Safety of an Intravenous Formulation of Voriconazole as an Intramuscular Injection in Pigeons (Columba livia f. domestica).

Aspergillosis is a common disease in birds. Currently, avian aspergillosis is treated with voriconazole administered orally, although intramuscular (IM) administration increases bioavailability and is more effective in treating generalized aspergillosis. The objective of this study was to evaluate the safety of the intravenous formulation of voriconazole as an IM injection in the pectoral muscles of pigeons (Columba livia f. domestica) as a model for other avian species. Sixteen healthy pigeons received IM injections of voriconazole (12.5 mg/kg) and sterile saline in the right and left pectoral muscles, respectively, twice a day for 7 days. Additionally, 4 birds acted as controls (no injections). Eight birds in the treatment group and 2 of the control pigeons were humanely euthanized 1 day (group 1) and 14 days (group 2) after the final injection. Hematologic and plasma biochemistry panels were performed prior to the birds being euthanized. Gross and histopathological evaluations of the pectoral muscles were completed postmortem. Statistical analysis revealed significant differences in multiple parameters, including aspartate aminotransferase and lactate dehydrogenase, but all biochemical analytes remained within the reference intervals for the species. The group 1 birds had advanced gross and histopathological pectoral muscle lesions associated with the voriconazole injections compared with the contralateral side, the group 2 birds, and the negative controls. After 14 days, the pectoral muscles did not reveal any gross or histopathological changes associated with the voriconazole or sterile saline injections. These results indicate that the intravenous formulation is safe for IM use twice per day for 1 week in pigeons. Further investigation is needed to extrapolate these findings to other avian species and to evaluate the roles of longer treatment periods and higher doses of voriconazole.

Disposition of posaconazole after single oral administration in large falcons (Falco spp): Effect of meal and dosage and a non-compartmental model to predict effective dosage.

Posaconazole has been used anecdotally to treat aspergillosis in falcons resistant to voriconazole. In human medicine, it is used prophylactically in immunosuppressed human subjects with invasive pulmonary aspergillosis. So far, no studies have been performed in birds. The aim of this study was to evaluate the in-vivo pharmacokinetic behavior of oral posaconazole after a single administration in six large falcons (i.e gyrfalcons, saker falcons). Posaconazole oral suspension (Noxafil, 40 mg/ml, Schering-Plough) was administered per os without meal in a single dosage of 12.5 mg/kg in 3 falcons. A comparison was done in two more falcons, one with a natural fatty meal at the same single dose, and one with a natural fatty meal and a higher dosage (20 mg/kg). Finally, six falcons received posaconazole pre-dissolved in corn oil with a natural low-fat meal in the higher single dose (20 mg/kg). No side effects were observed in the falcons in any of the experiments. In starved state posaconazole was poorly absorbed, more so than in other species. As expected, absorption of posaconazole was higher with the administration of meal or in the presence of plant (corn) oil, with a fourfold increase in apparent bioavailability. Despite the preferential absorption in the presence of fat, for both dosing schemes the AUC24 : MIC ratio was lower than described in human medicine to achieve a therapeutic effect. The AUCinf : MIC which is an indicator of efficacy after steady-state, while variable, did indicate that the drug is worth trying when susceptibility testing shows to be the only effective drug. LAY ABSTRACT: The focus of this work is to determine the pharmacokinetic parameters of oral posaconazole in large falcons for the first time after a single dose. Posaconazole has higher bioavailability when administered with meal and fatty components. No adverse reactions have been observed. The ratio of the area under the curve (AUC24) to minimum inhibitory concentration was lower compared to the therapeutic level in human.

Multicentric Septic Osteomyelitis and Arthritis Caused by Staphylococcus aureus in a Gyrfalcon (Falco rusticolus).

An adult female gyrfalcon (Falco rusticolus) was presented with a right-wing droop and weight loss. Radiographic images revealed osteolysis and osseous proliferation of the right shoulder and the mobile vertebra between the notarium and synsacrum. The tentative diagnosis was vertebral osteomyelitis secondary to septic arthritis. The bird did not respond to antibiotic and anti-inflammatory therapy and represented 10 days later, with feathers soiled with feces, an impacted, dilated cloaca, and an inability to stand due to spastic paralysis of the hind legs. The bird's condition did not improve with 24 hours of supportive care and its quality of life was considered poor; therefore, the patient was euthanatized and submitted for postmortem examination. Multicentric septic osteomyelitis and arthritis were confirmed in the mobile vertebra between the notarium and synsacrum and the right shoulder. Despite 10 days of antibiotic therapy, Staphylococcus aureus was isolated from within the 2 locations in which septic osteomyelitis and arthritis were identified. This report describes the clinical features, diagnosis, and pathologic findings of septic osteomyelitis and arthritis caused by S aureus in a falcon.

Serum protein electrophoresis by using high-resolution agarose gel in clinically healthy and Aspergillus species-infected falcons.

Serum protein electrophoresis has gained importance in avian medicine during the past decade. Interpretation of electrophoretic patterns should be based on species-specific reference intervals and the electrophoresis gel system. In this study, serum protein electrophoresis by using high-resolution agarose gels was performed on blood samples collected from 105 falcons, including peregrine falcons (Falco peregrinus), gyrfalcons (Falco rusticolus), saker falcons (Falco cherrug), red-naped shaheens (Falco pelegrinoides babylonicus), and hybrid falcons, that were submitted to the Dubai Falcon Hospital (Dubai, United Arab Emirates) between 2003 and 2006. Reference values were established in clinically healthy birds and compared with values from falcons infected with Aspergillus species (n = 32). Falcons with confirmed aspergillosis showed significantly lower prealbumin values, which is a novel finding. Prealbumin has been documented in many avian species, but further investigation is required to illuminate the diagnostic significance of this negative acute-phase protein.

Reference intervals for Cu, Mg, and Zn in captive gyrfalcons and other falcon species in the United Arab Emirates.

Falconry is a long-standing tradition in the United Arab Emirates (UAE), and in 2016, falconry was included by UNESCO in the list of intangible cultural heritage of humanity. The health and wellness of falconry raptors is a priority for the local culture; plasma chemistry analysis plays an important role in monitoring, assessing, and managing diseases in avian patients. Imbalances of Cu, Mg, and Zn have been linked to several diseases in avian species; therefore, determining the reference intervals (RIs) of these minerals has important implications in the clinical management of falcons. We determined the RIs in plasma for Cu, Mg, and Zn in captive (falconry-managed) falcons according to the Quality Assurance and Laboratory Standards Committee of the American Society for Veterinary Clinical Pathology, and the Clinical Laboratory Standards Institute guidelines. Blood chemistry analyses were carried out on 252 clinically healthy falcons examined at the Dubai Falcon Hospital in the UAE: 124 gyrfalcons (Falco rusticolus) and 128 falcons of other species. We observed no significant variation in RIs of Cu (1.5-7.0 µmol/L), Mg (0.49-0.78 mmol/L), or Zn (11.8-34.1 µmol/L) based on different species or sex.

An outbreak of cryptosporidiosis in a collection of Stone curlews (Burhinus oedicnemus) in Dubai.

We describe an outbreak of cryptosporidiosis in Stone curlews kept in a mixed-species rearing unit in Dubai. Cryptosporidium was the predominant intestinal pathogen detected, although microbiological investigations revealed a concurrent Salmonella infantis infection in two of the 29 Stone curlew chicks that died. Nineteen of 29 birds had catarrhal enteritis associated with histopathological findings of numerous Cryptosporidium developmental stages at the mucosal surface. Catarrhal enteritis was present without associated Cryptosporidium oocysts in five cases. Histology of the intestine, faecal examination by direct microscopy and antigenic detection by immunochromatography revealed the presence of Cryptosporidium spp. associated with catarrhal enteritis in intestinal sections and faeces. Clinical and histopathological outcomes of infection were severe, including disruption of intestinal epithelial integrity, the presence of numerous endogenous Cryptosporidium stages in intestinal epithelia and the excretion of large numbers of sporulated oocysts. The application of polymerase chain reaction and restriction fragment length polymorphism techniques at two 18S rRNA and one Cryptosporidium oocyst wall protein gene locus confirmed the presence of Cryptosporidium parvum DNA in faecal samples.

First detection of Cryptosporidium parvum in falcons (Falconiformes): Diagnosis, molecular sequencing, therapeutic trial and epidemiological assessment of a possible emerging disease in captive falcons.

Cryptosporidiosis in raptors and falcons is well-known to be caused by Cryptosporidium baileyi and associated mainly with respiratory pathology. This report presents the diagnosis of an atypical cryptosporidiosis event caused by Cryptosporidium parvum, that to the authors' knowledge, is a case observed for the first time in falcons. Two falcons (Gyrfalcon x Peregrine hybrids) were presented for annual check without any clinical signs. Hematology, biochemistry, fecal and crop parasitology, radiographic and endoscopic examinations were performed. Endoscopy revealed microcystic formation of the caudal lung field in the two falcons, adhesions and air sac alterations. Sampling and subsequent cytology revealed fungal spores and acid fast stain organisms (identified as Cryptosporidium spp.). Feces and affected lung tissue was further send for Cryptosporidium spp.-DNA detection. Fecal samples and lung tissue tested positive for Cryptosporidium spp. gp60 gene by PCR. By sequence analysis of the gp60 gene locus, diagnosis of C. parvum was confirmed with 100% homology. Despite the fact that falcons didn't recover after 1 month of therapy, eight months after the initial examination they were clinically healthy and had satisfactory flying performance. No other falcons were observed with C. parvum infections in the facility so far. The possible source, infection route and implications are discussed.

Urinalysis as a noninvasive health screening procedure in Falconidae.

Clinical signs of renal disorders in animals, including raptors, are not specific. Furthermore, serum or plasma biochemical parameters change only when 70% of kidney function is lost. In this study, reference values of urine variables were established in clinically healthy falcons. Urine samples were collected from 78 mature (> 1 year) and immature (6-12 months) male and female falcons belonging to 5 species. Droppings were assessed visually for urate color and consistency and color of the liquid urine. The liquid urine was collected by aspiration into a syringe and centrifuged, and the supernatant analyzed by commercial dipstick and by a wet chemistry analysis for alkaline phosphatase, gamma glutamyl transferase, glucose, chloride, and total protein concentrations. Sex, age, and species did not affect results of biochemical urine values (P > .05). Urine biochemical values did not differ significantly between fasted and fed birds. Total protein levels in urine samples decreased after 24-hour storage at 4 degrees C. Reference ranges for clinically normal birds are reported.

The use of voriconazole for the treatment of aspergillosis in falcons (Falco species).

To evaluate the clinical efficacy and safety of voriconazole for the treatment of aspergillosis in falcons, 20 falcons with aspergillosis admitted to the Dubai Falcon Hospital from August 2003 to May 2006 were treated with voriconazole. These falcons included 6 gyrfalcons (Falco rusticolus), 10 gyrfalcon hybrids, 1 lanner (Falco biarmicus), 1 saker (Falco cherrug), and 2 peregrine falcons (Falco peregrinus). Clinical signs were weight loss, inappetence, dyspnea, inspiratory stridor, tachypnea, and biliverdinuria. Aspergillosis was diagnosed from clinical signs, hematologic results, radiographic abnormalities, endoscopic examination of the lower respiratory tract, cytologic examination of biopsy samples from air sacs, and fungal cultures. Birds treated with voriconazole administered by crop gavage were divided into 2 groups: in group 1, birds were treated with 12.5 mg/kg q12 h for 3 days (loading dose), then q24h for an additional 18 to 87 days; in group 2, birds were treated with 12.5 mg/kg ql2h for the full period of 44 to 100 days. Treatment with voriconazole resulted in a successful clinical response in most cases, an acceptable survival rate, and few adverse effects. Complete clinical resolution occurred in 14 birds (70%), a partial response in 5 birds (25%), and 1 bird (5%) died during treatment. From these results, voriconazole appeared to be effective and safe for the treatment of aspergillosis in some species of falcons.

An outbreak of low pathogenic avian influenza in a mixed-species aviculture unit in Dubai in 2005.

This case describes an outbreak of low pathogenic hemagglutinin 9 neuraminidase 2 avian influenza virus (AIV) in two white-bellied bustards (Eupodotis senegalensis), one stone curlew (Burhinus oedicnemius), and a blacksmith plover (Antibyx armatus) in a private zoologic collection in Dubai, United Arab Emirates. The four birds showed signs of respiratory disease, and all died as a result of disease or euthanasia. Attention has been paid to the diagnostic process and common differential diagnosis for upper respiratory tract disease in bustards, curlews, and plovers. To the knowledge of the authors, AIV has not been previously described in these species.

Medical dilemmas associated with rehabilitating confiscated houbara bustards (Chlamydotis undulata macqueenii) after avian pox and paramyxovirus type 1 infection.

Projects to rehabilitate confiscated animals must carefully consider the risks of disease when determining whether to release these animals back into the wild or to incorporate them into captive breeding programs. Avipox and paramyxovirus type 1 (PMV-1) infections are important causes of morbidity and mortality during rehabilitation of confiscated houbara bustards (Chlamydotis undulata macqueenii). This paper presents key findings of an intensive health monitoring program (physical condition, hematology, serology, endoscopy, microbiology, and virology) of two flocks of houbara bustards that survived outbreaks of septicemic avipox and PMV-1 respectively. Mortality in each flock from avipox and PMV-1 infections were 47% and 25% respectively, and the clinicopathologic features and management of each outbreak are presented. Avipox and PMV-1 viruses were not isolated from surviving birds monitored monthly for 11 mo after initial infection nor were septicemic or diptheritic avipox and PMV-1 infections detected in the captive breeding collection into which surviving birds were ultimately integrated up to 24 mo later. Adenovirus was isolated from four birds during the study demonstrating that novel disease agents of uncertain pathogenicity may be carried latently and intermittently shed by confiscated birds. This paper demonstrates the risk of importing pathogens with illegally traded houbara bustards and reinforces the need for surveillance programs at rehabilitation centers for these birds. We recommend that confiscated houbara bustards integrated into captive breeding programs be managed separately from captive-bred stock. Other measures should include separate facilities for adult birds and rearing facilities for offspring derived from different stock lines and strict sanitary measures. Additionally, health monitoring of confiscated birds should continue after birds are integrated into captive flocks.

Plasma concentrations of vitamin E in six species of bustard (Gruiformes: Otididae).

Vitamin E (measured as alpha-tocopherol) and cholesterol concentrations were determined in plasma samples collected from 86 clinically healthy captive adult bustards of six species and 23 captive juveniles (6-12 mo old) of two of these species. Adult houbara bustards (Chlamydotis undulata macqueenii) had higher plasma alpha-tocopherol concentrations than juveniles (adult: mean +/- SE, 11.07 +/- 0.41 micrograms/ml, n = 32; juvenile: 6.33 +/- 0.48, n = 12) and higher alpha-tocopherol: cholesterol ratios (adult: 6.09 +/- 0.44, n = 12; juvenile: 2.94 +/- 0.22, n = 11). No age difference was evident for kori bustard (Ardeotis kori) plasma alpha-tocopherol concentrations (adult: 4.43 +/- 0.42, n = 21; juvenile: 4.46 +/- 0.26, n = 11) or alpha-tocopherol: cholesterol ratios (adult: 3.67 +/- 0.44, n = 20; juvenile: 3.71 +/- 0.36, n = 11). Adult houbara bustards had significantly higher (P < 0.01) alpha-tocopherol concentrations compared with adult rufous-crested (Eupodotis ruficrista; 6.64 +/- 0.33, n = 19) and white-bellied (Eupodotis senegalensis; 7.75 +/- 0.81, n = 8) bustards, but similar alpha-tocopherol: cholesterol ratios (rufous-crested: 5.56 +/- 0.32, n = 18; white-bellied: 5.83 +/- 0.43, n = 8). Juvenile houbara bustards had higher plasma alpha-tocopherol concentrations than juvenile kori bustards but similar alpha-tocopherol:cholesterol ratios. Adult houbara bustard plasma alpha-tocopherol levels and alpha-tocopherol:cholesterol ratios did not differ significantly between sexes. The vitamin E status of adult bustards appeared to be influenced by environmental conditions that varied due to species-specific husbandry regimens, but no clear relationship was seen with dietary vitamin E levels. Juvenile bustards did not have higher vitamin E levels than adults, despite being maintained on four-fold dietary vitamin E concentrations and in similar environmental conditions. This paper presents the first published data for plasma vitamin E concentrations in bustards. The plasma alpha-tocopherol and cholesterol concentrations and alpha-tocopherol:cholesterol ratios of captive bustards were similar to those previously reported for omnivorous avian species. Further research is required to determine which components of the identified environmental conditions affect bustard vitamin E status and to confirm whether differences exist between species independent of the variation in their management regimes.