Path. vet. 5: 51-58 (1968)
From the Department of Pathology, Michigan State University, East Lansing
Avian Amyloidosis
I. General Incidence in Zoo Birds
DANIEL
F. COWAN
Avian amyloidosis was probably first described by ROLLin 1867,
occurring in a pheasant (cited by HJARRE~).
Scattered reports up to
1901 described it in chickens, a turkey, pheasants, a peafowl, and a
whistling duck4. Fox3 reported amyloidosis in a variety of birds in
1923 in his review of diseases of zoo birds and mammals. HJARRE~
found deposits of amyloid in chickens, ducks, and a turkey. More
recently, THOMPSON
et al.15 found amyloid in white Pekin ducks
following injections of killed tubercle bacilli. RIGDON,in a series of
reports*-12, described amyloidosis in Pekin ducks and concluded that
it could develop spontaneously with age. DOUGHERTY
et al.2 found
spontaneous amyloidosis appearing in Pekin ducks held in dietary
experiments. In a special study in which they tried without success to
relate it to diet, the incidence of amyloidosis at 38 weeks of age was
100%. RAKHhfANove reported an incidence of 45% in ducks fattened
under a system of intensive management on poultry farms. BRASSARD^
reported amyloidosis in captive wild anserines and demonstrated a
tinctorial similarity to the deposits in human amyloidosis.
The records of the Penrose Laboratory of the Philadelphia Zoological Society were begun in 1901 and contain autopsy reports on all
deaths among the mammals and birds maintained in the zoo. Control
of infectious diseases and the virtual elimination of nutritional disease
through the introduction of standardized, high-quality diets in 1935
resulted in a great increase in the life expectancy and vigor of all
animals in the zoo. This, combined with a marked increase in the
numbers and variety of animals on display, particularly birds, led to
studies which have demonstrated the effects of environment and social
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52
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interaction on spontaneously occurring diseases such as arteriosclerosis' and cancerl3.
In this context, a comparison of incidences of amyloidosis in
various groups of birds, with an exploration of possible etiologic factors such as associated chronic diseases, age, sex, and adaptability to
zoo conditions, seemed indicated. Tinctorial qualities and sites of
deposition were also compared.
Materials and Methods
Autopsy records of birds dying in the thirty-year period 1936 to 1965 were
reviewed. Those birds that had lived under standardized zoo conditions for 12
or more months and for which adequate sections of liver, or spleen, adrenals,
kidneys, and heart had been taken were selected for analysis. The data analysed
included the taxonomic order and family, sex, time on exhibition, native habitat,
presence or absence of amyloidosis, and presence or absence of associated chronic
disease. New histologic sections were cut from paraffin blocks and stained with
hematoxylin and eosin, Congo red, crystal violet, periodic acid-Schiff-alcian blue,
phosphotungstic acid-hematoxylin, and Masson's trichrome (unmodified). Liver
from a human case of amyloidosis was used as a control.
Table I. Population Analysed for Amyloidosis and Contributing Factors
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
Order
Anseriformes
Apodiformes
Caprimulgiformes
Casuariformes
Charadriformes
Ciconiformes
Coliformes
Columbiformes
Coraciformes
Cuculiformes
Falconiformes
Galliformes
Gruiformes
Passeriformes
Pelicaniformes
Piciformes
Psittaformes
Rheiformes
Sphenisciformes
Strigiformes
Struthioniformes
Trogoniformes
Total
Families
2
1
1
1
7
6
1
1
5
2
4
4
6
22
3
3
1
1
1
2
1
1
76
Common Names
Number
Ducks, geese, swans, screamers
580
Hummingbirds
6
Goatsuckers
1
Cassowaries
9
Plovers, gulls, stilts, sandpipers
46
Storks, herons, ibises
70
Colys
2
Pigeons, doves
46
Kingfishers, hornbills, rollers
27
Cuckoos, touracous
4
Hawks, eagles, vultures
50
Turkeys, pheasants, guans
162
Bitterns, cranes, rails
78
Crows, finches, sparrows, orioles
341
Darters, pelicans, cormorants
19
Barbets, woodpeckers, toucans
41
Parrots
158
Rheas
11
Penguins
16
Owls
17
Ostriches
4
Quetzals, trogons
10
1698
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Anatidae
Family
578
Number
Examined
With
amyloid
262
45
% With
amyloid
None (164)
Tuberculosis (41) Mould (42) Nephrosclerosis*** (29) Hepatitis (29) Neoplasia (9) Osteomyelitis (1) Toxoplasmosis (1)
‘Nephritis’ (4) Hepatitis (1)
Myocardial abscess (1) Nephrosclerosis (1)
Associated chronic diseases**
Charadriif.
Charadriif.
Rheif.
Charadriif.
Passerif.
Gruif.
Laridae
Scolopacidae
Rheidae
Hematopodidae
Ploceidae
Rallidae
12
10
42
5
30
None (1)
3
11
3
27
None (2)
Pulmonary granuloma (1)
25
None (1)
4
1
69
7
10
None (4)
Nephrosclerosis (3)
35
3
9
None (2)
Pulmonary granuloma (1)
Gallif.
Phasianidae
155
13
8
None (10)
Pulmonary abscess (1) Nephrosclerosis (2)
Gruif.
Gruidae
38
3
8
None (2)
Tuberculosis (1)
Ciconif.
Phoenicopteridae
15
1
7
None (1)
‘Inanition’
18
1
6
Timaliidae
Passerif.
1
2
Nephrosclerosis (1)
46
Columbidae
Columbif.
158
1
0.6
Nephrosclerosis (1)
Psittacif.
Psittaddae
* Arteriosclerosis and its complications are not included; birds with or without amyloidosis may have had such lesions.
* * Often multiple diagnoses. Brackets indicate numbers of diagnoses.
*** This term includes a variety of ill-defined nephropathies.
Anserif.
Order
Tub/.ZZ. Proportionate Mortality Among Families with Amyloidosis, Listed in Descending Order of Incidence,
and Associated Conditions*
f’
P
a
z2.
zE.
*3
54
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Results
A total of 1698 birds from 22 orders and 76 families was examined
(Table I). Of these, 304 out of 1149 birds from 9 orders and 13 families
had amyloidosis (Table 11). The other 13 orders and 63 families, represented by 1 or more birds, had none with amyloidosis out of a
total of 549 birds. The incidence of amyloidosis among positive families ranged from a high of 45% (262 of 578) among Anadidae to a
low of 0.6% (1 of 158) among Psittacidae.
Clinical signs such as swelling of the feet, abdominal fullness,
dyspnea, and ascites, which RIGDONobservedll, were rarely encountered among the birds with amyloidosis. Amyloidosis was never recognised before autopsy.
Amyloidosis may be associated with various chronic diseases but
may occur in their absence (Table 11). Arteriosclerosis and its complications occurred in the vast majority of birds whether or not they had
amyloidosis and are not considered further in evaluating possible
associated factors. Tuberculous lesions found were often small and at
an early stage of development, especially in birds with far advanced
amyloidosis. ‘Mould disease’ or aspergillosis was seen as a chronic
granulomatous disease, especially in penguins, but it was more often
only the coup de grace to an extremely debilitated bird.
The staining reactions of the amyloid were remarkably constant
from family to family and were very similar to those seen in the human control, including birefringence with Congo red and metachromasia with crystal violet. PAS-alcian blue stained the amyloid light
blue-pink5. Phosphotungstic acid-hematoxylin was never taken up by
the amyloid. Masson’s trichrome stained parenchymal deposits pale
slate-blue and deposits in vascular walls magenta.
In some families, particularly the Ploceidae, the early deposits
were distinctly fibrillar. The frequency of deposits of amyloid in
different organs varied (Table 111). Sections of skeletal muscle and
Tablc ZZZ.Frequency of Deposition of Amyloid in Various Organs
Organ
Liver
Spleen
Adrenal
Parathyroid
Kidney
196
16
%
affected
84
82
71
50
275
49
Number
of organs
288
229
Organ
Thyroid
Pancreas
Intestine
Heart
Lung
Number
of organs
92
128
52
245
135
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%
affected
34
31
13
2
0
55
Avian Amyloidosis
tongue were not taken routinely at autopsy. The deposits may be
either parenchymal (adjacent to sinusoids or capillaries), or vascular
(in the inner layer of the media of small arteries and arterioles), or both.
Vascular deposition was most prominent in the kidney, where it
was often associated with glomerular sclerosis. Parenchymal deposition predominated in the liver, spleen, adrenal, and thyroid. The initially small, scattered deposits enlarged and eventually coalesced.
Of the families in which amyloidosis was diagnosed, 7 were represented by more than 30 birds each. The average and maximum
time on exhibit for these birds with amyloidosis was established and
compared to the average and maximum longevities which have been
determined for the families as a whole14 (Table 1 3 . There is a small
but consistent tendency for the disease to occur in an older age group,
but it is, as a rule, not found in the oldest birds.
Table W .Relation of Age (Months on Exhibition) to the Occurrence of
Amyloidosis
Family
All Birds
Number Average Maximum
ofbirds age
age
Birds with Amyloid
Number Average Maximum
ofbirds age
age
Anatidae
Ploceidae
Rallidae
Phasianidae
Gruidae
Columbidae
Psittacidae
900
189
58
322
51
60
346
262
7
3
13
3
1
1
74
57
61
54
99
61
70
310
230
183
247
408
184
368
84
68
66
58
47
92
79
310
I01
81
112
74
92
79
Because of the small numbers of birds involved in six of the seven
selected families, analysis for relation to sex was carried out only for
the Anatidae, where amyloidosis was found to occur with equal frequency in both sexes (45% of males and 47% of females).
Discussion
The rarity of clinical signs indicating the presence of amyloidosis
is not unexpected. Enclosures for display of large groups are used in
this zoo, especially for the waterfowl. These with their heterogeneous
and often crowded exhibits allow a great deal of interaction between
birds, and there is no effective inhibition of the tendency for even
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56
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‘gentle’ species to kill any member that shows weakness or unusual
behavior, usually before the development of clinical signs.
The tendency for the disease to be found in older, but not the
oldest birds indicates removal of a susceptible group from the population.
The relationship of amyloidosis to chronic disease is problematic.
Tuberculosis is a classic ‘cause’ of human amyloid disease, and there
is certainly a relationship between the two diseases in birds. However,
it is often nearly certain that the amyloid came first and that tuberculosis developed in birds nearly dead of amyloid disease. The same
applies even more strongly to aspergillosis. Chronic hepatitis and
various nephropathies are not customarily regarded as precipitants of
amyloid disease. The incidence of these two is very difficult to assess,
as far advanced amyloid replacement could easily mask any sign of
their pre-existence. Also, amyloid involvement of renal arteries and
arterioles probably could produce the sclerotic glomerular changes.
There is no difference in distribution or staining quality of the amyloids
arising independently or in association with other diseases. Attempts
to employ forced classifications such as ‘primary’ or ‘secondary’ are
probably specious.
Perhaps the most interesting and difficult to quantitate feature of
avian amyloidosis is its apparent predilection for exotic birds or for
relatively specialized birds from environments difficult or impossible
to approximate in the zoo. All but one of the Pfoceidae are from southeast Asia, most of the Phasianidae are oriental mountain-dwelling
pheasants, and all the Lat-idae are gulls. The maritime and some shore
birds are particularly susceptible, and within the Anatidae there is a
striking segregation of susceptibility according to environmental adaptation, which is not related to other disease. It should be easy to
create an environment in the laboratory to which no species could
satisfactorily adapt. This may account for the extraordinarily high
incidences of amyloidosis in ducks in laboratories2B 11 and on intensively managed poultry farmse. The relationship of amyloidosis to
adaptability will be discussed further in Part I1 of this paper in which
the Anatidae will be examined in detail, by genus and species.
Conclusions
Avian amyloidosis, a uniform disease, occiirs in a wide variety of
birds having little in common but age and a tendency to be exotic
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Avian Amyloidosis
57
or poorly adapted to zoo conditions. The preponderance of susceptible
families are adapted in some way to an aquatic or littoral environment;
thus the ducks, geese, swans, gulls, snipes, sandpipers, and oystercatchers have the highest incidences. Birds with marked structural or
behavioral modifications, such as the flightless rhea, are similarly
involved. The highly adaptable pigeons, doves, and parrots have a
correspondingly low incidence.
The true incidence of amyloidosis is difficult to assess, as many of
the families are represented by only a few individuals, and many others
are so poorly adapted and sensitive that they die at a very early age
realising only a small part of their potential longevity.
Evidence to support classifications such as ‘primary’ or ‘secondary’ is lacking, although some cases of amyloidosis are associated
with tuberculosis. There is no difference in the patterns of deposition
or staining quality of the amyloid in these cases. In many of them the
indications are that the amyloidosis preceded the tuberculosis.
It appears that avian amyloidosis may be a disease with multiple
causes, and that maladaptation may be one of the most important if
not the fundamental cause. This implies that in any laboratory studies
of avian amyloidosis the housing of the birds is of prime importance
and caging alone could in time produce the disease.
Summay
The incidence, staining qualities, organ distribution, age of affected individuals, and disease conditions associated with avian amyloidosis occurring in a
population of 1698 zoo birds were analysed. Amyloid disease occurs in older
birds, predominantly affecting the liver, spleen, and adrenals. The staining qualities
and morphology are very similar to mammalian amyloid. The disease occurs
mainly in exotic or poorly adapted birds, apparently related to environmental
factors rather than to any specific predisposing disease.
Zusammenfassung
Das Vorkommen, die Farbungs-Eigenschaften, Organverteilung, das Alter
einzelner Tiere sowie der Erkrankungsprozess der Amyloidose der Vogel wurde
in 1698 erkrankten Vogeln aus zoologischen Garten analysiert. Amyloidose erfasste altere Vogel und kam vorwiegend in der Leber, Milt und Nebenniere vor.
Die Farbungs-Eigenschaften sowie die Morphologie ahnelten der Amyloidose
der Saugetiere. Vor allem exotische oder wenig adaptierte Vogel waren von der
Erkrankung betroffen. Diese Tatsache wurde dahingehend interpretiert, dass die
Amyloidose mehr von Umweltsfaktoren als von spezifischen pradisponierenden
Erkrankungen abhangig war.
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Acknowledgement
This study was supported in part by Special Fellowship l-F3-GM-32,995-01
from the National Institutes of Health, and in part by Grants HE-05690 and
HE-01979 from the National Heart Institute, Bethesda, Maryland.
References
1. BRASSARD,
A.J.: Amyloidosis in captive anserines. Canad.J , comp. Med. Vet.
Sci. 59: 253-258 (1965).
2. DOUGHERTY,
E.; RICKARD,
C.G. and SCOTT,hf.L.: Subacute and chronic liver
diseases of the white Pekin duck. Avian Dis. 7: 217-234 (1963).
3. Fox, H.: Disease in Captive Wild Mammals and Birds, pp. 128, 227 (J.B.
Lippincott , Philadelphia 1923).
4. HJARRE,A. : Uber das Vorkommen der Amyloiddegeneration bei Tieren.
Acta path. microbiol. scand., supp. 16: 132-162 (1933).
5. MCMANUS,J.F.A. and MOWRY,R.W.: Staining Methods, Histologic and
Histochemical, p. 151 (Paul P. Hoeber, New York 1960).
6. RAKHMANOV,
A.M.: (Amyloidosis in ducks reared and fattened on poultry
farms). Acks. Path. 20: 59-62 (1958). (In Russian, summary in English).
7. RATCLIFFE,
H.L. : Age and environment as factors in the nature and frequency
of cardiovascular lesions in mammals and birds in the Philadelphia Zoological
Garden. Ann. hr.Y. Acad. Sci. 127: 715-735 (1965).
8. RIGDON,R.H.: Atypical cirrhosis in the duck produced by methylcholanthrene. Amer. J. Path. 31: 461-473 (1955).
9. RIGDON,R.H. : Amyloidosis-experimental production in ducks with methylcholanthrene. Texas Rep. Biol. and Med. 18: 93-102 (1960).
10. RIGDON,R.H.: Effect of tobacco condensate on respiratory tract of white
Pekin ducks. Arch. Path. 69: 55-63 (1960).
11. RIGDON,R.H.: Amyloidosis: Spontaneous occurrence in white Pekin ducks.
Amer.1. Path. 39: 369-378 (1961).
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white Pekin ducks. Amer. J. vet. Res. 23: 1057-1064 (1962).
13. SNYDER,R.L. and RATCLIFFE,
H.L.: Factors in the frequency and type of
cancer in mammals and birds at the Philadelphia Zoo. Ann. N.Y. Acad. Sci.
108 (3): 793-804 (1963).
14. SNYDER,
R.L. and MOORE,SUSAN:(Longevity of Birds in the Philadelphia
Zoo). To be published.
15. THOMPSON,
K.J.; FREUND,
J.; SOMMER,
H.E. and WALTER,A.W.: Immunization of ducks against malaria by means of killed parasites with or without
adjuvant. Amw. J. trop. Med. 27: 79-105 (1947).
Author’s address: Dn. DANIEL
F. COWAN, Penrose Research Laboratory, Philadelphia Zoologial Society, 34th dr
Girard Avenue, Pbiladtlpbia, Pennsylvania 19104 (U.S.A.).
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