Mycoplasma hyopneumoniae is one of the most important primary pathogens of the porcine respiratory system and is the causative agent of enzootic pneumonia (EP) (Fraile et al, 2010). M. hyopneumoniae is also a major contributor to development of the porcine respiratory disease complex (PRDC) (Garcia-Morante et al, 2016). M. hyopneumoniae is widespread throughout the pig population and is endemic on most farms worldwide. Pneumonic lung lesions as a result of M. hyopneumoniae are commonly observed in the slaughterhouse, with average herd level prevalence reported as 24%, ranging up to 88% (Maes et al, 2001), demonstrating the large variability observed between units depending on individual farm situation. Co-infections are very important in respiratory disease, as interaction of multiple pathogens has been shown to increase the severity of clinical signs (Saade et al, 2020) and therefore the impact on performance. Enzootic pneumonia has a large economic impact on the pig industry, primarily because of the cost of treatment, reduced performance and increased mortality as a result of secondary infections (Holst et al, 2015). Therefore, implementation of control measures is extremely important to improve animal health and consequently productivity on farm. Management practices form an integral part of this control plan, including improved biosecurity and hygiene, which may be accompanied with vaccination. There are numerous vaccines available which vary in the vaccination schedule, but the ultimate goal should be reduction of lung lesions and performance losses as a result of M. hyopneumoniae.
The pathogen
M. hyopneumoniae is 200–500 nm in size and requires complex media and aerobic and microaerophilic conditions to be cultured. Infection with M. hyopneumoniae occurs via inhalation of infected aerosols or via direct contact with infected animals. The pathogen establishes itself in the respiratory tract, attaching to the ciliated cells of the tracheal, bronchial and bronchiolar epithelium. Once in the respiratory tract, it can persist for weeks to months and causes pathological changes in the lungs. Lesions are thought to form in the lobes of the lung because of a lack of normal clearance of secretory products from the respiratory system, as a result of infection of the ciliated epithelium (Taylor, 1995), as well as the infiltration of mononuclear cells into the bronchi, bronchioles and small blood vessels. There can also be lymphoid hyperplasia of the lymphoid tissue (Vicca, 2005). Early lesions are observed as small dark red areas in the anterior lobes, which enlarge over time and after a few weeks lose their red colour and become more pink (Figure 1). Lesions resolve after 12 to 14 weeks with formation of interlobular fissures (Maes et al, 2008). This is important to note, as infections early in production may be resolved once the animal reaches the slaughterhouse, so any scarring (Figure 2) should be noted as losses may still have occurred during the growing and finishing stages.
Histologically, inflammation occurs and neutrophils can accumulate in the airways and bronchioles. Lymphocytes and macrophages will also be present 5 days after infection, followed by presence of large mononuclear cells, polymorphs, lymphocytes and plasma cells in the alveoli from day 7. Immunoglobulin (Ig) A forms in tracheal mucosa so may be detectable from day 30 on diagnostic testing of secretions, and IgG may also be present at a slightly later stage (Taylor, 1995).
Clinical signs
EP can clinically be acute or chronic in its form which have differ ent clinical presentations of disease. Pigs of all ages can be affected in the acute form and most likely will experience pyrexia, anorexia and respiratory distress, usually accompanied with a distinct cough (Taylor, 1995). Whereas, in the chronic form, few clinical signs may be observed, particularly in young growing pigs, where diarrhoea and a dry cough may be the only visible signs if present. Later in production, this cough may become a barking cough in the finishing house and what may be most apparent is the variation in size of pen mates, indicating performance has been compromised in some animals.
Diagnosis
In vivo diagnosis can be carried out by M. hyopneumoniae specific seroconversion or laryngeal swabs tested by polymerase chain reaction (Pieters et al, 2017). Examination of the lungs at slaughter can also be useful to report presence of pneumonic lesions, characterised by consolidated areas especially in the cranial lobes (Maes et al, 2001). Seasonal patterns are often observed with M. hyopneumoniae, with lung lesions' prevalence and severity increasing following the winter months. This was demonstrated by Ostanello et al (2007) where, as scored using the Madec and Kobisch method (1982), mean lung lesion score was significantly increased in batches of animals raised in the winter months (October–March) compared with the summer months (April–September), with scores of 2.33 and 1.81 respectively. Decreased growth rate and feed conversion ratio (FCR) may also be observed, typically with no or low mortality (Sibila et al, 2009).
Coinfections
M. hyopneumoniae is a primary pathogen and one of the main ones responsible for the development of PRDC. The pathogen modifies the immune response and facilitates the expression of co-infections. It is described as an inhibitor of macrophage phagocytic activity, and works to up-regulate IL-10 and down-regulate interferon (IFN)-γ, therefore, resulting in immunosuppression (Leal Zimmer et al, 2020), which may explain the chronicity of M. hyopneumoniae infections and the greater host susceptibility to other pathogens (Saade et al, 2020).
Co-infections can occur with both viral and bacterial diseases. There are three important diseases affecting the swine herd globally: porcine respiratory and reproductive syndrome (PRRS); swine influenza virus (SIV); and porcine circovirus (PCV2). M. hyopneumoniae potentiates PRRS induced lung lesions but not inversely. The bacteria facilitates the replication of the virus but PRRS does not increase the nasal excretion of M. hyopneumoniae. Therefore vaccination of pigs against M. hyopneumoniae is a priority if a farm is co-infected with both PRRS and M. hyopneumoniae (Chae, 2016).
In the case of co-infection with SIV, the lung lesions of co-in-fected pigs are more severe than those of pigs inoculated against M. hyopneumoniae only, even if the SIV strain is only slightly pathogenic (Yazawa, 2004). In the case of coinfection with PCV2, M. hyopneumoniae facilitates the replication in vitro of the virus, which could be up to 350% according to different strains of M. hyopneumoniae (Wang et al, 2016). Opriessnig et al (2004) indicated that M. hyopneumoniae potentiates the severity of PCV2-associated lung and lymphoid lesions, increases the amount and prolongs the presence of PCV2-antigen, and increases the incidence of post-weaning multisystemic wasting syndrome in pigs.
In relation to bacterial co-infections, the importance of M. hyopneumoniae is as crucial as with viruses. In pigs simultaneously in-fected with M. hyopneumoniae and Actinobacillus pleuropneumoniae, clinical signs and lung lesions are severe and correspond to the pathogenicity of the two bacterial strains combined. However, if the pigs are first infected with M. hyopneumoniae and later with A. pleuropneumoniae, these will be particularly affected with very severe clinical signs (Marois et al, 2009). Reducing the impact of M. hyopneumoniae through effective vaccination has been shown to also reduce the impact of pleuropneumoniae caused by A. pleuropneumoniae, reflected in both reduced pleurisy and severity of lesions (Velazquez and Gale, 2019), therefore demonstrating the importance of the interaction between the two pathogens.
Finally, in the case of Pasteurella multocida, one of the major receptors on epithelial cells for this pathogen is a sugar (L-fucose). In healthy lungs there is no L-fucose expressed. However, if infection with M. hyopneumoniae occurs on the ciliated epithelium in the lungs, the sugars are modified, meaning that P. multocida has access to L-fucose receptors and therefore results in increased adhesion (Park et al, 2016).
In general, M. hyopneumoniae plays a large role in increasing the severity of respiratory disease on farms where other pathogens are also present. Other bacteria such as Bordetella bronchiseptica, Glaesserella parasuis, Trueperella pyogenes, Streptococcus spp. or Staphylococcus spp. are also commonly found in field outbreaks of EP (Maes et al, 2018).
Economic importance of M. hyopneumoniae
M. hyopneumoniae is known to be one of the most prevalent swine pathogens worldwide, causing substantial economic losses within the swine industry (Maes et al, 2018). The economic impact primarily derived from the decreased performance in production parameters, including a reduced average daily weight gain (ADWG), reduced FCR, increased mortality and an increase in use of anti-biotics to control EP, as well as other pathogens involved in the PRDC (Maes et al, 2008). Straw et al (1989) demonstrated that pneumonia as a result of M. hyopneumoniae infection caused a decrease in ADWG and feed efficiency by 17% and 14% respectively. This is reflected in increased days to slaughter, which may contribute to increased cost of production.
The economic impact as a result of M. hyopneumoniae specifically is difficult to estimate because of the contribution of numerous co-infections (Maes et al, 2018). A study completed by Gillespie (2013) estimated the economic losses as a result of an M. hyopneumoniae outbreak in a naive herd was equal to £5.68 per pig. However, this cost has been shown to be higher if other respiratory pathogens such as PRRS or SIV are also present along with M. hyopneumoniae (Haden et al, 2012). A previous study has demonstrated that the severity of the impact on productive performance, and therefore economic losses, is correlated with the percentage of lung consolidation caused by M. hyopneumoniae, reporting a negative correlation between lung consolidation lesions and ADWG, where a 1% increase in lung area affected corresponded to a decrease of 3.74 g ADWG per day (Straw et al, 1989). In the same study, pigs with more than 15% lung lesions were compared with animals with no lesions, and the economic loss was calculated at £4.77 per affected pig. In addition, a previous study determined benefit-cost analysis of elimination of M. hyopneumoniae and reported that the benefit would be around £5.10 per pig marketed (Silva et al, 2019). Therefore, these few studies are similar in the economic impact of M. hyopneumoniae noted, however, it is important to remember that this value will always depend on the extent and severity of lesions.
Control and vaccination
Management practices
Management practices should be implemented to aid reduction in the impact of M. hyopneumoniae on farms. Methods include practising all-in-all-out systems (Maes et al, 2008) to allow for adequate cleaning and disinfection, which will help to reduce the bacterial load in the environment before new animals enter the accommodation. Action should be taken to avoid any practices that may affect the immunological stability of the herd, such as buying in infected gilts or other live animals (Maes et al, 2001). Stocking density has also been shown to be important in the case of some respiratory diseases, with increased stocking densities having a negative impact on respiratory health (Maes et al, 2000). Therefore, the correct balance should be found in terms of maximising the use of accommodation for production and the stocking level which does not dramatically impact animal health (Maes et al, 2008).
Slaughterhouse evaluation
Examination of lungs in the slaughterhouse is a very valuable tool to veterinarians and farmers as it allows an assessment of the impact of EP on the farm in terms of performance and consequently the economic losses. Innovative technology has made the process easier, for example the Ceva Lung Program (CLP), which can be used on a smartphone or tablet in the slaughterhouse. CLP consists of the modified Madec method for scoring enzootic pneumonia-like lesions (Madec and Kobisch, 1982). Cranio-ventral consolidation of the lungs is scored from 1–4 for each lobe, with a maximum possible score of 28 per lung. The EP index can then be calculated, which is the sum of all scores per batch of pigs examined, divided by the total number of lungs scored. The app generates immediate reports with the key information, such as percentage of bronchopneumonic lungs and EP index for pneumonia assessment, which can then be used by the veterinarian as part of their quarterly farm visit. Examination should be carried out frequently to get maximal benefit from the data collected, as seasonal variation may alter the prevalence of lesions observed for example, and this may result in incorrect interpretation of the success of control of M. hyopneumoniae on a farm. Examination of lungs is very useful when implementing new control measures, as a reduction in lung lesions in the slaughterhouse is an important indication that clinical disease is reducing in both prevalence and severity.
Vaccination strategies
Vaccination strategies vary based on the clinical presentation of disease, management practices on the unit and the choice of the veterinarian and farmer. Strategies include vaccination of piglets with either one or two shots, or vaccination of sows and gilts to provide maternal immunity to piglets. It is important that vaccination is carried out correctly, ensuring the correct angle of the needle depending on the type of administration, e.g. intramuscular or subcutaneous (Figure 3). Vaccine storage and preparation is also extremely important in achieving an effective vaccination (Figure 4).
Vaccination success
Vaccination is commonly used to control M. hyopneumoniae and has been shown to improve the daily weight gain by 2–8% and the FCR by 2–5%, therefore reducing losses as a result of EP (Segales et al, 2008). Vaccination with Hyogen® (Ceva Animal Health) has been shown to be effective at reducing both the percentage of pigs with EP-like lesions but also the severity of these lesions, as demonstrated by the Madec index which is calculated using a modified Madec score. The CLP is a tool for analysis of the lungs in the slaughterhouse and has been used in the UK t o demonstrate these reductions. Vaccination is also associated with reduced use of antimicrobials to control disease (Maes et al, 2008), contributing to achieving targets in reducing antimicrobial use across the industry.
A study completed by Michiels et al (2017) looked at the effect of vaccinating against two different M. hyopneumoniae strains using Hyogen® (Ceva Animal Health) in weaned piglets. Piglets were randomly assigned to three different groups, Group 1 was the control group (not vaccinated or infected), Group 2 was infected but not vaccinated and Group 3 was vaccinated and infected. The macroscopic lung lesions (MLL) were analysed and scored from 0–35 using the Lung Lesion Score system (Hannan et al, 1982). No MLL were seen in lungs from Group 1. There was a significant difference seen between MLL from Groups 2 and 3, with 91% less MLL seen in the group vaccinated with Hyogen® (Group 3). Coughing was also reduced significantly in Group 3 (over 50%), when compared with Group 2.
The positive impact vaccination against M. hyopneumoniae has on subsequent pig performance can be seen in a study completed by Maes et al, (2003), where approximately 500 pigs from 14 different pig herds in Belgium were involved in the trial, with 250 from each herd randomly assigned to either a vaccinated group or non-vaccinated group. Vaccination resulted in a significant (p<0.05) improvement in performance parameters in-cluding a mean difference in daily live weight gain (DLWG) of 22.3g/day and decreased feed conversion ratio by 0.07. As well as this, there was a significant (p<0.05) reduction seen in medication costs which equated to 38p/pig in the groups which had been vaccinated. Another study was carried out including 220 pigs split into two equal groups, half vaccinated with Hyogen® and half with another M. hyopneumoniae vaccine. Again, this study reported an increase in ADWG of 44g/day in Hyogen® vaccinated animals. The average number of recorded coughs in the whole fattening period and the percentage of severely affected lungs was also found to be significantly (p<0.005) lower in the Hyogen® group compared with the group vaccinated with another M. hyopneumoniae vaccine (Piel et al, 2017). These studies all demonstrate the benefits of effective vaccination against M. hyopneumoniae, particularly the performance improvement.
Conclusion
M. hyopneumoniae, as the causative agent of EP, is an important pathogen on swine farms worldwide, affecting animal performance and therefore economic efficiency of production. Coinfections with other pathogens, such as SIV, PRRS and PCV2 are extremely important as they can greatly increase the clinical and performance impacts of M. hyopneumoniae infection. Economic losses are primarily because of reduced ADWG, contributing to increased days to slaughter, and increased FCR, therefore increasing feed costs on the farm. Vaccination has been demonstrated to be effective in reducing the losses as a result of M. hyopneumoniae infection, working to reduce the lung lesion prevalence and severity, which has shown to be correlated with production losses. Therefore, vaccination combined with good management practices will help to reduce the impact of the pathogen as well as co-infections on farms.
KEY POINTS
- Mycoplasma hyopneumoniae is an economically important pathogen affecting pig farms worldwide.
- Examination of lungs at the slaughterhouse is important to evaluate the impact on lung health.
- M. hyopneumoniae plays a large role in increasing the severity of respiratory disease on farms where other pathogens are also present.
- Vaccination has been shown to be effective in controlling M. hyopneumoniae infections, reflected in reduced lung lesions and coughing.
- Vaccination also has economic benefits as a result of reduced mortality, increased average daily weight gain and improved feed conversion ratio.