COMPLETE REMISSION AFTER TREATMENT OF
NEWCASTLE DISEASE WITH POTASSIUM
ARSENITE IN 37 FALCONS
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.
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).
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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