Pharmacokinetics and in vitro effects of imipramine hydrochloride on the vas deferens in cattle

This project was divided into two studies. The first investigated the pharmacokinetics of imipramine hydrochloride (IMI) in bulls. IMI was administered intravenously to three bulls (600-705.5 kg) at a dose of 2mg/kg body weight (BW). Intravenous plasma concentrations of IMI over time were determined by fluorescence polarization immunoassay (FPIA). IMI plasma concentration versus time profile was best described by a two compartmental open model with first-order rate constants. IMI distributed rapidly, (t½a) at 7.2 ± 4.2 min, exhibited a very large apparent steady state volume of distribution (Vdss) of 4.2 ± 0.9 l/kg BW, had a very short terminal elimination half-life (t½b) of 140 ± 15 min and showed a rapid total body clearance (Cl) of 22.7 ± 7 ml/min/kg. Both IMI and the pharmacologically active metabolite, desipramine was negligible in serum at 24 hours. All three bulls treated with IMI showed pronounced central nervous system signs immediately post injection. Signs of generalised weakness and ataxia were evident. All CNS signs dissipated 15-20 minutes post injection and should therefore not influence the treatment interval. An interval of at least 23 hours between repeat treatments of IMI, representing a period of at least 10 half-lives, is recommended. The dose of 2 mg/kg BW used in this study was similar to that routinely used in stallions without fatal side effects. One of the three bulls exhibited spontaneous emission and ejaculation with this dose. The second study investigated the effects of IMI on ampullar strips of bulls in organ baths. Vasa deferentia were collected from 16 freshly slaughtered post-puberal bulls of various breeds. Longitudinal ampullar strips were prepared and placed into 20 ml modified Krebs bicarbonate solution, aerated with a mixture of 02 (95 %) and CO2 (5 %) in water-jacketed organ baths. The effect on the smooth muscle tissue of noradrenaline (NA) alone, NA in combination with IMI and IMI alone was evaluated. NA alone consistently produced dose-dependant smooth muscle tissue contractions. IMI doses equivalent to 0.1 mg to <1 mg/kg bwe partially blocked NA stimulating effects. Amplitude of rhythmic contractions increased while contraction frequency decreased at this level. This study supports the adrenergic potentiating effects of IMI at doses of 0.05-0.2 mg/kg bwe with higher doses having paradoxical effects. Doses of IMI < 2 mg/kg bwe completely blocked NA effects. Tissue response to NA, after IMI blockade, started to recover 146-186 minutes after application of IMI at <2 mg/kg bwe. In the absence of NA, IMI had no effect on smooth muscle activity. The time to an IMI effect on NA initiated smooth muscle activity was 8 minutes. On the basis of the results of this in vitro study, we propose that IMI can be used to enhance semen collection by means of electro-stimulation in domestic bulls and immobilised wildlife species such as buffalo, provided that the correct dose is used.Dissertation (MMedVet (Gyn))--University of Pretoria, 2005.Production Animal Studiesunrestricte

Factors affecting the use of biosecurity measures for the protection of ruminant livestock and farm workers against infectious diseases in central South Africa

Biosecurity measures have been introduced to limit economic losses and zoonotic exposures to humans by preventing and controlling animal diseases. However, they are implemented on individual farms with varying frequency. The goal of this study was to evaluate which biosecurity measures were used by farmers to prevent infectious diseases in ruminant livestock and to identify factors that influenced these decisions. We conducted a survey in 264 ruminant livestock farmers in a 40,000 km2 area in the Free State and Northern Cape provinces of South Africa. We used descriptive statistics, to characterize biosecurity measures and farm attributes, then multivariable binomial regression to assess the strength of the association between the attributes and the implementation of biosecurity measures including property fencing, separate equipment use on different species, separate rearing of species, isolation of sick animals, isolation of pregnant animals, quarantine of new animals, animal transport cleaning, vaccination, tick control and insect control. Ninety-nine percent of farmers reported using at least one of the 10 biosecurity measures investigated (median [M]: 6; range: 0–10). The most frequently used biosecurity measures were tick control (81%, 214 out of 264), vaccination (80%, 211 out of 264) and isolation of sick animals (72%, 190 out of 264). More biosecurity measures were used on farms with 65–282 animals (M: 6; odds ratio [OR]: 1.52) or farms with 283–12,030 animals (M: 7; OR: 1.87) than on farms with fewer than 65 animals (M: 4). Furthermore, farmers who kept two animal species (M: 7; OR: 1.41) or three or more species (M: 7) used more biosecurity measures than single-species operations (M: 4). Farmers with privately owned land used more biosecurity measures (M: 6; OR: 1.51) than those grazing their animals on communal land (M: 3.5). Farms that reported previous Rift Valley fever (RVF) outbreaks used more biosecurity measures (M: 7; OR: 1.25) compared with farms without RVF reports (M: 6) and those that purchased animals in the 12 months prior to the survey (M: 7; OR: 1.19) compared with those that did not (M: 6). When introducing new animals into their herds (n = 122), most farmers used fewer biosecurity measures than they did for their existing herd: 34% (41 out of 122) used multiple biosecurity measures like those of vaccination, tick control, quarantine or antibiotic use, whereas 36% (44 out of 122) used only one and 30% (37 out of 122) used none. Certain farm features, primarily those related to size and commercialization, were associated with more frequent use of biosecurity measures. Given the variation in the application of biosecurity measures, more awareness and technical assistance are needed to support the implementation of a biosecurity management plan appropriate for the type of farm operation and available resources.DATA AVAILABILITY STATEMENT : The data that support the study's findings and that can be disclosed per IRB protocol are available upon request from EcoHealth Alliance, 520 Eighth Ave Ste 1200, New York, NY 10018, from Melinda K. Rostal ([email protected]).The project depicted is sponsored by the U.S. Department of Defense, Defense Threat Reduction Agency.http://wileyonlinelibrary.com/journal/tbedhj2022Production Animal Studie

Farm-level risk factors of increased abortion and mortality in domestic ruminants during the 2010 Rift Valley fever outbreak in central South Africa

(1) Background: Rift Valley fever (RVF) outbreaks in domestic ruminants have severe socio-economic impacts. Climate-based continental predictions providing early warnings to regions at risk for RVF outbreaks are not of a high enough resolution for ruminant owners to assess their individual risk. (2) Methods: We analyzed risk factors for RVF occurrence and severity at the farm level using the number of domestic ruminant deaths and abortions reported by farmers in central South Africa during the 2010 RVF outbreaks using a Bayesian multinomial hurdle framework. (3) Results: We found strong support that the proportion of days with precipitation, the number of water sources, and the proportion of goats in the herd were positively associated with increased severity of RVF (the numbers of deaths and abortions). We did not find an association between any risk factors and whether RVF was reported on farms. (4) Conclusions: At the farm level we identified risk factors of RVF severity; however, there was little support for risk factors of RVF occurrence. The identification of farm-level risk factors for Rift Valley fever virus (RVFV) occurrence would support and potentially improve current prediction methods and would provide animal owners with critical information needed in order to assess their herd’s risk of RVFV infection

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Benefits of a one health approach: An example using Rift Valley fever

One Health has been promoted by international institutions as a framework to improve public health outcomes. Despite strong overall interest in One Health, country-, local- and project-level implementation remains limited, likely due to the lack of pragmatic and tested operational methods for implementation and metrics for evaluation. Here we use Rift Valley fever virus as an example to demonstrate the value of using a One Health approach for both scientific and resources advantages. We demonstrate that coordinated, a priori investigations between One Health sectors can yield higher statistical power to elucidate important public health relationships as compared to siloed investigations and post-hoc analyses. Likewise, we demonstrate that across a project or multi-ministry health study a One Health approach can result in improved resource efficiency, with resultant cost-savings (35% in the presented case). The results of these analyses demonstrate that One Health approaches can be directly and tangibly applied to health investigations. Keywords: One health, Study design, Resource efficiency, Public health, Epidemiology, Outbreak investigatio

Seroprevalence and factors associated with seropositivity to Rift Valley fever virus in livestock

ObjectiveThe objective of this study was to estimate the prevalence of antibodies to RVFV in domestic cattle, sheep, and goats in a study area in the central interior of South Africa, and to identify factors associated with seropositivity.IntroductionRift Valley fever (RVF) is a mosquito-borne viral zoonosis. This study aimed to estimate the prevalence of antibodies to RVF virus (RVFV) in cattle, sheep, and goats in South Africa, near the 2010-2011 outbreak epicenter and identify factors associated with seropositivity.MethodsA cross-sectional study was conducted during 2015-2016 within a ~40,000 km2 region between Bloemfontein and Kimberley. Farms were selected using random geographic points with probability proportional to the density of livestock-owning households. Livestock were randomly sampled from the farm closest to each selected point. A questionnaire was used to collect information concerning animal, management, and environmental factors. Sera samples were screened for RVFV antibodies using IgG inhibition ELISA. Data were analyzed using multilevel logistic regression models.ResultsOn 234 farms, 3,049 animals (977 cattle, 1,549 sheep and 523 goats) were sampled. Estimated RVF seroprevalence, adjusted for clustering and sampling weights, was 42.9% (95% CI: 35.7-50.4%) in cattle, 28.0% (95% CI: 21.3-35.4%) in sheep and 9.3% (95% CI: 5.8-13.9%) in goats. Compared to animals &lt;2y of age, seroprevalence was higher in animals 2-4y (OR=2.8, P&lt;0.001) and &gt;4y old (OR=17.0, P&lt;0.001). Seroprevalence was also higher on private vs. communal land (OR=4.3, P=0.001) and was positively associated with the presence of perennial rivers (OR=1.6, P=0.03) and seasonal pans (OR=1.8, P=0.005) on the farm. The odds of seropositivity was higher in domestic ruminants recently vaccinated between 2014-2015 (OR=2.1, P=0.007) compared to those never vaccinated.ConclusionsThe presence of IgG antibody against RVFV among domestic ruminants, born after the most recent outbreak (&lt;4y category), and association with known RVF risk factors, indicates the possibility that viral circulation has occurred during the inter-epidemic period

Factors affecting the use of biosecurity measures for the protection of ruminant livestock and farm workers against infectious diseases in central South Africa

Background: Biosecurity measures have been introduced to limit economic losses and zoonotic exposures to humans by preventing and controlling animal diseases. However, they are implemented on individual farms with varying frequency. Objective: The goal of this study was to evaluate which biosecurity measures were used by farmers to prevent infectious diseases in ruminant livestock and to identify factors that influenced these decisions. Method and Materials: We conducted a survey in 264 ruminant livestock farmers in a 40000km2 area in the Free State and Northern Cape provinces of South Africa. We used descriptive statistics, to characterize biosecurity measures and farm attributes, then multivariable binomial regression to assess the strength of the association between the attributes and the implementation of biosecurity measures including property fencing, separate equipment use on different species, separate rearing of species, isolation of sick animals, isolation of pregnant animals, quarantine of new animals, animal transport cleaning, vaccination, tick control and insect control. Results: Ninety-nine percent of farmers reported using at least one of the ten biosecurity measures investigated, (median [M]: 6; range: 0–10). The most frequently used biosecurity measures were tick control (81%, 214/264), vaccination (80%, 211/264) and isolation of sick animals (72%, 190/264). More biosecurity measures were used on farms with 65–282 animals (M:6; odds ratio [OR]:1.52) or farms with 283–12030 animals (M:7; OR:1.87) than on farms with fewer than 65 animals (M:4). Furthermore, farmers who kept two animal species (M:7; OR:1.41) or three or more species (M:7) used more biosecurity measures than single-species operations (M:4). Farmers with privately owned land used more biosecurity measures (M:6; OR:1.51) than those grazing their animals on communal land (M:3.5). Farms that reported previous Rift Valley fever (RVF) outbreaks used more biosecurity measures (M:7; OR:1.25) compared to farms without RVF reports (M:6) and those that purchased animals in the 12 months prior to the survey (M:7; OR:1.19) compared to those that did not (M:6).When introducing new animals into their herds (n = 122), most farmers used fewer biosecurity measures than they did for their existing herd: 34% (41/122) used multiple biosecurity measures like those of vaccination, tick control, quarantine or antibiotic use, whereas 36% (44/122) used only one and 30% (37/122) used none. Discussion and Recommendations: Certain farm features, primarily those related to size and commercialization were associated with more frequent use of biosecurity measures. Given the variation in the application of biosecurity measures, more awareness and technical assistance are needed to support the implementation of a biosecurity management plan appropriate for the type of farm operation and available resources

Evaluation of a novel liquid stabilised peste des petits ruminants vaccine: Safety and immunogenic efficacy in sheep and goats in the field in Jordan

A novel liquid stabiliser was tested with the Nigeria 75/1 Peste des Petit Ruminants (PPR) vaccine over two field studies carried out in sheep and goats. PPR seronegative sheep and goats were selected from farms surrounding Amman, Jordan and were vaccinated with either a stabilised liquid PPR vaccine that had been formulated 3 months prior to use and stored at 2–8 °C or a reconstituted lyophilised PPRV vaccine reconstituted on the day of vaccination. Sera were taken immediately before vaccination and at approximately 1.5, 3 and 6 months following vaccination, then subsequently tested using IDVet ID Screen® PPR competition ELISA and Serum Neutralisation tests to determine the presence of PPRV anti-N antibodies and neutralising antibodies, respectively. It was observed that the liquid-stabilised vaccine was able to provide comparable antibody responses in both species to those induced by the lyophilized vaccine. The ability to store liquid stabilised PPRV vaccine for field use would positively impact PPRV eradication efforts