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A field study of ovine listerial meningo-encephalitis with particular reference to cerebrospinal fluid analysis as an aid to diagnosis and prognosis
Br. vet.J. (1993). 149, 165
A FIEIJD S T U D Y O F O V I N E LISTERIAL MENINGO-ENCEPHAI.ITIS W I T H P A R T I C U L A R REFERENCE T O CEREBROSPINAL FLUID ANALYSIS AS A N AID T O D I A G N O S I S A N D P R O G N O S I S
P. R. SCOTI" Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, VeterinaryField Station, Easter Bush., Roslin, Midlothian EH25 9RG
SUMMARY In a field study of listerial meningo-encephalitis involving 21 sheep from six silage-fed flocks, the neurological signs included profound depression, circling, involvement of the trigeminal and facial cranial nerves and lateral recumbency with propulsive limb movements. Within the six flocks the incidence of listerial meningo-encephalitis did not exceed 1% of the adult sheep at risk. Eleven of 18 (61%) adult animals were 2 years old. Evidence of an intrathecal inflammatory response in suspected listerial meningo-encephalitis cases was indicated by an increased cerebrospinal fluid (CSF) protein concentration greater than 0.4 g / l in 18 of 21 cases (86%), increased white cell count above 0.012x109/1 in 17 cases (81%) and lymphocyte percentage below 50% in all animals. None of the CSF parameters proved to be a reliable prognostic indicator because of the range of CSF values obtained and the small number of sheep which recovered.
INTRODUCTION In the UK meningo-encepha.litis caused by Listeria monocytogenes infection is the most common bacterial infection of the central nervous system of adult sheep. The treatment response of ovine listerial meningo-encephalitis is reported to be poor (Barlow, 1983; Low & Donachie, 1991). However, as multiple treatments are commonly administered to sheep with neurological disease the treatment response is not an accurate aid to diagnosis of listerial meningo-encephalitis. The provisional diagnosis of listerial meningo-encephalitis can only be confirmed histologically (Low & Donachie, 1991). In the living animal, differentiation of listerial meningo-encephalitis from such metabolic diseases as ovine pregnancy toxaemia and polioencephalomalacia has been facilitated by the demonstration of an intrathecal inflammatory response in ovine listeriosis (Scott, 1992). 0007/1935/93/020165-06/$08.00/0
© 1993 Bailli~reTindall
166
BRITISH VETERINARY JOURNAL,. 149, 2
This study reports some aspects of the epidemiology of ovine listerial meningoencephalitis and investigates the application of cerebrospinal fluid (CSF) analysis as an aid to diagnosis and prognosis.
MATERIALS AND METHODS
A 2-year prospective survey was undertaken on six farms in East Central Scotland which experienced cases of ovine listerial meningo-encephalitis. The sheep were at pasture for most of the year but were housed in early January and throughout late pregnancy in purpose-built sheep sheds then returned to pasture in April following lambing. Grass silage was fed throughout the housed period. The neurological examination of suspected cases of ovine listerial meningoencephalitis was based on the report of bovine listeriosis (Rebhun, 1987). A lumbosacral CSF sample was collected under local anaesthesia from 21 sheep at the time of presentation using the method described previously (Scott & Will, 1991). Total CSF white cell counts were performed on a haemocytometer. Samples of CSF were concentrated by cytospin within 2 h of collection, air dried and stained with Leishman stain. The differential white cell count was based on a minimum of 20 cells. The CSF protein concentration was determined by the pyrogallol method (Randox Laboratories Ltd). Each animal received 1.1 m g / k g bodyweight of dexamethasone (Soludex®, Mycofarm) intravenously once at the start of treatment. Penicillin G was administered intramuscularly twice daily at a dose rate of 44 000 iu/kg bodyweight (Depocillin®, Mycofarm). The majority of animals were in late gestation and symptomatic treatment with a concentrated oral electrolyte solution (Liquid Lectade®, Smith, Kline Beecham) was administered twice daily at the manufacturer's recommended rate. If the neurological condition deteriorated, the animal was humanely destroyed and a second lumbosacral CSF sample collected. The diagnosis of listerial meningo-encephalitis was confirmed histologically. No bacteriological culture of brain tissue or CSF was undertaken.
RESULTS Listerial meningo-encephalitis was encountered in 21 sheep from six flocks which had been housed during January and fed grass silage ad libitum. All but one case of listerial meningo-encephalitis occurred during February or March. Four flocks had more than one case of listerial meningo-encephalitis but within each flock the overall incidence of listerial meningo-encephalitis did not exceed 1% of the total number of adult animals at risk. In each of the flocks which experienced multiple cases of listerial meningo-encephalitis all cases were encountered within a discrete 7 to 10 day period. The median age of affected sheep was 24 months with a range of 2.5 to 96 months. Eleven of the 18 adult animals (61%) were 2 years old. There was a range of neurological signs of listerial meningo-encephalitis on veterinary examination. In the majority of animals there was a history of depression, inappetance, isolation from other sheep in the group, compulsive circling and head-pressing. In six animals there was a brief history of compulsive circling which
OVINE LISTERJAL MENINGO-ENCEPHALITIS
167
had progressed rapidly to lateral r e c u m b e n c y with propulsive limb m o v e m e n t s . T h e s e animals were u n a b l e to maintain sternal r e c u m b e n c y a n d had an increased respiratory rate o f over 80 breaths per minute. In all animals with listerial meningo-encephalitis there was unilateral facial nerve involvement which included loss o f m e n a c e response, ptosis and d r o o p i n g o f the ear. In addition, in all o f these cases there was ipsilateral sensory and m o t o r trigeminal nerve deficits indicated by hypalgesia o f the facial skin and r e d u c e d c h e e k muscle tone with impaction o f f o o d material in some cases. In some sheep there was a secondary e x p o s u r e keratitis o f the ipsilateral eye. Lumbosacral CSF samples were collected from all animals at initial presentation. T h e r e was n o relationship between the severity o f neurological dysfunction and the CSF p r o t e i n c o n c e n t r a t i o n . T h e interval between d e t e c t i o n o f clinical signs suggestive o f listerial meningo-encephalitis and collection o f lumbosacral CSF varied from 3 to 24 h. Sixteen animals failed to r e s p o n d to t r e a t m e n t ( G r o u p B). T h e CSF protein c o n c e n t r a t i o n s are p r e s e n t e d in Table I. T h e m e d i a n CSF white cell c o u n t was 0.2×10:'1 (range 0.012 to 2.5x109/1, n o r m a l range <0.012x 10:'/1) with a m e d i a n lymphocyte p e r c e n t a g e o f 15 (range 0 to 50%, n o r m a l range >95%), m e d i a n n e u t r o p h i l p e r c e n t a g e o f 53 (range 0 to 100%, n o r m a l range <5%) and m e d i a n small m o n o n u c l e a r cells p e r c e n t a g e o f 10 (range 0 to 72%). T h e initial CSF protein c o n c e n t r a t i o n s and r e p e a t samples taken f r o m five animals immediately following euthanasia 2 to 21 days later are also p r e s e n t e d in Table I. T h e r e was little c h a n g e in the CSF protein c o n c e n t r a t i o n in f o u r o f these five animals. Five o f 21 (24%) suspected cases o f listerial meningo-encephalitis ( G r o u p A) r e s p o n d e d to the high dose penicillin G t r e a t m e n t regimen. T h e m e d i a n CSF white cell c o u n t in this g r o u p was 0.025 (range 0.012 to 0.4x109/1)
Table I Lumbosacral cerebrospinal fluid protein concentration (g/l) and response to treatment of 21 sheep affected with listerial meningo-encephalitis CSF concentration (g/#
Group A
5.0 4.5 4.0 3.5 3.0 2.5 2.0
Group B
GroupB(resampled)
X
X
X
X X
1.5 1.0
XXXX XXXX XX
0.5 0.4 . . . .
X
X X XX
XX
X
upper range normal CSF protein concentration
168
BRITISH VETERINARY JOURNAL. 149, 2
with a median lymphocyte percentage of 0 (range 0 to 26%) a median neutrophil percentage of 90 (range 2 to 100%) and a median small mononuclear cell percentage of 10 (range 0 to 72%).
DISCUSSION
Profound depression and circling were common presenting clinical signs of listerial meningo-encephalitis. While all sheep showed facial and trigeminal nerve deficits, in some animals these deficits were subtle and detailed examination was necessary to assess cranial nerve involvement in the disease process. A 61% incidence of listerial meningo-encephalitis in 2-year-old sheep was twice the expected prevalence rate as this age group comprised only 30% of the total flock at risk. The increased prevalence in this age group could be related to the eruption of the three premolars and third molar teeth around this age and infection of the trigeminal nerve root endings with centripetal infection of the brainstem. The susceptibility of yearling sheep to listerial meningo-encephalitis could not be determined in this study as this age group of sheep was managed separately and not fed silage. The low overall incidence of listerial meningo-encephalitis and the appearance of all cases within a discrete time period in this study may suggest that it would not be financially worthwhile to introduce flock control measures following one case of listerial meningo-encephalitis. However, as the prevalence of listerial meningoencephalitis was twice the expected rate in 2-year-old sheep it would be a sensible precaution to feed hay rather than silage to this age group. Alternatively, vaccination against listerial meningo-encephalitis (Gudding et al., 1985) in this cohort could be considered. The description of an outbreak of ovine pregnancy toxaemia described by Cantley et al. (1991) is not dissimilar to the clinical presentation of certain listerial meningo-encephalitis cases in this study. A case of polioencephalomalacia was also reported in a flock during an outbreak of listerial meningo-encephalitis (Low & Renton, 1985). The demonstration of an inflammatory reaction in the CSF samples from ewes in the present study may permit the elimination of ovine pregnancy toxaemia and polioencephalomalacia from the differential diagnosis list of listerial meningo-encephalitis cases. This diagnostic approach has proved to be a useful aid in establishing a provisional diagnosis in field investigations. The median CSF protein concentration for ovine listerial meningo-encephalitis cases of 1.0 g/1 was similar to the value of 0.8 g/1 reported for bovine listeriosis cases (Rebhun & de Lahunta, 1982). While the CSF protein concentration tended to be lower in those cases of ovine listerial meningo-encephalitis which responded to treatment, the two sets of data were not sufficiently different to permit accurate prognosis based on CSF protein concentration alone. In addition, too few sheep responded to treatment preventing meaningful statistical analysis. There had been little change in the lumbosacral CSF parameters in four of five sheep when samples were collected at euthanasia despite the marked deterioration of the animals' neurological condition that had occurred. The absence of a more marked intrathecal inflammatory response may indicate that there was no
OVINE I.ISTERIAL MENINGO-ENCEPHALITIS
169
f u r t h e r d e v e l o p m e n t o f the meningitis lesion. T h e d e t e r i o r a t i o n in clinical presentation o f these s h e e p could have b e e n the result o f f u r t h e r d e v e l o p m e n t o f the encephalitis lesions despite antibiotic therapy. A g o o d r e s p o n s e to high dose penicillin G t r e a t m e n t has b e e n r e p o r t e d for cases o f bovine listeriosis that are a m b u l a t o r y at the start o f t r e a t m e n t ( R e b h u n & de L a h u n t a , 1982). In the UK, the t r e a t m e n t r e s p o n s e o f ovine listerial m e n i n g o encephalitis cases is generally c o n s i d e r e d to be p o o r (Barlow, 1983; Low & D o n a c h i e , 1991). In this study the r e s p o n s e o f ovine listerial m e n i n g o - e n c e p h a l i t i s cases to high dose penicillin t r e a t m e n t was d i s a p p o i n t i n g despite the early recognition a n d p r e s e n t a t i o n o f cases for veterinary t r e a t m e n t . A r e p o r t f r o m J a p a n (Serikawa et al., 1989) details a 40% ( 1 0 / 2 6 ewes) t r e a t m e n t r e s p o n s e for mild cases o f listerial m e n i n g o - e n c e p h a l i t i s using oxytetracycline but there is no m e a n s o f c o n f i r m i n g the provisional clinical diagnosis. F u r t h e r work on antibiotic t r e a t m e n t o f listerial m e n i n g o - e n c e p h a l i t i s as reco m m e n d e d by Prescott a n d Baggot (1988) is necessary to provide clinicians with p r o v e n r e c o m m e n d a t i o n s for antibiotic t r e a t m e n t . It has b e e n postulated that it is the p e a k CSF penicillin G c o n c e n t r a t i o n which is i m p o r t a n t a n d not the d u r a t i o n o f effective m i n i m u m inhibitory c o n c e n t r a t i o n s in CSF (Prescott & Baggot, 1988). In this respect work is p r o g r e s s i n g to d e t e r m i n e if a single intravenous injection o f penicillin G can achieve 10-30 times the m i n i m u m bactericidal conce,atration o f L. mono~togenes in CSF a n d w h e t h e r this r e g i m e n provides a b e t t e r recovery rate than the t r e a t m e n t r e g i m e n p u r s u e d in the p r e s e n t study. In the interim p e r i o d it is r e c o m m e n d e d that the first penicillin G t r e a t m e n t should be a d m i n i s t e r e d intravenously at a dose rate not less than 44 000 i u / k g .
REFERENCES BARI.OW, R. M. (1983). I,isteriosis. In Diseases of Sheq~, ed. W. B. Martin. p. 81. Oxford: Blackwell Scientific Publications. CAXTH.:V,C. E. I,., FORI~,C. M., & HI-:ATH,M. F. (1991). Serum fructosamine in ovine pregnancy toxaemia: a possible prognostic index. Vet. Rec. 128, 525-6. Gt'l)Dlx, R., GROXSTOI.,H. & L\RSt':S,H.J. (1985). Vaccination against listeriosis in sheep. Vet. Rec. 117, 89-90. Lc~w,J. C. & Dox.-xc:Ht~:,W. (1991). Listeriosis. In Diseases of Sheep, 2nd edn., eds W. B. Martin & 1. D. Aitken, p. 177. Oxford: Blackwell Scientific Publications. Low, j. C. &: RESTOX, C. P. (1985). Septicaemia, encephalitis and abortions in a housed flock of sheep caused by I,isteria monocytogenes type 1/2. Vet. Rec. 116, 147-50. PR~:S~:O-l-r,J. F. & BA~;~;OT,J. D. (1988). In Antimicrobial Therapy in Vete14na~ Medicine, p. 78. London: Blackwell Scientific Publications. REBHt'N, W. (]. (1987). Listeriosis. In Bovine Neurolo~c Diseases, e d . J . C . Baker, pp. 75-84. The Veterinary Clinics of North America, Food Animal Practice, 3, (1), Philadelphia: W. B, Saunders. RI-ZBI-It'NW. , C. & l~l-:1.Atlt'NTA,A. (1982). Diagnosis and treatment of bovine listeriosis.J. Am. vet. med. Ass. 180, 395-8. S~:on, P. R. & WH.L, R. G. (1991). A report of Froin's syndrome in five ovine thoracolumbar epidural abscess cases. Br. Vet.J. 147, 582--4. Scoa-l, P. R. (1992). Analysis of cerebrospinal fluid from field cases of some common ovine neurological diseases. B~: Vet..]. 148, 15-22.
170
BRITISH VETERINARYJOURNAIJ, 149, 2
SE~lg.~Wa, S., Kvsar~R, N., OHGI, T. et al. (1989). An outbreak of listeriosis in ewe flocks ir Hokkaido.J.Jap. vet. med. Ass. 42, 781-5.
(,4cceptedfor publication 25 ,~eptember 1992)
A FIEIJD S T U D Y O F O V I N E LISTERIAL MENINGO-ENCEPHAI.ITIS W I T H P A R T I C U L A R REFERENCE T O CEREBROSPINAL FLUID ANALYSIS AS A N AID T O D I A G N O S I S A N D P R O G N O S I S
P. R. SCOTI" Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, VeterinaryField Station, Easter Bush., Roslin, Midlothian EH25 9RG
SUMMARY In a field study of listerial meningo-encephalitis involving 21 sheep from six silage-fed flocks, the neurological signs included profound depression, circling, involvement of the trigeminal and facial cranial nerves and lateral recumbency with propulsive limb movements. Within the six flocks the incidence of listerial meningo-encephalitis did not exceed 1% of the adult sheep at risk. Eleven of 18 (61%) adult animals were 2 years old. Evidence of an intrathecal inflammatory response in suspected listerial meningo-encephalitis cases was indicated by an increased cerebrospinal fluid (CSF) protein concentration greater than 0.4 g / l in 18 of 21 cases (86%), increased white cell count above 0.012x109/1 in 17 cases (81%) and lymphocyte percentage below 50% in all animals. None of the CSF parameters proved to be a reliable prognostic indicator because of the range of CSF values obtained and the small number of sheep which recovered.
INTRODUCTION In the UK meningo-encepha.litis caused by Listeria monocytogenes infection is the most common bacterial infection of the central nervous system of adult sheep. The treatment response of ovine listerial meningo-encephalitis is reported to be poor (Barlow, 1983; Low & Donachie, 1991). However, as multiple treatments are commonly administered to sheep with neurological disease the treatment response is not an accurate aid to diagnosis of listerial meningo-encephalitis. The provisional diagnosis of listerial meningo-encephalitis can only be confirmed histologically (Low & Donachie, 1991). In the living animal, differentiation of listerial meningo-encephalitis from such metabolic diseases as ovine pregnancy toxaemia and polioencephalomalacia has been facilitated by the demonstration of an intrathecal inflammatory response in ovine listeriosis (Scott, 1992). 0007/1935/93/020165-06/$08.00/0
© 1993 Bailli~reTindall
166
BRITISH VETERINARY JOURNAL,. 149, 2
This study reports some aspects of the epidemiology of ovine listerial meningoencephalitis and investigates the application of cerebrospinal fluid (CSF) analysis as an aid to diagnosis and prognosis.
MATERIALS AND METHODS
A 2-year prospective survey was undertaken on six farms in East Central Scotland which experienced cases of ovine listerial meningo-encephalitis. The sheep were at pasture for most of the year but were housed in early January and throughout late pregnancy in purpose-built sheep sheds then returned to pasture in April following lambing. Grass silage was fed throughout the housed period. The neurological examination of suspected cases of ovine listerial meningoencephalitis was based on the report of bovine listeriosis (Rebhun, 1987). A lumbosacral CSF sample was collected under local anaesthesia from 21 sheep at the time of presentation using the method described previously (Scott & Will, 1991). Total CSF white cell counts were performed on a haemocytometer. Samples of CSF were concentrated by cytospin within 2 h of collection, air dried and stained with Leishman stain. The differential white cell count was based on a minimum of 20 cells. The CSF protein concentration was determined by the pyrogallol method (Randox Laboratories Ltd). Each animal received 1.1 m g / k g bodyweight of dexamethasone (Soludex®, Mycofarm) intravenously once at the start of treatment. Penicillin G was administered intramuscularly twice daily at a dose rate of 44 000 iu/kg bodyweight (Depocillin®, Mycofarm). The majority of animals were in late gestation and symptomatic treatment with a concentrated oral electrolyte solution (Liquid Lectade®, Smith, Kline Beecham) was administered twice daily at the manufacturer's recommended rate. If the neurological condition deteriorated, the animal was humanely destroyed and a second lumbosacral CSF sample collected. The diagnosis of listerial meningo-encephalitis was confirmed histologically. No bacteriological culture of brain tissue or CSF was undertaken.
RESULTS Listerial meningo-encephalitis was encountered in 21 sheep from six flocks which had been housed during January and fed grass silage ad libitum. All but one case of listerial meningo-encephalitis occurred during February or March. Four flocks had more than one case of listerial meningo-encephalitis but within each flock the overall incidence of listerial meningo-encephalitis did not exceed 1% of the total number of adult animals at risk. In each of the flocks which experienced multiple cases of listerial meningo-encephalitis all cases were encountered within a discrete 7 to 10 day period. The median age of affected sheep was 24 months with a range of 2.5 to 96 months. Eleven of the 18 adult animals (61%) were 2 years old. There was a range of neurological signs of listerial meningo-encephalitis on veterinary examination. In the majority of animals there was a history of depression, inappetance, isolation from other sheep in the group, compulsive circling and head-pressing. In six animals there was a brief history of compulsive circling which
OVINE LISTERJAL MENINGO-ENCEPHALITIS
167
had progressed rapidly to lateral r e c u m b e n c y with propulsive limb m o v e m e n t s . T h e s e animals were u n a b l e to maintain sternal r e c u m b e n c y a n d had an increased respiratory rate o f over 80 breaths per minute. In all animals with listerial meningo-encephalitis there was unilateral facial nerve involvement which included loss o f m e n a c e response, ptosis and d r o o p i n g o f the ear. In addition, in all o f these cases there was ipsilateral sensory and m o t o r trigeminal nerve deficits indicated by hypalgesia o f the facial skin and r e d u c e d c h e e k muscle tone with impaction o f f o o d material in some cases. In some sheep there was a secondary e x p o s u r e keratitis o f the ipsilateral eye. Lumbosacral CSF samples were collected from all animals at initial presentation. T h e r e was n o relationship between the severity o f neurological dysfunction and the CSF p r o t e i n c o n c e n t r a t i o n . T h e interval between d e t e c t i o n o f clinical signs suggestive o f listerial meningo-encephalitis and collection o f lumbosacral CSF varied from 3 to 24 h. Sixteen animals failed to r e s p o n d to t r e a t m e n t ( G r o u p B). T h e CSF protein c o n c e n t r a t i o n s are p r e s e n t e d in Table I. T h e m e d i a n CSF white cell c o u n t was 0.2×10:'1 (range 0.012 to 2.5x109/1, n o r m a l range <0.012x 10:'/1) with a m e d i a n lymphocyte p e r c e n t a g e o f 15 (range 0 to 50%, n o r m a l range >95%), m e d i a n n e u t r o p h i l p e r c e n t a g e o f 53 (range 0 to 100%, n o r m a l range <5%) and m e d i a n small m o n o n u c l e a r cells p e r c e n t a g e o f 10 (range 0 to 72%). T h e initial CSF protein c o n c e n t r a t i o n s and r e p e a t samples taken f r o m five animals immediately following euthanasia 2 to 21 days later are also p r e s e n t e d in Table I. T h e r e was little c h a n g e in the CSF protein c o n c e n t r a t i o n in f o u r o f these five animals. Five o f 21 (24%) suspected cases o f listerial meningo-encephalitis ( G r o u p A) r e s p o n d e d to the high dose penicillin G t r e a t m e n t regimen. T h e m e d i a n CSF white cell c o u n t in this g r o u p was 0.025 (range 0.012 to 0.4x109/1)
Table I Lumbosacral cerebrospinal fluid protein concentration (g/l) and response to treatment of 21 sheep affected with listerial meningo-encephalitis CSF concentration (g/#
Group A
5.0 4.5 4.0 3.5 3.0 2.5 2.0
Group B
GroupB(resampled)
X
X
X
X X
1.5 1.0
XXXX XXXX XX
0.5 0.4 . . . .
X
X X XX
XX
X
upper range normal CSF protein concentration
168
BRITISH VETERINARY JOURNAL. 149, 2
with a median lymphocyte percentage of 0 (range 0 to 26%) a median neutrophil percentage of 90 (range 2 to 100%) and a median small mononuclear cell percentage of 10 (range 0 to 72%).
DISCUSSION
Profound depression and circling were common presenting clinical signs of listerial meningo-encephalitis. While all sheep showed facial and trigeminal nerve deficits, in some animals these deficits were subtle and detailed examination was necessary to assess cranial nerve involvement in the disease process. A 61% incidence of listerial meningo-encephalitis in 2-year-old sheep was twice the expected prevalence rate as this age group comprised only 30% of the total flock at risk. The increased prevalence in this age group could be related to the eruption of the three premolars and third molar teeth around this age and infection of the trigeminal nerve root endings with centripetal infection of the brainstem. The susceptibility of yearling sheep to listerial meningo-encephalitis could not be determined in this study as this age group of sheep was managed separately and not fed silage. The low overall incidence of listerial meningo-encephalitis and the appearance of all cases within a discrete time period in this study may suggest that it would not be financially worthwhile to introduce flock control measures following one case of listerial meningo-encephalitis. However, as the prevalence of listerial meningoencephalitis was twice the expected rate in 2-year-old sheep it would be a sensible precaution to feed hay rather than silage to this age group. Alternatively, vaccination against listerial meningo-encephalitis (Gudding et al., 1985) in this cohort could be considered. The description of an outbreak of ovine pregnancy toxaemia described by Cantley et al. (1991) is not dissimilar to the clinical presentation of certain listerial meningo-encephalitis cases in this study. A case of polioencephalomalacia was also reported in a flock during an outbreak of listerial meningo-encephalitis (Low & Renton, 1985). The demonstration of an inflammatory reaction in the CSF samples from ewes in the present study may permit the elimination of ovine pregnancy toxaemia and polioencephalomalacia from the differential diagnosis list of listerial meningo-encephalitis cases. This diagnostic approach has proved to be a useful aid in establishing a provisional diagnosis in field investigations. The median CSF protein concentration for ovine listerial meningo-encephalitis cases of 1.0 g/1 was similar to the value of 0.8 g/1 reported for bovine listeriosis cases (Rebhun & de Lahunta, 1982). While the CSF protein concentration tended to be lower in those cases of ovine listerial meningo-encephalitis which responded to treatment, the two sets of data were not sufficiently different to permit accurate prognosis based on CSF protein concentration alone. In addition, too few sheep responded to treatment preventing meaningful statistical analysis. There had been little change in the lumbosacral CSF parameters in four of five sheep when samples were collected at euthanasia despite the marked deterioration of the animals' neurological condition that had occurred. The absence of a more marked intrathecal inflammatory response may indicate that there was no
OVINE I.ISTERIAL MENINGO-ENCEPHALITIS
169
f u r t h e r d e v e l o p m e n t o f the meningitis lesion. T h e d e t e r i o r a t i o n in clinical presentation o f these s h e e p could have b e e n the result o f f u r t h e r d e v e l o p m e n t o f the encephalitis lesions despite antibiotic therapy. A g o o d r e s p o n s e to high dose penicillin G t r e a t m e n t has b e e n r e p o r t e d for cases o f bovine listeriosis that are a m b u l a t o r y at the start o f t r e a t m e n t ( R e b h u n & de L a h u n t a , 1982). In the UK, the t r e a t m e n t r e s p o n s e o f ovine listerial m e n i n g o encephalitis cases is generally c o n s i d e r e d to be p o o r (Barlow, 1983; Low & D o n a c h i e , 1991). In this study the r e s p o n s e o f ovine listerial m e n i n g o - e n c e p h a l i t i s cases to high dose penicillin t r e a t m e n t was d i s a p p o i n t i n g despite the early recognition a n d p r e s e n t a t i o n o f cases for veterinary t r e a t m e n t . A r e p o r t f r o m J a p a n (Serikawa et al., 1989) details a 40% ( 1 0 / 2 6 ewes) t r e a t m e n t r e s p o n s e for mild cases o f listerial m e n i n g o - e n c e p h a l i t i s using oxytetracycline but there is no m e a n s o f c o n f i r m i n g the provisional clinical diagnosis. F u r t h e r work on antibiotic t r e a t m e n t o f listerial m e n i n g o - e n c e p h a l i t i s as reco m m e n d e d by Prescott a n d Baggot (1988) is necessary to provide clinicians with p r o v e n r e c o m m e n d a t i o n s for antibiotic t r e a t m e n t . It has b e e n postulated that it is the p e a k CSF penicillin G c o n c e n t r a t i o n which is i m p o r t a n t a n d not the d u r a t i o n o f effective m i n i m u m inhibitory c o n c e n t r a t i o n s in CSF (Prescott & Baggot, 1988). In this respect work is p r o g r e s s i n g to d e t e r m i n e if a single intravenous injection o f penicillin G can achieve 10-30 times the m i n i m u m bactericidal conce,atration o f L. mono~togenes in CSF a n d w h e t h e r this r e g i m e n provides a b e t t e r recovery rate than the t r e a t m e n t r e g i m e n p u r s u e d in the p r e s e n t study. In the interim p e r i o d it is r e c o m m e n d e d that the first penicillin G t r e a t m e n t should be a d m i n i s t e r e d intravenously at a dose rate not less than 44 000 i u / k g .
REFERENCES BARI.OW, R. M. (1983). I,isteriosis. In Diseases of Sheq~, ed. W. B. Martin. p. 81. Oxford: Blackwell Scientific Publications. CAXTH.:V,C. E. I,., FORI~,C. M., & HI-:ATH,M. F. (1991). Serum fructosamine in ovine pregnancy toxaemia: a possible prognostic index. Vet. Rec. 128, 525-6. Gt'l)Dlx, R., GROXSTOI.,H. & L\RSt':S,H.J. (1985). Vaccination against listeriosis in sheep. Vet. Rec. 117, 89-90. Lc~w,J. C. & Dox.-xc:Ht~:,W. (1991). Listeriosis. In Diseases of Sheep, 2nd edn., eds W. B. Martin & 1. D. Aitken, p. 177. Oxford: Blackwell Scientific Publications. Low, j. C. &: RESTOX, C. P. (1985). Septicaemia, encephalitis and abortions in a housed flock of sheep caused by I,isteria monocytogenes type 1/2. Vet. Rec. 116, 147-50. PR~:S~:O-l-r,J. F. & BA~;~;OT,J. D. (1988). In Antimicrobial Therapy in Vete14na~ Medicine, p. 78. London: Blackwell Scientific Publications. REBHt'N, W. (]. (1987). Listeriosis. In Bovine Neurolo~c Diseases, e d . J . C . Baker, pp. 75-84. The Veterinary Clinics of North America, Food Animal Practice, 3, (1), Philadelphia: W. B, Saunders. RI-ZBI-It'NW. , C. & l~l-:1.Atlt'NTA,A. (1982). Diagnosis and treatment of bovine listeriosis.J. Am. vet. med. Ass. 180, 395-8. S~:on, P. R. & WH.L, R. G. (1991). A report of Froin's syndrome in five ovine thoracolumbar epidural abscess cases. Br. Vet.J. 147, 582--4. Scoa-l, P. R. (1992). Analysis of cerebrospinal fluid from field cases of some common ovine neurological diseases. B~: Vet..]. 148, 15-22.
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SE~lg.~Wa, S., Kvsar~R, N., OHGI, T. et al. (1989). An outbreak of listeriosis in ewe flocks ir Hokkaido.J.Jap. vet. med. Ass. 42, 781-5.
(,4cceptedfor publication 25 ,~eptember 1992)