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Fasciolosis (view source)

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Also known as: '''''Fascioliasis  — Fasciolasis — Fluke
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|backcolour =
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|linkpage =Parasites
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|linktext =PARASITES
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|pagetype=Bugs
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|sublink1=Trematodes
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|subtext1=TREMATODES
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}}
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<br>
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== Fasciolosis ==
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==Introduction==
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[[Image:Fasciola hepatica ruminant.jpg|thumb|right|150px|''Fasciola hepatica'' - Joaquim Castellà Veterinary Parasitology Universitat Autònoma de Barcelona]]
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Fasciolosis is a condition of ruminants which causes subclinical and clinical disease leading to ill thrift and deaths. The causative organism is the trematode ''[[Fasciola hepatica]]'' which primarily parasitises the bile ducts of sheep and cattle but may occasionally be found in the horse. ''Lymnaea truncatula'', a mud snail, is the intermediate host of ''[[Fasciola hepatica]]'', and transmission of disease is dependent on the presence of appropriate snail habitats. These habitats are more plentiful in areas of high rainfall, such as the western British Isles. However, infected animals may be found outwith these areas due to the transportation of livestock, or unusual weather patterns. The association of fasciolosis with wetter habitats lends a [[Fasciola hepatica#Epidemiology|seasonal nature to disease outbreaks]], and can help predict the severity of these.  
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[[Image:Fasciola hepatica.jpg|thumb|right|150px|''Fasciola hepatica - Wikimedia Commons]]
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[[Image:Fasciola hepatica adult.jpg|thumb|right|150px|''Fasciola hepatica'' adults from a horse - Castellà Veterinary Parasitology Universitat Autònoma de Barcelona]]
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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.
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=== Ovine Fasciolosis ===
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[[Image:Fasciola  hepatica.jpg|thumb|right|150px|''Fasciola hepatica''. Source: Wikimedia Commons; Author:Adam Cuerden(2007)]]
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'''Acute fasciolosis'''
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*Sudden death
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*Normally '''September-November'''
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*Enlarged pale, friable, haemorrhagic liver
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*More than 1000 immature flukes in liver parenchyma
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NOTE: Acute disease is rarely seen in cattle
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'''Sub-acute fasciolosis'''
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In sheep, "acute" disease caused by fluke larvae is the most common presentation, and generally occurs in the wetter Autumn and early Winter months in both lambs and ewes. Fasciolosis in cattle can occur at any time of year and tends to involve adult fluke, causing "chronic" disease.
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*Rapid weight-loss over 1-2 weeks
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*Occurs '''October-December'''
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*Normochromic anaemia
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*Enlarged liver with large haemorrhages
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*More than 500 flukes - 50:50 immature and adult
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'''Chronic fasciolosis'''
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A slightly larger trematode,  ''F. gigantica'', causes a similar condition in tropical regions.
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*Progressive weight-loss over weeks or months
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*Occurs '''January-March'''  
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*Normochromic anaemia often becoming hypochromic
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*Hypoalbuminaemia leading to oedema
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*Small, distorted cirrhotic liver
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*Enlarged bile ducts
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*More than 250 adult flukes
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  NOTE: Calcification of bile duct in cattle → 'pipe-stem' liver
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'''Sub-clinical effects'''
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==Signalment==
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*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.
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Fasciolosis affects both young and adult animals, primarily sheep and cattle.
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*Liver condemnations cause economic losses at slaughter
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*Longer finishing times to slaughter weight and reduced carcass value in beef cattle
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*Reduced milk yield and quality in dairy cows
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=== Migration and pathology ===
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==Diagnosis==
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==== Migration ====
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A diagnosis can usually be made using clinical findings and the seasonal occurrence of disease, and may be supported by a history of fasciolosis on the farm and post-mortem findings. Certain adjunctive tests may also prove useful.
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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
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*The prepatent period is 10-12 weeks
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==== Pathogenesis of acute fasciolosis ====
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===Clinical Signs===
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*'''Liver pathology'''
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[[Image:Fasciola  hepatica    adult.jpg|thumb|right|150px|''Fasciola hepatica'' adults from a  horse -   Castellà Veterinary Parasitology Universitat Autònoma de  Barcelona]]
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**Flukes develop from 0.1mm-1cm within the liver parenchyma causing trauma, necrotic tracts, and haemorrhages
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====Sheep====
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**Glutamate dehydrogenase (GDH) is released by damaged cells
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In sheep, fasciolosis may present as acute, chronic, or infrequently sub-acute manifestations.
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*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
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*Chronic damage to bile ducts → peribiliary fibrosis
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(Note: other complex events also occur, including disruption of haemodynamics, monolobular fibrosis, egg-granulomas etc.)
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'''Acute''' fasciolosis usually occurs between September and December and is caused by large numbers of immature ''[[Fasciola hepatica]]'' migrating through the liver parenchyma and causing massive damage. It arises within around two to six weeks of ingestion of metacercariae. If sheep are not exposed to at-risk pasture until later in the year, acute fasciolosis may occur as late as the following Feburary. Hepatic damage caused by migration of fluke larvae gives clinical signs including lethargy, pallor, dyspnoea and death in both young and adult animals. Handling of sheep may cause liver rupture and sudden death, and sudden death may also occur due to [[Infectious Necrotic Hepatitis|Black's disease]] (''[[Clostridium novyi]]'' type B) or [[Bacillary Haemoglobinuria|bacillary haemoglobinuria]] (''[[Clostridium haemolyticum|Clostridium novyi'' type D]]) in unvaccinated sheep. This is a result of necrosis caused by larval migration within the liver: anaerobic conditions are created, enabling multiplication of clostridial organisms and thus toxin production.  
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*'''Black disease (Infectious Necrotic Hepatitis)'''
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'''Chronic''' fasciolosis in sheep is caused by adult flukes in the bile ducts and is usually seen in February and March, 4-5 months after ingestion of metacercariae. However, cases may present in early summer if snails become infected during the winter. Progressive weight loss over weeks to months results in poor body condition, and anorexia is often seen. As adult flukes feed on blood and are capable of consuming 0.5ml each per day, [[Regenerative and Non-Regenerative Anaemias|anaemia]] and pallor frequently occur in chronic fasciolosis. Initially, this regenerative anaemia is normochromic, but becomes hypochromic as iron reserves are depleted. Hypoalbuminaemia may also result from whole blood loss, and from reduced hepatic production. This gives a reduced plasma oncotic pressure, leading to ascites and/or submandibular oedema in advanced cases.
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**caused by a toxin produced by ''Clostridium novyi'' type B.  
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**It is commonly associated with liver fluke infestation because migrating flukes → liver necrosis → anaerobic conditions → clostridial multiplication → toxin production → disease
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==== Pathogenesis of chronic fasciolosis ====
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In some cases, sub-acute fasciolosis may occur if infection has occurred over a prolonged period. In these instances, disease is caused by both adult flukes and larvae and ill thrift, lethargy, dyspnoea is seen from around December to March.
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*'''Bile duct damage'''
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**Adult flukes (2-5cm long) in bile ducts feed on epithelium and blood
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**Chronic inflammatory responses → fibrosis of bile duct wall (and, in cattle, calcification)
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**Gamma glutamyl transpeptidase released by damaged cells
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**Ulceration and haemorrhage of bile duct → epithelial hyperplasia and increased mucosal permeability
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*'''Anaemia'''
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**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.
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*'''Hypoalbuminaemia'''
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**Albumin (and other plasma proteins) lost into bile duct because of
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#Whole blood loss
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#Increased epithelial permeability
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** → Increased catabolic rate by 2.5x → increased nitrogen loss via urine
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**The effects seen depend on the magnitude of nitrogen loss
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#There is no obvious effect (although animal is still in abnormal physiological state)
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#Reduced weight-gain and/or wool growth and/or milk production
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#Loss of body tissue (i.e. weight-loss); hypoalbuminaemia → reduced plasma oncotic pressure → oedema
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=== Disease manifestations ===
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In addition to these presentations, ''[[Fasciola hepatica]]'' has subclinical effects on sheep. Fleece weight and fibre quality are affected by even small fluke burdens, and there is some evidence that lambing percentage and lamb growth rates may be negatively influenced. Condemnation of affected livers at slaughter also causes economic losses.
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*Large numbers of metacercariae ingested over a short period of time leads to acute disease
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*Smaller numbers ingested over a longer period of time leads to chronic disease
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*'''Feed intake'''
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**Fluke infections cause reduced food intake
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NOTE: chronic fasciolosis occurs at a time of year when animals are on a low plane of nutrition. This combined with the reduced food
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intake causes a significant effect on the development and severity of clinical and subclinical fasciolosis.
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*'''Species susceptibility'''
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**The proportion of flukes that reach the bile ducts is determined mainly by
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***The fibroplastic potential of the liver
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***The effectiveness of the protective immune responses (which are ineffective in sheep)
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**Therefore, establishment rate is
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'''sheep>cattle>pig'''
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=== Snail biology ===
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====Cattle====
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[[Image:Lymnaea truncatula.jpg|thumb|right|150px|''Lymnaea truncatula'' - Wikimedia Commons]]
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In cattle, fasciolosis is usually a disease of calves occuring between winter and spring, but may affect any animal at any time of year. Disease is usually chronic (caused by adult flukes) and signs tend to be less severe than in sheep. Poor nutrition and gastrointestinal parasitism do however exacerbate disease. As in sheep, subclinical losses include liver condemnation following slaughter and extended finishing times. Carcass values and milk yield may be reduced in beef and dairy cattle respectively. Milk quality may also be poorer in ''[[Fasciola hepatica]]'' infection.
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==== ''Lymnaea truncatula'' ====
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*5-10mm long
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*Brown-black shell with 5-6 spirals
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*1st spiral is greater than half the total length
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*The shell opens on the right (when held with the opening upwards)
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*Feeds on green slime
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*Multiplies rapidly when food is abundant
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*Most die during the British winter (unless very mild)
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*Survivors lay eggs in spring, which hatch in June
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==== Habitats ====
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===Laboratory Tests===
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*''Lymnaea'' are found in muddy areas (but not on highly acidic soils)
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A simple and effective test for ''[[Fasciola hepatica]]'' infection is examination of the faeces for fluke eggs. These are large, ovoid and golden brown, but may be few in number and thus difficult to find. It must also be remembered that eggs are produced only by adult flukes, and so will not be detectable in acute disease.
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*Habitats may be permanent (dry summer) or temporary (wet summer)
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=== Epidemiology ===
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Measurement of serum glutamate dehydrogenase  (GLDH) and/or glutamyl transpeptidase (GGT) levels may prove useful. GLDH is an enzyme released by damaged hepatic cells and becomes elevated within the first few weeks of infection. GGT indicates damage to the epithelial cells lining the bile ducts and rises later in disease, although high levels are maintained for longer. Fluke serology is possible by means of a reliable [[ELISA testing|ELISA test]] that identifies anti-fluke antibodies in the serum or in milk.
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In temperate areas, there are two superimposed epidemiological cycles, known as the summer and winter infections of the snail. On mainland Britain, the summer cycle predominates as a high proportion of snails perish during the winter, but very occasionally, weather sequences allow the winter cycle to affect the pattern of disease. On the west coast of Ireland, the winter cycle of events determines the timing of clinical outbreaks.
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=== Summer infection of the snail ===
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===Diagnostic Imaging===
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Fluke eggs passed in '''spring'''
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Although not commonly performed in the diagnosis of fasciolosis, ultrasonography can show hepatic changes that may be suggestive of fluke. The probe should be applied immediately caudal to the costal arch, approximately two-thirds of the way down the right hand side. This positioning may reveal an excess of peritoneal exudate and fibrinous adhesions between the liver and the small intestine or the body wall. The liver is seen to be enlarged, and the capsule appears hyperechoic due to fibrin deposition. The liver parenchyma also exhibits changes, appearing diffusely granular, rather than uniformly hypoechoic.
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→ hatch in '''June''' (i.e. coincident with snail hatch)
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===Biopsy===
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Biopsy or histopathology may reveal necrotic areas of liver, haemorrhage, hyperplastic bile ducts or indeed the presence of ''[[Fasciola hepatica]]'' within the section.
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→ miracidia infect newly hatched snails
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===Pathology===
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[[Image:Fasciola  hepatica - bile duct.jpg|thumb|right|150px|Bile duct fibrosis due to chronic ''Fasciola hepatica'' infestation. Source: Wikimedia Commons; Author: Flukeman]]
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The pathology of fasciolosis is similar in both sheep and cattle, although the species have a different incidence of acute and chronic disease, as described above.
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→ develop and multiply in snail hepatopancreas during '''summer'''
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In '''acute''' fasciolosis, immature flukes grow and migrate within the liver parenchyma, causing necrotic tracts and haemorrhage. On post-mortem, the liver is enlarged and a fibrinous peritonitis may be be present. Fibrin tags are often particularly apparent on the ventral lobe. Histologically, tracts are seen as areas of degenerate hepatocytes and haemorrhage, which may later become infiltrated with eosinophils and lymphocytes. In the long term, these areas will become fibrosed. In sub-acute fasciolosis, the liver again is enlarged on post-mortem, and haemorrhagic tracts can be seen.
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→ cercariae shed from '''late August''' onwards
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'''Chronic''' fasciolosis is associated with damage to the bile ducts by adult flukes. On post-mortem, the liver is distorted by areas of fibrosis caused by the migration of the original immature flukes. The bile ducts are dilated, and flukes may be expressed from within. The gall bladder may also be enlarged. The walls of the bile ducts may be ulcerated and haemorrhagic with areas of epithelial hyperplasia. The walls eventually become fibrosed and may calcify in cattle. Calcified bile ducts can be seen protruding from the liver surface - this is known as "pipe stem liver".
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→ metacercariae ingested by sheep
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==Treatment==
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Due to the reliance of disease transmission on appropriate snail habitats and therefore weather, it has been possible to develop models to predict the occurrence of fasciolosis to help its control within flocks and herds. These models evaluate the soil moisture content from May to October by considering rainfall patterns and evapo-transpiration, weighted for season. Although June is a particularly influential month in these models, a drought in late summer can reverse predictions of potentially high snail density, and so forecasts should not be issued prematurely. A complicating factor in the prediction of fasciolosis is the fact that snail density is insufficient for disease in the absence of infection (i.e. deposited fluke eggs), and so forecasts generated must be interpreted in the context of local biology.
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→ immature flukes migrate through liver
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Anthelmintic drugs are used in the control of fasciolosis. Not all flukicides are effective against each parasitic developmental stage, and so some may not be suitable for use in an outbreak of acute disease. Triclabendazole, a benzimidazole, is the flukicide with the broadest spectrum of activity against both immature and adult ''[[Fasciola hepatica]]'' and is therefore used to control acute disease. However, triclabendazole-resistant fluke populations are beginning to emerge. Albendazole, closantel, clorsulon and nitroxanyl all have a narrower spectrum of activity, primarily against adult fluke.
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→ '''acute''' disease '''September-November'''; or '''chronic''' diesease '''January''' onwards
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There are two objectives to anthelmintic control of fluke in sheep and cattle. The first is to limit shedding of fluke eggs onto snail habitats, which is achieved by the use of any adulticidal drug in late winter/early spring. The second aim is to protect animals grazing metacercariae-contaminated pasture against fluke infection, and the approach to this is not so simplistic. Here, the choice of drug, the timing of treatment and dosing interval is dependent on: a) whether acute or chronic disease is the (anticipated) problem; b) the likely intensity of challenge, based on local knowledge or fluke forecasting and c) the persistence of the selected drug. When treating for chronic fasciolosis it is important to provide good quality nutrition following anthelmintic dosing, and response and need for further treatment can be monitored using faecal egg counts.
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=== Winter infection of the snail ===
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Previously, molluscicides have been employed to control fasciolosis and were successful. However, these are now infrequently used. This is in part due to the need for application before the likely impact of fluke can be predicted, potentially creating an unnecessary cost. Molluscides can also be difficult to use effectively since careful application is needed to avoid rapid recolonisation of treated land from any habitat that has been missed.
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Fluke eggs passed in '''late summer'''
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→ infect snails
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The nature of fluke transmission means that is it possible to use environmental strategies to help control. Recognition of potential snail habitats allows areas to be fenced off or drained to limit snail numbers. Alternatively, animals may simply be grazed away from wet or boggy areas during high-risk periods.
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→ development halted when temperature <10°C (i.e. flukes trapped in hibernating snails through the winter)
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Finally, a [[Vaccines|vaccine]] against fluke in cattle is currently in development. This is a recombinant vaccine which is thought to provide around 70% protection by stimulating a range of immune responses not normally seen in chronically infected cattle, for example the [[T cell differentiation#TH1 Cells|Th1 response]].
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→ development resumes when temperature >10°C
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==Prognosis==
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→ cercariae shed from '''July'''
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With effective treatment, the prognosis for fasciolosis is reasonable, but this is dependent upon the severity of disease at diagnosis, for example the prognosis for chronic infections is better than that for acute fasciolosis. Clearly strategies aimed at prevention provide the optimum prognosis for herd/flock health.
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→ disease from '''August'''
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==Links==
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=== Geographical distribution of disease ===
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*''[[Fasciola hepatica]]''.
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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.
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*[http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/22702.htm The Merck Veterinary Manual - ''Fasciola hepatica'']
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*[http://www.who.int/neglected_diseases/diseases/fascioliasis/en/index.html World Health Organisation - Fascioliasis]
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*[http://www.sac.ac.uk/mainrep/pdfs/tn557liverfluke.pdf Treatment and Control of Liver Fluke (Scottish Agricultural College)]
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=== Weather patterns and disease risk ===
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==Test yourself with the Trematodes Flashcards==
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'''Wet summer'''
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Many fluke and snail eggs hatching and snail habitats expanded, therefore:
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→ snail population increases rapidly
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[[Trematodes_Flashcards|Trematodes Flashcards]]
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→ many infected snails
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→ many cercariae shed
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==Literature Search==
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[[File:CABI logo.jpg|left|90px]]
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→ high density of metacercariae on herbage
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→ '''increased''' risk of disease
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Use these links to find recent scientific publications via CAB Abstracts (log in required unless accessing from a subscribing organisation).
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<br><br><br>
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[http://www.cabdirect.org/search.html?rowId=1&options1=AND&q1=%28title%3A%28%22Fasciolosis%22%29+OR+title%3A%28Fascioliasis%29+OR+title%3A%28Fasciolasis+%29+OR+title%3A%28%22liver+fluke%22%29+OR+title%3A%28%22fasciola+hepatica%22%29%29+AND+od%3A%28cattle%29&occuring1=freetext&rowId=2&options2=AND&q2=&occuring2=freetext&rowId=3&options3=AND&q3=&occuring3=freetext&publishedstart=2000&publishedend=yyyy&calendarInput=yyyy-mm-dd&la=any&it=any&show=all&x=56&y=10 Fasciolosis in cattle publications since 2000]
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'''Dry summer'''
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[http://www.cabdirect.org/search.html?rowId=1&options1=AND&q1=%28%28title%3A%28%22Fasciolosis%22%29+OR+title%3A%28Fascioliasis%29+OR+title%3A%28Fasciolasis+%29+OR+title%3A%28%22liver+fluke%22%29+OR+title%3A%28%22fasciola+hepatica%22%29%29+AND+od%3A%28sheep%29%29&occuring1=freetext&rowId=2&options2=AND&q2=&occuring2=freetext&rowId=3&options3=AND&q3=&occuring3=freetext&publishedstart=2000&publishedend=yyyy&calendarInput=yyyy-mm-dd&la=any&it=any&show=all&x=68&y=9 Fasciolosis in sheep publiations since 2000]
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Few fluke and snail eggs hatching and snails restricted to permanent habitats, therefore:
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→ snail populations small and overcrowded
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==References==
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→ few infected snails, high mortality
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#Merck & Co (2008) '''The Merck Veterinary Manual (Eighth Edition)''', ''Merial''.
 +
#Aitken, I D (2007) '''Diseases of Sheep''', ''Blackwell''.
 +
#Pugh, D G (2002) '''Sheep and Goat Medicine''', ''Elsevier Health Sciences''.
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#Taylor, M A et al (2007) '''Veterinary Parasitology (Third Edition)''', ''Wiley-Blackwell''.
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→ few cercariae shed
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→ few metacercariae confined to restricted areas
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{{review}}
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[[Category:Liver Diseases - Cattle]] [[Category:Liver Diseases - Sheep]]  [[Category:Brian Aldridge reviewing]]
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→ '''reduced''' risk of disease
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=== Forecasting Fasciolosis ===
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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.
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A drought in late summer can reverse a potentially dangerous trend, and so unqualified forecasts should not be issued prematurely.
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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.
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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.
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=== Diagnosis ===
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'''Acute fasciolosis'''
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*Clincal history
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**Season
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**Grazing
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*Post-mortem examination
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'''Chronic fasciolosis'''
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*Clinical history
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**Season
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**Grazing
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**Lethargy
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**Weight loss
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**Anaemia (pallor)
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**Hypoalbuminaemia (bottle-jaw)
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**Gamma-glutamyl transpeptidase increase (i.e. increase in hepatic enzymes)
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**Fluke eggs in faeces
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  −
=== Control ===
  −
'''Anthelmintics'''
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*Few flukicides kill all parasitic developmental stages
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*Not all products, therefore, are suitable for controlling acute outbreaks
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*The anthelmintic with the broadest spectrum of activity against immature and adult ''F. hepatica'' is '''Triclabendazole'''
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<nb>*Triclabendazole-resistant ''F. hepatica'' populations are beginning to emerge
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*The more potent products tend to be the most expensive
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*Many flukicides bind to plasma protein and have long plasma half-lives
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'''Chemoprophylaxis'''
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*There are several control objectives
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**To prevent fluke eggs being dropped onto snail habitats
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***This is done by treating sheep/cattle with an adulticidal drug in the '''late winter/early spring'''
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**To protect animals grazing pasture known to be contaminated with metacercariae. The choice of drug, time of treatment and dosing interval will depend on
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#Whether you are trying to prevent acute or chronic disease
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#The likely intensity of challenge (local knowledge/fluke forecast)
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#The persistent effect of the drug (i.e. the period after dosing, during which the animal is protected from reinfection)
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  −
'''Vaccination'''
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*A recombinant vaccine providing approximately 70% protection for cattle is being developed
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*It exerts its effect by stimulating a range of immune responses not normally seen in chronically infected animals (including TH1-type responses)
  −
 
  −
'''Molluscicides'''
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*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'''
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*An ability to recognise and define the extent of snail habitats allows alternative cost-effective control options such as fencing and drainage
 
Bara
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