This article outlines a pathway to develop the business case for One Health. It describes the origin and development of One Health and then identifies five potential areas where One Health can add value and reduce costs. These are: (1) sharing health resources between the medical and veterinary sectors; (2) controlling zoonoses in animal reservoirs; (3) early detection and response to emerging diseases; (4) prevention of pandemics; and (5) generating insights and adding value to health research and development. Examples are given for each category along with preliminary estimates of the potential savings from adopting the One Health approach. The literature reviewed suggests that one dollar invested in One Health can generate five dollars worth of benefits and a global investment of US$25 billion over 10 years could generate benefits worth at least US$125 billion. Conservation implications: the time has come to make the bigger case for massive investment in One Health in order to transform the management of neglected and emerging zoonoses and to save the lives of millions of people and hundreds of millions of animals whose production supports and nourishes billions of impoverished people per annum.

Milk production using local cattle breed-types is an age-old practice in Malawi. Although dairy farming is becoming more common as a result of the increasing population and demand for milk and milk products, there is limited knowledge of the farmers’ awareness of zoonotic disease risks, their preventative practices and the disease burden in animals. This study determined dairy farmers’ general knowledge of zoonoses, assessed their risks for infection with zoonotic bovine tuberculosis (bTB) and brucellosis, and evaluated farm practices to prevent disease transmission. A questionnaire was drawn up and administered by the authors. It was used to collect information about the knowledge and preventive practices of 140 out of 684 registered dairy farmers at Mzuzu Agricultural Development Division, northern Malawi. During a second visit to 60 out of the 140 farms, a total of 156 and 95 cattle were tested for brucellosis and tuberculosis, respectively. Most farmers (77.1%) knew or had heard of zoonotic diseases, whilst 75.0% correctly named at least one zoonotic disease. More survey participants named tuberculosis as a zoonotic disease compared to brucellosis (74.3% versus 2.9%). The most commonly named means of transmission were milk (67.0%) and meat (56.0%). Almost all survey participants (96.4%) practised at least one farm activity that could lead to potential transmission of brucellosis or bTB, including sale (67.0%) and consumption (34.0%) of unpasteurised milk. Antibodies against brucellosis were found in 12 cattle (7.7%), whilst one animal (1.1%) reacted to the tuberculin skin test. General knowledge about possible transmission of diseases between humans and animals was high, although most farmers practised risk behaviours that could potentially expose the public to milk-borne zoonotic diseases such as brucellosis and bTB. Furthermore, some animals had positive results for brucellosis and tuberculosis tests. Therefore, improvement of zoonotic disease prevention programmes, as well as further investigation into the prevalence and risk factors for zoonoses, is recommended.

International audience | To determine pharmacodynamic cutoffs with pharmacokinetic-pharmacodynamic principles and Monte Carlo simulation (MCS) for use of amoxicillin in pigs to set interpretive criteria for antimicrobial susceptibility testing. 191 plasma disposition curves of amoxicillin obtained from 21 IV, 104 IM, and 66 PO administrations corresponding to 2,098 plasma concentrations. A population model of amoxicillin disposition in pigs was developed for PO and IM administration. The MCS method was then used to determine, for various dosage regimens, the proportion of pigs achieving plasma amoxicillin concentrations greater than a selection of possible minimal inhibitory concentrations (MICs) ranging from 0.0625 to 4 mg/L for at least 40% of a 24-hour period. A target attainment rate (TAR) of 90% was never achieved with the breakpoint recommended by the Clinical and Laboratory Standards Institute (0.5 mg/L) when the usual recommended dosage (20 mg/kg/d) was used. Only by dividing the orally administered daily dose into 12-hour administration intervals was a TAR > 90% achieved when the total dose was at least 40 mg/kg for a pathogen having an MIC ≤ 0.0625 mg/L. For the IM route, the TAR of 90% could only be achieved for MICs of 0.0625 and 0.125 mg/L with the use of 15 and 30 mg/kg doses, respectively. Population kinetics and MCS are required to determine robust species-specific interpretive criteria (susceptible, intermediate, and resistant classifications) for antimicrobial susceptibility testing breakpoints (taking into account interanimal variability).

The aim of this study was to develop and examine a model of apoptosis and necrosis of hepatocytes induced by a damaging factor - adriamycin, correlating time after its administration with cell death type, and to investigate the localisation within the liver acinus of hepatocytes dying in these two ways. The results obtained in the present and previous studies were compared in order to make a map of cell death localisation in the liver acinus, showing the effect of time in action and dose of adriamycin. The experiment was performed on 32 female Wistar rats, divided into four groups: I and II - experimental, and III and IV - control. Adriamycin (3 mg/kg b.w.) was administered intraperitoneally to rats in groups I and II, and the rats were decapitated after four (group I) and eight (group II) weeks. Animals in control groups III and IV were given 0.5 mL of 0.9% NaCl solution, and decapitated after four and eight weeks respectively. Sections of the liver were examined with a three-stage immunohistochemical method. This method allowed to examine hepatocytes qualitatively and quantitatively for the presence of proteins involved in three types of apoptosis: induced by the mitochondrial pathway (caspase 3, 9), the intrinsic pathway related to endoplasmic reticulum stress (caspase 3, 12), and the extrinsic pathway (caspase 3, 8). One of the inflammatory markers, caspase 1, was also examined. The zonal localisation of all three types of apoptosis was assessed in the liver tissue. More oxidated hepatocytes indicated only signs of the internal mitochondrial pathway, whereas less oxidated hepatocytes induced the internal reticular pathway and the external apoptotic pathway. The period between adriamycin administration and hepatic cell investigation was a main factor of the process. A longer period post insult resulted in a more pronounced effect of the activation of apoptosis. Sections explored eight weeks after treatment with different doses of the drug (3 and 5 mg/kg in the previous study) showed a similar intensity of apoptosis.

Objective-To evaluate antinociceptive effects and pharmacokinetics of butorphanol tartrate after IM administration to American kestrels (Falco sparverius). Animals-Fifteen 2- to 3-year-old American kestrels (6 males and 9 females). Procedures-Butorphanol (1, 3, and 6 mg/kg) and saline (0.9% NaCl) solution were administered IM to birds in a crossover experimental design. Agitation-sedation scores and foot withdrawal response to a thermal stimulus were determined 30 to 60 minutes before (baseline) and 0.5, 1.5, 3, and 6 hours after treatment. For the pharmacokinetic analysis, butorphanol (6 mg/kg, IM) was administered in the pectoral muscles of each of 12 birds. Results-In male kestrels, butorphanol did not significantly increase thermal thresholds for foot withdrawal, compared with results for saline solution administration. However, at 1.5 hours after administration of 6 mg of butorphanol/kg, the thermal threshold was significantly decreased, compared with the baseline value. Foot withdrawal threshold for female kestrels after butorphanol administration did not differ significantly from that after saline solution administration. However, compared with the baseline value, withdrawal threshold was significantly increased for 1 mg/kg at 0.5 and 6 hours, 3 mg/kg at 6 hours, and 6 mg/kg at 3 hours. There were no significant differences in mean sedation-agitation scores, except for males at 1.5 hours after administration of 6 mg/kg. Conclusion and Clinical Relevance-Butorphanol did not cause thermal antinociception suggestive of analgesia in American kestrels. Sex-dependent responses were identified. Further studies are needed to evaluate the analgesic effects of butorphanol in raptors.

Objective-To determine the pharmacokinetics of ceftiofur crystalline-free acid (CCFA) following SC administration of a single dose to sheep. Animals-9 healthy adult female Suffolk-crossbred sheep. Procedures-Each sheep was administered 6.6 mg of CCFA/kg, SC, in the cervical region once. Serial blood samples were collected at predetermined intervals for 14 days. Serum concentration of ceftiofur free-acid equivalents (CFAE) was determined by high-performance liquid chromatography. Pharmacokinetic parameters were determined by compartmental and noncompartmental methods. Results-Pharmacokinetics for CCFA following SC administration in sheep was best described with a 1-compartment model. Mean +/- SD area under the concentration-time curve from time 0 to infinity, peak serum concentration, and time to peak serum concentration were 206.6 +/- 24.8 μ•h/mL, 2.4 +/- 0.5 μg/mL, and 23.1 +/- 10.1 h, respectively. Serum CFAE concentrations ≥ 1 μg/mL (the target serum CFAE concentration for treatment of disease caused by Mannheimia haemolytica and Pasteurella multocida) were maintained for 2.6 to 4.9 days. No significant adverse reactions to CCFA administration were observed. Conclusions and Clinical Relevance-Results indicated that adequate therapeutic serum concentrations of CFAE for treatment of disease caused by M haemolytica and P multocida were achieved in sheep following SC administration of a single dose (6.6 mg/kg) of CCFA. Thus, CCFA might be useful for the treatment of common respiratory tract pathogens in sheep.

Objective-To determine effects of ambient temperature, relative humidity, wind speed, relative barometric pressure, and temperature-humidity index (THI) on nasal submucosal and rectal temperatures in cattle during extreme summer conditions. Animals-20 black crossbred beef heifers (mean body weight, 217.8 kg). Procedures-Nasal submucosal and rectal temperatures were monitored every 2 hours for 24 hours on 3 nonconsecutive days when ambient temperature was forecasted to exceed 32.2°C. Ambient temperature, relative humidity, wind speed, and relative barometric pressure were continuously monitored at a remote weather station located at the research facility. The THI was calculated and used in the livestock weather safety index (LWSI). Relationships between nasal submucosal or rectal temperature and weather variables were evaluated. Results-Nasal submucosal and rectal temperatures were related to all weather variables monitored. A positive relationship was determined for ambient temperature and THI with both nasal submucosal and rectal temperatures. A negative relationship was evident for nasal submucosal and rectal temperature with relative humidity, wind speed, and relative barometric pressure. Nasal submucosal and rectal temperatures increased with increasing severity of LWSI category. Conclusions and Clinical Relevance-Effects of environmental conditions on thermoregulation in calves exposed to extreme heat were detected. The positive relationship between nasal submucosal temperature and ambient temperature and THI raised concerns about the efficacy of intranasal administration of temperature-sensitive modified-live virus vaccines during periods of extreme heat. Environmental conditions must be considered when rectal temperature is used as a diagnostic tool for identifying morbid cattle.

Objective-To evaluate the cardiorespiratory effects of IV administration of propofol (4 mg/kg), ketamine hydrochloride and propofol (2 mg/kg each; K-P), or ketamine hydrochloride (5 mg/kg) and diazepam (0.2 mg/kg; K-D) before and after induction of anesthesia (IoA) in dogs sedated with acepromazine maleate and oxymorphone hydrochloride. Animals-10 healthy adult Beagles. Procedures-Each dog was randomly allocated to receive 2 of 3 treatments (1-week interval). For instrumentation prior to each treatment, each dog was anesthetized with isoflurane. After full recovery, acepromazine (0.02 mg/kg) and oxymorphone (0.05 mg/kg) were administered IV. Fifteen minutes later (before IoA), each dog received treatment IV with propofol, K-P, or K-D. Cardiorespiratory and arterial blood gas variables were assessed before, immediately after, and 5 minutes after IoA. Results-Compared with findings before IoA, dogs receiving the K-P or K-D treatment had increased cardiac output, oxygen delivery, and heart rate 5 minutes after IoA; K-P administration did not change mean arterial blood pressure or stroke volume and decreased systemic vascular resistance. Propofol decreased mean arterial blood pressure and systemic vascular resistance immediately after IoA but did not change heart rate, cardiac output, or oxygen delivery. All treatments caused some degree of apnea, hypoventilation, and hypoxemia (Pao2 < 80 mm Hg). Conclusions and Clinical Relevance-In dogs, K-P treatment maintained mean arterial blood pressure better than propofol alone and increased heart rate, cardiac output, or oxygen delivery, as did the K-D treatment. Supplemental 100% oxygen should be provided during IoA with all 3 treatments.

Objective—To develop a flow cytometric assay to quantify platelet-derived microparticles (PMPs) in equine whole blood and plasma. Sample—Citrate-anticoagulated whole blood from 30 healthy adult horses. Procedures—Platelet-poor plasma (PPP) was prepared from fresh whole blood by sequential low-speed centrifugation (twice at 2,500 × g). Samples of fresh whole blood and PPP were removed and stored at 4° and 24°C for 24 hours. Platelet-derived microparticles were characterized in fresh and stored samples on the basis of the forward scatter threshold (log forward scatter < 10(1)) and labeling with annexin V (indicating externalized phosphatidylserine) and CD61 (a constitutive platelet receptor). A fluorescent bead–calibrated flow cytometric assay was used to determine microparticle counts. Platelet counts, prothrombin time, and activated partial thromboplastin time were measured in fresh samples. Results—Significantly more PMPs were detected in fresh whole blood (median, 3,062 PMPs/μL; range, 954 to 13,531 PMPs/μL) than in fresh PPP (median, 247 PMPs/μL; range, 104 to 918 PMPs/μL). Storage at either temperature had no significant effect on PMP counts for whole blood or PPP. No significant correlation was observed between PMP counts and platelet counts in fresh whole blood or PPP or between PMP counts and clotting times in fresh PPP. Conclusions and Clinical Relevance—Results indicated that the described PMP protocol can be readily used to quantify PMPs in equine blood and plasma via flow cytometry. Quantification can be performed in fresh PPP or whole blood or samples stored refrigerated or at room temperature for 24 hours.