-28.2), ≤ 0.3 m distance of cervid water source to perimeter fenceline (OR:4.83; 95 % CI:1.5-16.1), and ≤ 5 km distance to nearest detected CWD-positive wild cervid (OR:4.10; 95 % CI:1.1-15.2). The risk factors associated with CWD herd status identified in this study indicated the importance of transmission through direct contact pathways with infected cervid herds (introduction of cervids from herds later identified as CWD-infected) and indirect contact pathways with infected wild cervids that could be related to other animals through the perimeter fence. Further studies are needed to confirm and clarify understanding of indirect pathways to allow development of improved biosecurity practices to prevent CWD introduction to cervid herds.

Comparison of spatiotemporal patterns of historic natural Anthrax outbreaks in Minnesota and Kazakhstan.

Disease spread in populations is a consequence of the interaction between host, pathogen, and environment, i.e. the epidemiological triad. Yet the influences of each triad component may vary dramatically for different settings. Comparison of environmental, demographic, socio-economic, and historical backgrounds may support tailoring site-specific control measures. Because of the long-term survival of Bacillus anthracis, Anthrax is a suitable example for studying the influence of triad components in different endemic settings. We compared the spatiotemporal patterns of historic animal Anthrax records in two endemic areas, located at northern latitudes in the western and eastern hemispheres. Our goal was to compare the spatiotemporal patterns in Anthrax progression, intensity, direction, and recurrence (disease hot spots), in relation to epidemiological factors and potential trigger events. Reported animal cases in Minnesota, USA (n = 289 cases between 1912 and 2014) and Kazakhstan (n = 3,997 cases between 1933 and 2014) were analyzed using the spatiotemporal directionality test and the spatial scan statistic. Over the last century Anthrax occurrence in Minnesota was sporadic whereas Kazakhstan experienced a long-term epidemic. Nevertheless, the seasonality was comparable between sites, with a peak in August. Declining number of cases at both sites was attributed to vaccination and control measures. The spatiotemporal directionality test detected a relative northeastern directionality in disease spread for long-term trends in Minnesota, whereas a southwestern directionality was observed in Kazakhstan. In terms of recurrence, the maximum timespans between cases at the same location were 55 and 60 years for Minnesota and Kazakhstan, respectively. Disease hotspots were recognized in both settings, with spatially overlapping clusters years apart. Distribution of the spatiotemporal cluster radii between study sites supported suggestion of site-specific control zones. Spatiotemporal patterns of Anthrax occurrence in both endemic regions were attributed to multiple potential trigger events including major river floods, changes in land use, agriculture, and susceptible livestock populations. Results here help to understand the long-term epidemiological dynamics of Anthrax while providing suggestions to the design and implementation of prevention and control programs, in endemic settings.

Tolvaptan use in cancer patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone: a post hoc analysis of the SALT-1 and SALT-2 trials.

Hyponatremia is a common electrolyte disorder in cancer patients and has been associated with poor prognosis. A frequent cause of cancer-related hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH). This study was a post hoc subgroup analysis of the SALT-1 (Study of Ascending Levels of Tolvaptan in Hyponatremia) and SALT-2 clinical trials. Hyponatremic subjects with SIADH and cancer received the oral selective vasopressin V2-receptor antagonist tolvaptan (n = 12) or matching placebo (n = 16) once-daily for 30 days. The initial tolvaptan dose (15 mg) was titrated over 4 days to 30 or 60 mg per day, as needed, according to serum sodium level and tolerability. Baseline serum sodium levels in the SIADH/cancer cohort of the SALT trials was 130 and 128 mEq/L for tolvaptan and placebo, respectively. Mean change from baseline in average daily serum sodium AUC for tolvaptan relative to placebo was 5.0 versus -0.3 mEq/L (P < 0.0001) at day 4, and 6.9 versus 1.0 mEq/L (P < 0.0001) at day 30; the observed treatment effects were similar to those in the overall SIADH population (i.e., with and without cancer) at both time points. Serum sodium normalization was observed in 6/12 and 0/13 subjects at day 4 and 7/8 and 2/6 subjects at day 30 in the tolvaptan and placebo groups, respectively (P < 0.05 for both). Common treatment-emergent AEs for tolvaptan were consistent with previously reported results. In this post hoc study of the SALT trial population, oral tolvaptan was an effective and safe therapy for the treatment of hyponatremia in subjects with SIADH and cancer.

Descriptive Epidemiology and Whole Genome Sequencing Analysis for an Outbreak of Bovine Tuberculosis in Beef Cattle and White-Tailed Deer in Northwestern Minnesota.

Bovine tuberculosis (bTB) was discovered in a Minnesota cow through routine slaughter surveillance in 2005 and the resulting epidemiological investigation led to the discovery of infection in both cattle and white-tailed deer in the state. From 2005 through 2009, a total of 12 beef cattle herds and 27 free-ranging white-tailed deer (Odocoileus virginianus) were found infected in a small geographic region of northwestern Minnesota. Genotyping of isolates determined both cattle and deer shared the same strain of bTB, and it was similar to types found in cattle in the southwestern United States and Mexico. Whole genomic sequencing confirmed the introduction of this infection into Minnesota was recent, with little genetic divergence. Aggressive surveillance and management efforts in both cattle and deer continued from 2010-2012; no additional infections were discovered. Over 10,000 deer were tested and 705 whole herd cattle tests performed in the investigation of this outbreak.

Endemic human mosquito-borne disease in Wisconsin residents, 2002-2006.

INTRODUCTION: West Nile virus (WNV) and La Crosse virus (LAC) are the primary mosquito-borne arboviruses associated with human disease in Wisconsin. We examined WNV and LAC human illness surveillance data collected during 2002 through 2006. METHODS: ELISA-based tests developed by the Centers for Disease Control and Prevention (CDC) were used to detect acute WNV and LAC infection in patient sera or cerebral spinal fluid. Public health personnel conducted patient follow-up using standard arbovirus reporting forms. CDC/Council of State and Territorial Epidemiologists definitions were used to determine cases. RESULTS: From 2002 through 2006, 114 confirmed human cases of WNV illness were reported in Wisconsin residents; 82% of illness onsets occurred during August or September. Median age of WNV case patients was 51 years, 49% reported neuroinvasive disease, 56% were hospitalized, and 7 cases were fatal. Confirmed LAC illnesses declined from a high of 27 cases during 2003 to a low of 3 cases during 2005 and 2006. Most LAC illnesses occurred in residents of Western Wisconsin; median age of LAC cases was 9 years. Mean annual incidences of reported confirmed WNV illnesses calculated for high, medium, and low population density groupings were very similar (range: 0.40-0.46 cases/100,000 population). CONCLUSIONS: Humans are at risk for mosquito-borne diseases in Wisconsin. Protection and prevention measures are important statewide, especially during July through September when the risk is greatest.

Mosquito surveillance for West Nile virus in southeastern Wisconsin--2002.

In 2001, West Nile virus (WNV) was identified among dead American crows and bluejays in five counties in southeastern Wisconsin. In response to the introduction of WNV, a pilot mosquito surveillance program was initiated in these five southeastern Wisconsin counties during the summer of 2002. Forty sites were selected for surveillance one night each week during a 17-week period. Mosquitoes were collected in carbon dioxide-baited light traps and gravid traps. During the study period 31,419 mosquitoes were collected, identified to species level and pooled into groups of up to 50 mosquitoes of like species from each collection site. Twenty-five different mosquito species were identified with the common pest mosquitoes, Aedes vexans and Ochlerotatus trivittatus, being the most abundant. Seventeen of the 25 mosquito species found in southeastern Wisconsin have previously been shown to be carriers of WNV in other parts of the U.S. Only 2/1,592 (0.126%) mosquito pools from Wisconsin were positive for WNV by cell culture and reverse transcription polymerase chain reaction (RT-PCR). Active mosquito surveillance is useful for identifying potential mosquito vectors of arboviruses in defined geographic areas, and to monitor population densities of those vectors. This information coupled with infection rate data can help guide public health policies related to vector control, and may help reduce the impact on human, veterinary and bird mortality.