Recipient Organization
UNIVERSITY OF CALIFORNIA, DAVIS
410 MRAK HALL
DAVIS,CA 95616-8671
Performing Department
Population Health & Reproduction
Non Technical Summary
Gastrointestinal issues are the most prevalent health disorder of preweaned dairy calves; approximately 21% of calves on US operations are affected and 76% of those are treated with antimicrobials. A recent meta-analysis study has shown smectite, an aluminosilicate clay, benefits pediatric patients with acute diarrhea. In a different study, feeding aluminosilicate minerals to newborn calves improved passive transfer of immunity and decreased incidence of diarrhea. Smectite's mechanism of action on the gastrointestinal tract is not clear; however, in recent animal studies smectite was shown to have various beneficial properties such as binding toxins, protecting the intestinal mucus barrier, performing as an antioxidant, and inhibiting pathogen growth. This proposal aims to evaluate if feeding smectite to preweaned calves in California operations can improve passive transfer immunity and decrease the incidence and severity of diarrhea. We expect that feeding smectite can be used as a strategy to reduce the use of antimicrobials in preweaned dairy calves. In this case, study results will be included in an outreach program on antimicrobial stewardship for dairy calves.
Animal Health Component
100%
Research Effort Categories
Basic
(N/A)
Applied
100%
Developmental
(N/A)
Goals / Objectives
Gastrointestinal issues are the most prevalent health disorder of preweaned dairy calves. In the US, approximately 21% of calves undergo an episode of diarrhea; most affected calves (76%) receive antimicrobial therapy (USDA APHIS, 2014). Based on current industry recommendations, calf diarrhea should be managed by providing fluids to restore the electrolyte and acid-base balance. Only systemically ill calves should be treated with antimicrobials. Although several adjuvant therapies are under study, only NSAID agents, meloxicam and flunixin meglumine, are supported by scientific evidence for the treatment of diarrhea in calves (Constable et al, 2009). Recent evidence generated from meta-analyses studies suggests smectite, a medicinal clay, can benefit pediatric patients with acute diarrhea [Pérez-Gaxiola et al. (2018), clinical trials only on smectite (n = 18); Florez et al. (2018), clinical trials on several adjuvant treatments including smectite (n = 174)].Smectite is a Na or Ca aluminosilicate clay, when hydrated it forms three-dimensional structures with two tetrahedral sheets. This physical structure provides smectite with a large surface area. The interlamellar space is populated by alkali and alkaline cations that attract positively charged molecules (i.e. heavy metals, mycotoxins, enterotoxins). Geologically, smectites are weathered volcanic ashes that were formed as early as the Jurassic era to as recently as the Pleistocene era (Patterson and Murray, 1983). The use of medicinal clays (internally and externally) was first documented by Hippocrates over 2,000 years ago (Adams, 1849). However, anthropological findings trace back geophagy (clay eating) to prehistoric times (Carretero et al., 2002). Geophagy is still practiced today, mostly by children and pregnant women living in tropical areas (high pathogen densities) undergoing gastrointestinal distress (Young et al., 2011). Likewise, it has been documented that herbivores (Johns, 1990; Kreulen, 1985), primates (Krishnamani & Mahaney, 2000), carnivores (Schaller, 1967), and birds (Diamond et al., 1999; Gilardi et al., 1999) crave clay.Medicinal clays could offer an affordable alternative on the management of diarrhea in preweaned calves. Feeding newborn calves aluminosilicate minerals for 10 d improved passive transfer of immunity and decreased incidence of diarrhea (Pourliotis et al, 2012). Also, in vitro studies have shown that clay minerals inactivate bovine coronavirus and rotavirus, two common pathogenic agents involved in preweaned diarrhea cases (Clark et al., 1988). The main mechanism of action of medicinal clays on the gastrointestinal tract remains unclear. However, studies conducted in the last two decades have provided some insight: the clays can act as a toxin binder (Harper et al., 2010; Wang et al., 2012), protect the intestinal mucus barrier (Almeida et al., 2013; Trckva et al., 2009), perform as antioxidants (Wang et al, 2012; Wu et al., 2013), and inhibit pathogen growth (Malachová et al., 2009; Wu et al., 2013).Justification: This study seeks to test a possible alternative to antimicrobials for newborn dairy calves on California operations.Experience of investigators: The PI has experience conducting studies on calves (Silva-del-Río et al., 2017; Lago et al, 2018). The investigator's team is developing an antimicrobial stewardship program. We are carrying out a systematic review of the efficacy of antimicrobials to treat diarrhea on preweaned calves (oral and parenteral antimicrobials) and adjuvant therapies (probiotics and smectite).Documented importance to California: Antimicrobial stewardship in animal operations is a priority for the State of California (https://www.cdfa.ca.gov/AHFSS/AUS/).2. RESEARCH HYPOTHESIS: We hypothesized that including smectite into the liquid feed of newborn calves (colostrum/milk) will improve passive transfer immunity and reduce the incidence and severity of diarrhea cases.3. OBJECTIVES: To evaluate the effects of adding smectite to the first colostrum feeding, or to all liquid feedings (colostrum/milk) from birth to 21 d of age on: 1) passive transfer immunity (serum Immunoglobulin G - IgG), 2) mortality, 3) morbidity, and 4) body weight.
Project Methods
A clinical trial will be conducted at a commercial calf ranch in the San Joaquin Valley (CA); newborn calves will be sequentially assigned to one of the following treatments: a) control; b) 10 g/d of smectite added to colostrum (improvement of passive transfer immunity should be mostly associated with the first colostrum meal); c) 10 g/d of smectite added to their liquid feed (colostrum/milk) from 0 to 21 d of age. The length of treatment administration corresponds to the time period when calves are most susceptible to diarrhea. The dose of 10 g/d used is based on the highest doses administered to treat acute diarrhea in infants (Pérez-Gaxiola et al., 2018). It represents ≈ 1.4% (6 L of milk) to 2% (4 L of milk) of total solids intake for milk with 12% solids. This inclusion rate is within the 2% limit of dry matter intake proposed by the European Commission Panel on Additives and Products or Substances used in Animal Feed (EFSA, 2012). Sample size calculation: A total of 108 calves are required to find a reduction on diarrhea incidence from 20% to 10% based on a two-sided sample size calculation with α=0.05 and β=0.2. Based on Pourliotis et al. (2012), aluminosilicate minerals reduced the incidence of diarrhea from 25.0% to 3.5%; the PIs have decided to use more conservative estimates for sample size calculations. Data collection: All samples and data will be collected by researchers. 1. Blood samples will be collected at 2 d of age. After coagulation serum will be harvested, aliquoted and stored at -20 °C until analysis. Radial immunodiffusion (RID) assay will be used to determine IgG (Triple J Farms kit, Bellingham, WA). 2. Colostrum samples will be collected prior to feeding into two 20 mL vials, placed on ice and transported to the lab. Samples will be stored at -20 °C until analysis of total bacterial count and IgG. 3. Health Evaluations. Daily health evaluations will be performed for the first 3 weeks of life: a) fecal consistency (5-score system) and attitude (3-score system) based on Berge et al. (2009); b) joints (swelling) and navels (swelling or discharge) will be inspected daily; navels will be palpated (health/pain) twice a week for the first 2 weeks of life (Steerforth et al., 2018); c) assessment of bovine respiratory disease using the scoring system developed by Love et al. (2014). 4. Health treatments. Researchers will administer treatments following protocols designed by the attending veterinarian. 5. Mortality. Records of death and culling dates will be collected from birth to 21 d of age. 6. Body weight gain. Researchers will measure withers height and weight at 7, 15, and 21 d of age using measuring tape and sticks. Researchers will weigh calves at 0 and 21 d of age using a digital portable scale. 7. Fecal samples will be collected using sterile cotton-tipped swabs at 0, 7, 15 and 21 d from a subset of 8 animals per group. Samples will be stored for future metagenomic analysis for diversity of bacterial communities using next-generation sequencing. Funding to do metagenomic analysis will be pursued only if treatment effects are observed. Data Analysis: 1. IgG serum will be analyzed with the Mixed procedure of SAS, including the fixed effect of treatment. The following covariates will be offered to the model in a forward stepwise selection method: body weight at 1 d, colostrum IgG and TBC (total bacterial count). Covariates will be included in the model whenever the variable effect had P < 0.15 or if it had a confounding treatment effect (the difference between crude and adjusted estimates of >10%). 2. Days animals are treated for a disease and number of antimicrobial treatments will be analyzed using the Genmode procedure of SAS with a zero-inflated negative binomial distribution (best fit tested with Akaike information criterion). 3. The effect of smectite on survival time (time to treatment or time to death) will be modeled using the Cox proportional hazards regression using the Phreg procedure of SAS. Animals that survived or showed no disease for the entire length of the follow-up period will be right-censored. 4. Body weight gain data will be analyzed as IgG in serum; the model will include the repeated statement.Anticipated results: We expect that feeding smectite to newborn calves will decrease their frequency of diarrhea and reduce the need to use of antimicrobials on calf operationsPitfalls: The PIs have used their best judgements to select the dose; but limited information on smectite use on calves is available. Toxicity cases have been reported after consuming doses several-fold above the recommended safety limit for lengthy periods; no negative effects are expected with the present treatment regimen.