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==Signalment==
==Di
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The adult liver fluke, ''[[Fasciola hepatica]]'', lives in the bile ducts of a wide range of animals, including sheep, cattle, rabbits and, less often, horses. It can infect humans causing a painful abdominal disease. The intermediate host in the UK is a mud snail, ''Lymnaea truncatula''. It causes significant economic losses in western parts of the British Isles due to deaths, clinical and subclinical cattle disease confined mostly to the younger stock. Fasciolosis is a seasonal disease with more serious outbreaks occurring in some years than in others. A similar but slightly larger species, ''F. gigantica'', occurs in wetter tropical regions.
The adult liver fluke, ''[[Fasciola hepatica]]'', lives in the bile ducts of a wide range of animals, including sheep, cattle, rabbits and, less often, horses. It can infect humans causing a painful abdominal disease. The intermediate host in the UK is a mud snail, ''Lymnaea truncatula''. It causes significant economic losses in western parts of the British Isles due to deaths, clinical and subclinical cattle disease confined mostly to the younger stock. Fasciolosis is a seasonal disease with more serious outbreaks occurring in some years than in others. A similar but slightly larger species, ''F. gigantica'', occurs in wetter tropical regions.
===Clinical Signs===
=== Geographical distribution of disease ===
===Laboratory Tests===
Transmission is dependent on the snail, and therefore associated with snail habitats. These are more plentiful in high rainfall areas such as found on the western side of the British Isles, or alongside drainage canals in low-lying areas such as the Romney Marsh (or the Netherlands). It is important to remember that sheep and cattle are often bred in Ireland or western Britain and transported to the east of the country for fattening. Infected animals may therefore be found in areas where no transmission occurs
===Pathology===
==Treatment==
=== Weather patterns and disease risk ===
'''Wet summer'''
==References==
=== Ovine Fasciolosis ===
Many fluke and snail eggs hatching and snail habitats expanded, therefore:
'''Acute fasciolosis'''
→ snail population increases rapidly
→ many infected snails
→ many cercariae shed
→ high density of metacercariae on herbage
→ '''increased''' risk of disease
'''Dry summer'''
Few fluke and snail eggs hatching and snails restricted to permanent habitats, therefore:
→ snail populations small and overcrowded
→ few infected snails, high mortality
→ few cercariae shed
→ few metacercariae confined to restricted areas
→ '''reduced''' risk of disease
*Large numbers of metacercariae ingested over a short period of time leads to acute diseasegnosis==
*Smaller numbers ingested over a longer period of time leads to chronic disease
*'''Feed intake'''
**Fluke infections cause reduced food intake
NOTE: chronic fasciolosis occurs at a time of year when animals are on a low plane of nutrition. This combined with the reduced food
intake causes a significant effect on the development and severity of clinical and subclinical fasciolosis.
*'''Species susceptibility'''
**The proportion of flukes that reach the bile ducts is determined mainly by
***The fibroplastic potential of the liver
***The effectiveness of the protective immune responses (which are ineffective in sheep)
**Therefore, establishment rate is
'''sheep>cattle>pig'''
=== linical
==== Ovine Fasciolosis ====
'''Acute fasciolosis'''
*Sudden death
*Sudden death
*Normally '''September-November'''
*Normally '''September-November'''
*Enlarged pale, friable, haemorrhagic liver
*Enlarged pale, friable, haemorrhagic liver
*More than 1000 immature flukes in liver parenchyma
*More than 1000 immature flukes in liver parenchyma
NOTE: Acute disease is rarely seen in cattle
NOTE: Acute disease is rarely seen in cattle
'''Sub-acute fasciolosis'''
'''Sub-acute fasciolosis'''
*Rapid weight-loss over 1-2 weeks
*Rapid weight-loss over 1-2 weeks
*Occurs '''October-December'''
*Occurs '''October-December'''
*Normochromic anaemia
*Normochromic anaemia
*Enlarged liver with large haemorrhages
*Enlarged liver with large haemorrhages
*More than 500 flukes - 50:50 immature and adult
*More than 500 flukes - 50:50 immature and adult
'''Chronic fasciolosis'''
'''Chronic fasciolosis'''
*Progressive weight-loss over weeks or months
*Progressive weight-loss over weeks or months
*Occurs '''January-March'''
*Occurs '''January-March'''
*Normochromic anaemia often becoming hypochromic
*Normochromic anaemia often becoming hypochromic
*Hypoalbuminaemia leading to oedema
*Hypoalbuminaemia leading to oedema
*Small, distorted cirrhotic liver
*Small, distorted cirrhotic liver
*Enlarged bile ducts
*Enlarged bile ducts
*More than 250 adult flukes
*More than 250 adult flukes
NOTE: Calcification of bile duct in cattle → 'pipe-stem' liver
NOTE: Calcification of bile duct in cattle → 'pipe-stem' liver
'''Sub-clinical effects'''
'''Sub-clinical effects'''
*In sheep, fleece weight and fibre quality are affected even by small fluke burdens. There is some evidence that reproductive performance (number of lambs born and growth-rate of lambs) is inversely influenced, but this has not been well documented.
*In sheep, fleece weight and fibre quality are affected even by small fluke burdens. There is some evidence that reproductive performance (number of lambs born and growth-rate of lambs) is inversely influenced, but this has not been well documented.
*Liver condemnations cause economic losses at slaughter
*Liver condemnations cause economic losses at slaughter
*Longer finishing times to slaughter weight and reduced carcass value in beef cattle
*Longer finishing times to slaughter weight and reduced carcass value in beef cattle
*Reduced milk yield and quality in dairy cows
*Reduced milk yield and quality in dairy cows
Metacercariae excyst → immature flukes present in the small intestine → migrate across the peritoneal cavity (about 1 week) → to the liver → migrate through the liver parenchyma for 6-7 weeks becoming more destructive as they grow → enter bile ducts
*The prepatent period is 10-12 weeks
Metacercariae excyst → immature flukes present in the small intestine → migrate across the peritoneal cavity (about 1 week) → to the liver → migrate through the liver parenchyma for 6-7 weeks becoming more destructive as they grow → enter bile ducts
*The prepatent period is 10-12 weeks
===Subactute Fascioliasis===
====Acute Fascioliasis====
The acute disease is a less common type of Fasciola hepatica, and generally occurs 2-6 weeks after large ingestion of metacercariae. The young liver flukes migrate through the liver parenchyma causing severe haemorrhaging, due to the damage to the [[Liver - Anatomy & Physiology|liver]] vasculature.
This is usually seen in late winter, early spring and is currently the most common fascoloiasis seen. It occurs around 4-5 months after ingestion of the metacercariae. Hypochromic and macrocytic anaemia and hypoalbuminaemia are common, as the adult flukes are capable of sucking up to 0.5ml of blood each day. In heavy infections, this can prove to be a severe loss.
This occurs in late autumn and winter, mainly between the months of August to October. Outbreaks of acute fascioliasis usually present as sudden deaths. On examination infected animals are weak, with pale mucous membranes. They may also have enlarged livers, and the liver surface may be cover with a fibrinous peritonitis, particularly evident on the ventral lobe. Tracts become filled with blood and degenerate hepatocytes later infiltrated with [[Eosinophils|eosinophils]], [[Lymphocytes|lymphocytes]] and replaced by fibrosis.
[[Image:Fasciola hepatica - bile duct.jpg|300px|thumb|right|'''Fasciola hepatica (Copyright Flukeman, Wikimedia Commons) ''']]
==== Pathogenesis of acute fasciolosis ====
====Subactute Fascioliasis====
This is caused by ingestion of metacercariae over a longer period of time. Some may have migrated to the bile ducts, causing [[cholangitis]], whilst other metacercariae are migrating through the liver causing lesions similar to those present in acute fascioliasis. The infected host may present with severe haemorrhagic anaemia, with [[hypoalbuminaemia]], rapid loss of body condition, reduced appetite, pale mucous membranes, and submandibular oedema may also be present. On post-mortem, an enlarged liver is common and haemorrhagic tracts are usually visible on the liver surface. If left untreated, it is often fatal. This form of fascioliasis occurs around 6-10 weeks after ingestion of the metacercariae by the host, and like acute fascioliasis occurs in late autumn and winter.
====Chronic Fascioliasis====
This is usually seen in late winter, early spring and is currently the most common fascoloiasis seen. It occurs around 4-5 months after ingestion of the metacercariae. Hypochromic and macrocytic anaemia and hypoalbuminaemia are common, as the adult flukes are capable of sucking up to 0.5ml of blood each day. In heavy infections, this can prove to be a severe loss.
Infected animals may present with progressive loss of body condtion, reduced appeptite, which along with hypoalbuminaemia can result in an gaunt animal. Other common signs include pale mucous membranes, and submandibular oedema, more commonly known as 'bottle jaw.' On biopsy the liver will have an irregular shape, distorted shape with areas of fibrous tissue replacing the cells damaged by the migrating flukes. The bile ducts appear dilated, and dark, and it is often possible to express numerous numbers of adult flukes from within the ducts. Pathology is similar in both sheep and cattle, expect in cattle you may see calcification of the bile ducts, and enlargement of the gall bladder. The calcified bile ducts are often seen protruding from the liver surface, which is known as 'pipe stem liver.'
==== Pathogenesis of acute fasciolosis ====
*'''Liver pathology'''
→ '''increased''' risk of disease
**Flukes develop from 0.1mm-1cm within the liver parenchyma causing trauma, necrotic tracts, and haemorrhages
**Glutamate dehydrogenase (GDH) is released by damaged cells
*Acute damage to liver causes post-necrotic scarring → shrinkage of affected tissues and hypertrophy of normal tissue → the typical appearance of the liver in chronic disease
*Chronic damage to bile ducts → peribiliary fibrosis
(Note: other complex events also occur, including disruption of haemodynamics, monolobular fibrosis, egg-granulomas etc.)
→ snail populations small and overcrowded
*'''Black disease (Infectious Necrotic Hepatitis)'''
**caused by a toxin produced by ''Clostridium novyi'' type B.
**It is commonly associated with liver fluke infestation because migrating flukes → liver necrosis → anaerobic conditions → clostridial multiplication → toxin production → disease
==== Pathogenesis of chronic fasciolosis ====
*'''Bile duct damage'''
→ few cercariae shed
**Adult flukes (2-5cm long) in bile ducts feed on epithelium and blood
**Chronic inflammatory responses → fibrosis of bile duct wall (and, in cattle, calcification)
**Gamma glutamyl transpeptidase released by damaged cells
**Ulceration and haemorrhage of bile duct → epithelial hyperplasia and increased mucosal permeability
*'''Anaemia'''
**250 flukes → up to 50ml of blood loss daily → 10 times increase in rate of erythropoiesis → normochronic anaemia until iron stores are exhausted → hypochromic anaemia.
*'''Hypoalbuminaemia'''
**Albumin (and other plasma proteins) lost into bile duct because of
#Whole blood loss
#Increased epithelial permeability
** → Increased catabolic rate by 2.5x → increased nitrogen loss via urine
**The effects seen depend on the magnitude of nitrogen loss
#There is no obvious effect (although animal is still in abnormal physiological state)
#Reduced weight-gain and/or wool growth and/or milk production
#Loss of body tissue (i.e. weight-loss); hypoalbuminaemia → reduced plasma oncotic pressure → oedema
==Treatment==
=== Forecasting Fasciolosis ===
Several prediction models have been developed. They evaluate the wetness of the soil from '''May''' to '''October''' by taking account of rainfall patterns and evapo-transpiration. Seasonal weighting factors are applied. '''June''' is a particularly influential month.
A drought in late summer can reverse a potentially dangerous trend, and so unqualified forecasts should not be issued prematurely.
A drought in late summer can reverse a potentially dangerous trend, and so unqualified forecasts should not be issued prematurely.
A high snail density will only lead to disease if infection is present (i.e. if fluke eggs have been deposited onto the habitat by farm or wild animals). Local biological interpretation of computer generated predictions is therefore required.
These forecasting models can provide valuable information for the farming community. MAFF (before DEFRA) used to provide an annual forecast, but this is now discontinued.
=== Control ===
=== Control ===
'''Anthelmintics'''
'''Anthelmintics'''
*Few flukicides kill all parasitic developmental stages
*Few flukicides kill all parasitic developmental stages
*Not all products, therefore, are suitable for controlling acute outbreaks
*Not all products, therefore, are suitable for controlling acute outbreaks
*The anthelmintic with the broadest spectrum of activity against immature and adult ''F. hepatica'' is '''Triclabendazole'''
*The anthelmintic with the broadest spectrum of activity against immature and adult ''F. hepatica'' is '''Triclabendazole'''
*Triclabendazole-resistant ''F. hepatica'' populations are beginning to emerge
*Triclabendazole-resistant ''F. hepatica'' populations are beginning to emerge
*The more potent products tend to be the most expensive
*The more potent products tend to be the most expensive
*Many flukicides bind to plasma protein and have long plasma half-lives
*Many flukicides bind to plasma protein and have long plasma half-lives
'''Chemoprophylaxis'''
'''Chemoprophylaxis'''
<br>There are several control objectives
<br>There are several control objectives
*To prevent fluke eggs being dropped onto snail habitats
*To prevent fluke eggs being dropped onto snail habitats
**This is done by treating sheep/cattle with an adulticidal drug in the '''late winter/early spring'''
**This is done by treating sheep/cattle with an adulticidal drug in the '''late winter/early spring'''
*To protect animals grazing pasture known to be contaminated with metacercariae. The choice of drug, time of treatment and dosing interval will depend on
*To protect animals grazing pasture known to be contaminated with metacercariae. The choice of drug, time of treatment and dosing interval will depend on
#Whether you are trying to prevent acute or chronic disease
#Whether you are trying to prevent acute or chronic disease
#The likely intensity of challenge (local knowledge/fluke forecast)
#The likely intensity of challenge (local knowledge/fluke forecast)
#The persistent effect of the drug (i.e. the period after dosing, during which the animal is protected from reinfection)
#The persistent effect of the drug (i.e. the period after dosing, during which the animal is protected from reinfection)
'''Vaccination'''
'''Vaccination'''
*A recombinant vaccine providing approximately 70% protection for cattle is being developed
*A recombinant vaccine providing approximately 70% protection for cattle is being developed
*It exerts its effect by stimulating a range of immune responses not normally seen in chronically infected animals (including TH1-type responses)
*It exerts its effect by stimulating a range of immune responses not normally seen in chronically infected animals (including TH1-type responses)
'''Molluscicides'''
'''Molluscicides'''
*These have been employed with success in the past, but are no longer used. This is because they have to be applied before any fluke forecast can be issued. (Farmers are unwilling to invest in control measures before they are known to be necessary). Also, they have to be applied very carefully as snails can rapidly recolonise sprayed land if any habitat has been missed
*These have been employed with success in the past, but are no longer used. This is because they have to be applied before any fluke forecast can be issued. (Farmers are unwilling to invest in control measures before they are known to be necessary). Also, they have to be applied very carefully as snails can rapidly recolonise sprayed land if any habitat has been missed
'''Alternative strategies'''
'''Alternative strategies'''
*An ability to recognise and define the extent of snail habitats allows alternative cost-effective control options such as fencing and drainage
*An ability to recognise and define the extent of snail habitats allows alternative cost-effective control options such as fencing and drainage
===Treatment===
===Treatment===
If the fuke is present treat with triclabendazole, which is effective against all stages of Fasciola hepatica. Treatment should be applied in September/October and again in January, if faecal egg count is still postitive. One may also treat against adult only stages in May/June, preventing any future pasture contamination. However, do not use the same treatment in September/October as used in May/June, as resistance to drugs is becoming a real problem within the UK due to overuse. If it has been a particularly wet season, it may be necessary to treat again, as Fasciola hepatica becomes more prevalent under such conditions.
If the fuke is present treat with triclabendazole, which is effective against all stages of Fasciola hepatica. Treatment should be applied in September/October and again in January, if faecal egg count is still postitive. One may also treat against adult only stages in May/June, preventing any future pasture contamination. However, do not use the same treatment in September/October as used in May/June, as resistance to drugs is becoming a real problem within the UK due to overuse. If it has been a particularly wet season, it may be necessary to treat again, as Fasciola hepatica becomes more prevalent under such conditions.
Isolation and treatment of all new animals entering from another farm has also be shown to be effective. Other control measures include fencing off wet areas, and increasing soil drainage.
==Prognosis==
==References==
=== Diagnosis ===