immune function - the new frontier in animal production steve puntenney, ph.d. omnigen research, llc
TRANSCRIPT
Immune Function - Immune Function - The New Frontier in The New Frontier in Animal ProductionAnimal Production
Steve Puntenney, Ph.D.Steve Puntenney, Ph.D.
OmniGen Research, LLCOmniGen Research, LLC
Mission StatementMission Statement
OmniGen Research is dedicated to OmniGen Research is dedicated to expanding the boundaries of science to expanding the boundaries of science to benefit animal health and productivity benefit animal health and productivity through the development of natural through the development of natural products for the livestock industryproducts for the livestock industry..
History of OmniGen ResearchHistory of OmniGen Research
1999 1999 HBS identified as a significant issue in HBS identified as a significant issue in OR & WA DairiesOR & WA Dairies
May 2001 Meetings w/ consulting veterinarians May 2001 Meetings w/ consulting veterinarians in WA indicated a high failure rate of in WA indicated a high failure rate of
autogenous vaccines & need for other autogenous vaccines & need for other intervention identifiedintervention identified
Feb 2002 Prototype OmniGen placed on 6 OR & Feb 2002 Prototype OmniGen placed on 6 OR & WA DairiesWA Dairies
May 2002 OmniGen Research, LLC formed May 2002 OmniGen Research, LLC formed with NEF to discover MOAwith NEF to discover MOA
Mar 2003 PAP began distribution of OAFMar 2003 PAP began distribution of OAF Jan 2004 OmniGen-AF Licensed to PAPJan 2004 OmniGen-AF Licensed to PAP
History of OmniGen ResearchHistory of OmniGen Research
July 2005July 2005 Construction on the OmniGen Construction on the OmniGen Research LabResearch Lab
June 2006June 2006 Established OmniGen Established OmniGen Research Research Farm Farm
Feb 2007Feb 2007 Beginning of construction of dairy Beginning of construction of dairy and lab animal facilities and lab animal facilities
Overview of presentationOverview of presentation
Part 1Part 1 Acquired and innate immunityAcquired and innate immunity
• MacrophagesMacrophages• NeutrophilsNeutrophils
Nutrition and immunity during Nutrition and immunity during transitiontransition
Immune function and udder Immune function and udder healthhealth
Part 2Part 2 OmniGen Mastitis StudiesOmniGen Mastitis Studies Mycotic AbortionsMycotic Abortions Mycotoxin BindingMycotoxin Binding OmniGen Use RatesOmniGen Use Rates
Adaptive (antibody-mediated) immunityAdaptive (antibody-mediated) immunity
Janeway et al., 2005
Vulnerable
Impact of periparturient Impact of periparturient immunosuppressionimmunosuppression
Increased susceptibility to diseasesIncreased susceptibility to diseases
-mastitis-mastitis
-metritis/retained placenta-metritis/retained placenta
-foot infections-foot infections
-respiratory infections-respiratory infections
-gastrointestinal disorders-gastrointestinal disorders
-lowered peak milk production-lowered peak milk production
Why focus on immune function?Why focus on immune function?
“ “A .5 kg increase in peak milk production is A .5 kg increase in peak milk production is equal to 108 kg of additional milk per equal to 108 kg of additional milk per lactation” (Utah State University)lactation” (Utah State University)
Innate immunity Innate immunity Allows time for adaptive immunity to developAllows time for adaptive immunity to develop
First line of defenseFirst line of defense Evolutionarily ancientEvolutionarily ancient Several componentsSeveral components
– Epithelial barriersEpithelial barriers– HClHCl– Digestive enzymesDigestive enzymes– Cellular componentCellular component
MacrophagesMacrophages NeutrophilsNeutrophils Natural killer (NK cells)Natural killer (NK cells)
Opsonization is the coating of microbes with Opsonization is the coating of microbes with complement components, such as C3b complement components, such as C3b (also IGg & antibodies, but later).(also IGg & antibodies, but later).
Opsonized particles are more easily Opsonized particles are more easily
phagocytosed due to the presence of phagocytosed due to the presence of complement receptors on the plasma complement receptors on the plasma membrane of phagocytic cellsmembrane of phagocytic cells
Picture of macrophage surface using scanning electron microscopy
Opsonization of Bacteria by C3b
C3bC3b
Cytokine releaseCytokine release
Neutrophil TrafficingNeutrophil Trafficing
Burton and Erskine, 2003
L-selectin
IL-8
Phagocytosis by the neutrophilPhagocytosis by the neutrophil
Bacterium
Recognition
Killing mechanisms: Respiratory burst Killing mechanisms: Respiratory burst via via ROSROS
Phagocytosis NADP oxidase
superoxide anion (O.
2-)
H2O2
O2+
SuperoxidedismutaseBacteriocidal
hypochloriteion OCl- Neutrophil
myeloperoxidase
Other oxygen-derivedfree radicals (OH.)
Macrophages: myeloperoxidase-Independent mechanism
killing
killing
ROS: Good and BadROS: Good and Bad
Good: kill pathogensGood: kill pathogens
Bad: tissue damageBad: tissue damage
““Immune cells” have Immune cells” have high intrinsic ROS high intrinsic ROS generation and, generation and, therefore, have high therefore, have high anti-oxidant demandanti-oxidant demand
““Immune cells” have Immune cells” have membranes high in membranes high in PUFAs which are PUFAs which are susceptible to ROS-susceptible to ROS-mediated damagemediated damage
Chew and Park, 2002
A primary mechanism by which nutrients support A primary mechanism by which nutrients support immunity is via protection against ROSimmunity is via protection against ROS
Phagocytosis NADP oxidase
superoxide anion (O.2-)
H2O2
O2+
SuperoxidedismutaseBacteriocidal
hypochloriteion OCl- Neutrophil
myeloperoxidase
Other oxygen-derivedfree radicals (OH.)
Macrophages: myeloperoxidase-independent mechanism
Cu/Zn
Anti-oxidants (scavenge free radicals)vitamin E, vitamin C
zinc, selenium, carotenoids, flavenoids
Nutrition and immunology at Nutrition and immunology at parturitionparturition
Three factors conspire to affect nutrition and Three factors conspire to affect nutrition and immunity at parturitionimmunity at parturition
– Surge in cortisolSurge in cortisol– Decline in feed intakeDecline in feed intake
NEFA spikeNEFA spike Ketone body spikeKetone body spike
– Impaired calcium homeostasisImpaired calcium homeostasis
Impact of periparturient Impact of periparturient immunosuppressionimmunosuppression
Increased susceptibility to diseaseIncreased susceptibility to disease
-mastitis-mastitis
-metritis/retained placenta-metritis/retained placenta
-foot infections-foot infections
-respiratory infections-respiratory infections
-gastrointestinal disorders-gastrointestinal disorders
Periparturient immunosuppressionPeriparturient immunosuppression
ParturitionParturition Drying offDrying off ShippingShipping Over-crowdingOver-crowding Environmental Environmental
(heat/hold)(heat/hold) Excess handlingExcess handling
Neu
trop
hil L
-sel
ectin L-selectin
Source: Burton and Erskine, 2003
Cortisol brings about immunosuppressionCortisol brings about immunosuppression
Healthy mammary tissue Mammary tissue in stress
Source: Burton and Erskine, 2003
Cytokines released from macrophages Cytokines released from macrophages signal neutrophil migrationsignal neutrophil migration
Increased mastitis incidence due to Increased mastitis incidence due to periparturient immunosuppressionperiparturient immunosuppression
Barkema et al., 1998
PrimiparousMultiparous
Dry Matter Intake during TransitionDry Matter Intake during Transition
6
8
10
12
14
16
18
20
22
Day Relative to Parturition
DM
I, kg
.
Control
Anionic
Puntenney & French 2006Puntenney & French 2006
Energy balance and parturitionEnergy balance and parturition
Puntenney & French 2006
-15
-12
-9
-6
-3
0
0 1 2 3
Week Relative to Parturition
EN
E B
alan
ce (
MC
al/K
g)
Control
Anionic
Plasma NEFAPlasma NEFA
Depressed dry matter intake and elevated blood NEFA Depressed dry matter intake and elevated blood NEFA concentrations during the 2 to 3 weeks prior to calving concentrations during the 2 to 3 weeks prior to calving have been associated with an increased occurrence of have been associated with an increased occurrence of ketosis (Duncan 1998, Goff 2006)ketosis (Duncan 1998, Goff 2006)
Mobilization of adipose tissue is related to the sudden Mobilization of adipose tissue is related to the sudden increase in demand for energy brought on by the onset increase in demand for energy brought on by the onset of lactation, not parturition itself (Goff 2002)of lactation, not parturition itself (Goff 2002)
Elevated NEFA is related to lower DMI at 14 d Elevated NEFA is related to lower DMI at 14 d postpartum and an increased incidence of metritis and postpartum and an increased incidence of metritis and mastitis (Goff 2006)mastitis (Goff 2006)
Impact of Plasma NEFA Concentration Impact of Plasma NEFA Concentration on neutrophil function (dairy)on neutrophil function (dairy)
Scalia et al. 2006
0
50
100
150
200
250
0 mM NEFA 2 mM NEFA
Oxi
dativ
e bu
rst
NEFAs inhibit ROSNEFAs inhibit ROSPhagocytosis NADP oxidase
superoxide anion (O.2-)
H2O2
O2+
SuperoxidedismutaseBacteriocidal
hypochloriteion OCl- Neutrophil
myeloperoxidase
Other oxygen-derivedfree radicals (OH.)
Macrophages: myeloperoxidase-independent mechanism
Cu/Zn
XX
ββ-hydroxybutyrate-hydroxybutyrate An indicator of KetosisAn indicator of Ketosis
Associated with negative energy balanceAssociated with negative energy balance
Cows with plasma BHB levels above 12 mg/dL, are Cows with plasma BHB levels above 12 mg/dL, are considered to be subclinically ketotic, above 15 mg/dL considered to be subclinically ketotic, above 15 mg/dL clinically ketotic (LeBlanc 2005)clinically ketotic (LeBlanc 2005)
Elevated BHB 14 d postcalving is associated with an Elevated BHB 14 d postcalving is associated with an increased incidence of metritis & mastitis (Goff 2006)increased incidence of metritis & mastitis (Goff 2006)
ββHB by Day Relative to ParturitionHB by Day Relative to Parturition
4
5
6
7
8
9
10
11
12
-1 0 1 7 14 21
Day Relative to Parturition
BH
B,
um
ol/
L
Puntenney & French 2006Puntenney & French 2006
Ketones suppress leukocyte functionKetones suppress leukocyte function
Hoeben Hoeben et alet al., 1999., 1999
HH22 OO
22 P
rodu
ctio
n
Pro
duct
ion
Ketones inhibit ROSKetones inhibit ROSPhagocytosis NADP oxidase
superoxide anion (O.2-)
H2O2
O2+
SuperoxidedismutaseBacteriocidal
hypochloriteion OCl- Neutrophil
myeloperoxidase
Other oxygen-derivedfree radicals (OH.)
Macrophages: myeloperoxidase-independent mechanism
Cu/Zn
XX
Hypocalcemia impairs immune cell Hypocalcemia impairs immune cell functionfunction
Kimura et al., 2006
Control cows
Cows with milk fever
Cal
cium
sig
nalin
g in
PB
MN
cel
ls
6
8
10
12
14
16
18
20
22
Day Relative to Parturition
DM
I, k
g.
Control
Anionic
What are the effects of OmniGen-AF What are the effects of OmniGen-AF on neutrophil function?on neutrophil function?
Respiratory burst Respiratory burst (ROS generation)(ROS generation)
Neutrophil NET Neutrophil NET formationformation
Phagocytosis AssayPhagocytosis Assay
Respiratory burst assayRespiratory burst assay
Combine -neutrophils (+/- OmniGen-AF)
-Cytochrome C -Zymosan A (from yeast)
Incubate 30 min, 37oC
Assess Cytochrome-C reduction by color change(655 nm)
Effects on Respiratory BurstEffects on Respiratory Burst
0
1
2
3
4
5
6
Control OmniGen
0 nM PMA
5 nM PMA
RO
S g
ener
atio
n
Omnigen-AF effect (P<0.01)
OmniGen-AF restored phagocytosis and OmniGen-AF restored phagocytosis and ROS generation in Stress ChallengeROS generation in Stress Challenge
Phagocytosis NADP oxidase
superoxide anion (O.2-)
H2O2
O2+
SuperoxidedismutaseBacteriocidal
hypochloriteion OCl- Neutrophil
myeloperoxidase
Other oxygen-derivedfree radicals (OH.)
Macrophages: myeloperoxidase-independent mechanism
Cu/Zn
Inactive neutrophils Activated neutrophils with NETs
Source: Brinkmann et al., 2004, Science
+ interleukin-8 (IL-8)
Production of NETs by neutrophils
Association of neutrophil “NETs” Association of neutrophil “NETs” with bacteriawith bacteria
S. aureus Salmonella Shigella
Gram + Gram - Gram -
Neutrophil NET assayNeutrophil NET assayNeutrophils +/- OmniGen-AF
Add to microplate with varyingConcentration of PMA (activator)
Incubate 30 minutes at 37oC
Add Sytox green (extracellularDNA marker)
Read in fluorescence plate reader485 excitation, 525 emmision
0
0.2
0.4
0.6
0.8
1
1.2
0 nM 0.5 nM 5 nM 50 nM
Control
OmniGen
OmniGen-AF enhanced NET release in immunosuppressed sheep neutrophils
Phorbol ester (PMA) concentration
Cha
nge
in D
NA
flu
ores
cenc
e re
lativ
e to
0 n
M P
MA
con
trol
OmniGen-AF as main effect (P<0.01)
Phagocytosis AssayPhagocytosis AssaySheep E. coli Strain 487
Neutrophils
Combine in ratio of 30 E. coli:1 neutrophil
Incubate 37oC, 2 hr
(allow killing of E. coli)
Add MTT
(live E. coli metabolize to formazin, purple)
Incubate 4 hr, 37oC in CO2
Stop rx, incubate 4 hr
Read at 655nm on plate reader
(+/- OmniGen)
OmniGen-AF enhanced phagocytosis in OmniGen-AF enhanced phagocytosis in stress challenged sheep neutrophilsstress challenged sheep neutrophils
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
Control OmniGen-AF
Kill
ing
of E
. co
li
P<0.01
Moving beyond molecular biologyMoving beyond molecular biology
DNA Cell function Organ function Whole animal Populations
L-selectinIL8R, ICEIL4Rthymopoeitin
MastitisMastitis
Mastitis is defined as an Mastitis is defined as an infection of part of the infection of part of the mammary glandmammary gland
Cost – about an Cost – about an average of $200/cow average of $200/cow annually. . . . .$2 billion annually. . . . .$2 billion to the industryto the industry
““A disease of man A disease of man transmitted to the cow”transmitted to the cow”
Impossible to eradicate, Impossible to eradicate, but practical to control.but practical to control.
Effect on Milk Composition & QualityEffect on Milk Composition & Quality
Rapid increase in somatic cell count Rapid increase in somatic cell count (leukocytes)(leukocytes)
Milk volume, milk fat, SNF, Milk volume, milk fat, SNF, protein, lactose, casein, protein, lactose, casein, calcium & shelf life calcium & shelf life
Whey protein, albumin, Whey protein, albumin, sodium, chloride & pH sodium, chloride & pH (bad things)(bad things)
Economic Loss due to MastitisEconomic Loss due to Mastitis
Anatomy of the Anatomy of the Mammary GlandMammary Gland
All pathogens enter through All pathogens enter through the streak canal viathe streak canal via
-employee hands-employee hands-contaminated -contaminated
beddingbedding-equipment insults-equipment insults-cow to cow -cow to cow
transfertransferDeLaval, Inc. 2006DeLaval, Inc. 2006
Teat Sphincter Streak canalTeat Sphincter Streak canal
PathogensPathogens Contagious Contagious
- - Streptococcus agalactiae Streptococcus agalactiae (very short life o/s the udder; responds to dc (very short life o/s the udder; responds to dc treatment and teat dips) treatment and teat dips) gramgram + +
- Staphylococcus aureus - Staphylococcus aureus (resistant to antibiotics; chronic) (resistant to antibiotics; chronic) gramgram + (CPS)+ (CPS) EnvironmentalEnvironmental
- - Other Strep. spp.Other Strep. spp.- Dysgalactiae Dysgalactiae (chronic mastitis) (chronic mastitis) gramgram ++- Uberis (contaminated bedding) gramgram ++
- - ColiformsColiforms
- - E. coli E. coli (hot mastitis, quick acting, (hot mastitis, quick acting, high temp & shock) high temp & shock) gramgram ––
- - Klebsiella spp. Klebsiella spp. (high incidence in (high incidence in wood shavings) wood shavings) gramgram – (CPS)– (CPS)
-Enterobacter sp. -Enterobacter sp. gramgram – –
-Aerobacter aerogenes -Aerobacter aerogenes gramgram – –
CPS type cell walls supress complement C3bCPS type cell walls supress complement C3b activity & resist phagocytosisactivity & resist phagocytosis Staph. aureusStaph. aureus
Other PathogensOther Pathogens Coagulase negative staph (live on skin; don’t cause clinical mastitis Coagulase negative staph (live on skin; don’t cause clinical mastitis gram + gram +
(CPS)(CPS) Psuedomonas aeruginosa (lives in water; responds to Cl) Psuedomonas aeruginosa (lives in water; responds to Cl) gramgram – (CPS)– (CPS) Corynebacterium pyogenes (antibiotic resistant) Corynebacterium pyogenes (antibiotic resistant) gram + (CPS)gram + (CPS) Nocardia spp. (standing water; acts like coliform) Nocardia spp. (standing water; acts like coliform) gram +gram + Mycoplasma spp. (spreads easily, shuts down milk Mycoplasma spp. (spreads easily, shuts down milk gram –gram –
production in 24 hours, equipment related)production in 24 hours, equipment related)occasional; dirty mastitis tubesoccasional; dirty mastitis tubes
Proteus spp. – not commonProteus spp. – not common gram- (CPS) gram- (CPS) Serratia spp. – chronic mastitisSerratia spp. – chronic mastitis gram – (CPS) gram – (CPS)
YeastsYeasts FungiFungi usually not significantusually not significant
Part 2Part 2
Mastitis Field Studies With OmniGenMastitis Field Studies With OmniGen Mycotic AbortionsMycotic Abortions Mycotoxin StudiesMycotoxin Studies OmniGen Use RatesOmniGen Use Rates
Case Study No. 7 - TexasCase Study No. 7 - Texas
- 3200 cow dairy, open lot design, silage based TMR3200 cow dairy, open lot design, silage based TMR
- Initiated an off/on/off protocol:- Initiated an off/on/off protocol:
Off - Aug. 1, 2003 - Sept. 27, 2003 (45 d)Off - Aug. 1, 2003 - Sept. 27, 2003 (45 d)
On - Sept. 28, 2003 - Dec. 30, 2003 (93 d)On - Sept. 28, 2003 - Dec. 30, 2003 (93 d)
Off - Jan. 1, 2004 - Mar. 3, 2004 (63 d)Off - Jan. 1, 2004 - Mar. 3, 2004 (63 d)
Case Study No. 7 - TexasCase Study No. 7 - TexasSummary of Cull/Dead Records by Feeding PeriodSummary of Cull/Dead Records by Feeding Period
Off Off OnOn OffOff (45 days) (93 days) (63 days) (45 days) (93 days) (63 days)
Total: Culls 109 163 144Total: Culls 109 163 144
Dead 36 45 43Dead 36 45 43
Respiratory: Culls 10 6 6Respiratory: Culls 10 6 6 Dead 4 7 5Dead 4 7 5
Digestive: Culls 12 8 18Digestive: Culls 12 8 18 Dead 14 15 16Dead 14 15 16
Mastitis: Culls 33 8 28Mastitis: Culls 33 8 28 Dead 1 4 6Dead 1 4 6
Case Study No. 7 - TexasCase Study No. 7 - Texas
Summary of culls and deaths by feeding periodSummary of culls and deaths by feeding period
Item Item Off Off OnOn (108 days) (93 days)(108 days) (93 days) Total: Culls 253 163 Total: Culls 253 163
Deaths 79 45 Deaths 79 45 ---------------------------------------------------------------------------------------------------------------------------------------------------------- Respiratory: Culls 16 6Respiratory: Culls 16 6 Deaths 9 7Deaths 9 7 Digestive: Culls 30 8Digestive: Culls 30 8 Deaths 30 15Deaths 30 15 Mastitis: Culls 61 8Mastitis: Culls 61 8 Deaths 7 4 Deaths 7 4
Case Study #9:Effect of OmniGen-AF on a Case Study #9:Effect of OmniGen-AF on a High SCC herd (4000 cows)High SCC herd (4000 cows)
Avg. SCC
350000
400000
450000
500000
550000
600000
7/3
0/2
006
8/1
3/2
006
8/2
7/2
006
9/1
0/2
006
9/2
4/2
006
10/8
/2006
10/2
2/2
006
11/5
/2006
11/1
9/2
006
12/3
/2006
12/1
7/2
006
Avg. SCC
OmniGen Added
Dominant Pathogen: Strep uberis; Minor Pathogen: E. coliDominant Pathogen: Strep uberis; Minor Pathogen: E. coli
Conditions Don’t Always Go Our Conditions Don’t Always Go Our Way!!Way!!
Case Study #10: Effect of OmniGen-AF Case Study #10: Effect of OmniGen-AF on a High SCC herd (3000 cows)on a High SCC herd (3000 cows)
OmniGen AddedOmniGen Added
Dominant Pathogen: Strep uberisDominant Pathogen: Strep uberis
High Incidence of New InfectsHigh Incidence of New Infects
PSCC | PSCCPSCC | PSCC
<200 | >=200 All<200 | >=200 All SCC 280 | 315 595SCC 280 | 315 595 >=200 12% | 13% 25%>=200 12% | 13% 25% --------+----------------+-------- SCC 1558 | 277 1835SCC 1558 | 277 1835 <200 64% | 11% 75%<200 64% | 11% 75% ==================================================== 1838 592 24301838 592 2430 76% 24% 100%76% 24% 100%
Reduced Incidence of NI Rate after Reduced Incidence of NI Rate after 30 days on OmniGen30 days on OmniGen PSCC | PSCCPSCC | PSCC
<200 | >=200<200 | >=200
SCC 212 | 291 503SCC 212 | 291 503 >=200 8% | 11% 19%>=200 8% | 11% 19% --------+----------------+-------- SCC 1702 | 335 2037SCC 1702 | 335 2037 <200 67% | 13% 80%<200 67% | 13% 80% ==================================================== 1914 626 25401914 626 2540 75% 24% 100%75% 24% 100%
Monitoring Fresh Cow Mastitis: Monitoring Fresh Cow Mastitis: Low SCC HerdLow SCC Herd
Cows 5 to 30 days in MilkCows 5 to 30 days in Milk LACT | LACTLACT | LACT
<2 | >=2 All<2 | >=2 All SCC 15 | 27 42SCC 15 | 27 42 >=200 6% | 10% 16%>=200 6% | 10% 16% --------+----------------+-------- SCC 82 | 145 227 SCC 82 | 145 227 <200 30% | 54% 84%<200 30% | 54% 84% ==================================================== 97 172 26997 172 269 36% 64% 100%36% 64% 100%
196,000 SCC196,000 SCC
Monitoring Fresh Cow Mastitis: Monitoring Fresh Cow Mastitis: High SCC HerdHigh SCC Herd
Cows 5 to 30 days in MilkCows 5 to 30 days in Milk LACT | LACTLACT | LACT
<2 | >=2 All<2 | >=2 All SCC 3 | 11 14SCC 3 | 11 14 >=200 5% | 20% 25%>=200 5% | 20% 25% --------+----------------+-------- SCC 9 | 32 41 SCC 9 | 32 41 <200 16% | 58% 74%<200 16% | 58% 74% ==================================================== 12 43 5512 43 55 21% 78% 100%21% 78% 100%
286,000 SCC286,000 SCC
Doing it Right!!!Doing it Right!!!
YIELD & DOLLAR LOSSES
Table 3. Use of DHIA somatic cell count (SCC) score to estimate production loss due to mastitis.
Difference in milk yield* (lb/305 days)
SCC SCS count (1000’s) Lactation 1 > Lactation 2
0 12.5 —— ——1 25 —— ——2 50 —— ——3 100 200 4004 200 400 8005 400 600 12006 800 800 16007 1600 1000 2000
* Comparisons are with lactation yields at SCC scores of 2.Source: Current Concepts of Bovine Mastitis. NMC, 1987.
Lost Production Revenue due to Lost Production Revenue due to MastitisMastitis
Economic loss in milk production due to mastitis compared to a herd with a SCC score of 3
Annualized Loss SCS cents/hd. 500 cow herd 1000 cow herd 3 ----- — — 4 16¢ $24,000 $ 48,000 5 32¢ $48,000 $ 96,000 6 48¢ $64,000 $128,000 7 64¢ $96,000 $192,000
Based on a milk price of $12.00/cwt.
Source: Current Concepts of Bovine Mastitis. NMC, 1987.
Economics of Reduced MastitisEconomics of Reduced Mastitis
100,000 drop in SCC = @15 per cwt. Bonus100,000 drop in SCC = @15 per cwt. Bonus75 lbs. of milk x $0.15 = $11.2 cents75 lbs. of milk x $0.15 = $11.2 cents
Clinical cases of mastitis cost $300 per cowClinical cases of mastitis cost $300 per cow (Guard, et al. 1996)(Guard, et al. 1996)
10% reduction in clinical cases = $10.0 cents per 10% reduction in clinical cases = $10.0 cents per head per dayhead per day
.5 SCS reduction = $8.0 cents in production revenue/day.5 SCS reduction = $8.0 cents in production revenue/day
AbortionsAbortions
Approximately 15% of abortions are mycoticApproximately 15% of abortions are mycotic
The value of a pregnancy is $278.00 (US)The value of a pregnancy is $278.00 (US)
The cost of a pregnancy loss is $555 (US)The cost of a pregnancy loss is $555 (US)
(DeVries 2006; JDS 89:3876 – 3885)(DeVries 2006; JDS 89:3876 – 3885)
Result in Extended LactationsResult in Extended Lactations
Mycotic abortionsMycotic placentitis observed in 131/1107 placentas obtained
Aspergillus hyphae isolated fromplacental tissue (78% incidence)
Phycomycete hyphae isolated fromplacental tissue (11% incidence)
67% of fetal stomachs contained Aspergillus hyphae
McCausland et al., 1997
OR/WA Abortion StudyOR/WA Abortion StudyAbortions
1
10
100
1000
10000
100000
1000000
Cow #20
Cow #63
7
Cow 617
Cow #23
49
Fetus
(617
)
Fetus
(234
9)
Canola
A. fumigatus(spores/ml)
Mycotic Abortions: Field StudiesMycotic Abortions: Field Studies
0
5
10
15
20Ja
n
Fe
b
Ma
r
Ap
r
Ma
y
Jun
Jul
Au
g
Se
p
Oct
No
v
De
c
New crop haylageNew crop haylage
AF addedAF added
Case Study SummaryCase Study Summary Incidence of HBS and Abortion Incidence of HBS and Abortion
----------------Number of Cases----------Number of Cases----------
No OmniGenNo OmniGen11 OmniGenOmniGen
Case No.Case No. Herd SizeHerd Size HBSHBS AbortionsAbortions HBS HBS AbortionsAbortions
112,3 2,3 1200 18 -- 0 -- 1200 18 -- 0 --
2 300 4 -- 0 --2 300 4 -- 0 --
4 350 -- 31 -- 154 350 -- 31 -- 15
5 4500 14 >100 0 05 4500 14 >100 0 0
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------11number of cases reported in the previous 6 month periodnumber of cases reported in the previous 6 month period22binder fed during pre-OmniGen periodbinder fed during pre-OmniGen period33history of vaccination program for clostridium Type Ahistory of vaccination program for clostridium Type A
case locations: 1 & 5; Washington, 2 & 4; Oregoncase locations: 1 & 5; Washington, 2 & 4; Oregon
OmniGen AF - Wisconsin Case StudiesOmniGen AF - Wisconsin Case StudiesMilk Yield & DMIMilk Yield & DMI
No OmniGenNo OmniGen OmniGenOmniGen
NovNov DecDec JanJan FebFeb MarMar AprApr MayMay
Case No. 9*Case No. 9*
Milk (lb) 78 79 84 85 90 90 91Milk (lb) 78 79 84 85 90 90 91
DMI (lb) 48 49 51 51 52 52 53DMI (lb) 48 49 51 51 52 52 53
Case No. 10**Case No. 10**
Milk (lb) 58 60 62 62 62 62 63Milk (lb) 58 60 62 62 62 62 63
DMI (lb) 44 45 50 50 50 50 50DMI (lb) 44 45 50 50 50 50 50
--------------------------------------------------------------------------------------------------------------------------------------------------------------------------
**OmniGen fed at 2oz./h/d beginning after December weigh day, reduced OmniGen fed at 2oz./h/d beginning after December weigh day, reduced to 1oz./h/d mid- Januaryto 1oz./h/d mid- January
**OmniGen fed at 2oz./h/d beginning after December weigh day, **OmniGen fed at 2oz./h/d beginning after December weigh day, reduced to 1oz./h/d at end of Januaryreduced to 1oz./h/d at end of January
In Vitro Mycotoxin Binding Studies with various In Vitro Mycotoxin Binding Studies with various commercial flow agentscommercial flow agents
University of Missouri, ColumbiaUniversity of Missouri, Columbia
% Binding by Other Commercial Products% Binding by Other Commercial Products
Mycotoxin Mycotoxin T-BindT-Bind MycotexMycotex MTB100MTB100 UltraSorbUltraSorb AB20AB20
Aflatoxin 100 99Aflatoxin 100 99 45 10045 100 100100
Fumonisin 100 NT NT NT 100Fumonisin 100 NT NT NT 100Ochratoxin 90 83 81 80 87Ochratoxin 90 83 81 80 87Vomitoxin 30 0 0 13 40Vomitoxin 30 0 0 13 40Zearalenone 61 70 76 100 60Zearalenone 61 70 76 100 60--------------------------------------------------------------------------------------------------------------------------------------------------------------------
Duplicate samples tested with 2 ppm aflatoxin, 2 ppmDuplicate samples tested with 2 ppm aflatoxin, 2 ppm fumonisin, 2 ppm fumonisin, 2 ppm ochratoxin, 4ppm vomitoxin and 2 ppm zearalenoneochratoxin, 4ppm vomitoxin and 2 ppm zearalenone
NT= interference, no results NT= interference, no results
In Vitro Mycotoxin Binding Studies with OmniGen AFIn Vitro Mycotoxin Binding Studies with OmniGen AFUniversity of Missouri, ColumbiaUniversity of Missouri, Columbia
% Binding __________% Binding __________
MycotoxinMycotoxin Sample 1Sample 1 Sample 2Sample 2
Aflatoxin 100 100Aflatoxin 100 100
Fumonisin 83 ntFumonisin 83 nt
Ochratoxin 95 88Ochratoxin 95 88
Vomitoxin 47 55Vomitoxin 47 55
Zearalenone 86 91Zearalenone 86 91
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Duplicate samples tested with 2 ppm aflatoxin, 2 ppm Duplicate samples tested with 2 ppm aflatoxin, 2 ppm fumonisin, 2 ppm ochratoxin, 4ppm vomitoxin and 2 ppm fumonisin, 2 ppm ochratoxin, 4ppm vomitoxin and 2 ppm zearalenonezearalenone
NT= interference, no resultsNT= interference, no results
OmniGen-AFOmniGen-AF
Product category - Nutritional SupplementProduct category - Nutritional Supplement Feeding Rate – 55 grams per headFeeding Rate – 55 grams per head Not sold as a mycotoxin binder …..Not sold as a mycotoxin binder …..
but recent Columbia University but recent Columbia University studies have shown it to be highly studies have shown it to be highly
efficaciousefficacious
ReviewReview All mastitis organisms enter through the streak All mastitis organisms enter through the streak
canal – milking technique, equipment maintenance canal – milking technique, equipment maintenance and hygiene are paramount to low sccand hygiene are paramount to low scc
NEFA & BHB inhibit neutrophil killing abilityNEFA & BHB inhibit neutrophil killing ability OmniGen experimentally increased phagcytosis OmniGen experimentally increased phagcytosis
against against e. colie. coli, increased ROS activity, & , increased ROS activity, & increased nutrophil net formation in vitroincreased nutrophil net formation in vitro
OmniGen-AF reduced SCC in OmniGen-AF reduced SCC in Strep uberisStrep uberis herds herds New infection rate is the driver of SCCNew infection rate is the driver of SCC There may be a good return on investment for There may be a good return on investment for
OAF in some mastitis applicationsOAF in some mastitis applications OmniGen may not be effective against bacteria OmniGen may not be effective against bacteria
forming capsulated cell walls (Klebsiella and forming capsulated cell walls (Klebsiella and Staph)Staph)
Questions?Questions?