By Prof. Dominiek Maes, DVM, MS, MSc, PhD, Dipl. ECPHM, Dipl. ECVPH, Unit Porcine Health Management, Faculty of Veterinary Medicine, Ghent University, Belgium
Mycoplasma hyopneumoniae (M. hyopneumoniae) is the primary agent of porcine enzootic pneumonia, a chronic respiratory disease causing major economic losses to the swine industry worldwide. The present paper discusses the importance of strain diversity in relation to pathogenesis and disease, and shortly reviews the most important measures to control the disease.
M. hyopneumoniae belongs to the Mollicutes taxon and ranks among the smallest (0.2 µm) self-replicating bacteria known to date. It has a very small and simple genome. M. hyopneumoniae is extremely sensitive to environmental conditions and in contrast to most prokaryotic organisms, it is characterized by the lack of a cellular wall. The pathogen is not able to survive for a long time outside its host, but in aerosols its survival time increases as it can remain infective for up to 31 days in water at 2-7oC.
The organism is characterized by a slow and fastidious growth in vitro and is extremely difficult to isolate. Therefore, isolation is not used for routine diagnosis. The J strain, originally isolated in 1973, has become a high passage laboratory strain that is considered as the reference strain for M. hyopneumoniae.
A parasitic way of life has been achieved through the manifestation of surface proteins. The organism can produce adhesins, modulins, aggressins and impedins that allow adhesion and modulation of the host immune system. Using molecular techniques, it appears that M. hyopneumoniae isolates show a large diversity at genomic and proteomic level. In addition, there are also important differences in virulence among M. hyopneumoniae isolates. Based on respiratory disease score, lung lesions scores, histopathology, immunofluorescence and serology, low, moderate and highly virulent isolates have been described. MLVA-typing has been used to investigate strain diversity within pig herds. It was shown that there are major differences in diversity and persistence of M. hyopneumoniae strains between pig herds and that pig can be infected with multiple strains. In some herds, only one strain is dominating, whereas in other herds, many different strains can be found.
Recent field studies by our research group showed that the same strain can persist in the same animals for at least 12 weeks, until slaughter age. This implies that the immune response of the animals following infection is not able to rapidly clear the infection from the respiratory tract. Other studies also demonstrated that pigs inoculated with low virulent isolates of M. hyopneumoniae are not protected against a subsequent infection with a highly virulent isolate 4 weeks later and may even develop more severe disease signs. This suggests that subsequent infections with different M. hyopneumoniae isolates may lead to more severe clinical disease in a pig herd. Further research is warranted on the clinical significance of strain diversity.
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PATHOGENESIS, CLINICAL SIGNS AND DIAGNOSIS OF M. HYOPNEUMONIAE INFECTIONS
The organism is primarily found on the mucosal surface of the trachea, bronchi, and bronchioles, and adherence of M. hyopneumoniae to the ciliated epithelium is a prerequisite for initiation of the infection. Zhang et al. (1995) identified the P97 protein to be a ciliary adhesin. Other adhesins may include a glycoprotein of 110 kDa, a P159 protein that is post-transitionally cleaved in proteins of 27, 51 and 110 kDa and a 146 kDa protein. M. hyopneumoniae affects the mucosal clearance system by disrupting the cilia on the epithelial surface and, additionally, the organism modulates the immune system of the respiratory tract.
Therefore, M. hyopneumoniae predisposes animals to concurrent infections with other respiratory pathogens including bacteria, parasites and viruses. A 54 kDa membrane protein of M. hyopneumoniae induced cytopathogenic effects in human lung fibroblast cell lines. Epithelial cell damage may also be caused by the mildly toxic by-products of mycoplasma metabolism, such as hydrogen peroxide and superoxide radicals.
Chronic, non-productive coughing, the main clinical sign, appears 10–16 days after experimental infection. The clinical course of infections under field conditions may vary significantly between pig herds depending on herd management strategies, secondary infections and environmental conditions. Also the virulence of the M. hyopneumoniae strains may determine the clinical outcome, which renders control of this pathogen a difficult task.
Macroscopic lesions, consisting of purple to grey areas of pulmonary consolidation, are mainly found bilaterally in the apical, cardiac, intermediate and the anterior parts of the diaphragmatic lobes. Recovering lesions consist of interlobular scar retractions, and in case of a pure M. hyopneumoniae infection macroscopic lesions are resolved 12 – 14 weeks after infection. Clinical signs and lesions can lead to a tentative diagnosis, but laboratory testing is necessary for a conclusive diagnosis. The organism can be detected by immunofluorescence testing, but this test has limited sensitivity. Serology can be used to show presence of the organism at a herd level, but is not suited for diagnosis on individual animals. At present, (nested or quantitative) polymerase chain reaction (PCR) testing is seen as the most sensitive tool to detect the infection.
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CONTROL OF M. HYOPNEUMONIAE INFECTIONS
Optimizing management and housing is primordial in the control of M. hyopneumoniae infections. Management changes that reduce the possibilities of spreading M. hyopneumoniae or result in decreased lung damage by other pathogens may significantly improve the control of enzootic pneumonia.
To control and treat respiratory disease including M. hyopneumoniae infections in pigs, tetracyclines and macrolides are most frequently used. Other potentially active antimicrobials against M. hyopneumoniae include lincosamides, pleuromutilins, fluoroquinolones, florfenicol, aminoglycosides and aminocyclitols. Fluoroquinolones and aminoglycosides have mycoplasmacidal effects. Since the organism lacks a cell wall, it is insensitive to β-lactamic antibiotics such as penicillins and cephalosporins. Acquired antimicrobial resistance ofM. hyopneumoniaehas been reported to tetracyclines, and recently also to macrolides, lincosamides and fluoroquinoles.
Treatment is generally effective to decrease lung lesions and clinical signs. However, the symptoms may reappear after cessation of the therapy. Pulse medication in which medication is provided intermittently during critical production stages can also be used. Pulse medication during extended periods of time as well as continuous medication during one or more production stages should be discouraged because of both the increased risk of spread of antimicrobial resistance and the possible risk for antimicrobial residues in the pig carcasses at slaughter. In endemically infected farms, strategic medication of the reproductive herd is sometimes practiced as an attempt to decrease the bacterial shedding from sows to the newly introduced gilts. Antimicrobial medication of recently weaned pigs has been shown to reduce the number of M. hyopneumoniae organisms in the respiratory tract, but further research is necessary.
Commercial vaccines, consisting of inactivated, adjuvanted whole-cell preparations, are widely applied worldwide. The major advantages of vaccination include reduction in the losses of daily weight gain (2-8%) and feed conversion ratio (2-5%) and sometimes a lower mortality rate. Additionally, shorter time to reach slaughter weight, reduced clinical signs, lung lesions and lower treatment costs are observed. Although protection against clinical pneumonia is often incomplete and vaccines do not prevent colonization, recent studies indicate that the currently used vaccines reduce the number of organisms in the respiratory tract and decrease the infection level in a herd.
Different vaccination strategies have been adopted, depending on the type of herd, the production system and management practices, the infection pattern and the preferences of the pig producer. Moreover, under field conditions, optimal vaccination strategies must balance the advantage of delayed vaccination with the need to induce immunity before exposure to pathogens. Since infections with M. hyopneumoniae may already occur during the first weeks of life, vaccination of piglets is most commonly used.
Vaccination of suckling piglets (early vaccination; < 4 weeks of age) is more common in single-site herds, whereas vaccination of nursery/early fattening pigs (late vaccination; between 4 and 10 weeks) is more often practiced in three-site systems where late infections are more common. Traditionally, double vaccination was the most frequent practice. During the last years, one-shot vaccines have been shown to confer similar benefits as two-shot vaccines and are more often used now. One-shot vaccination is especially popular because it requires less labor and it can be implemented more easily in routine management practices on the farm.
Vaccination of suckling piglets has the advantage that immunity can be induced before pigs become infected, and that less pathogens are present that can interfere with immune response. Vaccination of nursery pigs has no or less interference with possible maternally derived antibodies. However, nursery pigs may already be infected with M. hyopneumoniae. Finally, many infections such as PRRSV or PCV2 mainly take place after weaning and may affect the general health status of the pigs, and consequently also interfere with proper immune responses after vaccination. Only a few studies have assessed the effects of vaccination of sows during gestation. Vaccination of gilts is recommended in endemically infected herds to avoid destabilization of breeding stock immunity. This is particularly the case when gilts are purchased from herds that are free from M. hyopneumoniae.
Although vaccination confers beneficial effects in most infected herds, the effects vary between herds. This may be due to different factors such as improper vaccine storage conditions and injection technique, antigenic differences between field strains and vaccine strains, presence of disease at the time of vaccination, and interference of vaccine induced immune responses by maternally derived (colostral) antibodies.
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Infections with M. hyopneumoniae cause major economic losses to the pig industry worldwide. Different M. hyopneumoniae strains show major differences at genomic and proteomic level, and there are also differences in virulence between isolates. Infections cause damage in the respiratory tract, modulate the immune system and render pigs more susceptible to other respiratory pathogens. Control measures should focus on optimization of management practices and raising conditions, and if these are not sufficient, antimicrobial medication and/or vaccination can be used.
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This article appeared in Asian Pork, March 2013.©Copyright 2013, All Rights Reserved.