M. agalactiae in sheep. M. agalactiae, M. mycoides subsp. mycoides large colony type and M. capricolum subsp. capricolum in goats
Occurs on very continent but outbreaks and severe disease occur in the Mediterranean area and Africa. Introduction of infected animals. Direct spread by infected milk and ocular discharge to sucking young and to adults by contamination of bedding, feed, and milking machine equipment
Contagious agalactia is a disease of sheep and goats, particularly those used for milk production. M. agalactiae is the main causal agent in sheep and goats but M. agalactiae, M. mycoides subsp. mycoides large colony type and M. capricolum subsp. capricolum produce a similar if not identical clinical presentation. There is apparent variation in virulence between isolates from different countries and frequently, more than one of these agents can be isolated from the same outbreak.1-4
M. putrefaciens, first isolated from the joints of arthritic goats in California, has been isolated and implicated in some outbreaks of contagious agalactia but experimental challenge with this organism does not produce classical contagious agalactia.1M. putrefaciens can cause septicemia, pneumonia and mastitis in small ruminants that are predisposed by other diseases but it should be considered an opportunist when isolated from cases of contagious agalactia.5
Contagious agalactia is endemic in most European countries and Africa, and occurs in most other areas of the world including Asia and the Indian subcontinent, Australasia, the Middle-East and North America but with little documented occurrence in Britain or South America.1,5 The disease is endemic in most Mediterranean countries and is particularly widespread in Spain.3 An example of how it can become endemic is that it was recently reported for the first time in goats in the Canary Islands4 but is now recognized as being endemic on all islands.6
In endemic areas the disease is cyclic in occurrence with periods of outbreaks of severe disease interspersed with periods of chronic or mild disease.5
Peak rates of clinical disease occur after parturition in both the dams and their young with another peak occurring in association with the onset of machine milking after the young are removed from sucking. The mortality rate can be high (10–30%) and many adult females are culled because the udder is permanently damaged.
The organisms are present in the milk and ocular secretions of infected animals and in respiratory secretions where the pulmonary from of the disease is present. Transmission is by direct contact, aerosol transmission, ingestion and by contact with infected fomites. The young are infected through the ingestion of infection present in colostrums and milk. Infected milk can also contaminate bedding, feed7 and dairy equipment and spread occurs with machine milking.
The organisms are also resident in the ear canal of sheep and goats and transmission by ear mites is thought to occur.8-10 The common practice of transhumance and communal grazing in endemic areas also promotes transmission between herds and flocks either from direct contact or grazing over infected pastures. Illegal importation of animals from an endemically infected area to countries free of disease has also resulted in introduction of disease.11
The disease can be reproduced experimentally and reflects the natural disease with acute and chronic multifocal necrotizing mastitis, acute arthritis, conjunctivitis, and subacute enteritis. Shedding of the organism precedes the onset of clinical disease by 1 to 10 days.1,5,8,12 The experimentally produced disease is much more severe in pregnant animals.13
The relative severity of clinical disease in sheep versus goats depends on the infecting mycoplasmal and varies with region1,5 and there are breed differences in susceptibility. Septicemia and acute disease more common in young lambs and kids and lactating females with less severe disease in adult males and non-lactating non-pregnant females
There is regional variation in the virulence of isolates, or in some regional environmental factor. M. agalactiae, M. mycoides subsp. mycoides large colony type, M. capricolum subsp. capricolum and M. putrefaciens have all been isolated from goats in Australia and the USA over several decades but clinical disease in these countries associated with these organisms is extremely rare.
The classical signs of contagious agalactia include septicemia, arthritis, mastitis, conjunctivitis and localization in abscesses but these are not all consistently present in outbreaks.
In acute cases the onset is sudden with pyrexia, abrupt and complete agalactia, and unilateral or bilateral swelling of the udder with enlargement of the mammary lymph nodes and the development of multiple abscesses in the mammary gland. Induration of the udder may result in culling. In animals that survive mycoplasmal are excreted in the milk for several months8,13 and will persist in the udder to subsequent lactations.
Arthritis may be manifest by lameness or recumbency and its presence detected in the carpal and tarsal joints by the occurrence of heat and palpable joint fluid, and confirmed by aspiration and examination of joint fluid. Conjunctivitis progresses to keratitis with corneal revascularization in one or both eyes. Some cases have diarrhea.
In less acute cases, there is a long period of illness of from one to several months. Abortion may also occur and genital disease with vulvovaginitis and metritis occurs in some outbreaks.14
Herd diagnosis is possible by the isolation of the organism M. agalactiae from the bloodstream, joint fluid and mammary tissue. PCR can be used for identification.15,16
Herd diagnosis can also be made serologically by CFT which becomes positive soon after a clinical attack. There are also commercial ELISA tests available that have limitations in sensitivity and specificity but that can be used for serological diagnosis.17
Lesions are of indurative mastitis with abscessation, lymphadenopathy, arthritis and ocular disease.
Antimicrobial therapy is restricted to the reduction of the severity of the disease and mortality. The cost and practicality of therapy in many endemic areas is a consideration as is the concern that a bacteriological cure is unlikely with antimicrobials such as tetracycline. In vitro sensitivity testing of field isolates of M. agalactia found enrofloxin most effective followed by tylosin, tetracycline, lincomycin, and spectinomycin.18
High cure rates are reported with the use of lincomycin, spectinomycin, and tylosin.19
The majority of infections in healthy flocks come from introduction of carriers or contact with infected animals. Isolation from infected flocks and herds and a closed herd policy is important in the control of disease.
Where disease is restricted to a small number of flocks in a geographically isolated area slaughter of serologically or culturally positive flocks can be an effective method of control,11 but in most affected areas the disease is endemic, slaughter eradication is not an option, and control rests with immunoprophylaxis.6
However, the efficacy and duration of immunity is poor. Vaccination of sheep and goats with either an attenuated live vaccine or a killed adjuvant vaccine of M. agalactiae gives mixed results; in late pregnant ewes the former is rather too virulent, and the latter insufficiently so unless it is used in ewes before mating, when efficiency is good. Early vaccination is recommended because of the susceptibility of young animals but should not be carried out before 10 weeks of age. Extensive use of both vaccines over a period of 13 years has resulted in almost complete disappearance of the disease from Romania but live attenuated vaccines are banned in many countries.
Comparison between commercial vaccines shows that a saponized vaccine gives better results than a live, egg-cultured vaccine and saponin and phenol inactivated vaccines show better efficacy against experimental disease than do vaccines killed by heat or formalin.20 An M. agalactiae bacterin combined with a mineral oil adjuvant has given good results when three doses are given before, and one dose after each parturition, and the herd is kept isolated.3 Intramammary vaccination provides the highest level of antibody.21
Autogenous vaccines prepared from milk brain and mammary gland homogenates from infected sheep have been used for many years in parts of Europe but have been linked to outbreaks of scrapie.22
In infected herds, milking-time hygiene is important in limiting the spread of disease.
Stalheim OHV. Mycoplasmal respiratory disease of ruminants: a review and update. J Am Vet Med Assoc. 1983;182:403-406.
Bergonier D, Berthelot X, Poumarat F. Contagious agalactia of small ruminants: current knowledge concerning epidemiology, diagnosis and control. Rev Sci Tech Off Int Epiz. 1997;16:848-873.
Egwu GO, Ball HJ, Roderiquez F, Fernadez A. Mycoplasma capricolum subspecies capricolum, Mycoplasma mycoides subspecies mycoides LC and Mycoplasma mycoides subspecies capri in ‘agalactia syndrome’ of sheep and goats. Vet Bull. 2000;70:391-402.
1 Egwu GO, et al. Vet Bull. 2000;70:391.
2 Swanepoel R, et al. Vet Rec. 1977;101:446.
3 Vizcaino LL, et al. Vet Rec. 1995;137:266.
4 Real F, et al. Vet Rec. 1994;135:15.
5 Bergonier D, et al. Rev Sci Tech Off Int Epizoot. 1997;16:848.
6 Assuncao P, et al. Vet Rec. 2004;54:684.
7 Kinde H, et al. J Vet Diag Invest. 1984;6:423.
8 DeMassa AJ, Brooks DC. Small Rum Res. 1991;4:85.
9 DeMassa AJ, et al. J Vet Diag Invest. 1992;4:101.
10 Gil MC, et al. Vet J 158:152.
11 Cokrevski S, et al. Vet Rec. 2001;148:667.
12 Hasso SA, et al. Small Rumin Res. 1994;13:79.
13 Hasso SA, et al. Small Rumin Res. 1993;10:263.
14 Gil MC, et al. J Vet Med B. 2003;50:484.
15 Tola S, et al. Vet Microbiol. 1997;54:17.
16 Nicholas RAJ. Small Rumin Res. 2002;45:145.
17 Pepin M, et al. J Vet Diag Invest. 2003;15:281.
18 Loria GR, et al. Res Vet Sci. 2003;75:3.
19 Kwantes LJ, Harby HM. Small Rumin Res. 1995;16:287.
20 Tola S, et al. Vaccine. 1999;17:2764.
Contagious caprine pleuropneumonia (CCPP) is a classical disease of goats, associated with Mycoplasma capricolum subsp. capripneumoniae and commonly confused with other serious pneumonias of goats and sheep. It presents primarily as a pleuropneumonia. The causative agent is previously known as mycoplasma strain F38.1 This organism is difficult to grow which has led to poor differentiation of the disease from that induced by M. mycoides subsp. mycoides LC and M. mycoides subsp. capri.2 There are different strains and one study established four different lineages of M. capricolum subsp. capripneumoniae based on nucleotide sequence.3 These correlated relatively well to the geographic origin of the strains.
CCPP is one of the most serious fatal diseases of goats.4 The exact distribution of the disease is unknown but clinical disease has been reported from 38 countries, mostly from Africa and Asia. However, the causative organism has only been isolated from some of these due to the difficulty in growing it and the lack of mycoplasmal laboratories in many countries.3,5,6 The disease is called Abu Nini in the Sudan.7 CCPP has many similarities clinically and at necropsy to contagious bovine pleuropneumonia, but it is not transmissible to cattle. The incubation period is 6–10 d, infectivity is high with a morbidity of 100%, and the illness is acute and severe with a case– mortality rate of 60–100%. Morbidity and mortality rates in a recent outbreak in a herd in Eritria were 90 and 65% respectively.8
This represents the response to the introduction of infection into a susceptible flock. What the epidemiological picture would be in a naturally immunized flock receiving constant invasions of infected animals is not clear.
The following description does not fit most current descriptions of the disease. It is customary in them to include other serious pneumonias of goats associated with M. mycoides var. capri and M. mycoides which may manifest with disease in additional organ systems.
The clinical findings in contagious caprine pleuropneumonia are restricted to the respiratory system and include cough, dyspnea, lagging, lying down a lot (but the animal can stand and walk), fever (40.5–41.5°C; 104.5–106°F) and in the terminal stages, mouth-breathing, tongue protrusion and frothy salivation with death in two or more days. Under adverse climatic conditions the disease may occur in a septicemic form with little clinical or postmortem evidence of pneumonia.
Antigen can be detected in lung tissue and pleural fluid by PCR.2 Serological tests used to identify carrier animals include complement fixation, ELISA and a latex agglutination test. The latter is robust, available commercially and suitable for field use.2 The F38 monoclonal antibody is used in serological tests to identify caprine F38-type isolates by the disc growth inhibition method, which will include M. agalactiae, M. capricolum subsp. capricolum and the other members of the Mycoplasma mycoides cluster associated with goats.11 A blocking ELISA using monoclonal antibodies is highly specific for CCPP.12
The more usual necropsy findings are similar to those of contagious bovine pleuropneumonia except that sequestra are not formed in the lungs. Lesions are restricted to the lungs and pleura with hepatization of parts of the lung and an increase in pleural fluid with a fibrinous pleuritis. Histologically, contagious caprine pleuropneumonia is characterized by an interstitial intralobular edema rather than a thickening of the interlobular septa seen with other mycoplasmal infections.2 The lesions may be confined to one lung.
The other pulmonary mycoplasmoses from which this disease needs to be differentiated are those associated with Mycoplasma mycoides subsp. capri, M. mycoides subsp. mycoides (large colony type) and M. capricolum.8
Treatment of cases of CCPP with tylosin tartrate 10 mg/kg BW or oxytetracycline (15 mg/kg/d) is highly successful in limiting the severity of disease. The severity of the disease is reduced but treated animals are still sources of infection.
Herd biosecurity to prevent contact with infected animals is important. Vaccination with an inactivated mycoplasma F38 vaccine induces an immune response which is effective in reducing morbidity and mortality rates, and a booster dose 1 month after the first vaccination provides additional protection.13,14 Immunity is generally short-lived. Maternal antibody may interfere with the development of immunity and kids born to does that have been vaccinated while pregnant should themselves not be vaccinated prior to 12 weeks of age.
1 Leach RH, et al. Int J System Bacteriol. 1993;43:603.
2 Nicholas RAJ. Small Rumin Res. 2002;45:145.
3 Lorenzon S, et al. Vet Microbial. 2002;85:111.
4 Msami HM, et al. Vet Rec. 2001;148:22.
5 Thiaucourt F, Bolske G. Rev Sci Tech Off Int Epiz. 1996;15:1397.
6 Houshaymi B, et al. Small Rumin Res. 2002;45:139.
7 Harbi MSMA. Vet Res Commun. 1983;6:139.
8 Houshaymi B, et al. Trop Anim Hlth Prod. 2002;34:383.
9 Harbi MS, et al. Trop Anim Hlth Prod. 1983;15:51.
10 March JB, et al. Vet Microbiol. 2002;84:29.
11 Belton D, et al. Vet Rec. 1994;134:643.
12 Thiaucourt F, et al. Vet Microbiol. 1994;41:191.
The cause is Mycoplasma bovis.1 Mycoplasma alkalescens has also been isolated from 3-week-old calves affected with polyarthritis and a group 7 mycoplasma has been recovered from a calf with polyarthritis. M. bovis may be found in calves with polyarthritis and enzootic pneumonia, which may suggest a pneumonia– arthritis syndrome. M. californicum, usually isolated only from mammary disease, has also been isolated from the joints of cattle with arthritis in Germany.2
Mycoplasma arthritis of cattle has been reported in a number of countries including Canada, the United States, Europe and the United Kingdom. The causal organism and its associated diseases appears to be spreading in association with animal movement and occurring in areas where it has not previously been recorded.3-5 Commonly arthritis occurs in association with respiratory disease or otitis media in calves, or mastitis in adult cattle, and isolations from arthritis are much less common than isolations from these other diseases.4,6
Coincident with the geographic spread the age and type of animal affected is also changing, or expanding. Earlier reports suggested that it occurred most commonly in young feedlot cattle usually affecting many animals a few weeks after arrival and mingling in the lot. The morbidity ranged from 20–85% and the case– mortality rate from 3–50%. In Canada, the disease has been seen commonly in young cattle (6–8 months of age) following shipment from western rangelands to eastern feedlots, which suggests that long transportation and mixing of cattle of different origins may be important epidemiological characteristics. Calves affected with arthritis commonly have necropsy evidence of mycoplasma pneumonia and it is proposed that the pneumonia precedes the development of the arthritis. Calves sucking cows with experimental mastitis due to this organism may develop mycoplasmal arthritis, and a high incidence is recorded in calves in dairy herds where mycoplasmal mastitis was occurring.
In Ireland, infection has occurred in housed adult dairy cattle, without any evidence of pneumonia, producing severe polyarthritis with a clinical incidence in 12 farms that varied from 2 to 66%.5
In calves, the feeding of unpasteurized discard milk from cows with mycoplasmal mastitis is a risk factor.7
M. bovis arthritis is normally regarded as a sequel to pneumonia or mastitis and infection in the respiratory tract or in the mammary gland is believed to lead to bacteremia and localization in joints.2,3 However, arthritis can suddenly occur in regions or countries where mycoplasmal pneumonia has been recognized for many years suggesting that a new strain with different virulence or tropism has been introduced. Also, clinical disease in individual herds commonly follows the introduction of new animals to the herd.
Adherence to host cells of isolates from different pathologies has been examined as a possible explanation for this but does not appear a determinant for differences in disease presentation.8
The intra-articular injection of M. bovis into calves causes severe fibrinosuppurative synovitis and tenosynovitis, erosion of cartilage and its replacement by polypoid granulation tissue. Erosion of the cartilage is accompanied by chronic osteomyelitis and formation of pannus tissue. Histologically, there is extensive ulceration of synovial membranes of leukocytic infiltration of the subsynovium, congestion, hyperemia and thrombosis of the subsynovial vessels. Intratracheal inoculation of the organism results in pneumonia and severe lameness, which suggests that M. bovis is involved in pneumonia–arthritis syndrome.
A combined infection of M. bovis and bovine virus diarrhea (BVD) has been found in the joints of feedlot cattle that had chronic unresponsive arthritis.9
There is stiffness of gait, lameness, inappetence, moderate fever and progressive loss of weight. Swelling of the large movable limb joints and distension of tendon sheaths, associated with fibrinous synovitis and synovial fluid effusions, are characteristic.
Both forelimbs and hind limbs can be affected and commonly involvement of the carpal joints, the fetlocks and the proximal and distal interphalangeal joints can be clinically detected. In calves, pneumonia is a common finding in the affected group.
Some affected cattle spend considerable time in recumbency, lose weight and develop decubitus ulcers, and must be destroyed. Mildly affected cases recover spontaneously over a period of several weeks but severe cases become progressively worse, may develop discharging sinuses over affected joints, and must be culled.
Culture methods for the detection of M. bovis are restricted to culture and serology but both methods are time consuming, laborious, difficult and expensive.
A DNA probe and PCR test are now available to detect the organism in milk samples10 and may be applicable to samples from joint fluid and an ELISA can be used to detect the organism in lung tissue of animals with pneumonia.11
At necropsy, the fibrinous synovitis is remarkable. There is severe thickening and edema of the synovial membranes and large quantities of fibrinopurulent synovial fluid. The tendon sheaths are similarly affected. Microscopically, large numbers of lymphocytes and plasma cells are found within the hypertrophic synovial villi. There can be multiple foci of coagulative necrosis within the joint capsule. M. bovis can often be recovered from pneumonic lungs and has been linked to pulmonary foci of coagulation necrosis.2,12,13
Immunohistochemical studies suggest that this organism may also briefly localize in the kidney and liver.12 M. bovis has been associated with pleuritis and pericarditis and has been isolated from decubital ulcers of calves.14
The disease must be differentiated from other causes of joint swelling and lameness in feedlot cattle. There are usually several animals affected in a short period of time, which serves to distinguish it from other sporadic causes of arthritis in feedlot cattle. A diagnosis of infection by M. bovis should be considered when pneumonia and arthritis and synovitis occur at about the same time. For a definitive diagnosis, joint fluid must be placed immediately into laboratory media specially prepared for Mycoplasma spp. The failure to isolate the mycoplasma from the fluid of joints which have been affected for more than 14 d does not preclude a diagnosis of mycoplasma arthritis because the organism may have been eliminated from the joint.
Treatment is usually ineffective. Several antimicrobials, including tylosin, oxytetracycline, lincomycin and oleandomycin, have been used in natural, and experimental cases and while the organism is sensitive to these antibiotics in vitro, the response in affected animals has been unsatisfactory. The antimicrobial susceptibility of M. bovis strains, cultured from cases of pneumonia, arthritis, and mastitis of cattle, measured in vitro indicate that enrofloxacin was the only one which exhibited any measurable activity.15 Administration of tylosin at the onset of clinical signs has been reported to arrest the progression of the disease.5
Effective control of the disease is not yet possible. A formalinized M. bovis vaccine provided protection against experimentally induced mycoplasmal arthritis but was unsuccessful under naturally occurring conditions. The disease usually disappears from an affected group, which suggests that herd immunity may develop.
1 Adegboye DS, et al. J Am Vet Med Assoc. 1996;209:647.
2 Hewicker-Trautwein M, et al. Vet Rec. 2002;151:699.
3 Nicholas RAJ, Ayling RD. Res Vet Sci. 2003;74:105.
4 Byrne WJ, et al. Vet Rec. 2001;148:331.
5 Henderson JP, Ball HJ. Vet Rec. 1999;145:374.
6 Ayling RD, et al. Vet Rec. 2004;155:413.
7 Butler JA, et al. J Dairy Sci. 2000;83:2285.
8 Thomas A, et al. Vet Microbiol. 2003;91:101.
9 Haines DM, et al. Can Vet J. 2001;42:857.
10 Ghaderoshi A, et al. Vet Microbiol. 1995;56:87.
11 Ball HJ, et al. Vet Rec. 1994;135:531.
12 Adegboye DS, et al. J Vet Diag Invest. 1995;7:333.
13 Rodriguez F, et al. J Comp Path. 1996;115:151.
Mycoplasma conjunctivae is a significant cause but many agents can produce clinically identical disease
Spread by contact or mediate infection from carrier animal. Usually occurs as outbreak in summer months and when conditions are dry and dusty. Disease in lambs is less severe than in adults, and most severe in weaned
A variety of organisms have been isolated from the eyes of animals affected with this disease. Some are primary pathogens and others secondary invaders. It is difficult to attribute a primary etiological cause to a single agent as all the putative causal organisms have also been isolated from the eyes of normal sheep. Many of the agents are demonstrable in the eyes of sheep in a single outbreak. The management circumstances that lead to flock outbreaks of disease with each of these agents, and the clinical syndromes that result, are not sufficiently distinct to allow the differentiation of the various etiologies on clinical or epidemiological grounds. There have been limited studies on the relative prevalence of flock outbreaks of disease associated with the various putative causes but there is a developing literature to incriminate Mycoplasma spp. as the major cause. For this edition the disease is described under this chapter heading.
Mycoplasma conjunctivae is a common isolate in outbreaks of the disease but it is not present in all affected sheep and it can also be isolated, with lesser frequency, from the eyes of clinically normal sheep.1-4 Nevertheless the disease can be reproduced experimentally by the installation of pure cultures of this organism into the eye of sheep and the disease will spread to other sheep by contact transmission.4-8 Consequently, it is believed to be a principal cause of pinkeye in sheep and goats. It has been further suggested that the inclusion bodies believed typical for rickettsial infection in ovine keratoconjunctivitis are in fact extracellular mycoplasmas.5
Other Mycoplasma spp. are frequently identified in the eyes of sheep and goats with pinkeye.1-3,5,9 M. agalactiae is considered a primary cause of an outbreak in Spain.10 M. arginini and Acholeplasma oculi have been isolated from clinical cases of contagious ophthalmia but have not been implicated as causal agents.2,11,12 Diseases reproduced by other mycoplasmas such as M. capricolum, M. mycoides subsp. mycoides can be accompanied by conjunctivitis but other manifestations predominate.
Chlamydophila pecorum (Colesiota conjunctivae) was initially incriminated as a cause of contagious ophthalmia in sheep and goats in South Africa and Australia and has also been isolated from outbreaks of keratoconjunctivitis in sheep in the United States and the United Kingdom and the disease has been reproduced experimentally.7 Involved strains are related to those associated with polyarthritis in sheep and not to those associated with abortion.5 A rickettsial agent, Rupricapra rupricapae, has been isolated from keratoconjunctivitis in chamois (R. tragis) and ibex (Capra ibex) in the French Alps.13
A number of bacteria including Branhamella (Neisseria) ovis, Staphylococcus aureus and Escherichia coli can be isolated from the eyes of animals with contagious ophthalmia and the rates of isolation from affected eyes are higher than that from normal sheep. They have not been shown capable of producing disease by experimental challenge and are considered to be secondary infections and not to have a causal role.1,5,7,9 However, they may have a significant secondary role in the disease after resistance has been reduced by the primary inciting agent.14 B. ovis is considered a cause of follicular conjunctivitis.15 Similarly Moraxella bovis which is associated with contagious keratoconjunctivitis in cattle, has no apparent causal association with the disease in sheep or goats.1,5 Listeria monocytogenes may be a primary cause of keratoconjunctivitis and iritis in sheep.
The disease in sheep is widespread in most countries. All breeds of sheep are equally affected but the disease in lambs is less severe than in adults, and recently weaned animals are most severely affected.
Source of infection is infected or carrier animals. The disease is spread indirectly by flies, long grass and dust contaminated by the tears of infected sheep, or directly by means of exhaled droplets or immediate contact.16 M. conjunctivae also infects wild small ruminant species and can transmit between domestic and wild animals.16
The prevalence is highest during the warm, summer months and when conditions are dry and dusty, and the fly population is heavy. The morbidity rate varies widely depending on seasonal conditions. It is usually about 10–15% but may be as high as 80%. Resistance to infection is reduced by concurrent disease, poor nutrition and adverse weather conditions. The disease occurs as widespread outbreaks in some years and in such circumstances may cause appreciable losses in weight gains for unexplained reasons. Outbreaks during the mating season can reduce the incidence of twinning.
In many flocks at pasture, the disease causes only minor inconvenience and weight loss by interfering with grazing for a few days, however, in some it becomes endemic. Clinical experience suggests that the incidence and the severity of the disease in an affected flock is increased by the stress, dust and close contact associated with gathering and yarding of the flock. Thus a decision to treat an outbreak can be associated with an apparent exacerbation of clinical disease.
Rapid onset of acute inflammation of the conjunctiva is followed by hyperemia of the sclera, pannus, and opacity of the cornea.
Clinical findings are similar with all agents associated with the disease. There is conjunctivitis with lacrimation and blepharospasm followed by keratitis with cloudiness of the cornea and some increase in vascularity. There is profuse lacrimation and initial signs in the flock may be a brown discoloration below the eye associated with dust accumulation on lacrimal discharges.
Corneal opacity is initially most pronounced at the dorsal corneal–scleral junction and is followed by vascularization to produce a horizontal zone of opacity associated with an area of vertical-oriented vascularization in the upper area of the eye. In severe cases, the whole cornea is affected and there may be corneal ulceration. In some outbreaks there is severe corneal edema in affected sheep.
In most sheep in flocks experiencing an outbreak, the disease is mild providing there are no complicating circumstances; the initial watery discharge from the eye becomes purulent but recovery commences in 3–4 d and is complete at about 20 d. In some animals the cloudiness of the cornea may persist for several weeks or even permanently. Local ulceration of the cornea may cause collapse of the eyeball. One or both eyes may be affected but many sheep have both eyes affected in outbreaks and spread through the flock is rapid.
Conjunctivitis is followed by the development of granular lesions of follicular conjunctivitis on the palpebral conjunctiva and third eyelid, which are thought by some to be specific for infections involving B. ovis.
In goats, the disease is milder with little apparent ophthalmia or keratitis. A more severe keratoconjunctivitis than that associated with M. conjunctivae, and manifest with corneal edema, occurs in some outbreaks in goats but its cause has not been established.11 All age groups are affected and although the morbidity is usually 12–20%, it may reach 50%. Direct contact between animals appears to be necessary for spread of the infection, but the disease has not been transmitted experimentally. Conjunctivitis, opacity, vascularization and sometimes ulceration of the cornea are accompanied by an ocular discharge and blepharospasm. In some goats there is severe corneal edema with intracorneal edema accumulating to a degree to produce corneal vesicles. In mildly affected goats, recovery begins in 4–7 d but in severe cases, healing may not be complete for 2–4 weeks or longer.
Scrapings can be taken for exfoliative cytology from the palpebral conjunctiva following topical anesthesia. Samples should be collected from early clinical cases. Mycoplasma, Branhamella and Chlamydia have characteristic morphology and can be demonstrated in Giemsa-stained smears or by immunofluorescent staining.12 Samples can also be submitted for cultural identification and paired serum samples can be submitted for examination for antibodies to Chlamydia. The determination of the etiological agent currently has limited significance to the subsequent approach to the control of the disease and is largely academic. However PCR can be used to detect M. conjunctivae3,17 and PCR can be a better method of detection of infection than culture.17 Indirect ELISA has been used to detect infected sheep flocks.18
A decision for treatment needs to be taken with consideration of the adverse effects on the disease of the associated movement and close yarding of the flock. Repeated treatments of sheep pastured under extensive grazing are impractical and spontaneous recovery will occur within 3 weeks. Consequently, in extensive grazing conditions a decision for no treatment is often made.
A single intramuscular injection of long-acting tetracycline at 20 mg/kg halts further development of clinical conjunctivitis when given as clinical signs develop and results in rapid clinical cure in animals affected with keratoconjunctivitis produced by M. conjunctivae. However, neither parenteral or topical antibiotic treatment eliminates infection and relapse in individual animals and recurrence of outbreaks in flocks is common.19-21 Where the etiology is not known and treatment is deemed desirable, tetracyclines administered either topically or parenterally or topical treatment with cloxacillin ophthalmic ointment have been shown to be of benefit.19,22
1 ter Laak EA, et al. Vet Q. 1988;10:217.
2 Akerstedt J, Hofshagen M. Acta Vet Scand. 2004;45:19.
3 Motha MXJ, et al. NZ. Vet J. 2003;51:186.
4 van Halderen A, et al. Onderstepoort J Vet Res. 1994;61:231.
5 Egwu GO. Vet Bull. 1991;61:547.
6 Surman PG. Aust J Biol Sci. 1968;21:447.
7 Wilesmore AJ, et al. Vet Rec. 1990;127:229.
8 Dagnall GJR. Br Vet J. 1993;149:429.
9 Bankemper KW, et al. J Vet Diag Invest. 1990;2:76.
10 Rodriguez JL, et al. Small Ruminant Res. 1996;22:93.
11 Busch TJ, Belton DR. Aust Vet J. 1989;36:153.
12 Dagnall GJR. Vet Rec. 1994;135:127.
13 Bijlenda G, et al. Sci Vet Med Comp. 1983;85:267.
14 Egwu GO, Faull WB. Small Ruminant Res. 1993;12:171.
15 Dagnall GJR. Br Vet J. 1994;150:65.
16 Belloy L, et al. Appl Environ Microbiol. 2003;69:1923.
17 Baker SE, et al. Vet Rec. 2001;148:240.
18 Belloy L, et al. Vet Res. 2001;32:155.
19 Hosie BO. Vet Ann. 1990:93.
20 Hosie BD, Greig A. Aust Vet J. 1995;151:83.
Mycoplasma hyopneumoniae (once also called Mycoplasma suipneumoniae) is the primary causative agent and Pasteurella multocida is commonly a secondary invader.1 M. hyopneumoniae (M.hyo) inhabits the respiratory tract of pigs, appears to be host specific and survives in the environment for only a very short period of time. The disease has been reproduced with pure cultures and the organism can be demonstrated directly or indirectly in pigs with enzootic pneumonia worldwide. The isolation of M.hyo is complicated by the presence of other mycoplasmas in the upper respiratory tract of pigs including M. hyopharyngis,2 M. hyorhinis, M. sualvi, and Acholeplasma species. The agent is also a significant contributor to the Porcine Respiratory Disease Complex (PRDC) together with PRRS, PCV2, SIV, and secondary bacterial agents.3 This complex is characterized by slow growth, decreased food conversion efficiency, anorexia, fever, cough and dyspnea in grow/finish pigs typically around 16–22 weeks of age.
Enzootic pneumonia occurs in pigs worldwide and the incidence is high in intensive pig rearing enterprises. Lesions may be present in 40–80% of the lungs of pigs at abattoirs. The peak incidence of pneumonia occurs at 16–20 weeks of age, which is likely related to increased stocking density. In northern climates, the incidence of clinical disease and prevalence of lesions at slaughter are higher in the summer months.4 The prevalence of lung lesions is often highest in pigs slaughtered in the winter months compared to autumn-slaughtered pigs.5 In a survey of the gross lung lesions of 855 slaughter weight pigs from nine selected herds in Norway, pneumonic or pleuritic lesions were found in 84% of the lungs, ranging from 37% in the least affected herd to 97% in the one most affected.6 Bronchopneumonia suggestive of a primary M.hyo infection was present in 70% of the lungs, ranging from 9–82% in the individual herds. The amount of bronchopneumonic lesions in individual lungs ranged from 0–69%, with an average of 7.8%. A 2002 survey in the USA showed that 82.3% of finishing sites had at least one animal positive on antibody testing and 94.4% of breeding sites.7 Seroprevalences were higher in the clinically affected herds and most of the pigs were infected with M.hyo at a younger age.8
In infected herds, the morbidity rate is high during the growing period but the case–fatality rate is low. There is however an increase in the number of treatments of sick pigs in comparison with herds free of the disease and secondary bacterial pneumonia can be a significant cause of mortality in the weaning-to-market period. The morbidity rate falls markedly with increasing age and there is a much lower incidence of pneumonic lesions in sows, even though they may still harbor the organism. However, when enzootic pneumonia gains entry into a herd which has been previously free of the disease, all ages of pigs are affected and mortality, even in adults, can occur.
The organism is an inhabitant of the respiratory tract of pigs and transmission occurs by direct pig-to-pig contact. This is the main source of transmission. Airborne transmission9 and fomites are less important sources of transmission. Mycoplasma can be transmitted over 1, 75, and 150 meters.10 Airborne transmission was suggested on 80% of farms where acute respiratory disease was present. No airborne organisms were found on farms without acute respiratory disease. There is no other known host for the organism although infection and breakdown of closed pneumonia-free herds has occurred without any pig introductions. The number of organisms required for infection is very small and the possibility of wind-borne infection has been suggested. Transmission is by the respiratory route and in infected herds occurs primarily from the sow to the suckling piglets. In a study of shedding of M.hyo in different parities: gilts were 73% positive, parity 2–4 sows were 42% positive, parity 6–7 sows 50% positive and parity 8–11 sows were 6% positive.11 Generally, the nursery is considered the area where transmission occurs12 and infection spreads slowly.13 Within pen transmission measured by PCR is very slow.14 Animals can be PCR positive and not infectious for long periods of time and then can become very infectious. There is therefore a nonlinear excretion of M.hyo.14 It is thought that one infected nursery pig will infect on average one littermate.15 Boars can also infect sows when they are kept together in service areas but in these areas the disease spreads slowly.16 The disease is also transmitted and exacerbated during the grouping and stress of pigs that occurs at weaning. The highest clinical and pathological incidence occurs in the postweaning and growing period and in most herds this is maintained through the growing period to market age. The start of finishing is the critical point.17 Direct exposure (nose-to-nose contact) of pigs at 9–11 weeks of age to seropositive gilts results in seroconversion to the organism by 21 d and is most frequent by about 11 weeks after exposure.18 The presence of gross lesions of pneumonia correlated with the seroconversion.
Frequent coughing by infected, intensively reared pigs suggests that repeated aerosol exposure occurs and is an important natural mode of transmission of respiratory pathogens. There is general agreement that management and environmental conditions considerably influence the severity of the disease.
The reinfection of enzootic pneumonia-free herds, recurrences or so-called breakdowns, occurs at a rate of about 3% of herds every 6 months. In a study of swine herds which had participated in the Pig Health Control Association Scheme in the United Kingdom, the close proximity of the uninfected herds to infected herds appeared to be the most important risk factor which could explain the introduction of the infection. The size of the herd, the density of the pig population in the area, the distance to the next road regularly used for transportation of pigs and differences in topography were risk factors associated with reinfection.19 There was little evidence to indicate that unexplained breakdowns occurred in association with long-term latent infection in other herds from which animals had been imported. Clinical signs of enzootic pneumonia in these herds commonly did not occur for several months after the introduction of infected pigs.
M. hyopneumoniae was not transmitted during a 20-week period when personnel weekly contacted susceptible pigs in a naïve herd after they had been in contact with pigs in an infected herd.20
The prevalence, incidence and severity of pneumonia in swine herds are determined by interactions among infectious agents, the host, the environment and management practices. This being said a large survey of the seroprevalence of M.hyo in 50 finishing herds showed21 that there were no risk indicators. Each farm is an individual one with the farm itself exerting a great effect.22
Several factors such as breed, age, presence of diarrhea, the prevalence of atrophic rhinitis, birth weight, weaning weight, have been examined as animal risk factors. In some herds, the risk of coughing and pneumonic lesions increased with increasing age of pigs within a herd. In a survey of two different groups of pigs slaughtered at different ages, the age-specific prevalence of pneumonic lesions was 2.7% in pigs less than 16 weeks of age at slaughter, but increased rapidly when pigs were between 16 and 22 weeks of age at slaughter.23 Infection at an early age has a greater effect than infection later in life. Pigs coughing by 14 weeks of age were, on average, 6.2–6.9 kg lighter than those with onset of disease near market age.24 The highest seroconversion rate occurs between 3–4 months of age.25 In a recent experimental infection 77.7% of the infected animals were still positive 185 days later26 and 100% of the naturally infected animals were still infected at the same time. There may be selective differences in the colonization rates between litters.27 There may also be a sex effect on colonization as well.27
Atrophic rhinitis may also be present along with enzootic pneumonia and the two diseases in combination may have a greater economic effect than either disease alone. When outbreaks of respiratory disease in pigs occur, they are frequently the result of complex interactions between many agents. The importance of M.hyo is not only its effect as a primary pathogen but also its ability to act synergistically with other infecting agents to produce significant respiratory disease. M. hyopneumoniae causes a mild pneumonia, whereas P. multocida is not pathogenic alone but aggravates the pneumonia initiated by the former pathogen. The epidemiological associations between M. hyo and Actinobacillus pleuropneumoniae antibody titers and lung lesions in pigs at slaughter have been examined.28 Only titers to the mycoplasma pneumonia were associated with lesions.28
Pigs which recover from experimentally induced enzootic pneumonia are resistant to subsequent challenge. The nature of the immunity, whether serum or local antibody-mediated, T-cell mediated, or a combination of these factors, is not clear. Based on lymphocyte transformation tests of experimentally infected pigs, it is possible that cell-mediated immunity correlates with protective immunity. The median half-life of passively acquired antibodies to M.hyo is 16 d, the persistence of antibodies is related to the initial antibody concentration, and antibodies waned by 30–63 d after birth depending on initial concentration.29 It has been detected as late as 155 days of age.30 The titer of maternal antibodies is a major concern when pigs are vaccinated. The age of the piglet vaccinated is not the key factor.31 The level of the sow’s antibodies approximately 4 weeks prepartum are at their highest and similar to the levels in colostrums.32 Immunity is not conferred through colostral immunoglobulins and thus piglets born from immune dams are susceptible to infection and clinical disease. No significant correlations have been found between the colostral antibody levels and the colonization status of the sows.33 The level of immunoglobulins to M.hyo can be used to monitor infection in the herd.34-36 Pigs usually seroconvert to APP and then M.hyo.37
Pigs raised under unfavorable conditions develop pneumonic lesions more frequently than pigs raised under better conditions, regardless of their immune status.25 Pigs vaccinated with inactivated M. hyo organisms develop both a cell-mediated and humoral immune response, but they are not protected from challenge exposure by natural infection. Local immunity, particularly secretory IgA, is considered to be important in protection against mycoplasma infection. M. hyopneumoniae may suppress alveolar macrophage function, which may predispose the lung to secondary infection. The organism is very clever in evading the immune response probably by changing the nature of the immune response to one that is less effective. To do this it causes the production of cytokines IL-1 alpha and beta, IL-6, and TNF alpha by macrophages and monocytes and induces local inflammation.38 This is essentially moving the immune response from a TH1 type response to a T-helper type 2 response.39
M. hyopneumoniae adheres to the tracheal and bronchial mucosae and causes an extensive loss of cilia.40 An evaluation of the virulence factors of M.hyo field isolates has been made.41 The extent of the lesions produced may be influenced by other contributing factors to account for the variations in severity of lesions. Concurrent infection with lungworm, migrating ascarids and an adenovirus has resulted in lesions of greater severity and secondary invasion of pneumonic lesions by pasteurellae, streptococci, mycoplasmas and Bordetella bronchiseptica; Klebsiella pneumoniae is very common and largely influences the outcome of the disease in individual pigs. In some abattoir surveys of lungs, P. multocida can be cultured from 16% of normal lungs and from 55% of lungs with lesions resembling those of enzootic pneumonia. P. multocida and Haemophilus spp. may also be found in conjunction with M.hyo in the lungs of slaughter weight swine affected with pneumonia and examined at the abattoir. Those lungs with both M.hyo and P. multocida had the most macroscopic pneumonia and those lungs with either of the agents alone had much less pneumonia. M. hyopneumoniae renders the lungs susceptible to P. multocida colonization and infection.1
Along with M.hyo, other mycoplasma species such as M. hyorhinis, Acholeplasma granularum and Acholeplasma laidlawii have been isolated from the lungs of pigs at slaughter, but their significance is unclear. M. hyopneumoniae and Mycoplasma hyorhinis have been isolated from 30% and 50% of pneumonic lungs, respectively, from pigs examined at slaughter. M. hyopneumoniae was also isolated from 12% of lungs with no gross lesions of pneumonia. In a survey in Norway, M.hyo, P. multocida and M. hyorhinis were detected in 83%, 43%, and 37% of the pneumonic lungs respectively.42 Most of the macroscopic pneumonia – up to 25% – occurred in lungs with all three pathogens. M. flocculare was the most frequently isolated organism in the non-pneumonic lungs.
Mycoplasma hyopneumoniae potentiates the severity of PCV2 associated lung and lymphoid lesions, increases the amount and perhaps the presence of PCV2 antigen. It also increases the incidence of PMWS in pigs.43
Several environmental and management factors are associated with a high prevalence of pneumonic lesions at slaughter. They include continuous vs all-in/all-out production, open herds, large temperature fluctuations, semisolid pen partitions, and large numbers of pigs in a common air space. These factors may operate individually or in combination synergistically. Housing pigs in a clean, isolated, disease free and low stress environment positively influences the health of pigs.44
The primary and secondary pathogens of the disease produce their most detrimental economic effects and the highest level of morbidity and mortality during the finishing period when the economics of production necessitate indoor housing and intensification.45
Four main groups of environmental factors which contribute to high levels of clinical disease and lesions at slaughter include:
Meterological factors include wide fluctuations in the temperature indoors, wide variations in relative humidity, irregular ventilation rates and winter housing. However, experimentally, elevated concentrations of ammonia and fluctuating ambient temperature did not influence the severity of the pneumonia nor its effect growth rate.46
Population factors which contribute to an increased prevalence of pneumonia are increasing herd size, increased population density and decreased air space and floor space per pig. All management practices influence the microclimate, and the quality of housing and management influence the incidence of pneumonic lesions at slaughter. Larger-than-average swine farms milling their own feed and with characteristics of modern buildings (mechanized inlets, slatted floors) and in close proximity to other farms tend to have a higher risk of enzootic pneumonia.47 Extensively housed pigs with above-average pen space and air volume have a reduced prevalence of enzootic pneumonia lesions.48
Management factors associated with enzootic pneumonia include family farms which feed pigs on the floor47,48 and feeder barns which obtain pigs from multiple sources compared to those with good facilities and where the pigs originate directly from breeding units.45 The disease is a particular problem in continuous-flow herds. In pigs reared in all-in all-out groups in the farrowing house, nursery, and growing-finishing unit, any mycoplasmas transmitted from sows to pigs or between pigs do not necessarily result in clinical signs or lesions of pneumonia. Pigs reared in all-in all-out systems do not have lesions or minimal lesions at slaughter and gained at a faster rate than littermate pigs reared in a continuous system.46
In small herds, the factors commonly associated with a high prevalence of enzootic pneumonia were larger numbers of pigs per pen section, larger group sizes and drafty farrowing and weaner accommodation.
Airborne pollution in pig houses is thought to contribute to an increased incidence of clinical disease and prevalence of lesions at slaughter but this has not been well documented. Toxic levels of ammonia, high concentrations of aerial dust, and high colony counts of aerial bacteria may contribute to an increased incidence and prevalence of pneumonia but these factors have not been quantified and are commonly based on subjective evaluations by the observer. A large study of 960 pigs has shown that there are no influences of ammonia or dust on the respiratory health of pigs.49 Environmental air contaminants such as dust, ammonia, carbon dioxide and microbes in swine barns measured over a period of 12 months were associated with lesions of pneumonia and pleuritis at slaughter.
In large herds, factors associated with a high prevalence were higher pen stocking rate and air space stocking rate, and a trend toward higher atmospheric ammonia levels in the summer months. The trend to increased herd size has not been accompanied by the satisfactory control of pneumonia.
A computer-based guide can indicate how the prevalence of the disease can be influenced by the combined effect of risk factors.50 The expected prevalence is estimated by consideration of 11 risk factors which include the following:
| 1. | Number of pigs in the same room |
| 2/3. | All-in/all-out vs continuous flow of pigs |
| 4. | Type of partitions separating adjacent pens |
| 5/6. | Presence or absence of diarrhea as a clinical problem |
| 7/8. | Liquid vs solid manure disposal |
| 9. | Ascarid control efficiency |
| 10/11. | Presence or absence of active |
| Aujeszky’s disease. |
The temperature and humidity influence the penetration into the lungs of both primary and secondary pathogens by influencing the size of infected aerosol particles and the protective mechanism in the respiratory tract. Temperature and humidity also influence the sedimentation of infected particles in the air, and the ventilation and stocking density. Pigs kept at high stocking densities and subjected to environmental temperature fluctuations, cold drafty conditions and poor nutrition are more likely to suffer greater adverse effects from this disease.
In annual surveys completed by the American Association of Swine Practitioners, pneumonia consistently ranks as the most economically important disease in finishing pigs.51 The prime importance of enzootic pneumonia is in its economic effects on pig rearing. The disease adversely affects feed conversion efficiency and daily rate of gain under certain circumstances. However, the magnitude of these effects depends on the conditions in which the pigs are reared and has been a subject of much controversy. The complexity of pneumonia and its interactions with the environment make measuring the effect of pneumonia on performance very difficult.51
An accurate assessment of the biological and economic effects of enzootic pneumonia has been difficult because of the difficulty of conducting a controlled experiment in which pigs of equivalent genetic merit, both free of the disease and infected, are raised in an identical manner. In addition, studies on the association between performance parameters and the severity of lesions of the lungs have yielded widely variable results dependent on the management and environmental conditions and the different research design and techniques used. In general, there is a proportional relationship between severity of pneumonia and depression of performance51 but in other observations, this relationship was not found.52 Where pigs are raised under good management, infection of herds previously free of the disease has resulted in no adverse economic effect other than during the initial period of acute infection in the herd. However, in other situations adverse economic effects are associated with the disease. One study estimated a reduction of feed conversion efficiency as high as 22% and although the effect of the disease is probably not this severe in most piggeries, a significant economic reduction can occur even under good management conditions.53
Because there is no universally accepted method of measuring the extent or prevalence of pneumonia in pigs at slaughter, the results of studies of correlations between the lesions and performance have been difficult to compare. In general, the economic loss associated with respiratory disease ranges from a 2–25% reduction in average daily gains. Some methods have been compared and the most informative procedure is to assess the percentage of lung involved and calculate a mean value for the herd sample. The relationship between the weight of pneumonic lesions from pigs at slaughter and their performance indicated that within a range between 3.32 and 74.5% for the weight of a pneumonic lung, a 10% increase in the weight of pneumonic lung was associated with a decrease in mean daily gain of 31.4 g and a 13.2 d increase to slaughter at 104 kg liveweight.54 There is a high correlation between rapid gross lung scores and detailed examination, which indicates that lungs can be visually scored accurately as they pass on a slaughter line.55 On average, mean daily gain decreases from 23–37 g for every 10% of the lung affected by pneumonia.56 However, the rapid subjective scoring of the lungs, adjusted for lung proportions, is considered adequate for estimating naturally occurring pneumonia and just as informative as detailed dissection of the lungs.57
Because the prevalence of pneumonia peaks at about 60–65 kg BW and then declines steadily to a very low level in pigs that are 125 kg or more, the age and weight at slaughter must be considered when evaluating the effects of the lesions on performance and when comparing results between different observations. Weight losses are more substantial in pigs affected early in life.18 In some studies, lung lesion scores detected at slaughter did not significantly correlate to growth indicators during any season.52 The gross lesions of mycoplasmal pneumonia heal over a 2-month period, which may explain why significant correlations are not found between growth indicators and lung lesions scores.52 The effects of the lesions on mean daily gains over an entire growth period may vary from one study to another because of the different times during growth when the lesions exerted their effects and in part to compensatory regrowth following recovery from the lesions.58,59 Radiographic examination of the lungs of pigs from 21–150 d of age, and gross examination of the lungs at slaughter revealed that lesions progress and regress dynamically throughout the life of the animals and examination at slaughter is an inadequate indicator of lifetime pneumonia.60
Little is as yet known about the virulence factors of M.hyo. A wide variety of proteins are produced. Mycoplasmas have the smallest genomes of organisms capable of separate existence. This genome encodes for several immunogenic proteins including a cytosolic protein p36 (which may have lactic dehydrogenase activity), membrane proteins p46, p65, and p74 (can produce neutralizing antibodies) and an adhesin p97.61 The p97 adhesin mediates adherence of M.hyo to swine cilia.62 An adhesin-like protein (p110) composed of a p54 and 2 p28 units has also been found.63 Attachment is a complex process involving many gene products. A recent study of the total protein profile, glycoprotein profile and size differences in the amplified PCR product of p97 adhesin genes suggests that there is an intraspecies variation in the M.hyo population in the USA.64
The mycoplasma penetrate the mucus layer and attach to cilia. They appear only to attach to the cilia.65,66 They release calcium++ ions from the endoplasmic reticulum of the ciliated cells. As a result there is a clumping and a loss of cilia and excess production of mucus by goblet cells. As a result there is a dysfunction of mucociliary clearance. The secondary bacteria attach to the damaged epithelium.
In experimental infections of tracheal explants with M.hyo it was shown that IL-10 was produced, and this was a possible mechanism for the enhancement of the duration and severity of pneumonia with PRRSv and a mechanism to modulate the immune response.67
The experimental inoculation of the J strain of M.hyo into piglets causes gross pneumonic lesions which are detectable 7–10 d later. Moderately extensive pneumonia is present 6 weeks after inoculation, progressive recovery can be observed after 10 weeks and residual lung lesions are detectable in a few pigs up to 37 weeks after inoculation.
M. hyopneumoniae causes peribronchiolar lymphoreticular hyperplasia and mononuclear accumulation in the lamina propria, which causes obliteration of the bronchial lumina. There is also perivascular lymphoid hyperplasia. The bronchial mucous glands undergo hypertrophy; there are increased numbers of polymorphonuclear cells in the bronchial lumina and macrophages in the alveoli. Lymphocytes, together with plasma cells and macrophages are responsible for the increase in the thickness of the interlobular septa as the disease progresses. The hyperplastic BALT (bronchial and bronchiolar associated lymphoid tissue) in enzootic pneumonia cases consisted of macrophages, dendritic cells, T and B lymphocytes, and IgG+ and IgA+ cells. In these aggregates CD4+ predominated over CD8+ cells.68 The cells in the BALT released IL-2, IL-4 TNF alpha and to a lesser extent IL-1 alpha and beta. IL-1 alpha and TNF alpha were also released in bronchoalveolar lavage fluids and IL-6 and IL-8 were found in the mononuclear cells of the alveolar septa.68,69
Hyperplasia of Type II alveolar epithelial cells is progressive as the disease becomes worse. Affected pigs cough persistently, show labored respiration and reduced exercise tolerance. The lesions are similar to those of chronic bronchitis. After infection, M.hyo multiplies in tracheal and bronchial mucosae, adheres to the ciliated cells and causes a cytopathic effect and exfoliation of epithelial cells.70 There is a significant increase in the gland/wall ratio and a decrease in the ratio of respiratory to expiratory resistance.45
The effects of this chronic pulmonary lesion have been the subject of considerable investigation. It is thought that the presence of mycoplasmal lesions uncomplicated by secondary bacterial infections has minimal effect on the production of the pig if the environmental conditions are suitable. The lesions will heal and any loss in production from the initial infection will be regained by compensatory regrowth. Severe lesions or those accompanied by secondary bacterial bronchopneumonia and pleuritis will usually cause a significant decrease in average daily gain and feed efficiency. Secondary infection with Pasteurella spp. results in acute episodes of toxemic bronchopneumonia and pleuritis. Dual infections are usually more severe than single infections. For example SIV and M.hyo together are more severe.71
The pulmonary and hematological changes in experimental M.hyo pneumonia cause no significant changes in heart rate, respiratory rate and rectal temperature, even though at necropsy well-demarcated pulmonary lesions were present. There were several measurable changes in respiratory functions due to the atelectasis: partial occlusion of the bronchioles with exudate, localized pulmonary edema and a reduction in oxygen perfusion to the alveoli leading to a decrease in the partial pressure of oxygen in the arterial blood. There are no remarkable changes in the hematology. The body weight gains are decreased compared to the control animals.
The distribution of lesions is characteristic. They occur in the right middle lobe, the right cranial and left middle lobes, the left cranial and diaphragmatic lobes, in that order of frequency. It has been suggested that their distribution is in part due to the more commonly affected lobes.
A natural incubation period of 10–16 d is shortened to 5–12 d by experimental transmission. Two forms of the disease are described. In the relatively rare acute form, a severe outbreak may occur in a susceptible herd when the infection is first introduced. In such herds pigs of all ages are susceptible and a morbidity of 100% may be experienced. Suckling piglets as young as 10 d of age have been infected. Acute respiratory distress with or without fever is characteristic and mortality may occur. The usual course of this form of the disease within a herd is usually about 3 months after which it subsides to the more common chronic form.
The chronic form of the disease is much more common and is the pattern seen in endemically infected herds. Young piglets are usually infected when they are 3–10 weeks of age and clinical signs may be seen in suckling piglets. More commonly, the disease shows greatest clinical manifestation after weaning and in the growing period. The onset of clinical abnormality is insidious and coughing is the major manifestation. Initially only a few pigs within the group may show clinical abnormality, but then the incidence generally increases until coughing may be elicited from most pigs. It may disappear in 2–3 weeks or persist throughout the growing period. In affected herds, individual pigs may be heard to cough at any time, but coughing is most obvious at initial activity in the morning and at feeding time. Coughing may also be elicited by exercising the pigs around the pen and it occurs with greater frequency in the period immediately following the exercise. A dry or crackling, hacking cough, which is usually repetitive, is characteristic. Respiratory embarrassment is rare and there is no fever or obvious inappetence. Subsequently there is retardation of growth which varies in severity between individuals so that uneven group size is common. Some pigs affected with the chronic form of the disease may later develop acute pneumonia due to secondary invasion with pasteurellae or other organisms.
Clinical disease becomes less obvious with increasing age and is rarely detected in the sow herd, though gilts and young sows frequently harbor M.hyo.
Simultaneous occurrence of Aujesky’s disease does increase the severity of acute mycoplasmal pneumonia.72
A series of investigations has shown that PRRSv does not predispose to M.hyo infection although lesions are more severe in those pigs that both infections. M.hyo does potentiate PRRSv induced disease and lesions.73,74 There may be an association between the seroconversion to PRRS virus and the transmission of M.hyo.75
Serological tests have included the CFT (low sensitivity), indirect hemagglutination test (good for early detection as it detects IgM) and the latex agglutination test. The unsatisfactory sensitivities and specificities of these tests led to the development of ELISA systems, DNA probe technology and polymerase chain reaction to accurately diagnose enzootic pneumonia. The ELISAs detect all classes of IgG, are very sensitive, but detect the onset of seroconversion not infection.
An ELISA using a commercially available antigen (Auspharm) is highly sensitive (95.6%) and specific (98.8%) for antibodies against M. hyo when pig sera from commercial herds of known infection status were evaluated.76 An improved ELISA is also available and the two ELISAs are able to distinguish populations of gross pathology-negative pigs in endemic herds from pigs in true specific pathogen-free (SPF) herds.77 Pigs from the former group have significantly higher ELISA activity with both tests and would represent recovered or exposed non-diseased pigs, or pigs with only histological lesions in endemic herds. The ELISA is ideal for diagnostic laboratories and should obviate much of the need for culture and immunofluorescent histopathology, reducing the cost of diagnosis. The ELISA can also detect antibodies in the colostrum of sows with a high specificity.78,79 A recent study comparing three ELISAs has shown that the sensitivities of the tests were lower than previously reported especially for vaccinated animals. Animals within 21 days post-infection were also not easily detected.80 The blocking ELISA was the most sensitive. All three were highly specific. There is also a blocking ELISA against a p40 protein.81
The organism can be detected in lung tissues by culture, immunofluorescence, polymerase chain reaction and antigen-ELISA, and all have high sensitivity in the acute stages of pneumonia.82 A polymerase chain reaction (PCR)-based assay can also differentiate M. hyopneumoniae, M. flocculare, and M. hyorhinis and also detect low numbers of organisms.83-86 It can also be used on the bronchoalveolar lavage.87 The identification of the p36 and p46 protein genes has enabled them to be used in a PCR for M.hyo with a sensitivity of 86.6% and a specificity of 96.7%.88 Nested PCR is much better.89 There is a good correlation between the results of nested-PCR and histology.90 In situ hybridization shows M.hyo on the surface of the epithelial cells not in the cytoplasm with an occasional signal in the cytoplasm of the alveolar and interstitial macrophages.91
The determination of the presence or absence of enzootic pneumonia within a herd for certification purposes can be difficult and should be approached with caution. It should not be based on a single examination procedure. It requires a surveillance system which combines regular farm visits and serological, cultural and tissue examination of selected pigs and of those sent to slaughter. The herd should be examined clinically for evidence of the disease and the lungs from several shipments of pigs should be examined at the abattoir and subsequently histologically. There can be seasonal variation in the severity of lung lesions and at certain times market-age pigs may not have visible gross lesions, even though infection may be present in the herd. If doubt exists, the lungs of younger pigs, preferably clinically suspect pigs, or recently weaned pigs, should be examined after elective slaughter. The herd should also be examined for the presence of antibody to M.hyo.
Except in severe cases, the damage is confined to the cranial and middle lobes, which are clearly demarcated from the normal lung tissue. The lesions are commonly more severe in the right than in the left lung. Plum-colored or grayish areas of lobular consolidation are evident. Enlarged, edematous bronchial lymph nodes are characteristic. In acute cases, there is intense edema and congestion of the lung and frothy exudate in the bronchi. When secondary invasion occurs, pleuritis and pericarditis are common and there may be severe hepatization and congestion with a suppurative bronchopneumonia.
Evaluation of the pneumonic lesions at slaughter has been used extensively for herd health monitoring. Scoring of the lesions is typically done on both lungs (the entire pluck). To overcome the logistical problems associated with examining entire plucks during the slaughtering procedure, an alternate system based on scoring the right lung only has been investigated.92 The overall right lung relative sensitivities for the detection of catarrhal pneumonia or chronic pleuritis were 81% and 72%, respectively. It is suggested that an evaluation of the right lung pathology is a useful alternative when the purpose of the survey is to demonstrate the presence or absence of lesions, or when scoring the severity of the lesion is the objective.
The microscopic changes of enzootic pneumonia include lymphohistiocytic peribronchiolar cuffing with increased numbers of mononuclear leukocytes in the bronchial lamina propria. There is hyperplasia of the bronchiolar epithelium and filling of alveoli with macrophages, protein-rich fluid and small numbers of lymphocytes and plasma cells. Hyperplasia of Type II alveolar epithelial cells occurs as the disease progresses.
In one study, a definitive diagnosis of mycoplasmal pneumonia of swine was based on the demonstration of M.hyo in lung sections using specific antisera or successful culture of the organism. Utilizing these techniques, it was found that up to 19% of grossly normal lungs may be infected with M.hyo. Conversely, the organism could not be demonstrated in about 33% of the lungs of pigs from herds thought to be affected with mycoplasmal pneumonia, even though typical gross lesions were present. The sensitivity of these techniques may be surpassed by newer PCR methods. The organism can also be detected in formalin-fixed paraffin-embedded porcine lung by the indirect immunoperoxidase test. The results of immunofluorescence tests performed on piglets with experimentally induced pneumonia revealed that M.hyo organisms are located primarily on bronchial and bronchiolar epithelial surfaces of lungs with gross lesions of pneumonia. Fluorescence was most intense 4–6 weeks after infection and began to decrease at 8–12 weeks. This suggests a decrease in the number of M.hyo in the more advanced stages of the disease. When assessing plucks at slaughter to determine the severity of pneumonia in a group, it must be remembered that in most instances the lesions observed represent a chronic, partially resolved disease process. Therefore the clinical effects of the infection may have caused a greater degree of respiratory compromise than is apparent at slaughter.
• Touch preparations using Giemsa stained slides have been used
• Histology – formalin-fixed lung (LM, IHC). Simple histopathology may not always indicate mycoplasma infection. For example Aujesky’s disease together with P. multocida may be difficult to differentiate from M.hyo. Lesions may be characteristic but not pathognonomic.93 Indirect immunofluorescence (IF) and indirect immunoperoxidase (IHC) for M.hyo in tissues are extremely useful.94 However IF has a lack of sensitivity and IHC is time consuming and expensive
• Mycoplasmology – lung (MCULT, FAT, PCR). Isolation of M.hyo is complicated by the overgrowth that occurs from M. hyorhinis and M. flocculare. The organism is fastidious. Many animals that are culture positive do not have gross or microscopic lesions. The PCR can be used as a one step test but is not good for nasal swabs. The nested PCR can be used for these but it does tend to produce some false positives. Correct samples give a better diagnosis. Samples from lavage and tracheobronchial sites were the best for nested PCR and lung tissue and nasal swabs are not the most reliable.95
There is no effective treatment to eliminate infection with M.hyo, although the severity of the clinical disease may be reduced.
Isolates of the organism from the United States were susceptible to lincomycin-spectinomycin, tylosin and oxytetracycline.96 Isolates from the United Kingdom were susceptible to doxycycline and oxytetracycline.97 Doxycycline, a semi-synthetic tetracycline has a greater antimicrobial activity, is better absorbed orally and is more widely distributed in tissues than the first generation tetracyclines (oxytetracycline, tetracycline and chlortetracycline).
In some early studies, a mixture of tylosin tartrate at a dose of 50 mg/kg BW and tiamulin at 10 mg/kg BW orally daily for 10 d significantly reduced the pulmonary lesions associated with the experimental disease. However, the use of 60 mg, 120 mg or 180 mg of tiamulin per liter of drinking water for 10 d was not effective in suppressing the lesions of experimentally induced M.hyo pneumonia or infection in disease-free pigs.
The newer fluoroquinolones have good in vitro activity against M.hyo and exhibit superior activity to tylosin, tiamulin, oxytetracycline and gentamicin. Ciprofloxacin is particularly active against M.hyo.
Tilmicosin is particularly effective since it appears to prevent the attachment of M.hyo to the surface of the epithelial cells.98
Tetracyclines will either prevent transmission or suppress lesion formation in experimental pigs but the levels required are high and in an infected herd continuous administration would be necessary, which would be uneconomic. Treatment is generally restricted to individual pigs showing acute respiratory distress as a result of a severe infection or secondary invaders. Broad-spectrum antimicrobials are used, usually tetracyclines, but the response is only moderately good. The occurrence of severe signs within a group of pigs may necessitate treatment. Tetracyclines, tylosin or spiramycin fed at 200 mg/kg feed for 5–10 d are recommended. A combination of 300 g of oxytetracycline and 30 g of tiamulin per tonne of finished feed fed for 2–3 d/week over a 16-month period has been used to reduce the incidence of enzootic pneumonia in a large herd.99 Lung lesions were reduced, average daily gain increased, and efficiency of feed conversion increased with an overall increase in profitability. Valnemulin may prove to be effective in the treatment of enzootic pneumonia.100 There is a higher susceptibility to valnemulin and tiamulin when used in conjunction with doxycycline as a treatment.101
Tulathromycin administered as a single injection at a standard dosage of 2.5 mg/kg is effective in the treatment of swine pneumonia associated with mycoplasmosis.102
There is no evidence for resistance to lincomycin/spectinomycin, oxytetracycline, doxycycline, gentamicin, flufenicol, and tiamulin. There is evidence for some resistance to tylosin, tilmicosin, fluquinolone and enrofloxacin.103
M. hyopneumoniae infects only pigs and transmission requires close pig-to-pig contact. If transmission can be prevented it is possible to limit or even eradicate the disease from a herd. There are thus two levels at which control can be practised:
The principles of control of enzootic pneumonia include the following strategies:
• Regular inspection of the herd for clinical evidence of disease and slaughter checks of lungs
• Rigorous biosecurity of animals being introduced into the herd and control of visitors
• Provision of adequate environmental conditions including air quality, ventilation, temperature control and stocking density
• The use of the all-in all-out system of production in which groups of pigs by age or stage of production are moved through the herd from the gestation barn, farrowing barn, nursery rooms and finishing units as groups and the pens previously occupied are cleaned, disinfected and left vacant for several days before animals are reintroduced. Since most infection is believed to occur between 4–12 weeks nursery depopulation has become an effective way of controlling the infection in nursery pigs.12
This method of control is the most satisfactory and is probably mandatory for large breeding companies, and herds supplying replacement stock to other herds and for large intensive farrow-to-finish enterprises. It is based on the principle that the source of infection for the young pig is the gilt or the sow and this chain of infection must be interrupted to prevent infection. In the past the 10-month cutoff point has been used in eradication programs but in view of the colonization studies26 this may be too soon. This is especially so in off-site production systems where the time of infection is delayed.
There are three different principles.104 First, there is total depopulation followed by re-stocking with non infected stock (Danish SPF system). Second, test and removal of all positives and inconclusives. Third, eradication without total depopulation and restocking.
Eradication without restocking has been described105 and here the secret was to wait until farrowing finished, then vaccinate all sows and treat with tiamulin at 6 mg/kg daily for 3 weeks and then monitor with blood tests.
Several methods of eradication have been attempted but the most satisfactory is repopulation with specific pathogen-free (SPF) pigs. The principle underlying this method is that the piglet in utero is free of infection with M.hyo. If it is taken from the uterus at term by suitable sterile hysterectomy or hysterotomy techniques and reared artificially in an environment free of pigs, it will remain free of this infection. In practice this has been carried out in special units and the piglets have been subsequently used to repopulate existing farms where all pigs have been removed 30 d prior to the introduction of the SPF pigs and a thorough cleaning program completed. This method was initially developed for the control of enzootic pneumonia and atrophic rhinitis. Moreover, if suitable precautions are taken and if the piglets are used to populate new units that have had no previous exposure to pigs, then freedom from other important diseases such as internal and external parasitism, leptospirosis, brucellosis, swine dysentery and others can be achieved. The progeny of these primary SPF herds can subsequently be used to repopulate other or secondary SPF herds known as minimal disease pigs. The details of these procedures are available in the textbook Herd Health.106
Because of the cost and technical difficulty of this method, other methods of eradicating enzootic pneumonia have been attempted but they are generally less satisfactory and have a higher failure rate. These include ‘snatching’ of pigs at birth and isolated farrowing. In the former the piglets are caught and removed from the sow immediately at birth and reared as previously described or foster-suckled on SPF sows in another environment. Although enzootic pneumonia may be eliminated by this method, fecal contamination during parturition of the vulva and vagina and consequently of the piglet is common and this method is less satisfactory for disease control than removal by hysterectomy.
Isolated farrowing techniques have proved successful in small herds but have a high failure rate when practiced on a large scale. Older sows believed to be free of infection are farrowed in isolation in individual pens erected outside on pasture and each sow and litter is kept as a separate unit. The litter is inspected clinically at regular intervals and subsequently a proportion of the litter, usually excess males and gilts undesirable for breeding, are examined at slaughter for evidence of pneumonia. Any litters with clinical, pathological or laboratory evidence of pneumonia are eliminated from the program. Litters that pass inspection are kept for repopulation of the herd. Because of the difficulties in detecting carrier pigs without lesions, eradication by methods using these principles frequently fails.
Minimal disease herds have been established in most countries with significant pig populations either by breeding companies or private purebred breeders. As a result there is, in most countries, a nucleus of enzootic pneumonia-free stock which is a major swine-producing enterprise worldwide. The establishment of primary SPF herds is technically difficult, very costly and should not be undertaken lightly. There is also a considerable delay in cash flow between the time of initial population and build-up of herd numbers to the time when significant numbers of pigs are available for sale. Because of this, if eradication by repopulation is intended, it is preferable to purchase pregnant gilts from established primary SPF herds unless the maintenance of existing genetic lines dictates otherwise. Before recommending eradication by this method it is essential that the pig owner understands the principles of this method of control and the restrictions that will need to apply if it is to be successful. Farrow-to-finish enterprises established by this method should be run as closed herds and if further genetic material is required it should be introduced by hysterectomy techniques or by purchase from the initial source herd. The use of artificial insemination is an alternate method; however, isolation of M.hyo from semen is recorded.
The problem of certifying and maintaining herds free of enzootic pneumonia is a major task.
Reinfection of enzootic pneumonia-free pig herds occurs despite high standards of isolation and strict precautions whereby complete protective clothing and showering routines are required for all visitors entering the unit. All visitors are debarred entry if they have been to a possible source of infection during the previous 48 h and even up to 7 d. Also, the majority of breakdowns occur in herds which have not imported infected stock recently. In reinfected herds which imported stock there was no concurrent evidence of breakdown in the parent herds, which supported the contention that the importation of infected pigs was an unlikely source of the infection. An epidemiological investigation of these reinfections suggests that close proximity of uninfected herds to infected herds may be an important factor. The organism does not survive for more than a few days under dry conditions; however, it can survive in diluted tapwater and rainwater for 2–3 weeks and it has been suggested that the organism may be transported in moist air and that airborne infection between piggeries is a possible method of transmission. In Switzerland 107 farms were reinfected of 3983 that eradicated during the period 1996–1999 (2.6%).107 The significance of known risk factors such as farm size, high density of pigs, and farm type was confirmed in this analysis.
Some preliminary estimates of risk indices based on the proximity of other pig units has indicated that the most important factor was the reciprocal of the square of distance to the nearest other unit. The crucial distance for maximum survival was about 3.2 km. A breakdown was described recently in which a whole variety of measures were included in an attempt to control the disease.108
Eradication has also been attempted by antimicrobial treatment of newborn piglets with oxytetracycline on days 1, 7 and 14, weaned on day 14 and moved to offsite nursery.109 This is known as a low-cost modified medicated-early-weaning program. This can be followed by serological testing of the breeding herd and culling of positive reactors. Control by vaccination on the one hand and by the use of tilmicosin on the other produced similar results when measured by serological results and the prevalence of macroscopic lung lesions.110 Lincocin with or without vaccination considerably improves the growth and performance.111 Doxycycline in the feed at 11 mg/kg bodyweight is effective in controlling pneumonia due to P. multocida and M.hyo in feeder pigs.112
The alternative to eradication is to limit the effects of the disease in those herds where eradication is either not desirable or feasible. The effects of the disease are generally less severe in non-intensive rearing situations, in small herds where individual litters are reared separately and where litters from older sows can be reared separately from other pigs. Where litters are grouped at weaning, a low stocking density with less than 25 pigs in initial pen groups and 100 pigs in a common air space may also reduce the severity of the disease.
Temperature, humidity and ventilation also have an important influence on the disease. It is possible to determine an optimal air temperature zone for growing-finishing pigs based on the measurement of behavioral and health-related problems. They are interrelated with stocking density and housing. The subject is too broad for treatment here and the requirements for pigs at different ages and under different housing situations may be found in standard texts on pig housing and production. The environmental risk factors associated with the incidence of enzootic pneumonia should be assessed in each circumstance. Some important environmental variables which should be assessed and modified include:45
• Cleaning and disinfection techniques used
• Number of air changes per hour
• Number of temperature fluctuations in a 24-hour period
• Direction of the flow of air in the building
• Concentrations of ammonia and hydrogen sulfide in the building
• Feeding and watering systems
• Whether or not the all-in/all-out system is being used effectively.
The original medicated early weaning program was based on medication of the sows with tiamulin at the time of farrowing and the early weaning of the piglets to an off site location. A variation of this method is to prevent the spread of infection by:113
• Isolation of the breeding stock
• Strategic antimicrobial medication of the breeding stock
• Reintroduction of the breeding stock to the original but empty and disinfected gestation barn
• Separate rearing of the piglets before and after initiating the program
• Regulation of flow of animals through the herd. Farrowing barns are emptied out when possible and cleaned, disinfected and left empty. After weaning their piglets, sows are transferred to the dry sow barns. Sows about to farrow are treated with tiamulin and moved to the farrowing barn.
Where possible the purchase of weaners or pigs for finishing units should be from herds free of the disease or from a single source. Purchase through saleyards or the purchase of coughing or uneven litters is not advisable. When pigs from infected herds are purchased it may be necessary to medicate the feed prophylactically with one of the tetracycline group of antibiotics or tylosin or spiramycin at 100–200 mg/kg of feed for a 2-week period after introduction. Medication of the feed of finishing pigs with tiamulin at 20 and 30 mg/kg of feed over an 8-week period on farms with histories of severe complicated enzootic pneumonia resulted in improved weight gains and feed efficiency, but the extent and severity of the lung lesions did not change.114 The level of 30 mg/kg in the feed was superior to the level of 20 mg/kg. Tiamulin at 100 mg/kg combined with chlortetracycline at 300 mg/kg of feed for 7 d was effective in herds with a history of enzootic pneumonia complicated by the presence of P. multocida and Actinobacillus pleuropneumoniae.115
Introduced pigs should be isolated from the rest of the herd and preferably they should be reared as a batch through a house on the all-in/all-out system.116 A high stocking density should be avoided and internal parasites should be controlled.
Mycoplasma hyopneumoniae vaccines are generally bacterins consisting of outer membrane proteins or whole organisms. The vaccines give little protection against initial infection and often incomplete protection against clinical pneumonia. The vaccines produce a TH1 response and also IgA and IgG in the lavage fluids. Natural maternal antibodies do not seem to inhibit vaccination but vaccination of sows may inhibit subsequent immunity.
Vaccination with killed M.hyo induces protection in pigs against experimental challenge exposure with the organism. A cost benefit analysis shows that the vaccination is economically beneficial.21 The relationships between maternally derived antibodies, age and other factors in vaccine response have been discussed.117-120
A killed M.hyo vaccine evaluated in a single herd reduced the prevalence of pneumonic lesions in slaughter pigs from 69% to 36% and the prevalence of pleuritis from 20% to 13%.121 There was a small decrease in the number of days to market. It usually results in a 2–8% increase in daily gain. The mortality rate is usually only better numerically. Feed conversion efficiency increases by about 2–3%.122 Other limited studies indicate that vaccination can reduce the severity and prevalence of lung lesions detected at slaughter123 (4–6% compared to 12% in controls). It improves feed efficiency and increases average daily gain during the finishing period.124 In other studies the average daily gain was not improved.125 Vaccination of sows against M.hyo reduced the prevalence of positive piglets at weaning and could be used to control M.hyo infections126 as judged by a nested PCR. PRRS vaccination does not interfere with M.hyo vaccination.127 Needle less intradermal vaccination has also been described.128
Both dual and single injection vaccines are available but the protection obtained is similar.129,130 The single dose vaccine131 gives protection for up to 23 weeks.132 The level of protection will probably last 4 months.133 Vaccination is economically attractive.134
DNA vaccination using a p42 heat stable protein gene has also been used and this induces rises in IL-2, IL-4, and IFN gamma which indicates that it induces both a TH1 and aTH2 response.135 Vaccination for mycoplasma generally induces local mucosal immunity, humoral and cellular immunity.136
Stark K. Epidemiological investigations of the influence of environmental risk factors on respiratory diseases in swine; a selective review. Vet J. 2000;159:39.
Desrosiers R. A review of some aspects of the epidemiology, diagnosis and control of M. hyopneumoniae infections. J Swine Health Prod. 2001;9:233-237.
1 Amass SF, et al. J Am Vet Med Assoc. 1994;204:102.
2 Friis NF, et al. Acta Vet Scand. 2003;44:103.
3 Thacker EL, et al. Pig J. 2001;48:66.
4 Cowart RP, et al. J Am Vet Med Assoc. 1992;200:190.
5 Scheidt AB, et al. J Am Vet Med Assoc. 1992;200:1492.
6 Lium BM, Falk K. Acta Vet Scand. 1991;32:55.
7 Erlandson KR, et al. Proc Am Assoc Swine Vet. 2002:31.
8 Vicca T, et al. J Vet Med B. 2002;49:349.
9 Stark KD, et al. Appl Environ Microbiol. 1998;64:543.
10 Cardona AC, et al. Vet Rec. 2005;156:91.
11 Calsamiglia M, Pijoan C. Proc 15th Int Pig Vet Soc Cong 1998; p.146.
12 Sur D-K, et al. Swine Hlth Prod. 1998;6:151.
13 Meyns T, et al. Proc 18th Int Pig Vet Soc Cong 2004; p. 168.
14 Torremorell M, et al. Proc 16th Int Pig Vet Soc Cong 2000; p. 47.
15 Meyns T, et al. Prev Vet Med. 2004;66:265.
16 Wallgren P, et al. Vet Microbiol. 1998;60:193.
17 Leon E, et al. Vet Microbiol. 2001;78:331.
18 Morris CR, et al. Prev Vet Med. 1995;21:323.
19 Stark KDC, et al. Vet Rec. 1992;131:532.
20 Batista L, et al. J Swine Hlth Prod. 2004;12:75.
21 Maes D, et al. J Vet Med B. 1999;46:341.
22 Sibila M, et al. Can J Vet Res. 2004;68:12.
23 Gardner IA, Hird DW. Am J Vet Res. 1990;51:1306.
24 Morris CR, et al. Can J Vet Res. 1995;59:197.
25 Yagihashi T, et al. Vet Rec. 1993;34:155.
26 Fano E, et al. Proc 18th Int Pig Vet Soc Cong 2004; p. 167.
27 Utrera V, et al. Proc17th Int Pig Vet Soc Cong 2002; p. 284.
28 Van Til LD, et al. Can J Vet Res. 1991;55:347.
29 Morris CR, et al. Prev Vet Med. 1994;21:29.
30 Cornaglia E, et al. Proc Am Assoc Swine Vet. 2002:83.
31 Hodgins DC, et al. J Swine Hlth Prod. 2004;12:10.
32 Wallgren P, et al. Vet Microbiol. 1998;60:193.
33 Calsamiglia M, Pijoan C. Vet Rec. 2000;146:530.
34 Levonen K. Res Vet Sci. 1994;56:111.
35 Rautianinen L, et al. Proc 14th Int Pig Vet Soc Cong 1996; p. 303.
36 Levonen K, et al. J Vet Diag Invest. 1999;11:547.
37 Andreasen M, et al. Prev Vet Med. 2000;45:221.
38 Thacker EL. Am J Vet Res. 2000;61:1384.
39 Thacker EL, et al. Proc Am Assoc Swine Vet. 2001:467.
40 Zielinski GC, Ross RF. Am J Vet Res. 1993;54:1262.
41 Vicca J, et al. Vet Microbiol. 2003;97:177.
42 Falk K, et al. Acta Vet Scand. 1991;32:67.
43 Opriessnig T, et al. Vet Pathol. 2004;41:624.
44 Jolie R, et al. Swine Hlth Prod. 1999;7:269.
45 Done SH. Vet Rec. 1991;128:582.
46 Clark LK, et al. Swine Health Prod. 1993;1:10.
47 Hurnik D, et al. Prev Vet Med. 1994;20:147.
48 Hurnik D, et al. Prev Vet Med. 1994;20:135.
49 Done SH, et al. Vet Rec. 2005;157:71.
50 Morrison RB, Morris RS. Vet Rec. 1985;117:268.
51 Straw BE, et al. Prev Vet Med. 1990;9:287.
52 Scheidt AB, et al. J Am Vet Med Assoc. 1990;196:881.
53 Caruso JP, Ross LF. Am J Vet Res. 1990;51:227.
54 Hill MA, et al. Res Vet Sci. 1994;56:240.
55 Hurnik D, et al. Can J Vet Res. 1993;57:37.
56 Straw BF, et al. J Am Vet Med Assoc. 1989;195:1702.
57 Davies PR, et al. Am J Vet Res. 1995;56:709.
58 Paisley LG, et al. Acta Vet Scand. 1993;34:319.
59 Paisley LG, et al. Acta Vet Scand. 1993;34:331.
60 Noyes EP, et al. J Am Vet Med Assoc. 1990;197:1025.
61 Hsu T, Minion FC. Gene. 1998;214:13.
62 Minion FC, et al. Infect Immun. 2000;68:3056.
63 Chen JR, et al. Vet Microbiol. 1998;62:97.
64 Lin BC. Proc Am Assoc Swine Vet. 2001:225.
65 Park S-C, et al. J Vet Clin. 2001;18:93.
66 Park S-C, et al. Infect Immun. 2002;70:2502.
67 Thanawongnuwech R, et al. Clin Diag Immunol. 2004;11:901.
68 Sarradell J, et al. Vet Pathol. 2003;40:395.
69 Rodriguez F, et al. J Comp Path. 2004;130:306.
70 Blanchard B, et al. Vet Microbiol. 1992;30:329.
71 Yazawa S, et al. Vet Microbiol. 2004;98:221.
72 Shibata I, et al. J Vet Med Sci. 1998;60:295.
73 Thacker EL, et al. J Clin Microbiol. 1999;37:620.
74 Thacker EL, et al. Vaccine. 2000;18:1244.
75 Bosch J. Proc Am Assoc Swine Pract. 2000:175.
76 Sheldrake RF, Romalis LF. Aust Vet J. 1992;69:255.
77 Djordjevic SP, et al. Vet Microbiol. 1994;39:261.
78 Levonen K. Res Vet Sci. 1994;56:111.
79 Rautiainen L, et al. Acta Vet Scand. 1998;39:325.
80 Erlandson KR, et al. J Swine Hlth Prod. 2005;13:198.
81 Levonen K, et al. J Vet Diag Invest. 1999;11:547.
82 Sorensen V, et al. Vet Microbiol. 1997;54:23.
83 Stemke GW, et al. Am J Vet Res. 1994;55:81.
84 Calsamiglia M, et al. J Vet Diag Invest. 1999;11:246.
85 Verdin E, et al. Mol Cell Probes. 2000;14:365.
86 Verdin E, et al. Vet Microbiol. 2000;76:31.
87 Baumeister AK, et al. J Clin Microbiol. 1998;36:1984.
88 Caron J, et al. J Clin Microbiol. 2000;38:1390.
89 Stemke GW. Lett Appl. Microbiol. 1997;25:327.
90 Calsamiglia M, et al. Vet Microbiol. 2000;76:299.
91 Kwon D, Chae C. Vet Pathol. 1999;36:308.
92 Mousing J, Christensen G. Acta Vet Scand. 1993;34:151.
93 Sorensen VP, et al. Vet Med. 1997;54:23.
94 Bouh KCS. Clin Diag Lab Immunol. 2003;10:549.
95 Kurth T, et al. J Vet Diag Invest. 2002;14:463.
96 Tanner AC, et al. Vet Microbiol. 1993;36:306.
97 Bousquet E, et al. Vet Rec. 1997;141:37.
98 Thacker EL, et al. Vet Ther. 2001;2:293.
99 Kavanaugh NT. Irish Vet J. 1994;47:58.
100 Hannan PCT, et al. Res Vet Sci. 1997;63:157.
101 Stipkovits L, et al. Proc 18th Int Pig Vet Soc Cong 2004; p. 518.
102 McKelvie J, et al. Proc 18th Int Pig Vet Soc Cong 2004; p. 528.
103 Vicca J, et al. Proc 18th Int Pig Vet Soc Cong 2004; p. 535.
104 Baekbo P, et al. Proc Am Assoc Swine Pract. 1999:479.
105 Lorenzen JB, et al. Danske Vet 83:6.
106 Radostits OM, Leslie KE, Fetraw J. Herd health. Food animal production medicine, 2nd edn. Philadelphia: WB Saunders.
107 Zellweger K, et al. Proc 18th Int Pig Vet Soc Cong 2004; p. 166.
108 Bargen LE. Can Vet J. 2004;45:543.
109 Dee SA. Swine Health Prod. 1994;2:6.
110 Mateusen B, et al. J Vet Med B. 2001;48:733.
111 Van Burgh J, et al. Proc Am Assoc Swine Vet. 2001:119.
112 Bousquet E, et al. Vet Rec. 1998;143:269.
113 Wallgren P, et al. J Vet Med Series B. 1993;40:157.
114 Burch DGS, et al. Vet Rec. 1984;114:209.
115 Burch DGS, et al. Vet Rec. 1986;119:108.
116 Clark LK, et al. Vet Med. 1991;86:946.
117 Burch DGS, et al. Pig J. 2003;51:242.
118 Pallares FJ, et al. Vet Res. 2000;31:573.
119 Pallares F, et al. Vet Rec. 2001;148:104.
120 Maes D, et al. J Vet Med B. 1998;45:49.
121 Dohoo IR, Montgomery ME. Aust Vet J. 1996;57:299.
122 Maes D, et al. Proc Am Assoc Swine Pract. 2000:327.
123 Maes D, et al. Vaccine. 1999;17:1024.
124 Scheidt AB, et al. Swine Health Prod. 1994;2:7.
125 Morrow WEM, et al. Swine Health Prod. 1994;2:13.
126 Ruiz AR, et al. J Swine Hlth Prod. 2003;11:131.
127 Boettcher TB, et al. J Swine Hlth Prod. 2002;10:259.
128 Jones GF. J Swine Hlth Prod. 2005;13:19.
129 Morris J, et al. Proc Am Assoc Swine Pract. 2001:157.
130 Dawson A. Vet Rec. 2002;151:535.
131 Moreau IA, et al. Vaccine. 2004;22:2328.
132 Dawson A. Pig J. 2001;50:83.
133 Rapp-Gabrielson VJ, et al. Proc Am Assoc Swine Pract. 2002:105.
134 Maes D, et al. Livestock Prod. 2003;83:85.
Mycoplasmal arthritis occurs in suckling and growing pigs and is characterized clinically by dyspnea and lameness.
M. hyorhinis causes arthritis and polyserositis in young pigs, and M. hyosynoviae causes arthritis in growing pigs. M. hyorhinis has also been isolated from pigs with otitis media.1,2 M. hyoarthrinosa has been associated with a syndrome similar to that produced by M. hyosynoviae but they may be the same species. Other mycoplasmas including M. flocculare and Acholeplasma spp. have been isolated from pigs but appear to have no propensity to produce arthritis.
M. hyorhinis is an inhabitant of the respiratory tract and conjunctivae3,4 of pigs and is a common secondary infection in pre-existing respiratory disease.5 It probably spreads pig to pig through nasal contact or by aerosol. It colonizes the mucosa of suckling piglets within the first few weeks of life and may spread with subsequent polyserositis and arthritis but more commonly does so following stress. Disease is essentially restricted to pigs between 3 and 10 weeks of age and occurs in older suckling pigs and following weaning, but may occur occasionally in older pigs. Disease occurs sporadically in most herds and is a significant cause of sporadic runting and general poor bodily condition in young pigs. There is some evidence to show that pigs with high and low immune responses differ in their cytokine response to M. hyorhinis but there is no characteristic cytokine response in association with the relative susceptibility to infection in high immune expression pigs.6 In some cases there may be no external signs except bursitis and septic fluctuating joints. Affected pigs limp, shift weight, and are unable to rise. Outbreaks can occur with multiple cases within and between litters. Morbidity may reach 20–35% but mortality is rarely high. The case fatality rate seldom exceeds 10% but chronically affected pigs fail to grow and become runts. M. hyorhinis is also associated with otitis media in pigs.1,2,7
M. hyosynoviae is a causative organism with a very wide heterogeneity8 and is resident on the pharyngeal mucosa and tonsil. Shedding is less frequent than with M. hyorhinis and the organism cannot usually be isolated from the pharynx of piglets prior to 7 weeks of age and is regarded as rare before 12 weeks by some authors.9 This is true even when most of the sows in a herd are tonsillar carriers.9,10 There is a very varied pattern of carriage. It appears that this transference is fairly rare but when it does occur can be the source of infection for the other littermates.9 There is some variation in virulence between strains. With virulent strains, bacteremia with subsequent arthritis follows within a few days of minor stress such as vaccination, movement, regrouping or a change in weather. The overall prevalence of clinical disease appears to be low but it achieves significance in certain herds which experience a persistent problem. The reasons for this are still unclear.11 These authors have shown that infection profiles between herds vary considerably.9 In some herds in the UK the incidence may be higher with 21% of sows culled because of lameness primarily associated with M. hyosynoviae. In these herds the sows are nearly always culled for lameness before the 4th parity which constitutes a huge economic loss. Failure to treat leads to chronic lameness.12,13 When gilts and sows are treated they do not appear to have a reduced overall survival time indicating that treatment is cost effective. Clinical disease occurs primarily in pigs over 3 months of age and in replacement stock brought into these problem herds. It appears that there is a latent period between the tonsillar infection and the development of generalized infection and arthritis9 which may be accounted for by the long persistence of maternal antibodies of 8–16 weeks. The active serological response possibly indicating immunity only seems to occur when there is the onset of arthritis9 but others disagree14,15 and not even when there is hematogenous spread. In only a few pigs was a rising OD ratio observed before the onset of generalized infection. It is more prevalent in heavily muscled pigs with straight-legged conformation and there is variation in breed susceptibility. Morbidity in problem herds is generally 5–15% but may reach 50%. Mortality is rare but 2–15% may become chronically affected.
Abattoir studies have suggested that 5–10% of pigs may be affected.16 Transmission of infection is by direct contact or possibly by aerosol infection.
M. hyosynoviae can survive drying for up to 4 weeks and may be capable of survival in the environment for longer periods than most mycoplasmas. A further consideration of the importance of these diseases must be given to their possible contribution to the occurrence of carcass condemnation from arthritis.
The most important thing is that pigs can carry the infection in their tonsils and their synovial fluid without clinical signs of lameness and may therefore not be diagnosed as carriers and can act as a potential source of infection to others.17,18
Systemic infection by mycoplasma may occur following stress. Clinical disease is manifest if localization occurs but this is probably the exception rather than the rule. In the experimental disease the incubation period varies from 4–10 days. After experimental intranasal infection with M. hyosynoviae septicemia usually takes about 2–4 days. The reason for the variation in age susceptibility between the two diseases is unknown. M. hyorhinis produces a polyserositis in which fibrinous pericarditis, pleuritis and occasionally pneumonia, or polyarthritis, may be the predominant features. Acute eustachitis associated with M. hyorhinis occurs as early as 1 week of life and precedes inflammation of other sites of the ear. M. hyosynoviae produces synovitis with some arthritis, especially in the larger joints of the hindlimbs.
Diagnosis of both infections is often difficult to make clinically and it is essential that a good clinical diagnostic test or tests are produced in the near future.
Pigs affected with M. hyorhinis are usually 3–10 weeks and show initial transient fever, depression and inappetence. Normally, however fever is absent. The first presenting sign may be just stiff legs. Dyspnea with abdominal breathing and a pleural friction rub may be present. There is polyarthritis with lameness, reluctance to rise and moderate swelling and heat in affected joints. Pigs may recover spontaneously in 1–2 weeks but more commonly become unthrifty. Acute outbreaks may occur in suckling pigs 3–8 weeks of age but more commonly the disease is more sporadic and insidious, producing moderate ill-thrift in a proportion of the sucklers which then show severe runting following weaning. With M. hyosynoviae infection there is a sudden onset of acute lameness in one or more limbs, usually without fever. Lameness may be referable to one or more joints and the stifle, hock and elbow joints are most commonly affected. In many cases the pigs may lie in sternal recumbency. The lameness is severe although clinical swelling of the affected joint may be minimal. In the majority of affected pigs clinical recovery occurs after 3–10 days but some may become permanently recumbent. Otitis media is characterized by anorexia, circling and tilting of the head and neck, leaning against the wall,19 and eventually recumbency with the affected side down.
In the UK, the condition is often associated with delivery of high herd health gilts to more conventional farms, with the condition occurring 2–4 weeks after the delivery or with a change of housing. Other outbreaks have followed the introduction of pigs to straw yards whereas contemporary animals kept in fully slatted accommodation have been unaffected.20 Both mycoplasma infections may require humane slaughter.
Blood cell counts remain within the normal range but there is an increase in leukocytes and protein in synovial fluid. The organisms may be detected by immunofluorescent techniques, and complement fixing antibody develops following infection.
A serofibrinous pleuritis, pericarditis and peritonitis are present with M. hyorhinis infections. Chronic cases show fibrous pleural and pleural–pericardial adhesions. Synovial hypertrophy with an increased amount of serosanguinous synovial fluid occurs in affected joints with both mycoplasmal species. Sometimes the amount of fluid is considerable. Chronic cases show thickening of the joint capsule with a varying degree of articular erosion and pannus formation.12 Joint lesions are most likely to be found in the carpus, shoulder, stifle and tarsus. Quite often with M. hyosynoviae infections one joint usually the hock is affected.
Microscopically, there is usually edema, hyperemia, hyperplasia of synovial cells, and an increased density of subsynovial cells. Lymphocytes and plasma cells are present in the affected serosal and synovial membranes of subacute to chronic cases. There is often a significant villus hypertrophy of the synovial membrane. In the chronic phase there may be some fibrosis.21 A full description of the phases of infection has recently been described.22 With both infections, the organism is more easily demonstrated during the acute stage of the disease. A synergistic link between M. hyorhinus and PRRS virus has been suggested to contribute to some cases of pneumonia.23 This species of mycoplasma may also play a role in porcine otitis media, possibly via ascension of the eustachian tubes.23,24
• Histology – synovial membrane, liver, lung, heart. Sometimes the mycoplasmas can be seen between the synoviocytes on the tips of the villi of the synovial membrane
• Mycoplasmology – culture swabs from serosal surfaces, joints. Friis’s medium suppresses the growth of M. hyorhinis in mixed cultures. It can be recovered from blood for 7–11 days from 1–4 days post-exposure. It can be recovered from the joints for 5–21 days and from the tonsils from 6–61 days25,26
• M. hyosynoviae is best grown in anaerobic conditions where it outgrows M. hyorhinis
• Synovial fluid has been taken from the hock joint under general anaesthesia and cultured. It was shown27 that isolation from the joints of lame pigs was twice as high as from littermates that were not lame. About 8–9% of synovial fluid samples from non-patent arthritis samples from Danish slaughterhouse pigs were positive.28 The same authors also showed that blood culture was also effective
• Antigen detection. An in situ hybridization technique for the differentiation of M. hyosynoviae, M. hyorhinis and M. hyopneumoniae has been described for use with formalin fixed tissues29
• PCR can be used to amplify a p36 or p46 gene to differentiate M. hyorhinis and M. hyosynoviae infections30
• Serology. It has been shown that herds with M. hyosynoviae arthritis had higher serological responses and more carriers amongst growers of 16 week old pigs than did the unaffected herds, but by the end of the finishing period the serological response and carrier prevalence were as high in herds with arthritis as without
• An indirect ELISA has been developed using membrane lipoprotein antigens.31,32
The differential diagnosis of mycoplasma infections must include S. suis, and H. parasuis.
Treatment with tylosin at 1–2 mg up to 15 mg/kg BW IM or lincomycin at 2.5 mg/kg BW IM for three consecutive days has been recommended.14,15 The lincomycin was effective in one outbreak but as soon as it was removed the outbreak flared up again.20 Oxytetracycline also can be used.33 Early treatment of M. hyosynoviae arthritis with 8 mg of betamethasone IM has been found to reduce the occurrence of chronic lameness. Tiamulin at both 10 and 15 mg/kg BW IM daily for 3 days is effective for treatment of pigs affected with arthritis associated with M. hyosynoviae and is as effective as lincomycin. Recently, enrofloxacin has been used at 2.1 mg/kg for 3 days. It is essential to treat the incontacts34 and to isolate the treated animals until the clinical signs have disappeared. Valnemulin was highly active against M. hyosynoviae,35 whereas tiamulin and enrofloxacin were much less active.
The control of both diseases rests largely in the avoidance of stress situations. The administration of tylosin or tetracyclines in the drinking water or feed during unavoidable stress such as weaning can reduce the incidence.36 The use of tiamulin as a single im injection prior to moving pigs from one house to another was sufficient to prevent 50% of the cases of the disease.15 Early weaning at 3–5 weeks of age has been recommended as a method of preventing infection of pigs with M. hyosynoviae and thus of reducing the occurrence of the disease in growing pigs. However, in a recent study37 it was shown that M. hyosynoviae was not eliminated in herds where the piglets were commingled after 4 weeks and reared in herds using all in/all out management. In fact the herd had widespread infection when the herd was 4 months old. The authors concluded that elimination of M. hyosynoviae requires that the pigs are moved immediately from weaning at an age of no more than 4 weeks.
1 Kazama S, et al. Res Vet Sci. 1994;56:108.
2 Morita T, et al. Vet Pathol. 1995;32:107.
3 Friis NF. Acta Vet Scand. 1976;17:343.
4 Rogers DG, et al. J Am Vet Med Ass. 1991;198:450.
5 Friis NF, Feenstra AA. Acta Vet Scand. 1994;35:93.
6 Reddy NRJ, et al. Inf Imm. 2000;68:1150.
7 Friis NF, et al. Acta Vet Scand. 2002;43:191.
8 Kokotovic B, et al. 2002;85:221.
9 Hagedorn-Olsen T, et al. J Vet Med A. 1999;46:555.
10 Ross RF, Spear ML. Am J Vet Res. 1973;34:373.
11 Hagedorn-Olsen T, et al. Proceedings of the 15th Int Pig Vet Soc Cong 1998; p. 203.
12 Ross RF, et al. Am J Vet Res. 1971;32:1743.
13 Roberts DH, et al. Vet Rec. 1972;90:307.
14 Burch DGC, Goodwin RFW. Vet Rec. 1984;115:594.
15 Blowey RW, Pott JM. Proc 12th Int Pig Vet Soc Cong 1992; p. 286.
16 Hariharan H, et al. J Vet Diag Invest. 1992;4:28.
17 Nielsen EO, et al. Proc 16th Int Pig Vet Soc Cong 2002; p. 252.
18 Nielsen EO, et al. Danske Vetmed. 2002;85:6.
19 Blowey RW. Pig Vet J. 1993;30:72.
20 Smith WJ. Vet Rec. 1999;145:440.
21 Hagedorn-Olsen T, et al. J Vet Med A. 1999;46:317.
22 Hagedorn-Olsen T, et al. Acta Path Micro Scand. 1999;107:201.
23 Kawashima K, et al. J Comp Path. 1996;114:315.
24 Morita T, et al. Vet Path. 1999;36:174.
25 Friis NF, et al. Acta Vet Scand. 1991;32:425.
26 Nielsen E, et al. Proc14th Int Pig Vet Soc Cong 1996; p. 224.
27 Nielsen EO, et al. Proc 14th Int Pig Vet Soc Cong 1998; p. 205.
28 Buttenshon J, et al. J Vet Med A. 1995;42:633.
29 Boye M, et al. APMIS, Acta Path Micro Scand. 2001;109:656.
30 Caron J, et al. J Clin Microbiol. 2000;38:1390.
31 Jungersen G, et al. Proc 17th Int Pig Vet Soc Cong 2002; p. 264.
32 Goethe R, et al. Vaccine. 2000;19:966.
33 Aarestrup FM, et al. Acta Vet Scand. 1998;39:145.
34 Madeiros CA. Vet Rec. 1984;115:446.
35 Hannan PCT, et al. Res Vet Sci. 1997;63:157.
36 Nielsen HC, et al. Proc 14th Int Pig Vet Soc Cong 1996; p. 236.
37 Nielsen EO, Busch ME. Proc 15th Int Pig Vet Soc Birm. 1998;2:204.
Subclinical infection common and clinical disease precipitated by stress. Horizontal transmission by blood. Vertical transmission important in swine
Acute icteroanemia or chronic ill-thrift in sheep and swine. Reproductive inefficiency and neonatal anemia in swine. Syndromes in cattle less defined
The disease is associated with hemotrophic mycoplasmas that were, until recently, thought to be ricketsial parasites and were classified as Eperythrozoon. Species in farm livestock that have been associated with disease are Mycoplasma (Eperythrozoon) ovis in sheep, M. haemosuis in swine and M. wenyonii in cattle.1,2 They cannot be grown in culture.
Eperythrozoonosis occurs in sheep, swine, cattle, and llamas but has greater clinical occurrence in swine and sheep. Latent eperythrozoonosis also occurs in mule deer, elk and goats. The organisms appear species specific although M. ovis has been transmitted from sheep to goats. The distribution is as follows:
• Sheep. Eperythrozoonosis of lambs associated with M. ovis is recorded in Africa, Iran, the United States, Canada, Great Britain, France, Norway, Germany, Poland, Australia, and New Zealand
• Pigs. Disease is recorded mainly in the United States, Canada, Great Britain, and continental Europe
• Cattle. Eperythrozoonosis in cattle is apparently widely distributed with reports from North and South America, Africa, Australasia, the British Isles, western Europe, and the Middle East1
• Llamas. Infection with Eperythrozoon spp. is reported in llamas in the United States and apparently has widespread occurrence.3 Infection has been detected in animals that also had other disease problems or as the result of specific survey studies, and it is likely that the organism acts primarily as a secondary opportunistic pathogen in llamas
The reservoir of infection is the persistently infected animal and the disease can be transmitted by any mechanism that transfers infected blood. It is proposed that in sheep the minimal infective dose is one parasitized erythrocyte.4 Horizontal and vertical transmission is possible.
The method of natural spread of the infection in sheep is probably via biting insects. Serological studies in Australian sheep show that the prevalence of farms with infection is high and that spatial differences are probably due to differences in vector occurrence.5 In an infected flock or herd the disease can also be spread by management practices that transfer infected blood. In sheep these include vaccination, ear-tagging, shearing and mulesing, although these risk factors have not been associated with infection in flock epidemiologic studies.5
Skin parasites and blood-contaminated needles and instruments have been shown to transmit disease in swine.6 Transplacental transmission is also an important route in swine.
Seasonal differences in disease prevalence occur – it is more common in the summer and autumn. Regional differences in the clinical severity of the disease has led to postulations of differences in virulence between strains of the organism. There may also be genetic difference in host susceptibility and field observations are that the Merino is more susceptible to infection and disease.
Several studies suggest that subclinical infection is common and that the development of clinical disease requires the presence of some other debilitating factor or stress for manifestation. Viral infections with porcine reproductive and respiratory syndrome (PRRS) and swine influenza appear to predispose its occurrence in swine.7
Following experimental infection there is a variable prepatent period, usually 1–3 weeks, which is followed by a period of intense parasitemia. Ring form, coccoid and rod-shaped organisms are evident in stained blood smears. The organism is epicellular, infecting the surface and periphery of erythrocytes and is also found free in the plasma in blood examinations. There is a profound hypoglycemia during the parasitemic phase which is believed to be due to direct consumption of glucose by the parasite.2,8,9 The period of intense parasitemia lasts for a period of 5–10 days following which visible organisms in the blood become much less frequent and anemia develops. Parasitized erythrocytes are removed from the circulation by the spleen. It is believed the parasite alters the erythrocyte membrane, exposing new antigenic determinants and stimulating the development of antierythrocyte antibodies. The severity and duration of the anemia varies between individuals but commonly lasts from 1–2 months. Upon recovery there may be further cycles of parasitemia and anemia which are less severe. Sheep that develop a high antibody titer tend to rapidly clear the parasitemia whereas sheep that have a poorer antibody response tend to show persistent parasitemia and recurrent episodes of anemia. Once an animal is infected it is probably infected for life.
Sudden death and deaths associated with exercise, accompanied by hemoglobinuria and icterus, may be a feature in some sheep and some outbreaks but, more commonly, the disease is manifest with fever and depression followed by the development of anemia, exercise intolerance and ill-thrift. In some areas it may be the principal cause of ill-thrift in lambs.10 There is reduced wool yield and in the experimental disease in lambs at pasture a retardation of growth of up to 2 kg has been recorded 5 weeks after infection.11 Lambs suckled by infected ewes are passively immunized via the colostrum until weaning.
Acute icteroanemia is the classical syndrome and occurs in feeder pigs. It is characterized by weakness of the hind legs, mild fever (40°C, 104°F), increased pulse rate, pallor of the mucosae and emaciation. Jaundice is a frequent but inconstant feature of the disease. Case fatality is high and death occurs 1–5 days after the onset of clinical signs. Although once quite common, the prevalence of this form has decreased, possibly due to the use of feed additives containing arsenicals and to effective ectoparasite control.12
Anemia and weakness in neonatal pigs accompanied by low piglet viability and affecting several litters is another manifestation.12,13 Affected pigs are pale and lethargic and there is marked variation in birthweight within affected litters. Low birthweight piglets die shortly after birth. The anemia increases in severity between birth and weaning age, the pigs have skin palor, exercise intolerance, and there is considerable variability in weaning weights. The syndrome may or may not be accompanied by reproductive inefficiency characterized by delayed estrus cycles and embryonic death. Anemia, jaundice and poor growth rate can also present primarily in weaner pigs.14
Subclinical infections associated with subclinical anemia are reported to result in reproductive failure, anestrus and delayed estrus, reduced sow body condition, increased susceptibility to enteric and respiratory disease, and failure of feeder pigs to gain weight at the expected rate.12-14
Clinical disease has been considered uncommon and has largely been a problem in cattle that have been splenectomized for experimental use, disease occurring 1–4 weeks after the splenectomy. However, clinical disease is recorded in adult commercial dairy cattle15 manifest with lassitude, stiffness, pyrexia, diarrhea, and a fall in milk production.
Eperythrozoonosis has also been associated with a syndrome occurring in heifers in early to mid-lactation during the late summer and early autumn in which there was fever, swelling of the teats and the hindlimbs, lymph node enlargement and a fall in milk production. Signs of infection resolved in 7–10 days regardless of treatment.1 A similar transient disease occurring in the spring and summer months, and manifest with scrotal and hindlimb edema and infertility, has been recorded associated with eperythrozoonosis in young bulls.16
The presence of the organism can be established by examination of a blood smear taken during a clinical episode and when the animal has fever. In countries where there is no serological test available this may be the only method of diagnosis. Parasitemia is most intense prior to the development of clinical anemia and appears as 0.5–1.0 mm, coccoid, rod- or ring-shaped basophilic particles on red cells or free in plasma. Parasitemia is difficult to detect once clinical signs of disease are evident and very difficult in chronic disease. It is recommended that blood samples from a number of animals in the group be examined if eperythrozoonosis is suspected.
Lowered values for hemoglobin and packed cell volume (PCV) are evident on hematological examination of clinically affected animals and there is marked red cell anisocytosis and polychromasia with basophilic stippling and the presence of many Howell–Jolly bodies in sheep. A profound hypoglycemia may be demonstrated and there are elevated concentrations of unconjugated and total bilirubin.
The recent development of PCR-based assays has allowed a more precise and efficient method of detection and diagnosis and is much more sensitive than blood smear.2,17,18
Complement fixation test and an indirect fluorescent antibody test (IFA) have been used. With the complement fixation test sera from affected animals give positive reactions on the 3rd day of clinical illness, remain positive for 2–3 weeks, and then gradually revert to negative. Chronic carriers of the disease are usually negative reactors. The IFA test or an ELISA test are more suitable for serological studies as infected animals remain seropositive for significantly longer periods.5
The indirect hemagglutination test and ELISA test can be used in swine and are of value in herd diagnosis but may not detect infection in an individual pig, especially those under 3 months of age.12,19 Experimental challenge of splenectomized piglets may be used to determine the presence of infection. PCR may resolve laboratory detection diagnostic problems.20
A single intramuscular injection of tetracycline or oxytetracycline (3 mg/kg BW or more) is an effective treatment in sheep, with clinical improvement occurring in 24 hours in the early stages of the disease. Chronic infections are less responsive. Treatment of affected lambs with neoarsphenamine (30 mg/kg BW) or Antimosan (6 mg/kg BW antimony) is effective in relieving clinical illness, but does not completely eliminate the parasite. Imidocarb dipropionate also is effective in treatment but recrudescence at 2–4 weeks is common.
Control of disease in sows and neonates has been reported with the inclusion of chlortetracycline in the sow feed at 300 g/tonne, or by intramuscular administration of oxytetracycline to sows at 14 and 7 days before the expected farrowing date.12 Tetracyclines can also be used in feed or by in-line water medication in feeder pigs. With large flocks of sheep in enzootic areas, reinfection or recrudescence occurs so quickly that control by treatment may be an unwarranted expenditure.
In confined swine operations, the detection carrier pigs by PCR, and their subsequent removal has been proposed as a possible control procedure.17
1 Neimark H, et al. Int J Syst Evol Microbiol. 2004;54:365.
2 Messick JB. Vet. Clin Pathol. 2004;33:2.
3 McLaughlin BC, et al. J Am Vet Med Assoc. 1990;197:1170.
4 Mason RW, Statham P. Aust Vet J. 1991;68:116.
5 Kabay MJ, et al. Aust Vet J. 1991;68:170.
6 Heinritzi K. Tierarztl Umsch. 1992;47:588.
7 Gresham ACJ. Pig J. 1996;37:20.
8 Smith JE, et al. J Vet Med B. 1990;37:587.
9 Burkhard MJ, Garry F. Vet Clin Pathol. 2004;33:244.
10 Burroughs GW. S Afr Vet J. 1988;59:195.
11 Sutton RH, Jolly RD. Aust Vet J. 1973;21:160.
12 Gwaltney SM. Swine Hlth Prod. 1995;3:25.
13 Henderson JP, et al. Vet Rec. 1997;140:144.
14 Gresham A, et al. Vet Rec 134:71.
15 Goff WL, et al. Exp Parasitol. 1986;61:103.
16 Wells EG, et al. Theriogenology. 1995;43:427.
17 Hoelzle LE, et al. Vet Microbiol. 2003;93:185.
18 Vandervooort JM, et al. J Am Vet Med Assoc. 2001;219:1432.
19 Schuller W, et al. Berl Mnch Tierarztl Wochenschr. 1990;103:9.