Bovine respiratory disease is the second leading cause of death in preweaned dairy calves, only exceeded by neonatal calf diarrhea.1 The estimated annual cost of BRD in preweaned calves is $14.71/calf at risk of disease.1 Calves are at greatest risk of developing BRD during stressful periods, such as processing (ie, vaccination, dehorning, and castrating) and weaning, and the number of weaned dairy calves that die because of BRD has been increasing.2 Therefore, it is important to investigate options to enhance the immune system of calves prior to stressful events.
Such events (eg, weaning) can lead to immunosuppression, which makes calves more susceptible to viral respiratory pathogens, such as bovine respiratory syncytial virus, bovine herpesvirus 1, parainfluenza virus type 3, and bovine viral diarrhea virus. Viral infection can damage the respiratory tract mucosa and exacerbate immunosuppression, which facilitates the establishment of secondary bacterial infections caused by the migration of normal pharyngeal flora or other bacterial pathogens, such as Mannheimia haemolytica, Pasteurella multocida, Mycoplasma bovis, and Histophilus somni, into the lower portion of the respiratory tract.3–5
Antimicrobial resistance of bacteria is an emerging global issue that necessitates the development or identification of alternative strategies to prevent and treat bacterial infections.6,7 Dairy heifers are commonly vaccinated against respiratory viral pathogens by a parenteral route prior to breeding, but parenteral administration of vaccines to young dairy calves may not be effective owing to the presence of maternal antibodies that interfere with processing of vaccine antigens by the immune system.8,9 Vaccines against BRD pathogens that can be administered by the intranasal route have been developed for cattle. Intranasal administration of vaccines stimulates primarily mucosal immunity rather than systemic immunity but typically avoids maternal antibody interference, which may be beneficial in young calves.
Augmentation of the host's immune system is another alternative for prevention of BRD. The upper portion of the respiratory tract (nose, nasal cavity, paranasal sinuses, pharynx, and larynx; upper respiratory tract) of cattle has multiple innate defense mechanisms, one of which is dependent on the presence of peroxidases in airway surface liquid.10,11 Lactoperoxidase is produced in epithelial submucosal glands, and hydrogen peroxide is produced by dual oxidase enzymes on the respiratory epithelium.10,11 The substrate for the reaction is either a halide or a pseudohalide ion.10,11 In the natural system, lactoperoxidase catalyzes a reaction between hydrogen peroxide and thiocyanate, a pseudohalide secreted by the NaI symporter in the basolateral plasma membrane, resulting in the formation of hypothiocyanite within the airway surface liquid.10,11 Hypothiocyanite has antibacterial properties.12,13 If iodine is available during that reaction, hypoiodous acid will be produced, which has potent antibacterial and antiviral properties.10,11
Results of an experimental study14 indicate that the lactoperoxidase-hydrogen peroxide-iodide reaction inactivates or inhibits bovine herpesvirus 1, parainfluenza virus type 3, M haemolytica, and Bibersteinia trehalosi in vitro, and oral administration of NaI (70 mg/kg) to weaned beef calves causes a marked increase in the iodine concentration of nasal secretions for at least 72 hours. In fact, the iodine concentration achieved in the nasal secretions of the treated calves exceeded the minimal iodine concentration necessary for inactivation of respiratory pathogens in vitro (6.35 μg/mL).14 In cattle, NaI is commonly administered IV for the treatment of infections caused by Actinomyces bovis and Actinobacillus lignieresii at a dose of 70 mg/kg. In the United States, NaI has a legacy label for these indications, which does not include withdrawal times for meat and milk.
Scientific evidence that supports the use of NaI to enhance the innate immunity of calves against respiratory tract pathogens would be beneficial to the cattle industry for many reasons, including the improved health and production of the animals as well as a decrease in antimicrobial use and treatment costs for BRD. The study reported here had 2 primary objectives. The first was to determine the pharmacokinetics of NaI following oral administration of a single dose (20 mg/kg) of the compound to preweaned dairy calves. The second objective was to assess the efficacy of NaI (20 mg/kg, PO, 2 doses 72 hours apart) for prevention of BRD in preweaned dairy calves at a large calf-raising facility. Our hypotheses were that high concentrations of iodine would be secreted in the respiratory fluids of preweaned dairy calves following oral administration of NaI and that preweaned dairy calves orally administered NaI would have lower thoracic ultrasound and respiratory scores and be less likely to require treatment for BRD, compared with similar calves that did not receive NaI.
Supported by the University of California-Davis Center for Food Animal Health USDA Formula Funds (Animal Health). The funding source was not involved in the study design, data analysis and interpretation, or writing and publication of the manuscript.
Presented in abstract form at the Conference for Research Workers in Animal Disease, Chicago, December 2017, and at the American College of Veterinary Internal Medicine Forum, Seattle, June 2018.
Area under the concentration-time curve
Bovine respiratory disease
Time to maximum concentration
Thoracic ultrasound score
Optimum Calf Milk Replacer, Calva Products, Acampo, Calif.
VetOne, MWI Animal Health, Boise, Idaho.
Covidien Monoject, Tyco Health Care Group, Mansfield, Mass.
Bioseal, Covidien Inc, Mansfield, Mass.
BD Falcon Conical tubes, BD Biosciences, San Jose, Calif.
Mediatech Inc, Manassas, Va.
Inorganic Ventures, Christiansburg, Va.
Inforce 3, Zoetis Animal Health, Parsippany, NJ.
Entervene D, Boehringer Ingelheim Vetmedica Inc, St Joseph, Mo.
Once PMH, Merck Animal Health Intervet Inc, Madison, NJ.
IBEX, EI Medical Imaging, Loveland, Colo.
Healthsum, The Healthsum Syndicate LLC, Sunnyside, Wash.
Phoenix WinNonlin, version 6.2, Certara, Princeton, NJ.
SAS, version 14.3, SAS Institute Inc, Cary, NC.
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