What do we still have to learn about Mycoplasma hyopneumoniae infections in pigs?

Introduction

Talk about traditional bacteria in pigs, and Mycoplasma hyopneumoniae (M. hyopneumoniae) will be among the first ones to be mentioned. The “tradition” of this microorganism may be based on the fact that it has been recognized as a swine-specific pathogen for more than five decades, that it is prevalent in most areas where pigs are raised, and that it is common to accept its circulation in pig herds. Nevertheless, our understanding of this bacterium and the disease it causes has changed significantly in recent years, and keeps changing as you read this document. Thus, it is clear that we still have lots to learn regarding M. hyopneumoniae infection in pigs.

Some aspects remain unchanged and are still challenging

Regardless of its significant importance in swine production, progress on the understanding of M. hyopneumoniae has been hindered due to several factors:

Mycoplasma hyopneumoniae is a bacterium only affecting swine. The bacterium has been detected via PCR in the nose of humans exposed to pigs. However, there are no reports in the literature suggesting that this pathogen affects any other host species. Thus, the methods and research tools commonly employed for in vitro investigation on this bacterium have not benefited from assay development in other host species, as it can be the case with multi-host pathogens. For example, the lack of commercially available monoclonal antibodies is a significant limiting factor for M. hyopneumoniae research advancement.
Being a bacterium, one could assume that classic bacteriology would be sufficient to detect the microorganism in tissues, pig fluids and secretions, or in the environment, in order to obtain field isolates and to characterize them. Nevertheless, M. hyopneumoniae has proven to be a challenging pathogen to work with in laboratory, as well as in field conditions. Always considered a hard to be grown pathogen, M. hyopneumoniae bacterial isolation is seldom requested due to a very low success rate. It is important to mention that recent comparative studies have investigated the potential to develop methods for improved bacterial isolation, like specific media for bacterial growth. However, new recipes for improved Mycoplasma media are not currently publicly available.
As a pathogen, M. hyopneumoniae can cause disease by itself. However, poly-microbial infections are very common when observing the clinical signs associated with M. hyopneumoniae infections. Concomitant infections with other respiratory bacteria and/or viruses, in the form of Porcine Respiratory Disease Complex is extremely common. This particular feature has made the assessment of the clinical effect of M. hyopneumoniae infections complicated, hard to pinpoint and difficult to quantify. The lack of accurately determined disease costs for swine production has allowed for an underestimation of the health problem this bacterium causes and leads to the use of partially efficient control measures.
Infections with M. hyopneumoniae are highly prevalent and ubiquitous. Although this is a reality that can change significantly in the future, infections with this bacterium are considered present in a majority of farms, regardless of the type of production system and the geographical location. This aspect remains a significant drawback for disease control.

Changes have occurred in recent years

It is common to hear that M. hyopneumoniae has changed, that the disease problems associated with its infection can be more severe and less “controllable” in the field. While this hypothesis could be true, one can argue that the way we raise pigs has changed as well, and that the pig itself is different, but one other aspect that is significantly important is the fact that we have changed what is understood of M. hyopneumoniae infections.

Mainly, a shift in the state of knowledge of M. hyopneumoniae epidemiology has been evident in the most recent decade. A disease formerly considered exclusive of the growing pig has become focus of control strategies applied at the sow farm. Identification of risk factors in the sow farm has led to the development of targeted tools, allowing producers and veterinarians to generate stability in sow farms and harvest the benefits of raising piglets that are minimally colonized (and sometimes even negative) to the bacterium.

It is important to recognize that progressive swine medicine and production has been key to the adoption of new knowledge and application of innovative tools for disease control. However, there are many unanswered questions regarding M. hyopneumoniae infection in pigs, which should be addressed in order to move disease elimination efforts forward.

What we still have to learn

Doubtlessly, a comprehensive list of unresolved aspects regarding M. hyopneumoniae and the infections it cause would be long. Here, several factors, which may have key implications for the course of disease presentation, are listed:

A significant amount of information has been generated in recent decades showing that the virulence of M. hyopneumoniae strains differ. The difference in virulence is expressed in various ways, from laboratory assays, to clinical presentation, to lack of efficacy of control measures. Mainly, differences in virulence have been assessed inexperimental settings, which allows for proper characterization of strains. However, a practical assay, which could be applied in the field, indicating the capability of M. hyopneumoniae to cause more severe disease is not available to-date. Development of such diagnostic capacity would be crucial to define specific measures directed at disease control. In ideal situations, one could characterize the M. hyopneumoniae strain circulating on a herd, be capable to accurately predict disease presentation and apply specific treatments depending on strain virulence.
Similar to bacterial virulence, the genomic difference in M. hyopneumoniae strains is frequently observed in the field and in the laboratory. Several methods, such as sequencing and typing, have been standardized for the characterization of clinical specimens and have allowed for the analysis of samples from distinct geographical locations, production systems and times. To date, molecular characterization data has been used mainly to aid comparing strains for outbreak investigations. However, inferring evolution or predicting of cross-protection has not been accomplished employing current methods evaluating strain differences.
An extremely long persistence in the host (surpassing seven months) is now widely recognized as part of the epidemiology of M. hyopneumoniae. Importantly, the infectious capability of persistently infected pigs has been documented and constitutes a silent risk factor for pathogen circulation in pig farms. Remarkably, pigs may not even show clinical disease during this chronic infection phase. Efforts have been made to attempt shortening the persistence period. The use of vaccine and antimicrobial agents has been explored on this scenario, but found to be unsuccessful. However, factors driving M. hyopneumoniae persistence in the host remain unknown and are a major limitation to the design and application of preventive measures or treatments to decrease the infectious period.

A long infection period has different implications based on the production system and phase pigs are raised in. For example, growing pigs are likely to be positive to (and shed) M. hyopneumoniae at the end of the growing period if they were infected earlier in life. On the other hand, the implications of M. hyopneumoniae infection timing are far more crucial for gilts and sows, which are housed for years in pig farms. A late M. hyopneumoniae infection, combined with a long infection period, can lead to shedding of the bacterium during farrowing and lactation periods, which can translate into exposure of the offspring to M. hyopneumoniae. Thus, gilt acclimation practices specific for this bacterium are gaining popularity, especially in North America, in order to generate stability in breeding herds.

Gilt acclimation for M. hyopneumoniae can be challenging based on several of the limiting factors mentioned above. Disease preventive measures are usually partially protective and do not prevent colonization with this bacterium. Antibacterial treatments help easing problems associated with clinical presentation, but do not lead to complete elimination of M. hyopneumoniae from the host. Thus, purposeful exposure of gilts to M. hyopneumoniae at a young age, allowing ample time for recovery from disease, is becoming a standard practice in some countries. It is important to note that gilt purposeful exposure is a new method that needs to be further validated for safety and efficacy. Therefore, the development and validation of science based protocols for this purpose has to be a priority for the industry.
A standing question involving immunology, epidemiology, and disease elimination is whether previously infected pigs are protected from reinfection for life, or whether they can be reinfected with M. hyopneumoniae once the persistency period has ended. Resistance to reinfection is assumed for this disease, although little data can be identified in the literature addressing this question. One of the assumptions of current M. hyopneumoniae eradication protocols is resistance to reinfection. For that reason addressing the reinfection issue results critical for total M. hyopneumoniae disease control, although it may not be simple to accomplish.
The fact that diagnostics for M. hyopneumoniae are less than ideal cannot be ignored. Practitioners and investigators have summed efforts and have evaluated novel (and non-conventional) samples and have combine it with highly accurate methods for pathogen detection. Still, M. hyopneumoniae is stealth and hard to detect in many situations. Simple sample collection with a high degree of sensitivity and specificity for M. hyopneumoniae detection is certainly in the wish list for swine health professionals. In addition to detection, take the development of assays for evaluation of antimicrobial susceptibility without the need to perform bacterial isolation or the ideal situation to differentiate exposure from infection using ELISA based tests.
Certainly puzzling, the isolation or detection of M. hyopneumoniae in tissues and body sites other than the respiratory tract are becoming more frequent. Whether this a mere reflection of improved diagnostic capabilities, the potential implications of such findings can be substantial in swine production. For example, addressing biosecurity can become extremely challenging when a pathogen can be hidden in unexpected locations in the body of the host.

Closing remarks

Regardless of the fact that it is still considered limited, the knowledge on M. hyopneumoniae as a pathogen and its associated disease has grown significantly in recent years and has allowed swine professionals to propose novel approaches for disease control and eradication. However, more information is certainly needed to reach a common health objective regarding M. hyopneumoniae control and eradication.

Published in the proceedings of the International Pig Veterinary Society Congress – IPVS2020. For information on the event, past and future editions, check out https://ipvs2022.com/en.