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Controlling Mycoplasma hyopneumoniae

by 5m Editor
30 October 2001, at 12:00am

By F. Joisel, S. Randoux, J. B. Hérin & F. Bost, Merial, France. - Multiple interactions between pathogens and herd management factors make pig respiratory diseases become more and more complex. Many bacteria and viruses may be involved, among which Mycoplasma hyopneumoniae (M.h.) is one of the most prevalent.

Management and breeding conditions also play an important role in not only the occurrence but also the severity of respiratory disorders. The diagram adapted from Muirhead and Alexander, Figure 1, shows, that as more pathogenic agents and more bad management conditions accumulate, the respiratory disease situation worsens.

Fig. 1: Complexity of interactions in respiratory diseases


Not only does the status change from a farm to another but it also may vary as time goes by. The variety of the situations encountered and their evolution are mainly due to:
  • Simultaneous infections,
  • M.h. epidemiology,
  • Herd management changes,
  • Development of emerging diseases.

Interactions between respiratory pathogens

M.h. is known to potentiate other pathogens. It destroys the mucociliary escalator (M. C. DeBey et al.), allowing the mechanical penetration of foreign bodies in the depth of the lung and enhances lung infections by bacteria as Pasteurella multocida and Actinobacillus pleuropneumoniae (R. F. Ross, 1999).

The increasing importance of the so-called porcine respiratory disease complex (PRDC) particularly in the multi-site pig farms in the USA has led for the last few years number of researchers to try to find an explanation to this particular late acute respiratory syndrome. The most commonly isolated pathogens in the lungs of pigs affected by PRDC are PRRSV, M.h. and swine Influenza virus (SIV). E. Thacker et al. have shown that M.h. increased the PRRSV induced lung lesions and also that PRRSV infection was interfering with anti-M.h. vaccination with commercial bacterins.

The porcine circovirus type 2 (PCV2) has also been clearly identified as responsible for respiratory tract lesions in 67.5% of pigs suffering from post-weaning multisystemic wasting syndrome (PMWS) necropsied after death (F. Madec et al., 1999).

More recently, diagnosticians from the Iowa State University diagnostic Lab reported that along the year 1999, PCV was detected in 8.8% of total pneumonia cases, PRRSV in 35% of total pneumonia cases and that just a bit more than 60% of PCV cases have concurrent PRRSV diagnosis.

However, PCV2 has been isolated as the single pathogen in several cases. This virus should be considered now as a new player in the "game" of respiratory disease, alone or associated with others. Furthermore, the PCV2 virus is suspected to affect macrophages, monocytes and histiocytes and, therefore, alter the lymphoid system by causing immunosuppression.

Modifications of Mycoplasma hyopneumoniae epidemiology

Infection mechanism at the individual level
Mycoplasma hyopneumoniae is a pig specific, non-invasive bacteria, without cell-wall. M.h. is a tedious micro-organism exhibiting a slow replication both in vivo and in vitro.

At the individual level, the direct contamination occurs mainly by contact or aerosol (cough). After transmission to the piglet, contamination occurs either vertically by the dam or horizontally by an other piglet. The infectious bodies penetrate in the respiratory tract by inhalation and adhere to cilia (Q. Zhang et al., 1995), through an adhesion protein system. They then are able to slowly replicate and colonize the mucosa border in several weeks.

The infection results in a ciliostasis and the loss of cilia (M. C. DeBey et al., 1992) and an inflow of inflammatory cells in the surrounding tissue. The inflammatory phenomenon due to a strong, hypersensitive-like immune reaction induce the onset of characteristic but however non pathognomonic lesions of enzootic pneumonia (EP).

The devastation of the mucociliary escalator is one of the main predisposing factor to super-infections. Clinical signs, essentially represented in the typical form by a dry cough enhanced when animals are moved in the pen, may vary according to super-infections. Seroconversion is commonly seen few days after infection but can be sometime delayed to several weeks after it.

Fig 2: Clinical expression and seroconversion kinetics in 200 SPF pigs following artificial challenge with M.h.


Figure 2 (V. Sørensen, 1994) shows the events after experimental infection of 200 pigs. The onset of clinical signs took place roughly 4 weeks after contamination and pigs seroconvert from 3 to 5 days after clinical signs.

These periods of time may vary from a farm to another, field experience showed that the schedule determined by experimental infection is on an average not so far from what is actually seen in commercial farms. Infection dynamics at farm level
The disease may break out after a sufficiently large number of piglets have been infected and shed M.h.. Using PCR, it was demonstrated that the critical percentage of infected pigs necessary for the onset of clinical signs is estimated to be 50% (C. Pijoan et al. 1998).

The epidemiology at the herd level depends on the global M.h. infectious pressure and the repartition of the age of sows. As a matter of fact, gilts have been shown to shed more M.h. than older females (C. Pijoan et al. 1998). Infection comes sooner in continuous flow than in all in all out management. Furthermore, contamination and infection are still more delayed in three site farms.

Fig 3a: Diagram of the disease dynamics at the farm level with early and high level of M.h. infection.


Figure 3a shows a diagram of the disease dynamics at the farm level with early and high level of infection. The dotted line indicates the threshold for the number of piglets that triggers the clinical sign off. Mostly but not only in continuous flow farms, M.h. infectious pressure is high and the number of contaminated piglets is rapidly increasing. Clinical enzootic pneumonia occurs at the end of the post-weaning or at the beginning of the fattening period.

Fig 3b: Diagram of the disease dynamics at the farm level with an average level of M.h. infection.


In the pattern shown in figure 3b, M.h. infectious pressure is average and the number of contaminated piglets is more slowly increasing. The critical threshold for the clinical expression of enzootic pneumonia is then delayed and coughing starts by the middle of the fattening period. This is the most usual situation in European countries that all in all out management farms have to face.

Figure 3c: Diagram of the disease dynamics at the farm level with low early level of M.h. infection.


In this last pattern shown in figure 3b, M.h. infective challenge is weak in the farrowing pens and the number of contaminated piglets at weaning is small. It then takes time for the threshold to be reached and clinical expression is then delayed at the end of the fattening period. Sometimes, cough can hardly be heard and only EP lesions are seen at the slaughterhouse. This situation is more and more frequent. It is fairly common in the three site farms in the USA (C. Pijoan, personnel communication, 2000) but also is encountered in European countries. In the USA, this epidemiological pattern leads to the PRDC complex.

Influence of sow age

Aside piglet co-mingling, sow parity repartition is probably one of the key factors that differentiate the different dynamic patterns at the farm level.

Fig 4: Microbiological profile of sows in a 2200 sow farrowing farm in the USA. (C. Pijoan et al. 1998)


Using PCR from nasal swabs and a classification by parity, these authors showed that shedding was different according to the age of the breeding animals. In conventional breeding systems, gilts are likely to shed more M.h. than older animals because of more recent contracted infection in their early life.

At farm level, the infection may develop more or less rapidly; the vaccination program must therefore be optimised accordingly.

Interference with maternally derived antibodies

Passive and active immunity against M.h. has been also established to exert an influence over vaccination intake. Maternally derived antibodies level and persistence in piglets is highly variable.

Morris et al. (1994) showed that the median half life of M.h. antibodies in piglets born to positive sows was 15.8 days. P. Wallgren (1998) confirmed that in different litters from the same farm, huge variations in passive immunity could be seen (figure 5). In that experiment, some litters become negative on an average by the middle of the second week although others were found positive up to the sixth week of life.

Fig 5: Average anti-M.h. antibody level from different litters.


Several studies have pointed out the risks of maternal antibody interference with mycoplasma vaccination. B.Thacker, (1998) showed that the amount of antibody induced by vaccination is reduced when pigs were passively immune at the time of vaccination.

According to J. Quinlan (1998), "waiting until the pigs are 6-8 weeks old gives time for the natural degradation of maternal antibodies to have taken place, so a greater portion of the vaccinated population can develop a protective response". Furthermore, "sows which have recently recovered from the infection have high serum antibody titres and transfer strong and persisting colostral immunity.

The ability of the mononucleated cells of piglets to produce antibodies increases with age. "Optimal time points for potential vaccinations against M.h. ought to be validated" noted P. Wallgren, (1998). Numerous other workers have also warned that if sows have high serum antibody titres that are transferred to their piglets, vaccination should be postponed (S. Amass (1999), S.C. Daniels (1999), B. Thacker (2000)).

Optimization of the anti-M.h. vaccination program

M.h. infection can be monitored in the farm using observation of clinical signs and / or serological profiling. In order to prevent the disease and the related economic losses, the infection must remain below the threshold of infected pigs.

Fig 6: proposal for a retro-schedule for the optimization of Mycoplasma vaccination with HYORESP®


Based on challenge experiments, clinical signs occur approximately 4 weeks after infection, followed quickly 4 days later by seroconversion. Ten 16 week-old and ten 22 week-old pigs are blood sampled and the sera are tested for anti-M.h. antibodies using a qualitative ELISA test.

Figure 6 shows a proposed retro-schedule designed to help in the implementation of vaccination at the right time. Pigs are at the top of their secondary immune response and then at top of the protection level few weeks after the second injection of the vaccination. Then, pigs must have been injected with HYORESP® for the second time 6 weeks before the clinical signs and/or the seroconversion and for the first time 9 weeks before. This can constitute a basis for practitioner and breeder thinking. Results of the serological examinations may be helpful if the precise break point is unknown or if of other respiratory pathogens are involved in the farm.

As an additional tool easily usable in the field, a table is proposed that summarizes the different types of herd profile and the vaccination program that can be recommended accordingly (table 1).

Table 1: Guidelines for anti-M.h.-vaccination according to clinical observation and serological profile.
Type of Enzootic Pneumonia Clinical Expression Time M.h. serology
(% positive & suspicious)
Vaccination Program

16 weeks (%)

22 weeks (%)

Early End of post-weaning period - start of fattening period

80-100

80-100

1-4 weeks

Conventional Mid-fattening period

25-80

80-100

4-7 weeks

Late Second half of fattening period

<25

60-100

7-10 weeks

Not visible

0

<60

Single at 10 weeks

Conclusion

In conclusion, herd management progresses and M.h. infection tends to develop later in time. Simultaneous infections may increase the severity of the situation and also interfere with vaccination. Maternal antibodies interfere with early vaccination.

Practitioners must bear in mind that every herd is a single case that has to be addressed separately. Prescribing the ideal M.h. vaccination program to each herd has to take into account the infection dynamics at the farm level, the risks of interference with maternal antibodies, concurrent diseases, practical and economical facts (as manpower, for example).

New M.h. vaccines such as HYORESP®, that allow the largest flexibility to adapt to all vaccination programs are adding value in the fight against respiratory diseases.
References
S. Amass (1999). A review of Mycoplasmal pneumonia. Proceedings of the North American Veterinary Conference. Large Animal Edition, 13. C.S. Daniels, B.J. Thacker, S. Sornsen & E.L. Thacker (1999). Survey of Mycoplasma hyopneumoniae Maternally-Derived Antibodies in suckling pigs, Proceedings of the Allen D. Leman Conference, 41. M.C. DeBey, C.D. Jacobson & R.F. Ross (1992). Histochemical and morphological changes in porcine airway epithelial cells in response to infection with Mycoplasma hyopneumoniae. Am J Vet Res, 53, 1705-1710. F. Madec, E. Eveno, P. Morvan, L. Hamon, H. Morvan, E. Albina, C. Truong, E. Hutet, R. Cariolet, C. Arnaud & A. Jestin (1999). La maladie de l'amaigrissement du porcelet (MAP) en France 1- Aspects descriptifs, impact de l'élevage. Proceedings of the 31ème Journées de la Recherche Porcine en France - Paris, 31, 347-354. C.R. Morris, I.A. Gartner, S.K. Hietala, T.E. Carpenter R.J. Anderson & K.M. Parker (1994). Persistence of passively acquired antibodies to Mycoplasma hyopneumoniae in a swine herd, Prevent Vet Med, 21, 29-41. M. Muirhead & T. Alexander, (1997). Managing pig health and the treatment of disease, 5M Enterprises Ltd. C. Pijoan et al. (1998) Evolution de la pneumonie enzootique chez le porc, adapter la stratégie de contrôle, Prospective, 7, 2-5. Pharmacia & Upjohn Edts. J. Quinlan (1998). Delayed vaccination fights late pneumonia, Pig international, 28 (5), 28-29. R.F. Ross, (1999). Mycoplasmal diseases in Diseases of Swine 8th Ed. B. Straw et al. Ed., 495-510. V. Sørensen, et al. (1994). The humoral response to experimental Mycoplasma hyopneumoniae infection in pigs in relation to clinical signs and pathological lesions. Proceedings of the 13th IPVS Congress, Bangkok, p.190. B.J. Thacker, T. Boettcher, T. Anderson, E.L. Thacker & T. Young (1998). The influence of passive immunity on serological responses to Mycoplasma hyopneumoniae vaccination, Proceedings of the 15th IPVS Congress, Birmingham, 2, 154. E.L. Thacker, P.G. Halbur, R.F. Ross, R. Thanawongnuwech & B. Thacker (1999). Mycoplasma hyopneumoniae potentiation of Reproductive and respiratory syndrome virus-induced pneumonia, J Clin Microbiol, 37 (3), 620-627. E.L. Thacker & B.J. Thacker (2000). Vaccination as a means of controlling Mycoplasma hyopneumoniae, Proceedings of the Allen D. Leman Conference, 84-86. P. Wallgren, G. Bölske, S. Gustafsson, S. Mattsson & C. Fossum (1998). Mycoplasma hyopneumoniae; Humoral immune response in sows and offspring following an outbreak of disease. Proceedings of the 15th IPVS Congress, Birmingham, 2, 147. Q. Zhang, T.F. Young & R.F. Ross (1995). Identification and characterization of a Mycoplasma hyopneumoniae adhesin, In