Ovine pulmonary adenocarcinoma (OPA) - recent
developments in early pre-clinical detection using ultrasound
Ovine pulmonary adenocarcinoma (OPA) is a contagious lung tumour
of sheep resulting from infection with a betaretrovirus called
Jaagsiekte sheep retrovirus (JSRV). The disease is also
commonly known as Jaagsiekte, ovine pulmonary carcinoma, or sheep
pulmonary adenomatosis. Tumour growth replaces the normal lung
structure and consequently impairs lung function. In addition
the tumour cells may secrete large volumes of fluid, also impairing
lung function. Transmission of JSRV occurs mostly through the
aerosol route but also via colostrum and milk.
Tumour growth has replaced the normal lung structure affecting
the ventral portions of all lung lobes.
This sheep would have been excreting large volumes of virus
before clinical signs of OPA were observed.
OPA is common in the UK but the disease is grossly
under-reported because few sheep deaths are investigated. It
is generally considered a chronic wasting disease with progressive
respiratory distress and is invariably fatal. In the field,
the incubation period from infection with JSRV to the appearance of
clinical signs is many months or years with clinical disease most
commonly observed in three to four year-old sheep, though it is
occasionally seen at less than one year old. The time from
appearance of obvious respiratory signs to time of death ranges
from days to several months.
The sheep's appetite remains good throughout the disease
process. As the disease progresses, affected sheep become
increasingly tachypnoeic at rest with an increased abdominal
component to their breathing effort. OPA lesions may
predispose to secondary bacterial pneumonia causing sudden death
despite antibiotic treatment. Thoracic auscultation does not
aid diagnosis. Post mortem examination of the lungs backed by
histology remains the gold standard diagnostic test for OPA.
Fluid gathers within the respiratory tract and first appears as
a scant serous nasal discharge, and during the advanced stages of
clinical disease may flow freely from both nostrils when the head
is lowered during feeding. This quantity may exceed 50 ml if
the hindquarters are raised when the head is simultaneously lowered
(colloquially referred to as the "wheelbarrow test"). Sheep showing
a positive "wheelbarrow test" test should be euthanased immediately
for welfare reasons as they are often severely dyspnoeic afterwards
and death is not uncommon in the next 24 hours. In addition,
because the fluid contains a high concentration of infectious virus
it is imperative to remove affected animals from the flock to
reduce the risk of transmission. Although a positive
"wheelbarrow test" is pathognomonic for OPA, about one third of OPA
cases produce no detectable fluid even in the advanced stages of
disease. Sheep with early OPA or with advanced OPA but no
apparent fluid production will also be excreting JSRV into the air
and are potentially infectious. Therefore improved
pre-clinical detection will be vital for effective OPA control and
potential disease elimination, especially because there is no
imminent prospect of a vaccine for JSRV.
About one third of OPA cases produce no detectable fluid even
in the advanced stages of disease.
JSRV-infected sheep do not make a detectable antibody response
to the virus thus ruling out serological tests for diagnosis of
infection. A PCR-based test to detect infected cells in the
blood proved insufficiently sensitive to be useful in field
applications. Clinical imaging techniques such as computed
tomography have been proposed for OPA diagnosis but is far too
expensive for commercial sheep, the method requires general
anaesthesia, the equipment is available only in a small number of
universities with veterinary departments, and biocontainment
measures within the facility would prove difficult to operate.
Ultrasonography has previously been shown to readily
differentiate chronic lung lesions in adult sheep including
detection of OPA lesions as small as 2 cm in diameter involving the
visceral pleura. An early evaluation phase prospective study has
demonstrated the accuracy of trans-thoracic ultrasound examination
using a 5-6.5 MHz sector ultrasound machine widely available in
veterinary practice in the United Kingdom to diagnose OPA.
Restraint, preparation and examination time was restricted to
5 minutes per sheep to represent the cost limitations of commercial
sheep farming. One hundred sheep were examined and all 41
cases identified with suspect OPA lesions during trans-thoracic
ultrasound examination had the diagnosis confirmed at necropsy,
whilst sheep without ultrasonographic changes characteristic of OPA
had no gross lesions of OPA at necropsy. This study
demonstrated the specificity of trans-thoracic ultrasound for
diagnosis of OPA. Trans-thoracic ultrasound examination should be
considered for a second opinion on an initial diagnosis of OPA, for
screening purchased adult flock replacements for OPA, or for
screening sheep in a known OPA-affected flock but a negative scan
cannot provide a guarantee that the animal is free of JSRV
infection nor early OPA.
Classical appearance of small 2-3 cm hypoechoic OPA lesion in
the ventral portion of the lung lobe displacing the lung medially
Necropsy findings of early OPA lesion (see previous ultrasound
Suspect early 1-2 cm OPA lesion was shown at necropsy to be a
lungworm lesion (see below).
Lungworm lesions have been mis-diagnosed as very early OPA
3768 adult sheep in four flocks (500, 648, 700 and 1920 breeding
ewes, respectively) were screened for ovine pulmonary
adenocarcinoma (OPA) during autumn/winter 2015/16 using a 6.5 MHz
microconvex probe connected to a real-time, B-mode ultrasound
machine. Trans-thoracic ultrasonographic examination of both
sides of the chest was undertaken at a rate of 60-80 sheep per
hour. This ultrasound examination rate was recognised as a
compromise between accuracy and cost with a target cost of
approximately £1 per sheep considered acceptable to commercial
farmers. All sheep with suspected OPA were culled from the
flocks and necropsied. OPA was confirmed in 6/8, 26/29 and 23/36
suspected cases; one flock had no OPA cases. Seven of 16 false
positive sheep had extensive lung abscessation with no primary OPA
lesion. Seven of 16 false positive sheep had 1-3 cm lungworm
(Muellerius capillaris) lesions involving the visceral pleura.
Three sheep in one flock have been diagnosed with OPA in the 3-8
months following initial ultrasound scanning.
Extensive lung consolidation associated with marked secondary
abscessation has been a common error in OPA diagnoses.
Ultrasound scan revealing lung consolidation and multiple
abscesses. This sheep was mis-diagnosed as OPA.
Ultrasound scan reveals lung consolidation and multiple
abscesses. This sheep was correctly diagnosed as OPA with
Secondary abscessation is common in OPA lesions.
OPA or fibrosis surrounding abscesses?
Extensive fibrosis surrounding lung abscesses. Such
pathology looks similar to OPA on ultrasound examination (see above
Two separate errors were generated in the ultrasound diagnosis
OPA in this study; namely 1-3 cm lesions of lung consolidation
associated with lungworm (Muellerius capillaris) infestation and
secondly, extensive lung consolidation associated with marked
secondary abscessation. The first error could be overcome by
not considering such small lesions as OPA and repeat scanning such
small lesions after 3-6 months where there would progression of the
lesion if OPA but not with lungworm lesions. Biocontainment is poor
on most sheep farms especially for small numbers of sheep, and the
farmers in this study simply wanted to remove all suspected OPA
cases. Sheep in the second category with extensive lung
pathology would have been culled because they would likely have
been unproductive. There are few reports of such extensive lung
consolidation and abscessation in the absence of OPA.
The surface of normal aerated lung (visceral or pulmonary
pleura) is characterised by the continuous (across the whole image)
white linear echo which moves in time with respiration. 5MHz sector
(micro-convex) scanner. The probe head is at the top of the
image, dorsal is to the left, centimetre markers in the right hand
margin. The heart can be identified at the ventral margin of
the lung lobes immediately beneath the chest wall. The heart
is clearly imaged towards the end of this recording. For
sheep within a weight range from 30 to 100 kg, the field depth is
set at 6 cm and increased when there is lung pathology present.
6.5MHz sector scanner.
The surface of normal aerated lung (visceral or pulmonary
pleura) is characterised by the uppermost white linear echo which
moves in time with respiration. 5MHz sector scanner. The
probe head is at the top of the image, dorsal is to the left,
centimetre markers in the right hand margin. The field depth is set
at 6 cm including chest wall. This recording was taken over the 5th
-7th intercostal spaces. 6.5MHz sector scanner.
Loss of the bright linear echo formed by normal aerated lung
tissue (visceral or pulmonary pleura) at the ventral margin of the
lung lobe replaced by a 2 cm deep hypoechoic area representing a
very early OPA lesion. The heart is clearly visible ventrally (to
the right). 6.5MHz sector scanner.
recording early OPA
Abrupt loss of the bright linear echo formed by normal aerated
lung tissue at the ventral margin of the lung lobe replaced by a
3-4 cm deep hypoechoic area representing an early OPA lesion. The
heart is clearly visible distally at the end of the
recording. 6.5MHz sector scanner.
Sharply demarcated area of consolidation dorsally representing
OPA tumour extending for approximately 6 cm into the lung
parenchyma. The heart (represented by the anechoic area in the
bottom right of the sonogram) is displaced by the tumour mass
ventrally. 6.5MHz sector scanner.
Purchase of OPA-infected but clinically normal breeding
replacement stock (both ewes and rams) is the major risk factor for
introducing OPA into clean flocks. Ideally, breeding
replacements would be obtained from flocks declared free of OPA but
confirmation of such status in the absence of commercially
available tests is not possible. Best practice is to identify and
cull out sheep with any sign of the disease as early as possible.
Some flocks impose a harsh policy to try to reduce the incidence of
OPA where they cull thin, tachypnoeic or coughing sheep.
Culling out on the basis of weight loss and respiratory signs
inevitably means that a proportion of the sheep culled will not in
fact have OPA.
Ultrasound screening would allow more accurate selection. In
addition, detection of OPA lesions by ultrasound examination should
allow culling at an earlier stage than recognition of clinical
signs by the farmer, and would permit culling while the sheep is
still in good body condition, is fit to travel and has greater
value for slaughter. In addition, the ability to identify
affected animals at an earlier stage will be a positive step
forward in reducing transmission of JSRV. Tumour cells
produce the virus and release it into the respiratory secretions,
so sheep with larger tumours are likely to be a greater risk for
transmission to other sheep.
Prevention of spread from neighbouring premises can be effected
by maintaining a closed disease-free flock with double ring fencing
around the perimeter of the farm.
Biocontainment - the main route of infection is by respiratory
aerosol with close confinement during housing or trough feeding
increasing the rate of spread of infection therefore housing must
only be undertaken if essential for flock management purposes.
Maintaining sheep in single age groups has been shown to be the
most important management factor in reducing clinical disease.
Maintain sheep in single age groups has been shown to be the
most important management factor in reducing clinical OPA.