Recipient Organization
UNIVERSITY OF CALIFORNIA, DAVIS
410 MRAK HALL
DAVIS,CA 95616-8671
Performing Department
Population Health & Reproduction
Non Technical Summary
In 2004, in response to multiple randomized clinical trials conducted with children in developing countries, the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) recommended that oral rehydration solutions (ORS) be supplemented with zinc to decrease the duration and severity of infant diarrhea.5-7 Benefits of zinc-supplemented ORS in the treatment of childhood diarrhea include increased recovery rates, reduced mortality, reduced hospital admissions and decreased use of antibiotics and antidiarrheals.6,8 Decreased use of antibiotics helps minimize development of antimicrobial resistance, thus ensuring continued efficacy of antimicrobials.Adaptation of zinc-supplemented ORS to treat diarrhea in calves presents a unique opportunity to minimize both the impact of one of the most economically important diseases of dairy calves and the use of antibiotics in food producing animals. Finding an inexpensive, non-antibiotic treatment to decrease the incidence and severity of diarrhea, decrease the length of time calves shed C. parvum and increase weight gain in calves with diarrhea would be an innovative approach not only to improve calf health and performance but also to decrease antibiotic resistance in food producing animals.
Animal Health Component
100%
Research Effort Categories
Basic
(N/A)
Applied
100%
Developmental
(N/A)
Goals / Objectives
Diarrhea is the leading cause of illness and the most common reason for treatment with antibiotics in pre-weaned dairy heifers.1,2 Based on the results of two national surveys, 23.9% and 25.3% of pre-weaned heifer calves on dairies and heifer raising facilities, respectively, experienced diarrhea.1,2 Approximately 18% of all pre-weaned heifers are treated with antibiotics for gastrointestinal diseases, including diarrhea or scours.1,2 Additionally, 49.9% and 59.2% of all pre-weaned heifers on dairies and heifer raising facilities, respectively, are routinely fed milk replacers containing antibiotics.1,2 Diarrhea is also the leading cause of death for pre-weaned heifers on dairies, accounting for 56.5% of all deaths.1 Similarly, in humans, there are over 1 billion cases of diarrhea, resulting in 2.5 million deaths each year, mostly in developing countries. Diarrhea is the leading cause of death in children under 5 years of age.3,4 In 2004, in response to multiple randomized clinical trials conducted with children in developing countries, the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) recommended that oral rehydration solutions (ORS) be supplemented with zinc to decrease the duration and severity of infant diarrhea.5-7 Benefits of zinc-supplemented ORS in the treatment of childhood diarrhea include increased recovery rates, reduced mortality, reduced hospital admissions and decreased use of antibiotics and antidiarrheals.6,8 Decreased use of antibiotics helps minimize development of antimicrobial resistance, thus ensuring continued efficacy of antimicrobials. Despite multiple studies showing the effectiveness of zinc supplemented ORS in children, the underlying mechanism of action remains unknown.5 However, several mechanisms have been presented including a mucosal-protective role, a diarrhea-induced zinc deficiency, an essential element in cell-mediated immunity and a modifier of intra-luminal electrolyte secretion and absorption.9-11 The revolutionary impact of zinc-supplemented ORS on childhood diarrhea ushered in what is now known as the "zinc era".7 Adaptation of zinc-supplemented ORS to treat diarrhea in calves presents a unique opportunity to minimize both the impact of one of the most economically important diseases of dairy calves and the use of antibiotics in food producing animals. We conducted a preliminary study, with a sample size based on the serum zinc levels in infants with and without diarrhea, using 79 Holstein calves, which was the first randomized clinical trial testing the effect of zinc supplemented ORS in neonatal calves with diarrhea.12 The trial identified several clinically important results, however small sample size led to lack of statistical significance. Calves treated with zinc methionine (ZM) gained weight as compared to placebo-treated calves, which lost weight.12 C. parvum-positive calves treated with ZM were 16 times more likely to test negative at exit from the trial than placebo-treated calves.12 Calves treated with zinc oxide recovered from diarrhea, on average, one day sooner than placebo-treated calves.12 Now that several more focused hypotheses were identified through the preliminary study, we propose a more focused experiment to investigate the effect of zinc at the previously studied dose and treatment regimen for the first 14 days of life to prevent and treat calf diarrhea. Based on our findings, a sample size of 213 calves per treatment group is needed to detect a statistically significant difference in mean daily weight gain between the ZM and placebo groups. Such a sample size can be easily attained on most dairy or calf-raising facilities in California.12 Finding an inexpensive, non-antibiotic treatment to decrease the incidence and severity of diarrhea, decrease the length of time calves shed C. parvum and increase weight gain in calves with diarrhea would be an innovative approach not only to improve calf health and performance but also to decrease antibiotic resistance in food producing animals.RESEARCH HYPOTHESES1) Calves supplemented with zinc methionine daily for the first 14 days of life will have a decreased incidence, severity and duration of diarrhea compared to calves supplemented with a placebo.2) Calves supplemented with zinc methionine daily for the first 14 days of life will have increased average daily gain from birth to weaning compared to calves supplemented with a placebo.OBJECTIVES.1) To compare fecal scores, incidence and duration of diarrhea, and mortality in 1-60 day old Holstein calves randomly assigned to receive either zinc methionine or placebo supplementation for the first 14 days of life.2) To compare weaning weights and pre-weaning average daily gain in Holstein calves randomly assigned to receive either zinc methionine or placebo supplementation for the first 14 days of life.
Project Methods
This study will be conducted in Tulare, CA on a client herd of the VMTRC using pre-weaning Holstein and Jersey calves (1-60 days of age). Results of our previous zinc supplementation study indicated that a sample size of 213 calves per group (α = 0.05, β = 0.10, power 90%) would be needed to show a difference in average daily weight gain of 107g between groups. Allowing for a 15% loss to follow-up, a total of 500 day-old calves will be randomly assigned to receive either zinc methionine or a placebo (milk replacer powder) mixed in the milk once a day for the first 14 days of life. Calves will receive 381.54 mg zinc methionine equivalent to 80mg of elemental zinc (based on an average birth weight of 40kg) and Jersey calves will receive 305.22mg zinc methionine equivalent to 64mg of elemental zinc (based on an average birth weight of 32kg). An equivalent amount of milk replacer powder will be added to the milk of calves in the placebo group for each breed. Placebo and ZM will be proportioned in coded vials to maintain blinding during administration of treatment. Average birth weights for each breed are based on results obtained from the colostrum supplement study conducted on the same dairy by our research team. Holstein heifer and bull calves and Jersey heifer calves will be included in the study. Calves with congenital abnormalities and Jersey bull calves will be excluded. A serum sample will be collected from each calf at enrollment (24hrs of age) for analysis of total protein using a refractometer to estimate passive transfer of immunity. Once a week, calves will be weighed at enrollment (age 1-7 days) and exit from the study at weaning (50-57 days of age). Calves will be monitored daily for the duration of the study period and attitude and fecal consistency score will be recorded. Fecal consistency will be assessed using a modification of the Wisconsin calf health scoring chart.16 Any calves that die during the study period will be necropsied to determine the cause of death. Outcomes to be assessed include age at onset of diarrhea, duration (days) of diarrhea, morbidity, weaning weights and average daily gain. Study personnel enrolling and monitoring the calves will be blinded to treatment.