Avian Vibrionic Hepatitis (Avian infectious hepatitis) - By David G S Burch BVetMed MRCVS, Octagon Services Ltd - The condition was described first in 1954, as a chronic degeneration of the liver characterised by low morbidity and variable mortality in caged egg-producing flocks. Further cases, with 10% morbidity, 35% depression of egg production and a cumulative flock mortality of 15% were also reported in mature laying hens in the USA.

David Burch qualified from the Royal Veterinary College in 1972. After two years as houseman and five years in practice, he developed an interest in pig and poultry production and medicine, and joined the pharmaceutical industry. He worked on the development of the antibiotic tiamulin for pigs and poultry during the 1980s, and valnemulin, the first EU-approved medicated feed premix, during the 1990s. He now runs a consultancy company, Octagon Services, and is involved mainly in antimicrobial development and registration. He is currently Chairman of the Pig Veterinary Society and produces its biannual publication The Pig Journal.

Background

The lesions in the liver were described as focal to diffuse hepatic necrosis with subcapsular haemorrhage. Histological examination revealed lymphocytic and granulocytic foci and bile duct proliferation.

Vibrio-like organisms were isolated from liver homogenates, and these bacteria were able to induce liver necrosis in susceptible chicks and mature hens after specialised culture methods. Subsequently, it was thought that the organism was similar to the organism that caused entero-colitis in man and is now known as Campylobacter jejuni. It was shown to be susceptible to the antimicrobials oxytetracycline and furazolidone.

The enigma regarding this condition is its disappearance from about 1965 and it is only in the last few years that reports are starting to reappear in the literature, concerning suspected sporadic cases in laying flocks.

Description of the disease
Crawshaw and Young (2003) gave a comprehensive description of the condition in the UK. In the summer, there was a sudden increase in mortality in an 8,000 hen flock, part of a 50,000 free-range layer site. The affected flock was at peak lay, when birds in good condition died quickly (see Graph 1). Some were found alive but dull with high temperatures and enlarged livers. Egg production in the house fell dramatically in the acute phase and never fully recovered (see Graph 2).

The excess mortality above standard was reported at 10.8% by week 60 (standard is approximately 0.5% per month or 0.125% per week) and egg production was down 22% by week 40.

Three other flocks broke down with the disease at point of lay, during the next three months but excess mortality was kept below 10% and there was still a reduction in egg production of 14.3 - 18.9% (see Graph 3).

Improvements in hygiene were made, and two subsequent flocks repopulated in the winter did not did not break down with the disease. However, in the spring the problem returned and affected the subsequent repopulations.

At post-mortem examination the birds appeared to have died suddenly as there was often food in the crop and an egg in the uterus. There was an excess of peritoneal and pericardial fluid. The main consistent finding was the swollen liver with 1-2mm whitish grey focal lesions. A less consistent finding was a perihepatitis (see Photo 1).

Campylobacter jejuni were isolated from the intestines and occasionally from the liver but in very fresh liver samples, the organism was not isolated. No other bacteria were demonstrated on histopathological staining of the liver. Other diagnostic procedures including serology and virus isolation, did not establish a cause.

Initially the flocks were treated with chlortetracycline in feed and reduced the excess mortality to below 10% but did not appear to eliminate the infection.

Other recent reports

There have been a number of additional sporadic reports of similar cases in the UK and Ireland. (VLA, October 2005: SAC, August 2005; RVL Cork, May 2005)

All of the sites were associated with free-range hens although originally they were reported in caged birds. The flock sizes were variable, but in three reports they had repeated cases on the same farm or even house. They seemed to occur in the spring to autumn season. Two were known to be in close proximity to cattle herds. One also reported the presence of Heterakis gallinarum infections, but two positively reported the absence of the worm infestation and one is unknown.

Cause
The original cause was thought to be due to vibrio-like organisms. It is only subsequently that these have been classified as Campylobacter jejuni so there is some degree of doubt. In the above cases, C. jejuni was isolated in the original flocks from the intestines and occasionally from the liver, but never on a consistent basis from the lesions. In most cases, they could not isolate campylobacter from the liver. Escherichia coli have been isolated on occasion (Harding, C. - personal communication) but not on a consistent basis. In a way this is surprising as campylobacter can be regularly isolated from chickens, especially the intestines and to a lesser level in the liver and bile.

Campylobacter can cause red or yellow mottling of the liver in newly-hatched chicks and focal hepatic necrosis was caused in 60% of chicks which were immuno-suppressed with cyclophosphamide prior to infection. Could the physiological stress at point of lay and the production stress at peak laying reduce the resistance of the hen and make her more susceptible to a challenge from pathogenic strains of C. jejuni?

A number of factors have been associated with the transmission of campylobacter infections in chickens: - houseflies (seasonality), boots of farm personnel and cattle (seasonal grazing). Indirect mechanical transmission of C. jejuni from cattle on a farm to flocks is possible by personnel, wild birds, vermin, rodents and domestic pets in the absence of appropriate biosecurity procedures, which are difficult to control in free-range flocks. Other insects such as beetles may also transmit C. jejuni and along with rodents, may act as reservoirs for re-infection in subsequent flocks.

Other infections, either bacterial or viral, may be associated but not determined as yet. One aspect that has confounded investigators is why it disappeared in the mid sixties and possibly why is it re-occurring now? It is postulated that a possible co-infection factor may have been eliminated by comprehensive vaccination programmes that are currently used in laying flocks. One other possible cause for the recurrence of the disease might be the withdrawal of furazolidone, which appears to be particularly active against C. jejuni and the growth of free-range flocks, which permits a higher risk of exposure. It is difficult to know at this stage.

Treatment
Responses to different treatments, in general, have been reported as disappointing, for example, chlortetracycline in feed only mitigated the effects of the disease (Crawshaw and Young, 2003) however, Power (personal communication) found it to still work well in Ireland.

Recently, field reports (Young - personal communication) have found that tiamulin at 25mg/kg bodyweight administered in the drinking water for 5 days, has proven to be very effective in the therapy of this condition, in birds not too severely affected and are still able to drink.

Presuming the aetiological agent is C. jejuni, Aitken and Morgan (1992) tested the susceptibility of five avian isolates of C. jejuni against five antimicrobials (see Table 2), using a doubling-dilution broth technique to determine the minimum inhibitory concentration (MIC) of the antimicrobial.

This concurs with the early reports that the vibrio-like organism was susceptible to oxytetracycline and especially furazolidone.

Tiamulin could also be considered active against C. jejuni, especially as tiamulin concentrates in the liver after absorption and where it is mainly metabolised and excreted. Levels of 93.8µg equivalents/g were recorded in liver of radiolabelled 3H tiamulin (i.e. tiamulin and metabolites) after 5 days dosing with 50mg/kg bodyweight (EMEA/MRL/578/99-Final). At 25mg/kg this would be still approaching 47µg equivalents/g, which is well in excess of its MIC. In addition, like chlortetracycline, tiamulin also has a zero withdrawal period for eggs in the UK.

I would like to thank the contributors, Stuart Young, Tim Crawshaw and Eugene Power and I would be pleased to hear from colleagues who have come across further cases in the field, whether in free-range or caged flocks to build up a more accurate picture of the disease and its cause.

References

AITKEN, I.A. & MORGAN, J.H. (1992) Novartis Report - data on file
Burch, D.G.S. (2005) Avian vibrionic hepatitis in laying hens. Veterinary Record, October 22, Vol 157, 528 (www.bvapublications.com)
COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS (1999) Tiamulin Summary Report (1) EMEA/MRL/578/99-FINAL, August 1999
CRAWSHAW, T. and YOUNG, S. (2003) Increased mortality on a free-range layer site. Veterinary Record, November 22, 2003, 664
Power, E. (2005) Cork RVL highlights. May 2005
SCOTTISH AGRICULTURAL COLLEGES (2005) SAC surveillance report. Veterinary Record, August 20, Vol 157, 213-216
SHANE, S.M. (1997) Chapter 10. Campylobacteriosis. In: Diseases of Poultry, 10th Edition. Editor-in-Chief, Calnek, B.W. Iowa State Press, Iowa, USA, pp 235-245
SHANE, S.M. and STERN, N.J. (2003) Chapter 17. Campylobacter infection. In: Diseases of Poultry, 11th Edition. Editor-in-Chief, Saif, Y.M. Iowa State Press, Iowa, USA, pp 615-630
VETERINARY LABORATORIES AGENCY (2005) VLA surveillance report. Veterinary Record, October 1, Vol 157, 399-402

Source: David Burch, Octagon Services - April 2006.