.COMPLETE REMISSION AFTER TREATMENT OF NEWCASTLE DISEASE WITH POTASSIUM ARSENITE IN 37 FALCONS Walter Tarello, DVM Al Wasl Veterinary Clinic P.O. Box 75565 DUBAI (United Arab Emirates) SUMMARY Fifty-two non vaccinated falcons showing clinical and serological evidence of Newcastle disease were treated with potassium arsenite 0.05% intramuscularly for 10 days. All birds presented clinical signs, including torticollis (80.8%), ataxia (40.4%), incoordination (25%), head tics (15.4%), tremors (15.4%), apparent blindness (13.5%), wings and leg paralysis (7.7%). In 37 falcons (71.2%), neurological signs disappeared within 1-8 days after treatment with potassium arsenite and no side effect was ever noticed. Relapses did not occur during the following 3 months. Haemoagglutination inhibition tests showed increased antibody levels in serum samples obtained at day 1 and day 10 of therapy in 24 falcons, confirming a recent onset of the condition. This study suggests that potassium arsenite can be an effective therapy for clinically manifested Newcastle disease in falcons. INTRODUCTION Newcastle disease is a worldwide distributed disease of birds caused by the avian Paramyxovirus serotype 1 (Wernery, 2003). Nine serotypes of avian paramyxovirus have been differentiated so far. However, only paramyxovirus-1 (PMV-1) has been isolated in falcons, which contract the infection through ingesting infected birds such as chickens, quails and pigeons (Wernery et al, 2004). In falcons, PMV-1 produces encephalitis and clinical signs such as ataxia, opistotonus, head tics, tremors, wing and leg paralysis and torticollis (Wernery et al, 2004). These signs are associated with neurotropic velogenic (highly virulent) or mesogenic (intermediate virulence) strains and with high to moderate mortality (Wernery, 2003). Lentogenic (avirulent or mildly virulent) strains produce sub- clinical respiratory and enteric infections (Wernery, 2003). Definitive diagnosis is based on culturing the virus from feces or respiratory discharges or from affected organs at necropsy (Rupley, 1997). Serology can also be used for diagnosis of paramyxovirus type 1 infection (Rupley, 1997). Newcastle disease virus can be differentiated from other viruses by haemoagglutination inhibition tests (Wernery, 2003). The association of neurological signs and increased antibody levels by haemagglutination inhibition (HI) test in serum samples obtained in the acute and in the remission phase is diagnostic for PMV-1 infection of recent onset. There is no cure for Newcastle disease. Hyper-immune serum can be used to protect exposed birds, but it is ineffective once clinical signs are present (Rupley, 1997). The aim of this study was to provide a safe and effective treatment for clinically manifested Newcastle disease in falcons. To this purpose, chemotherapy was based on the use of potassium arsenite, a solution of arsenic trioxide with potassium bicarbonate where arsenic trioxide is the active molecule, which proved recently successful in inhibiting viruses such as the Human Herpes Simplex virus type 1 (Burkham et al, 2001), the hepatitis C virus (Hwang et al, 2004) and the HTLV-1 and HTLV-2 viruses (Mahieux and Hermine, 2005). Figures: Torticollis in reported falcons with Newcastle virus infection. Movie 1: Head tics in falcon n. 42 with Newcastle virus infection. MATERIALS AND METHODS Between May 2003 and March 2005, fifty-two birds of prey belonging to 4 species (Falco peregrinus, Falco cherrug, Falco rusticolus and Falco pelegrinoides) were diagnosed with naturally acquired Newcastle disease (Table 1) at the International Veterinary Hospital (Kuwait). No bird had been previously vaccinated against PMV-1. The criteria for inclusion in this study were based on the presence of highly evocative clinical signs, the demonstration of antibodies against PMV-1 by the haemoagglutination inhibition test (HI-NDV) and the absence of concurrent conditions, such as vitamin B deficiency, aspergillosis and lead toxicosis, which may show a similar symptoms pattern. Captive falcons used for hunting are a category given constant special care by the falconers in the Middle East. Consequently, reports on their health status and clinical signs, even the slightest one, were precise and extremely detailed. Information evaluated included signalment, date of consultation, clinical signs, test results and therapy outcomes (Table 1). Reported duration of the disease varied from 1 day to 6 months. Fourteen (27%) falcons that after therapy found complete remission, showed neurological anomalies during 5-180 days before starting the treatment (Table 1). Recorded clinical signs were as follows: torticollis (42; 80.8%) (Figs. 1-5), ataxia (21; 40.4%), incoordination (12; 25%), head tics (8; 15.4%), tremors (8; 15.4%)(Movie n. 1), apparent blindness (7; 13.5%), anorexia (5; 9.6%), wing and leg paralysis (4; 7.7%), self- traumatism (2; 3.8%), circling (2; 3.8%) and bloody diarrhoea (2; 3.8%). Blood serum samples were collected in day 1 and/or day 10 of therapy and submitted to the haemoagglutination inhibition test for Newcastle disease virus (HI-NDV). Falcons were treated intramuscularly with potassium arsenite 0.05% at doses of 1 ml/kg/day, thus 0.37 mg of As/Kg/day, for 10 consecutive days. A physical check was performed on the day of the last injection. A further check was performed by phone call to the owner 3 months after the end of therapy. RESULTS Thirty-seven (71.2%) falcons experienced complete clinical recovery from Newcastle disease-associated nervous signs by the day of the last (10th) injection of potassium arsenite 0.05% (see Movie 1 and 2) and no relapse was reported during the following three months in any of them (Table 1). According to the owner's observations, neurological signs disappeared during the 1st day of therapy in 1 falcon, the 3rd day in 2 falcons, the 4th day in 15 falcons, the 5th day in 8 falcons, the 6th day in 6 falcons, the 7th day in 4 falcons and the 8th day in 1 falcon. Average recovery time was 4.8 days. Fifteen falcons (28.8%) found no cure and 6 (11.5%) of these died during the therapy. All birds tested positive to the HI-NDV. Results of HI- NDV tests done on serum samples obtained 10 days apart showed increased antibody titers in 24 cured falcons with a recent onset (1-7 days) of the symptoms. One-log increase was seen in 3 birds, 2-log increase in 13 birds, 3-log increase in 7 birds and 4-log increase in 1 bird. No increased titer was seen in five recovered falcons, whereas 8 falcons that also find complete cure were tested only once (Table 1). Movie 2: Complete recovery from clinical signs within 10 days after treatment with potassium arsenite in falcon n. 42. DISCUSSION Potassium arsenite 0.05% was both fast and effective in eliminating neurological signs associated with serological evidence of Newcastle disease in 37 (71.2%) out of 52 diseased falcons. Clinical signs most commonly observed in the study group were those predominantly recorded in falcons affected by paramixovirus-1 infection (Wernery et al, 2004) such as torticollis (80.8%), ataxia (40.4%), incoordination (25%), head tics (15.4%) and tremors (15.4%). It is rather intriguing to observe that all cured birds looked neurologically normal before the end of the 10-day course of therapy (see Movie 1 and 2). Spontaneous remission is possible nonetheless the average recovery time of 4.8 days indicates that the elimination of clinical signs was strictly linked to the administration of potassium arsenite. It is also of note that 14 (27%) cured falcons showed neurological abnormalities during a period of 5-180 days before the treatment. All birds in this study tested HI-NDV positive at least once. Twenty-four falcons showing clinical signs that appeared 1-7 days prior consultation demonstrate increased antibodies levels in serum samples obtained ten days apart, thus confirming the recent acquisition of the infection. Prevalence of antibodies against PMV-1 is high in captive birds of prey that are exposed to the virus through the use of avian-derived infected food (Hofle et al, 2002). Apparently healthy captive birds of prey can also show high titers as a result of a previous natural exposure to the virus (Okoh, 1979). Nonetheless, it is acknowledged that the association of peculiar neurological signs with positive HI-NDV tests is diagnostic for active PMV-1 infection and that a substantial antibodies rise within a short period of time occurs only in PMV-1 infection of recent onset. The recent acquisition of the infection was also confirmed in 13 cases by the negative results of the first HI-NDV test followed by a positive HI-NDV test result ten days later (Table 1). Virulence of Newcastle disease greatly change and is measured as a neuropathic index (NI) determined by intracerebral inoculation of 1-day old chicks (Wernery, 2003). This test was not performed in the current study. Consequently, it may be argued that lentogenic (non virulent or mildly virulent) strains were also involved in such cases. However, it is acknowledged that only neurotropic velogenic (highly virulent) and mesogenic (intermediate virulent) strains produce in falcons the severe neurological signs and the mortality rate (11.5%) observed in this study (Wernery, 2003). Lack of response to therapy in 15 (28.8%) falcons adds credit to the supposedly high virulence of the strains involved, although, at present, it is difficult to understand why some birds responded to therapy and some did not. Clinical signs and mortality rate observed in this study are compatible with those recorded during infections due to velogenic strains (Cooper, 1985). Potassium arsenite is a solution of arsenic trioxide with potassium bicarbonate, which was used empirically to treat a variety of disorders in the XIX-XX centuries and, more recently, for the treatment of pododermatitis (Tarello, 2002) and of Chronic Fatigue Syndrome in falcons (Tarello, 2004). The active molecule of this solution, arsenic trioxide, has recently showed inhibitory effects against hepatitis C virus (Hwang et al, 2004), Herpes simplex virus type 1 (Burkham et al, 2001) and HTLV-1 and HTLV-2 viruses (Mahieux and Hermine, 2005). Therefore, it should be not controversial to observe similar anti-viral effects in birds infected with PMV-1 virus, although the positive results obtained in this study were not expected as obvious. To date there is no cure for Newcastle disease and this assumption motivated this clinical trial with potassium arsenite which showed no side effects at all. Additionally, arsenic trioxide is today successfully used for treating a variety of blood and solid cancers (Waxman and Anderson, 2001) and this excludes a potential carcinogenetic risk. In short, potassium arsenite should be regarded as a promising medication against Newcastle disease in falcons, since it produces fast, complete and lasting remission within an average time of 4.8- day in 71.2% of cases. REFERENCES Burkham, J., Coen D.M., Hwang, C.B., Weller, S.K. (2001) Interaction of Herpes Simplex Virus type 1 with ND10 and recruitment of PML to replication compartments. Journal of Virology, 75, 2353-67. Cooper, J.E. (1985) Newcastle disease. In: Veterinary Aspects of Captive Birds of Prey. 2nd edn. The Standfast Press Gloucestershire, pp 76-77. Hofle, U., Blanco, J.M., Kaleta, E.F. (2002) Seroprevalence of avian paramyxovirus 1,2 and 3 in captive and free-living birds of prey in Spain (preliminary results): implications for management of wild and captive populations. Annals of the New York Academy of Science, 969, 213-6. Hwang, D.R., Tsai, Y.C., Lee, J.C., Huang, K.K., Lin, R.K., Ho, C.H., Chiou, J.M., Lin, Y.T., Hsu, J.T., Yeh, C.T. (2004) Inhibition of hepatitis C virus replication by arsenic trioxide. Antimicrobial Agents and Chemotherapy, 48, 2876-82. Mahieux, R., Hermine, O. (2005) In vivo and in vitro treatment of HTLV-1 and HTLV-2 infected cells with arsenic trioxide and interferon-alpha. Leukemia and Lymphoma, 46, 347-55. Okoh, A.E. (1979) Newcastle disease in falcons. Jornal of Wildlife Diseases, 15, 479-80. Rupley, A. E. (1997) Paramixovirus. In: Manual of Avian Practice. Philadelphia, W.B. Saunders Company, pp. 278-279. Tarello, W. (2002) A possible relationship between bumblefoot responsive to potassium arsenite and micrococci in the blood of 3 birds of prey. Acta Veterinaria Hungarica, 50, 143-150. Tarello, W. (2004) Complete remission after treatment of Chronic Fatigue Syndrome (CFS) in 118 falcons using potassium arsenite 0.05%. Proceeding from the World Conference on Dosing of Anti-infectives (WCDA), Nurnberg, Germany, September 9-11, p. 138. Waxman, S., Anderson, K. C. (2001) History and development of arsenic derivatives in cancer therapy. Oncologist, 6, 3-10. Wernery, U. (2003) Newcastle disease. In: Avian Medicine. 2nd edn. Eds J. Samour. Edimburgh, Mosby, Elsevier Science Limited, pp. 264-266. Wernery, R., Wernery, U., Kinne, J., Samour, J. (2004) Paramixovirus-1 infection. In: Colour Atlas of Falcon Medicine. Hannover, Schlutersche Verlagsgesellschaft mBH & Co., pp. 46-49. Table 1 - NEWCASTLE DISEASE INFECTION & RESPONSE TO POTASSIUM ARSENITE THERAPY IN 52 FALCONS No. Species, sex and age, Duration of Clinical signs HI (NDV) Titer Therapy outcomes date of visit the disease before & after therapy 1 Peregrine, M, 3 year 1 month Torticollis, incoordination 4 log (low) --- not done Clinical recovery from the 4th day 28 May 2003 2 Saker, M, 3 years 2 weeks Head tics, incoordination 5 log (moderate) – not done No recovery 01 June 2003 3 Saker, M, 1 year 6 months Torticollis, incoordination 6 log (moderate) – not done Clinical recovery from the 5th day 01 June 2003 4 Saker, F, 5 years 10 days Torticollis, incoordination 4 log (low) – not done Clinical recovery from the 6th day 2 October 2003 5 Saker, M, 3 years 2 weeks Torticollis, tremors, ataxia 3 log (low) – not done Clinical recovery from the 4th day 11 October 2003 6 Peregrine, F, 2 years 10 days Torticollis 4 log (low) -- not done Clinical recovery from the 5th day 18 October 2003 7 Saker, F, 2 years 1 day Torticollis, head tics, ataxia 1 log (negative) -- 3 log (low) Clinical recovery from the 4th day 12 December 2003 8 Peregrine, M, 6 months 5 days Torticollis, incoordination, 3 log (low) – 4 log (low) Clinical recovery from the 6th day 17 December 2003 ataxia 9 Peregrine, M, 1 year 2 days Torticollis, tremors, anorexia 1 log (negative) – 3 log (low) Clinical recovery from the 4th day 13 January 2004 10 Saker, M, 3 years 1 day Torticollis, tremors, ataxia 4 log (low) - 4 log (moderate) Clinical recovery from the 4th day 22 January 2004 11 Saker, F, 1 year 1 month Torticollis, apparent blindness 7 log (high) ---- not done No recovery 24 February 2004 12 Saker, M, 1 year 2 days Torticollis, circling clockwise, 4 log (low) --- 6 log (moderate) Clinical recovery from the 4th day 17 March 2004 apparent blindness 13 Saker, F, 1 year 2 days Torticollis, self-traumatism, 6 log (moderate) – not done No recovery: dead in the 2d day 20 March 2004 ataxia 14 Peregrine, F, 4 years 1 day Wing and leg paralysis, 4 log (low) --- 7 log (high) Clinical recovery from the 6th day 20 March 2004 bloody diarrhoea 15 Saker, F, 1 year 1 week Torticollis, incoordination 4 log (low) --- 5 log (moderate) Clinical recovery from the 7th day 23 March 2004 16 Peregrine, M, 1 year 5 days Torticollis, ataxia 5 log (moderate) ---not done Clinical recovery from the 4th day 07 April 2004 17 Saker, F, 1 year 4 days Torticollis, incoordination 5 log (moderate) – not done No recovery 11 April 2004 18 Saker, F, 5 years 1 day Torticollis, ataxia 1 log (negative) - 3 log (low) No recovery 25 April 2004 19 Saker, F, 2 years 2 days Torticollis, apparent blindness, 1 log (negative) --- 4 log (low) Clinical recovery from the 6th day 01 May 2004 ataxia, dyspnoea, lethargy 20 Saker, F, 2 years 4 days Torticollis, ataxia, lethargy 1 log (negative) --- 3 log (low) Clinical recovery from the 6th day 03 May 2004 21 Saker, F, 3 years 1 day Ataxia, apparent blindness, 3 log (low) --- 5 log (moderate) Clinical recovery from the 5th day 04 May 2004 incoordination, head tics 22 Saker, M, 1 year 1 day Torticollis, ataxia 1 log (negative) --- 3 log (low) Clinical recovery from the 4th day 06 May 2004 23 Peregrine, F, 2 years 3 days Torticollis 3 log (low) --- 5 log (low) Clinical recovery from the 5th day 22 May 2004 24 Peregrine, M, 2 years 1 month Ataxia 5 log (moderate) – not done No recovery 24 May 2004 25 Gyrfalcon, M, 3 years 1 week Torticollis, ataxia 3 log (low) - 4 log (low) Clinical recovery from the 3d day 27 May 2004 26 Saker, F, 1 year 1 day Torticollis, incoordination 1 log (negative) – 4 log (low) Clinical recovery from the 4th day 08 June 2004 ataxia, anorexia 27 Peregrine, F, 3 years 1 week Severe disequilibrium, torticollis, 3 log (low) --- 3 log (low) Clinical recovery from the 5th day 06 July 2004 ataxia, incoordination 28 Peregrine, M, 3 years 1 day Torticollis, tremors, ataxia 1 log (negative) – 3 log (low) Clinical recovery from the 4th day 16 July 2004 29 Saker, M, 2 years 1 month Torticollis, ataxia 4 log (low) – not done Clinical recovery from the 5th day 21 August 2004 30 Saker, F, 2 years 2 days Torticollis, ataxia 1 log (negative) – 4 log (low) Clinical recovery from the 4th day 15 September 2004 31 Barbary falcon, F, 2 years 3 months Torticollis, anorexia 6 log (moderate) – not done No recovery 25 September 2004 32 Saker, M, 1 year 2 weeks Torticollis 5 log (low) – 5 log (moderate) Clinical recovery from the 8th day 27 September 2004 33 Saker, F, 3 years 3 days Torticollis 3 log (low) – not done Clinical recovery from the 4th day 29 September 2004 34 Saker, F, 3 years 2 days Self-traumatism, torticollis, 3 log (low) – 5 log (moderate) Clinical recovery from the 4th day 05 October 2004 ataxia 35 Saker, F, 5 years 1 day Torticollis, incoordination 3 log (low) - 7 log (high) Clinical recovery from the 1st day 07 October 2004 36 Saker, F, 3 years 1 month Torticollis 4 log (low) - 4 log (low) Clinical recovery from the 6th day 11 October 2004 37 Saker, M, 3 years 1 week Torticollis, ataxia 4 log (low) – not done No recovery 16 October 2004 38 Saker, F, 3 years 2 days Torticollis 1 log (negative) – 3 log (low) Clinical recovery from the 4th day 21 October 2004 39 Gyrfalcon, M, 1 year 2 days Head tics, torticollis 3 log (low) – 5 log (moderate) Clinical recovery from the 7th day 30 October 2004 40 Hybrid Gyr, F, 4 years 1 month Torticollis, head tics 3 log (low) – 3 log (low) Clinical recovery from the 7th day 08 Nov 2004 41 Saker, F, 4 years 5 days Wing & leg paralysis, tremors, 6 log (moderate) ---- not done No recovery = dead in the 4th day 10 Nov 2004 apparent blindness, head tics 42 Saker, F, 2years 1 day Head tics, tremors [MOVIE 1] 1 log (negative) --- 4 log (low) Clinical recovery from the 7th day 15 Nov 2004 [see MOVIE 2] 43 Saker, M, 4 years 5 days Torticollis, anorexia 4 log (moderate) --- not done No recovery: dead in the 8th day 22 Nov 2004 44 Saker, F, 1 year 1 day Incoordination, leg paralysis 4 log (moderate) -- not done No recovery 27 Nov 2004 45 Hybrid Gyr, M, 2 years 4 days Apparent blindness 1 log (negative) – 3 log (low) Clinical recovery from the 5th day 27 Nov 2004 46 Saker, F, 1 year 1 day Tremors, head tics, incoordination 4 log (low) – not done No recovery: death in the 7th day 10 December 2004 bloody diarrhoea 47 Gyrfalcon, M, 1 year 2 days Tremors, head tics, circling 1 log (negative) – 3 log (low) Clinical recovery from the 5th day 18 December 2004 48 Saker, M, 3 years 3 days Torticollis 3 log (low) – not done No recovery 25 December 2004 49 Saker, F, 4 years 2 days Severe torticollis 3 log (low) - 6 log (moderate) Clinical recovery from the 3d day 25 February 2005 50 Saker, M, 1 year 1 day Torticollis, apparent blindness, 7 log (high) – not done No recovery: dead in the 5th day 04 March 2005 tremors, 5-day anorexia 51 Saker, F, 3 years 2 days Torticollis, ataxia 1 log (negative) – 4 log (low) Clinical recovery from the 4th day 08 March 2005 52 Saker, F, 3 years 5 days Severe tremors & torticollis, 4 log (low) – not done No recovery: dead in the 4th day 13 March 2005 5-day anorexia Home • Journals • Search • Rules for Authors • Submit a Paper • Sponsor us All pages copyright ©Priory Lodge Education Ltd 1994-2016priory.com HomeJournalsSearchRules for AuthorsSubmit a Paper Sponsor Us Search: Find a MedicoLegal Expert
