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mouths are being examined for the presenc(e of FMD infection. However, where there is a high perce ntage of these lesions, some consideration should be ma de of herbage length, herbage contamination by poachirig, presence of feeding blocks, and stress factors. With no evidence that such factors may be inducing the OMAGOD le sions, then evidence for any possibility of FMD infection sho tuld be followed
up.

Such factors are speculative, but, because2 of constraints upon time and the inability to submit blood samples due to FMD-induced restrictions, it was not possible 1to carry out any other epidemiological investigations, or any diagnostic tests, other than histopathology.

ACKNOWLEDGEMENTS
The SAC carried out the histopathological testtS. MAFF permanent staff in Dumfries sought special permiss,ion for these to be done: the authors' gratitude goes to them for facilitating this.

The efficacy of closantel has already been reported (Coles and others 2000). The present study was undertaken to determine the efficacy of a range of other fasciolicides against adult triclabendazole-resistant fluke. The isolate of F hepatica used in this study originated in County Sligo, Ireland. Fluke eggs collected from treated ewes were used to infect Lymnaea truncatula, and metacercariae from these snails were used to infect two lambs. When the infection was 114 days old the lambs were treated with 10 mg/kg triclabendazole. Eggs from surviving fluke were collected and used to infect further snails. Thus, the present infection was laboratory selected, unlike the previous study (Coles and others 2000) where the isolate came directly from the field. Metacercariae from the selected isolate were used to infect 48 weaned, crossbred lambs which had been reared on a flukefree farm. Approximately 200 metacercariae in a gelatin capsule were administered orally to each lamb. The lambs were grazed outside for five weeks until very wet conditions necessitated they be brought inside. They were given constant access to hay and water and fed a measured concentrate ration each day. Twelve weeks after infection, the lambs were weighed, ranked into groups of six based on weight, and randomly distributed from these groups into six treatment groups. Group 1 was left untreated, group 2 was dosed orally with 7-5 mg/kg albendazole (Valbazen SC 2-5 per cent; Pfizer), group 3 ivermectin (Ivomec Super for cattle; Merial), group 4 was injected subcutaneously with 10 mg/kg nitroxynil (Trodax 34 per cent; Merial), group 5 was given orally 15 mg/kg oxyclozanide together with levamisole (Nilzan Super; ScheringPlough Animal Health) and group 6 triclabendazole in a combination product with levamisole (Combinex; Novartis). Two lambs were removed shortly after treatment due to jaagsiekte disease and one, which showed no sign of infection, was removed postmortem. At the time of infecting the lambs one gelatin capsule had been found on the floor. To stagger the fluke counts, group 1 was humanely euthanased 12 days after the date of treatment, group 6 after 13 days, groups 3 and 4 after 14 days, and groups 2 and 5 15 days after treatment. The numbers of fluke in the livers were counted as described by MAFF ( 1986). Data were compared with the Student's t test (Instat Instant Biostatistics). Triclabendazole plus levamisole (group 6) had no effect on fluke counts, but nitroxynil (group 4) and oxyclozanide (group 5) both showed excellent activity (P<0-001) (Table 1). Albendazole at 7-5 mg/kg (group 2) reduced fluke counts by 94 per cent (P<0-001), but clorsulon (group 3) only caused a 73 per cent reduction in the numbers of fluke (P=0-003). Both nitroxynil (Lucas 1967) and oxyclozanide (Walley 1966) are known to be effective against adult fluke. Since closantel was effective against adult triclabendazole-resistant F hepatica (Coles and others 2000), it was expected that nitroxynil and oxyclozanide would also be effective, as all three may act as uncouplers of adenosine triphosphate formation (Fairweather and Boray 1999). However, cross resistance has been reported between closantel and nitroxynil, but not between closantel and oxyclozanide (Fairweather and Boray 1999). Albendazole at a dose of 7-5 mg/kg removed approximately 95 per cent of adult fluke (Johns and Dickeson 1979) and a similar result was obtained in the present study (94 per cent). Fairweather and Boray (1999) have suggested that triclabendazole acts on tubulin in F hepatica. If this is correct, the change conferring resistance to triclabendazole must be occurring at a different site to that affected by albendazole. Clorsulon is an effective fasciolicide and, although not registered for use in sheep in the UK, treatment of infected sheep at 2 mg/kg killed 99 per cent
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received

Activity of oxyclozz nitroxynil, clorsule in and albendazole again. adult triclabendaz4 ile resistant Fasciola hepatica
snide

subcutaneous

dose

of 2

mg/kg of clorsulon

with

st

Veterinary Record (2001) 148, 723-724

G. C. Coles, MA, PhD,
CBiol, FIBiol, K. A. Stafford, BSc, LIB,

G. C. COLES, K. A. STAFFORD
IN spite of its long life cycle and the relatively few treatments given each year, the liver fluke, Fasciola hepatic,a, has been able to develop resistance to fasciolicides both inithe laboratory and in the field (Boray 1990, Overend and Bo wen 1995). The resistance to triclabendazole is of immediate concern, as this is the most widely used fasciolicide due to its excellent activity against immature fluke. To enable veterin ary surgeons to advise on therapy of fluke infections, it is imp)ortant to know which fasciolicides will kill the triclabendazole -resistant fluke.

Department of Clinical Veterinary Science, University of Bristol, Langford House, Bristol BS40 5DU

Group

Lambs
1 2 3 4 5 6 7 8 Mean 95 per cent Cl upper 95 per cent ci lower Percentage cure

Control Albendazole Clorsulon Nitroxynil Oxyclozanide

117 144 66 46 93 21 57 _

Triclabendazole
92 115

77-7
117 38

0 0 17 0 1 10 4 _ 4.6 10-6 0 94-1

7 16 26 29 21 25 33 9 20-8 28-6 12.9 73-2

0 0 0 0 0 0 0 0 0 0 100

0 0 0 1 0 1 0

55
22 75
134 104

0-29 0.7 0 99.6

115.8

56-7 0

Cl Confidence interval
The Veterinary Record, June 9, 2001

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of adult fluke based on postmortem examinations (Rehbein and Visser 1999) or 98 per cent based on faecal egg counts (Corba and others 1996). The efficacy in the present study was lower (74 per cent). However, using faecal egg counts, Moll and others (2000) found a high efficacy of clorsulon against triclabendazole-resistant fluke in cattle, suggesting that there is no cross resistance between triclabendazole and clorsulon. Based on the present data, off-licence use of clorsulon in sheep against triclabendazole-resistant fluke is not recommended. It is currently not known how widespread triclabendazoleresistance has become in the UK. There have only been two reports of failure to control adult fluke in the UK (Mitchell and others 1998 and Thomas and others 2000). However, one reason for the increase in numbers of fluke-infected animals reported by the Scottish Agricultural College (Anon 2000), an observation supported from liver condemnations at a major abattoir in south-west England (K. Smith, personal communication), could be widespread, low-level triclabendazole resistance. Resistance can be detected in young fluke before it is detected in adults (Boray 1990). Reduced efficacy of triclabendazole against immature fluke would result in eggs being passed onto pasture from treated animals before expected, and result in enhanced pasture contamination. Whether this has played a significant role in the increase in cases of fascioliasis is unknown. It could be due to wetter summers, since weather conditions and disease correlate (Ollerenshaw and Rowlands 1959). Since reduced efficacy of triclabendazole against immature fluke is unlikely to be noticed, except in cases of heavy infections, there is a strong case for looking at egg-reappearance periods after treatment of fluke-infected sheep and cattle. The present results show that, if triclabendazole resistance is more widespread than current information suggests, there are three products (closantel, nitroxynil and oxyclozanide) available that can be used with confidence to kill adult triclabendazole-resistant fluke. A fourth product, albendazole, will considerably reduce adult fluke burdens.

sheep in the Netherlands. Veterinary Parasitology 91, 153-158 OLLERENSHAW, C. B. & ROWLANDS, W. T. (1959) A method of forecasting the incidence of fascioliasis in Anglesey. Veterinary Record 71, 591-598 OVEREND, D. J. & BOWEN, F. L. (1995) Resistance of Fasciola hepatica to triclabendazole. Australian Veterinary Journal 72, 275-276 REHBEIN, S. & VISSER, M. (1999) Efficacy of an injectable ivermectin/clorsulon combination against Fasciola hepatica in sheep. Veterinary Record 145, 468 THOMAS, I., COLES, G. C. & DUFFUS, K. (2000) Triclabendazole-resistant fluke in south-west Wales. Veterinary Record 146, 200 WALLEY, J. K. (1966) Oxyclozanide (3,3',5,5',6-pentachloro-2,2'-dihydroxybenzanilide -'Zanil') in the treatment of the liverfluke Fasciola hepatica in sheep and cattle. Veterinary Record 78, 267-276

_ ABSTRACTS
Treatment of superficial squamous cell carcinoma in cats by photodynamic therapy
ELEVEN cats with squamous cell carcinomas, 10 on the nasal planum, two on the ears and one on an eyelid, were treated photodynamically; 5-aminolaevulinic cream was first applied repeatedly to the lesions over four to six hours and they were then exposed for 30 minutes to red light of wavelength 635 nm, supplied by a light-emitting diode placed 1 cm from the lesion. Nine of the 10 lesions on the nose, one of those on the ears and the lesion on the eyelid resolved completely after a single treatment. However, seven of those lesions recurred after between 19 and 56 weeks.
STELL, A. J., DOBSON, J. M. & LANGMACK, K. (2001) Photodynamic therapy of feline superficial squamous cell carcinoma using 5-aminolaevulinic acid. Journal of Small Animal Practice 42, 164-169

ACKNOWLEDGEMENTS
The authors are grateful to E. G. Graham for the production of metacercariae and to Schering-Plough and Merial for financial support.

References
ANON (2000) Fascioliasis widely reported in Scotland. Veterinary Record 146, 332-334 BORAY, J. C. (1990) Drug resistance in Fasciola hepatica. In Resistance of Parasites to Antiparasitic Drugs. Eds J. C. Boray, P. J. Martin, R. T. Roush. Rahway, MSD AGVET. pp 51-60 COLES, G. C., RHODES, A. R. & STAFFORD, K. A. (2000) The activity of closantel against triclabendazole-resistant Fasciola hepatica. Veterinary Record 146,504 CORBA, J., VARADY, M., PRASLICKA, J. & TOMASOVICA, 0. (1996) Efficacy of INOMEC-F against naturally acquired gastrointestinal worms, lungworms (Dictyocaulus filaria) and liver flukes (Fasciola hepatica) in sheep. Helminthologia 33, 133-135 FAIRWEATHER, I. & BORAY, J. P. (1999) Fasciolicides: efficacy, actions resistance and its management. Veterinary Journal 158, 81-112 JOHNS, D. R. & DICKESON, S. J. (1979) Efficacy of albendazole against Fasciola hepatica in sheep. Australian Veterinary Journal 55,431-432 LUCAS, J. M. S. (1967) 4-Cyano-2-iodo-nitrophenol, M&B 210,755. British VeterinaryJournal 123,198-211 MAFF (1986) Manual of Veterinary Parasitological Laboratory Techniques. London, HMSO MITCHELL, G. B. B., MARIS, L. & BONNIWELL, M. A. (1998) Triclabendazole-resistant fluke in Scottish sheep. Veterinary Record 143, 399 MOLL, L., GAASENBEEK, C. P. H., VELLEMA, P. & BORGSTEEDE, F. H. M. (2000) Resistance of Fasciola hepatica against triclabendazole in cattle and

Osteoarthritis as a systemic disorder

IN osteoarthritis substantial changes are increasingly recognised in many tissues, and not all are localised to the affected joints. There is also a well established link with obesity. The mesenchymal cells that maintain these tissues have a common origin. This paper proposes the hypothesis that primary generalised osteoarthritis is a metabolic disorder in which systemic factors induce changes in skeletal tissues by modification of the formation and biosynthetic activity of cells derived from mesenchymal precursors. If proven, this hypothesis could have important implications for new approaches to pharmacological intervention in early stages of the disease process.
ASPDEN, R. M., SCHEVEN, B. A. A. & HUTCHINSON, J. D. (2001) Osteoarthritis as a systemic disorder. Lancet 357, 1118

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The Veterinary Record, June 9, 2001

Downloaded from veterinaryrecord.bmj.com on November 27, 2013 - Published by group.bmj.com

Activity of oxyclozzanide, nitroxynil, clorsulon and albendazole against adult triclabendazole resistant Fasciola hepatica
G. C. Coles and K. A. Stafford Veterinary Record 2001 148: 723-724

doi: 10.1136/vr.148.23.723

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