Fasciolosis

PARASITES TREMATODES

Fasciolosis

Fasciola hepatica - Joaquim Castellà Veterinary Parasitology Universitat Autònoma de Barcelona

The adult liver fluke, Fasciola hepatica, lives in the bile ducts of a wide range of animals, including sheep, cattle, rabits 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. Significant economic losses occur in western parts of the British Isles. Deaths, clinical and subclinical disease in cattle is confined to a 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.

Ovine Fasciolosis

Acute fasciolosis: sudden death; normally September-November; enlarged pale, friable, haemorrhagic liver with more than 1000 immature flukes in liver parenchyma. (In cattle, acute disease is rarely seen).

Sub-acute fasciolosis: rapid weight-loss over 1-2weeks; October-December; normochromic anaemia; enlarged liver with large haemorrhages; more than 500 flukes - 50:50 immature and adult.

Chronic fasciolosis: progressive weight-loss over weeks or months; January-March; anaemia normochronic, leads to hypochromic; hypoalbuminaemia, which leads to oedema; small distorted cirrhotic liver; enlarged bile ducts; more than 250 adult flukes. (In cattle, calcification of bile ducts leads to 'pipe-stem' liver).

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.
• Liver conemnations cause economic losses at slaughter. (Note: in beef cattle - sub-clinical infection leads to longer finishing times to slaugter weight, reduced carcass value).
• In dairy cows - reduced milk yield (and quality).

Migration and Pathology

Migration

Metacercariae excyst, so immature flukes are present in the small intestine. They then migrate across the peritoneal cavity (takes approximately 1week) to the liver. They meander through the liver parenchyma for 6-7weeks, becoming more destructive as they grow, and then enter bile ducts. The prepatent period is 10-12weeks.

Pathogenesis of Fasciolosis

• Liver pathology - in parenchyma, flukes develop from 0.1mm-1cm, which causes trauma (glutamate dehydrogenase (GDH) released by damaged cells), necrotic tracts, and haemorrhages, leading to acute disease.
• Acute damage to liver causes post-necrotic scarring, which in turn causes shrinkage of affected tissues and hypertrophy of normal tissue (this causes the typical appearance of the liver in chronic disease).
• Chronic damage to bile ducts leads to peribiliary fibrosis.

(Note: other complex events also occur, including disruption of haemodynamics, monolobular fibrosis, egg-granulomas etc.)

• Black disease (Infectious Necrotic Hepatitis) - is 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.

Adults in Bile Ducts

• Bile duct damage - adult flukes (2-5cms long) in bile ducts feed on epithelium and blood; chronic inflammatory responses → fibrosis of bile duct wall (and, in cattle, calcification).
• Bile duct damage - adult flukes feed on biliary epithelium (gamma glutamyl transpeptidase released by damaged cells) and blood, leading to ulceration and haemorrhage, which causes epithelial hyperplasia and increased mucosal permeability.
• Anaemia - 250 flukes can cause up to 50ml of blood loss daily → 10 times increase in rate of erythropoiesis → normochronic anaemia until iron stores are exhausted → hypochromic anaemia.
• Hypoalbuminaemia - anaemia (and other plasma proteins) lost into bile duct because of:

a) whole blood loss, and

b) increased epithelial permeability

→ catabolic rate incereased by 2.5times → increased nitrogen loss via urine.

• Depending on magnitude of nitrogen loss:

a) no obvious effect (although animal is still in abnormal physiological state)

b) reduced weight-gains and/or wool growth and/or milk production

c) loss of body tissue (i.e. weight-loss); hypoalbuminaemia → reduced plasma oncotic pressure → oedema.

Disease Manifestations

• Large numbers of metacercariae ingested over a short period of time leads to acute disease.
• 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 and the effectiveness of the protective immune responses (which are ineffective in sheep). Therefore, establishment rate: sheep>cattle>pig.

Snail Biology

Lymnaea truncatula

• is 5-10mm long
• has a brown-black shell with 5-6spirals
• first spiral is greater than half the total length
• the shell opens on the right (when held with the opening upwards)
• feeds on green slime
• can multiply rapidly if food is abundant
• most die during the British winter (unless very mild)
• survivors lay eggs in spring, which hatch in June.

Habitats

• Lymnaea is found in muddy areas (but not on highly acidic soils)
• habitats may be permanent (dry summer) or temporary (wet summer).

Epidemiology

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.

Summer Infection of the Snail

Fluke eggs that are passed in spring:

→ hatch in June (i.e. coincident with snail hatch)

→ miracidia infect newly hatched snails

→ develop and multiply in snail hepatopancreas during summer

→ cercariae shed from late August onwards

→ metacercariae ingested by sheep

→ immature flukes migrate through liver

→ acute disease September-November; or chronic diesease January onwards.

Winter Infection of the Snail

Eggs dropped in late summer:

→ infect snails

→ development halted when temperature <10°C (i.e. flukes trapped in hibernating snails through the winter)

→ development resumes when temperature >10°C

→ cercariae shed from July

→ disease from August.

Geographical Distribution of Disease

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 th country for fattening. Infected animals may therefore be found in areas where no transmission occurs.

Weather Patterns and Disease Risk

Wet summer: Many fluke and snail eggs hatching and snail habitats expanded, therefore:

→ 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.

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 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.

Diagnosis

Acute fasciolosis:

• clincal history (season, grazing)
• post-mortem examination.

Chronic fasciolosis:

• clinical history (season, grazing):
  • lethargy, weight loss
  • anaemia (pallor)
  • hypoalbuminaemia (bottle-jaw)
  • gamma-glutamyl transpeptidase increase (i.e. increase in hepatic enzymes)
  • fluke eggs in faeces.

Control

• Anthelmintics - few flukicides kill all parasitic developmental stages. 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. Triclabendazole-resistant F. hepatica populations are beginning to emerge. The more potent products tend to be the most expensive. Many flukicides bind to plasma protein and have long plasma half-lives.

• Chemoprophylaxis - there are several control objectives:

a) to prevent fluke eggs dropping onto snail habitats - this can be done by treating sheep/cattle with an adulticidal drug in the late winter/early spring.

b) to protect animals grazing pasture known to be contaminated with metacercariae - the choice of drug, time of treatment and dosing interval will depend on:

i) whether preventing acute or chronic disease

ii) the likely intensity of challenge (local knowledge/fluke forecast)

iii) the persistent effect of the drug (i.e. the period after dosing, during which the animal is protected from reinfection).

• Vaccination - a recombinant vaccine which provides 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).

• Molluscicides - 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 - an ability to recognise and define the extent of snail habitats allows alternative cost-effective control options such as fencing and drainage.