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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

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