A multisite,randomized field trial to evaluate the influence of lactoferrin on the morbidity and mortality of dairy calves with diarrhea

Diarrhea is one of the most common causes of antimicrobial use and mortality in young calves. To reduce antimicrobial use and resistance on dairy farms, research on alternative therapies for calf diarrhea is necessary. Our laboratory previously conducted a randomized clinical trial investigating the effectiveness of lactoferrin, an iron-binding protein found in colostrum, as a treatment for calf diarrhea. The trial showed significantly reduced calf mortality in diarrheic calves that were administered lactoferrin. Thus, the objective of this study was to corroborate the results of our prior clinical trial across multiple farms and to investigate the effect of lactoferrin on the morbidity and mortality of preweaned calves with naturally occurring cases of diarrhea. This randomized field trial was conducted on 5 commercial dairy farms in Ohio. In total, 485 calves (≤21 d of age) were enrolled at first diarrhea diagnosis (fecal score ≥2 defined as loose to watery) and randomly assigned to receive an oral dose of lactoferrin (3 g of lactoferrin powder dissolved in 30 mL of water) or 30 mL of water (control) once daily for 3 consecutive days. Health assessments were conducted on the day of diarrhea diagnosis (d 0) and 1, 2, 3, 7, 14, 21, 28, and 35 d following diagnosis. Producer records of disease treatment and mortality were collected 120 d following diagnosis. A Poisson regression model was used to test differences between treatments in disease frequency through 35 d post-diarrhea diagnosis and the incidence risk of treatment and mortality risk 120 d post-diarrhea diagnosis; the model controlled for calf age at enrollment, farm, and treatment. Median calf age at enrollment was 11 d and ranged from 1 to 26 d of age. At study enrollment, 51.3% (123/240) and 52.2% (128/245) of calves in the control and lactoferrin treatment groups, respectively, were diagnosed with severe diarrhea (fecal score = 3). The frequency of disease (diarrhea, dehydration, depression, signs of respiratory disease) through 35 d following diarrhea diagnosis was not significantly different for calves in the lactoferrin and control groups. Overall mortality risk for enrolled calves was 9.9%, and 10.7% (22/243) and 9.1% (26/242) of calves in the lactoferrin and control groups, respectively, died or were culled in the 120 d following diarrhea diagnosis. The relative risk of death or culling did not differ between treatment groups, however. Therefore, as performed in this study, lactoferrin as a treatment for calf diarrhea was not beneficial.     

Targeting therapy to minimize antimicrobial use in preweaned calves: Effects on health, growth, and treatment costs

Prophylactic and therapeutic antimicrobial use in food animals is questioned because of the potential for development of resistant bacteria and future inability to use some antimicrobials for human or animal disease. The objectives of this study were to determine the effect of raising preweaned dairy calves without antimicrobials in the milk and minimizing therapeutic antimicrobial treatment on morbidity, mortality, weight gain, and treatment costs. Newborn calves (n = 358) were allocated to 1 of 4 groups, housed outdoors in individual hutches, and monitored for 28 d. Calves in the conventional therapy (CT) group were treated as per dairy protocol with sulfamethoxazole/trimethoprim, spectinomycin, penicillin, and bismuth-pectin for diarrhea. The targeted therapy (TT) group included bismuth-pectin for diarrhea and antimicrobial treatment only in cases of fever or depressed attitude. Within CT and TT groups, calves were equally assigned to receive neomycin and tetracycline in their milk for the first 2 wk of life (AB-milk) or no antimicrobials (NoAB-milk). Daily health evaluations included fecal consistency, respiratory disease, attitude, and hydration status as well as milk and grain consumption. A negative binomial model evaluated the total number of days with diarrhea days in each group. General linear models were used to assess average daily weight gain and grain consumption. Conventionally treated calves had 70% more days with diarrhea than TT calves, and AB-milk calves had 31% more days with diarrhea compared with NoAB-milk calves. The TT calves tended to have a higher average daily gain by 28 d and consumed more grain compared with CT calves. If antimicrobials were used only for diarrhea cases with fever, inappetence, or depression and no in-milk antimicrobials were used, a $10 per calf savings could be realized. Targeting antimicrobial therapy of calf diarrhea cases is prudent not only to save the drugs for future use but also to prevent the potential for antibiotic-associated diarrhea and reduce calf-rearing costs.     

Evaluation of the effects of oral colostrum supplementation during the first fourteen days on the health and performance of preweaned calves

Increasing concerns about antimicrobial resistance have led to the development and implementation of alternatives to antimicrobial use in animal production. The objective of this clinical trial was to determine the effect of colostrum supplementation of the milk replacer ration on morbidity, mortality, feed intake, and weight gain of preweaned calves. Ninety 1-d-old calves on each of 3 commercial calf ranches were randomly allocated to 1 of 3 groups. Treatment-group calves received 10 g of supplemental immunoglobulin G (IgG) in the form of 70 g of colostrum powder in the milk replacer twice daily for 14 d. The placebo-group calves received a nutritionally equivalent supplement lacking IgG in the milk replacer twice daily for 14 d. Control calves received milk replacer without supplements twice daily. Calves were housed in individual hutches and were weighed on d 1, 28, and 60. Serum was collected on d 2 for serum IgG determination. Daily health evaluations for the first 28 d of life were performed by study personnel blinded to treatment group assignment. Observed illness was treated based on health assessment, rectal temperature, and specific calf ranch protocols. Feed consumption (milk and grain) was recorded. Calves receiving supplemental colostrum had less diarrhea and received fewer antimicrobial treatments than control and placebo calves. The results indicated that calf diarrhea was associated with low serum IgG levels and low-weight calves. Grain consumption and weight gain over the first 28 d of life were significantly greater in colostrum-supplemented calves compared with control calves. No differences in mortality or respiratory disease incidence among groups were detected. Supplemental colostrum during the first 2 wk of life can reduce diarrheal disease in preweaned calves on calf ranches and thereby reduce the amount of antimicrobial treatments needed.     

Lactoferrin supplementation to Holstein calves during the preweaning and postweaning phases

Sixty Holstein calves (30 bulls, 30 heifers) were used to examine the effects of supplemental lactoferrin on feed intake, growth, and health during the preweaning and postweaning periods. One of 3 levels of lactoferrin was supplemented from 3 to 56 d in either whole milk or water to produce 3 dietary treatments: 1) 0 g/d, 2) 0.5 g/d, and 3) 1 g/d. Whole milk (3.8 L/d) containing lactoferrin supplements was fed from bottles until weaning at 35 d. From d 36 to 56, lactoferrin supplements were added to water (15 to 25 mL) and fed from bottles. Lactoferrin supplementation had no effect on feed intake, body weight, average daily gain, heart girth, body temperature, fecal scores, respiratory scores, or haptoglobin concentrations. Calves were housed in individual pens in either an open-sided barn or hutches. Calves raised in the barn consumed more calf starter and therefore grew better than calves raised in hutches. Under the conditions of this study, lactoferrin supplementation was not beneficial. Further research is needed to fully elucidate the role of lactoferrin, and possible benefits during different feeding conditions or milk sources.     

Supplemental lactoferrin improves health and growth of Holstein calves during the preweaning phase

Lactoferrin is a milk protein that exhibits broad-spectrum antimicrobial properties. Previous studies indicated that supplemental lactoferrin may alter the microbial populations in the gut of nonruminants and increase preweaning weight gains in calves. In the present study, 40 Holstein calves were used to examine the effects of supplemental lactoferrin (0, 1, 2, or 3 g/d) on health, growth, and feed intake from 3 d of age to 2 wk postweaning. Lactoferrin was mixed and fed with a nonmedicated milk replacer. Calves were housed in individual pens and offered a textured, nonmedicated starter and water for ad libitum consumption. Body weight and heart girth were measuredweekly. Intakes of milk replacer and starter were determined daily. Fecal consistency was monitored three times per week. Calves were weaned when they met certain criteria based on body weight gain and starter intake. Preweaning fecal score responded quadratically, with the group fed 1 g/d of lactoferrin having the lowest score. Overall and preweaning number of days medicated responded in the same manner as fecal score. Preweaning average daily gain and gain-to-feed ratio increased linearly with lactoferrin supplementation, whereas postweaning gain-to-feed ratio decreased linearly with lactoferrin. Overall average daily heart girth gain increased linearly with lactoferrin. Body weight, weaning age, and dry matter intake were not different among treatments. Based on the observed improved gain-to-feed ratios, increased average daily gains, improved fecal scores, and reduced morbidity in preweaned calves, it appears that lactoferrin may be a beneficial supplement in the diets of neonatal calves prior to weaning.     

The effect of neomycin inclusion in milk replacer on the health,growth, and performance of male Holstein calves during preweaning

The prophylactic use of oral antimicrobials, such as neomycin, in milk replacer (MR) or whole milk is a common practice in calf-rearing that is thought to aid in preventing disease. Heavy reliance on antimicrobials is of concern not only because of the development of antimicrobial resistance, but also because of the potentially negative effects on health. The objective of this study was to investigate the effects of neomycin on calf health and growth performance. One hundred and sixty calves (approximately 3–10 d of age), distributed across 2 experimental periods, were stratified by body weight (BW) and serum total protein, and assigned to 1 of 3 treatments: control (CON; nonmedicated MR, n = 60), short-term antibiotic (ST; neomycin mixed in MR from d 1–14, n = 50), or long-term antibiotic (LT; neomycin in ?MR from d 1–28, n = 50). Arrival BW (47.69 ± 0.87 kg) and serum total protein (5.67 ± 0.09 g/dL) were not different between treatment groups. Neomycin in ST and LT was dosed in MR at a rate of 20 mg/kg of BW and was adjusted weekly according to BW. Calf BW was measured weekly for 49 d, and health indicators (fecal score, attitude score, respiratory score, and rectal temperature), MR intake, starter intake, and the use of additional electrolytes and antimicrobials were recorded daily. Calves in the CON group experienced a higher proportion of days with diarrhea (20.32 ± 0.02%) compared with ST (14.70 ± 0.02%) or LT (13.80 ± 0.02%) calves, as well as longer bouts of diarrhea (7.45 ± 0.38 d, 5.69 ± 0.46 d, and 5.62 ± 0.45 d for CON, ST, and LT calves, respectively). Calves in the CON group also experienced higher fecal scores (score of 0.64 ± 0.04) than ST (score of 0.53 ± 0.04) or LT (score of 0.49 ± 0.04) calves, especially at d 7. However, no differences were observed in other health-related measures. The time to reach first diarrhea and first respiratory illness was not different between treatments, nor was the time to recover from respiratory illness. The time to intervention with additional electrolytes or antimicrobials was not different between treatment groups. Furthermore, growth performance, feed intake, and feed conversion ratio were not different. No differences were found when comparing ST and LT, except in the defined daily dose of total antimicrobials received. Calves in the LT group received a higher overall dose than ST calves, and both ST and LT calves received a higher dose than CON calves, which received no prophylactic antimicrobials. Given that there were no differences in performance variables and no additional health benefits aside from reduced fecal scores in calves fed neomycin, current practices involving the use of antimicrobials on dairy and veal operations need to be considered more prudently.     

Lactoferrin supplementation to dairy calves

Twenty-one Holstein calves (12 bulls, 9 heifers) were used to evaluate the effects of supplemental lactoferrin (0, 1, and 10 g/d) added to colostrum, milk, and milk replacer in a 56-d study. Calves fed lactoferrin (LF) weighed more during wk 2, 3, 4, 5, and 6 than control calves. Calves fed LF had increased preweaning daily weight gains and heart girth gains compared with calves not fed lactoferrin. Calves fed 1 g/d LF had a greater preweaning average daily gain than calves fed 10 g/d of lactoferrin. Hematocrit and serum Fe were unaffected by treatments. Calves were weaned when they had consumed 0.7 kg of calf starter grain for 2 consecutive d and were at least 28 d of age. All calves were weaned by 35 d of age, regardless of starter intake. Calves fed LF consumed more calf starter grain during the preweaning period and met weaning criteria at a younger age. This study indicates that supplementing calf diets with LF is advantageous to calf performance.     

Effects of spray-dried animal plasma in calf milk replacer on health and growth of dairy calves

Male Holstein calves (n = 120) purchased from local dairy farms were fed one of three calf milk replacers for 42 d. Experimental milk replacers were formulated to contain whey protein concentrate (WPC) as the primary protein source or WPC plus 5% spray-dried bovine plasma (SDBP) or spray-dried porcine plasma (SDPP). The SDPP was heated to remove heat-insoluble materials and provide products with similar IgG content. Calves were also fed commercial calf starter and water for ad libitum consumption. Intake, change in body weight (BW), feed efficiency, morbidity and mortality were determined. Mortality was 10, 3, and 2 in calves fed WPC, SDBP, and SDPP treatments, respectively. Morbidity, measured as the number of days that calves had diarrhea was reduced by 30% when SDBP or SDPP were fed. Calves had diarrhea for 6.9, 3.9, and 4.7 d during the 42-d study when fed commercial calf milk replacer containing WPC, SDBP, and SDPP, respectively. Fecal scores tended to be reduced and feed efficiency tended to be improved when SDBP or SDPP were fed. Mean intakes of total dry matter during the 42-d study were greater when calves were fed SDBP or SDPP and were 661, 710, and 684 g/d for calves fed WPC, SDBP, and SDPP, respectively. Mean BW gains from d0 to 42 were 231,261, and 218 g/d, respectively. Calves fed SDPP tended to have lower BW gain during the first 28 d of the study. However, difference in daily BW gain from d 1 to 28 was only 39 g/d. Inclusion of SDBP or SDPP in milk replacer reduced morbidity and mortality of milk-fed dairy calves.     

Bovine respiratory disease (BRD) cause-specific and overall mortality in preweaned calves on California dairies: The BRD 10K study

Mortality in preweaned dairy calves is a significant source of economic loss for dairy producers. In particular, bovine respiratory disease (BRD) is a leading cause of death in preweaned dairy calves. The objectives of this study were to investigate management practices and their effects on mortality, both that specifically attributed to BRD and overall mortality due to all causes, in preweaned dairy calves. Rates of failure of passive transfer of immunity (FPT) are also reported. The study consisted of a convenience sample of 5 dairies across California, selected based on management practices, calf records, location, and size. Trained study personnel performed comprehensive calf management surveys on every dairy at least once every season. Calves were enrolled in the study at birth and followed until weaning. Mixed-effect logistic regression models were specified for the outcomes all-cause mortality (any death before weaning) and mortality attributed to BRD. The 2 final models included a total of 11,470 calves that were born on the study dairies and followed until weaning. The study cohort's overall crude mortality was 2.8%, with crude mortality of individual dairies ranging from 1.7 to 7.2%. The proportion of mortality attributed to BRD was 19.3%, with a range of 0 to 27.1% on the study dairies. Increasing the frequency of changing maternity pen bedding was associated with a decreased risk of mortality due to BRD. Calves diagnosed with BRD in the spring had an increased risk of mortality compared with calves born in the summer; mortality in calves with fall and winter BRD diagnoses did not different significantly from that in summer. Season of mortality was not significant in either model. Feeding ≥5.7 L of milk per day per calf (vs. ≤3.7 L/d) decreased the risk of mortality in calves over 21 d of age. Twins had a 68% increased risk of all-cause mortality compared with calves born as singletons. Both mortality models showed an association between administration of a modified live vaccine in dams (targeting BRD pathogens) and a decreased risk of mortality in calves. Using a serum total protein cut-off of 5.2 g/dL, 16.8% of calves had FPT, with a mean serum total protein concentration of 5.94 ± 0.06 g/dL across all calves sampled.     

Growth characteristics of calves fed an intensified milk replacer regimen with additional lactoferrin

The objective of this study was to evaluate the effect of lactoferrin addition to milk replacer varying in crude protein (CP) on dry matter intake, growth, and days medicated. Thirty-four Holstein heifer calves were assigned to 4 treatments in a 2 × 2 factorial arrangement of treatments in a randomized complete block design. Treatments were as follows: 562 g daily of a nonmedicated conventional milk replacer (20% CP:20% fat) feeding regimen with or without 1 g of supplemental bovine lactoferrin (n = 9 for both treatments) or a nonmedicated intensified milk replacer feeding regimen (28% CP:20% fat) fed on a metabolizable energy basis (0.2 Mcal/kg BW^0.75) from d 2 to 9, and at 0.27 Mcal/kg BW^0.75 from d 10 to 42 with or without 1g supplemental bovine lactoferrin (n = 8 for both treatments). Calves were fed pelleted starter (25% CP) in 227.5-g increments beginning on d 2 and had free access to water. Calves remained on the study for 14 d postweaning. Dry matter intake was determined daily. Growth measurements were taken weekly. Blood samples were taken twice weekly for determination of blood urea N. On d 10 of life, calves were subjected to a xylose challenge. Calves on conventional treatments ate more starter preweaning, during weaning, and postweaning. Preweaning, intensively fed calves had higher dry matter intakes. Weights of intensified-fed calves were greater at weaning. Intensified milk replacer-fed calves had greater average daily gain preweaning and overall and higher gain:feed ratios preweaning, but conventionally fed calves had higher gain:feed ratios during weaning. Intensified milk replacer-fed calves had greater hip heights during weaning and postweaning and greater heart girths preweaning, weaning, and postweaning. Days medicated were greater preweaning and overall for intensified-fed calves. There were no differences among treatments for xylose absorption. Calves on conventional treatments had increased blood urea nitrogen concentrations preweaning. There were no effects of lactoferrin on any experimental variable. Intensified milk replacer-fed calves consumed less starter but had higher average daily gains overall and larger frames and greater BW than conventionally fed calves. An intensified milk replacer feeding regimen promotes faster growth during the preweaning period when compared with calves fed conventional treatments, but supplemental bovine lactoferrin was not beneficial under these experimental conditions.