Enzootic Pneumonia in Pigs: An Inherent Threat to Swine Industry
Sagar M Patel1, Monalisa Sahoo2 , Jigarji C Thakor3, Akash Balasaheb Mote4 , Varsha Jayakumar4 Nihar Ranjan Sahoo5 and Ajay Kumar6
1Livestock Development Officer, Animal Husbandry Department, Maharashtra, India
2Senior Scientist, ICAR-International Center for Foot and Mouth Disease, Argul, Khordha, Odisha, India
3Ph.D Scholar, Division of Pathology, ICAR-IVRI, Izatnagar, U.P, India
4Ph.D Scholar, Division of Veterinary Public Health, ICAR-IVRI, Izatnagar, U.P, India
5ICAR-International Center for Foot and Mouth Disease, Argul, Khordha, Odisha, India
6Scientist, Division of Biochemistry, ICAR-IVRI, Izatnagar, U.P, India
Abstract
Mycoplasma hyopneumoniae (Mhp) is the primary pathogen of enzootic pneumonia, globally distributed, causing major economic losses to the pig industry. Close contact between infected and susceptible pigs is the main route of its transmission. The organism is primarily found on the mucosal surface of the trachea, bronchi and bronchioles. The destruction of the mucociliary apparatus, together with modulating the immune response, enhances the susceptibility of infected pigs to other secondary pathogens. The clinical sign of enzootic pneumonia is mainly characterized by chronic, intermittent and dry cough, fever, labored breathing, anorexia, lethargy, emaciation, reduced rate of average daily weight gain, and reduced feed conversion efficiency. Primary lesions in histopathological examination are bronchopneumonia or broncho-interstitial pneumonia with Broncho-associated lymphoid tissue (BALT) hyperplasia. The successful implementation of strategies for control or elimination of infectious diseases primarily depends on the detailed aspects of pathogenesis and epidemiology. Control and prevention of Mhp infections can be accomplished by regular use of vaccination with adoption of housing and good management practices.
Introduction
Indian livestock sector accounts for one-quarter of agricultural GDP. Among various livestock species, pig rearing has been gaining tremendous attention across the society due to faster economic returns from this species as it has unique traits of high fecundity, superior feed conversion efficiency, early maturity, and short generation interval that were lacking in other species. Moreover, in setting up a piggery, start-up cost is very less as compared to other livestock rearing. In India, pork production accounts for 9% of the country’s animal protein sources with overall available 10.29 million (Livestock census, 2012). Out of various pathogens affecting the pig health, respiratory diseases always topped the diseases results causing huge financial losses due to reduced feed efficiency, reduced growth rate; high costs due to expensive medication. Out of various pathogens affecting the swine respiratory system, Mycoplasmal pneumonia is an emerging problem causing enormous losses to the global pork industry. Mycoplasma hyopneumoniae (Mhp) is the primary pathogen causing chronic respiratory infectious disease in pigs, which is also known as swine enzootic pneumonia (EP) causing high morbidity and low mortality in herds (Shen et al., 2017). EP of pigs is highly contagious and infectious disease characterized by high fever, sporadic, dry and non-productive cough, asthma, anorexia, retarded growth rate and inefficient utilization of feed among herds (Mayor et al., 2007). It often causes secondary infections in association with other pathogens, such as P. multocida, Actinobacillus pleuropneumoniae, Streptococcus suis, and Porcine Circovirus 2 (PCV2), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) aggravating the lung lesions, decreased daily weight gain and increases the mortality rate of infected swine (Tao et al., 2019). Enzootic pneumonia (EP) is highly prevalent within the intensive pig farming industry (Mayor et al., 2007; de Oliveira et al., 2017; Maes et al., 2020). The disease causes high
Economic Significance
Fig. 1. Economic losses due to Enzootic Pneumonia in pigs.
Etiology
Mycoplasma hyopneumoniae is one of the smallest fastidious bacteria with a small genome and devoid of any cell wall. It is present in the majority of swine herds throughout the world (Thacker et al., 2004).
Transmission
Mycoplasma hyopneumoniae is highly transmitted by nose-to-nose direct contact among pigs or sharing of the same air space with infected pigs. It is also transmitted by vertical transmission from dams to piglets (Balestrin et al., 2019). The chance of transmission from a sow to its offspring is higher in gilts and low parity sows. The affected pigs may shed Mhp for 200 days post infection, thereby infected can be source of infection to the other susceptible animals (Michiels et al., 2017). It also persists in respiratory tract for longer period of time, either in apparently healthy animals or even after successful treatment of the disease (Michiels et al., 2017). Dams and piglets in the breeding herds are considered as the reservoir of Mhp for the entire production system (Maes et al., 2018).
Pathogenesis
Inhalation of M. hyopneumoniae through direct or indirect contacts
Binding to cilia of epithelial cells in trachea, bronchi, and bronchioles by using adhesins proteins
Proliferate and colonize in cilia of respiratory tract and globble up the cilium
Clumping and loss of cilia
Reduction in function of mucociliary apparatus
Evasion or alteration of host immune response
Immunosuppression and increased susceptibility to secondary pathogens
Porcine Respiratory Disease Complex
Bronchopneumonia or broncho-interstitial pneumonia
Death
Fig. 2. Sequential events in pathogenesis of Mycoplasma hyopneumoniae.
Clinical Signs
The clinical sign of Enzootic Pneumonia is mainly characterized by chronic, Intermittent and dry cough, fever, labored breathing, anorexia, lethargy, emaciation, reduced rate of average daily weight gain, and reduced feed conversion efficiency (Assao et al., 2019). The decrease in productivity and the cost of medication used to treat this disease causes significant economic losses to the swine industry throughout the world (de Oliveira et al., 2017). In Mhp infection, chronic non-productive cough which appears between 10 and 16 days post infection and ceases 6–8 weeks after the onset. Once clinical signs are not apparent, pigs may remain infected for long periods of time, becoming asymptomatic carriers, capable to infect susceptible pigs (Thacker et al., 2004; Pieters et al., 2009).
Lesions
Gross findings
In Enzootic pneumonia, lesions mostly occur at the cranioventral lung areas, mainly bilaterally in the apical, cardiac, and intermediate lobes. The lesions are demarcated from healthy tissue, and consist of purple and grey areas of pulmonary consolidations with a moderately firm consistency (Ferraz et al., 2020). In case of mixed secondary bacterial infections, pigs show heavier and firmer lungs affecting higher proportion of tissues, and grey-to-white mucopurulent exudate in the airways (Maes et al., 2018).
Fig. 3. In gross examination, A&B shows cranioventral grey areas of pulmonary consolidation.
Microscopic findings
Primary lesions in histopathological examination are bronchopneumonia or broncho-interstitial pneumonia (Lee et al., 2016). The classification of lung infected with Mhp according to microscopic changes: Lesion Score 1 (discrete peribronchial, peribronchiolar and perivascular diffuse lymphocytic infiltrate, with discrete hyperplasia of type II pneumocytes); Lesion Score 2 (moderate peribronchial, peribronchiolar and perivascular diffuse lymphocytic infiltrate, with moderate hyperplasia of type II pneumocyte and discrete pulmonary bronchus-associated lymphoid tissue (BALT) hyperplasia); Lesion Score 3 (intense peribronchial, peribronchiolar and perivascular diffuse lymphocytic infiltrate, with hyperplasia of type II pneumocytes and moderate BALT hyperplasia); and Lesion Score 4 (intense and diffuse BALT hyperplasia) (Ferrarini et al., 2018; Maes et al., 2018; Ferraz et al., 2020).
Fig. 4. Microscopic examination after H&E Staining 1 – Lesion Score 1, moderate lymphocytic infiltrate and presence of hyaline cartilage around the bronchus (100x); 2 – Lesion Score 2, presence of intense peribronchiolar lymphocytic infiltrate (200x); 3 – Lesion Score 3, intense peribronchial, peribronchiolar and perivascular diffuse lymphocytic infiltrate with hyperplasia of type II pneumocytes (200x); 4 – Lesion Score 4, presence of bronchus-associated lymphoid tissue (BALT) hyperplasia (100x).
Diagnosis
Tentative diagnosis can be made by history, clinical signs and gross pneumonic findings. For confirmatory diagnosis, microscopic lesions of lungs, isolation and identification of organism and diagnostic laboratory techniques are required. Laryngeal swabs, tracheal swabs and oral swabs of infected swine can be used as diagnostic material for the detection and isolation of Mhp. (Thacker et al., 2004). The organism is difficult to grow and growth takes several weeks. Therefore, molecular detection is gaining popularity for the prompt diagnosis of Enzootic pneumonia. Nested PCR has been preferred across the laboratories for the detection of Mhp (Mayor et al., 2007; Boonsoongnern et al., 2012). Serology is a common tool used to diagnose the presence or absence of an organism within a herd (Thacker et al., 2004).
Treatment
Treatment of Mhp infections can be done by using antibiotics active against Mhp and major secondary invading bacteria. Potentially active antimicrobials against M. hyopneumoniae include tetracyclines, macrolides, lincosamides, pleuromutilins, amphenicols, aminoglycosides, aminocyclitols and fluoroquinolones. Tetracyclines, potentiated sulfonamides and macrolides are most frequently used against porcine respiratory diseases. Improvement in management and housing conditions is also required to ensure the long-lasting effects of treatment (Maes et al., 2020).
Prevention and Control
Management and biosecurity
The key success to remain free from Mhp infections depends on to avoiding the introduction of Mhp into negative farms. Although, Mhp-specific biosecurity measures have not been developed, the use of general strategies is recommended to maintain a Mhp-free status or to elude the introduction of new bacterial strains into herds. For example, the use of farm air filtration system is popular in sow farms of North America to avoid infections with PRRSV. Mhp can survive on certain plastic surfaces and dust up to 8 days at low temperature (4°C). This highlights the need of regular disinfection and decontamination systems to avoid the introduction of Mhp into the herd. The entry of new incoming pigs to the existing Mhp free herd may increase the probability of susceptibility to the infection. The development of diagnostic protocols for the rapid detection and surveillance of Mh is the need of the hour for the effect control (Maes et al., 2018; Tao et al., 2019).
Vaccination
Vaccination against M. hyopneumoniae has been shown to be a useful tool for the effective control of M. hyopneumoniae infections. Since the pathogenesis has not yet been fully elucidated, the control of disease is mainly based on prevention and optimization of management conditions. The early piglet vaccination at 3 days of age has an economic advantage than older age of piglet vaccination for prevention of Mhp infections to greater extent. The commercially available vaccines in the market are M+PAC® bacterin, Inglevac MycoFlex, and Respisure-one. The current commercial vaccines consist of inactivated whole-cell adjuvanted formulations throughout the world. Although they improve productive performance, but failed to prevent the pathogen from colonizing the respiratory tract and inducing the immunity. In order to identify an alternative vaccine that can overcome the limitations associated with the available bacterin vaccines, a reverse vaccinology approach has been used (de Oliveira et al., 2017). On the one hand, for prevention, there are many live vaccines and inactivated vaccines have been approved for the prevention of the disease. The encouraging results have been achieved through vaccination, which manifested in terms of reduced clinical signs and lung lesions. Besides, good management practices should be adopted looking into the involvement of various pathogens and the bacterial population from lungs of swine (de Oliveira et al., 2017; Tao et al., 2019). The combined vaccine may yield promising result to prevent the multiple diseases at the same time. The available vaccines are Mypravac suis mhP & S. suis), and Mhyosphere PCVID (MhP & PCV2), Respisure 1 one (MhP & PCV2), CIRCUMVENT® PCV-M G2 (MhP & PCV2), and Flexcombo (MhP & PCV2). Genetic engineering vaccines has shown a good prospect of application. However, due to its higher cost and longer time period of development, conventional virus vaccines are more common used at present. Therefore, many safeties and efficacy of these routine vaccines need to be further evaluated before their use in field (Tao et al., 2019).
Control
The successful implementation of strategies for control or elimination of infectious diseases greatly depends on the detailed insight in to the pathogenesis and epidemiology (Pieters et al., 2009). Control and prevention of Mhp infections can be accomplished by optimization of housing and management practices, and vaccination. Control of Mhp infections in pig herds can be accomplished in a number of different ways. Firstly, management and biosecurity practices and housing conditions should be optimized within the herd. These relate to proper purchase policy and gilt acclimation strategies, age-segregation and all-in/all-out production, limiting factors that may destabilize herd immunity, maintaining optimal stocking densities, prevention of other respiratory diseases, and optimal housing and climatic conditions. Improvements in these factors may decrease the infection level and/or improve the clinical outcome of Mhp infections. However, they will not eliminate the pathogen from the farm and will not always lead to the expected results. In addition, it might not always be possible to implement changes in management and housing because of financial, logistic and practical constraints. Secondly, vaccination against Mhp has been shown to be a very useful strategy to control Mhp infections. Vaccination is frequently practiced worldwide and different commercial Mhp vaccines are available. In infected herds, vaccination can improve the health and performance of animals and reduce antimicrobial usage. However, vaccination provides only partial protection and does not prevent infection. If control by improvement of management and biosecurity and the implementation of vaccination is insufficient and clinical disease occurs, then treatment of affected animals is needed to maintain animal health and welfare (Arsenakis et al., 2016; Maes et al., 2020). Eradication programs have evolved and adapted to current production systems, herd closure and medication consisting of stopped replacement entry and antibiotic treatment, and whole herd medication, using antibiotics without herd closure, are the most commonly used methods for Mhp eradication. This alternative can bring economic benefits by lowering the costs of medication and vaccination and improving the performance of pigs in daily weight gain, feed conversion, and mortality. Certainly, the longer the herd remains negative, the greater the financial advantage on downstream performance (Ferraz et al., 2020). Although several techniques for disease eradication have been designed, their practical application still represents a challenge for the practitioner and the researcher (Pieters et al., 2009).
Fig. 5. Current problems related to pathogens and corresponding control strategy.
Conclusions
The pathogenesis and interaction among Mhp, host, and other pathogens should also be clarified to successfully eliminate Mhp from pig herds. Further study should be directed to understanding the effect of strain virulence and intervention strategies, such as management practices, vaccination or medication, and the duration of Mhp infections. Finally, under the situation of the diversity and interaction of swine diseases, the research of combined vaccines may be the main trend in vaccine research.
References
Mayor, D., Zeeh, F., Frey, J. and Kuhnert, P., 2007. Diversity of Mycoplasma hyopneumoniae in pig farms revealed by direct molecular typing of clinical material. Veterinary research, 38(3), pp.391-398.
Tao, Y., Shu, J., Chen, J., Wu, Y. and He, Y., 2019. A concise review of vaccines against Mycoplasma hyopneumoniae. Research in veterinary science, 123, pp.144-152
de Oliveira, N.R., Jorge, S., Gomes, C.K., Rizzi, C., Pacce, V.D., Collares, T.F., Monte, L.G. and Dellagostin, O.A., 2017. A novel chimeric protein composed of recombinant Mycoplasma hyopneumoniae antigens as a vaccine candidate evaluated in mice. Veterinary microbiology, 201, pp.146-153.
Maes, D., Boyen, F., Haesebrouck, F. and Gautier-Bouchardon, A.V., 2020. Antimicrobial treatment of Mycoplasma hyopneumoniae infections. The Veterinary Journal, 259, p.105474.
Shen, Y., Hu, W., Wei, Y., Feng, Z. and Yang, Q., 2017. Effects of Mycoplasma hyopneumoniae on porcine nasal cavity dendritic cells. Veterinary microbiology, 198, pp.1-8.
Thacker, E.L., 2004. Diagnosis of Mycoplasma hyopneumoniae. Animal Health Research Reviews, 5(2), pp.317-320.
Balestrin, E., Kuhnert, P., Wolf, J.M., Wolf, L.M., Fonseca, A.S.K., Ikuta, N., Lunge, V.R. and Siqueira, F.M., 2019. Clonality of Mycoplasma hyopneumoniae in swine farms from Brazil. Veterinary microbiology, 238, p.108434.
Michiels, A., Vranckx, K., Piepers, S., Del Pozo Sacristán, R., Arsenakis, I., Boyen, F., Haesebrouck, F. and Maes, D., 2017. Impact of diversity of Mycoplasma hyopneumoniae strains on lung lesions in slaughter pigs. Veterinary Research, 48(1), pp.1-14.
Maes, D., Sibila, M., Kuhnert, P., Segalés, J., Haesebrouck, F. and Pieters, M., 2018. Update on Mycoplasma hyopneumoniae infections in pigs: knowledge gaps for improved disease control. Transboundary and emerging diseases, 65, pp.110-124.
Assao, V.S., Scatamburlo, T.M., Araujo, E.N., Santos, M.R., Pereira, C.E.R., Guedes, R.M.C., Bressan, G.C., Fietto, J.L.R., Chang, Y.F., Moreira, M.A.S. and Silva-Júnior, A., 2019. Genetic variation of Mycoplasma hyopneumoniae from Brazilian field samples. BMC microbiology, 19(1), pp.1-12.
Pieters, M., Pijoan, C., Fano, E. and Dee, S., 2009. An assessment of the duration of Mycoplasma hyopneumoniae infection in an experimentally infected population of pigs. Veterinary microbiology, 134(3-4), pp.261-266.
Ferraz, M.E.S., Almeida, H.M.S., Storino, G.Y., Sonálio, K., Souza, M.R., Moura, C.A.A., Costa, W.M.T., Lunardi, L., Linhares, D.C.L. and de Oliveira, L.G., 2020. Lung consolidation caused by Mycoplasma hyopneumoniae has a negative effect on productive performance and economic revenue in finishing pigs. Preventive veterinary medicine, 182, p.105091.
Ferrarini, M.G., Mucha, S.G., Parrot, D., Meiffrein, G., Ruggiero Bachega, J.F., Comte, G., Zaha, A. and Sagot, M.F., 2018. Hydrogen peroxide production and myo‐inositol metabolism as important traits for virulence of Mycoplasma hyopneumoniae. Molecular microbiology, 108(6), pp.683-696.
Arsenakis, I., Panzavolta, L., Michiels, A., Del Pozo Sacristán, R., Boyen, F., Haesebrouck, F. and Maes, D., 2016. Efficacy of Mycoplasma hyopneumoniae vaccination before and at weaning against experimental challenge infection in pigs. BMC Veterinary Research, 12(1), pp.1-7.
Boonsoongnern, A., Jirawattanapong, P., Lertwatcharasarakul, P., Phatthanakunanan, S., Poolperm, P., Urairong, S., Navasakuljinda, W. and Urairong, K., 2012. The prevalence of Mycoplasma hyopneumoniae in commercial suckling pigs in Thailand. World J Vaccines, 2(3), pp.161-163