Mathematical modeling and simulation in animal health. Part III: Using nonlinear mixed‐effects to characterize and quantify variability in drug pharmacokinetics

A common feature of human and veterinary pharmacokinetics is the importance of identifying and quantifying the key determinants of between‐patient variability in drug disposition and effects. Some of these attributes are already well known to the field of human pharmacology such as bodyweight, age, or sex, while others are more specific to veterinary medicine, such as species, breed, and social behavior. Identification of these attributes has the potential to allow a better and more tailored use of therapeutic drugs both in companion and food‐producing animals. Nonlinear mixed effects (NLME) have been purposely designed to characterize the sources of variability in drug disposition and response. The NLME approach can be used to explore the impact of population‐associated variables on the relationship between drug administration, systemic exposure, and the levels of drug residues in tissues. The latter, while different from the method used by the US Food and Drug Administration for setting official withdrawal times (WT) can also be beneficial for estimating WT of approved animal drug products when used in an extralabel manner. Finally, NLME can also prove useful to optimize dosing schedules, or to analyze sparse data collected in situations where intensive blood collection is technically challenging, as in small animal species presenting limited blood volume such as poultry and fish.     

Understanding utilitarian and hedonic values determining the demand for rhino horn in Vietnam

We examined utilitarian and hedonic values as motivations for rhino horn use in Vietnam. We also evaluated consumers’ response to consequences of the illegal trade in behavior modification campaigns and the likely outcome of a legalized trade. The most prevalent use was for treatment of hangovers indicating utilitarian values, although difficult to separate from the hedonic value in projecting success in business. A ritualized way of honoring terminally ill relatives represented a hedonic value replacing belief in effective treatment. Demand reduction campaigns need to appropriately reflect all relevant values determining specific uses. The plight of rhino populations, Vietnam’s penal code, and the possible contribution to international crime mattered little to consumers. Horn from wild rhino was preferred over farmed, and respondents would demand more if available in a legalized trade. This suggested that a legalized trade could maintain or even increase demand for poached rhino horn.     

Host selection and establishment of striped mealybug, Ferrisia virgata, on cotton cultivars

The striped mealybug, Ferrisia virgata (Hemiptera: Pseudococcidae), is a polyphagous and cosmopolitan species, which attacks a wide variety of crops, including cotton. Lately, it has been found infesting colored fiber cotton and emerging as an important pest in the Northeast of Brazil. Therefore, this study investigated the effects of colonization, establishment, plant distribution and dispersal of F. virgata on cotton cultivars. Preference experiments were set up in the laboratory and in the greenhouse, in which cultivars were offered simultaneously to nymphs or females and the number of insects on each cultivar was counted after 24 h, 48 h, 22 days and 60 days, respectively. Meanwhile, attack of different plant structures and dispersal were investigated under field conditions. Results showed that F. virgata is able to become established on colored cotton fiber cultivars (BRS Verde, BRS Rubi, and BRS Safira) as well as on white cotton cultivars (BRS 201 and CNPA 7H) without showing any preference among these cultivars. Females produce a large number of offspring to enhance nymph survival and host plant colonization, since the number of first instars successfully established after migration is low (<10%). In addition, its short range dispersal can easily occur from plant to plant. Therefore, strategies to manage F. virgata will be needed to facilitate colored cotton production, especially in organic farms infested by this mealybug species.     

Effect of bupivacaine liposome suspension administered as a local anesthetic block on indicators of pain and distress during and after surgical castration in dairy calves

Castration is a routine procedure performed on beef and dairy operations in the United States. All methods of castration cause behavioral, physiologic, and neuroendocrine changes associated with pain. The American Veterinary Medical Association and the American Association of Bovine Practitioners recommend that anesthesia and analgesia be administered during castration. The objective of this study was to evaluate the effectiveness of bupivacaine liposome suspension, a novel, long-acting, local anesthetic formulation administered as a nerve block at castration. The authors chose to investigate this novel formulation as an alternative to the current industry standards using lidocaine nerve blocks alone or in combination with meloxicam. Thirty male Holstein calves, 16 to 20 wk of age, were enrolled and randomly assigned to one of the four treatment groups prior to surgical castration: 1) bupivacaine liposome suspension block + oral placebo (BUP), 2) lidocaine block + oral placebo (LID), 3) lidocaine block + oral meloxicam (1 mg/kg) (LID + MEL), and 4) saline block + oral placebo (CON). Biomarkers were collected at −24 h and from 0 to 120 h post-castration and included infrared thermography, pressure mat gait analysis, chute defense and behavior scoring (pain and activity), and blood sampling for serum cortisol and prostaglandin E₂ metabolites (PGEMs). Responses were analyzed using repeated measures, with calf nested in treatment as a random effect, and treatment, time, and their interaction designated as fixed effects. The results from pressure mat gait analysis show that the CON had a shorter front limb stance time from baseline (−8.73%; 95% confidence interval [CI]: −24.84% to 7.37%) compared with BUP and LID + MEL (>5.70%; 95% CI: −22.91% to 23.79%) (P < 0.03). The CON tended to have an increase in front limb force from baseline (6.31%; 95% CI: −1.79% to 14.41%) compared with BUP, LID, and LID + MEL (<−5.06%; 95% CI: −14.22% to 0.95%) (P < 0.04). The CON displayed higher counts of hunched standing (2.00; 95% CI: 1.68 to 2.32) compared with LID + MEL (1.43; 95% CI: 1.13 to 1.72) (P = 0.05). The CON had higher cortisol concentrations at 24 h (7.70 ng/mL; 95% CI: 1.52 to 13.87 ng/mL) relative to BUP (3.11 ng/mL; 95% CI: −2.56 to 8.79 ng/mL) (P = 0.002). At 4 and 24 h, LID + MEL had lower PGEM concentrations from baseline (−32.42% and −47.84%; 95% CI: −78.45% to −1.80%) compared with CON (27.86% and 47.63%; 95% CI: 7.49% to 82.98%) (P < 0.02). The administration of bupivacaine liposome suspension as a local anesthetic block at the time of castration was as effective at controlling pain as a multimodal approach of lidocaine and meloxicam.     

Behavioral and performance response associated with administration of intravenous flunixin meglumine or oral meloxicam immediately prior to surgical castration in bull calves

The objective of this study was to determine the effects of flunixin meglumine or meloxicam on behavioral response and performance characteristics associated with surgical castration in crossbred bulls. Intact male Bos taurus calves (n = 252; averaging 176 kg) were randomly allocated into one of three treatment groups within pen: control (CON), flunixin meglumine (FLU; 2.2 mg/kg intravenous injection), or meloxicam (MEL; 2.0 mg/kg per os). The individual animal was the experimental unit. Calves were individually weighed on days 0 and 14 of the trial to evaluate performance outcomes. On study day 0, treatments were administered, according to their random allocation, immediately prior to surgical castration using the Henderson tool method. Visual analog scale (VAS) assessment and categorical attitude score (CAS) were collected on days −1, 0 (6 h post-castration), 1, 2, 3, and 4 in the study. The VAS was assigned using a 100 mm horizontal line with “normal” labeled at one end of the line and “moribund” at the other end of the horizontal line. The masked observer assigned a mark on the horizontal line based upon the observed severity of pain exhibited by that individual animal. The CAS was assigned by the same observer using five different categories with a score of 0 being “normal”. Average daily gain tended (P = 0.09) to be associated with the treatment group, and MEL had a greater (P = 0.04) average daily gain through day 14 compared with CON. A significant (P < 0.01) treatment by day interaction was indicated for VAS score, and MEL had lower VAS scores on days 0, 1, 2, and 3 post-castration compared with CON; FLU had lower VAS scores on days 0 and 1 compared with CON. A significant treatment by day interaction was not present (P = 0.25) for CAS. The FLU had lesser percent CAS ≥1 (17.5%; P = 0.05) compared with CON (29.4%); MEL has lesser percent CAS ≥1 observations (14.9%; P = 0.01) compared with CON. The median VAS increased as CAS was more severe. Results indicated MEL and FLU calves temporally improved behavioral responses following surgical castration with positive numerical trends for a 14 d average daily gain (ADG). The VAS system appeared to be an effective method of subjective evaluation of pain in beef calves in this study. Route of administration, duration of therapy, and low relative cost make oral meloxicam a reasonable analgesic treatment in calves when administered at the time of surgical castration.     

The Impact of Access to Animal Health Services on Donkey Health and Livelihoods in Ethiopia

This study was carried out to assess the impact of animal healthcare services on poor donkey owners in Ethiopia. The services provided by the Donkey Sanctuary were used as a case study. A questionnaire survey was designed and carried out in the areas around Debre Zeit in the Highlands of Ethiopia. The staff carried out a survey at 10 sites. Six of these were in Donkey Sanctuary project areas and four were in control areas. The results showed that in project areas donkeys were significantly healthier and more productive than in non-project areas. Donkey owners in project sites felt better off for having access to animal healthcare services; donkey owners in non-project sites were less confident about their incomes and the health of their animals.