D6921.PDF

Rev. sci. tech. Off. int. Epiz., 1983, 2 (2), 311-334.
Respiratory diseases
induced in small ruminants
by viruses and mycoplasma*
W.B. MARTIN**
Summary : In this paper the primary virus and mycoplasma invaders of
the respiratory tract of sheep and goats are considered, including those
which do not produce clinically apparent disease.
Among acute viral infections, the widespread occurrence of parain­
fluenza 3 virus and the established findings that it allows other more
sinister organisms to invade the lower respiratory tract would indicate
that it is a virus of considerable economic importance. Little is known
about the significance of infections caused by adenoviruses and reoviruses. Peste des petits ruminants (PPR), caused by a rinderpest-like
virus, is of considerable economic importance in West Africa. The her­
pesvirus of infectious bovine rhinotracheitis (IBR) is capable of infect­
ing goats and sheep. Infections caused by pox viruses and the border
disease virus are not primarily respiratory diseases.
Sheep pulmonary adenomatosis, maedi-visna and retrovirus infec­
tion in goats are the main virus infections associated with progressive
pneumonias of small ruminants.
At present six identified species of mycoplasma have been recovered
from the respiratory tract of sheep and goats, not all of which have
been associated with disease. M. ovipneumoniae is considered to be res­
ponsible for chronic respiratory infection which progresses slowly; Pasteurella haemolytica is a frequently associated pathogen. Contagious
caprine pleuropneumonia (CCPP) is a serious and economically impor­
tant disease, affecting exclusively goats. Three mycoplasmas have been
considered as its aetiological agent : M. mycoides subsp. capri, M.
mycoides subsp. mycoides, and the unclassified strain F 38.
INTRODUCTION
Respiratory problems are c o m m o n in all species and m a n y agents have
now been recovered from the respiratory tracts of animals. T h o u g h one agent
* Report presented at the 50th General Session of the O.I.E., Paris, 24-29 May 1982
(Technical Item III).
** Moredun Research Institute, 408 Gilmerton Road, Edinburgh, EH17 7JH, U.K.
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may be the primary invader, most respiratory infections are complicated by
the presence of secondary or opportunist organisms. Indeed these secondary
organisms may be those which cause the most severe lesions or result in a
fatal outcome.
In this paper the primary virus and mycoplasma invaders of the respira­
tory tract of sheep and goats are considered. Some m a y be capable of infect­
ing without producing clinically apparent disease. The term « disease » has
been loosely interpreted therefore and information o n agents has been includ­
ed even if their pathogenicity for the respiratory tract is limited.
I. — A C U T E V I R A L I N F E C T I O N S
A. P A R A I N F L U E N Z A 3
There is no doubt that infection with the virus of parainfluenza type 3
(PI 3) is one of the most prevalent in the world.
The first isolation of this Paramyxovirus from sheep was m a d e by H o r e
(1966). Since then evidence of infection in sheep, by the isolation of virus or
the presence of antibodies, has been recorded in m a n y countries and it is pro­
bable that the virus is present in most, if not all countries.
The percentage of sheep showing antibodies varies according to each sur­
vey and the country in which the survey has been carried out. In general a
high percentage of sheep show antibodies to this virus, for example over 7 0 %
of sheep sera contain antibody in the U . S . A . (Fischman, 1967), France (Faye,
Charton and Le Layec, 1967), Turkey (Erhan and Martin, 1969), Australia
(St. George, 1971) and South Africa (Erasmus, Boshoff and Pieterse, 1967).
Clearly infection with P I 3 is both frequent and widespread in sheep.
1. Clinical disease.
The clinical signs of infection with PI 3 probably go undetected in the
field in most cases though signs of a mild infection, mainly of the upper res­
piratory tract, may occasionally be seen (Hore et al., 1968; Belak and Palfi,
1974a). Clinical signs following experimental infection are variable but com­
bined intratracheal and intranasal inoculation can produce transient pyrexia,
nasal discharge, coughing and other respiratory signs (Hore and Stevenson,
1969).
The relatively mild respiratory disease produced by experimental infection
of specific pathogen free (SPF) lambs with P I 3 is markedly altered when
Pasteurella haemolytica of biotype A is given by aerosol, about seven days
after the initial viral infection (Sharp et al., 1978; Davies et al., 1977). C o m ­
bined infections of this type will result in a high percentage of lambs develop­
ing moderate to severe pneumonic lesions in which high counts of pasteu-
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relia can be found. Pasteurella haemolytica without a previous PI 3 infection
does not generally produce a high percentage of severe disease when given in
an aerosol.
It seems probable that infection in the field situation with PI 3 is one way
in which biotype A Pasteurella haemolytica can infect the lungs of sheep to
produce outbreaks of respiratory disease (Gilmour, 1978).
Immunity to P I 3 virus is not absolute so that nasal shedding of virus may
follow infection even in sheep with moderate levels of circulating antibodies.
2. Pathology.
The apical lobes are most frequently affected. Usually small red, linear
areas of consolidation are present. On cross-section the consolidated lesions
are distributed extensively and follow smaller bronchi and bronchioles.
Pseudo-epithelialization of alveoli, hyperplasia of bronchiolar epithelium,
infiltration of alveolar septa and acidophilic cytoplasmic inclusions in bron­
chiole and alveolar epithelial cells are evident microscopically (Hore and Ste­
venson, 1969).
3. Diagnosis.
Serum neutralization (SN), haemagglutination-inhibition (HI) and E L I S A
tests are used to determine evidence of previous infection. Generally a four­
fold rise in H I titre is taken as indicating recent infection but such a rise does
not always occur despite evidence of infection confirmed by recovery of virus
in nasal secretions. Virus can only be isolated from lungs for u p to 7-10 days
following infection.
4. Immunity and control.
PI 3 infection is usually considered to be relatively mild and unnecessary
to control. However the complications which m a y follow invasion by other
organisms has led to an increasing interest in P I 3 vaccines. Live attenuated
vaccines and subunit vaccines are likely to become available for sheep.
Experimentally live PI 3 virus administered intranasally will stimulate the
production of specific IgA antibody into nasal secretions (Smith et al., 1975).
5. Economic significance.
The widespread occurrence of this virus and the established findings that
it allows other more sinister organisms to invade the lower respiratory tract
would indicate that it is a virus of considerable economic importance.
B. O T H E R P A R A M Y X O V I R U S E S A N D O R T H O M Y X O V I R U S E S
There is no confirmed evidence that either of the Paramyxoviruses,
parainfluenza 1 and 2, is an important pathogen of sheep. Because of the
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heterologous reactions which m a y occur between members of this group
some doubt exists as to the value which can be placed on surveys which sug­
gest that antibody to these viruses is present in sheep.
Sheep do not appear to be important reservoirs of influenza virus, though
evidence of infection has been reported from H u n g a r y (Romvary et al.,
1962). Experimental infection of sheep with influenza A did not result in cli­
nical illness (McQueen and Davenport, 1963).
C. A D E N O V I R U S
All serotypes of m a m m a l i a n adenovirus share a c o m m o n group-specific
antigen which can be detected by complement-fixation (CF) and gel-diffusion
(GD) tests. These tests have been used to show that adenovirus infection
occurs in sheep. The first isolation of adenovirus from sheep was reported in
1969 by McFerran et al.
Surveys carried out in a n u m b e r of countries have shown a variable per­
centage of sheep with antibodies : Iran : 14% (Ashfar, 1969), Greece : 3 1 %
(Pashaleri-Papadopoulou, 1968), but less t h a n 1% in Britain (Darbyshire and
Pereira, 1964) and the Republic of Ireland (Timoney, 1971).
Five serotypes of sheep adenovirus which can be distinguished by SN
tests, have been isolated, though several isolates are as yet untyped. A survey
in Scotland has shown the following percentage of sheep with antibodies t o
4 types : type 1 : 2 0 . 8 % , type 2 : 4 0 . 4 % , type 3 : 6 7 . 8 % and type 4 : 7 1 . 1 %
(Sharp, 1977). The high percentage of infection found in this survey contrasts
with the low prevalence in the earlier British surveys. T h e use of different test
methods (viz. G D and SN) is probably the major reason for the differing
results.
1. Clinical disease.
Little is k n o w n about adenovirus infections in sheep. Adenoviruses have
been isolated from apparently healthy sheep (Bauer et al, 1975) and from
lambs with respiratory signs (Sharp, 1977). It is not clear what natural infec­
tion with adenovirus may produce and experimental infection has generally
not resulted in notable clinical disease, though the virus may replicate and
produce lesions. In experiments described by Sharp et al. (1976) virus was
recovered following infection (p.i.) from nasal swabs (days 1-8 p.i.) and rec­
tal swabs (days 3-9 p.i.). Even when experimental adenovirus infection is fol­
lowed by an aerosol of Pasteurella haemolytica biotype A , n o serious disease
results (Sharp, 1977; Davies et al., 1981).
2. Pathology.
Ovine adenovirus type 4 has been shown to be capable of causing p u l m o ­
nary oedema and mild hepatic lesions (Sharp et al., 1976; Rushton and
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Sharp, 1977). Histology of the lungs showed accumulation of fluid in peri­
vascular and peribronchiole areas. In the liver focal necrosis was evident and
basophilic inclusion bodies were present in hepatocytes and lymphatic endo­
thelial cells (Rushton and Sharp, 1977).
Virus has been recovered u p to 14 days p.i. from tissues in the respiratory
and enteric tracts of lambs infected experimentally, which developed areas of
atelectasis and in some consolidation of the lungs. Microscopically there was
proliferative bronchiolitis and b r o n c h o p n e u m o n i a with cytomegaly and
karyomegaly of epithelial cells. In some nuclei basophilic inclusions were
seen containing crystalline arrays of virus particles (Davies et al., 1981).
3. Diagnosis.
Serum antibody can be determined by SN tests and some strains of virus
will agglutinate red blood cells of certain species. Rising titres are indicative
of recent infection but the isolation of virus is confirmatory of infection.
4. Immunity and control.
Colostral antibody levels decline progressively and lambs are free from
such antibody after 3-5 m o n t h s . New infections can then result in active
immunity and at the same time a concomitant increase in p n e u m o n i a has
been noted in the lambs in such flocks suggesting rapid spread of infection
through a susceptible population (Davies et al., 1980).
Vaccination of pregnant ewes has been suggested to provide passive
immunity for lambs during the first few weeks of life (Palfi et al., 1980). Suc­
cessful vaccination of lambs using U . V . inactivated virus adsorbed o n t o alu­
minium hydroxide has been reported but the i m m u n e response was signifi­
cantly reduced by the presence of colostral antibody (Palfi et al., 1980).
5. Economic significance.
At present the importance of adenovirus infections in sheep is not known.
The work of Davies et al. (1980) suggests that adenovirus causes varying
degrees of pneumonia and could therefore result in economically significant
loss of productivity.
6. Infection of sheep with bovine adenovirus.
The isolation of a type 2 bovine adenovirus from sheep has been reported
(Belak and Palfi, 1974b). This virus was isolated from lambs with enteritis
and p n e u m o n i a , some of which died. Inoculation of the virus into lambs p r o ­
duced clinical respiratory disease and enteritis, similar to the disease seen in
the original outbreak (Belak et al., 1975).
7. Adenovirus infections of goats.
T w o serologically different adenoviruses have been isolated from goats
with « peste des petits ruminants » in Nigeria. These isolates are not related
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to known ovine or bovine adenoviruses, and should probably be considered
as two caprine serotypes of adenovirus. Both isolates were considered to be
unassociated with the disease (Gibbs et al., 1977).
D. R E O V I R U S
Reoviruses have been isolated from several species of domestic animals
but their relationship to disease is doubtful.
Antibodies to reovirus have been found in sheep sera. In one small survey
96% of sheep sera had HI antibodies to reovirus type 3 and 1 5 % to types 1
and 2 (Stanley et al., 1964). SN antibodies to type 3 were shown to be IgG by
Pringle and Cartwright (1969) who concluded that reovirus infection was
widespread in sheep in Scotland. Antibodies to reovirus type 3 were present
in 4 6 % sheep sera in Northern Ireland but no antibodies to the other types
were found (McFerran et al., 1973).
Type 3 reovirus was first reported as isolated from sheep in 1973 (McFer­
ran et al., 1973), type 1 in 1974 (Belak and Palfi, 1974c) and type 2 in 1976
(Snodgrass et al., 1976).
1. Clinical disease.
Type 1 was recovered from lambs with respiratory and enteric disease
(Belak and Palfi, 1974c). When the virus was inoculated intratracheally and
intranasally into lambs, fever, enteritis and respiratory signs were evident
(Belak and Palfi, 1974d). In contrast no disease or lesions were produced fol­
lowing the inoculation of type 3 into lambs, though the virus replicated and
produced a serological reaction (McFerran et al., 1974).
2. Pathology.
The lesions described following experimental infection with type 1 were
mainly diffuse interstitial pneumonia and alveolar collapse (Belak and Palfi,
1974d).
3. Control and economic significance.
There is no substantial evidence that reovirus produces a sufficiently
serious infection in sheep to require control measures or that it is of econo­
mic importance.
E. R E S P I R A T O R Y S Y N C Y T I A L VIRUS (RSV)
The first reported evidence of RSV infection in sheep came from C a n a d a
where Berthiaume et al. (1973) recorded the presence of complement-fixing
antibodies in 8 1 % of 31 sheep. Smith et al. (1975) also found SN antibodies
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in sheep in U . S . A . N o antibodies to RSV were present in an intensive flock in
Britain where respiratory disease was a constant problem (Sharp, 1977).
RSV is a difficult virus to isolate but to date no report exists of its isola­
tion from natural infections in sheep.
Lehmkuhl and Cutlip (1979) inoculated a bovine strain of RSV into lambs
and produced a transient, mild disease with fever and serous nasal discharge.
Post-mortem examination showed mild interstitial p n e u m o n i a . F r o m 2 / 5
lambs virus was recovered from nasal or tracheal secretions or lung tissue.
RSV in goats.
A caprine RSV has been isolated from pygmy goats in America during an
outbreak of severe respiratory disease (Lehmkuhl and Smith, 1980). The cli­
nical signs observed in the goats during the outbreak included severe cough­
ing, oculo-nasal discharge, corneal opacity and fever. T h e virus, which was
isolated from the ocular and nasal secretions, was closely related antigenically but considered to be distinct from bovine RSV.
F. ENTEROVIRUS
Of the viruses classified within the 3 genera of the Picornaviridae
viz.
Enterovirus, Rhinovirus and Calicivirus only enteroviruses have been isolated
from sheep (McFerran et al., 1969; Snodgrass and Sharp, personal communi­
cation). At least one isolate differs from k n o w n bovine enteroviruses.
Though sheep enteroviruses have been isolated from lambs with diarrhoea no
disease has been attributed to these viruses following experimental inocula­
tion. N o serological surveys on the prevalence of the picornaviruses in sheep
appear to have been published.
G. P E S T E DES P E T I T S R U M I N A N T S V I R U S ( S Y N O N Y M — K A T A )
Peste des petits ruminants (PPR) is a rinderpest-like virus disease affect­
ing sheep and goats which is recognised in West Africa.
Although not primarily a respiratory disease respiratory signs can occur
during the acute phase of infection. Bronchopneumonia is a frequent compli­
cation which may be associated with secondary infection by Pasteurella
(Rowlands et al., 1969). Histology of the lung shows a giant cell p n e u m o n i a
and occasionally eosinophilic inclusion bodies in the epithelial cells of the res­
piratory tract.
The virus of P P R has been isolated in lamb kidney cells and was shown to
be distinct but related to the virus of rinderpest (Taylor and Abegunde,
1979).
The economic importance of this disease in West Africa is considerable.
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H. HERPESVIRUSES
The herpesvirus of infectious bovine rhinotracheitis (IBR) appears to be
capable of infecting goats and sheep.
IBR virus has been isolated from a single lamb « suffering from a respira­
tory disorder » (Trueblood et al., 1978). Natural infection with IBR virus
apparently caused severe respiratory disease and keratitis in 2 goats, from the
eyes and nose of which virus was recovered (Mohanty et al., 1972).
Antibody to IBR virus has been found in goats and sheep, particularly the
former. Of 561 goats surveyed in Chad, 1 3 % had antibodies to IBR virus
(Maurice and Provost, 1970); 12% of goats h a d antibody in Tanzania where­
as sheep were negative (Jesset and R a m p t o n , 1975), and in a survey in Nige­
ria 11.2% of goats had antibody whereas only 2 . 9 % of sheep showed evi­
dence of infection (Taylor et al., 1977).
A further herpesvirus, apparently distinct from IBR, has been isolated
from goat kids with a generalised fatal infection in which lesions were confin­
ed to the alimentary tract (Saito et al., 1974).
On intranasal inoculation into adult female goats fever was produced and
virus could be recovered from nasal secretions. In kids intranasal inoculation
resulted in fever, oculo-nasal discharge and bronchial sounds. This herpes­
virus was not pathogenic when inoculated into lambs and calves (Berrios et
al., 1975).
I. P O X V I R U S E S
Although sheep pox and goat pox are n o t primarily respiratory diseases,
lesions can apparently occur in the lungs of severely affected animals. Borrel
(1903) described hard, dense, hyaline nodules of varying size in the lungs of
sheep with sheep pox. The characteristic sheep pox cells, the « cellules claveleuses » may be found in such lesions as in the skin. Lung lesions occur in
many cases of sheep pox and inhalation is thought to be a m a i n route of
infection (Davies, 1976).
It is unlikely that sheep pox or goat pox would be recognised by the respi­
ratory signs which may occur but are more likely to be diagnosed by the m o r e
obvious skin lesions.
Occasionally, in a badly affected case of contagious pustular dermatitis
(« orf ») in sheep bronchopneumonia m a y occur, but this m a y b e the result
of the inhalation of large numbers of bacteria from orf lesions a r o u n d the
nostrils and m o u t h where these are extensive and severe.
J. B O R D E R D I S E A S E VIRUS
The Pestivirus which causes this disease is related antigenically and in
other characteristics to the viruses of mucosal disease - virus diarrhoea and
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swine fever (hog cholera). Although border disease is not primarily a respira­
tory disease, four clinico-pathological syndromes are recognised in one of
which pneumonitis may occur together with lymphoid infiltrations in a wide
range of organs ( R . M . Barlow, personal communication).
II. — V I R U S I N F E C T I O N S A S S O C I A T E D
WITH PROGRESSIVE PNEUMONIAS
A. S H E E P P U L M O N A R Y A D E N O M A T O S I S ( J A A G S I E K T E )
Sheep pulmonary adenomatosis (SPA) is a contagious t u m o u r of the
lungs of sheep. S P A has been reported from over 20 countries and most con­
tinents, but not from Australia or New Zealand.
T u m o u r s have been found in m a n y breeds and n o clear association with
any breed or sex of sheep has been established (Martin et al., 1979). N o defi­
nite information is available on the prevalence of this disease in sheep in any
country, probably because satisfactory diagnostic tests have not been availa­
ble.
T w o viruses have been associated with pulmonary adenomatosis : a her­
pesvirus (Mackay, 1969 a & b) (sometimes called Herpesvirus ovis or bovid
herpesvirus 4) and a retrovirus (Perk et al., 1974), both of which m a y be
involved in the production of the tumours (Martin et al., 1979). T h e herpes­
virus has been isolated from the lung t u m o u r of sheep in several countries :
Britain (Mackay, 1969 a & b), Kenya (Malmquist et al., 1972) and South
Africa (Verwoerd et al., 1979). T h e close association of this virus with the
t u m o u r is thus established. Its precise role, if any, in the development of the
t u m o u r has not been elucidated however. No correlation was found between
genome sequences of the herpesvirus and the presence of the t u m o u r (De Villiers and Verwoerd, 1980).
The retrovirus has not been isolated in cell cultures but its presence in
tumours has been detected by the determination of an RNA-dependant D N A
polymerase (reverse transcriptase enzyme) in virus particles with other cha­
racteristics of a retrovirus such as a buoyant density of 1.15-1.20 g / m l and
60-70 S R N A (Perk et al., 1974). It seems probable that this virus is the cause
of S P A but experimental proof is awaited.
1. Clinical disease.
Clinical disease is seldom seen in lambs, but generally in mature sheep of
2-4 years old. The incubation period is long and experimentally is usually lon­
ger t h a n 5 m o n t h s .
Only when tumours become sufficiently large or extensive to reduce nor­
mal lung function do clinical signs develop. Signs usually develop therefore in
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an individual sheep which shows respiratory disease but has no fever. Exag­
gerated respiratory movements, which increase on exercise, are evident.
Coughing and fever are not features. On auscultation both inspiratory and
expiratory sounds are present sometimes accompanied by very obvious
adventitious sounds. Loss of weight is marked. Death is the inevitable out­
come, sometimes as a result of intercurrent Pasteurella pneumonia.
A valuable and diagnostic clinical feature is the discharge of fluid from
the nose which occurs when the head is lowered and the hind legs are raised.
2. Pathology.
Tumours of S P A are confined to the lungs and very occasionally to the
associated lymph nodes. Ventral areas of the lungs are most frequently
affected with the tumours which are solid, grey or light purple. Lungs are
usually heavy and a copious quantity of frothy fluid is present in the respira­
tory passages. Pleurisy is sometimes present over the t u m o u r area.
On histological section the thin alveolar cells are replaced by columnar or
cuboidal cells, and in the bronchioles proliferation may be seen (Markson
and Terlecki, 1964).
3. Diagnosis.
No satisfactory confirmed diagnostic tests are recognised. Hyperglobulinaemia does occur (Hod et al., 1977) but such alterations in serum proteins
can arise from other causes of cachexia.
4. Immunity and control.
Limited observations suggest that antibodies to the herpesvirus are fre­
quently present in the serum of sheep in Scotland (Martin et al., 1979) and in
South Africa 60-70% of sheep have antibodies to the herpesvirus (Verwoerd et
al., 1979). At present nothing is known about the prevalence of the retrovirus.
Because of the lack of a suitable means of diagnosing subclinical infection
control in a flock is based on the early culling of sheep which show respira­
tory signs or wasting. In such flocks care should be taken to examine all
sheep which are over 2 years old, at frequent intervals.
International movement of sheep can result in the introduction of infec­
tion into the sheep flocks of a country. As no diagnostic test is available an
accurate history of the flock of origin and of the other flocks in the area
should be taken and local veterinary advice sought before agreement to the
importation of sheep is given.
5. Economic significance.
When the disease first appears in flocks losses may be heavy but endemic
infection is considered to cause an annual loss of a r o u n d 1-2% (Mackay and
Nisbet, 1966).
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The importance of this disease is probably low in international economic
terms, but importation should be avoided as in susceptible flocks losses may
be very high (Palsson, 1976).
B. M A E D I - V I S N A
Maedi is a progressive interstitial p n e u m o n i a and visna a meningoleucoencephalitis.
Both diseases are slowly progressive, afebrile diseases of sheep caused by
closely related or identical viruses belonging to the family Retroviridae,
sub­
family Lentivirinae.
Antigenically distinct strains have been described
(Narayan et al., 1978). The virus nucleoid contains reverse transcriptase.
Maedi-visna virus has now spread to sheep in most E u r o p e a n countries
and is recognised in several countries in Asia and Africa. In the U . S . A . the
disease has been termed (Montana) progressive p n e u m o n i a and in the Nether­
lands, « zwoegersiekte » (De Boer et al., 1978). Maedi is histologically simi­
lar to the disease described in France as « la bouhite » (Lucam, 1942).
The prevalence of infection is not known in many countries but infection
would appear to be increasing in the last decade or so (De Boer and H o u w e r s ,
1979). In the U . S . A . evidence of infection has been found in over 4 0 % of
sheep sera from the midwest and northwest states (Cutlip et al., 1977). In
another survey, in a western range flock of sheep in the U . S . A . , 6 4 % had
antibodies (Huffman et al., 1981). In the Netherlands one survey indicated
that about 3 0 % of sheep had antibodies (De Boer et al., 1978).
1. Clinical disease.
Clinical signs of maedi only appear after a long incubation period which
varies with the extent of the exposure and may be u p to 5 years (De Boer et
al., 1978). An affected sheep shows signs of progressive respiratory embar­
rassment, loss of weight and discolouration of the fleece. Despite the increas­
ing respiratory signs and weight loss, appetite is maintained t h r o u g h o u t the
course of the illness which can last for several m o n t h s .
The nervous form of the disease (visna) is encountered much less fre­
quently than maedi. In visna, fine muscular tremors progress to paresis and
eventually paralysis.
Hypochromic anaemia and a lymphocytic leucocytosis have been reported
in cases of maedi (Palsson, 1976).
2. Pathology.
In the early stages of infection no lesions may be evident in the lungs.
However in more advanced cases of maedi the lungs are generally greatly
enlarged and heavy (e.g. 2-4 times normal weight). Such lungs feel inelastic
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and have been likened to a plastic or rubber sponge. Some lungs may be pale
whereas others are mottled alternatively grey and brown. Secondary bacterial
infections can alter the appearance of affected lungs. The associated lymph
nodes are very enlarged.
Microscopically there is thickening of the interalveolar septa resulting
from infiltration by mononuclear cells and proliferation of the septal cells. A
prominent feature is focal hyperplasia of lymphoid tissue a r o u n d bronchi
and vessels in the lung. Gradually the cell infiltrates are replaced by fibro­
blasts and collagen fibre accompanied by proliferation of alveolar epithelium
and smooth muscle tissue so that there is extensive obliteration of alveoli.
3. Diagnosis.
A diagnosis of maedi-visna virus infection may be made on the presence
of serum antibodies (preferably GD or ELISA), the isolation of virus (from
white blood cells or tissues), or histopathology of the lung. Frequently two or
more methods may confirm the presence of infection, but sometimes only a
single method gives a positive result.
4. Immunity and control.
Sheep which become infected generally produce antibodies t h o u g h there
may be a delay of several months before antibodies can be detected. The pre­
sence of antibody however does not eliminate the virus which can still be
recovered from peripheral leucocytes and other tissues. It is important there­
fore to emphasise that the presence of antibody indicates that the sheep is
infected and may transmit infection to other sheep.
Infection is spread by the respiratory route, particularly where contact is
close, but also via the milk of infected ewes. Two methods of control have
been advocated (De Boer et al., 1978). One is the rearing in isolation of lambs
caught at parturition before they are able to suck or obtain colostrum from
their mother. The other method relies on serological testing of flocks at inter­
vals of about 6 months with the elimination from the flocks of any positive
sheep. In both methods isolation of the clean sheep from the infected flock is
essential. Infection is probably not transmitted to the lambs in utero (De
Boer et al., 1979).
Because of improved serological diagnostic techniques and greater aware­
ness of this slow virus disease, the international spread of this infection
should be reduced in future.
5. Economic significance.
The slow insidious nature of this disease may be disarming but its econo­
mic significance should not be underrated.
When maedi-visna infection has become endemic in flocks, losses have
sometimes been remarkably high. In Iceland losses were estimated as 15-30%
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annually (Palsson, 1976), and in the Netherlands a continuous annual morta­
lity of 1 5 % was noted on some individual farms (Ressang et al., 1968).
C. R E T R O V I R U S I N F E C T I O N IN G O A T S
An infectious disease of goats known as leukoencephalomyelitis, caprine
arthritis-encephalitis (CAE) syndrome or goat leukoencephalitis-arthritis, has
been described (Cork et al., 1974; Clements et al., 1980). C A E has been
reported in goats in America (Cork et al., 1974), Australia (O'Sullivan et al.,
1978) and in Sweden (Sundquist et al., 1981).
C A E is caused by a retrovirus with a virion-associated reverse transcrip­
tase enzyme and antigenic determinants which cross react with the P 30 com­
ponent of the virus of maedi-visna. It has been suggested that C A E virus is a
variant of the maedi-visna virus (Narayan et al., 1980).
1. Clinical disease.
The clinical syndrome may take 3 forms viz. :
a) progressive paresis leading to paralysis which is mainly seen in young
goats,
b) chronic progressive synovitis and periarthritis in older goats,
c) both of these syndromes may be accompanied by subclinical interstitial
pneumonia, which may also occur alone (Robinson, 1981).
The disease affects goat kids within the first few m o n t h s of life. T h e
disease is afebrile and characterised by progressive ataxia leading to paralysis
within a few weeks of onset and there is an accompanying interstitial pneu­
monia of varying extent. It is believed that goats may become infected in
utero or immediately after birth (Cork et al., 1974).
2. Pathology.
In addition to the lesions of leukoencephalomyelitis in which there is
dense perivascular cuffing with monocytes, infiltration of the parenchyma
with macrophages, proliferation of glial cells and demyelination, there is
interstitial p n e u m o n i a with hyperplasia of peribronchiolar lymphoid tissue.
A somewhat similar disease to C A E , termed g r a n u l o m a t o u s encephalitis
(GE) has been described in adult goats. In addition to the granulomas in the
brain this infection may result in chronic interstitial pneumonia and is believ­
ed to be caused also by a retrovirus related to maedi-visna (Robinson, 1981).
Although certain points of pathological difference exist between C A E and
G E the precise aetiological difference, if any, between these two diseases is
uncertain.
3. Control and economic significance.
The economic significance of retrovirus infections in goats is not clear at
present. However with the increasing interest in goats and a possible increase
— 324 —
in international trade in goats, the presence of these infections must be borne
in mind. Serological tests similar to those used for maedi-visna will detect the
presence of antibody.
III. — M Y C O P L A S M A
INFECTIONS
The first isolation of mycoplasma from the respiratory tract of small
ruminants was reported from sheep in 1955 (Greig, 1955). Since then the
number of isolates has increased, particularly in the last decade. At present 6
identified species of mycoplasma have been recovered from the respiratory
tract of sheep and goats, not all of which have been associated with disease.
Confirmed isolations of the following species of mycoplasma from the
respiratory tracts of sheep and goats have been reported :
— M. agalactiae from goats (Cottew and Lloyd, 1965) and sheep (Arisoy
et al., 1967).
— M. arginini from goats (Arisoy et al,
1968).
1967) and sheep (Barile et al.,
— M. mycoides
1949).
subsp. capri (« P G 3 ») from goats (Chu and Beveridge,
— M. mycoides
Aubaidi, 1972).
subsp. mycoides
— M. ovipneumoniae
1977).
— Acholeplasma
from goats and rarely from sheep (Al-
from sheep (Mackay et al., 1963) and goats (Harbi,
laidlawii from sheep (Krauss and W a n d e r a , 1970).
A . M.
OVIPNEUMONIAE
M. ovipneumoniae
is probably a world-wide inhabitant of the respiratory
tract of sheep and has been isolated from apparently healthy as well as
diseased sheep. The isolation of this mycoplasma has been reported from
several countries including Australia (Sullivan et al., 1973), America
(St. George and Carmichael, 1975), Britain (Foggie et al., 1976), Germany
(Stipkovits and Schimmel, 1977), Iraq (Al-Sultan and Zubaidy, 1978), the
Sudan (Harbi et al., 1981), Iceland (Friis et al., 1976) and H u n g a r y (Stipko­
vits et al., 1975).
1. Clinical disease.
M. ovipneumoniae
is considered to be responsible for chronic respiratory
infection which progresses slowly. Infection probably starts in lambs shortly
after birth having spread from carrier ewes, from which the mycoplasma can
be recovered repeatedly by swabbing the nasal mucosa. The number of
infected lambs increases progressively till, under intensive conditions, over
— 325 —
9 0 % of the lambs are infected when 3.5-4 m o n t h s old (Jones et al., 1979).
P o o r growth, exercise intolerance and even p n e u m o n i a have been ascribed to
infection with M. ovipneumoniae
(St. George et al., 1971).
2. Pathology.
The lungs of naturally-infected lambs are stated to be greyish in appea­
rance with red areas of collapse of varying size (St. George et al., 1971). T h e
main histological features are interstitial thickening due to proliferation of
septal cells, accumulation of monocytes in alveoli and lymphoid hyperplasia
a r o u n d bronchioles and vessels (St. George et al., 1971). When lambs are
exposed experimentally to infection with M. ovipneumoniae
a proportion
develop these changes (Sullivan et al., 1973; Foggie et al., 1976).
Rarely, however, is natural infection uncomplicated. A frequently asso­
ciated pathogen is Pasteurella haemolytica (Thurley et al., 1977). Dual infec­
tion with M. ovipneumoniae
and Pasteurella haemolytica of biotype A has
been shown experimentally to produce « proliferative-exudative » lung chan­
ges (Gilmour et al., 1979), indistinguishable from the « atypical p n e u m o n i a »
described by Stamp and Nisbet (1963). This is a c o m m o n disease of lambs
less than 1 year old. Acute disease is followed by a chronic condition in which
lung lesions and infection with mycoplasma may persist for 7 m o n t h s or lon­
ger (Gilmour et al., in press).
The economic importance of combined infection in lambs is believed to
be considerable. In addition to losses due to death of lambs, infected lambs
fail to gain weight as rapidly as non-infected control lambs and require to be
fed over a longer period before they achieve a satisfactory weight (Jones et
al., in press).
3. M. ovipneumoniae
in goats.
M. ovipneumoniae
has been isolated from the respiratory tract of goats in
Sudan (Harbi, 1977), America (Livingston and Gauer, 1979) and Australia
(Cottew, 1980), but the pathogenicity of this organism for goats is u n k n o w n .
B. M.
ARGININI
M. arginini is a c o m m o n inhabitant of the respiratory tract of sheep but
its ability to produce pathological changes, as a single infection, is doubtful
(Foggie and Angus, 1972; Jones, 1976). It m a y possibly act synergistically to
alter or exacerbate respiratory infections.
C. C O N T A G I O U S C A P R I N E P L E U R O P N E U M O N I A ( C C P P )
C C P P is one of the most serious and economically important diseases of
goats but fortunately sheep are not affected. C C P P has been reported as
occurring in 31 countries (McMartin et al., 1980).
— 326 —
The term C C P P is often applied to any mycoplasma p n e u m o n i a of goats
and considerable confusion has arisen over the precise mycoplasma causing
this infection. Several reviews have been written on this disease and its cause
(Swift, 1978; Cottew, 1979a; McMartin et al., 1980).
Three mycoplasmas have been isolated from C C P P - t y p e disease, each of
which has been considered to be the aetiological agent. These mycoplasmas
are M. mycoides subsp. capri, M. mycoides subsp. mycoides and an unclassi­
fied mycoplasma strain F 38 isolated by M a c O w a n and Minnette (1976).
M. mycoides subsp. capri (type strain P G 3) is considered to be the classi­
cal causal agent (Cottew, 1979a). Natural infection with M. mycoides subsp.
capri produces a respiratory disease which is confined to goats although both
sheep and goats can be infected experimentally but the disease is not conta­
gious.
M. mycoides subsp. mycoides isolates from goats with pleuropneumonia
(e.g. Perreau, 1971, 1979; Bar-Moshe and R a p p a p o r t , 1979) comprise two
morphological forms, namely small and large colony types (Cottew, 1979b).
The small colony types include the classical agent of contagious bovine pleu­
ropneumonia and are experimentally pathogenic for cattle, sheep and goats.
The large colony forms appear to be pathogenic only for goats and sheep
(MacOwan, 1976; Rosendal, 1981). One strain (F 30) of this organism, not
only p r o d u c e d p l e u r o p n e u m o n i a in sheep a n d g o a t s
following
intratracheal/endobronchial inoculation, but was also shown to cause
oedema at the site of subcutaneous inoculation and as the condition was not
transmissible by contact, MacOwan (1976) considered that this disease was
not classical C C P P .
McMartin et al. (1980) argue that only mycoplasma F 38 is capable of
causing classical C C P P . These authors emphasise that strain F 38 can pro­
duce disease with the three essential features noted in the original description
(Hutcheon, 1881, quoted by McMartin et al., 1980). These three points
were :
(1)
(2)
(3)
neous
the disease was readily contagious to susceptible goats,
sheep and cattle were not affected, and
local oedematous reactions did not occur in goats following subcuta­
inoculation.
On the basis of these findings McMartin et al. (1980) consider that only
mycoplasma F 38 is capable of causing classical C C P P . This view is support­
ed by the recent isolations of an F 38-type mycoplasma from goats with
C C P P in the Sudan (Harbi et al, 1981).
A fourth mycoplasma M. capricolum (« p p goat ») is pathogenic for
goats and for sheep but pneumonia is not a feature of the disease. This orga­
nism mainly causes septicaemia and polyarthritis.
— 327 —
1. Clinical disease.
After an incubation period of 2-28 days (generally 8-10 days) symptoms
of C C P P develop rapidly. Affected goats show fever and acute respiratory
distress. Breathing becomes difficult and the affected goat stands coughing,
with its m o u t h open, tongue protruding, drooling saliva a n d bleating in a dis­
tressed way. The course may be short with death occurring within 2 days but
frequently the illness continues for 3-4 weeks (Hutyra et al., 1938). Morbidity
is generally about 100% and a b o u t 50-90% of affected goats may die.
2. Pathology.
Lesions of C C P P are confined to the thorax. In the early stages lungs
may show yellow nodules surrounded by zones of congestion but as the
disease progresses these coalesce to include large areas of lung. Sero­
fibrinous pleurisy develops over the affected area which m a y involve a whole
lobe or even the entire lung. Thickening of interlobular tissue has been
described in some cases but McMartin et al. (1980) quote the original descrip­
tion by H u t c h e o n in 1881 who maintained that n o thickening of the interlo­
bular septa occurs. The bronchial and mediastinal lymph nodes are markedly
swollen but other organs in the b o d y are n o r m a l .
3. Immunity and control.
Classical C C P P is highly contagious and spreads rapidly to other goats
but not to sheep and cattle (McMartin et al., 1980). A combination of slaugh­
ter, isolation and vaccination has been used to control the disease. Strep­
tomycin given on the third day of fever has improved recovery a n d such
goats are completely i m m u n e (Rurangirwa et al., 1981). Tylosin and Oxyte­
tracycline may also be valuable therapeutically. Sonicated F 38 mycoplasma
in complete F r e u n d ' s adjuvant stimulated H I antibodies and protected goats
against in-contact challenge infection (Rurangirwa et al., 1981).
4. Economic importance.
C C P P is of major economic importance where goats form an important
sector of the livestock of any area or country.
D. CHLAMYDIAL INFECTIONS
Chlamydia are neither true viruses nor bacteria and have therefore not
been considered in this paper. They have however never been shown to be
important pathogens of the respiratory tract of sheep in Britain.
*
* *
— 328 —
Appendix
50th G E N E R A L SESSION O F T H E O . I . E .
R E S O L U T I O N N o . XVI
RESPIRATORY DISEASES OF SMALL R U M I N A N T S
INDUCED BY VIRUSES A N D M Y C O P L A S M A
CONSIDERING THAT
more research is required into the syndrome of respiratory diseases of
sheep and goats;
it is recognised that certain viruses, for example parainfluenza 3, adenovi­
rus, reovirus and maedi-visna virus m a y produce clinical disease per se.
However, in certain countries or under certain conditions, additional
microorganisms, for example bacteria or mycoplasma may be necessary for
clinical disease to be produced;
one well-recognised and important disease, contagious caprine pleuro­
pneumonia, which apparently is confined to Africa, is caused by a still
unnamed mycoplasma-type organism (F 38);
in general, the cause and epidemiology of much respiratory disease are
still largely unknown,
accordingly
THE COMMITTEE
RESOLVES T O R E C O M M E N D T H A T
1. Research efforts should be directed to clarify the aetiology and epide­
miology of respiratory disease,aimed at achieving more satisfactory control
measures.
2. Veterinary authorities in all countries should be aware of the danger of
importing such infections through normal international traffic in live sheep
and goats.
3. « Slow virus disease » in particular presents a problem in detection due
to the protracted nature of the disease process and the difficulty of determi­
ning the presence of infection by serological means. Thus any positive serolo­
gical result in a flock of sheep should be accepted as indicating the presence
of infection in that specific flock.
4. The availability of simple diagnostic methods would facilitate the disse­
mination of information on the presence of respiratory viruses and myco­
plasma and the application of appropriate measures of control.
(Adopted
by the International
Committee
*
* *
of the O.I.E. on 29 May
1982.)
— 329 —
REFERENCES
I. — Acute Viral Infections
1. ASHFAR A . (1969). — Vet. Rec, 84, 571-72.
2. BAUER K . , MILLER H . and GÜRTÜRK S . (1975). — Zentralblatt für
Veterinärmedi­
zin, 22 B, 656-65.
3. BELAK S. and PALFI V. (1974a). — Acta Vet. Acad. Sci. Hung., 24, 281-5.
4. BELAK S. and PALFI V. (1974b). — Arch. ges. Virusforsch., 46, 366-9.
5. BELAK S. and PALFI V. (1974c). — Arch. ges. Virusforsch., 44, 177-83.
6. BELAK S. and PALFI V. (1974d). — Acta Vet. Acad. Sci. Hung., 24, 241-7.
7. BELAK S., PALFI V. and TURY E . (1975). — Acta Vet. Hung., 25, 91-5.
8. BERRIOS P . E . , MCKERCHAR D . G . and KNIGHT H . D . (1975). — Am. J. vet. Res.,
36, 1763-9.
9. BERTHIAUME L . , JONCAS J . , BOULAY G . and PAVILANIS V. (1973). — Vet. Rec.,
93, 337-8.
10. BORREL A . (1903). — Ann. Inst. Past., 17, 6-100.
11. DARBYSHIRE J . H . and PEREIRA H . G . (1964). — Nature, London, 201, 895-7.
12. DAVIES D . H . , DUNGWORTH D . L . , HUMPHREYS S. and JOHNSON A . J . (1977). —
New Zealand vet. J., 25, 263-5.
13. DAVIES D . H . , DAVIES G . B . and PRICE M . C . (1980). — New Zealand vet. J., 28,
125-7.
14. DAVIES D . H . , DUNGWORTH D . L . and MARIASSY A . T . (1981). — Vet. Microbiol.,
113-28.
15. DAVIES D . H . , HERCEG M . , JONES B . A . H . and THURLEY D . C . (1981). — Vet.
Microbiol., 6, 173-82.
16. DAVIES F . G . (1976). — J. Hyg., Camb., 76, 163-71.
17. ERASMUS B . J . , BOSHOFF S . T . and PIETERSE L . W . (1967). — Bull. Off. int. Epiz.,
68, 657-64.
18. ERHAN M . and MARTIN W . B . (1969). — Pendik Vet. Kont Ve Arastirma Enstitüsü Derg., 11, 90-5.
19. FAYE P . , CHARTON A . and L E LAYEC C . (1967). — Bull. Acad. vét. France, 40,
203-7.
20. FISCHMAN H . R . (1967). — Am. J. Epidemiol., 85, 272-81.
21. GIBBS E . P . J . , TAYLOR W . P . and LAWMAN M . J . P . (1977). — Res. vet. Sci., 23,
331-5.
22. GILMOUR N . J . L . (1978). — Vet. Rec., 102, 100-2.
23. HORE D . E . (1966). — Vet. Rec., 79, 466-7.
— 330 —
2 4 . HORE D . E . , STEVENSON R . G . , GILMOUR N . J . L . , VANTSIS J . T . and THOMPSON
D . A . (1968). — J. comp. Path., 78, 2 5 9 - 6 5 .
2 5 . JESSETT D . M . and RAMPTON C S . ( 1 9 7 5 ) . — Res. vet. Sci., 18, 2 2 5 - 6 .
2 6 . LEHMKUHL H . D . and CUTLIP R.C. ( 1 9 7 9 ) . — Am. J. vet. Res., 40, 5 1 2 - 4 .
2 7 . LEHMKUHL H . D . and SMITH M . H . ( 1 9 8 0 ) . — IInd Int. Symp. of Vet. Lab. Diag­
nosticians, 264-7.
2 8 . MCFERRAN J . B . , NELSON R., MCCRACKEN J.M. and Ross J . G . ( 1 9 6 9 ) . —
Nature, London,
221, 194-5.
2 9 . MCFERRAN J . B . , NELSON R. and CLARK J . K . ( 1 9 7 3 ) . — Arch. ges.
40, 7 2 - 8 1 .
Virusforsch.,
30. MCFERRAN J . B . , BASKERVILLE A . and NELSON R. ( 1 9 7 4 ) . — Res. vet. Sci., 17,
356-9.
3 1 . MCQUEEN J.L. and DAVENPORT F . M . ( 1 9 6 3 ) . — Proc. Soc. exp. Biol. Med., 112,
1004-6.
32. MAURICE Y . and PROVOST A . (1970). — Rev. Elev. Méd. vét. Pays trop., 23, 4 1 9 23.
3 3 . MOHANTY S.B., LILLIE M . G . , CORSELIUS N . B . and BECK J . D . ( 1 9 7 2 ) . — J. Am.
vet. Med. Assoc., 160, 879-80.
34. PALFI V . , BELAK S. and PALYA V . ( 1 9 8 0 ) . — Vet. Microbiol.,
5, 7 3 - 7 .
3 5 . PASHALERI-PAPADOPOULOU E. (1968). — Hellenike Kteniatrike,
Thessaloniki,
11, 1 8 8 - 9 3 .
3 6 . PRINGLE C R . and CARTWRIGHT L . N . ( 1 9 6 9 ) . — J. Med. Microbiol,
3 7 . ROMVARY J . , TAKATSY G . , BARB K . and FARKAS E. ( 1 9 6 2 ) . — Nature,
193, 9 0 7 - 8 .
2, 1 1 7 - 2 3 .
London,
3 8 . ROWLANDS A . C . , SCOTT G . R . and H I L L D . H . ( 1 9 6 9 ) . — J. Path., 98, 8 3 - 7 .
3 9 . RUSHTON B . and SHARP J . M . ( 1 9 7 7 ) . — J. Path., 121, 163-7.
4 0 . SAITO J . K . , GRIBBLE D . H . , BERRIOS P . E . , KNIGHT H . D . and MCKERCHAR D . G .
(1974). — Am. J. vet. Res., 35, 8 4 7 - 8 .
4 1 . SHARP J . M . , RUSHTON B . and RIMER R . D . ( 1 9 7 6 ) . — J. comp. Path., 86, 6 2 1 - 8 .
4 2 . SHARP J.M. (1977). — Thesis, University of Edinburgh.
4 3 . SHARP J . M . , GILMOUR N . J . L . , THOMPSON D . A . and RUSHTON B . ( 1 9 7 8 ) . — J.
comp. Path., 88, 237-44.
44. SMITH W . D . , WELLS P . W . , BURRELLS C . and DAWSON A . McL. ( 1 9 7 5 ) . — Arch.
Virol, 49, 329-37.
4 5 . SNODGRASS D . R . , BURRELLS C . and WELLS P . W . ( 1 9 7 6 ) . — Arch.
143-9.
Virol., 52,
4 6 . STANLEY N . F . , LEAK P . J . , GRIEVE G . M . and PERRET D . ( 1 9 6 4 ) . — Aust. J. exp.
Biol. Med. Sci., 42, 373-84.
— 331 —
47. ST. GEORGE T . D . (1971). — Aust. vet. J., 47, 370-4.
48. TAYLOR W.P., OKEKE A . N . C . and SHIDALI N . N . (1977). — Trop. Anim.
Hlth.
Prod., 9, 171-5.
49. TAYLOR W . P . and ABEGUNDE A. (1979). — Res. vet. Sci., 26, 94-6.
50. TIMONEY P . J . (1971). — Brit. vet. J., 127, 567-71.
51. TRUEBLOOD M . S . , SWIFT B.L. and MCHOLLAND-RAYMOND L. (1978). — Canad.
J. comp. Med., 42, 97-9.
II. — Progressive
Pneumonias
1. CLEMENTS J . E . , NARAYAN O . and CORK L.C. (1980). — Biochemical Characteri­
sation of the Virus Causing Leukoencephalitis and Arthritis in Goats. J. gen.
Virol., 50, 423-7.
2. CORK L.C., HADLOW W . J . , CRAWFORD T.B., GORHAM J . R . and PIPER R.C.
(1974). — Infectious leukoencephalomyelitis of young goats. J. Inf. Dis., 129, 13441.
3. CRAWFORD T.B., ADAMS D . S . , CHEEVERS W . P . and CORK L.C. (1980). — Chro­
nic Arthritis in Goats caused by a Retrovirus. Science, 207, 997-9.
4. CUTLIP R.C., JACKSON T.A. and LAIRD G.A. (1977). — Am.
J. vet. Res., 38,
2091-3.
5. D E BOER G . F . , TERPSTRA C. and HOUWERS D . J . (1978). — Bull. Off. int. Epiz.,
89, 487-506.
6. D E BOER G.F. and HOUWERS D . J . (1979). — Epiz. of maedi-visna in sheep. In :
« Aspects of Slow and Persistant Virus Infections », Ed. D . A . Tyrrell. P u b .
ECSC, EEC, EAEC Brussels, 198-220.
7. D E BOER G.F., TERPSTRA C. and HOUWERS D . J . (1979). — Res. vet. Sci., 26,
202-8.
8. D E VILLIERS E. and VERWOERD D . W . (1980). — Onderstepoort J. vet. Res., 47,
109-12.
9. H O D I., ZIMBER A. and KLOPPER U . (1977). — Brit. vet. J., 133, 56-61.
10. HUFFMAN E . M . , KIRK J . H . , WINWARD L. and GORHAM J . R . (1981). — J.
Am.
vet. Med. Assoc., 178, 708-710.
11. LUCAM F. (1942). — Rec. Méd. Vét, 118, 273-258.
12. MACKAY J . M . K . and NISBET D . I . (1966). — Vet. Rec., 78, 18-24.
13. MACKAY J . M . K . (1969a). — J. comp. Path., 79, 141-6.
14. MACKAY J . M . K . (1969b). — J. comp. Path., 79, 147-154.
15. MALMQUIST W . A . , KRAUSS H . H . , MOULTON J . E . and WANDERA J . G . (1972). —
Lab. Invest., 26, 528-33.
16. MARKSON L . M . and TERLECKI S. (1964). — Path. Vet., 1, 269-288.
— 332 —
17. MARTIN W . B . , ANGUS K . W . , ROBINSON G . W . and SCOTT F . M . M . (1979). —
Comp. Immun. Microbiol. Inf. Dis., 2, 313-25.
18. NARAYAN O., GRIFFIN D . E . and CLEMENTS J . C . (1978). — J. gen. Virol, 41,
343-52.
19. O'SULLIVAN B . M . , EAVES F . W . , BAXENDELL S . A . and ROWAN K.J. (1978). —
Leukoencephalomyelitis of goat kids. Aust. vet. J., 54, 479-83.
20. PALSSON P . A . (1976). — Maedi and Visna in Sheep. In : « Slow Virus Diseases of
Animals and Man », Ed. R . H . Kimberlin, Pub. North Holland Publishing Co.,
17-43.
21. PERK K., MICHALIDES R . , SPIEGELMAN S . and SCHLOM J. (1974). — J. Nat. Can­
cer Inst., 53, 131-5.
22. RESSANG A . A . , D E BOER G . F . and D E WIJN G . C . (1968). — Path. Vet., 5, 353-
69.
23. ROBINSON W . F . (1981). — Chronic Interstitial Pneumonia in Association with a
Granulomatous Encephalitis in a Goat. Aust. vet. J., 57, 127-31.
24. SUNDQUIST B . , JONSSON L . , JACOBSSON S . and HAMMARBERG K. (1981). — Acta
Vet. Scand., 22, 315-30.
25. VERWOERD D . W . , MEYER-SCHARRER E . , BROCKMAN J . and D E VILLIERS E . M .
(1979). — Onderstepoort J. vet. Res., 46, 61-3.
III. — Mycoplasmas
1. AL-AUBAIDI J . M . , DARDIRI A . H . and FABRICANT J . (1972). — Int. Journal of
Systemic Bacteriology, 22, 155.
2. AL-SULTAN I.I. and ZUBAIDY A . J . (1978). — Vet. Path., 15, 682.
3. ARISOY F . , ERDAG O., COTTEW G . S . and WATSON W . A . (1967). — Turk.
Vet.
Hekimleri Dernegi Derg., 37, 11-17.
4. BARILE M . F . , D E L GINDICE R . A . , CARSKI T . R . , GIBBS C . J . and MORRIS J . A .
(1968). — Proc. Soc. exp. Biol. Med., 129, 489-94.
5. BAR-MOSHE B . and RAPPAPORT E. (1979). — Refuah Vet., 36, 53-54.
6. CHU H.P. and BEVERIDGE W.I.B. (1949). — Quoted by Cottew, 1979a.
7. COTTEW G.S. and LLOYD L . C . (1965). — J. comp. Path., 75, 363-74.
8. COTTEW G.S. (1979a). — In : « The Mycoplasmas ». Ed. J . G . Tully and R . F .
Whitcomb. Pub. Academic Press, New York, Vol. 2, 119.
9. COTTEW G.S. (1979b). — Zbl. Bakt. Hyg. I., A 245, 164-70.
10. COTTEW G.S. (1980). — I.O.M. International Research Programme on Compara­
tive Mycoplasmology (1978-80).
11. FOGGIE A. and ANGUS K.W. (1972). — Vet. Rec, 90, 312-313.
12. FOGGIE A., JONES G.E. and BUXTON D. (1976). — Res. vet. Sci., 21, 28-35.
— 333 —
13. FRIIS N . F . , PALSSON P . A . and PETURSSON G . (1976). — Acta vet. Scand., 17,
255-7.
14. GILMOUR J . S . , JONES G . E . and RAE A . G . (1979). — Comp. Immun.
Infect. Dis., 1, 285-93.
Microbiol.
15. GILMOUR J . S . , JONES G . E . , KEIR W . A . and R A E A . G . — J. comp. Path. (in
press).
16. GREIG A . S . (1955). — Canad. J. comp. Med., 19, 265-71.
17. HARBI M . S . M . A . (1977). — Bull. Anim. Hlth. Prod. Afr., 25, 91-5.
18. HARBI M . S . M . A . , E L TAHIR M . S . , M A C O W A N K . J . and NAYIL A.A. (1981). —
Vet. Rec., 108, 261.
19. HUTYRA F . , MAREK J . and MANNINGER R. (1938). — « Special Pathology and
Therapeutics of the Diseases of Domestic Animals », Pub. Bailliere, Tindall and
Cox, London, 1, 455-72.
20. JONES G . E . (1976). — Ph. D. Thesis, University of Edinburgh.
21. JONES G . E . , BUXTON D. and HARKER D . B . (1979). — Vet. Microbiol., 4, 47-59.
22. JONES G . E . , FIELD A . C . , GILMOUR J . S . , RAE A . G . and NETTLETON P . — Vet.
Rec. (in press).
23. KRAUSS H . and WANDERA J.A. (1970). — J. comp. Path., 80, 389-97.
24. LIVINGSTON C . W . Jr. and GAUER B . B . (1979). — I.O.M. International Research
Programme on Comparative Mycoplasmology (1978-80).
25. MACKAY J . M . K . , NISBET D . K . and FOGGIE A. (1963). — Vet. Rec., 75, 550-1.
26. MCMARTIN D.A., MACOWAN K . J . and SWIFT L . L . (1980). — Brit. vet. J., 136,
507.
27. MACOWAN K . J . (1976). — Ph. D. Thesis, University of Edinburgh.
28. MACOWAN K . J . and MINETTE J.E. (1976). — Trop. Anim. Hlth. Prod., 8, 91-5.
29. PERREAU P . (1971). — Rev. Elev. Méd. vét. Pays trop., 24, 343-8.
30. PERREAU P . (1979). — Bull. Acad. vét. France, 52, 575-81.
31. ROSENDAL S. (1981). — Vet. Path., 18, 71-81.
32. RURANGIRWA F . R . , MASIGA W . N . and MUTHOMIA E. (1981). — Vet. Rec,
109,
310.
33. STAMP J . T . and NISBET D.I. (1963). — J. comp. Path., 73, 319-28.
34. ST. GEORGE T . D . , SULLIVAN N . D . , LOVE J.A. and HORSFALL N . (1971).
—Aust.
vet. J., 47, 282-3.
35. ST. GEORGE T . D . and CARMICHAEL L.E. (1975). — Vet. Ree, 97, 205-6.
36. STIPKOVITS L., BELAK S., PALFI V. and TURY E. (1975). — Acta Vet. Acad. Sci.
Hung., 25, 267-73.
— 334 —
37. STIPKOVITS L . and SCHIMMEL D . (1977). — Arch, für exper. Veterinärmedizin, 31
(2), 187-9.
38. SULLIVAN N . D . , ST. GEORGE T . D . and HORSFALL N . (1973). — Aust. vet. J., 49,
57-68.
39. SWIFT L.L. (1978). — MSc. Thesis, University of Edinburgh.
4 0 . THURLEY D . C . , BOYES B . W . , DAVIES D . H . , WILKINS M.F., O'CONNELL E. and
HUMPHREYS S. (1977). — New Zealand vet. J., 25, 173-6.