AN EMERGING WASTING SYNDROME IN PEREGRINE FALCONS(Falco peregrinus)
Richard Jones BVSc MSc MRCVS*,Neil Forbes BVetMed DipECZM(avian) FRCVS, Mark F.
Stidworthy MA VetMB PhD FRCPath MRCVS and Tristan Cogan BSc PhD
Over the past 3 years approximately 30 adult peregrine and peregrine hybrid falcons from at least 3 separate collections as well as privately owned falconry birds in the UK have succumbed to an enteritis and 'wasting' syndrome apparently unresponsive to traditional treatment regimes. Based on the results of ongoing work our current working hypothesis is that this is a form of post infectious inflammatory bowel disease (IBD). CLINICAL AND LABORATORY FINDINGS Symptoms include general poor condition, weight loss (despite polyphagia), food begging vocalisations, mucoid diarrhoea, pale feet, cere and talons, polydipsia, regurgitation and in many cases progression to death despite culture-based antimicrobials and aggressive fluid/nutritional support. Although no single common food item or source has been identified most of the birds were fed mainly day old cockerels and/or quail. Intensive ante- and post mortem investigations including faecal bacteriology and parasitology, electron microscopy, viral culture and high-throughput molecular techniques have failed to consistently identify any single virus, bacteria, yeast or parasite. A weak signal for Northern Aplomado adenovirus was obtained on microarray but further PCR testing using both avian and pan adenovirus primers failed to amplify a PCR product to support this finding. Gross post mortem and histopathological changes mainly involved the intestinal tract, with histological evidence of segmental chronic lymphoplasmacytic enteritis (with variable numbers of heterophils), particularly in jejunum and ileum. Villi in these segments were wide and blunt (villous atrophy) in comparison with reported descriptions of normal1, with occasional villous fusion. There was crypt hyperplasia. Although classically associated with viral infection, villus atrophy and crypt hyperplasia may be attributable to a wide variety of insults to the intestinal mucosa, including bacterial, protozoal and metazoan infections, food allergies/intolerances and drug reactions. Some cases remain idiopathic. No protozoa or viral inclusions were recognised in any case, but small to excessive numbers of intraluminal bacteria of mixed morphologies were present. In one case, membranoproliferative glomerulopathy with tubular protein loss was present in the kidneys, a lesion typically associated with the deposition of circulating immune complexes from persistent inflammatory stimuli. In parallel, biopsies were taken from the small and large intestine from selected end-stage cases under terminal general anaesthesia. These were snap frozen or placed immediately into RNAlater. Snap frozen biopsies were fixed in formalin, wax embedded and examined by fluorescence in situ hybridisation to identify and localise bacterial infection. For biopsies in RNAlater, mRNA was extracted using a Promega kit. Levels of TGF beta, IFN gamma, IL-10, TNF alpha and IL-6 were analysed by qPCR using a Stratagene 1 step qRT-PCR kit with primers designed using available DNA sequences for Falco spp. from GenBank. Affected birds had large numbers of bacteria colonising the intestinal mucosa, most of which were considered to be intestinal commensals, although clostridia were often identified. Biopsies from affected birds showed higher levels of IFN gamma, TNF alpha and IL-6 than those from control birds (wildlife trauma cases euthanased on humane grounds). These are all proinflammatory cytokines, and this profile is consistent with that seen in human IBD. The marked difference was that in humans elevated TGF beta is also seen, an elevation absent in the affected birds. Elevated TGF beta causes excess collagen deposition in the submucosa in humans with IBD, and is responsible for thickening of the gut wall and the development of fibrosis2. Histology showed that affected birds did not show fibrosis. In humans,
IBD is a Th-1 disease, and the activity of these cytokines is co-regulated by the transcription factor T-bx21. Our analysis of avian genomes indicates that chickens do not have a homologue of this factor. It is likely that regulation occurs by a different mechanism that does not involve TGF beta or promote fibrosis. The clinical presentation of IBD in birds could therefore differ from that in mammals. The picture suggests that an initial inciting infection compromises intestinal barrier function before resolution/clearance. Excessive numbers of commensal bacteria remain colonising the intestinal mucosa, promoting a feedback loop of inflammation, breakdown in epithelial barrier function, further bacterial colonisation and persistent inflammation, as described for chronic human IBD3
CURRENT MANAGEMENT RECOMMENDATIONS The authors recommend that falcons presenting with these clinical signs undergo complete physical examination with faecal analysis for the presence of intestinal parasites, protozoa or microbial pathogens, which should then be treated with appropriate culture-based therapeutics. Meloxicam, oral aqueous aloe vera and probiotic/competitive exclusion products e.g. Flightpath (Microbial Developments Ltd.) are useful adjunct therapies in such cases. Affected birds may respond to dietary conversion to a novel protein, perhaps reflecting an underlying hypersensitivity to antigens breaching the intestinal mucosal barrier during an inflammatory episode. With polydipsia a common feature of this syndrome it is essential such birds have unlimited access to fresh water to avoid dehydration. In refractory cases, based on the hypothesis of IBD, a number of protocols including oral sulphasalazine, metronidazole, budesonide and intramuscular dexamethasone have been attempted with varying results. Although such therapies have proved useful in the management of acute 'flare ups', at the time of writing our clinical impression is that this may be a lifelong condition. AKNOWLEDGMENTS The authors would like to thank The Hawk Board, Honeybrook Animal Foods, Falcon Mews, M&J Raptors, Pinmoore Animal Laboratories, Richard Ashcroft, Dr Tom Bailey, Prof. Michael Lierz, Dr.Akbar Dastjerdi, Prof. Peter Kaiser and Dr. Arnaud Van Wettere for their input, help and support with ongoing work. CITATION INDEX
1 Heidbrink, Stephanie. Morphological examination of the digestive tract of different raptor birds with regard to their respective feeding habits. Doctoral thesis, Freie Universitat Berlin, 2003.
2 Guarner F. What is the role of the enteric commensal flora in IBD?.Inflammatory bowel diseases. Vol 14, issue supplement 2. Pages S83-S84 October 2008. http://onlinelibrary.wiley.com/doi/10.1002/ibd.20548/pdf 3 Pucilowska J B, Williams L and Lund P K. Fibrogenesis IV. Fibrosis and inflammatory bowel disease:cellular mediators and animal models. American Journal of Physiology. 2000. Vol. 279 number 4. G653-G659.
*AUTHOR ADDRESS: Richard Jones BVSc MSc MRCVS Avian Veterinary Services Knutsford WA160SX UK e-mail: email@example.com
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