A. Mycobacterium paratuberculosis - an acid-fast bacterium now known to share greater than 90 percent DNA homology with Mycobacterium avium, but still usually referred to as a distinct species. It has been proposed that it be classed as a subspecies of M avium.

 

B. Mycobacterium paratuberculosis is capable of causing disease (Johne’s disease) in all ruminants and paratuberculosis has been described in several wild and captive exotic species. Recent research has shown that Mycobacterium paratuberculosis may be involved in some cases of Crohn’s disease in humans.

 

C. May survive for extended periods in soil, water and manure in the environment; lives intracellularly in the animal and resists attempts by macrophages to kill inside the phagolysosome; is resistant to many common disinfectants but may be killed by cresylic acid compounds and sodium orthophenylphenol (Amphyl and O-Syl - National Laboratories)

 

D. Worldwide, various "strains" have been isolated from sheep, goats, and red deer in New Zealand. A pigmented and an "Icelandic" strain have been described from Europe. The existence of "strains" is now an accepted premise and has been documented by RFLP and DNA probing.

 

 

A. Contaminated food, water, bedding, and soiled udders are thought to be the major routes of spread of the organism. Recent studies in cattle suggest that colostrum and milk may provide significant exposure in some herds. To this author’s knowledge, no studies of milk-borne transmission in sheep have been reported, however, it is likely that it occurs.

 

B. Young animals less than aiz months of age are thought to be the most susceptible animals to infection; older animals may be more resistant to infection and development of disease but can develop a delayed hypersensitivity or serological response thus interfering with some diagnostic tests.

C. Intrauterine infection of the fetus in cattle has been well documented; ultimate disease status of the offspring is unknown. A confirmed isolation of Mycobacterium paratuberculosis from a sheep fetus in our laboratory was found in 1989 and again in 1990. Another report has demonstrated antibodies to Mycobacterium paratuberculosis in the serum of colostrum-deprived lambs.

 

D. Organisms enter the intestine and may enter the lamina propria via the dome or "M" cells of the Peyer’s patches in the small intestine. These cells are involved with the uptake of macromolecules and other particles. This is an active process which may contribute to the presentation of bacteria to macrophages. Macrophages phagocytize the organisms but generally are unable to kill them. Organisms multiply inside the macrophage which eventually dies.

Cellular responses to the proliferating organisms and bacterial and host cell remnants create the typical thickening and macro and microscopic distortion of the gut wall. Hypersensitivity reactions may increase the cellular response. Infected macrophages and cellular debris enter lymph vessels and travel to the mesenteric lymph nodes. Spill over of the processes may lead to cecal and colon involvement but this disease is basically a small intestinal disease.

 

Evidence suggests that, at times, a bacteremia may occur which may send organisms to other parts of the body. Organisms have been isolated from the endometrium and placentomes in the female bovine. The bacterium is also known to be present in the milk of some infected cows.

 

Recent research suggests that Mycobacterium paratuberculosis may stimulate cytokine production, such as tumor necrosis factor and possibly others, by the infected macrophage. Cytokines may serve to modulate the disease process, upregulate the activity of other agents such as that of OPP virus, or directly cause the wasting seen in this disease. All these actions have been demonstrated in AIDS patients with opportunistic infections such as M avium. It is now well accepted that much of the change seen in paratuberculosis and Crohn’s disease occurs as a result of an abnormal immune response.

 

E. Changes in the intestinal wall may lead to enteric protein loss and malabsorption. Cytokine production may contribute to the observed signs but the possible mechanisms are yet not well characterized. The characteristic sign in sheep is wasting and emaciation with normal stools or intermittent diarrhea. Profuse watery diarrhea as seen in cattle is not a common feature of the disease in sheep and goats.

 

 

A. Emaciation or wasting disease unresponsive to anthelmintics and antibiotics is the usual sign.

 

B. Appetite is often good, in spite of weight loss, until the animal is near death.

C. Normal stools are the usual observation even in clinically-diseased animals, but intermittent diarrhea or softened, pasty stools are occasionally observed.

 

D. Intermittent low grade fever may be observed.

 

E. Intermandibular edema, lethargy, and depression are sometimes seen.

 

 

A. intestinal parasitism

 

B. chronic malnutrition

 

C. caseous lymphadenitis with internal abscesses

 

D. ovine progressive pneumonia

 

E. environmental toxins, and neoplasia

 

 

A. Fecal or tissue culture may be unreliable in sheep using standard techniques used for cattle feces. It is the generally recognized "official" test and may require eight-24 weeks for colonies to be observed. Most laboratories hold cultures 12-16 weeks before reporting. Several reports from around the world have described difficulties in growing the bacteria from known infected sheep tissues and feces.

 

In goats fecal and tissue culture using cattle-adapted techniques seems to work satisfactorily. The existence of host-adapted "strains" may occasionally cause problems, however.

 

B. Necropsy and histopathology - may have some gross and microscopic lesions atypical of cattle

 

1. Corrugations of the mucosa of the small intestine and cecum are not always seen as is common in cattle.

2. The colon and rectum are not regularly involved grossly - disease is more often confined to the small intestine.

3. Cording, or prominence of the mesenteric lymphatics, is common as are swollen mesenteric lymph nodes.

4. Histopathologically, a great amount of variation can exist in the type of lesions seen ranging from low to very high numbers of bacteria observed on acid-fast staining, and diffuse epithelioid cell proliferation versus tubercle formation with giant cells. Necrosis, caseation, calcification, and fibrous tissue encapsulation may be observed more commonly in sheep than cattle. This variation may be a result of strain differences of organisms and of differences in the ability of the animal to mount an effective immune response.

 

C. Acid-fast staining of mucosal smears or lymph node smears reveals the presence of typical clumps of bacteria and acid-fast bacteria within macrophages

 

D. Intradermal johnin testing may yield many false positive and false negatives; however, the absence of any positives in a screening test of all animals may suggest that the herd or flock is negative. This test is not widely practiced in sheep and goats.

 

E. Serology

 

1. Complement fixation is the official test in some countries for cattle, but may be less frequently used in sheep. Cross reactions with Corynebacterium spp. have been reported, and the test has low sensitivity.

2. ELISA - may be very useful in the future but, problems with specificity make it less useful in culling individual animals except perhaps in high prevalence flocks. This assay lacks standardization at present and the difficulty of using culture as the "gold standard" complicates validation of tests.

3. Agar gel immunodiffusion (AGID) has had limited description for use in field cases. Most reported work done in sheep has been by the ADRI in Ontario, Canada, and investigators in Spain and at The Ohio State University. This test may be our most sensitive and specific serologic test in sheep, however, it may still lack sufficient sensitivity in subclinical animals to screen flocks.

 

The results of our studies (OSU) suggest low sensitivity but good specificity making it a good test for confirmation of clinical disease; use as a screening test in infected flocks may result in the finding of some non-clinical animals, but it will not find all of them.

 

F. DNA probe - The current probe available from IDEXX will detect the organism reliably, but the format and processing steps are only approved for cattle. The specificity is very high so that positives are true positives, but research has indicated that current technology requires that 103 or 104 organisms per gram of feces before the test will be positive. Fecal culture techniques used in cattle detect fewer numbers of bacteria in that species. The probe technique can be useful, but is currently quite expensive in most labs making it impractical for flock screening purposes.

 

 

A. Maintain a sanitary environment at lambing/kidding time. Clean the teats of ewes before the lamb nurses if feasible. Move young lambs to "clean" pasture as soon as is feasible.

 

B. Identify weight loss ewes or does and isolate them from the flock and young lambs until a diagnosis is made or until culled. Do not place these ewes in contact with young animals.

 

 

C. Because AGID testing seems to correlate well with bacterial load and shedding, test the infected flock with AGID tests prior to lambing to remove the heaviest shedders.

 

 

D. Consider depopulation, however, it may be difficult to repopulate with stock that can be verified free of infection.

 

 

E. Some flocks may be able to raise valuable lambs or kids as orphans in a separate, clean area in order to establish a new flock; in other words, establish two flocks much as is done for control of ovine progressive pneumonia. Lambs should not be allowed to nurse the ewe and should be raised on milk replacer. The possibility of in utero infection exists and can cause this technique to fail. As a precaution, progeny from infected ewes should be culled.

F. Be cautious when using cow colostrum for newborn lambs or kids. Infected cows may shed Mycobacterium paratuberculosis in their colostrum and milk, and many dairy herds in some areas of the US are infected. Pasteurization of colostrum may render it physically unsuitable but can be used. Some recent reports question the efficacy of pasteurization in destroying M. paratuberculosis. Be aware also that acute, fatal anemia has been occasionally reported in lambs following the use of cow colostrum.

 

 

G.Vaccination has been shown in cows, goats, and sheep to lower the number of clinical cases in the herd or flock but will not prevent all animals from becoming infected. Some vaccinates shed bacteria and a proportion will develop clinical signs. Much work needs to be done with vaccines to evaluate their usefulness as reports from around the world are somewhat contradictory. Currently available vaccines may interfere with ELISA and other serology and frequently cause reactivity in tuberculin testing. There is no licensed vaccine available for sheep in the US, and in most states the cattle vaccine is used at the discretion of the state veterinarian’s office.

 

 

H. Maintain a closed flock if possible.

 

 

I. When purchasing animals, ask questions of the seller concerning the paratuberculosis status of his flock and consider serology using ELISA or AGID prior to purchase or addition of animals to the flock. Alternatively, DNA probe testing may be feasible and offers the advantage of detecting animals shedding the bacteria.

 

Synonyms: OPP, maedi, maedi-visna, la bouita, zwoegerzietke

Ovine progressive pneumonia is a true "slow virus" infection in sheep related antigenically to the viruses of caprine/arthritis/encephalitis and a newly isolated retrovirus of sheep.

A. Occurrence is worldwide and relatively recently described with signs appearing in not only the respiratory system, but also the joints, mammary gland, and CNS. Recent reports from the United States and Canada (not statistically based surveys) suggest that about 60 percent of flocks surveyed had at least one infected animal.

B. Signs are related to the presence of a non-oncogenic retrovirus whose target cell is the macrophage, predominantly those of the above systems. Cellular response to the viral-infected cell creates the pathology in the animal.

C. Viral strains of at least two immunogroups are described, and published literature supports the hypothesis that the infecting strain may influence disease progression rate and severity. Exposure dose, and management variables such as ventilation, population density, and breed may influence the extent of disease seen. Some flocks with relatively high infection rates have a low incidence of clinical signs. Others seem to have extensive signs related to the virus.

D. Recent evidence from tissue culture work and extrapolation from AIDS patients (the virus may mimic pediatric and CNS AIDS) suggests that presence of intracellular (macrophage) Pasteurella hemolytica and Corynebacterium pseudotuberculosis may enhance production of tumor necrosis factor and alpha interferon which could serve to accelerate viral replication and expression. Since viral expression enhances the cellular response, this phenomenon may explain differences in flock presentation with the disease.

E. The virus is spread by colostrum, direct contact with nasal secretions, and aerosols but is dependent on cellular transmission. Since the presence of cells in circulating macrophage populations (as in the blood) is very low, iatrogenic transmission is unlikely in contrast to bovine leukosis, a retrovirus located in "C" type lymphocytes.

F. Incubation period from exposure to seroconversion is from one to six months based on current serological methods. Newer methods (ELISA and Western Blot) suggest that essentially all infections result in seropositivity with adequate test methods. New ELISA technology may offer greater sensitivity than current agar gel immunodiffusion testing (AGID).

G. Goats can be infected with OPP virus and sheep with CAE virus. Serology by AGID detects either virus with the same test. Experimentally, it does not appear that these viruses cause disease in the alternate specie even though very closely related.

 

A. Usually no clinical signs are seen before two years-of-age although pathology can be observed in lambs histologically. Clinical signs can be observed experimentally as early as two months-of-age with specific strains and infecting doses. (a model for pediatric AIDS)

B. Signs in the respiratory system are produced by the body’s cellular response to virus-infected macrophages. Cellular proliferation, predominantly lymphocytes, cause septa to thicken, alveolar cells to transform to cuboidal, and peribronchiolar and perivascular tissues to undergo thickening and hyperplasia. Germinal centers may form. Eventually, functional tissue is crowded out and the animal is hypoxic. Bacterial complications of the tissues are common and superimposed on the progressive change.

C. Signs are those of hypoxia and are gradual and progressive. Weight loss is usual and may be related to cytokine production as well as tissue change. Tumor necrosis factor (formerly known as "cachexin") has been implicated as a possible cause of the weight loss. Bacterial complications may produce signs of bacterial pneumonia. The "thin ewe syndrome" includes OPP.

D. Signs related to arthritis, non-indurative mastitis ("hard bag syndrome"), and CNS lesions may accompany the respiratory signs and are similarly related to the body’s response to the infected macrophage.

 

A. Signs and post mortem lesions are characteristic. Post mortem reveals heavy non-collapsing lungs with red to reddish-brown coloration. Lungs may weigh more than 2X normal (normal = 300-500 grams, diseased = 1200 grams), and the pulmonary lymph nodes may be enlarged to cigar size. Cut sections of the lungs resemble liver.

B. Serum testing by agar gel immunodiffusion is available and has high specificity. However, sensitivity may be lower than desired for flock testing. A positive serum test does not indicate a symptomatic animal has advanced lesions of OPP. As with other retroviral infections, the infection is permanent, the animal is usually seropositive within 6 months of infection, and remains so for life. Like bovine leukemia virus, many animals in a flock may be infected and only some of them will show clinical disease. A positive serum test (AGID) for OPP, therefore, only indicates the animal has the virus.

C. Histopathology is usually diagnostic but early lesions can resemble those of Mycoplasma infections.

D. AGID testing is currently available but may only detect 65-75 percent of the animals with the virus. ELISA testing, using recombinant DNA antigen production, has been developed and looks promising. This test has not yet had extensive field testing but should be an improvement over AGID.

 

 

A. There is no treatment.

B. Prevention can only be accomplished by establishing an uninfected flock by serosurvey and culling. Pre-purchase testing, quarantine, and retesting after six months are necessary to prevent introduction to the flock. Alternatives to eradication can be developed for specific flock needs and center around testing and culling selectively with the ultimate goal of reducing the number of infected animals to a low level. Removing lambs at birth, before they can ingest the dam’s colostrum, and rearing them using milk replacer and heat treated colostrum, or bovine colostrum, will result in significant reduction in the prevalence of infected animals and possible eradication. It is labor intensive and potentially costly but may be preferable to testing and culling in heavily infected flocks.

C. Controversy currently exists as to the economic importance of this disease. Some studies have failed to show significant economic loss in terms of lamb growth and conception rate. Others have suggested that conception rates in seropositive ewes may only be 66 percent of those of seronegative ewes - a significant loss. Decisions about eradication and prevention must be made at the flock level with producer goals and disease history of the flock in mind.