STUDIES ON FOWL PARALYSIS (NEUROLYMPHOMATOSIS GALLINARUM) : I. CLINICAL FEATURES AND PATHOLOGY.
ABSTRACT 1. Fowl paralysis (neurolymphomatosis gallinarum) is a disease entity, with characteristic clinical and pathological features. 2. The disease occurs in all parts of the United States, Holland, Austria and probably South America. 3. The disease appears to be endemic in certain foci. Having once appeared, the disease tends to persist through successive years. 4. It occurs with about equal frequency in both sexes; all common breeds may be affected. 5. Symptoms appear between the 3rd and 18th months. Typical clinical cases have not been observed outside of these limits. 6. The conspicuous symptoms are (a) asymmetrical, partial and progressive paralysis of the wings and both legs, and rarely of neck muscles; (b) occasional grey discoloration of iris, with blindness. Nutrition is usually preserved. 7. The duration is variable; the outcome is usually fatal, but spontaneous recovery may rarely occur. 8. The principal pathological changes are found in the nervous system. In the peripheral nerves, the essential feature is an intense infiltration of lymphoid, plasma cells, and large mononuclears. This is accompanied by a myelin degeneration in the more advanced lesions, but the cellular infiltrations appear to precede the degenerative changes. In brain, cord and meninges, there are similar infiltrations predominantly perivascular. Infiltrations of the iris with lymphoid and plasma cells are found in the cases showing gross discoloration of the iris. Visceral lymphomata, originating usually in the ovary, are associated in a certain percentage of the cases. Evidence is presented in favor of the view that this association is not accidental, and that the lymphomata are a manifestation of the disease. 9. Infiltrations of the spinal cord and brain, rarely of the peripheral nerves, are frequently present in birds showing no clinical symptoms. These are interpreted as mild cases of the same disease. 10. No microorganisms of etiological significance have been demonstrated in the tissues or by cultural methods.
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ABSTRACT: Marek's disease virus (MDV) infection in the eye was studied chronologically after inoculating 1-day-old chickens with a very virulent MDV strain, Md5. The ocular lesions could be classified as early lesions (6-11 days postinoculation [dpi]) and late lesions (26 and 56 dpi), based upon the location and severity of the lesions. The early lesions involved iris, ciliary body, and choroid layer, and were characterized by endothelial cell hypertrophy, vasculitis, and infiltration of lymphocytes (mainly CD8+), plasma cells, macrophages, and heterophils. Expression of early MDV-antigen pp38 in the cells infiltrating choroid layer was detected as early as 11 dpi. Late lesions consisted of severe lymphohistiocytic uveitis, keratitis, pectenitis, vitreitis, retinitis, and segmental to diffuse retinal necrosis. Cell infiltration included macrophages, granulocytes, plasma cells, and both CD4+ and CD8+ cells of various sizes. Expression of early MDV-antigen pp38 was readily found within the retina, uveal tract, and corneal epithelium. No expression of late-antigen gB or oncoprotein meq was detected in any of the eyes examined. A second experiment was conducted to study the effect of vaccination on the development of ocular lesions. Both HVT and CVI988 were able to protect against the development of early ocular lesions in chickens infected with very virulent plus strain MDV 648A. However, only CVI988 conferred complete protection against the development of late ocular lesions. HVT conferred partial protection, as it reduced the frequency and severity of the late ocular lesions. These results enhance our understanding of the nature and pattern of MDV infection in the eye.Avian Diseases 01/2009; 52(4):572-80. · 1.73 Impact Factor
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ABSTRACT: Gallid herpesvirus 2 (GaHV-2), commonly known as Marek's disease virus serotype-1 (MDV-1), causes T cell lymphomas in chickens. Vaccines prepared from the attenuated CVI988/Rispens MDV-1 strain currently offer the best protection. Although attenuated CVI988/Rispens is non-oncogenic, it codes for at least two forms of the MDV oncoprotein Meq, and these proteins (CVI-Meq and CVI-LMeq) have not been fully characterized. Here, we report that both CVI-Meq proteins, like the Meq protein of Md5 (a very virulent oncogenic strain), were capable of transforming Rat-2 and NIH3T3 cells. Both CVI-Meq and CVI-LMeq proteins activated the meq promoter only in the presence of chicken c-Jun (CK-Jun) whereas Md5-Meq activated the same promoter irrespective of CK-Jun co-expression. However, Meq proteins of both Md5 and CVI988 bound the meq promoter in a ChIP assay regardless of whether CK-Jun was co-expressed. To understand the role of Meq DNA binding and transactivation/repression domains in transcription, we constructed three chimeric Meq proteins, namely, Md5-CVI-Meq, CVI-Md5-Meq, and Md5-CVI-L by exchanging domains between Md5 meq and CVI meq genes. Although these chimeric Meq proteins, unlike CVI-Meq proteins, transactivated the meq promoter, the activation was significantly less than Md5-Meq. To determine the role of individual amino acids, point mutations were introduced corresponding to the amino acid changes of CVI-Meq into Md5-Meq. Amino acid residues at positions 71 and 320 of the Md5-Meq protein were found to be important for transactivation of the meq promoter. All three Meq proteins activated the MDV gB, MMP-3 and Bcl-2 promoters and suppressed transcription from the MDV pp38/pp14 bidirectional promoter. Although no significant differences were observed, decreased transactivation activity was observed with CVI-Meq proteins when compared to Md5-Meq. Collectively, the data presented here indicate that CVI-Meq proteins are generally weak transactivators, which might contribute to the non-oncogenic phenotype of CVI988 virus in chickens.Virus Research 02/2009; 142(1-2):57-67. · 2.75 Impact Factor
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ABSTRACT: Marek's disease (MD) is a lymphoproliferative disease of chickens that, in the absence of control measures, is capable of causing devastating losses in commercial poultry flocks. MD has been successfully controlled by vaccination since 1968. However, vaccine efficacy has decreased concomitantly with the increase in virulence of Marek's disease virus (MDV). The constant evolution of MDV has forced the development of new vaccines or vaccine strategies that control the more virulent emergent strains. However, this race between the introduction of new vaccines and the evolution of MDV represents a major threat for the poultry industry. In addition to vaccination, other factors might have contributed to the evolution of MDV (intensive methods of chicken production, early exposure of the chickens to MDV and administration of vaccines at very low doses). From all the possible factors influencing MDV evolution, the effect of vaccination has received the greatest attention. MD vaccines protect with great efficacy against the development of the disease but they do not prevent infection or transmission. Sterilizing immunity could be a solution to stop the evolution of the virus but it has been proven to be extremely difficult, if at all possible, to obtain with MDV or with other herpesviruses. Other solutions to improve vaccine-induced protection are discussed in this paper.Vaccine 08/2008; 26 Suppl 3:C31-41. · 3.49 Impact Factor
STUDIES ON FOWL PARALYSIS (NEUROLYMPHOMATOSIS
I. CLINICAL FEATURES AND PATHOLOGY.
BY ALWIN M. PAPPENttEIMER, M.D., LESLIE C. DUNN, PH.D., AND
VERNON CONE, M.D.
(From the Storrs Agricultural Experiment Station, Storrs, and the Department of
Pathology, College of Physicians and Surgeons, Cobumbia University,
l~Ax~S 6 xo 12.
(Received for publication, August 23, 1928.)
The disease known to poultrymen as fowl paralysis or range paraly-
sis is one whidh, in spite of its economic importance and great biological
interest, has been little studied.
The first account of the disease to which we have found reference is that of
Marek (1) in 1907. In four roosters, three of them Orpingtons, and all from the
same farm, there developed during the winter months, symptoms of paresis of
the legs and wings, unequal on the two sides, and accompanied by more or less
muscular atrophy. The diet was adequate, comprising potatoes, barley, bran,
clover and mixed grains, and the chickens were allowed free range. Two of the
birds made a partial recovery, one died after 25 days, one was killed 5 weeks after
the onset of symptoms, and the description of the pathology is based upon the
careful study of this bird.
Grossly, there was noted marked thickening of the right lumbar plexus (the
side on which the paralysis was more marked).
especially on the right side, were also thicker than normal.
Microscopic examination was made of four segments of the cervicodorsal and
lumbosacral regions of the cord with their nerve roots, of the lumbar plexus, sciatic
and femoral nerves and the extensor quadriceps femoris muscle. The tissue was
Most of the spinal nerve roots,
* Preliminary reports of this work have been presented at the November meet-
ing of the New York Pathological Society, 1925; at the Cleveland meeting of the
American Society of Experimental Pathology, December 28, 1925; and at the
World Poultry Congress in Ottawa, August 2, 1927. Much of the material in
this and the following paper has been included in Bulletin 143 of the Storrs
Agricultural Experiment Station, 1926.
64 FOWL PARALYSIS. I
fixed in Mueller's fluid, stained with Weigert-Wolters and counterstained with
alum-cochineal and Van Gieson.
In the plexus and sciatic nerves, there was almost a complete loss of nerve
fibers. There was a dense and uniform infiltration of mononuclears, in places
aggregated into dense clumps. The perineurium was but slightly thickened and
contained only scattered cells. Nests of mononuclears were present in the sur-
rounding connective tissue, chiefly in the vicinity of small blood vessels.
The spinal cord and the nerve roots, especially upon the right side, were also
infiltrated. In the cord, the cellular infiltrations were almost limited to the white
matter, but in one segment, there was a perivascular accumulation in the central
The degeneration of the nerve fibers was regarded by Marek as secondary to
the cellular invasion. The cause of the polyneuritis could not be determined, but
the disease was obviously not identical with the neuritis described by Eijkman
(2) in chickens fed on polished rice. In the latter condition, death ensued within
10 days, and the changes in the nerves were purely degenerative.
Kanpp (3) in 1921 reported rather fully upon observations first made in 1914.
In this paper, reference is made to outbreaks occurring in North Carolina, Mary-
land, Virginia, New Hampshire, New ~ersey, Connecticut and Massachusetts.
No information could be obtained by him as to the occurrence of a similar disease
in foreign countries.
The clinical features as described by Kaupp are lameness in one or both legs,
drooping of wings, partial blindness, finally diarrhea, complete paralysis and death
days or weeks after the onset. Recovery, in Kaupp's experience, never occurred.
All breeds were susceptible.
As regards the lesions, Kaupp found no changes in the cerebellum, medulla,
crura or brachial plexus. In the cord, however, corresponding segmentally to the
paralysed part, there was congestion of peripheral veins, round cell infiltration in
both ganglionic and non-ganglionic portions of the cord, chiefly perivascular.
There was degeneration of the ganglion cells, atrophy of the fibers and at times
a liquefaction necrosis. The process was interpreted as a transverse myelitis.
Kaupp studied the disease experimentally, but without arriving at any definite
results. Repeated efforts to isolate a causative organism were without success.
Inoculation of heart blood, liver, kidneys, spleen, various parts of brain and cord,
espedally of the affected segments, into rabbits, guinea pigs, young and year old
fowls all failed to reproduce the disease.
Kaupp regarded the disease as infectious.
An interesting paper treating of an apparently identical disease occurring in
the Netherlands, is that of Van der Walle and Winkler-Junius (4). The authors
studied an epizootic which occurred in the months of October and November,
1921. A large number of fowl were affected with paralysis, which ended acutely
after a few days or weeks. Most of the affected birds died, but the appetite and
general appearance of the chickens was unchanged even in the last stages of the
In spite of these negativeexperiments,
A. M. PAPPEN~IMER, L. C. DUI~N, AND V. CONE 6S
copper, lead nor zinc.
Two of the cases were examined pathologically. Inflammatory infiltrations
of polynuclear and mononuclear leucocytes were found in the swollen dorsal
ganglia; the meninges and spinal cord were likewise infiltrated, and in one of the
birds, the sacral and lumbar plexus showed mononndear infiltration.
The alterations of the nerve elements were regarded as secondary to the infil-
trations, and the apparently inflammatory nature of the lesions suggested the
term "neuromyelitis gaUinarum" for the disease.
of the brain.
A number of experiments to demonstrate the infectious nature of the disease
led the authors to conclude that this epizootic was due to a filtrable virus. We
shall discuss these in connection with our own experiments on transmission of the
May, Tittsler and Goodner (5) in December, 1925, issued a preliminary report
of field observations and laboratory findings in paralysis of the domestic fowl.
The lesions are very briefly and incompletely described.
microscopic examination of brain and spinal cord has given little information in
regard to the seat of the disease. Sections of brain and cord confirmed Kaupp's
findings, but the lesions are not described in detail, and no mention is made of
alterations in the peripheral nerves. Both aerobic and anaerobic cultures from
the tissues of infected birds consistently failed to show any infective organisms.
Attempts to transmit the disease by association and contact, by feeding material
from paralysed birds or by inoculation of blood, emulsified brain or spinal cord,
intravenously, intraperitoneally or intraspinally were all negative. None of the
inoculated animals developed paralysis during an observation period of 2 months.
The authors discuss the possible r61e of intestinal parasites and reach the con-
clusion that there is no relation, or at least that the presence of intestinal worms
or coccidia does not necessarily produce paralysis.
The most recent paper on the subject is that of Doyle (6) from the Indiana
Agricultural Experiment Station. Both the symptoms and the pathology of the
disease are very completely described. The disease occurs in birds from 4 to 8
months old, and is more prevalent in s~lmrqer and fall. The symptoms depend
upon the portion of nervous system involved. The occurrence of encephalitis is
responsible for the lethargic symptoms frequently noted. Iritis, when present,
causes a contracted, non-responsive pupil. There is a good description of the
histopathology of the brain, cord and peripheral nerves.
Efforts to demonstrate the infectious nature of the disease were fruitless; the
author's experiments will be considered in detail in the second paper, but it is
interesting to note here that in spite of his failure to establish the transmissibility
of the disease, he is still convinced that it is due to an infectious agent.
Avitaminosis could be excluded, and the food contained neither arsenic,
No mention is made of lesions
The authors state that
66 FOWL PARALYSIS. I
Clinical Features of the Disease.
The first appearance of the disease is usually signalized by drooping
of a wing on one side, a lack of coordination in walking, followed by
a lame or limping gait, and ending in complete prostration. The
limbs are not symmetrically affected, even in advanced cases. The
chickens usually lie upon the side showing the greater paralysis, and
the impairment of mobility is at first unilateral, or at least more
marked upon one side than the other.
In the earlier stages of the disease, there is little muscular atrophy,
but after the chicken has been helpless for a longer period, the wasting
may become extreme. Whether the atrophy is due to the affection of
the nerves, to the inactivity or to the inability of the chicken to pro-
cure food has not been determined.
The paralysis is more often spastic than flaccid, and sometimes
accompanied by increased reflexes or even by clonlc spasms. The
paralysis is only exceptionally complete, and even in birds which lie
immobile and helpless, the struggles during anesthetization are at-
tended by vigorous movements of flexion or extension. Reflex move-
ments and muscular reaction to mechanical nerve stimulation have
been noted in the paralysed limbs after death.
assumed by the paralysed birds are illustrated by Figs. 1 and 2.
The duration of the disease, as judged from the onset of the paralytic
symptoms to the termination in death or rarely in recovery, is very
variable. With proper care, life may be prolonged indefinitely, and
the nutrition and general condition is often surprisingly good, even
after months of complete helplessness when the birds are kept in
confinement with access to food and water. Thus one of ten early
cases in the station flock at Storrs became prostrated early in October,
1922. With careful feeding in an individual coop, it lived until
January 1, 1923. Recovery has been noted in several instances, and
we have gained the impression that there frequently occur periods of
transient improvement. On the other hand, death may suddenly
occur with few premonitory symptoms, the diagnosis being revealed
only by the pathological study of the cases.
The onset of the paralysis may be very sudden. We have observed
one case in which complete toss of power in the legs developed in less
than 3 hours.
The curious postures
A. M. PAPPEN-AIEIMER, L. C. DI~, A_N'D V. CONE
Partial or complete blindness in one or both eyes, accompanied by
a change in the color of the iris from yellow-brown to slate-grey, was
observed in several paralysed chickens, and in two non-paralysed
birds from the same flock. The alterations which underlie this
condition will be described below.
As regards the age incidence, it would appear that young birds are
most frequently affected. In our experience, the earliest symptoms
in a spontaneous case were observed at 12 weeks, and the oldest case
in our records developed paralysis at 15 months, 18 days. In the
experimental material, the earliest clinical case was observed at 10
weeks of age. As will become apparent later, the characteristic lesions
do not always reveal themselves in typical paralytic symptoms. We
shall show also that mild cases exist in which the diagnosis cannot
be made from symptoms alone.
Epidemiology and Distribution.
The records of the Storrs Experiment Station flock of White Leg-
horns in which each year about 1500 growing chicks and 800 adult
chickens come under observation, have yielded data of some value in
regard to the natural history of the disease, and instructive information
has been obtained from visits to affected farm flocks. It is impossible
to present an analysis of these data within the confines of this present
article, but we may refer briefly to some of the more interesting
(1) The disease appears to be epidemic and to reappear year after
year on the same farm. In cases where its origin has been observed,
it has appeared suddenly and has thereafter persisted and become
endemic in certain foci. Efforts to prevenf its recurrence by rearing
new flocks on new ground on the same farm, have, in several cases,
shown no significant effect on the persistence of the disease. (2)
Paralysis occurs in both sexes and in all of the chief breeds of fowls.
There is some indication of breed differences in susceptibility to the
disease, although the observations on which these are based are in no
sense experimentally controlled and the difference may have been due
to other conditions. (3) The disease first appears usually in growing
chickens from 3 to 6 months of age, and new cases continue to de-