production research priorities and prg endophyte toxicity
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Production Research Priorities and PRG Endophyte Toxicity. By R A Leng Emeritus Professor UNE. An animal nutritionist interest in endophyte toxicity?. - PowerPoint PPT PresentationTRANSCRIPT
Production Research Production Research Priorities and PRG Priorities and PRG Endophyte ToxicityEndophyte Toxicity
ByByR A LengR A Leng
Emeritus ProfessorEmeritus ProfessorUNEUNE
An animal nutritionist interest An animal nutritionist interest in endophyte toxicity?in endophyte toxicity?
Prior to 1996 –As a nutrition researcher never considered Prior to 1996 –As a nutrition researcher never considered possibility of endophyte ill thrift—Puzzled by low possibility of endophyte ill thrift—Puzzled by low productivity of experimental animals particularly in New productivity of experimental animals particularly in New Zealand grazing PRG. Zealand grazing PRG.
Since 1996 ---increasing awareness of ill thrift and sudden Since 1996 ---increasing awareness of ill thrift and sudden death of livestock in many different grazing areas I visited death of livestock in many different grazing areas I visited on lecture tourson lecture tours
Led me to research literature on ill thrift which ultimately Led me to research literature on ill thrift which ultimately convinced me of major insidious problems associated with convinced me of major insidious problems associated with endophytic fungus [Leng 2000]endophytic fungus [Leng 2000]
Few if any nutrition or production researchers consider Few if any nutrition or production researchers consider endophytes. e g team at Lincoln NZ working on effects of endophytes. e g team at Lincoln NZ working on effects of parasites/nutrition interaction. Blaxter’s energy parasites/nutrition interaction. Blaxter’s energy requirements team [Autumn PRG vs Spring PRG]requirements team [Autumn PRG vs Spring PRG]
•Producers who are not looking for a fescue toxicity problem [and PRG toxicity] are much less likely to detect one than someone who is - so endophyte effects may go unnoticed [Ball 1997].
•The effects of endophytes on annual gains and reproduction are much greater than is generally realized. [Ball 1997]
•Research fund providers in Australia have not recognised the economic losses from endophyte toxicosis [Leng 2000]
Endophyte Toxicosis Goes Endophyte Toxicosis Goes Largely UnrecognisedLargely Unrecognised
Australia’s research Australia’s research contribution has been contribution has been
miniscule and has not even miniscule and has not even attempted a survey of the attempted a survey of the
economic losses economic losses Most research has been done on endophyte Most research has been done on endophyte
toxicosis intoxicosis in Southern states of USA with Tall Fescue pastures Southern states of USA with Tall Fescue pastures
growing in hot conditionsgrowing in hot conditions New Zealand with perennial rye grass under cool New Zealand with perennial rye grass under cool
conditionsconditions Research in Australia has been minimal.Research in Australia has been minimal. Considerable production research has been Considerable production research has been
done on PRG without knowing alkaloid done on PRG without knowing alkaloid content.content.
Rye Grass Pastures Are Normally Rye Grass Pastures Are Normally Heavily Infected [60-80%] With Heavily Infected [60-80%] With
N.Lolli N.Lolli in Australiain Australia
Endophyte Endophyte [[Neotyphodium LolliNeotyphodium Lolli]] in the stem of PRG.in the stem of PRG.
Neotyphodium sppNeotyphodium spp are not are not restricted to PRGrestricted to PRG
A number of grasses A number of grasses contain Endophytes contain Endophytes Including Australian Including Australian native native Echinopogan Echinopogan Ovatus that is found Ovatus that is found in all Statesin all States and and contains a contains a Neotyphodium sp that Neotyphodium sp that caused staggers and caused staggers and death of sheep in the death of sheep in the Tenterfield area as far Tenterfield area as far back as 1890back as 1890
Anecdotal evidence of Anecdotal evidence of production losses in cattle production losses in cattle
and sheep in Australiaand sheep in Australia
PRG staggers is common in Victoria and Tasmania on the spring PRG shoot
Diarrhea in lambs on PRG, appears to be associated with Endophyte toxicosis.The amounts of dags and fly strike are highly correlated. Diarrhea and endogenous proteinloss are associated
Heat stress has been associated with consumption of endophyte PRG. Death rates from crowding into dams with subsequent drowning have been recorded on PRGpastures in hot weather
0
10
20
30
40
50
60
70
80
0 20 40 60 80 100 120 140 160
Dry weigtht of dags[g/lamb]
% la
mbs
wit
h fl
y st
rike
Sheep and cattle even on relatively cool days will get into water or seek shade for no apparent reason
When you go looking for endophyte toxicity symptoms they are apparent through out the country
Evidence of likely production Evidence of likely production losses from NZ [cool climate] losses from NZ [cool climate]
and Southern USA [warm and Southern USA [warm climate] researchclimate] research
Growth rates of lambs on rye Growth rates of lambs on rye grass and cattle on fescue grass and cattle on fescue
pasturespastures
0102030405060708090
Live weight change of lambs[g/d]
0 25 50 75 100
% PRG pasture as endophyte infected
00.10.20.30.40.50.60.70.80.9
Live weight change [kg/d]
Ala. Geo. Miss. Tenn. Virg.
Plus endophyte No endophyte
Lambs on rye grass in NZ
Cattle on fescue in Southern USA
Heat stress associated with lowered Heat stress associated with lowered feed intake, is an important factor in feed intake, is an important factor in
ill-thrift on endophyte infected ill-thrift on endophyte infected
pasturespastures Cattle generally are poor thermo-regulators. Cattle generally are poor thermo-regulators.
[Their capacity to sweat is about 0.2 of [Their capacity to sweat is about 0.2 of humans]humans]
Breeds with higher capacity to regulate body Breeds with higher capacity to regulate body temperature [greater ability to sweat] are less temperature [greater ability to sweat] are less effected.effected.
The major measured effectsThe major measured effects Depressed cow and calf live weightDepressed cow and calf live weight Reduced fertility particularly in lactating dairy and Reduced fertility particularly in lactating dairy and
beef cowsbeef cows Reduced milk production in dairy and beef cattleReduced milk production in dairy and beef cattle
0
5
10
15
20
25
-18 -12 -9 0 10 20 25 27.5 30 40
Environmental temperature [oC]
[kg
/da
y]
0
1
2
3
4
5
70 72 74 76 78 80 82
Thermal humidity index
Re
du
cti
on
in
mil
k y
ield
[k
g/d
ay]
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10
20
30
40
50
60
70
10 15 20 25 30 35 40
Maximum daily temperature[oC]
% t
ota
l g
razin
g i
n t
he
da
yti
me
Sheep decrease feed intake a environmental temperature rises
Friesians reduce feed intakeand milk yield as environmental Heat stress increases
Grazing Friesian cows changetheir feeding behavior astemperature rises
Ergovaline and lolitrem are Ergovaline and lolitrem are both implicated in heat stress both implicated in heat stress
in ruminantsin ruminants Ergovaline decreases blood flow to skin reducing heat dissipation but Ergovaline decreases blood flow to skin reducing heat dissipation but
lolitrem has a heating effect. High body temperatures are associated lolitrem has a heating effect. High body temperatures are associated with low feed intake and often assumed to be the main cause of ill with low feed intake and often assumed to be the main cause of ill thrift.thrift.
Body temperature and respiration rate in sheep given a dose of Body temperature and respiration rate in sheep given a dose of lolitrem B[75ug/kg LW] under cool conditions [McLaey 1999lolitrem B[75ug/kg LW] under cool conditions [McLaey 1999]]
36.4
36.6
36.8
37
37.2
37.4
37.6
37.8
38
38.2
38.4
-1 0 1 2 3 4 5 6 7 8
Hours from injection of lolitrem
Bo
dy
te
mp
era
ture
oC
0
20
40
60
80
100
120
140
160
180
200
Re
sp
ira
tio
n r
ate
Body temp. Respiration rate
Australia Is the Sun Burnt Australia Is the Sun Burnt Country and THI Is Often Very Country and THI Is Often Very
HighHigh
One January day in Australia
Research Priorities-1. Research Priorities-1. MonitoringMonitoring
Pasture monitoringPasture monitoring To provide information on variations in To provide information on variations in
endophyte alkaloids endophyte alkaloids levels of toxins in PRG and how they are effected by levels of toxins in PRG and how they are effected by
soil, soil fertility climate and grazing management soil, soil fertility climate and grazing management level of toxin effects intake or selection of pasture by level of toxin effects intake or selection of pasture by
cattle, sheep or other herbivorescattle, sheep or other herbivores To provide information on economic losses To provide information on economic losses
deaths, body weight, milk, wool, reproductive deaths, body weight, milk, wool, reproductive efficiencyefficiency
To provide information where research is being To provide information where research is being undertaken on other management factor e g undertaken on other management factor e g
Parasite control and productionParasite control and production Supplementary feeding strategies etcSupplementary feeding strategies etc
Research Priorities 2.Thermal Research Priorities 2.Thermal stressstress
Establish the production responses to Establish the production responses to endophyte alkaloids in relation to thermal endophyte alkaloids in relation to thermal stress [THI].stress [THI].
Potential for early warning of risk problems Potential for early warning of risk problems and for establishing heat ameliorating and for establishing heat ameliorating management practices.management practices. ShadeShade Yard workYard work Supplementary feeding [e g substitute feeding or Supplementary feeding [e g substitute feeding or
alternative pastures]alternative pastures]
Research Priorities 3 –other Research Priorities 3 –other economic effectseconomic effects
DiarrhoeaDiarrhoea IncidenceIncidence Effects in animals under thermo-neutral Effects in animals under thermo-neutral
and hot conditions and hot conditions Cost Cost
DaggingDagging Fly strikeFly strike Production lossesProduction losses
Implication of diarrhoeaImplication of diarrhoea
Ill-thrift has many causes either single or Ill-thrift has many causes either single or multiple and interactivemultiple and interactive
The symptoms are simply reduced production The symptoms are simply reduced production [which is often clear to the producer] [which is often clear to the producer] associated with reduced feed intake [which is associated with reduced feed intake [which is not apparent to the producer]not apparent to the producer]
Reduced feed intake is very often associated Reduced feed intake is very often associated with inflammatory cytokines and leptin with inflammatory cytokines and leptin secretionsecretion
The persistent diarrhoea may implicate The persistent diarrhoea may implicate inflammation of the gut wall and indirectly the inflammation of the gut wall and indirectly the immune systemimmune system
Research Priorities 4 Research Priorities 4 InteractionsInteractions
Seems safe to suggest that if there are Seems safe to suggest that if there are animals dying from heat stress or animals dying from heat stress or misadventure caused by heat stress then misadventure caused by heat stress then most animals will be subject to reduced feed most animals will be subject to reduced feed intake and some form of ill-thrift.intake and some form of ill-thrift.
Grazing animal production is complex and Grazing animal production is complex and there are potentially many interacting there are potentially many interacting factors as is clear from recent studies on the factors as is clear from recent studies on the interaction of protein requirements with interaction of protein requirements with parasites, immuno nutrition and parasites, immuno nutrition and physiological state physiological state
Research Priorities 5. Protein Research Priorities 5. Protein nutrition, parasite/disease nutrition, parasite/disease
challenge/climate challenge/climate
The highest levels of alkaloids in PRG The highest levels of alkaloids in PRG occur in mature pasture on fertilised occur in mature pasture on fertilised
land.land.
0
500
1000
1500
2000
2500
3000
Autumn
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20
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60
80
100
120
Pasture availability Green Pasture Rainfall [mm]
0
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15
20
25
Concentration [ppm]
Winter Spring Summer Autumn
Peramine Lolitrem Ergovaline
0
0.5
1
1.5
2
2.5
3
3.5
Ergovaline [ppm]
Oct. Nov. Dec. Jan. Feb.
Plus N fertilizer No fertizer0
5
10
15
20
25
30
Cru
de p
rote
in in
pas
ture
[%
]
Green pasture
Dry pasture
Deficientmedium
Digestibleforage
Fermentationintermediates
Microbialcells
Short chain organic acids
+methane
+heat
Digestibleforage
Fermentationintermediates
Microbialcells
Short chain organic acids
+methane
+heat
Well balance growth medium
10. 10.
017. 083034
066
Deficiencies of Growth Factors Alter the Flow of Fer mentation Intermediates Into Absorbed Nutrients
Priorities for Research—6 Priorities for Research—6 Implications of the immune Implications of the immune
systemsystem Environments where the sum of Environments where the sum of
environmental and immunological stressors is environmental and immunological stressors is high divert nutrients away from accretion in high divert nutrients away from accretion in muscle, milk and wool to liver anabolism and muscle, milk and wool to liver anabolism and host defence mechanisms [Husband 1995]host defence mechanisms [Husband 1995]
Physical and psychological stressors can Physical and psychological stressors can activate the acute phase response with activate the acute phase response with potential [Colditz 2002] [calves on slippery potential [Colditz 2002] [calves on slippery floors]floors]
Immune activation then is a primary factor in Immune activation then is a primary factor in reduced feed intake and reduced productionreduced feed intake and reduced production
0
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400
600
800
1000
1200
1400
Feed
intake[g/
day]
30 60 90 120
ControlInfected
0
500
1000
1500
2000
2500
3000
-10 -7 -3 0 3 7 10 14 17 21
Days prior to and after lambing
Fa
ec
al
eg
g c
ou
nt
Normal diet Plus bypass protein
0
2
4
6
8
10
12
14
16
-36 -18 0 18 36 44 62 80 98 114 130 148
Days of infection
Cumulative Live Weight
[kg]
100g fish meal 100g FM infected 0g FM 0g FM infected
Parasites of the small intestine progressively reduce feed intakeSteele 1996
Essential amino acids, in late pregnancy and early lactation are prioritised for lamb and milk production. Lowering immune function Donaldson 1999
Both the immune competence and the feed intake effects are overcome by increasing in metabolisable proteinintakeVan Houtert et al 1996
Gut
Epithelia cellturnover tissue repair
Plasmaproteinleakage
Local inflammatory response
PeripheralInflammatory response
Albumin/globulinsfrom liver
Microbe &diet protein
VFA Energy
Muscle
Skeletal
Wool orHair
Milk
decreaseincrease
Effects of parasitism on the nutrient economy of small ruminants
Muscleprotein breakdownincrease
Growth of foetus
Endophyte toxicosis is likely to interact Endophyte toxicosis is likely to interact with climate, physiological state and with climate, physiological state and
demand for nutrients and disease demand for nutrients and disease incidenceincidence
Ruminants on imbalanced feeds[ dry forages] reduce feed Ruminants on imbalanced feeds[ dry forages] reduce feed intake and increase wasteful metabolism and therefore are intake and increase wasteful metabolism and therefore are more prone to heat stress[ the need for a balanced rumen more prone to heat stress[ the need for a balanced rumen vs imbalanced]vs imbalanced]
Metabolisable protein requirements are increased Metabolisable protein requirements are increased in late preg. early lactation and at weaningin late preg. early lactation and at weaning when the immune system is stimulated by foreign bodies, when the immune system is stimulated by foreign bodies,
stress and deficiencies of key nutrientsstress and deficiencies of key nutrients by the need to repair damaged areas of the gut by the need to repair damaged areas of the gut by increased secretion of mucous in the intestinesby increased secretion of mucous in the intestines by increased drain of endogenous and microbial protein to the by increased drain of endogenous and microbial protein to the
lower gutlower gut The metabolisable protein requirements to prevent The metabolisable protein requirements to prevent
the periparturient rise in parasite egg production in the periparturient rise in parasite egg production in ewes is about 350g protein or 30% greater then book ewes is about 350g protein or 30% greater then book requirements requirements
Research Priorities- 7 Discipline Research Priorities- 7 Discipline oriented oriented
Study metabolism in the rumen and the site of Study metabolism in the rumen and the site of absorption of the alkaloids--- using labelled absorption of the alkaloids--- using labelled alkaloids and cannulated animal [Hill 2005]alkaloids and cannulated animal [Hill 2005]
Study potential of a range of chemicals to adsorb Study potential of a range of chemicals to adsorb the alkaloidsthe alkaloids
Examine the effects of alkaloids on the immune Examine the effects of alkaloids on the immune systemsystem
Understand the effects on the gutUnderstand the effects on the gut Understand transfer to foetus and milk[?].Understand transfer to foetus and milk[?]. Measure their effects on the immune system, illeum Measure their effects on the immune system, illeum
wall and protein flow to the caecum large wall and protein flow to the caecum large intestine[ site of provitamin B12 absorption]intestine[ site of provitamin B12 absorption]
Radiolabelled Peptide Ergot Alkaloids. 83.Mitteilung über MutterkornalkaloideEmil SchreierBiopharmaceutical Department, Division of Pharmaceutical Research and Development, Sandoz Ltd., CH-4002 BaselHerrn Dr. Albert Hofmann zum 70. Geburtstag gewidmet
0
10
20
30
40
50
60
Aflatoxin Reduction in
Milk [%]
Bentonite-Na Bentonite-Ca Mycosorb ActivatedCharcoal
0
5
10
15
20
25
30
35
40
Relative
wool
growth
[g/patch/d]
0 5 10 15 20 25
Bentonite given[g/day]
A number of binders including bentoniteprevent absorption of aflatoxins
Bentonite increases wool growth [Fenn and Leng 1985] in sheep by increasing microbial protein supply [Klieve 2002]
Bentonite clays strongly bind ergot alkaloids between ph 2-8but dissociate at Ph 8.5Site of absorption of lysergic acid is from the rumen [Hill 2005]
Grazier observation. Under field conditions wool growth is increased by feeding bentonite and scouring is eliminated or reduced in sheep .
Recombinant DNA ?Recombinant DNA ?
Is their a role for recombinant RNA to Is their a role for recombinant RNA to metabolise endophyte alkaloids.metabolise endophyte alkaloids.
Soil organisms will degrade alkaloidsSoil organisms will degrade alkaloids Recent work inducing Fluroacetate Recent work inducing Fluroacetate
detoxification by rumen organisms detoxification by rumen organisms suggests any thing is possible[ Greig suggests any thing is possible[ Greig et al 2004] et al 2004]
It is likely that the industry will have to live with endophyte infected pastures for a long time, therefore remedial strategies must be developed.
Wild card could be climate change in the long term The 3 hottest years of the past century have occurred since 2000
The Aussie Cow is just as susceptible to endophyte toxicosis as overseas cows
The End