NEGATIVELY CONTROLLED RANDOMIZED FIELD TRIAL EVALUATING THE EFFECT OF TREATMENT OF PNEUMONIA WITH TILDIPIROSIN OR FLORFENICOL + FLUNIXIN MEGLUMINE ON HEALTH AND UPPER RESPIRATORY TRACT MICROBIOTA OF PREWEANED HOLSTEIN DAIRY HEIFERS

Abstract

As a major economic and health concern in the livestock industry, bovine respiratory disease (BRD) is still highly prevalent on U.S. farms, causing high morbidity and mortality rates in young calves. Controlling BRD can be complicated because it is a multifactorial and polymicrobial disorder that occurs due to complex interactions between the calf's immune system, causative pathogens, and on-farm management systems. The pathogens that cause pneumonia in calves are also commensal inhabitants of the upper respiratory tract (URT), which can cause illness as a consequence of dysbiosis. The best way to prevent the disease is to eliminate the risk factors that can trigger the imbalance of microorganisms in the URT. Among the stressors and risk factors associated with pneumonia are unproper maternity management, comingling, weaning, and poor air and bedding quality. When we fail to prevent pneumonia, the use of antibiotics remains the most effective strategy for controlling the disease. Several drugs are commercially available for treatment of pneumonia, including synthetic antibiotics such as tildipirosin and florfenicol in combination with flunixin meglumine, a nonsteroidal anti-inflammatory drug (NSAID). Studies evaluating the efficacy of therapeutics available on the market can help producers and veterinarians in decision-making for the disease treatment. Furthermore, in-depth studies evaluating health and blood parameters, and the microbiota of animals with pneumonia can advance our epidemiological knowledge of BRD. In Chapter 1 of this thesis, we summarize some of the most important topics about BRD, including pathogenesis, risk factors, economic impact and harmful consequences, diagnostic tools, and strategies to prevent and treat this disease in dairy and beef operations. The main objective of Chapter 1 is to create a knowledge base about the BRD complex with a focus on infectious pneumonia which served as a reference for the research described in the following chapter.In Chapter 2, we describe the results of a randomized clinical trial evaluating the effect of therapeutically administered tildipirosin or florfenicol + flunixin meglumine against fever-associated respiratory diseases compared to untreated pneumonic animals. As specific aims, we evaluated the URT bacterial microbiome, blood, and health parameters of the animals. Both drugs were effective in reducing clinical signs of pneumonia and rectal temperature, with florfenicol + flunixin meglumine promoting a greater reduction of rectal temperature. Reduction of systemic inflammation was also confirmed through analyses of blood parameters, such as haptoglobin. Considering untreated calves as reference, both antibiotics reduced pneumonia and/or otitis retreatment. Finally, both drugs were effective in reducing the mean relative abundance (MRA) of important genera associated with pneumonia (Mannheimia and Pasteurella), although an increase in the Mycoplasma MRA was observed in tildipirosin-treated calves. In Chapter 3, we describe our final thoughts on BRD in dairy calves, the results and implications of our study, and future research directions for this topic. In summary, BRD remains a challenging disease to animal health due to its complexity and multifactorial nature. Farms should focus primarily on prevention strategies such as proper administration of quality colostrum to newborn calves and reduction of environmental and management stressors that can impair the immunity of calves. In herds at high risk for disease, the use of vaccines can also help to reduce morbidity and mortality in calves. Our research study comparing outcomes from two antibiotic interventions to untreated calves confirmed the importance and benefits of timely diagnosis and proper treatment of group-housed dairy calves during the preweaning period. In addition, we found exciting results in terms of URT composition and dynamics when comparing healthy calves to pneumonic animals untreated or receiving antibiotic interventions.