Vestibular Syndrome Associated to Ranavirus in Farmed American Bullfrogs

Frog farming is a consolidated aquaculture activity in Brazil. American bullfrogs (Rana catesbeiana, Shaw 1802/Lithobates catesbeianus) are raised intensively with high population densities and fed with artificial diets. Those culture conditions trigger disease occurrence favored by close animal contact, increased pathogen densities and stress-induced immune depletion (Bondad-Reantaso et al., 2005).

A common chronic syndrome, with high prevalence in frogs’ farms, is characterized by diverse degree of postural and locomotive dysfunctions. Despite morbidity will be high in some conditions, low mortality was reported and farmers did not show great concern with this problem. The most common measures are isolating those frogs into a “hospital pen” with low densities and strong water recirculation. According to farmers’ experience, some recoveries were reported after this management. From a clinical point of view, signs observed in sick frogs resemble a vestibular disease in another species. To our knowledge, no description of this syndrome is available in farmed American bullfrogs and etiology, pathogenesis and affected tissues are completely unknown.

The bullfrog ear, as inmost amphibian consists of a middle ear and an inner ear, but no external ear. The inner ear consists of a system of fluid-filled tubes and sacs called the labyrinth. Vestibular system is highly preserved across vertebrate phylogeny and frogs have been used as models for several studies concerning this organ and its functions [2,3]. Early experimental work with frogs (Goltz, 1870 and Edwald 1892, cited by Straka et al. 2016) showed semicircular canals were distinct organs responsible for posture and equilibrium in three spatial orientations, and the semicircular canals sense head rotations [4].

For a more detailed description of labyrinth and vestibular system [5], gives useful information. In summary, the brain integrates balance signals sent through the vestibular nerve from the right and left ear. Vestibular sensory system has functional significance for gaze and posture stabilization, and has the capability to ensure accurate spatial orientation perception and navigation [4].

Vestibular neuritis and labyrinthitis result from an infection that inflames the inner ear or the nerves connecting the inner ear to the brain damaging normal connections between them and, consequently, faulty signals are sent. The brain thus receives mismatched information and infected individuals may showa complex syndrome of static (in the absence of body motion) and dynamic (during body motion) ocular, motor, postural and cognitive deficits that may include vertigo, dizziness, and difficulties with balance, vision or hearing [2,5,6]. To assess possible etiologies involved in farmed frogs’ vestibular syndrome, a bibliography research was performed. Results showed that many cases of inner ear infections in humans are usually viral [5] and may be consequence of a systemic viral illness, such as infectious mononucleosis or measles, herpes viruses (such as the ones that cause cold sores or chickenpox and shingles), influenza, rubella, mumps, polio, hepatitis, respiratory syncytial virus and Epstein-Barr [6], usually affecting only one ear. In domestic animals, some viruses that have been associated with vestibular neuritis or labyrinthitis include canine distemper in dogs, and feline infectious peritonitis in cats. These syndromes have been described as a paradoxical vestibular syndrome and labyrinthitis [7,8,9,10]. Surveillance on Ranavirus presence in Brazilian farms showed high prevalence, with few disease signs or mortality episodes in frogs, but several disease outbreaks with high mortality were reported in young tadpoles [11]. This high viral prevalence, associated to the information reported from other species induced the authors to analyze possible involvement of Ranavirus in vestibular syndrome, despite infections have been described as sudden death with a variety of clinical signs depending on the affected species and development stage but few nervous symptoms were related to these pathogens [12,13]. Ranaviruses are double stranded DNA viruses which have worldwide distribution being identified as responsible for an emerging systemic disease with global occurrence affecting ectothermic vertebrates, both in the wild and in captivity [14,15,16]. Due to their severity and potential threat to wild populations Ranaviruses became a notifiable disease of amphibians according to the World Organization for Animal Health [17].

These agents have been already detected in Brazilian frog farms affecting young tadpoles [18,19], but they were not yet confirmed as pathogens for adult American bullfrogs, as this species seems to be quite resistant to these viruses and may become healthy carriers [12,20].

The clinical pattern resembling labyrinthitis and vestibular syndrome induced the authors to thoroughly study those frogs, focusing on possible lesions in central nervous system (CNS) and ear region. Several necropsies were performed and gross lesions affecting posterior CNS regions with unilateral extension to the ear were observed (see results) confirming the clinical suspect about the vestibular origin of the syndrome.

Considering these issues, the objective of this work was to study the vestibular syndrome in farmed adult American bullfrogs to identify affected organs, type of lesions and possible etiology focused on Ranavirus.