The natural history of Anaplasma marginale

The intracellular pathogen Anaplasma marginale (Rickettsiales: Anaplasmataceae), described by Sir Arnold Theiler in 1910, is endemic worldwide in tropical and subtropical areas. Infection of cattle with A. marginale causes bovine anaplasmosis, a mild to severe hemolytic disease that results in considerable economic loss to both dairy and beef industries. Transmission of A. marginale to cattle occurs biologically by ticks and mechanically by biting flies and by blood-contaminated fomites. Both male ticks and cattle hosts become persistently infected with A. marginale and serve as reservoirs of infection. While erythrocytes are the major site of infection in cattle, A. marginale undergoes a complex developmental cycle in ticks that begins by infection of gut cells, and transmission to susceptible hosts occurs from salivary glands during feeding. Major surface proteins (MSPs) play a crucial role in the interaction of A. marginale with host cells, and include adhesion proteins and MSPs from multigene families that undergo antigenic change and selection in cattle, thus contributing to maintenance of persistent infections. Many geographic strains of A. marginale have been identified worldwide, which vary in genotype, antigenic composition, morphology and infectivity for ticks. Isolates of A. marginale may be maintained by independent transmission events and a mechanism of infection/exclusion in cattle and ticks. The increasing numbers of A. marginale genotypes identified in some geographic regions most likely resulted from intensive cattle movement. However, concurrent A. marginale strain infections in cattle was reported, but these strains were more distantly related. Phylogenetic studies of selected geographic isolates of A. marginale, using msp4 and msp1α, provided information about the biogeography and evolution of A. marginale, and msp1α genotypes appear to have evolved under positive selection pressure. Live and killed vaccines have been used for control of anaplasmosis and both types of vaccines have advantages and disadvantages. Vaccines have effectively prevented clinical anaplasmosis in cattle but have failed to block A. marginale infection. Vaccines are needed that can prevent clinical disease and, simultaneously, prevent infection in cattle and ticks, thus eliminating these hosts as reservoirs of infection. Advances in genomics, proteomics, immunology and biochemical and molecular technologies during the last decade have been applied to research on A. marginale and related organisms, and the recent development of a cell culture system for A. marginale has provided a format for studying the pathogen/tick interface. Recent advancements and new research methodologies should provide additional opportunities for development of new strategies for control and prevention of bovine anaplasmosis.     

Vaccination mitigates the impact of PRRSv infection on the pharmacokinetics of ceftiofur crystalline‐free acid in pigs

The pharmacokinetics of intramuscularly administered ceftiofur crystalline‐free acid (CCFA) were determined in pigs that were clinically healthy (n = 8), vaccinated with a Porcine reproductive and respiratory syndrome modified live virus (PRRS MLV) (n = 10), challenged with wild‐type porcine reproductive and respiratory syndrome virus (PRRSv) VR‐2385 (n = 10), or vaccinated with PRRS MLV and later challenged with wild‐type PRRSv VR‐2385 (n = 10). Animals were given a single dose of CCFA intramuscularly at 5 mg/kg body weight. Blood was collected at 0 (pretreatment), 0.25, 0.5, 1, 6, 12, 24, 48, 96, 144, 192, and 240 h postinjection. Plasma was analyzed using liquid chromatography‐mass spectrometry. Plasma concentration–time curves for each group were evaluated with noncompartmental modeling. When compared to control animals, those receiving the PRRSv wild‐type challenge only had a lower AUC_0‐last, higher Cl/F, and higher Vz/F. The PRRSv wild‐type challenge only group had the longest T_1/2λ. The C_max did not differ among all four treatments. Control animals had no statistically significant differences from animals vaccinated with PRRS MLV alone or animals vaccinated with PRRS MLV and later challenged with wild‐type PRRSv. Our results suggest that PRRSv wild‐type infection has the potential to alter CCFA pharmacokinetics and PRRS MLV vaccination may attenuate those changes.     

The Eucalyptus shoot and leaf pathogen Teratosphaeria destructans recorded in South Africa

Species of Teratosphaeria include some of the most important fungal pathogens of plantation-grown eucalypt trees. During routine disease surveys, symptoms and signs of leaf spot and blight were observed on the foliage of one-year-old E. grandis × E. urophylla hybrids in the Zululand region of KwaZulu-Natal, South Africa. These were distinct from those caused by the well-known and leaf-infecting fungus Teratosphaeria suttonii, which is not considered an important pathogen in the country. Culture and morphological characteristics as well as DNA sequences for three gene regions were used to compare the fungus isolated from the newly emerging symptoms with those for known Teratosphaeria species. DNA sequences were the same as those for T. destructans and this was consistent with the distinctive morphology of the asexual spores and the symptoms on leaves. Teratosphaeria destructans is an aggressive pathogen and actions will be needed to ensure that it does not impart serious losses to the local forestry industry.     

Armillaria root rot spreading into a natural woody ecosystem in South Africa

Signs and symptoms of a disease similar to those of armillaria root rot have recently been observed on various native woody plants on the foothills of Table Mountain in South Africa, one of the most botanically diverse natural environments globally. This is of concern because the root rot fungus Armillaria mellea has previously been shown to be an alien pathogen of European origin in planted gardens in the City of Cape Town. An aim of this study was to identify the cause of the root rot disease on infected plants. Based on DNA‐sequence phylogeny, it was shown that isolates collected from at least 16 native tree and woody shrub species represented the non‐native A. mellea. Microsatellite markers were then used to determine the genetic diversity and population structure of the A. mellea isolates from Table Mountain and two planted gardens where the pathogen has previously been found. Population genetic analyses revealed low levels of gene diversity and no population differentiation amongst the three populations. The results provide the first firm evidence that A. mellea has escaped the planted environment and invaded a sensitive and ecologically important natural woody environment in South Africa. This is only the second definitive case of a non‐native tree pathogen invading a natural ecosystem in the country.     

Pharmacokinetics and tissue disposition of meloxicam in beef calves after repeated oral administration

The objective of this study was to investigate the pharmacokinetics and tissue disposition of meloxicam after repeated oral administration in calves. Thirteen male British × Continental beef calves aged 4 to 6 months and weighing 297–392 kg received 0.5 mg/kg meloxicam per os once daily for 4 days. Plasma meloxicam concentrations were determined in 8 calves over 6 days after first treatment. Calves were randomly assigned to be euthanized at 5, 10, 15 (n = 3/timepoint), and 19 days (n = 4) after final administration. Meloxicam concentrations were determined in plasma (LOQ= 0.025 μg/mL) and muscle, liver, kidney, and fat samples (LOQ = 2 ng/g) after extraction using validated LC–MS–MS methods. The mean (± SD) C_max, C_min, and C_average plasma meloxicam concentrations were 4.52 ± 0.87 μg/mL, 2.95 ± 0.77 μg/mL, and 3.84 ± 0.81 μg/mL, respectively. Mean (± SD) tissue meloxicam concentrations were highest in liver (226.67 ± 118.16 ng/g) and kidney samples (52.73 ± 39.01 ng/g) at 5 days after final treatment. Meloxicam concentrations were below the LOQ in all tissues at 15 days after treatment. These findings suggest that tissue from meloxicam‐treated calves will have low residue concentrations by 21 days after repeated oral administration.     

Pharmacokinetics of tulathromycin in nonpregnant adult ewes

The objectives of this study were to determine plasma concentrations and pharmacokinetic parameters of tulathromycin after a single subcutaneous administration in the cervical region in sheep using the cattle labeled dose of 2.5 mg/kg. Six adult healthy ewes were administered tulathromycin on day 0. Blood samples were collected just prior to dosing and at selected time points for 360 h. Plasma samples were analyzed to determine tulathromycin concentrations, and noncompartmental analysis was performed for pharmacokinetic parameters. The mean maximum plasma concentration was 3598 ng/mL, the mean time to maximum concentration was 1.6 h, and the apparent elimination half‐life ranged from 68.1 to 233.1 h (mean 118 h). When comparing our results to goats and cattle, it appears sheep are more similar to cattle in regard to the concentrations observed and pharmacokinetic parameters. In summary, the pharmacokinetics of tulathromycin in sheep appear to be similar enough to those in goats and cattle to recommend similar dosing (2.5 mg/kg SC), assuming that the target pathogens have similar inhibitory concentrations.     

Efficacy of enrofloxacin against severe experimental Anaplasma marginale infections in splenectomized calves

Four Anaplasma marginale-infected splenectomized calves with greater than 25% parasitized erythrocytes received enrofloxacin at 12.5 mg/kg SC twice, 48 hours apart. Two infected splenectomized calves were designated as untreated controls. A precipitous decline in percent parasitized erythrocytes from 39.13% to less than 1% was observed over 12 days following treatment. However, a self-limiting recrudescence of A. marginale parasites was observed within 30 days after treatment. Untreated control calves became moribund and were euthanized. These data indicate that the regimen of enrofloxacin tested herein ameliorates, but does not eliminate, A. marginale infections in splenectomized calves.     

Comparison of the efficacy of enrofloxacin, imidocarb, and oxytetracycline for clearance of persistent Anaplasma marginale infections in cattle

This study compared enrofloxacin and imidocarb dipropionate treatments with an oxytetracycline regimen proposed by the World Organization for Animal Health for elimination of persistent Anaplasma marginale infections in cattle. The effect of therapy on competitive ELISA and polymerase chain reaction (PCR) reactivity was also assessed. Twelve A. marginale-infected carrier calves were randomly assigned to groups receiving either enrofloxacin (5 mg/kg IV q24h for 5 days), imidocarb (5 mg/kg IM twice, 7 days apart), or oxytetracycline (22 mg/kg IV q24h for 5 days). One calf infected with an Oklahoma isolate in the imidocarb group and one infected with a Virginia isolate in the oxytetracycline group failed to infect a splenectomized calf following blood subinoculation. Both became competitive ELISA negative by 44 days after treatment, but the imidocarb-treated calf remained PCR positive. None of the tested treatments reliably eliminated persistent A. marginale infections in all cattle. Furthermore, PCR was not a reliable means of determining the success of chemosterilization in calves.     

Effect of oral meloxicam on health and performance of beef steers relative to bulls castrated on arrival at the feedlot

Castration in weaned calves is stressful and affects profitability by reducing ADG and increasing susceptibility to disease. This study evaluated the effect of meloxicam, a nonsteroidal anti-inflammatory drug (NSAID), on performance and health of calves received as steers compared with bull calves surgically castrated on arrival at the feedlot. British × Continental bulls (n = 145) and steers (n = 113; BW = 193 to 285 kg) were transported for 12 h in 3 truckloads (d 0), weighed, and randomly assigned to receive either lactose placebo (CONT; 1 mg/kg) or meloxicam (MEL; 1 mg/kg) suspended in water and administered per os, 24 h before castration. On d 1, bulls were surgically castrated (CAST) and steers were processed without castration (STR). Combinations of CONT/MEL and CAST/STR were allocated to 24 pens (6 pens per treatment) of 8 to 14 calves each. Pen was the experimental unit. Plasma meloxicam concentrations at the time of castration (d 1) were determined by HPLC-mass spectroscopy. Pen-level ADG, DMI, and G:F were estimated using BW obtained on d 0, 14, and 28 and weigh-back of feed. Individual animals were classified as sick based on a depression score of ≥2 on a 5-point scale and a rectal temperature of ≥39.8°C. On d 0, 1, and 14, calf chute temperament was evaluated using a 4-point scale. Data were analyzed using generalized linear mixed models and survival curve analyses. Castration reduced pen ADG (P < 0.001) and G:F (P < 0.001) from d 1 to 14, yet no effects (P > 0.45) were apparent by d 28. For all treatment groups, DMI increased with days on feed (P < 0.0001) but was less in CAST compared with STR calves (P < 0.016) throughout the study. From d 15 to 28, ADG increased (P = 0.0011) in CAST but not STR calves, and G:F decreased (P = 0.0004) in STR but not CAST calves. In CAST calves only, MEL treatment reduced the pen-level first pull rate (P = 0.04) and reduced bovine respiratory disease morbidity rate (P = 0.03). The frequency of chute escape behavior was greater on arrival and at castration in CAST vs. STR calves (P < 0.01) but not significantly different at d 14 (P = 0.22). Mean MEL concentrations at castration were no different between treated STR and CAST calves (P = 0.70). Meloxicam administration before castration in postweaning calves reduced the incidence of respiratory disease at the feedlot. These findings have implications for developing NSAID protocols for use in calves at castration with respect to addressing animal health and welfare concerns.     

Pharmacokinetics of meloxicam in mature swine after intravenous and oral administration

The purpose of this study was to compare the pharmacokinetics of meloxicam in mature swine after intravenous (i.v.) and oral (p.o.) administration. Six mature sows (mean bodyweight ± standard deviation = 217.3 ± 65.68 kg) were administered an i.v. or p.o. dose of meloxicam at a target dose of 0.5 mg/kg in a cross‐over design. Plasma samples collected up to 48 h postadministration were analyzed by high‐pressure liquid chromatography and mass spectrometry (HPLC‐MS) followed by noncompartmental pharmacokinetic analysis. Mean peak plasma concentration (C_MAX) after p.o. administration was 1070 ng/mL (645–1749 ng/mL). T_MAX was recorded at 2.40 h (0.50–12.00 h) after p.o. administration. Half‐life (T½ λ_z) for i.v. and p.o. administration was 6.15 h (4.39–7.79 h) and 6.83 h (5.18–9.63 h), respectively. The bioavailability (F) for p.o. administration was 87% (39–351%). The results of this study suggest that meloxicam is well absorbed after oral administration.