A One Medicine Mission for an Effective Rabies Therapy.

Despite the disease's long history, little progress has been made toward a treatment for rabies. The prognosis for patient recovery remains dire. For any prospect of survival, patients require aggressive critical care, which physicians in rabies endemic areas may be reluctant or unable to provide given the cost, clinical expertise required, and uncertain outcome. Systematic clinical research into combination therapies is further hampered by sporadic occurrence of cases. In this Perspective, we examine the case for a One Medicine approach to accelerate development of an effective therapy for rabies through the veterinary care and investigational treatment of naturally infected dogs in appropriate circumstances. We review the pathogenesis of rabies virus in humans and dogs, including recent advances in our understanding of the molecular basis for the severe neurological dysfunction. We propose that four categories of disease process need to be managed in patients: viral propagation, neuronal degeneration, inflammation and systemic compromise. Compassionate critical care and investigational treatment of naturally infected dogs receiving supportive therapy that mimics the human clinical scenario could increase opportunities to study combination therapies that address these processes, and to identify biomarkers for prognosis and therapeutic response. We discuss the safety and ethics of this approach, and introduce the Canine Rabies Treatment Initiative, a non-profit organization with the mission to apply a One Medicine approach to the investigation of diagnostic, prognostic, and therapeutic options for rabies in naturally infected dogs, to accelerate transformation of rabies into a treatable disease for all patients.

Computed Tomography Determined Changes in Position of the Hepatobiliary and Gastrointestinal Systems after CO2 Insufflation to Determine Optimal Positioning for Abdominal Laparoscopy.

OBJECTIVE: To evaluate changes in body position and effect of CO2 insufflation on the hepatobiliary and gastrointestinal systems using computed tomography (CT) to determine optimal laparoscopic approach. STUDY DESIGN: Experimental study. ANIMALS: Healthy intact female Beagles (n = 6) of similar age, weight, and body condition score. METHODS: Urinalysis, peripheral blood smear, and abdominal ultrasonography were performed to determine dog health. A series of pre insufflation (PrI) CT scans in ventrodorsal routine (VDR), ventrodorsal Trendelenburg (VDT), left lateral (LL), and right lateral (RL) recumbency were performed before and after abdominal insufflation (PoI) with CO2 (10-14 mm Hg). Pre-determined measurements were made on PrI and PoI scans and differences compared. RESULTS: Liver position was affected by body position and under gravitational influence moved to the dependent part of the abdominal cavity. The gallbladder was best exposed in LL. Stomach position was not significantly changed after insufflation. Different areas of small intestine were dependent on gravitational effects. The pancreas maintained a similar position after insufflation. CONCLUSIONS: VDR was the ideal position for all laparoscopic procedures of the liver. The LL position could be used for surgery of the gallbladder but likely provides poor exposure to the rest of the liver. In approaching the stomach and intestines, the area of interest should be used to determine the best position.

Seasonal patterns of body temperature daily rhythms in group-living Cape ground squirrels Xerus inauris.

Organisms respond to cyclical environmental conditions by entraining their endogenous biological rhythms. Such physiological responses are expected to be substantial for species inhabiting arid environments which incur large variations in daily and seasonal ambient temperature (T(a)). We measured core body temperature (T(b)) daily rhythms of Cape ground squirrels Xerus inauris inhabiting an area of Kalahari grassland for six months from the Austral winter through to the summer. Squirrels inhabited two different areas: an exposed flood plain and a nearby wooded, shady area, and occurred in different social group sizes, defined by the number of individuals that shared a sleeping burrow. Of a suite of environmental variables measured, maximal daily T(a) provided the greatest explanatory power for mean T(b) whereas sunrise had greatest power for T(b) acrophase. There were significant changes in mean T(b) and T(b) acrophase over time with mean T(b) increasing and T(b) acrophase becoming earlier as the season progressed. Squirrels also emerged from their burrows earlier and returned to them later over the measurement period. Greater increases in T(b), sometimes in excess of 5°C, were noted during the first hour post emergence, after which T(b) remained relatively constant. This is consistent with observations that squirrels entered their burrows during the day to 'offload' heat. In addition, greater T(b) amplitude values were noted in individuals inhabiting the flood plain compared with the woodland suggesting that squirrels dealt with increased environmental variability by attempting to reduce their T(a)-T(b) gradient. Finally, there were significant effects of age and group size on T(b) with a lower and less variable T(b) in younger individuals and those from larger group sizes. These data indicate that Cape ground squirrels have a labile T(b) which is sensitive to a number of abiotic and biotic factors and which enables them to be active in a harsh and variable environment.

Bacterial colonization of intravenous catheters in young dogs suspected to have parvoviral enteritis.

OBJECTIVE: To determine the prevalence of bacterial colonization of IV catheters among young dogs suspected to have parvoviral enteritis, to identify the organisms responsible for catheter colonization, and to determine the antimicrobial susceptibility of organisms that were obtained. DESIGN: Case series. ANIMALS: 100 dogs. PROCEDURE: Catheters were aseptically removed when fluid therapy was discontinued, the catheter was replaced, or the dog died. The distal tip of the catheter was cut off, split open, and vortexed with sterile saline (0.9% NaCl) solution. The saline solution was plated on culture plates, which were then incubated and examined for bacterial growth every 24 hours for 72 hours. All bacteria cultured were identified, and antimicrobial susceptibility was determined. RESULTS: Bacteria were isolated from 22 catheters. Most bacteria that were isolated were of gastrointestinal tract or environmental origin (Serratia odorifera, S. liquefaciens, S. marcescens, Acinobacter anitratus, Citrobacter freundii, Klebsiella pneumoniae, K. oxytoca, Escherichia coli, Enterobacter spp). Only 2 gram-positive organisms were isolated (Staphylococcus intermedius and Streptococcus spp). High percentages of organisms were resistant to penicillin, lincomycin, cloxacillin, erythromycin, and cephalexin. Percentages of organisms resistant to amikacin, enrofloxacin, chloramphenicol, potentiated sulfonamides, and amoxicillin-clavulanic acid were low. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that IV catheters may be colonized with bacteria in 22% of young dogs suspected to have parvovirus infection.