Climatic and calf-related risk factors associated with failure of transfer of passive immunity in Holstein calves in a hot environment.

This retrospective observational study aimed to assess the effect of temperature-humidity index (THI) at calving and in the last trimester of pregnancy and calve-related factors affecting passive transfer of maternal immunoglobulin using Brix refractometry in Holstein calves. Blood samples from 4411 Holstein calves from a single large dairy farm in spring 2022 were used. A subset of data containing 6318 calvings was used to determine the effect of climatic conditions on the occurrence of agammaglobulinemia. Risk factors predictive of failure of passive transfer (FPT) were calculated using multiple logistic models. Females were 1.4 times more likely not to have FPT (56%; Brix% > 8 equivalent to ≥ 10 g/L IgG) than males (47.2%). Calves born as singles increased the likelihood of not presenting FPT (52.6%) than calves born as twins (42.9%). Calves from cows with no dystocic delivery had a lower risk for FPT (odds ratio = 2.3) than calves from cows with dystocia. Agammaglobulinemia was 1.5 and 1.8 times more likely to occur in calves with THI ≥ 80 and ≥ 82 in the last trimester of gestation and at calving, respectively, than in calves not experiencing heat stress. Agammaglobulinemia was twice as likely to occur in male than in female calves. Calves with birth weight ≥ 37 kg and gestation length ≥ 275 kg were less likely to present agammaglobulinemia than lighter calves and calves with shorter gestation periods. This study raises questions for management practices in Holstein calves undergoing in utero heat stress and around calving to avoid agammaglobulinemia.

Serum immunoglobulin G concentration after plasma transfusion in neonatal foals with hypogammaglobulinemia in various health status.

Due to the time-limited intestinal uptake of colostral immunoglobulins, the suggested treatment of hypogammaglobulinemia in new-born foals is usually plasma transfusion. The aims of this study were twofold: firstly, to investigate the course of serum IgG concentration after plasma transfusion in newborn foals; and secondly, to determine the amount of transfusion required for a significant increase in serum IgG concentration. For this purpose, the IgG concentration was measured in 23 foals at three different points in time: before transfusion, 1 hour after transfusion, and 24 hours after transfusion. There was an increase in IgG concentration in the blood of 18 foals (78.3%). In five foals (21.7%), no increase in serum IgG concentration were detected after plasma transfusion. Transfusion of 1 mg IgG caused an average increase in IgG level of 0.03 mg/dl (0.001-0.268 mg/dl) 1 hour after transfusion. After 24 hours, the same amount of IgG caused a larger increase of 0.05 mg/dl (0.002-0.537 mg/dl). None of the foals demonstrated adverse reactions to the plasma transfusion. These values provide a guidance how much IgG is needed to increase serum IgG concentration to a desired level. However, this study has shown that there is a high variability in serum IgG concentration after plasma transfusion. Which highlights the necessity for monitoring IgG concentration following transfusion.

Hypogammaglobulinaemia and other causes of death in neonatal lambs.

This focus article has been prepared by Amanda Carson, veterinary lead of the APHA's Small Ruminant Expert Group.

Failure of transfer of passive immunity and agammaglobulinaemia in calves in south-west Victorian dairy herds: prevalence and risk factors.

OBJECTIVES: To determine the prevalence of failure of transfer of passive immunity (FTPI) and agammaglobulinaemia in calves in south-west Victorian dairy herds and identify associated risk factors for both outcomes. DESIGN: Cross-sectional study. METHODS: Serum total protein was measured in 1018 calves from 100 south-west Victorian dairy herds. The proportions of calves with FTPI and agammaglobulinaemia were determined and logistic regression with random effects used to identify calf- and herd-level variables associated with both conditions. RESULTS: In total, 38% of calves had FTPI and 8% of calves had agammaglobulinaemia. Two-thirds of herds had more than 25% of calves with FTPI. Jersey and Jersey-cross calves were less likely than Holstein-Friesian calves to have FTPI (odds ratio (OR) 0.53 and 0.57, respectively). Dairy-beef crossbreed calves were more likely to have agammaglobulinaemia than Holstein-Friesian calves (OR 3.52) and bull calves were more likely to have agammaglobulinaemia than heifer calves (OR 2.22). Removal of calves from the calving area less than twice a day was associated with increased odds of FTPI (OR 1.61) and agammaglobulinaemia (OR 1.97) relative to more frequent removal. CONCLUSION: There is considerable potential to improve the transfer of passive immunity in dairy herds in south-west Victoria. The prevalence of both FTPI and agammaglobulinaemia is likely to be reduced by collecting calves from the calving area twice daily and hand-feeding them extra colostrum immediately after their removal from the calving area.

Hypogammaglobulinemia in racing Alaskan sled dogs.

BACKGROUND: Serum immunoglobulin dynamics have not been studied in racing sled dogs, despite hypoglobulinemia having been reported during racing events. HYPOTHESIS/OBJECTIVES: Hypoglobulinemia in racing sled dogs is associated with decreases in serum IgA, IgE, IgG, and IgM concentrations during prolonged exercise. ANIMALS: One hundred and fifty-seven Alaskan sled dogs that successfully completed a 1,000 mile race. METHODS: Serum was obtained from 118 sled dogs within 1 month before the race and within 12 hours after completing the race. Serum also was obtained after 4 months of rest from 51 dogs that successfully completed the race, including 12 previously sampled dogs. Serum total protein ([TP]), albumin, and globulin ([Gl]) were measured, and serum IgA, IgE, IgG, and IgM were quantified by ELISA. RESULTS: The proportion of dogs with [Gl] < or = 2.2 g/dL was significantly greater immediately after racing (38 of 118 dogs, 32.2%) than before racing (21 of 118 dogs, 17.8%, P = .005). Four months after racing, [Gl] was < or = 2.2 g/dL in 23.5% (12 of 51) of dogs. [IgG] was significantly lower before (8.21 +/- 4.95 mg/mL) and immediately after (7.97 +/- 5.62) racing compared with 4 months after racing (18.88 +/- 5.76). Serum [IgM] and [IgE] were higher and [IgA] was lower before racing compared with immediately after racing. CONCLUSIONS AND CLINICAL IMPORTANCE: Sled dogs participating in long-distance racing have substantial decreases in [IgG] in addition to decreases in [IgM] and [IgE]. The pronounced hypogammaglobulinemia observed in a large proportion of racing sled dogs might predispose them to infectious disease.

[Cryptosporidiose (C. parvum) in a foal with diarrhea]. / Cryptosporidiose (C. parvum) bei einem Fohlen mit Durchfall.

The protozoon parasite Cryptosporidium parvum is an important cause of diarrhea in farm animals, but it can also infect other animals and humans. In this case report, oocysts of Cryptosporidium spp. were microscopically detected by modified Ziehl-Neelsen staining in the feces of a 9 day old Arabian colt presented with yellowish, foul smelling, diarrhea and fever of 40 degrees C. PCR and sequencing of the isolate revealed C. parvum (bovine genotype). Hemato-chemical analysis of the foals blood revealed a marked hypogammaglobulinaemia (IgG 108mg/dl). The colt responded well to a supportive therapy and administration of plasma (until a gammaglobulin-concentration of 620 mg/dl was reached) and was released in good health from the clinic after 10 days. Follow-up testing for Cryptosporidium oocycsts remained negative. Cryptosporidiosis with life-threatening diarrhea is a rare diagnosis in foals in Switzerland. Immunodeficiency increases the risk for cryptosporidiosis. We hypothesize that the low concentration of gammaglobulins together with the weak INF-gamma response normally observed in young foals may have favored the clinical manifestation with diarrhea. Foals with diarrhea should be screened for cryptosporidia with specific tests.

Immunodeficiency disorders in horses.

Immunodeficiencies are characterized as primary (genetic) or secondary (acquired). Primary immunodeficiencies are relatively uncommon; however, clinically, they present a significant challenge to the practitioner, especially if the underlying disorder goes unrecognized. Secondary immunodeficiencies may present at any age, but failure of passive transfer in neonatal foals is most commonly encountered. This article provides a general overview of clinical signs and diagnosis of primary and secondary immunodeficiencies currently recognized in horses.

Application of the glutaraldehyde test in cattle.

In a cohort study involving 62 cows from an experimental farm, the kinetics of the glutaraldehyde test (GAT) according to Sandholm (1974) was examined by testing samples of EDTA blood, lithium heparinate blood, serum, and plasma taken at various intervals. Total protein was measured in serum, and fibrinogen was determined in plasma. Gamma globulin was measured by electrophoresis. All glutaraldehyde tests were performed in duplicates, and the relation of the two results was used as measurement of precision. Optimal cut-off of the GAT time was determined as the zenith of the sum of sensitivity and specificity of various intervals for detecting combinations of gamma globulin and fibrinogen levels above 32 g/l. Precision was the best in EDTA blood. The relation between coagulation time and gamma globulin plus fibrinogen is best described by an exponential curve. The maximum value for the sum of sensitivity and specificity was found at 7 and 8 min. Seven days was the shortest interval observed between a negative test result (>15 min) and a strongly positive test result (<3 min). Twenty-one days was the shortest interval observed between a strongly positive test result and a negative test result. EDTA blood should be used for the GAT. A cut-off of 8 min yields the highest efficiency. Test results must be viewed in light of clinical findings.

Common variable immunodeficiency in three horses with presumptive bacterial meningitis.

Three adult horses were evaluated for signs of musculoskeletal pain, dullness, ataxia, and seizures. A diagnosis of bacterial meningitis was made on the basis of results of CSF analysis. Because primary bacterial meningitis is so rare in adult horses without any history of generalized sepsis or trauma, immune function testing was pursued. Flow cytometric phenotyping of peripheral blood lymphocytes was performed, and proliferation of peripheral blood lymphocytes in response to concanavalin A, phytohemagglutinin, pokeweed mitogen, and lipopolysaccharide was determined. Serum IgA, IgM, and IgG concentrations were measured by means of radial immunodiffusion, and serum concentrations of IgG isotypes were assessed with a capture antibody ELISA. Serum tetanus antibody concentrations were measured before and 1 month after tetanus toxoid administration. Phagocytosis and oxidative burst activity of isolated peripheral blood phagocytes were evaluated by means of simultaneous flow cytometric analysis. Persistent B-cell lymphopenia, hypogammaglobulinemia, and abnormal in vitro responses to mitogens were detected in all 3 horses, and a diagnosis of common variable immunodeficiency was made.

Immunoglobulin G2 deficiency with transient hypogammaglobulinemia and chronic respiratory disease in a 6-month-old Holstein heifer.

A 6-month-old Holstein heifer that was nonresponsive to medical treatment was evaluated for chronic respiratory disease. Complete blood count and serum chemistry revealed neutrophilic leukocytosis and low globulin levels. Assays for bovine leukemia virus, bovine virus diarrhea, and bovine leukocyte adhesion deficiency were negative. Serum globulin subclass assays revealed transient low concentrations of immunoglobulin (Ig) G1 and IgA, persistent low IgG2, and subnormal IgM. Vaccination with 2 doses of multiple, inactived viruses induced seroconversion for most viruses. Flow cytometric analysis of blood lymphocyte subpopulation demonstrated an increase in CD5+ B-cells. Blood lymphocyte proliferation and neutrophil function tests were normal. Results of immunologic assays indicated IgG2 deficiency with transient hypogammaglobulinemia.

[Reliability of the glutaraldehyde test to measure gamma-globulin levels in foals and the use of this test to check colostrum intake of foals]. / Een onderzoek naar de betrouwbaarheid van de glutaaraldehydetest voor de bepaling van het gammaglobulinegehalte in het serum van veulens en naar de bruikbaarheid van deze test in de praktijk bij het controleren van de colostrumopname bij veulens.

The glutaraldehyde coagulation test is a semi-quantitative test used to determine the gammaglobulin concentration in serum. The purpose of this study was to examine the reliability of the different modifications of this test by determining the sensitivity, specificity, positive and negative predictive value, and the prevalence of hypogammaglobulinemia in foals. The results of the glutaraldehyde coagulation test were compared with the serum gammaglobulin concentration as a reference value, determined by measuring total serum protein and the serum protein spectrum. It was concluded that the glutaraldehyde coagulation test is a suitable test to use in the field for determining the serum gammaglobulin concentration in foals. The test has good sensitivity, specificity, positive and negative predictive value when using a 5% glutaraldehyde solution and when results are evaluated at 30 minutes for a serum concentration of 8 g/l and at 50 minutes for a serum concentration of 5.5 g/l, a concentration below which therapy is recommended.

Immunological anomalies and thrombocytopenia in 117 dogs and cats diagnosed with chronic fatigue syndrome (CFS).

Retrospective analysis of immune dysfunctions found in 55 dogs and 62 cats diagnosed with Chronic Fatigue Syndrome (CFS), revealed leukopenia in 11% of dogs (n = 6) and 22.5% of cats (n = 14), lymphopenia in 14.5% of dogs (n = 8) and 10% of cats (n = 6), hypogammaglobulinaemia in 9% of dogs (n = 5) and 13% of cats (n = 8) and thrombocytopenia in 20% of dogs (n = 11) and 68% of cats (n = 42). All patients had creatine kinase enzyme levels above the normal range (CK = 5-100 IU/L) and carried micrococcus-like organisms on erythrocytes. Blood cultures proved positive for Staphylococcus spp. in 16 cases. After low-dosage arsenic-based therapy (thiacetarsamide sodium) all animals experienced complete clinical remission. Subsequent controls demonstrated immune restoration in 4 representative FIV-FeLV negative cats, previously diagnosed with CFS associated with leukopenia, lymphopenia, hypogammaglobulinaemia and thrombocytopenia. The main conclusion is that a CFS-like disease in dogs and cats, characterised by the common hallmarks of high CK levels, absence of known causes of chronic fatigue in animals and presence of micrococcus-like organisms in the blood, can be associated with humoral and/or cellular immune deficiencies in 9-22.5% of cases and with thrombocytopenia in 20-68% of cases. Considerations are made on the possible role of micrococci in the aetiology of the condition and on the similarities with CFS in humans.

Common variable immunodeficiency in a horse.

A 12-year-old Quarter Horse mare that was nonresponsive to medical treatment was evaluated for chronic respiratory disease and hepatobiliary disease. Serum immunoglobulin concentrations were measured by use of radial immunodiffusion that revealed trace to nondetectable concentrations of IgG, IgG(T), IgM, and IgA. Use of serum protein electrophoresis confirmed agammaglobulinemia by the absence of the expected peak in the gamma region. In addition, vaccination with tetanus toxoid did not result in specific immunoglobulin production. Flow cytometric analysis of blood lymphocyte subpopulations revealed the absence of B cells in blood. Immunohistochemical analysis of tissue sections revealed the absence of B lymphocytes in bone marrow and spleen, with occasional B cells in the peripheral lymph nodes. Blood lymphocyte proliferation assays revealed weak responses to pokeweed mitogen and no response to stimulation with lipopolysaccharide. Considering the age and sex of the horse, results of the immunologic tests suggested a diagnosis of common variable immunodeficiency.

Passive transfer of colostral immunoglobulin G in neonatal llamas and alpacas.

OBJECTIVE: To evaluate precolostral hypogammaglobulinemia in neonatal llamas and alpacas, to determine when postcolostral peak serum IgG concentrations develop, to determine whether differences in postcolostral serum IgG concentrations between llamas and alpacas exist, and to determine postcolostral half-life of serum IgG in llamas and alpacas. DESIGN: Prospective observational study. ANIMALS: 29 llama and 10 alpaca crias. PROCEDURE: Blood samples were collected prior to suckling and on days 1, 2, and 3 after parturition and analyzed for serum IgG concentration by use of a commercial radial immunodiffusion assay. Additional samples were collected on days 8, 13, and 18 from 8 crias to determine mean half-life of IgG. RESULTS: Llamas and alpacas are born severely hypogammaglobulinemic. Mean serum IgG concentrations for day-1, -2, and -3 samples for llamas were 1,578 mg/dl, 1,579 mg/dl, and 1,401 mg/dl, respectively, and for alpacas were 2,024 mg/dl, 1,806 mg/dl, and 1,669 mg/dl, respectively. Peak serum immunoglobulin concentration developed between days 1 and 2. Mean half-life of IgG for all crias was 15.7 days. CONCLUSIONS AND CLINICAL RELEVANCE: Although increased mortality has been linked to failure of passive transfer, it is clearly possible to raise crias that have low serum immunoglobulin concentrations. Llamas and alpacas do not differ significantly with respect to immunoglobulin absorption or IgG concentration in neonates. The optimal sampling time for passive transfer status is between 1 and 2 days.

Primary immunodeficiencies of horses.

Primary immunodeficiency disorders are genetically determined failures of immune defense that increase susceptibility to infectious agents. This article reviews the salient features of equine primary immunodeficiency disorders, summarizes the molecular mechanisms of each disorder, and updates information that facilitates diagnosis and management of affected horses. The central theme is to encourage clinicians to ask, "I wonder if this horse has an underlying primary immunodeficiency disorder?" when caring for horses suffering from chronic and recurring infections and responding poorly to standard therapy.

Prevalence (treatment days) and severity of illness in hypogammaglobulinemic and normogammaglobulinemic foals.

Serum samples for determination of IgG concentration were obtained between postpartum hours 18 and 48 from 132 Standardbred foals. Results of the IgG assay were not known to farm personnel. None of the foals was given plasma IV for treatment of hypogammaglobulinemia. Foal health records were examined retrospectively to determine prevalence of infectious-type illness (foal treatment days [FTD]), prevalence of life-threatening infectious illness (foal treatment days-serious condition [FTD-SC]), and number of diseases (NOD) per foal. Values for FTD, FTD-SC, and NOD per foal were compiled for the first 21 days of life and for the first 90 days of life. The FTD, FTD-SC, and NOD per foal values were compared for foals with less than 400 mg of IgG/dl and for foals with greater than or equal to 400 mg of IgG/dl; the same variables were compared for foals with less than 800 mg of IgG/dl and for foals with greater than or equal to 800 mg of IgG/dl. Statistical analysis indicated that IgG concentration was not associated with FTD, FTD-SC, or NOD in foals of any of the groups. Also, despite a large subpopulation of hypogammaglobulinemic foals (13.6% with less than 400 mg of IgG/dl and 44.7% with less than 800 mg of IgG/dl), the 21-day and 90-day overall survival rates were 100 and 99.2%, respectively. The data strongly suggest that serum IgG concentration was not related to prevalence or severity of illness or to survival rate in this population of foals.

Comparison of four screening techniques for the diagnosis of equine neonatal hypogammaglobulinemia.

Using radial immunodiffusion as a standard, 4 screening techniques for detection of failure of passive transfer in equine neonates were compared for sensitivity, specificity, positive and negative predictive values, efficiency, and cost. The techniques compared were latex agglutination test, membrane filter ELISA, dipstick ELISA, and glutaraldehyde coagulation (GC) test. Test results of 50 serum samples from foals 24 to 60 hours old revealed consistently highest accuracy in the GC test at IgG concentrations of 400 and 800 mg/dl, and lowest cost per test, using the GC test. Two hundred fifty-three serum samples from foals 24 to 60 hours old were evaluated for comparison of results of GC and radial immunodiffusion tests. Overall efficiency was 92 and 91% at serum IgG concentrations of 400 and 800 mg/dl, respectively. Under most field circumstances, the GC test would be the preferred screening test for detection of failure of passive transfer in equine neonates.

Detection of hypogammaglobulinaemia in neonatal foals using the glutaraldehyde coagulation test.

The glutaraldehyde coagulation test was adapted to foal serum to determine adequacy of the colostral-intestinal transfusion of IgG. The test is performed simply by mixing one volume of reagent with 10 volumes of serum and observing the coagulation time. The required glutaraldehyde concentration was established for various threshold levels of IgG as determined by radial immunodiffusion. The analysis consisted of 140 serum samples from foals. Sera with low IgG levels require high glutaraldehyde concentrations and vice versa. The 4 g/l threshold generally accepted for IgG adequacy, was achieved at the optimum diagnostic sensitivity and specificity level by using 10% solution of glutaraldehyde and observing the coagulation at 20 minutes. The use of a 5% glutaraldehyde solution resulted in a cut off level at 5.5 g/l, respectively. The glutaraldehyde test is the cheapest field test for IgG-adequacy.