Dosing and therapeutic drug monitoring of voriconazole in bottlenose dolphins (Tursiops truncatus).

Bottlenose dolphins (Tursiops truncatus) can suffer from fungal infections, which can be treated with voriconazole. In common practice, the voriconazole doses are extrapolated from human doses by adjusting for body weight only, because no dose regimen is available yet. Therefore, the aim of this study was to define a dose regimen for voriconazole in bottlenose dolphins. Dolphins treated with voriconazole between November 2005 and September 2015 at the Dolfinarium Harderwijk, the Netherlands, and TDM was performed were included. Voriconazole plasma concentrations were analyzed with a HPLC-UV method. A population pharmacokinetic model was developed using Mw/Pharm in which the elimination rate constant (ke) and apparent total distribution volume (Vd) was calculated. The loading dose was calculated using the central Vd (Vdc). The maintenance dose was simulated in Mw/Pharm using ke and total Vd.Eleven dolphins were included. Ke was estimated to be 0.0026 ± 0.0007 hour-1 (mean ± SD), Vd 5.3 ± 3.2 l/kg (mean ± SD), and Vdc ranged between 1.8 and 2.8 l/kg (mean 2.2 l/kg). In order to obtain a median top plasma concentration of 5 mg/l, the loading dose was calculated to be 10 mg/kg (range 9.0-14.2 mg/kg) divided in three administrations (3.3 mg/kg every 24 hours). The maintenance dose was calculated to be 4 mg/kg once a week (range 1.7-6.0 mg/kg); 17% of the dolphins did not reach the therapeutic window of 1-5 mg/l without TDM. A TDM-guided dosing algorithm was developed in order to obtain therapeutic plasma concentrations in this population.

Is dolphin morbillivirus virulent for white-beaked dolphins (Lagenorhynchus albirostris)?

The virulence of morbilliviruses for toothed whales (odontocetes) appears to differ according to host species. In 4 species of odontocetes, morbilliviruses are highly virulent, causing large-scale epizootics with high mortality. In 8 other species of odontocetes, including white-beaked dolphins (Lagenorhynchus albirostris), morbilliviruses have been found as an incidental infection. In these species, the virulence of morbilliviruses is not clear. Therefore, the admission of 2 white-beaked dolphins with morbillivirus infection into a rehabilitation center provided a unique opportunity to investigate the virulence of morbillivirus in this species. By phylogenetic analysis, the morbilliviruses in both animals were identified as a dolphin morbillivirus (DMV) most closely related to that detected in a white-beaked dolphin in Germany in 2007. Both animals were examined clinically and pathologically. Case No. 1 had a chronic neural DMV infection, characterized by polioencephalitis in the cerebrum and morbillivirus antigen expression limited to neurons and glial cells. Surprisingly, no nervous signs were observed in this animal during the 6 months before death. Case No. 2 had a subacute systemic DMV infection, characterized by interstitial pneumonia, leucopenia, lymphoid depletion, and DMV antigen expression in mononuclear cells and syncytia in the lung and in mononuclear cells in multiple lymphoid organs. Cause of death was not attributed to DMV infection in either animal. DMV was not detected in 2 contemporaneously stranded white-beaked dolphins. Stranding rate did not increase in the region. These results suggest that DMV is not highly virulent for white-beaked dolphins.

Escherichia coli septicemia associated with lack of maternally acquired immunity in a bottlenose dolphin calf.

Stillbirth and neonatal mortality are substantial problems in captive bottlenose dolphins (Tursiops truncatus). The cause of these problems often is unknown. We report a case of Escherichia coli septicemia in a male 3-day-old bottlenose dolphin calf. Lesions included omphalitis, synovitis, and hepatic necrosis associated with the presence of Gram-negative bacilli. E. coli was isolated in pure culture from multiple organs. A serum gammaglobulin level of 1.5 g/L indicated a lack of maternally acquired immunity. The observed failure to nurse may have resulted from brain injury due to perinatal asphyxia. Evidence for perinatal asphyxia was the diffuse presence of a moderate amount of meconium in the lungs.