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. For llamas, 48 hours is considered optimal.

  • Radial immunodiffusion (RID): This used to be considered the “gold standard” and 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: This has become the gold standard and produces repeatable, quantitative results, with 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 FPTI 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 the biuret method, Brix refractometry, 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 estimated or measured with a number of methods.

  • Total protein measurement (refractometer)
    • Calves: Several studies have been done, showing various sensitivities versus IgG concentrations, e.g. 5.0 g/dL cut-off = 83% sensitivity for FPT using an IgG of 1000 mg/dL; 5.5 g/dL cut-off = 85%. Concentrations generally used are <5.0 or 5.2 g/dL in healthy calves and < 5.5 g/dL in dehydrated animals. 
    • 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.
  • Brix refractometry: This refractometer reflects the sugar content of a solution (1 degree = 1 g sugar in 100 g solution) but can also provide an approximate measure of the content of other dissolved solids.
    • Calves: Various cut-offs have been evaluated (7.8-8.8%).  In a study from Cornell, an optimal Brix cut-off was 8.5% (100% sensitivity, 89% specificity), whereas in the same cohort, a total protein by refractometer of <5.2 g/dL showed similar sensitivity (100%) and specificity (80%) (Hernandez et al 2016).
  • Total protein (Biuret)
    • Llamas: Various cut-offs; <4.5 g/dL was a good indicator of FPT, < 4.7 g/dL associated with IgG < 1000 mg/dL at 48 hours of age (optimal for llamas).
  • Globulin measurement
    • Llamas/alpacas: In one study, a globulin concentration < 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 activities are 60-160x adult values then decline to adult values by 5 weeks of age, if they have suckled. Serum GGT activity was directly related to IgG1 values in calves in one study. For adequate passive transfer, 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 FPTI in one study. In another study, this cut-off had a 93% sensitivity. In a study in beef calves, the authors suggested GGT activity only be used for FPTI in beef calves < 8 days of age.
    • Dogs: GGT activity is increased in 1-3 day old puppies (range 163-3558 U/L) after suckling as is ALP (618-8760 U/L), ALT (17-337 U/L) and AST (45-194 U/L). GGT activity 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 in one study, this test 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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