Bovine RespiratoryDisease Complex andDesigning Effective

Vaccination ProgramsChris Chase

Department of Veterinary &Biomedical Sciences

South Dakota State UniversityBrookings, SD 57007

On The Road to ControlRespiratory Disease

• What is BRDC• Multi-factorial Diseases• Management of BRDC• BRDC Vaccine

Credits

• Immunobiology, 6th edition• David Topham, University of

Rochester• Dr. Chris Schneider, University of

Idaho• Dr. Nichols, Australia

Bovine Respiratory Disease Complex(BRDC)

• Single most significant infectious disease in cattle• Multifactorial

– Stress– Viruses– Bacteria

• All of these pathogens are in the normal bovine population• Incidence in the first 40 days on feed

– 10 – 30 days peak challenge• Up to 90% of morbidity• Up to 70% of mortality

BRDC

• Bronchopneumonia– Most common cause of dairy calf

mortality– Greater economic losses than any

other disease in feedlot calves• Dairy calves- enzootic pneumonia• Beef calves- shipping fever

BRDC

• Major challenge to cattle industry• 31% of cattle/calf death in US• $625 M impact/year• Feedlot Industry

– 65-79% of sickness– 44-72% of death

Bovine Respiratory DiseaseComplex

• Cost of BRD– Mortality– Morbidity

• Hospitalization• Medication costs• Increasing

feeding time• Labor costs

– Subclinical• Reduction of ADG

and FCR

Other Contributing Factors• Breed - Bos taurus vs bos indicus• Origin - saleyard vs direct off property ,

northern vs southern States• Age• Immune status• Temperament

Disease Triangle

Bovine Respiratory Diseaseis Multifactorial

Stress

TransportMixingDehydrationLack of feed

ProcessingHandlingMixingDustHeatColdWaterFeedCompetition

Viruses

IBRBVDVBRSVBRCV?PI3Adenovirus

Bacteria

M. haemolyticaP. multocidaH. somnusM. bovis

BRD

Stress• Stress is anything that reduces immune response

capability• Adaptation to intensive production is stressful

– Anything that improves adaptation will reduce costs and improveproduction

• The reason that this condition is seen more in intensiveoperation rather than extensive

Stress – Prior to Entry• Weaning• Saleyards• Co-mingling or mixing• Transport• Dehydration• Time off feed• Injury

Stressors at the Feedlot

• Co-mingling• Injury• Water - palability

and supply• Feed - time to

first• Pen density• Pen total number

• Handling andmovements

• Pen “add-ons”• Weather

extremes• Dust• COMPETITION

Morbidity Percent by Origin – Major Feedlots (2002).

6 - 10%Custom Fed

13 - 16%Private Purchase

20 - 25%Auction

Treatment PercentCattle Origin

Effect of Co-mingling

Pathogens Stressors

Viruses Mycoplasma Bacteria

Uncomplicatedrespiratory Disease

Damage

Bacterial pneumonia

Physical Environmental

Immune System

Psychological

X

Stress will decrease chemotaxis

Inflammatory Response

Neutrophil Chemotaxis and Phagocytosis

What Does Stress Do to Neutrophil Motility and Phagocytosis?

What Does MLV BVDV Do to Neutrophil Motility andPhagocytosis?

Bovine RespiratoryDisease(BRD)

• Viruses– IBR– BVDV– BRSV– PI3– Bovine

Coronavirus(BCV)

• Bacteria– Mannheimia

haemolytica– Pasteurella

multocida– Histophilus

somnus– Mycoplasma

bovis– Plus others

Sources of Pathogens

• Reactivation of “normal flora”• “Swap” pathogens• Mechanical

Respiratory Pathogens

• Bacterial agents normally inhabitURT-Normally there– Mannheimia haemolytica– Pasteurella multocida– Mycoplasma bovis

• Begin growing with stress &immunosuppression

Respiratory “Swap” Pathogens

• Aerosol, secretions, excretions– Trucks– Sales barns– Hospital pens

Respiratory Pathogens

• Mechanical transmission- needbiosecurity and disinfection– Handling facilities– Hospital crew

• Pathogens– Viruses

Bovine Viral Diseases

BRCVBRCV

BVD- Not a pathogen oflung- immunosuppressive

• For the last 15years at theSDSU DiagnosticLab, NCP BVDVhas been themajor isolate(>50% of all viralrespiratoryisolates).

• Type 2 vs Type 1

• Isolated from nasal swabs ofcalves

• Increasing importance?

Bovine RespiratoryCoronavirus

Bacterial Agents

• Mannheimia hemolytica A1– Most common isolate of fatal BRD cases

• Pasturella multocida– Affects younger cattle– Slow developing

• Histophilus somnus– Geographic significance-Northern Part of

North America

Mycoplasma bovis

• Arthritis• Chronic pneumonia• Otitis media

– Dairy calves primarily• Skin abscesses

Mycoplasma bovis

• Concern of stocker, feedlots, andreplacement heifers on the dairy

• Primary issue in stockers• Major problem since 1999• Vaccination efficacy poor• Outbreak Bison??

Strategies to decreaseincidence of BRD

• Aim to– Decrease mortality– Decrease morbidity

• Decrease treatment costs• Subclinical cost

– Improve performance• ADG• FCR

Prevention of BRDC

• Management– Eliminate stress factors where possible

– Recognize the “Critical Period” for diseasedetection (3 weeks that follow weaning;placing on feed; shipping of cattle)

Prevention of BRDC

• Management– Avoid co-mingling cattle from different

sources during critical 3-week period

– Keep new cattle close to feed and water

– Don’t over crowd (especially early in feedingperiod)

– Control dust and mud

Summary

• Environmental factors• Reducing group size is desirable• Ventilation and dust control are important• Transport time, rest, food water• Commingling should be avoided• Weaning before shipping decreases stress• Gradual feed changes with proper supplements are

beneficial

Diet and Immunity

• Immune system doesn’t get a freeride- energy consumer- calves on poornutrition- poor response to vaccines• Multiple demands on energy for the calf-overvaccination can effect growth anddevelopment• Calves-Vaccinating prior to acclimationto feed (weaning; feedyard) Acidosis, poorvaccine response

EnergyAvailable

Maintenance

Growth & LeanDeposition

Young Calf

Immune response

Nutrition & ImmunologyOrder of importance of nutrients toimmune system

• Energy• Protein• vitamin A• vitamin E• Copper, Zinc, Selenium• IRON

Summary

• Acidosis affects memory• Energy is important for immune response• Vitamin A deficiency can decrease mucosal

homing• Zinc is very important at times of stress• Vitamin E/Selenium important for many

immune responses

Harvey Dunn (1884-1952) Prairie is My Garden, South DakotaArt Museum

Prevention of BRDC

• Management

• Vaccines

Intranasal Vaccines

• Nasalgen– Day old calves

• Onset– Conducted in young calves (3-8 days of age)– Challenged with virulent strains of IBRV, BVD 1,

BVD 2, BRSV, PI3, Pasteurella multocida – 21to 28 days post-vaccination

• Enforce -3 BRSV Nasal studies 14 day oldcalves

Respiratory Immmunlogy

Respiratory Immunology

• Mucosal Immune Response is the mostimportant defense system

• Almost all bovine pathogens enter via theairways and the mucosa surface

• Viruses- BHV-1, BVDV, PI3, BRSV, BRCV• Bacteria- M. haemolytica, P. multicida, H.

somnus, M. bovis

Mucosal Immunity - Local response

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Mucosal Immunity - Local response

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U YYYYUYY YYU

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Stop them before they infect

When Do We BeginVaccinating Calves?

• At a week of age• At a month of age• At 2-3 months of age• Before they are born by

vaccinating the cow-High qualitycolostrum

What RespiratoryInfectious Agents are

Important• Calves

– 3 weeks- 3-4 months• Pasteurella multicida• Mannheimia (Pasteurella) hemolyticae-herd history• Clostridial diseases• BRSV- herd history, summer pneumonia• Leptosporosis• Mycoplasma bovis (pneumonia, inner ear)??• BVDV???

What Respiratory InfectiousAgents are Important

• Calves– 3-4 months- 12 months

• Brucella abortus*• Pasteurella multicida• Mannheimia (Pasteurella) hemolyticae• Leptospirosis• Clostridial diseases• Mycoplasma bovis-arthritis• BVDV• BRSV• PI3• IBR

Beef Vaccination Schedules• Calves (<4 months)

• Respiratory Diseases• MLV

– Calves on Vaccinated Cows-MLV Intranasal vaccines– Depends on Maternal Antibody levels-MANY MLV IM or

SC NOT EFFECTIVE-ONLY adjuvanted MLV IM or SC)• Inactivated- Well adjuvanted, not affected by Maternal

Antibody• NOT Vaccinate with MLV BVDV before 1 month

Better after 2-3 months of age

Beef Vaccination Schedules• Calves (>4 months)

– Respiratory Diseases• 2-3 weeks prior weaning

– MLV-1 dose– Inactivated-2 doses

• At weaning- avoid– MLV-Immunosuppressive– Inactivated-2 doses

• 2-3 weeks post weaning– MLV-1 dose– Inactivated-2 doses

Stress +Immunosuppressive Viruses=Super Immunosuppresssion

IBR and BVDV MLV are immunosuppressive

Timing of Boosters

Timing and the Adaptive Immune Response-Anamnestic Response

Lymphocyteapoptosis

Lymphocyteproliferationto Ag A

1° responseto antigen A

A A4 16128 20 64 68 72

Magnitudeof specificresponse

Days

2° responseto antigen A

What is the Best Time Interval for Boostering?

Timing and Immune Response- Young AnimalsPrimary vs Booster Response

A A

147 21 28 35

Per

cent

Sus

pect

ible

Days Post VaccinationA

00

50

100Active Immunity

Window ofSusceptibility

Passive Immunity

70%

21%

Booster Time Interval and Response451 CalvesBranding time 67 days3 weeks prior to weaning 167 daysWeaning 190 days

Group 1 vacc 67d and 190d ~120d intervalGroup 2 167d and 190d ~25d intervalo % seroconverted to each virus was sameo No difference in morbidity and mortality, feedlot performance or carcass qualityKirkpatrick et al. 2008 JAVMA 233:136-142

Timing of Boosters

• MLV 2-3 doses by time 8-10months

• Inactivated 2-3 doses by time 8-10months

Boostering MLV vs Inactivated-

• Evidence in either sequenceMLV/Inactivated orInactivated/MLV results insimilar responses

Grooms et al 2002; Royan 2009

Use them in combination-Better adjuvants

Vaccine efficacyRemember BRD is

MultifactorialStress

TransportMixingDehydrationLack of feed

ProcessingHandlingMixingDustHeatColdWaterFeedCompetition

Viruses

IBRBVDVBRSVPI3Adenovirus

Bacteria

M. haemolyticaP. multocidaH. SomnusM. bovis

BRD

Summary

• Vaccination of dams 4-6 weeks prior to calvingimproves colostral antibodies

• Passive antibodies (colostrum) are protective• Vaccinate before shipping• Vaccinate at least a few days after shipping- a

week or two later is best

Summary

• In general we vaccinate calves too much andtoo soon

• No need to vaccinate for BVD before 2-3months of age (don’t do it before 1 month)

• Better colostrum management, less need tovaccinate

• Intranasal vaccines in young calf especially forBRSV important- if BRSV is a problem

Summary

• Interval for boosting needs to bemore 21 days- length depends onvaccine

• Too short a vaccination intervalcan cause problems