Foal - Failure of Passive Transfer

Question 1

Foal Immune System vs Adults

Answer 1

• Foals are born without a fully developed immune system
• Components of the foals immune system are there
• They are just not fully functional
• Different components mature at different
  rates
• So they are IMMUNOCOMPETANT AT BIRTH
• But they are IMMUNOLOGICALLY NAÏVE
• They rely on colostrum and non-specific defense mechanisms for their first two months of life

Question 2

Neonate Innate Immunity

Answer 2

• Low levels of soluble factors such as complement and lactoferrin (increase after colostral transfer)
• Complement activity decreased
• Phagocyte numbers comparable to adult but reduced oxidative burst activity and pathogen killing
• Resultant inflammation caused by Macrophages and dendritic cells triggers the adaptive immune response

Question 3

Neonatal Adaptive Immunity

Answer 3

• Decreased antigen presenting capacity
• Lymphocyte numbers comparable to adults but activity reduced (although some sources say B lymphocyte number is reduced)
• Limited ability to produce inteferon gamma and effective Th1 (intracellular killing) response?
• Foals can produce antibodies soon after birth
• The type of response is age dependent with IgGb only detected after 63 days.

Question 4

Equine Placenta

Answer 4

• Epitheliochorial placenta prevents transfer of maternal globulins to foal

Question 5

Colostrum

Answer 5

• They rely on antibody transfer via milk: colostrum
• This goes directly into the blood stream as immunoglobulins (+ other immune cells)
• Colostrum is produced by the mare under hormonal control
• Last 2- 3 weeks of pregnancy as a unique event
• Thick, sticky liquid
• Immunoglobulins are transported to the mammary gland
• PASSIVE TRANSFER only occurs for 6 – 12/36 hours after birth

Question 6

Pinocytosis

Answer 6

• Rapidturnoverofenterocytesmakes process time dependent
• Maximumabsorptionatbirth(50-60%of immunoglobulin absorbed)
• Efficiencyreducedby1/3at9hours
• Littleabsorptivecapacityafter12hours
• Detectableat4–6hours
• IgGpeaksat18–24hours
• Colostralproteinisnotbrokendownin the gastrointestinal tract because colostrum contains a trypsin inhibitor
• Colostralproteinsareabsorbedintactby specialized enterocytes through the process of pinocytosis

Question 7

Colostrum Contents

Answer 7

• Not just IgG, also IgM, IgA
• Lymphocytes
• Cytokines
• Complement
• Hormones
• Growth factor
• ALL ENHANCE innate immune response
• Also high in energy, fat and protein

Question 8

Innate Immunity & Colostrum

Answer 8

• Complement activity 13% of adult values at birth
• Neutrophil chemotaxis and phagocytosis reduced
• Function improves after absorption of opsonins in colostrum

Question 9

Adaptive Immunity & Colostrum

Answer 9

• Maternally derived T lymphocytes can be detected in foal’s circulation
• May directly act as effector cells
• Can release cytokines to modulate neonatal immune response

Question 10

Normal Transfer of Passive Immunity

Answer 10

• IgG used as a marker of adequacy of passive transfer
• A healthy foal consuming 1 - 2L of good quality colostrum will have an IgG concentration >800mg/dl or 8g/l by 24 hours

Question 11

Colostral Antibodies

Answer 11

• Maternal antibodies produced in response to local diseases or recent vaccinations will be concentrated in colostrum
• Preferable for mare to be kept at foaling location at least 4 - 6 weeks prior to foaling

Question 12

Failure of Transfer of Passive Immunity

Answer 12

1. Insufficient
2. Poor quality (mare has “run her milk”)
   * The foals immune system will be weakened with infection, septicaemia and potentially death more likely
   * There’s considerable individual variation in the quality and quantity of colostrum produced by individual mares.
   * The concentration of total IgG does not reflect individual specific antibody levels .

Question 13

Definition of Failure of Passive Immunity Transfer

Answer 13

• Defined as an IgG concentration <8g/l
• Partial failure = 4-8g/l
• Complete failure = <4g/l

Question 14

Causes of FPTI - Mare Factors:

Answer 14

Colostrum quality varies between mares
Factors that cause poorer quality:
* Maiden and aged mares
* Illness - placentitis
* Poor nutrition
* Milk leakage before foaling
* Premature delivery

Question 15

Causes of FPTI - Foal Factors:

Answer 15

Failure of ingestion
* Weakness
* Disease eg NMS
* Orthopaedic problems
* Inexperienced mare/ maternal aggression
* Physical separation

Prematurity
Disease / illness reducing gut perfusion or health eg enteritis, NMS

Question 16

-ve Outcomes of FTPI:

Answer 16

Death
Systemic sepsis
Local sepsis

Question 17

FTPI in Different Environments:

Answer 17

• In extensively managed situations strong association between FTPI and non-survival
• In hospitalised foals some association between FTPI and non- survival
• In more intensively managed situations no clear association with FTPI and non-survival

Question 18

Measurement of IgG Conc:

Answer 18

• Radial immunodiffusion = gold standard but slow
• Immunoturbidimetric still quantitative but much quicker
• SNAP ELISA is common semi-quantitative test
• High sensitivity and -ve predictive value
• 64% agreement with RID
• Inaccurate in 4 - 8gl range
• Measurement of Total Protein concentration by optical refractometer may be helpful
• 5.7g/l cut-off had 100% sensitivity for identifying IgG concentration <8g/l * CARE: sick foals, haemoconcentration

Question 19

Interpreting IgG Conc

Answer 19

Essential tx = <4g/L
Recommended tx = <4-8g/L
No tx = 8g/L

Question 20

Factors Affecting IgG Conc Interpretation

Answer 20

• High risk foal
• Concurrent dx
• Env conditions
• On farm dx status
• Routine haematology/ inflammatory markers
• Age of foal

Question 21

Timing of Testing:

Answer 21

Test from 12hrs
24hrs = ideal
Better too early than too late

Question 22

Treatment

Answer 22

• After closure of gut barrier (12 hours), immunogloublins can only be given by IV route
• Commercial plasma from hyperimmunised donors is most convenient way to do this
• 1 litre will usually raise IgG by 2- 3g

Question 23

Commercial Plasma

Answer 23

• Keep frozen
• Defrost slowly
• Can have specific types (Rhodococus equi)
• Must use blood giving set with filter

Question 24

Self Harvested Plasma

Answer 24

• Ideally should ensure adequate IgG content of donor (>1200mg/dl) and cross match
• Collect whole blood and separate plasma
• Increased risk of neonatal isoerythrolysis if filly becomes broodmare
• TEST for infectious disease
  Dont have to cross match the 1st time but will have to afterwards

Question 25

Signs of Plasma Transfusion Reaction

Answer 25

* Increased RR, HR, Temp * Restlessness * Collapse * Respiratory distress * Arrhythmia * Death

Question 26

Treating a Transfusion Reaction

Answer 26

Adrenaline at ready Flunixine

Question 27

Monitor Plasma Infusion

Answer 27

* Severeanaphylaxiscanoccurin foals given plasma after certain colostrum substitutes * Thismayberelatedtothe presence of antibodies/ IgE against bovine serum albumin (BSA) in plasma * BSA is commonly found in equine vaccines and hence antibodies are common in equine plasma

Question 28

Sedatives for Plasma Transfusion:

Answer 28

Diazepam & torb - avoid a-2

Question 29

The Madigan Squeeze

Answer 29

tie ropes - around neck and chest stims foal - feels as if being born again sends them to sleep and then they wake up as if being born

Question 30

Other Tx:

Answer 30

* Monitor for signs of infection * Check inflammatory markers * Consider use of antimicrobials * Recheck IgG concentration (sick foals catabolise IgG quickly)

Question 31

Prevention

Answer 31

* Good protocols to maximise adequate colostral quality * Good maternal nutrition * Vaccination * Disease management - stud & mare * Mare monitoring

Question 32

Test Colostrum Quality:

Answer 32

Few drops of colostrum on a Brix sugar refractometer * >30% excellent * 25 – 30% very good * 20 – 25% acceptable * <20% poor * Collect 250mls of colostrum from mares with a good supply of colostrum and a refractometer reading > 25% * Label and freeze to create a colostrum bank

Question 33

Donor Colostrum

Answer 33

* ID foals at high risk for FPT due to low colostral quality * Supplement with donor colostrum * Colostrum must be defrosted slowly in warm water and never microwaved * Administer by bottle or stomach tube

Question 34

Other Preventions

Answer 34

* Immunoglobulin products available * Critically evaluate source of immunoglobulin * Care if future plasma transfusions given * Bovine colostrum if no other source available * Mare vaccination !