Bait flavor preference and immunogenicity of ONRAB baits in domestic dogs on the Navajo Nation, Arizona

Rabies is responsible for an estimated 59,000 human deaths worldwide, and domestic dogs are the primary reservoir and vector of the disease. Among some nations, widespread vaccination has led to elimination of rabies in domestic dogs, yet dogs are still susceptible to rabies infection from interactions with wildlife reservoirs. On Tribal lands in the United States, less than 20% of domestic dogs are vaccinated for rabies, and parenteral vaccination is often unfeasible. Oral rabies vaccination may provide a solution, but a suitable bait flavor and vaccine must be identified. We evaluated 5 bait flavors (bacon, cheese, egg, fish, and sweet) in pairwise flavor-preference trials using placebo Ultralite baits in 26 domestic dogs on the Navajo Nation, Arizona. Each bait flavor was offered a total of 104 times. In all paired comparisons, bacon was more frequently preferred to the alternative. The sweet flavor (the flavor used operationally for oral rabies vaccine (ORV) distribution in Canada) was least preferred. Forty domestic dogs were offered baits containing ONRAB ORV: 14 received the sweet-flavored bait packet and 26 received bacon-flavored baits. Serum was collected from dogs before vaccination and at day 14 and 30 or 37 days after vaccination. Thirty-seven dogs consumed the baits, 2 baits (both sweet flavored) were chewed and spit out, and 1 (sweet flavored) was swallowed without apparent chewing (gulped). Eight dogs had preexisting rabies virus neutralizing antibody (RVNA) titers and 13 naïve dogs failed to seroconvert during the study period. Overall, 27 dogs (67.5%) showed increased RVNA titers after vaccination, including 1 dog who chewed and spit out the bait and all dogs with positive baseline RVNA titers. Geometric mean titers for all dogs that seroconverted during the study period peaked at day 14 (1.2 IU/ mL; n = 24) and decreased slightly by the final sampling day (0.8 IU/mL; n = 27).We conclude that bacon flavor may be a suitable bait flavor for ORV distribution in loosely kept or free-roaming domestic dogs. Seroconversion among dogs who ingested ONRAB-filled baits was variable. Why 13 dogs who consumed ORV baits failed to seroconvert remains unknown. Additional research to improve seroconversion rates in domestic dogs after vaccination with ONRAB is recommended

Bait flavor preference and immunogenicity of ONRAB baits in domestic dogs on the Navajo Nation, Arizona

Rabies is responsible for an estimated 59,000 human deaths worldwide, and domestic dogs are the primary reservoir and vector of the disease. Among some nations, widespread vaccination has led to elimination of rabies in domestic dogs, yet dogs are still susceptible to rabies infection from interactions with wildlife reservoirs. On Tribal lands in the United States, less than 20% of domestic dogs are vaccinated for rabies, and parenteral vaccination is often unfeasible. Oral rabies vaccination may provide a solution, but a suitable bait flavor and vaccine must be identified. We evaluated 5 bait flavors (bacon, cheese, egg, fish, and sweet) in pairwise flavor-preference trials using placebo Ultralite baits in 26 domestic dogs on the Navajo Nation, Arizona. Each bait flavor was offered a total of 104 times. In all paired comparisons, bacon was more frequently preferred to the alternative. The sweet flavor (the flavor used operationally for oral rabies vaccine (ORV) distribution in Canada) was least preferred. Forty domestic dogs were offered baits containing ONRAB ORV: 14 received the sweet-flavored bait packet and 26 received bacon-flavored baits. Serum was collected from dogs before vaccination and at day 14 and 30 or 37 days after vaccination. Thirty-seven dogs consumed the baits, 2 baits (both sweet flavored) were chewed and spit out, and 1 (sweet flavored) was swallowed without apparent chewing (gulped). Eight dogs had preexisting rabies virus neutralizing antibody (RVNA) titers and 13 naïve dogs failed to seroconvert during the study period. Overall, 27 dogs (67.5%) showed increased RVNA titers after vaccination, including 1 dog who chewed and spit out the bait and all dogs with positive baseline RVNA titers. Geometric mean titers for all dogs that seroconverted during the study period peaked at day 14 (1.2 IU/ mL; n = 24) and decreased slightly by the final sampling day (0.8 IU/mL; n = 27).We conclude that bacon flavor may be a suitable bait flavor for ORV distribution in loosely kept or free-roaming domestic dogs. Seroconversion among dogs who ingested ONRAB-filled baits was variable. Why 13 dogs who consumed ORV baits failed to seroconvert remains unknown. Additional research to improve seroconversion rates in domestic dogs after vaccination with ONRAB is recommended

Endemicity of Zoonotic Diseases in Pigs and Humans in Lowland and Upland Lao PDR: Identification of Socio-cultural Risk Factors

In Lao People's Democratic Republic pigs are kept in close contact with families. Human risk of infection with pig zoonoses arises from direct contact and consumption of unsafe pig products. This cross-sectional study was conducted in Luang Prabang (north) and Savannakhet (central-south) Provinces. A total of 59 villages, 895 humans and 647 pigs were sampled and serologically tested for zoonotic pathogens including: hepatitis E virus (HEV), Japanese encephalitis virus (JEV) and Trichinella spiralis; In addition, human sera were tested for Taenia spp. and cysticercosis. Seroprevalence of zoonotic pathogens in humans was high for HEV (Luang Prabang: 48.6%, Savannakhet: 77.7%) and T. spiralis (Luang Prabang: 59.0%, Savannakhet: 40.5%), and lower for JEV (around 5%), Taenia spp. (around 3%) and cysticercosis (Luang Prabang: 6.1, Savannakhet 1.5%). Multiple correspondence analysis and hierarchical clustering of principal components was performed on descriptive data of human hygiene practices, contact with pigs and consumption of pork products. Three clusters were identified: Cluster 1 had low pig contact and good hygiene practices, but had higher risk of T. spiralis. Most people in cluster 2 were involved in pig slaughter (83.7%), handled raw meat or offal (99.4%) and consumed raw pigs' blood (76.4%). Compared to cluster 1, cluster 2 had increased odds of testing seropositive for HEV and JEV. Cluster 3 had the lowest sanitation access and had the highest risk of HEV, cysticercosis and Taenia spp. Farmers which kept their pigs tethered (as opposed to penned) and disposed of manure in water sources had 0.85 (95% CI: 0.18 to 0.91) and 2.39 (95% CI: 1.07 to 5.34) times the odds of having pigs test seropositive for HEV, respectively. The results have been used to identify entry-points for intervention and management strategies to reduce disease exposure in humans and pigs, informing control activities in a cysticercosis hyper-endemic village

Three red suns in the sky: A transiting, terrestrial planet in a triple M-dwarf system at 6.9 pc

We present the discovery from Transiting Exoplanet Survey Satellite (TESS) data of LTT 1445Ab. At a distance of 6.9 pc, it is the second nearest transiting exoplanet system found to date, and the closest one known for which the primary is an M dwarf. The host stellar system consists of three mid-to-late M dwarfs in a hierarchical configuration, which are blended in one TESS pixel. We use MEarth data and results from the Science Processing Operations Center data validation report to determine that the planet transits the primary star in the system. The planet has a radius of ${1.38}_{-0.12}^{+0.13}$ ${R}_{\oplus }$, an orbital period of ${5.35882}_{-0.00031}^{+0.00030}$ days, and an equilibrium temperature of ${433}_{-27}^{+28}$ K. With radial velocities from the High Accuracy Radial Velocity Planet Searcher, we place a 3σ upper mass limit of 8.4 ${M}_{\oplus }$ on the planet. LTT 1445Ab provides one of the best opportunities to date for the spectroscopic study of the atmosphere of a terrestrial world. We also present a detailed characterization of the host stellar system. We use high-resolution spectroscopy and imaging to rule out the presence of any other close stellar or brown dwarf companions. Nineteen years of photometric monitoring of A and BC indicate a moderate amount of variability, in agreement with that observed in the TESS light-curve data. We derive a preliminary astrometric orbit for the BC pair that reveals an edge-on and eccentric configuration. The presence of a transiting planet in this system hints that the entire system may be co-planar, implying that the system may have formed from the early fragmentation of an individual protostellar core.Accepted manuscrip

Does Cataract Surgery Alleviate Poverty? Evidence from a Multi-Centre Intervention Study Conducted in Kenya, the Philippines and Bangladesh

BACKGROUND: Poverty and blindness are believed to be intimately linked, but empirical data supporting this purported relationship are sparse. The objective of this study is to assess whether there is a reduction in poverty after cataract surgery among visually impaired cases. METHODOLOGY/PRINCIPAL FINDINGS: A multi-centre intervention study was conducted in three countries (Kenya, Philippines, Bangladesh). Poverty data (household per capita expenditure--PCE, asset ownership and self-rated wealth) were collected from cases aged ≥50 years who were visually impaired due to cataract (visual acuity<6/24 in the better eye) and age-sex matched controls with normal vision. Cases were offered free/subsidised cataract surgery. Approximately one year later participants were re-interviewed about poverty. 466 cases and 436 controls were examined at both baseline and follow-up (Follow up rate: 78% for cases, 81% for controls), of which 263 cases had undergone cataract surgery ("operated cases"). At baseline, operated cases were poorer compared to controls in terms of PCE (Kenya: $22 versus £35 p = 0.02, Bangladesh:$16 vs $24 p = 0.004, Philippines:$24 vs 32 p = 0.0007), assets and self-rated wealth. By follow-up PCE had increased significantly among operated cases in each of the three settings to the level of controls (Kenya: $30 versus £36 p = 0.49, Bangladesh:$23 vs $23 p = 0.20, Philippines:$45 vs $36 p = 0.68). There were smaller increases in self-rated wealth and no changes in assets. Changes in PCE were apparent in different socio-demographic and ocular groups. The largest PCE increases were apparent among the cases that were poorest at baseline. CONCLUSIONS/SIGNIFICANCE: This study showed that cataract surgery can contribute to poverty alleviation, particularly among the most vulnerable members of society. This study highlights the need for increased provision of cataract surgery to poor people and shows that a focus on blindness may help to alleviate poverty and achieve the Millennium Development Goals

Whole Genome Sequencing Reveals Local Transmission Patterns of Mycobacterium bovis in Sympatric Cattle and Badger Populations

Whole genome sequencing (WGS) technology holds great promise as a tool for the forensic epidemiology of bacterial pathogens. It is likely to be particularly useful for studying the transmission dynamics of an observed epidemic involving a largely unsampled &lsquo;reservoir' host, as for bovine tuberculosis (bTB) in British and Irish cattle and badgers. BTB is caused by Mycobacterium bovis, a member of the M. tuberculosis complex that also includes the aetiological agent for human TB. In this study, we identified a spatio-temporally linked group of 26 cattle and 4 badgers infected with the same Variable Number Tandem Repeat (VNTR) type of M. bovis. Single-nucleotide polymorphisms (SNPs) between sequences identified differences that were consistent with bacterial lineages being persistent on or near farms for several years, despite multiple clear whole herd tests in the interim. Comparing WGS data to mathematical models showed good correlations between genetic divergence and spatial distance, but poor correspondence to the network of cattle movements or within-herd contacts. Badger isolates showed between zero and four SNP differences from the nearest cattle isolate, providing evidence for recent transmissions between the two hosts. This is the first direct genetic evidence of M. bovis persistence on farms over multiple outbreaks with a continued, ongoing interaction with local badgers. However, despite unprecedented resolution, directionality of transmission cannot be inferred at this stage. Despite the often notoriously long timescales between time of infection and time of sampling for TB, our results suggest that WGS data alone can provide insights into TB epidemiology even where detailed contact data are not available, and that more extensive sampling and analysis will allow for quantification of the extent and direction of transmission between cattle and badgers

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Preclinical and clinical biomarker studies of CT1812:A novel approach to Alzheimer's disease modification

INTRODUCTION: Amyloid beta (Aβ) oligomers are one of the most toxic structural forms of the Aβ protein and are hypothesized to cause synaptotoxicity and memory failure as they build up in Alzheimer’s disease (AD) patients’ brain tissue. We previously demonstrated that antagonists of the sigma-2 receptor complex effectively block Aβ oligomer toxicity. CT1812 is an orally bioavailable, brain penetrant small molecule antagonist of the sigma-2 receptor complex that appears safe and well tolerated in healthy elderly volunteers. We tested CT1812’s effect on Aβ oligomer pathobiology in preclinical AD models and evaluated CT1812’s impact on cerebrospinal fluid (CSF) protein biomarkers in mild to moderate AD patients in a clinical trial (ClinicalTrials.gov NCT02907567). METHODS: Experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer binding to synapses in vitro, to human AD patient post mortem brain tissue ex vivo, and in living APP(Swe)/PS1dE9 transgenic mice in vivo. Additional experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer-induced deficits in membrane trafficking rate, synapse number, and protein expression in mature hippocampal/cortical neurons in vitro. The impact of CT1812 on cognitive function was measured in transgenic Thy1 huAPP(Swe/Lnd+) and wild-type littermates. A multicenter, double-blind, placebo-controlled parallel group trial was performed to evaluate the safety, tolerability, and impact on protein biomarker expression of CT1812 or placebo given once daily for 28 days to AD patients (Mini-Mental State Examination 18–26). CSF protein expression was measured by liquid chromatography with tandem mass spectrometry or enzyme-linked immunosorbent assay in samples drawn prior to dosing (Day 0) and at end of dosing (Day 28) and compared within each patient and between pooled treated versus placebo-treated dosing groups. RESULTS: CT1812 significantly and dose-dependently displaced Aβ oligomers bound to synaptic receptors in three independent preclinical models of AD, facilitated oligomer clearance into the CSF, increased synaptic number and protein expression in neurons, and improved cognitive performance in transgenic mice. CT1812 significantly increased CSF concentrations of Aβ oligomers in AD patient CSF, reduced concentrations of synaptic proteins and phosphorylated tau fragments, and reversed expression of many AD-related proteins dysregulated in CSF. DISCUSSION: These preclinical studies demonstrate the novel disease-modifying mechanism of action of CT1812 against AD and Aβ oligomers. The clinical results are consistent with preclinical data and provide evidence of target engagement and impact on fundamental disease-related signaling pathways in AD patients, supporting further development of CT1812