Passive transfer failure

 

Failure of transfer of passive immunity (FTPI) is a major cause of neonatal infectious disease and mortality in foals, calves and crias. These species are hypogammaglobulinemic or agammaglobulinemic at birth and depend on transfer of immunoglobulins from maternal colostrum until they can produce their own immunoglobulins. This takes approximately 10-14 days in the foal and 8-16 days in the calf. Enterocytes of the neonate are capable of absorbing the large immunoglobulin molecules only for the first 24 hours after birth, and many different factors can result in decreased or absent transfer (these will not be covered in detail here). In order to assess for FTPI blood is drawn between 18 and 24 hours after birth and IgG can be measured by several methods

  • Radial immunodiffusion (RID): Considered the “gold standard”. RID is more accurate than ELISA (may not yield low immunoglobulin results in FPT). However, turnaround time is slow, taking a minimum of 18 hours.
  • Immunoturbidometry: Produce quantitative results and has a relatively fast turnaround time.
  • ELISA and latex agglutination: Several point of care tests are available, they are rapid and easy to use, but are less sensitive to decreased IgG than RID or immunoturbidometry.
  • Other tests are available but reliability tends to be lower and varies by species. These include: Total protein by refractometry or biuret, globulin measurement, methods dependent on protein precipitation (ZnSO4 turbidity, Na2SO3 precipitation, glutaraldehyde coagulation test).

IgG measurement for failure of passive transfer in different species

IgG can be measured with a number of methods.

  • Total protein measurement (refractometer)
    • Calves: A 5.0 g/dL cut-off had a 83% sensitivity in calves. In this study, a total protein concentration of 5.2 g/dL was equivalent to 1000 mg/dL IgG1. In another study, the sensitivity of a 5.5 g/dL cut-off in calves was 85%.
    • Llamas: considered inaccurate, although one study suggests a cut-off of < 4.9 g/dL in neonatal llamas/alpacas is associated with IgG < 1000 mg/dL at 48 hours old.
  • Total protein (Biuret)
    • Llamas: <4.5 g/dL was a good indicator of FPT. TP < 4.7 g/dL was associated with IgG < 1000 mg/dL at 48 hours of age (optimal for llamas).
  • Globulin measurement
    • Llamas/alpacas, a globulin < 2.3 g/dL was associated with IgG < 1000 mg/dL.
  • GGT in all species other than mare (horses do not have high GGT levels in colostrum)
    • Calves: GGT are 60-160x adult values then decline to adult by 5 weeks of age, if they have suckled. Serum GGT was directly related to IgG1 values in calves in one study. For PT, calves should have GGT > 200 U/L at 1 day old, > 100 U/L at 4 days old and > 75 U/L at 1 week old. A GGT < 50 U/L indicated FPT in one study. In another study, this cut-off had a 93% sensitivity in calves. In another study, they suggested GGT only be used for FPT in beef calves < 8 days of age.
    • Dogs: GGT is increased in 1-3 day old puppies (range 163-3558 U/L) after suckling as is AP (618-8760 U/L), ALT (17-337 U/L) and AST (45-194 U/L). GGT is much higher in colostrum than ALP (thoughts are that the increases in ALP after suckling is not from colostrum, but not sure from where it is coming).
  • Zinc sulfate turbidity: This is not considered as good as immunoglobulin measurement. It is affected by carbon dioxide and hemolysis.
    • Calves: In one study, this was 100% sensitive and 52% specific for FPT.
    • Llamas: Inaccurate in one study.
  • Sodium sulfite precipitation:
    • Calves: Using a 1+ endpoint, this had 85-86% sensitivity (in 2 studies) and 87% specificity.
    • Llamas: Insensitive but easy to use. In one study, a commercial SST kit at 300 mg/dL cut-off had good sensitivity and specificity in 48 hour old llamas and alpacas. However, all of the assays lacked sensitivity and specificity. A low value confirms FPT but a high value does not rule it out.
    • Foals: It is not valid.
  • Glutaraldehyde coagulation test (GC): Glutaraldehyde forms intermolecular crosslinks with basic proteins, resulting in the formation of insoluble complexes. It reacts with fibrinogen and IgG so serum samples are preferred. A limitation is that severe hemolysis may shorten times and overestimate IgG concentrations.
    • Calves: The whole blood GC test is inadequate due to low sensitivity and poor correlation to IgG1 (r2=0.034).
    • Llamas: Equivocal. This test was accurate but insensitive in llamas in one study.
    • Horses: In one study, the GC test had 92% and 91% efficiency at serum IgG concentrations of 400 and 800 mg/dL, respectively.
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