mycoplasma infection in swine - prevention and control

Arlette Laval Ecole Nationale Vtrinaire de Nantes, Nantes, France

Introduction
Due to the high prevalence of the infection caused by Mycoplasma hyopneumoniae (M. hyo), the control of enzootic pneumonia (EP) is a major concern in the swine industry. Keeping the herd free of infection is obviously the best way, but it is not always feasible. Thus, management, treatment and vaccination must be used.

The Enzootic Pneumonia-free breeding herd

Most breeding organisations can supply breeding stock free of M. hyo. They are obtained by eradication and restocking with non-infected animals. The use of SPF piglets is essential in the case of setting up a new farm or of repopulation of old ones. The difficulty will be to remain free of M. hyo. If the first infected pig farm is less than 3 km away, there is a definite chance that sooner or later the herd will become contaminated by wind-borne infection. The risk increases the larger the infected herd. It decreases if the land is hilly or coastal. In pig dense regions it is impossible to remain Mycoplasmafree. Even the Danish SPF system failed. This system is founded on a large scale total depopulation method widely deployed since 1968. However many Danish SPF herds became re-infected with M. hyo, apparently due to the airborne spread of the bacteria (Baekbo 2000). Apart from total depopulation, less expansive methods were also tried. Test and removal of infected animals has been successfully applied for Aujeszkys disease but results for M. hyo were not satisfactory. Eradication by partial depopulation is a less expensive alternative for restocking with SPF animals and allows preserving the genetic potential of the breeding animals. The production is not completely stopped during the eradication

phase. This method is very effective for M. hyo infections (Baeckbo). In short, young animals (weaners, growers and finishers) are removed from the infected farm. During a period of 14 days only breeding animals older than 10 months remain on the farm. There is no farrowing during this 14-day-period and all breeder animals are heavily medicated with a suitable antibiotic, for instance tiamulin 6-8 mg/body weight. Obviously, the farm as well as the place where young animals are provisionally kept must be in an appropriate geographic position. Studies from different countries (Lium 1992, Damgaard et al., 2000, Lorenzen et al., 2000) have shown that eradication programmes with Denagard medication are a safe and reliable method to eliminate M. hyopneumoniae from infected herds. Another possibility to eliminate the disease is segregated early weaning. This method is very popular in North and South America as well as some Asian countries. It is well adapted to very large farms with several thousand sows, and requires multi-site facilities. Piglets are weaned between 7 and 15 days of age, before infection from the infected sow. They grow up in specially adapted nurseries and are moved once more for fattening. A heavy antibiotic treatment is given at least 2 weeks after weaning. Results are good, as other pathogens are controlled by this way. But it seems that, year after year, Mycoplasma infections reappear due to their high prevalence in the environment. Strict management of the staff is also necessary. After eradication, the herd must remain free of M. hyo infection. For this purpose, the herd must be totally closed and if necessary, air filtration should be in operation. A strict bio-security program must be applied. Breeders must be purchased from a safe, disease-free source, if possible always the same source or, at least, from the same

breeding pyramid. Incoming pigs must be isolated for 8 weeks and checked by any method (usually serologically) for M. hyo infection before moving into the herd. Nave pigs may be mixed in the quarantine with the newly purchased pigs as markers to detect any persistent infection. Their blood is tested and their lungs examined before the end of the quarantine. The objective of this technique is also to help the young gilts to gradually adapt to the health status of the herd.

The EP-affected herd

Everything must be done to keep the infection at the lowest level as possible. Sanitary measures Gilts can be purchased from breeding herds with M. hyo infection, it is even safer. But they must be free from mange, swine dysentery, App and PRRS. Isolation and monitoring procedures are the same as for disease-free herds, but the quarantine can be limited to 6 weeks. However, the present tendency favours a global increase of the quarantine, safer not only for M. hyo but also for many other pathogens. If the herd has a low health status it is better to medicate the feed for incoming gilts and to vaccinate them if it was not done before. The general monitoring of the herd must take into account the following : Keep a broad parity in sows: immunity is better and Mycoplasma carriage is lower in old sows than in gilts. They pass a better immunity to their piglets and the bacterial contamination is lower. Thus, it is important to respect a good balance between young and old sows.

l Be strict about worm control, all-in-all out procedures, cleaning and disinfection of the rooms l Avoid overcrowding especially in large rooms l Control temperature, draughts, dust, ammonia and carbon dioxide l Avoid purchasing pigs from different sources l Avoid stress, pig movements, mixing, especially between animals of different ages l Provide feed and water in appropriate conditions Strictly control other diseases and pathogens: PRRS, Aujeskys disease, App, swine influenza, PCV-2, Porcine Respiratory Corona Virus. If necessary, vaccinate or medicate against these pathogens following appropriate procedures. For M. hyo itself, it is often necessary to vaccinate and to administer antibiotic treatments.

Table I. Sensitivity of M. hyopneumoniae (g/ml) to different antibiotics (Hungarian data) Stipkovits, L. et al., (2004)
Antimicrobial Doxycycline Chlortetracycline Tylosin Tilmicosin Lincomycin Tiamutin mIC range 0.5 - 32.0 4.0 - 32.0 0.25 - 16.0 0.125 - 2.0 0.25 - 8.0 0.06 - 1.0 mIC50 4.0 16.0 2.0 0.25 2.0 0.25 mIC90 16.0 32.0 16.0 2.0 8.0 1.0

Table 2. Sensitivity of Korean fields isolates of M. hyopneumoniae to seven antimicrobials ( Koh H.B. et al.,1994) (mIC90 in g/ml)
Antimicrobial MIC90 Antimicrobial Tiamutin 0.8 Tylosin Danofloxacin 1.6 Norfloxacin Enrofloxacin 1.6 Lincomycin/ Oxytetracyclin 3.2 Spectinomycin

Treatments
Several antibiotics are active against Mycoplasma hyopneumoniae. They reduce symptoms and economic losses and it is even possible to eradicate the infection by selecting the correct antibiotic and dose rate. Mycoplasma spp., are very sensitive to macrolides, lincosamines and, in particular, the pleuromutilins (tiamulin, valnemulin). Tetracyclines are effective, but to a lesser extent. The synergy between tetracyclines and the pleuromutilins can be used to increase the activity on Mycoplasma and to broaden the spectrum of activity especially against Gram-negative bacteria, especially the omnipresent Pasteurella multocida (Fodor et al., 2004, Stipkovits et al., 2004, Koh et al., 2006). Fluoroquinolones are very active, but their use cannot be recommended in the context of prudent use of antibiotics because they are also active against Gram-negative bacteria. When

Spectinomycin MIC90 3.2 3.2 6.3

Table 3. Sensitivity of M. hyosynoviae field isolates (g/ml) to different antibiotics (Stipkovits L. et al., 2004)
Antimicrobial Doxycycline Chlortetracycline Tylosin Tilmicosin Lincomycin Tiamutin mIC range 0.25 - 4.0 8.0 - 32.0 2.0 - 32.0 2.0 - 32.0 0.5 - 8.0 0.03 0.25 mIC50 1.0 8.0 4.0 4.0 2.0 0.125 mIC90 2.0 32.0 16.0 16.0 4.0 0.25

regularly used fluoroquinolones can select resistent Escherichia coli or Salmonella spp., with serious consequences for human health. The aminoglucosides possess less inhibitory activity. Mycoplasma spp., are not sensitive to beta-lactam antibiotics, polymixins, rifampicine and the sulfonamides. M. hyopneumoniae and M. synoviae are very sensitive to tiamulin (refer Tables 1, 2 and 3). Results may differ according to the countries, but tiamulin is always more effective than macrolides and even fluoroquinolones. The MIC values of florfenicol range from 0.25 to 1 g/ml against M. hyopneumoniae and 0.25 to 2 g/ml against M. hyorhinis (Zhou and Wu, 2006). Some studies indicate that the pleuromutilin, valnemulin, is more active than tiamulin. Treatment can be given by injection in acute cases and especially for the treatment of M. synoviae polyarthritis. However, it is more common to treat by oral route, in-feed or in-water in case of enzootic pneumonia or M. hyorhinis polyserositis. The time and the dosage of the treatment are critical for the efficacy. It must be given when mycoplasmas begin to multiply, after the maternal antibodies disappear. Usually, treatment is given at weaning, in-feed or in-water for 5 to 21 days at different dosages, according to the molecule, as well as the presentation and severity of the infection. Oral treatments can also be given for the same duration before or just after entering the fattening unit. Treatments are also necessary in case of mixing of animals of differing health status. Due to the high frequency of secondary infections with Gramnegative bacteria, remember to broaden the spectrum to include antibiotics that are active against Gram-negative bacteria. Vaccines and vaccination The development of really efficacious vaccines, for now more than 10 years has completely modified the fight against M. hyopneumoniae. All vaccines are inactivated. They are made of whole cells or membrane preparations and require adjuvants. Adjuvants must be very

immunogenic and be able to activate macrophages. Several good vaccines are available, but it must be remembered that they do not eliminate infection, Mycoplasma colonisation and even clinical disease. They reduce economic losses, especially growth retardation, mortality, time to reach slaughter weight and they reduce the number of Mycoplasma organisms. Current vaccines can be used with one or 2 shots, 3 weeks apart. Vaccination is performed on piglets, but the age at which the first injection is given is critical. Obviously vaccination must be performed before the onset of clinical signs, very early, at the age of 5-7 days with a booster at 21-28 days in severely affected herds. When the herd begins to be immunised, the clinical signs will move to older pigs. In this case it becomes imperative to delay the first injection. Late vaccination, at 6 and 8 weeks of age or even later, is the better choice in this case (Lee, 2004). The one shot vaccination is less effective, but sufficient when the infection is less severe. Certainly it is important to apply an specific protocol suited to each individual farm in order to induce the best protection. Vaccination programs must be applied for prolonged periods for all animals to obtain good results. Serological data founded on serological profiles can help to estimate precisely when the natural seroconversion takes place and to choose the best moment for vaccination. Immunity is acquired about 5 weeks after the first injection. The role of maternal antibodies is important for the control of the disease. It is both positive and negative. It is beneficial for the piglets because passive immunity delays and reduces Mycoplasma colonisation. However, it may interfere with vaccination. Although there is no correlation between maternal antibodies and protection, the level of maternal antibodies is important in understanding the disease with in a herd and deciding when to vaccinate. Other factors can interfere with vaccination, especially concurrent PRRS virus (PRRSv) circulation. It is important to vaccinate against Mycoplasma hyopneumoniae before

the circulation of PRRSv. Stresses and other concurrent infections can also reduce the efficacy of the M. hyo vaccine.

Conclusions
Eradication is a really expensive measure and therefore can only be justified in exceptional cases. However, it is very important to control Mycoplasma infections, because these bacteria are the pivotal agent in respiratory diseases of pigs. Vaccination can be very effective but the schedule must be adapted to the farm and production system. However, even the best vaccine cannot eradicate the infection, and additional antibiotic treatments are often necessary. Mycoplasma pathogens show particular sensitivity to the pleuromutilin antibiotics (tiamulin, valnemulin). The use of these therapeutics prophylactically or in strategic medication programmes has to be adapted to the specific disease situation on the farm.

References
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STIPKOVITS L. et al., 1992. Comparative studies of the antimicrobial sensitivity of mycoplasmas and bacteria isolated from the respiratory tract of swine. Proceedings of the 12th IPVS Congress, The Hague, Holland, 318. STIPKOVITS L. et al., 2004. Sensitivity testing of Mycoplasma pathogens to antimicrobials. Proc. 18th IPVS Congress, Hamburg, Germany Vol.2 p.518 ZHOU C. and WU CC. 2006. In vitro activity of florfenicol against Mycoplasma hyopneumoniae and Mycoplasma hyorhinis. Proceedings of the 19th IPVS Congress, Copenhagen, Denmark, 467.

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