Polar bear encephalitis: establishment of a comprehensive next-generation pathogen analysis pipeline for captive and free-living wildlife.

This report describes three possibly related incidences of encephalitis, two of them lethal, in captive polar bears (Ursus maritimus). Standard diagnostic methods failed to identify pathogens in any of these cases. A comprehensive, three-stage diagnostic 'pipeline' employing both standard serological methods and new DNA microarray and next generation sequencing-based diagnostics was developed, in part as a consequence of this initial failure. This pipeline approach illustrates the strengths, weaknesses and limitations of these tools in determining pathogen caused deaths in non-model organisms such as wildlife species and why the use of a limited number of diagnostic tools may fail to uncover important wildlife pathogens.

Lyssavirus distribution in naturally infected bats from Germany.

In Germany, to date three different lyssavirus species are responsible for bat rabies in indigenous bats: the European Bat Lyssaviruses type 1 and 2 (EBLV-1, EBLV-2) and the Bokeloh Bat Lyssavirus (BBLV) for which Eptesicus serotinus, Myotis daubentonii and Myotis nattereri, respectively, are primary hosts. Lyssavirus maintenance, evolution, and epidemiology are still insufficiently explored. Moreover, the small number of bats infected, the nocturnal habits of bats and the limited experimental data still hamper attempts to understand the distribution, prevalence, and in particular transmission of the virus. In an experimental study in E. serotinus a heterogeneous dissemination of EBLV-1 in tissues was detected. However, it is not clear whether the EBLV-1 distribution is similar in naturally infected animals. In an attempt to further analyze virus dissemination and viral loads within naturally infected hosts we investigated tissues of 57 EBLV-1 positive individuals of E. serotinus from Germany by RT-qPCR and compared the results with those obtained experimentally. Additionally, tissue samples were investigated with immunohistochemistry to detect lyssavirus antigen in defined structures. While in individual animals virus RNA was present only in the brain, in the majority of E. serotinus viral RNA was found in various tissues with highest relative viral loads detected in the brain. Interestingly, viral antigen was confirmed in various tissues in the tongue including deep intralingual glands, nerves, muscle cells and lingual papillae. So, the tongue appears to be a prominent site for virus replication and possibly shedding.

Anecortave acetate for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: Anecortave acetate is a novel angiostatic cortisene being evaluated clinically for treatment of exudative age-related macular degeneration (ARMD). A randomized, placebo-controlled, efficacy and safety dose duration study of anecortave acetate for depot suspension (3 mg, 15 mg, 30 mg) in this patient population was completed in June 2003. As part of this trial, 128 patients with subfoveal choroidal neovascularization (CNV) secondary to ARMD were enrolled and treated for up to 2 years by 18 clinical sites in the United States and European Union. METHODS: Study patients were evaluated clinically with detailed ophthalmic examinations, general physical examinations, assessments of best-corrected logMAR visual acuity, and angiographic evaluations. The Digital Angiography Reading Center (New York City, NY) assessed lesion eligibility while the clinical investigators assessed overall patient eligibility prior to treatment. As part of this study, study medication was delivered as a posterior juxtascleral depot using a specially designed curved cannula at 6-month intervals if in the masked investigator's opinion the patient's lesion could benefit from additional treatment. RESULTS: The 2-year efficacy results of this placebo-controlled study demonstrated that RETAANE 15 mg (anecortave acetate for depot suspension) was statistically superior to placebo for stabilization of vision (<3 logMAR line change from baseline) and for inhibition of neovascular lesion growth. There were no serious treatment-related safety issues associated with either the study medication or the procedure for administration. CONCLUSIONS: Anecortave acetate 15 mg for depot suspension is clinically efficacious compared to placebo for treatment of subfoveal exudative ARMD lesions when administered at 6-month intervals as a posterior juxtascleral depot.