Vet. Path.

8: 63-80 (1971)

The Histopathology of Maedi

A Slow, Viral Pneumonia of Sheep

and P.A. PALSSON

G. GEORGSSON

Institute for Experimental Pathology, University of Iceland, Keldur, Reykjavik

Abstract. The histopathology of natural and experimental maedi, a slow-viral pneu-

monia of sheep, was studied. The main histological features are chronic interstitial inflam-
mation with dense cellular infiltration, hyperplasia of smooth musculature in alveolar
septa, and slight fibrosis; peribronchial and perivascular lymphoid hyperplasia, and
epithelial proliferation in small bronchi and bronchioles accompanied in far advanced
cases by epithelialization of the alveoli.
The histopathology of maedi bears a close resemblance to pulmonary diseases of sheep
reported under different terms in various parts of the world.

In 1939 GISLASON [8] recognized maedi, a slowly progressing pneumonia

of sheep in' Iceland, as a separate disease entity. Since then, maedi has been
intensively studied with the main effort concentrated on elucidating the
etiology of the disease, which belongs to the group of diseases upon which
SIGURDSSON [29] based his concept of slow infections. Much work has been
done on the epidemiology [29], experimental transmission [32], and isolation
of the causative agent. These studies led to the isolation from maedi-affected
lungs of a virus [28], which was shown to be the causative agent [lo]. How-
ever, the histopathology of naturally occurring maedi has not been studied
in detail, although short descriptions of its main histological features have
been published [9, 311. Since slow pneumonias of sheep, clinically similar
to maedi, have been reported from various parts of the world, a more
thorough study of the histopathology of maedi was desirable for comparative
purposes. Another stimulus for this study was the availability of sheep with
64 GEORGSSON/PP;LSSON

maedi, which had been kept in isolation for years and were relatively free
from lungworm infestation. Affected sheep from the field are usually heavily
infested with parasites, which obscures to some extent the changes of maedi.
Lastly, the course of the infection had been followed for years by serological
methods and the diagnosis verified at autopsy by isolating the virus of maedi
in tissue culture.

Materials and Methods

This study is based on 6 sheep with naturally acquired maedi and 2 experimentally
infected sheep (table I). Four additional sheep with spontaneous maedi were discarded
from this study because of heavy infestations with lungworm. The sheep with naturally
acquired maedi were from a group bought in 1961 from a farm, where a severe outbreak of
maedi had been detected the same year. In this group there were adult sheep, clinically
affected with maedi, and their lambs, which at the beginning did not show any clinical sign.
The sheep were kept together in isolational cubicles and killed, when they displayed
severe clinical signs, dyspnoea, and/or prostration. One sheep (1072)was killed relatively
early (aged 3 years) after an accident associated with lumbar puncture. This animal had
no clinical sign of maedi, and its lungs were the lightest in weight in this series (table I).
One of the 2 experimentally infected sheep (1263)was infected by means of a deep intra-
cerebral injection of a suspension of maedi-virus, and the other (1321)was given a suspen-
sion of maedi-virus in the right lung. To confirm the diagnosis, complement fixation tests
for antibodies against maedi-virus were done on a number of blood samples during the
period of isolation and at death (table I). The lungs, mediastinal lymph nodes, and spleen
were tested for maedi-virus post mortem by means of tissue culture [lo], and all contained
virus (table I).

Table I. Age of animals, weight of lungs, and results of virological examination

~~ ~~~~~~

Sheep No. Age at death Weight of lungs Compl.fix. Virus cult.

years i?

1082 7 720 + +
1073 8 460 + +
1072 3 360 + +
1080 8-9 570 + +
1066 7 1,050 + +
1067 6-7 400 + +
1263 4 670 + +
1321 4 900 + +
 Histopathology of Maedi 65

The sheep were anaesthetized with evipan intravenously and decapitated. Specimens for
histological examination were taken from various parts of the lungs and from some other
organs including tracheobronchial and mediastinal lymph nodes, spleen, liver, and kidney.
The tissues were fixed in 4% aqueous formaldehyde and embedded in p a r a 5 . Sections
from the lungs were stained with haematoxylin-eosin, VAN GIESON’S stain and GOLDNER’S
modification of the MASSONtrichrome stain for connective tissue, WEIGERT’S resorcin-
fuchsin method for elastic fibres, GOMORI’S silver impregnation for reticular fibres,
LENDRUM’S phloxine-tartrazine stain for inclusion bodies, and the periodic aCid-SCHIFF
reaction for mucopolysaccharides.

Results

Gross Findings
The macroscopic appearance of the lungs in advanced cases in our series
was typical. Thus, the lungs were voluminous and did not collapse, or did
so only slightly, when the thorax was opened. They were heavier than nor-
mal, weighing between 360 and 1,050 g with a mean weight of 641 g (table I).
The pleura was for the most part smooth and glistening and rarely had dull,
granular areas indicating a healed pleuritis. There was no pleural exudate.
The lungs were grey-brownish, firm, often of somewhat fleshy consistence,
and, in far advanced cases, lacked any normal crepitating, air-filled area. In
cases not so far advanced there were air-filled areas of normal colour and
texture, mainly on the anterior margins of the diaphragmatic, cardiac, and
apical lobes. Only in the 2 sets of lungs with the lowest weight, 360 and 400 g,
was the surface of normal colour and the consistence normal, except in the
central parts which were somewhat firmer. The cut surface was homogene-
ous, grey-reddish, and of a dry appearance. The bronchial mucosa was
seldom reddened, mostly of normal whitish colour, while the bronchial
lumen often contained sparse, glairy, viscous mucus. A terminal broncho-
pneumonia had supervened in 3 sheep.
Macroscopical worm lesions in the lungs in our series were on the whole
minimal and in some animals practically absent. The main macroscopic
features indicating parasitic infestation were small, often calcified, subpleural
nodules localized mainly posteriorly and basally on the diaphragmatic lobes ;
this is typical both in character and localization for infestation with Muel-
lerius capillaris. The bronchial tree did not contain any worm.
The tracheobronchial and mediastinal lymph nodes were enlarged and
soft, their cut surface being homogeneous and whitish. We did not find any
constant macroscopic change in other organs.
66 GEORGSSONIPLLSON

Histopathology
The lungs were similarly affected in all cases, natural and experimental,
varying only in degree. The most characteristic and impressive histopatho-
logical feature was diffuse thickening of the interalveolar septa (fig. I), often
very pronounced, which encroached upon the alveoli. In some areas this
lead to obliteration of the alveoli and consolidation with practically no
patent alveoli. In the totally consolidated areas, atelectasis was an additional
factor. The thickening of the interalveolar septa was mainly caused by
cellular infiltration, which was accompanied by distinct muscular hyperplasia
and fibrosis of a moderate degree. In the cellular infiltrate, histiocytes or
alveolar septa1 cells with large, oval nuclei, with loose chromatin and often
one or more nucleoli, dominated. The cytoplasm was often abundant and
sometimes vacuolated (fig. 2). Where the cellular reaction was intense,
lymphocyteswere also frequent. On the other hand, plasma cells were rare, and
there were practically no polymorphonuclearleucocytes, except in areas where
terminal acute bronchopneumonia had supervened. There was a moderate
fibrosis with few fibroblasts and sparse collagenous fibres. Only where the
thickening of the interalveolar septa was very pronounced did fibrosis occur
to some extent. There was always hyperplasia, often very prominent, of the
smooth muscles (fig. 3). This hyperplasia was almost entirely localized at the
level of the alveolar ducts and extended into the adjacent interalveolar septa.
It often formed knob-like thickenings at the end of the septa that adjoined
the alveolar ducts. These knobs were often numerous (fig. 4a). They were
sometimes hyalinized with a dense network of reticular and elastic fibres and
often lined with hyperplastic cuboidal epithelium, which occasionally ex-
tended into adjacent alveoli (fig. 4b). This epithelium corresponds to the
bronchiolar cell rests of Macklin. The smooth musculature of the bronchi
was not hyperplastic, but occasional nodular thickenings of the smooth
muscles occurred in bronchioles.
There was a marked increase in reticular fibres forming a dense network
in the interalveolar septa (fig. 5), whereas elastic fibres in these septa were
rather sparse and often fragmented.

Fig. 1. Diffuse thickening of the interalveolar septa with dense mononuclear infiltrate
and partial obliteration of the alveoli. Perivascular accumulate of lymphoid cells on the
lower left and knob-like thickenings on the ends of the interalveolar septa on the upper
left. HE,x 160.
Fig.2. High power detail of the cellular infiltrate in the interalveolar septa. Alveolar
cells or histiocytes predominate, with scattered lymphocytes. The alveolar epithelium is
partly transformed to cuboidal form (arrow). HE, x 640.
Histopathology of Maedi 67
68 GEORGSSON/PkLSSON
 Histopathology of Maedi 69

A constant and characteristicfeature was proliferation of lymphoid tissue,

which was mainly arranged in regular follicles and in most of the cases was
very pronounced (fig. 6 , 7). There were also foci of lymphocytes without
arrangement into follicles. The lymphoid tissue was predominantly peri-
bronchial (fig. 6), but partly perivascular. Some of the accumulates had no
apparent relation to bronchi or vessels, which was probably due to the plane
of section. There were phagocytosis of cellular debris and an occasional
mitotic figure in the germinal centers. The lymphoid tissue adjacent to
bronchi was mainly external to the musculature but often there was a discrete
infiltrate into the lamina propria of the bronchial epithelium.
The lining epithelium of the alveoli was partly transformed into a cuboidal
epithelium, especially where the thickening and fibrosis of the interalveolar
septa were most pronounced. In occasional areas the architecture of the lung
was totally disorganized and replaced by irregular cyst-like cavities lined
with cuboidal epithelium (fig. 8). These changes were adjacent to disorga-
nized bronchi and bronchioles, which occasionally communicated with the
cavities. Alveoli between the cyst-like cavities were obliterated by cellular
fibrous tissue.
Intra-alveolar exudate, inconspicuous on the whole, consisted of des-
quamated macrophages and sparse eosinophilic material. The alveolar
macrophages appeared now and then to be fused together, forming bi- and
trinucleated cells, but multinucleated giant cells as typically seen in tissue
cultures infected with maedi-virus were not found. Dense cellular exudate
occurred in the alveoli only where terminal acute bronchopneumonia had
supervened.
The epithelium of the smaller bronchi was often hyperplastic with a
mucoid metaplasia with preponderance of goblet cells (fig. 9). The bronchial
mucous glands were sometimes widened and filled with mucus; the bronchi
often contained mucus. The hyperplasia of the bronchial epithelium was
often conspicuous adjacent to lymphoid accumulates in the bronchial wall
(fig. lo). The bronchioles often had hyperplasia of the epithelium, which
sometimes plugged the lumen or covered intraluminal polyps, which had a
fibrous core infiltrated with mononuclear cells.

Fig.3. Conspicuous hyperplasia of smooth muscles in the interalveolar septa. Lymph

follicle on the lower right. HE, x 180.
Fig. 4. a Knobs on the ends of interalveolar septa mainly consisting of hyperplastic
smooth muscles. HE, x450. b Detail of a knob, lined with hyperplastic cuboidal epi-
thelium. HE, x 720.
70 GEORGSSON/PkLSSON

Fig. 5. a Low power view demonstrating the great increase of reticular fibres in the
interalveolar septa. GOMORI,x 160. b High power detail of the area marked in (a). x 400.

Vascular changes occurred only in far advanced cases and even then were
of a moderate degree. They consisted of hyperplasia of the media of arterioles
and small arteries and splitting of the elastic lamina and slight intimal
thickening in the larger arteries and veins.
Inclusion bodies were not demonstrated with certainty. Intracytoplas-
matic phloxinophilicgranules occurred regularly only in the germinal centres
of lymph follicles, but these looked more like phagocytized cells or nuclear
remnants.
The above histological changes were complicated by parasitic lesions
which on the whole were slight or minimal. They consisted of subpleural,
circumscribed, granulomatous inflammatory foci with pronounced hyper-
plasia of the smooth muscles primarily in the walls of bronchioles and small
bronchi but also in interalveolar septa.
 6

7
Fig.6. Peribronchial lymphoid hyperplasia with 3 distinct lymph follicles. HE, x 160.
Fig. 7. High power detail of peribronchial lymph follicle with distinct germinal centre.
HE, x400.
 72 GEORGSSON/PLLSSON

9
 Histopathology of Maedi 13

Fig. 10. Hyperplastic bronchial epithelium overlying lymphoid accumulate in the

bronchial wall. HE, x 400.

In 3 sheep with far advanced maedi, there were bronchopneumonic foci

with dense infiltration of polymorphonuclear leucocytes in bronchi and
adjacent alveoli.
In the tracheobronchial and mediastinal lymph nodes there was a diffuse
hyperplasia, nodes appearing homogeneous, with densely packed lympho-
cytes obscuring the normal structure. Furthermore, some lymph nodes
contained partly calcified granulomatous foci.
There was no constant histological change in other organs, except the
kidneys. There was diffuse proliferation of mesangial and endothelial cells
in the glomeruli.

Fig. 8. Cyst-like cavities, lined with cuboidal or low cylindrical epithelium. MASSON-
x 160.
GOLDNER,
Fig. 9. Hyperplasia of the bronchial epithelium with mucoid metaplasia. The goblet
cells stain black. PAS-reaction, x 400.
74 GEORGSSONIPP;LSSON

Discussion

The macroscopic appearance of the lungs in our cases of maedi conforms

with the description given in previous publications [9, 311. One salient
feature is a distinct increase in weight of the lungs. In our material the mean
weight of the lungs was 641 g per animal, more than double the weight of
lungs in normal sheep housed in isolation for long periods. According to
SIGURDSSON et al. [32] the latter weigh 301 f 11 g which is distinctly less
than for sheep living under normal conditions. The 2 lightest pairs of lungs
in our material weighed 360 and 400 g respectively, which falls within the
normal variation in weight. These lungs were practically normal grossly,
however, histologically they had slight but distinct signs of maedi. In both,
as in all our cases, the diagnosis was confirmed by positive complement-
fixation tests on series of blood samples obtained during the course of the
infection and by isolation of the maedi virus in tissue culture at death. These
cases serve to emphasize that it is not possible to exclude maedi on macro-
scopic examination alone [32]. Similarly, in a study on zwoegerziekte, a
chronic viral pneumonia of sheep in Holland closely resembling maedi,
DEBOER[3] found initial microscopic lesions in 10% of his cases, which did
not display any gross change.
The main histopathological change in maedi is chronic interstitial inflam-
mation with thickening of the interalveolar septa sometimes leading to total
obliteration of the alveoli. The thickening of the alveolar septa is mainly due
to infiltration with large mononuclear cells and to a lesser extent with
lymphocytes. Another conspicuous alteration is hyperplasia of smooth
muscles in the interalveolar walls with knob-like thickenings on the ends of
interalveolar septa. Fibrosis is discrete except in far advanced cases. There
is a marked proliferation of lymphoid tissue, especially peribronchially and
perivascularly. A constant feature is hyperplasia of the epithelium in small
bronchi and bronchioles that is sometimes accompanied by disorganization
and epithelialization of adjacent alveoli. This histologic picture is essentially
the same as that described in closely related, if not identical, pulmonary
diseases of sheep in various parts of the world. These include Montana
progressive pneumonia in the United States [23], Graaf-Reinet disease in
South Africa [15], “la bouhite” in France [20], zwoegerziektein Holland [25],
Scottish atypical pneumonia [34], and progressive interstitial pneumonia in
Kenya [37] and Germany [27, 381.
The viral cause of maedi has been proved. Recently KENNEDY et al. [14],
in a preliminary communication, reported isolating a virus from the lungs of
 Histopathology of Maedi 75

sheep affected with Montana progressive pneumonia. This virus probably is

the causative agent, although further experimental work is in progress to
elucidate definitely its role in progressive pneumonia. In Holland DEBOER
[3] has established that zwoegerziekte is caused by a virus. The viruses
isolated from sheep with either progressive pneumonia or zwoegerziekte
seem to be closely related to the maedi-virus.
Comparison of the histopathology of these 2 diseases with maedi is there-
fore of great interest. The recent detailed account by RESSANGet al. [25] of
the histopathology of zwoegerziekte shows that there are distinct similarities
of the lesions of that disease and maedi. There seems only to be differences
in the degree of fibrosis, which is slight in maedi, and in the degree of hyper-
plasia of the smooth musculature, which is more prominent in maedi.
Obviously related to the different response of the musculature is that the
knob-like thickening on the tips of interalveolar septa, observed in maedi,
is not described in zwoegerziekte. This peculiar feature is also lacking in
Montana progressive pneumonia. The muscular hyperplasia in maedi and
related pulmonary diseases could be a secondary phenomenon, representing
a compensatory response to the diminished elastic recoil of the lung caused
by thickening of the interalveolar septa and fragmentation and destruction
of elastic fibres, which occur in maedi and in zwoegerziekte [25]. Similar
hyperplasia occurs in various chronic pulmonary diseases in man, e.g.
emphysema [19]. Although such a conception of the mechanical cause of
hyperplasia of the smooth musculature seems plausible, one can not exclude
the possibility that the causative virus in some way directly stimulates the
hyperplasia. But in any case this feature is not pathognomonic for maedi,
because it is also found in infestation with lungworms [17]. According to
our experience, chiefly with infestation with Muellerius capillaris, the hyper-
plasia of smooth muscle is more pronounced in bronchial and bronchiolar
musculature, although the interalveolar septa may also be affected, and
sometimesin heavily infested lungs, knob-like thickenings of these septa occur.
The origin of the large mononuclear cells in the interalveolar septa in
maedi and related conditions is debatable. They have been variously named
histiocytes [20, 251, mesenchymal cells [3 I], and monocytes or macrophages
[25, 341. These terms are used more or less as synonyms for the same type
of cell. But it remains an open question whether they be infiltrating elements
from the blood or be alveolar septal cells, which proliferate in these disorders.
Morphologically and functionally, histiocytes and alveolar septal cells are
similar. The alveolar septal cells are classified as cells of the reticulo-endo-
thelial system [2], and it is not possible with the usual histological methods
76 GEORGSSON/PhSSON

to distinguish histiocytes from alveolar septal cells with certainty. That we

did not observe mitotic division of the large mononuclear cells in the inter-
alveolar septa speaks against local proliferation of the septal cells. One
must bear in mind, however, that maedi progresses extremely slowly over
a period of years, and the expected mitotic rate would be low.
Lymphoid hyperplasia in maedi is variable, but sometimes it is the most
prominent histological lesion. In our earliest cases, lymphoid hyperplasia
was discrete and increased as the pulmonary lesions progressed. According
to SIGURDSSON et al. [32], lymphoid hyperplasia is one of the earliest histo-
pathological signs in maedi. -SANG et al. [25] came to the same conclusion
in their study on zwoegerziekte. As to the nature of the lymphoid hyper-
plasia, we agree with the generally held opinion that it is a reactive response
to the infection and not a neoplastic process, as LUCAMPO], impressed by
the prominent lymphoid hyperplasia in “la bouhite”, assumed. We did not
find anything supporting the view that the lymphoid accumulates in the lung
be neoplastic. The hyperplasia of the tracheobronchial and mediastinal
lymph nodes is reactive, and there was no change in lymphoid tissue else-
where or in other organs indicating a lymphoma. RESSANCet al. [25] found
lymphoblastic leucosis of 2 of their sheep with zwoegerziekte, but in their
opinion this could have been a coincidental association of 2 different diseases.
We have not observed concomitant malignant lymphoma in sheep affected
with maedi. THORMAR [36], however, has pointed out that the virus of maedi
seems to be related to the viruses of avian and murine leukaemias.
We agree with MARSH[24] that the lymphoid accumulate in the lungs
represents local proliferation of lymphoid tissue normally in the lung and is
not a true infiltrative process. Another possible source of the lymphoid tissue
is the undifferentiated mesenchymal cells in loose connective tissue. It is
relatively common to see lymph follicles in chronic inflammation in tissues
where normally there is no lymphoid tissue. Lymphoid hyperplasia seems
to be a non-specific response to various agents and therefore it is not path-
ognomonic for maedi or other viral pneumonias. The increase of lymphoid
tissue with age is, according to JERICHO’S study on hysterectomy-produced
and colostrum-deprived piglets [131, directly related to challengewith various
irritating substances or agents. Various agents that cause pneumonia in pigs,
e.g. bacteria, viruses, and helminths, provoke lymphoid proliferation in the
lungs. INNES et al. [12], in a study on chronic murine pneumonia of rats
characterized by massive hyperplasia of lymphoid tissue in the lungs, suc-
ceeded in breeding rats free of pulmonary diseases and came to the conclusion
that all except microscopic collections of intrapulmonary lymphoid tissue
 Histopathology of Maedi I7

without follicular formation are pathological. In our experience, lungworm

infestation in sheep is accompanied by lymphoid proliferation, but it is
never so extensive as in maedi. The massive response of lymphoid tissue in
maedi and related conditions could possibly be the expression of some
common pathogenetic mechanism, such as an auto-immune reaction. For
example, such a reaction is known to play a definite role in HASHIMOTO'S
goitre. Also it has been suggested to be a factor in lymphoid interstitial
pneumonia, recently described in man and characterized by massive diffuse
proliferation of lymphoid tissue in the lungs [18]. We must leave this question
open. The part played by auto-immune mechanisms in maedi awaits further
study.
The hyperplastic response of the epithelium of small bronchi and bronchi-
oles together with alveolar epithelization is common to maedi and closely
related pneumonias of sheep. This epithelial hyperplasia can occasionally
lead to the formation of nodules, which may resemble the lesions in pulmo-
nary adenomatosis or jaagziekte, a neoplastic process of world-wide occur-
rence and probably of viral origin [6, 21, 22, 301. The epithelial nodules in
maedi are secondary to the inflammatory lesions in the pulmonary paren-
chyma. Epithelial proliferation is slight in early cases of maedi and such
nodules are only seen in far advanced cases. As MARSH[24] observed in
Montana progressive pneumonia, we found this lesion to be most prominent
in cases complicated either by bacterial infection or parasitic infestation.
This is in sharp contrast to the pure epithelial proliferations without ac-
companying inflammatory lesions frequently observed in both natural [5]
and experimental cases of pulmonary adenomatosis in Iceland [6, 301. Fur-
thermore, we found neither invasive growth nor metastasis.
From our experience in Iceland, there can be no doubt that maedi and
pulmonary adenomatosis are different disease entities. Pulmonary ade-
nomatosis was eradicated from this country in 1952and has not been observed
since, whereas repeated outbreaks of maedi - the last one in 1965 - have
occurred in spite of drastic methods of eradication. One must bear in mind
that where both diseases are prevalent, one will frequently k d both in the
same animal. It is also possible that some of the confusion about pulmonary
adenomatosis and chronic progressive pneumonia of sheep dates back to
1927, when COWDRY and MARSH[4] came to the conclusion that Montana
progressive pneumonia and the South African condition known as jaagziekte
were identical. But as MARSH [24]later pointed out, this confusion was created
because in South Africa jaagziekte and Graaf-Reinet disease were not
clearly separated until the 'work of DE KOCK[15] appeared. In their study
78 GEORGSSON/P,&LSSON

COWDRY and MARSH[4] apparently compared cases of Graaf-Reinet disease

with those of Montana progressive pneumonia.
The proliferation of epithelium in the terminal air passages in maedi and
related conditions is not specific. Similar changes are observed in various
viral pneumonias in man [33] and in lambs infected experimentally with
parainfluenza virus [111. Furthermore, epithelial proliferation has been noted
in sheep infected with Bedsonia-agents [7]. Infestation with lungworm can
provoke a similar response.
Transformation of the alveolar lining cells to cuboidal epithelium has
been variously named epithelization or foetalization. This transformation
can be a relatively non-specific response to thickening of the interalveolar
septa due to various causes [26]. The pathogenetic mechanism in maedi may
be twofold : both direct transformation of the lining cells and ingrowth from
the terminal bronchioles and bronchiolar cell rests, which are commonly
observed in maedi. There is some evidence that the normal renewal of alve-
olar lining cells is effected by mitosis and migration of these cells [l].
We did not observe hyalinized subepithelial nodules in the terminal
bronchioles in maedi except in cases complicated with worm infestation.
Such lesions are occasionally observed in zwoegerziekte [25] and are similar
to the tuberculoid nodular scars originally described in Scottish atypical
pneumonia [34]. According to STEVENSON [35], however, such change have
not been noticed during the last 4 years; perhaps they were caused by some
complication.
We did not find with any certainty cytoplasmic inclusion, as described in
GIEMsA-stained smears of lung from sheep affected with maedi [311and zwoe-
gerziekte [25]. It is possible that the LENDRUM phloxine-tartrazine method
does not stain the inclusionsin histologic sections.Also, possibly the inclusions
be transient as, for example, in infections with parainfluenza virus [l 11.
The proliferative glomerulonephritis observed in our animals probably
has nothing to do with the infection with maedi-virus. According to a pre-
liminary survey, spontaneous proliferative glomerulonephritis is common in
adult, apparently healthy, Icelandic sheep. This agrees with similar obser-
vations in the United States [16].
Finally, the histopathological lesions in maedi are not pathognomonic.
The main features bear a resemblance to chronic pneumonias caused by
various viruses, and some of the changes can be provoked by other organisms,
especially Bedsonia-agents and lungworms. Nevertheless, the overall his-
tologic picture, i.e. chronic interstitial inflammation with distinct lymphoid
hyperplasia and epithelial proliferation together with typical macroscopic
 Histopathology of Maedi 79

and clinical features, should arouse the suspicion that the causative agent
might be maedi-virus, or a closely related virus. The final proof will of
course rest on the identification of the causative agent.

Acknowledgements

We are indebted to Professor M. GUDNAD~TTIR for carrying out the serological tests
for technical assistance.
and viral isolations and to Mr. P. SIGURDSSON

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Author’s address : Dr. G. GEORGSSON, University of Iceland, Institute for Experimental

Pathology, Keldur, Reykjavik (Iceland)