Improving the Control of Liver Fluke in Cattle

Professor Diana Williams

Veterinary Parasitology

University of Liverpool

What is fluke?

• Fasciola hepatica • Flat worm (i.e. not a

roundworm) • Juvenile flukes migrate

through the liver • Adult fluke live in the bile

ducts • Found in temperate and

high altitude tropical regions throughout the world

Liver fluke infects many different hosts

• Fluke affects sheep, cattle, horses, buffalo, rabbits, hares, deer...

• 2.5 million humans infected in South America, Iran, Egypt, Vietnam

Disease

• Sheep are affected by acute fasciolosis, leads to death of sheep

• Both cattle and sheep can get chronic fasciolosis.

• Sub-clinical infections – reduced productivity, fertility & growth rates.

Impact of fluke on production

• 600+ high yielding dairy herds in England, Wales, Scotland

• Improving their health and welfare

• Impact of fluke on production

• Prevalence – 80%

Impact of infection on production

• No effect on butterfat or protein

• No effect on somatic cell count, bacterial count, services/conception or calving index

• Milk yield: – compared low (PP-33) with

high (PP-77)

– Reduction of 1140litres/cow/year

(853-1427)

Reduction in milk yield of 15%

Fluke – a growing problem in Europe

• Increasing prevalence and distribution of fluke infection in UK • Effects of recent and projected

climate change

• EU Agri-environmental schemes

• Animal movements

• Rapid emergence of resistance to flukicide, triclabendazole

• Increased susceptibility to other diseases

Prevalence of fluke infection in cattle in the UK (APHA – VIDA)

0

0.5

1

1.5

2

2.5

1975 1985 1995 2005 2015

Sweden vs UK

• Similar production systems: • Cattle grazed during summer months (May-October)

• Dairy and Beef

• Prevalence higher in UK (~80% cf 25% in dairy herds) • But increasing in both UK and Sweden

• Mean herd size of dairy herds • ~80 in Sweden

• 100+ in UK

• Drivers of infection similar in UK and Sweden

IMPACT OF CLIMATE CHANGE ON PREVALENCE OF FLUKE

Predicted changes in prevalence of fluke infection across Europe

F. hepatica antibody detection in bulk tank milk from dairy cattle sampled in the GLOWORM study area, modelled across Europe

C. Caminade et al. - Geospatial Health 9(2), 2015, pp. 301-308

Conclusions

• Liver fluke infection is likely to become more prevalent and the transmission season is likely to be extended over the coming decades.

• What does this mean for control?

• Control currently relies on the use of flukicides (dewormers)

FLUKICIDES AND FLUKICIDE RESISTANCE

Dewormers licensed for use against liver fluke (sheep and cattle)

Active ingredient:

• Triclabendazole (all stages)

• Closantel (6-8wks+)

• Nitroxynil

• Clorsulon (adults)

• Albendazole

• Oxyclozanide

• Flukicides have no residual activity

• Limited number of products available for use in dairy cows

• Fasinex 240 at drying off

• Albendazole 60hrs withdrawal

• Oxyclozanide 72hrs withdrawal

Resistance to triclabendazole

• TCBZ first introduced onto the market in mid-1980’s

• Resistance to TCBZ first reported in 1995

• Resistance reported in S. America, Europe, Australia

• Closantel treatment failure in Sweden reported in cattle in 2015 (Novobilsky & Hoglund)

• Albendazole treatment failure reported in sheep in Sweden in 2016 (Novobilsky et al)

How widespread is TCBZ resistance?

• Developed a faecal egg count reduction test to evaluate drug failure (sheep, TCBZ)

• 20 farms recruited to represent typical farming conditions in NW England.

Results FARM PRE

(epg) POST (epg)

% REDUCTION

A 2991 640 79

B 5316 1764 67

C 4492 2380 47

D 4062 2394 41

E 6380 4793 25

F 676 661 2

G 218 497 0

H 391 419 0

I 243 406 0

J 1545 3315 0

K 4376 7947 0

L 6954 13137 0

M 21664 65000+ 0

For a susceptible population the % reduction should be >90%

5 farms had partial efficacy

8 farms had evidence of drug failure

There is increasing evidence of resistance to triclabendazole resistance in the UK

• Triclabendazole resistance is emerging even in areas where fluke is not traditionally thought to be common.

• Farmers are aware and are increasingly moving to using closantel rather than triclabendazole

• Closantel resistance has been reported in Sweden

• The same parasite affects sheep AND cattle

• Reports of triclabendazole resistance in cattle in UK

DIAGNOSING FLUKE INFECTION

Diagnosis of fluke infection

• Faecal egg counts

– High specificity (NB Rumen fluke)

– Composite samples*

– Poor sensitivity, laborious, only detects patent infection

• Copro-antigen ELISA

– No better than FEC

• Antibody detection ELISA – Milk or bulk tank milk, serum

– Detects historical infection

Diagnosis of fluke infections

• Composite dung samples – Sample 10 cows – Create one composite sample – Count eggs in faeces – If negative, repeat count (spring,

autumn) – 95% confident that there is no

infection in the herd.

• Penside tests – Antibody detection – Lateral flow technology

• Penside test to aid in targeted treatments

• Test dairy cattle at drying

off • Test beef cattle at housing

• Sheep in the autumn

Improving control of fluke

• How can we improve fluke control whilst relying less on drug treatments?

• Need to understand factors leading to high fluke risk

• Understanding the life cycle is critical

The life cycle of Fasciola hepatica

Eggs shed in the dung onto pasture

Eggs develop

Eggs hatch and swim through plane of water to find a snail

Fluke multiplies in the snail

Cysts on pasture are eaten by cows as they

graze

Adult fluke in liver of cattle

Intermediate host are mud snails

Flukes leave the snail and encyst on grass

Fluke is a seasonal disease

• Dependent on weather – Rainfall

– Warm, wet summers

– Mild winters

• Complex life cycle – Transmitted through a mud

snail

• Disease risk highest in Autumn

• Rainfall single biggest explanatory variable

• Summer rainfall • Previous five years

• Temperature • Mild winters • Cool summers (= rainy)

• Physical factors • Altitude, slope, • soil type, • minerals

What factors drive the distribution of fluke?

Models explain about 78% of variation between post-code areas

What about at the farm level?

• Within a post code area there are big differences between farms, sometimes neighbouring farms

• Can we capture reasons for those differences?

5 – 27(negative)

27 – 50 (low positive)

50 – 100 (medium positive)

100 – 190 (high positive)

Identification of on farm risk factors

• Identified area of England – farm to farm variation in exposure but same weather (rainfall)

• 195 farms were visited Oct 2014 –Apr 2015

• Detailed Questionnaires completed

• Data collected on – Demography and herd health

– Herd, pasture and farm management

– Cattle production and fertility

• 373 variables

Main risk factors for fluke

• Buying in cattle (quarantine)

• Presence of sheep (reservoir of infection)

• Length of the grazing season (avoid flukey habitat)

Presence of snail habitat

• 40 farms were revisited September 2016

• Bulk milk tank samples tested for fluke antibodies

• Snail habitat on those farms mapped

• Snails collected, species identified, infection status measured

• Soil chemistry, pH, plant community recorded

Galba truncatula • The dwarf pond snail

• Warm and wet conditions

• Resistant to drought and frost

• They are tiny!

• Amplification of the parasite within the snail

Identifying snail habitat

A mud snail (G. truncatula), on damp ground feeding on a thin layer of algae.

Perfect snail habitat

Such areas include: • Depressions caused by tractor tyre ruts,

poaching, natural landscape features • Cleared drainage ditches • Banks on the sides of streams or ponds • Soft ground around leaking water taps

or pipes

• Wet (but not underwater) • Bare mud (but not recently

disturbed) • Open (not shaded by hedges, trees

or long vegetation)

Conclusions

• Snails were found on infected farms

• Suitable snail habitats were very localised and could cover very small areas

• Snail habitats were not fully occupied

– How do snails move into new niches?

• Some farms had no fluke but did have snail habitat and snails.

Controlling liver fluke

• Low numbers of cysts on pasture all year round. • Persist on grass for weeks/months/year, especially if it is cool • Peak pasture contamination:

– Summer infection of snails, cysts on pasture August-September – Winter infection of snails, cysts on pasture May-June

• Other animals can act as reservoirs of infection (sheep, cattle, rabbits, hares, deer)

• Quarantine ALL bought in animals (sheep and cattle) • No snails = no fluke

– Molluscicides – highly toxic, damage aquatic ecosystems – Drainage schemes, but affects whole ecosystems – Identify and fence off/avoid fluke habitat at dangerous times of year

Four point plan

1. Pasture protection - don’t let the

snails get infected!

2. Reduce snail population - drainage,

topping rushes, improving poached areas etc.

3. Avoid high cyst challenge - graze

animals away from known/suspected high risk areas

4. Strategic treatment of ‘at risk’ animals - treat right animals at right time

with appropriate product

Spring

Summer

Autumn

Winter

Acknowledgements • Farmers and vets collaborating in these studies • Uof L - John Graham-Brown, Nicola Beesley, Alison Howell,

Juriah Kamuludeen, Jane Hodgkinson, Matthew Baylis • Collaborators – Philip Skuce, Sue Tongue, Mattie O’Hare, • Roger Daniel, Rebecca Mearns, Tilly Stephens and Jane

Learmont, APHA • Funding from the EU, BBSRC, AHDB, HCC, QMS, Agrisearch

NI, Tesco, Norbrook, Merial. • http://www.cattleparasites.org.uk/ • Http://www.scops.org.uk/ • http://www.liv.ac.uk/infection-and-global-health/research/liver-fluke