2020-21 Rapid Ag: Increasing Mycoplasma Hyopneumoniae Eradication Success by Investigating Antimicrobial Susceptibility
Veterinary Population Medicine
Respiratory disease accounts for a significant proportion of mortality in finishing pigs. Mycoplasma hyopneumoniae infections are the most significant bacterial respiratory disease affecting pigs. Mycoplasma infections have a direct effect of pig performance and are predisposing factors to other respiratory diseases. Controlling Mycoplasma infections in the field is challenging due to their chronic and endemic nature, the partial protection of vaccine products, and the fact that pathogen eradication is not always achieved when using antibiotics. However, several strategies, including management practices, immunizations, and antibiotic treatments have proven successful for disease eradication. Mycoplasma eradication is a growing trend in the swine industry. Nevertheless, eradication failures occur, even using protocols that have been successful in other farms. Little is known about M. hyopneumoniae antimicrobial susceptibility, as antibiograms are not routinely performed. In fact, the most current data on antimicrobial susceptibility for M. hyopneumoniae in the US is more than 15 years old. Therefore, we will investigate the role of antimicrobial resistance on Mycoplasma eradication, to generate a PCR based test for M. hyopneumoniae selected antimicrobial susceptibility, and to evaluate the predictive value of the test in eradication success. Altogether, these results will lead to greater disease eradication successes and judicious antimicrobial use.
Infections caused by M. hyopneumoniae are present in almost every country where pigs are raised (Thacker and Minion, 2012). M. hyopneumoniae is the causative agent of enzootic pneumonia (Mare and Switzer, 1965; Goodwin et al., 1965), a chronic respiratory disease affecting pigs worldwide (Maes et al., 2017). Enzootic pneumonia results in significant economic losses to the pork industry (Maes et al., 2008). Economic losses due to M. hyopneumoniae infection are associated with the direct effect of the bacterium as a primary pathogen, capable of producing growth retardation and decreased pig performance, as well as the involvement in the development of PRDC (Thacker and Minion, 2012). Co-infection of M. hyopneumoniae with PRRSv, swine influenza virus, porcine circovirus type 2, Actinobacillus pleuropneumoniae, and Pasteurella multocida have been demonstrated. Herds either infected or co-infected with M. hyopneumoniae usually require the prolonged use of high levels of antibiotics.
Herd level control of M. hyopneumoniae can be partially achieved by applying different strategies that include the use of vaccines, antibiotics, and/or changes in management practices. Commercial vaccines usually offer only partial protection against infection (Haesebrouck et al., 2004), do not prevent bacterial colonization and do not reduce transmission to naïve pigs (Meyns et al., 2006; Pieters et al., 2010). Antibacterial drugs usually reduce the mycoplasmal-induced disease and may decrease the bacterial load, but do not clear the pathogen from the pig and do not shorten bacterial persistence (Le Carrou et al., 2006; Painter et al., 2012). To complicate matters, it has been shown that resistance to antibiotics has been demonstrated in vitro for M. hyopneumoniae (Vicca et al., 2004). Farm management practices, e.g. all-in/all-out can be employed to minimize the effect of M. hyopneumoniae and other infectious agents; however, these practices may not sufficient to avoid infection. Despite the availability of the previous noted tools of vaccines and antibiotics for control, proper control of M. hyopneumoniae infection is not usually achieved, leaving producers and practitioners with few options.
Several strategies for M. hyopneumoniae eradication have been used in the swine industry for over 30 years (Holst et al., 2015). Total depopulation and repopulation, partial depopulation (Zimmermann et al., 1989), herd closure and medication, and whole herd medication are amongst the most frequently applied strategies for elimination of infection with M. hyopneumoniae (Holst et al., 2015). The strategies vary in design, likelihood of application depending on the livestock production system, expected success rate, and needed resources, however they are all directed at a unique goal, which is to eradicate the disease and ideally, the pathogen from the herd. Reported prevalences long periods after the application of elimination protocols suggest that although success of M. hyopneumoniae disease eradication varies depending on the strategy, it is greater than 80% when herd closure is applied and greater than 60% for whole herd medication (Yeske et al., 2017). However, the success of eradication protocols is not perfect, and eradication failures occur.
Sorting out the causes of failure to eradicate M. hyopneumoniae in swine herds may be a difficult process, due to the fact that multiple factors can have an effect and farms can be difficult to compare with others. However, several factors, such as eradication strategies will have a significant effect on disease elimination, as shown by Yeske et al. (2017). In this series of studies, we propose to perform a profound investigation of an overlooked factor in disease eradication programs, potential antimicrobial resistance.
In Europe, regular evaluation of antimicrobial resistance is performed for major swine pathogens, including M. hyopneumoniae, in isolates obtained in a period of 5 years (MycoPath; Klein et al., 2015). However, in the US there is not such program and the antimicrobial resistance of pathogen hard to culture is not routinely assessed. It is our hypothesis that M. hyopneumoniae resistance to antimicrobial agents may be responsible for the lack of success in various disease eradication programs. Thus, we propose to investigate the phenotypic and genotypic characteristics of historic and modern M. hyopneumoniae isolates, to perform a comparative analysis for phenotype and genotype and to develop a PCR based test that could be used to guide the use of antibiotic selection in elimination programs. The short-term benefit of this investigation will be the generation of antimicrobial susceptibility information for circulating M. hyopneumoniae isolates, which will guide antibiotic use in the field. The mid-term benefit will be reflected in the use of a PCR based test that will allow for constant monitoring of antimicrobial susceptibility of a pathogen that is extremely difficult to grow, which will allow modifications to antimicrobial therapies based on pathogen response to treatment. In the long-term, results from this investigation will help position producers and veterinarians at the forefront of disease eradication for overall improved pork production.
Objectives and Goals
The overall objective of this proposal is to improve the likelihood of M. hyopneumoniae eradication if field conditions by investigating the effect one of the potential underlying causes of eradication failure. In order to accomplish this objective, the following specific aims are proposed:
- To test the in vitro antimicrobial susceptibility of current and historic M. hyopneumoniae isolates (phenotype)
- To perform whole-genome sequencing of current and historic M. hyopneumoniae isolates (genotype)
- To perform the comparative analysis of the phenotype and genotype of M. hyopneumoniae (from aims 1 and 2)
- To develop a PCR based test for detection of antimicrobial resistance to important point mutations for major antimicrobial agents
- To estimate the predictive value of the PCR test for success of M. hyopneumoniae eradication using banked DNA samples from recent elimination programs
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