By Ulrich Klein, Dr.med.vet, International Technical Services Manager, Novartis Animal Health, Inc., Basel Switzerland
ulrich.klein@ah.novartis.com

Introduction
 

Swine dysentery is a contagious mucohaemorrhagic diarrheal disease found in all major pig-producing countries, including those in the European Union. It is characterized by extensive inflammation and necrosis of the large intestine’s epithelial surface (Meyer 1978, Harris et al. 1999). Pigs of all ages may be affected, but swine dysentery is most often seen in growers and finishers.
 

Although it is considered a relatively common disease of pigs, little is known about the true prevalence of swine dysentery. Recent surveys suggest the prevalence ranges from 10% to 33% in herds around the world (Hampson IPVS 2000). There are conjectures that the incidence of clinical swine dysentery increased following the withdrawal of antibiotic growth promoters in European piggeries.
 

Information about risk factors for swine dysentery also is lacking. The few reports that are available indicate that overheating, chilling, co-mingling of carrier and naïve pigs, the use of slurry systems and herd size may contribute to swine dysentery outbreaks.
 

It is well known that swine dysentery has serious consequences. The disease results in depressed growth, impaired feed conversion and increased mortality (Harris et al. 1999, Hampson et al. 1997). Swine dysentery obviously can be a very costly disease and its control has presented a formidable challenge to pork producers around the globe.
 

Cause, Spread and Severity
 

The pathogen that causes swine dysentery was first identified and characterized in 1971 (Taylor and Alexander 1971). It was named Treponema hyodysenteriae (Glock and Harris 1972). Based on the results of gene analysis, this anaerobic spirochaete has since been renamed Brachyspira hyodysenteriae (Ochiai et al. 1997)
 

It is well known that the severity of swine dysentery varies in affected herds. When swine dysentery first enters a herd, there is low exposure to infectious doses and often only one or two pigs develop the disease. As infectious feces accumulate, however, the disease spreads to remaining herd members. The rate of spread depends on the type of contact with the infected material.
 

Once the infection becomes endemic within a piggery, the disease spectrum can vary from mild, transient or inapparent to severe and even fatal. Medication strategies in individual piggeries may mask clinical signs.
 

Whether or not obvious disease is present, B. hyodysenteriae may persist in infected pigs (up to 90 days after infection), in other reservoir hosts such as mice or in the environment. All these sources carry the potential of transmitting the disease between herds. In addition, B. hyodysenteriae can survive in pig feces for up to 48 days under certain conditions and in water up to 60 days (Chia and Taylor 1978). It is killed by drying and disinfection.
 

Currently, swine dysentery is prevented by the administration of medication at therapeutic levels. There is no vaccine against swine dysentery registered for use anywhere in the world.
 

Antimicrobial Sensitivity of B. hyodysenteriae
 

The sensitivity of B. hyodysenteriae strains to chemotherapeutic drugs have been studied by many authors (Molnar 1996, Moller 1996, Cizek et al. 1998, Aitken et al 1999, Karlsson & Franklin 2000). B. hyodysenteriae has demonstrated sensitivity primarily to three groups of antimicrobial drugs: 1) pleuromutilins, which include valnemulin and tiamulin, 2) lincosamides and 3) macrolides. Other substances with an effect on enteric spirochaetes, such as carbodox and olaquindox, are not licensed for use in the EU.
 

At one time, B. hyodysenteriae was uniformly sensitive to the antimicrobials used to treat swine dysentery. However, over the last few years, the organism has become less sensitive to some therapeutics.
 

For example, widespread resistance of B. hyodysenteriae to tylosin has been reported in several countries (Molnar 1996, Buller 1994, Ronne 1990, Hommez 1998). Isolates with lower sensitivity to lincomycin and tiamulin have been recovered from pigs in several European countries (Molnar 1996, Gresham 1998), and a genetic basis for macrolide and lincosamide resistance in B. hyodysenteriae has been described (Karlsson 1999, 2000).
 
 

In Vitro Results
 

Recently obtained data from in vitro studies indicate that B. hyodysenteriae isolates are highly susceptible to pleuromutilins, particularly valnemulin, Econor’s active ingredient (Table1).
 

In addition, most strains that show resistance to macrolides (tylosin) and lincosamides (lincomycin) are sensitive to valnemulin, a finding that demonstrates there is no development of cross-resistance.
 

Table 1: Minimum Inhibitory Concentrations (MICs mcg/ml) of different antimicrobials for field isolates of B. hyodysenteriae isolated in different European countries and in Australia.
 

	Moller `96 Range (n=10)	Aitken `99 MIC 50 (n=10)	Karlsson `00 Range (n=50)	Ritzmann `00 Range (n=9)	Karlsson `02 MIC 50 (n=25)
Valnemulin (Econor)	0.0156 – 1.0	0.1	< 0.016 – 1.0	< 0.039	0.031
Tiamulin	0.125 –1.0	0.3	0.031 – 2.0	< 0.039 – 0.15	0.125
Lincomycin	64 -> 128	50	-	50	8
Tylosin	128 ->128	200	< 2.0 -> 256	-	> 256
Dimetridazole	0.5 – 64	30	-	0.62 –1.25	-

Moller (1996) found that all of 10 B.hyodysenteriae strains isolated in Denmark were highly sensitive to valnemulin. More recently, Aitken et al. (1999) tested the susceptibility of Brachyspira strains isolated in the United Kingdom. Valnemulin was the most effective of the drugs tested, with MIC50 values from 500- to 2000-fold lower than those of lincomycin and tylosin.
 

Karlsson et al. (2000) confirmed in her study that valnemulin was the most active product of the antimicrobials she tested against B. hyodysenteriae. In fact, valnemulin was even more effective than tiamulin. Depending on the isolate, MIC values for tiamulin were between 0 to 8 times higher than those for valnemulin. High resistance to tylosin was demonstrated in the study. This finding was confirmed by Taylor (1999), who found that in most cases, B. hyodysenteriae resistance to macrolides was complete.
 

B. hyodysenteriae also proved to be considerably sensitive to valnemulin in German field trials. When Ritzmann (2000) tested both in vitro and in vivo efficacy, the sensitivity of isolates to valnemulin was about 1,000 higher than to lincomycin.
 

Australian B.hyodysenteriae strains showed high sensitivity to valnemulin and less susceptibility to other antimicrobials in the study by Karlsson (2002).
 

Susceptibility testing of B. hyodysenteriae isolates in Thailand demonstrated the pronounced efficacy of valnemulin against B. hyodysenteriae (Luengyosluechakul et al. 2002). Lower MIC values were found for valnemulin (0.25 mcg/ml) in comparison to other antimicrobial agents (8 – 512 mcg/ml).
 

In conclusion, Econor has demonstrated excellent in vitro activity against B. hyodysenteriae strains isolated in several different European countries and those outside of Europe. Based on these results, it can confidently be stated that Econor is the most active agent available against B. hyodysenteriae.
 

Control of Swine Dysentery
 

In the past, control of swine dysentery was accomplished by administration of different routinely used antimicrobials. Due to reduced susceptilibity of B. hyodysenteriae isolates to some antimicrobials, however, as well as withdrawal from the market of some previously available antimicrobials, the number of therapeutic options for control of swine dysentery is diminishing. As noted before, there is no vaccine currently available for the prevention of swine dysentery.
 

As with any infectious disease, it is essential that the use of antimicrobials be based on proper diagnosis. Correct diagnosis of swine dysentery requires that the veterinarian be familiar with the symptoms of the disease and post mortem findings.
 

The clinical signs of swine dysentery include fresh blood and mucus in diarrhoeic faeces. Affected animals normally do not show fever. Post mortem findings include a large intestine with a thickened, flaccid wall and fluid contents with blood, mucus and necrotic debris.
 

Laboratory tests can be used to confirm the clinical diagnosis. These tests would include a culture from faeces and biochemical and PCR testing to distinguish B. hyodysenteriae from other spirochaetes.
 

However, the macroscopic lesions may not always be pathognomonic for a particular disease such as swine dysentery; salmonellosis, swine dysentery and porcine proliferative enteritis can easily be confused because the clinical signs and macroscopic lesions may be quite similar.
 

- Prevention
 

The efficacy of Econor against swine dysentery has been confirmed in numerous studies (Madsen et al. 1998, Burrows et al. 1996) by administration of preventive dose levels.
 

Madsen (1998), for instance, conducted trials on two farms in Denmark under typical field conditions to evaluate the efficacy of Econor by medication over a 4 week period (dose: 25ppm). The presence of swine dysentery was confirmed before the trials were initiated. There were 102 animals included in each of the treatment groups (Table 2).
 

Table 2. Results from Danish field trials show Econor prevented the development of swine dysentery.
 

	Control (untreated)	Econor (25 ppm)	Improvement (%)
Daily gain (g)	721	849	17.8
FCE*	2.52	2.24	11.1
Pigs with swine dysentery (%)	32.4	0	100
Faeces samples with spirochaetes (%)	24.5	0	100
No. of faeces samples with blood/mucus	19/37	1/1

*FCE = feed conversion efficacy
 

On both farms, swine dysentery occurred after pigs were introduced and mixed in the fattening house. Moderate to severe challenge with swine dysentery occurred on both sites.
 

Econor effectively prevented the clinical signs of swine dysentery. None of the pigs in the Econor group showed swine dysentery and their faeces were free of spirochaetes. Econor -medicated pigs gained more weight and showed substantially improved feed conversion efficacy.
 

- Treatment
 

In the United Kingdom, the efficacy of Econor for clinical cases of haemorrhagic dysentery was tested on four different farms (Wade West and Ripley 1998). Investigators administered Econor at the rate of 75 ppm for 7 days (Table3).
 

Swine dysentery was effectively treated in these trials. Spirochaete shedding was almost completely suppressed by the end of each trial. In all trials, there were significant differences in daily gain and in the number of swine dysentery cases found in treatment groups.
 

Table 3: Summary results from four field studies in the UK.
 

	Control (untreated)	Econor (75ppm)	Improvement (%)
Daily gain (g)	299	542	81
FCE*	1.83	1.5	18
Pigs with swine dysentery (%) Day 0   Day 8	39 44	38 7	84
Pigs FAT** +ive (%) B. hyodysenteriae Day 0   Day 8	44 38	39 4	89

*FCE = feed conversion efficacy
** FAT = fluorescent antibody testing
 

Pejsak et al. (2002) investigated the efficacy of pleuromutilins at a commercial Polish farm with significant swine dysentery problems affecting the units periodically for over 20 years. Due to unfavourable housing conditions, the animals also were affected by porcine respiratory disease complex (PRDC) during the fattening period.
 

Pleuromutilins were administered in a pulse medication program in the following manner and the trial results are shown in Table 4.
 

Econor 75ppm (3.75mg/kg bw)
1 to 4week old pigs for 10 days
8wk old pigs for 7 days
12 to 16wk old pigs for 5 days.
 

Tiamutin 200ppm (10mg/kg bw)
4, 8, 12, 20, 24 week old pigs for 7 days
 

Table 4. Efficacy of Econor compared to tiamutin on a Polish farm affected by swine dysentery.
 

	Control (n=436)	Econor (n=420)	Tiamutin (n=433)
Initial weight (kg)	6.14	6.21	6.37
Weight at slaughter (kg)	96.42	104.62	100.58
ADG* in g (in % to control))	582	635 (+9.1%)	607 (+4.3%)
No./% of treatments due to swine dysentery	116/36.2	1/0.31	18/5.62
No./% of treatments due to respiratory infection	107/33.4	56/17.5	61/19.06

*ADG = average daily gain
 

Substantial clinical improvement was found in animals medicated with Econor. The number of additional individual treatments due to swine dysentery was much lower in the Econor group compared to controls. Animals in the Econor group also showed improved performance and higher daily gain.
 

The excellent efficacy of Econor in this trial indicates that under field conditions, Econor may be more effective than tiamulin in the treatment of swine dysentery. The finding substantiates the experience of veterinarians who have reported that Econor is the most effective product against swine dysentery.
 

- Econor Eradication Programs
 

Successful eradication plans have been carried out in different EU countries using Econor. On one farm in Denmark, the farm had tried before but failed by using a combination of other antimicrobials. Econor eradicated swine dysentery (Table 5).
 

Table 5. Econor eradication program in Denmark.
 

	Pre-eradication	Post-eradication	Post-eradication	Improvement (%)
	1 Jul 96 to 30 Sep 96	1 Oct 96 to 31 Dec 96	1 Jan97 to 31 Mar 97
No of pigs produced/ sow /year	21.6	22.5	22.7	4.6
Mortality after weaning (%)	5.3	2.2	3.2	49
DWG* (g)	367	374	429	16.9
Cost of medicines (DKr)	11.058		2.249	80

*DWG = daily weight gain
 

Discussion
 

Pigs, which can recover from swine dysentery without antibiotic treatment, have been shown to be potential carriers of B. hyodysenteriae for several months after recovery. In addition, under certain condition, B. hyodysenteriae can survive in pig faeces for up to 48 days (Chia and Taylor, 1978).
 

In most cases, macrolide resistance is complete in B. hyodysenteriae (Taylor 1999). Therefore, only limited number of therapeutic drugs are still effective for future use. The application of a therapeutic should be based on the outcome of the in vitro tests.
 

Based on the results of numerous trials, valnemulin, the active ingredient in Econor, is in most cases the drug of choice for treatment of swine dysentery, along with good hygiene and extreme care in rearing. Econor should be used only after careful diagnosis, which will help preserve its effectiveness into the future.
 

It is essential that Econor be administered at recommended dose levels . Any reduction in the prescribed dose could result in failure.
 

Conclusion
 

Swine dysentery, a severe form of colitis due to the pathogen B. hyodysenteriae, is a serious and damaging disease of swine in countries where pigs are reared. Resistance to antimicrobials used in the past to treat swine dysentery is on the upswing, limiting the treatment options available to swine producers.
 

Numerous studies indicate that Econor, which contains valnemulin, a new-generation pleuromutilin, offers the best treatment available for the control, treatment and elimination of B. hyodysenteriae.
 

References
 

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Buller N.B. and D.J.Hampson. Antimicrobial susceptibility testing of Serpulina hyodysenteriae. Australian Veterinary Journal 1994;71:211-214.
 

Chia SP, Taylor DJ. Factors affecting the survival of Treponema hyodysenteriae in dysenteric pig faeces. Vet Rec 1978;103:68-70.
 

Cizek A, Smola J, et al. In vitro activity of six anti-dysenteric drugs on Serpulina hyodysenteriae and S.pilosicoli strains isolated in the Czech Republic. The 15 th International Pig Veterinary Society Congress. 1998
 

Gresham AC, Hunt, BW, et al. Treatment of swine dysentery – problems of antibiotic resistance and concurrent salmonellosis. Vet.Rec . 1998:143;619.
 

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