Paratuberculosis Importance Paratuberculosis is a chronic intestinal disease, caused by avium ssp. paratuberculosis, that primarily affects and camelids. When this organism exists Johne’s Disease in a herd and no control measures are employed, animals usually become infected early in life, many become asymptomatic chronic carriers, and a few carriers develop overt disease, usually after several years. Symptomatic animals generally die from or are culled Last Updated: October 2017 due to the illness. None of the currently available drugs seems to be able to eliminate M. avium ssp. paratuberculosis from an infected animal. Unless testing is done, paratuberculosis can exist undetected in a herd for years. Clinical cases can be particularly difficult to recognize in , which often have more subtle clinical signs than cattle. In herds or flocks with uncontrolled paratuberculosis, the prevalence of tends to gradually increase, and greater numbers of animals become sick. This disease can also cause production losses, such as decreased yield. M. avium ssp. paratuberculosis can infect animals other than its usual hosts, but the significance of these is still mostly unclear. This organism has been proposed to have a causative role in Crohn’s disease, a chronic enteric disease of humans. While this is still controversial and unproven, concerns about a potential zoonotic role have helped stimulate the development of control programs for paratuberculosis. To date, these programs have generally been more successful in reducing the prevalence of infection and clinical cases than in eliminating the organism from a herd. Etiology Paratuberculosis results from infection by Mycobacterium avium subspecies paratuberculosis, an acid-fast rod in the M. avium complex of organisms, within the family Mycobacteriaceae, order Actinomycetales. Its name is frequently abbreviated as MAP. Former names for this organism include Mycobacterium paratuberculosis and M. johnei. M. avium ssp. paratuberculosis strains have been divided into at least two groups, which seem to have some degree of host preference. Type II strains (which are also known as type C) were originally identified in cattle, but they have a broad host range that includes sheep, goats, camelids and both and nonruminant wildlife. Type I (type S) strains are found most often in small ruminants; however, they have increasingly been reported in other species including cervids, South American camelids and camels, as well as in some cattle in close contact with sheep. Type III strains were once a separate “intermediate” group, but are now considered to be a subtype of type I. There are also two different bison type (B) strains, one in North America and the other in Asia. The latter is a sublineage of type II, and is known as “Indian Bison type.” It has been found in cattle, water buffalo, sheep, goats, deer, bison, rabbits, wild boar and other animals, and is the predominant strain in some parts of Asia. A goat-specific strain was proposed to exist in Norway, where paratuberculosis mainly seems to affect goats, and only sporadic infections have been reported in cattle and sheep. One genetic analysis found evidence for a distinct goat strain, but other studies have been unable to confirm this, and management factors or breed-related resistance in cattle could also explain the situation in Norway. Species Affected Paratuberculosis mainly affects ruminants and camelids. Some animals reported to develop clinical signs include cattle, sheep, goats, water buffalo, South American camelids, dromedary (Camelus dromedarius) and Bactrian (Camelus bactrianus) camels, moose, reindeer (Rangifer tarandus), bison (Bison bison), wild relatives of small ruminants (e.g., bighorn sheep, Ovis canadensis; Rocky Mountain goats, Oreamnos americanus) and various species of deer, antelope and elk. M. avium ssp. paratuberculosis infections have also been reported in captive or wild ruminants and camelids not (yet) reported to have clinical signs. Domesticated ruminants are thought to be the primary reservoirs for this organism. Wildlife mostly seem to become infected from domestic herds, although a few wild cervid populations may maintain this organism locally.

www.cfsph.iastate.edu Email: [email protected] © 2003-2020 page 1 of 11 Paratuberculosis M. avium ssp. paratuberculosis has also been found in saliva of cattle, but the significance of this finding is diverse other hosts, i.e., members of families other than the currently unclear. The offspring of a number of species, Ruminantiae and Camelidae. Some species reported to be including cattle, sheep, red deer and chamois, can be born susceptible to infection include European rabbits infected. In cattle and sheep, this is more likely if the dam is (Oryctolagus cuniculus), wild hares (Lepus europaeus), in an advanced stage of paratuberculosis. However, prenatal dogs, cats, horses, pigs, wild boar (Sus scrofa), red foxes transmission is reported to be very high in both symptomatic (Vulpes vulpes), stoats (Mustela erminea), Eurasian otters and asymptomatic red deer. Animals can also shed M. avium (Lutra lutra), weasels (Mustela nivalis), beech marten ssp. paratuberculosis, to varying degrees, in colostrum and (Martes foina), Egyptian mongooses (Herpestes milk. Shedding appears to be more common in clinically ichneumon), badgers (Meles meles), skunks (Mephetis affected than asymptomatic animals, and bacterial numbers mephetis), brown bears (Ursus arctos), raccoons (Procyon seem to be highest during the first 2 months of the lactation. lotor), armadillos, coyotes (Canis latrans), opossums M. avium ssp. paratuberculosis has been detected in semen. (Didelphis virginiana), and various species of nonhuman Although young animals can be born infected, most primates, Australian marsupials, rodents and shrews. Rabbits cattle and sheep are thought to acquire M. avium ssp. have been proposed as possible reservoir hosts in some areas. paratuberculosis during the first few months after birth, Illnesses and/or gross lesions consistent with probably when they nurse (via colostrum, milk or fecal paratuberculosis have been reported in wild rabbits, contamination of the udder) or are housed in contaminated nonhuman primates, pigs and dogs, as well as in pens. Animals can also become infected later in life, experimentally infected horses inoculated intravenously, but including as adults, but susceptibility (and/or the ability to a causative role was not always proven (see Clinical Signs control the infection) seems to decrease with increased age. section for details). M. avium ssp. paratuberculosis has also In cattle, susceptibility appears to be highest in calves < 6 been found in some birds, including members of the months of age, and lowest in adults > 1 year. Calves are Corvidae (jackdaws, rooks, crows), starlings, house sparrows considered to be at greatest risk when they are exposed to the (Passer domesticus) and gulls. feces of infected adults, but infected calves sometimes shed the organism and can transmit it to each other. Zoonotic potential M. avium ssp. paratuberculosis can be spread on M. avium ssp. paratuberculosis can be found in the fomites, and some animals might be infected via aerosolized intestinal tract of some healthy people. This organism is also contaminated dust. This organism is common in the proposed to have a role in causing Crohn's disease, a chronic environment, especially on contaminated farms; however, it intestinal illness of unknown etiology. There is evidence does not multiply outside a living host. It can survive for a both for and against this hypothesis, and a causative role is year or more on some pastures, although infectivity is currently unproven (see Public Health). Some investigators reported to decrease significantly within a few months. have suggested that M. avium ssp. paratuberculosis might Survival is greatest in full shade and lower in sunny areas. play a role in the onset or progression of a variety of other M. avium ssp. paratuberculosis has also been reported to diseases (e.g., sarcoidosis, diabetes mellitus types 1 and 2, persist in some water sources for maximum periods ranging multiple sclerosis, HIV infection, Hashimoto’s thyroiditis), from 9 months to nearly 2 years; in barn dust for at least based mainly on the presence of antibodies to this organism. several weeks; and in bovine feces for up to 8-11 months. One review described weak but consistent evidence for a Uptake into plants has been demonstrated, although one field possible association with diabetes mellitus type 1 in some study suggested that this organism is more likely to persist in studies, but not all. For the other diseases, any role appears soil than harvested crops. Some data suggest that it could to be speculative at this time. become dormant for a limited time in the environment. M. Geographic Distribution avium ssp. paratuberculosis has been reported to form spore- M. avium ssp. paratuberculosis is thought to occur like structures that may help it survive adverse conditions. It worldwide. Some countries report never having detected this might also survive (and possibly multiply) in free-living organism. However, only Sweden and some states in amoebae, but whether this occurs to any significant extent in Australia are currently proven to be paratuberculosis-free. nature is currently unclear. Insects have been proposed as An unusual situation exists in Norway, where this disease possible mechanical vectors. affects goats but infections in other species seem to be Little is known about the transmission of M. avium ssp. uncommon. paratuberculosis in nonruminant hosts, but fecal-oral spread is probably important. In rabbits, this organism has been Transmission isolated from the feces and milk, and from fetuses and the M. avium ssp. paratuberculosis is transmitted mainly by testes. Both horizontal and vertical transmission seems to the fecal-oral route. Some asymptomatic and sick animals occur in wild rabbit populations. Predation might be a route shed large numbers of organisms in the feces. Others may of transmission to carnivores or omnivores. shed intermittently, transiently or not at all during the subclinical stage. Nucleic acids have been detected in the

© 2003-2020 www.cfsph.iastate.edu  Email: [email protected] page 2 of 11 Paratuberculosis Disinfection While the clinical signs are generally similar in other M. avium ssp. paratuberculosis is resistant to most ruminants and camelids, there can be some differences, disinfectants, and tuberculocidal agents should be employed. particularly in the presence and extent of . Weight Some disinfectants reported to be effective against members loss and exercise intolerance are prominent signs in sheep of the M. avium complex include sodium hydroxide, chlorine and goats, and affected animals may trail the flock. Diarrhea dioxide, ethylene oxide, 0.35% peracetic acid and is less common than in cattle, it is more likely to appear as orthophthalaldehyde. M. avium ssp. paratuberculosis may soft feces than frank diarrhea, and it may be intermittent. survive drinking water treatment, including chlorination. Some small ruminants have submandibular ("bottle jaw") without other evidence of edema, and the wool is often While of milk kills large numbers of M. damaged and easily shed. Anemia is also reported to be avium ssp. , some reports indicate that a small common. South American camelids may also have no percentage of the organisms might survive, depending on apparent diarrhea despite other signs of advanced their initial numbers and the specific combination of heat and paratuberculosis. However, diarrhea is a common sign in time. Other reports suggest that pasteurization is effective, some cervids, and it is reported to be severe in some camels. and unrealistically high initial pathogen concentrations or The course of the illness may be unusually rapid in both defects in the pasteurization conditions could account for cervids and camels. most studies reporting treatment failures. Standard heat treatments for colostrum, such as 56-59°C Other species (133-138°F) for 60 minutes, can significantly decrease the The effects of M. avium ssp. paratuberculosis on other number of M. avium ssp. paratuberculosis, but they do not hosts are still largely unknown. Many infected animals were necessarily kill all of the organisms. Complete destruction identified during surveillance for this organism, and either may not be achievable, as colostral antibodies must be did not have clinical signs or were not observed before death preserved and the colostrum should not become too viscous (e.g., surveys of hunter-killed animals). Intestinal lesions to feed. consistent with paratuberculosis and/or illnesses have been reported in a few species. Incubation Period M. avium ssp. paratuberculosis can cause diarrhea and The incubation period for paratuberculosis ranges from weight loss in orally inoculated rabbits, but whether it affects months to years. Incubation periods of 2-5 years are common naturally infected animals is controversial. Some studies in cattle, which rarely show clinical signs before they are 2 have found gross lesions in wild rabbits, but others only years old. In rare cases, the incubation period may be as long detected microscopic lesions. This organism was also found as 15 years. Paratuberculosis can appear sooner in small in a South African dog that had a fever, progressive weight ruminants, cervids and some camelids. In these species, it is loss and debilitation, associated with granulomatous ileitis, not unusual to see clinical cases in animals that are less than splenomegaly and abdominal lymphadenopathy. A survey a year old. Some cervids may become ill as soon as 5-8 found nucleic acids in intestinal biopsies from some dogs months of age. with gastrointestinal signs due to food allergies or Clinical Signs inflammatory bowel disease, as well as some dogs that had mild or no lesions and might have been affected by non-GI Ruminants and camelids causes of vomiting and diarrhea. Paratuberculosis typically presents as sporadic clinical Reports of paratuberculosis in pigs and horses are rare, cases in most species, including cattle and small ruminants. and date from before the advent of nucleic acid methods However, it can appear as an outbreak in cervids, affecting (e.g., PCR) for definitive identification of this even young animals. microorganism. A pig suspected to have paratuberculosis In cattle, the major clinical signs are diarrhea, typically had intestinal lesions ("hyperplastic enteritis") containing without blood, mucus or epithelial debris, and . The acid fast bacilli; however, other M. avium serotypes can initial signs can be subtle, and may be limited to weight loss, cause granulomatous enteritis in pigs, and the organism's decreased milk production or roughening of the hair coat. identity was not confirmed. In a later report, a Diarrhea can be intermittent at first, but it becomes more mycobacterium was found in a herd of asymptomatic pigs constant and severe over weeks or months. Tenesmus is not with lesions, and the organism's identity was seen. Some cattle also develop subcutaneous edema, established by experimental inoculation into calves. especially submandibular and/or ventral edema, as the result Experimentally infected pigs appeared to be unaffected in of decreased plasma concentrations. Body one study, but grew more slowly than control pigs, without temperature and appetite are usually normal, and animals are obvious clinical signs, in another report. Pigs developed alert. Paratuberculosis is progressive; affected animals lymph node lesions (caseous nodules) in both studies. One of become increasingly emaciated and usually die with terminal the studies reported that they also had intestinal lesions cachexia and dehydration. consisting of diffuse areas of granulomatous inflammation in the and infrequently the large intestine.

© 2003-2020 www.cfsph.iastate.edu  Email: [email protected] page 3 of 11 Paratuberculosis A report of M. avium ssp. paratuberculosis in a horse Limited information is available for nonruminant described the isolation of a mycobacterium from the species. Thickened, often corrugated, intestinal walls, and mesenteric lymph nodes, but did not mention any clinical enlarged, edematous, and granulomatous to abscess-like signs. The isolated organism produced paratuberculosis tuberculous lesions in the regional lymph nodes have been lesions when it was inoculated into calves. This article also reported in rabbits. Intestinal lesions are reported to be most mentioned that MAP-like organisms were found in the common in the cecal appendix, sacculus rotundus and cecum mesenteric lymph nodes of a farm horse with profuse in this species. Microscopic lesions have sometimes been diarrhea and a corrugated small intestine in 1913. reported in other species including foxes and stoats; Experimentally infected horses developed intestinal lesions however, gross lesions are usually mild or absent. Few or no (granulomatous inflammation), lymph node lesions and lesions have been reported in wild and rodents. clinical signs (weight loss, rough hair coat, transient diarrhea) after intravenous inoculation. However, horses fed Diagnostic Tests bacteria had no lesions or signs of illness. The best tests to identify infected animals can vary depending on the stage of the disease. Animals in the early Post Mortem Lesions Click to view images stages of the infection may not be recognizable with any of The carcasses of animals with advanced disease are the current tests. usually thin or emaciated. There may be dependent edema Ziehl–Neelsen stains can be used for a presumptive and/or fluid in the body cavities. diagnosis in clinical cases; clumps of small, strongly acid- The characteristic lesion in cattle is a thickened, often fast bacilli in the feces suggest that the signs might be caused corrugated, intestinal wall, most apparent in the distal small by M. avium ssp. paratuberculosis. Organisms may also be intestine. In some advanced cases, lesions may extend from found in smears from the intestinal mucosa or the cut the jejunum to the colon. Discrete plaques may be present surfaces of lymph nodes. Bacteria can be sparse or absent in early in the disease, and can sometimes be detected by some infected animals. Histopathology can also be helpful in holding the intestines up to a light source. The intestinal diagnosis. Immunostaining methods can detect organisms in mucosa is not usually ulcerated. The mesenteric lymph nodes tissue samples, but the antibodies may cross-react with other and other regional nodes (e.g., ileocecal nodes) are often mycobacteria. enlarged and edematous, and subserosal lymphatics tend to M. avium ssp. paratuberculosis or its nucleic acids can be prominent. Gross lesions are usually absent or subtle in be found in the feces, intestinal tract and associated lymph subclinical carriers, and they are occasionally absent or nodes at necropsy. Commonly recommended samples for minimal in clinical cases. The lesions in South American culture include the , mesenteric and ileocecal lymph camelids are reported to be similar to those of cattle, but there nodes and liver, although the organism may also be detected may also be lymph node necrosis and mineralization. at other sites. Posterior jejunum and the ileocecal lymph Affected areas of the intestines are often only slightly nodes were the most valuable necropsy samples for detecting thickened in sheep, and may appear normal even in sick mild lesions in subclinically infected red deer. Biopsies of animals. Certain type I (S) strains of M. avium ssp. the ileum and regional lymph nodes may occasionally be paratuberculosis, which are more common in sheep than useful in valuable domesticated animals. Milk can also be cattle, produce a pigment that stains the intestinal lesions tested, and environmental sampling is sometimes used to yellow or brownish–yellow. Caseated or calcified foci are detect infected herds. sometimes found in the intestines and associated lymph nodes M. avium ssp. paratuberculosis may grow on a number of sheep, goats and cervids. Some goats have lesions that are of specialized culture media, but some strains, such as those similar to those of sheep, with little or no thickening of the belonging to type I (S), are more difficult to isolate. One intestinal wall. However, there are also reports of naturally group found that a number of type I and type II strains all infected goats with severe, diffuse intestinal lesions that are grew on Middlebrook 7H10 and 7H11 media with especially prominent in the proximal jejunum. Reported mycobactin J, although some did not grow on other lesions in some of these animals included a thickened commonly-used media. Some authors suggest culturing intestinal wall; mucosal lesions described as “cobblestone- organisms on more than one medium. M. avium ssp. like,” with hyperemia, ulcerations and fibrinous exudates; and paratuberculosis grows slowly, and depending on the strain fibrous peritoneal adhesions and intestinal strictures in some and culture medium, results may not be available for several cases. Some experimentally infected goats developed typical weeks or months. paratuberculosis lesions (e.g., caseous nodules or segmentally PCR assays are rapid, and are often used for diagnosis. thickened, corrugated small intestinal mucosa). Others had Loop-mediated isothermal amplification (LAMP) methods crater-like lesions, which sometimes progressed to become have also been published. Specialized genetic techniques, confluent, in the small intestines. Granulomatous lesions have such as pulsed-field electrophoresis and restriction fragment also been noted occasionally in other organs, especially the length polymorphisms, are useful for epidemiological liver, of sheep, wild small ruminants, cervids, South American investigations, and can distinguish type I and II strains. camelids and captive saiga antelope (Saiga tatarica).

© 2003-2020 www.cfsph.iastate.edu  Email: [email protected] page 4 of 11 Paratuberculosis Serology can be useful for the presumptive M. avium ssp. paratuberculosis exists in a herd or flock. identification of infected animals, or to help confirm Control programs, such as the voluntary Johne's Disease paratuberculosis in animals with clinical signs. Enzyme- Herd Status Program in the U.S., can identify herds at low linked immunosorbent assays (ELISAs), complement risk for being infected. Minimizing contact between wildlife fixation and agar gel immunodiffusion tests are available. and livestock decreases the risk that a wild animal might ELISAs are more sensitive and more likely to detect infect a MAP-free herd, or (more likely) that an infected herd subclinically infected cattle, but CFT and AGID are also will transmit paratuberculosis to wild species. useful in clinical cases. ELISAs that detect antibodies in milk Once paratuberculosis has entered a farm, the basic are available. Detectable titers are slow to develop in infected control techniques are 1) to protect animals from exposure to animals: serum titers usually appear 10-17 months after infectious manure, colostrum and milk while they are young infection, but may take longer. Serological responses can be and most susceptible to infection, and 2) to decrease overall weak in some infected animals that are not shedding bacteria. exposure to M. avium ssp. paratuberculosis in the herd. Conversely, animals that have cleared the infection may be While these measures may not eliminate the organism, they seropositive. False positive reactions can be caused by other can decrease the prevalence of infection and result in fewer mycobacteria and some other organisms. animals with clinical signs. Intradermal testing with johnin or avian purified protein Test and removal programs reduce the level of exposure derivative tuberculin can detect delayed-type by periodically testing a herd or flock, and separating and/or hypersensitivity (DTH) reactions to M. avium ssp. culling the infected animals, especially those shedding large paratuberculosis; however, this test is insensitive and numbers of organisms. The offspring of infected dams, nonspecific reactions are common. The gamma interferon particularly dams that are sick, may also be considered for assay, an in vitro test that detects cell-mediated immunity to removal. Good manure management and disposal are M. avium ssp. paratuberculosis, can identify some expected to help reduce environmental exposure. Manure subclinically infected animals before antibodies can be found build-up should be prevented, and surfaces should be kept in serological tests. Cross-reactivity with other organisms clean. Food and water troughs may be elevated to reduce can result in false positive reactions in both tests. contamination. Piped water is less likely to be contaminated Both antibody levels and cell-mediated immunity can than ponds. Occasionally (e.g., in disease-free countries), diminish or become undetectable in advanced disease. entire herds may be culled and restocked with uninfected animals. One study found that high pressure washing, Treatment disinfection and a 2-week waiting period reduced There is no known cure for paratuberculosis. A few environmental contamination below detectable levels. animals have been treated with various drugs including In infected cattle herds, management practices help isoniazid, rifampin, clofazimine, aminoglycosides and other protect calves during the period when they are most agents. The use of probiotics has also been explored. susceptible to M. avium ssp. paratuberculosis. Cows should Treatment may result in clinical improvement and prolong the give birth in clean, dedicated maternity pens to minimize their animal’s life, but lifelong treatment is thought to be necessary, offspring’s exposure to infectious feces at birth. One study and some animals nevertheless relapse. Milk or meat from suggested that individual calving pens are more effective than treated animals should not be used for human consumption. group pens. Calves are also removed from their dams at birth, Control fed colostrum from cows free of M. avium ssp. tuberculosis (or colostrum replacement products) and raised separately Disease reporting from the adult herd. Milk replacer or pasteurized milk, rather Veterinarians who encounter or suspect paratuberculosis than raw milk, should be fed until the calves are weaned. should follow their national and/or local guidelines for (Because this organism might still be present in some disease reporting. Paratuberculosis is a reportable disease in pasteurized milk, milk replacer is thought to be safer.) U.S. many U.S. states; state regulations should be consulted for paratuberculosis programs recommend that calves remain more specific information. separated from adult cattle for at least their first year. Some authors suggest it would be ideal to also separate calves of Prevention different infection status; however, this may be impractical or M. avium ssp. paratuberculosis is usually introduced even impossible to accomplish. Chemoprophylaxis with into a herd in an infected animal and persists in breeding monensin has been investigated in some calves. stock. While it may be useful to test herd additions, Similar management measures can be used in young diagnostic tests on individual animals are unreliable for animals of other species, to the extent that they are practical. ensuring freedom from infection, especially in animals < 3 The practice of feeding bovine colostrum to some neonatal years of age. For this reason, farmers should buy replacement alpacas has been mentioned as a possible risk factor in this animals from test-negative herds with good records and species. In all species, feeding pooled milk or colostrum management practices. Multiple tests, conducted over a increases the risk that young animals will be exposed to an prolonged period, are often necessary to determine whether adult shedding M. avium ssp. paratuberculosis.

© 2003-2020 www.cfsph.iastate.edu  Email: [email protected] page 5 of 11 Paratuberculosis Vaccines are available in some countries for cattle, in cattle that are able to control the infection, and the most sheep and goats, and they have also been investigated in red significant losses occur in animals that will progress to develop deer. Vaccines can decrease the incidence of clinical signs, clinical signs. and may also reduce shedding of the organism. They are an What proportion of carriers will eventually develop important component of some control programs in sheep. clinical signs is still uncertain; however, some studies suggest Consistent vaccine use in this species, generally in young that most infected cattle and sheep are able to control the replacement animals, appears to reduce the prevalence of organism and do not become ill within their expected lifetimes. infection within a flock. Some countries restrict vaccine use, In calves, lambs and red deer, progression to disease seems to usually due to concerns about interference with tuberculosis be more likely if they are infected when young. While testing. experimentally infected cattle can repeatedly start and stop Control programs for paratuberculosis have been shedding high numbers of mycobacteria, one recent study established in a number of countries. They range in size and suggests that only a small percentage of naturally infected cattle scope from small independent programs to large (<10%) become high shedders, and these animals usually die government-run initiatives. Most programs assist farmers in or are culled within a year. In this study, animals that identifying and maintaining paratuberculosis-free herds continuously shed M. avium ssp. paratuberculosis were likely and/or help infected farms reduce the prevalence of to become high shedders, even if the numbers of organisms infection. Eradication is the eventual goal of a few national were initially low. Animals that shed organisms intermittently programs, such as those in Denmark and the Netherlands. A and in low numbers appeared less likely to progress to clinical few countries have strict programs that keep herds in signs. There is also some evidence that genetic background paratuberculosis-free regions from becoming infected. may influence disease progression in cattle and red deer; however, the genes involved are not well understood. Morbidity and Mortality M. avium ssp. paratuberculosis is common in many Public Health dairy-producing countries, where approximately 20-50% or Possible association with Crohn’s disease more of the dairy cattle herds are often infected. This M. avium ssp. paratuberculosis has been proposed to organism can also be a significant problem in sheep, goats have a role in some human diseases. In particular, some and captive red deer. Its overall prevalence is usually much studies suggest that this organism might be involved in lower in beef cattle; nevertheless, paratuberculosis can be a Crohn’s disease, a chronic enteritis of humans. Crohn’s health issue in some beef herds. A number of zoos have disease is characterized by periods of malaise, abdominal reported finding M. avium ssp. paratuberculosis, including pain, chronic weight loss and diarrhea, with remissions and some that have detected it in exotic ruminants. This organism relapses. It often begins between the ages of 16 and 25 years, has been described in pigs, but infections seems to be and persists lifelong. The cause of Crohn’s disease is not uncommon in this species. Its prevalence also tends to be low known; however, it may result from several interacting in most wildlife populations, although reservoirs do seem to factors including a genetic predisposition, an abnormal exist in some regions. immune response, and environmental factors such as Most cattle and sheep that are exposed to M. avium ssp. responses to intestinal microorganisms. paratuberculosis either eliminate the organism or become M. avium ssp. paratuberculosis can be found in both asymptomatic carriers, while a minority develops clinical healthy people and Crohn's disease patients. However, some signs. Affected animals eventually die. Clinical cases tend to studies suggest that the organism itself, its nucleic acids be sporadic in most species, and the is and/or serological evidence for exposure are more common approximately 1% in most dairy cattle herds. However, captive in people with Crohn’s disease. These studies vary in their deer can experience outbreaks of rapidly progressive disease, methodology and quality, and not all show a link. One issue with morbidity rates up to 20% reported in some herds of red with the MAP hypothesis is that recent studies could not find deer. In a newly infected cattle herd, M. avium ssp. an association between Crohn's disease and living on a farm, paratuberculosis usually spreads for years before the first contact with infected domesticated animals, or the clinical cases appear. If no preventive measures are taken, the consumption of dairy products. Nevertheless, it should be number of infected animals tends to gradually rise, young kept in mind that wider environmental or food sources could animals are exposed to increasing doses of bacteria, and clinical also be sources of exposure. Another issue is that studies to cases appear more frequently – first in older animals and later, date have not been able to demonstrate a direct or indirect as the exposure level increases, also in younger animals. In causative role for M. avium ssp. paratuberculosis in the herds where the organism is widespread, clinical signs can be pathogenesis of Crohn’s disease. Even if this organism is seen in second- and first-calf cows, and even in springers or common in patients, it might simply be an “innocent bred heifers. Paratuberculosis can also cause production losses, bystander” that is more likely grow in an inflamed intestinal including reduced milk yield, in subclinically infected cattle. wall. Therefore, whether M. avium ssp. paratuberculosis The extent of milk production losses is controversial. One plays a role in Crohn's disease is currently unclear, but the recent study suggested that milk yield might return to normal possibility cannot be discounted.

© 2003-2020 www.cfsph.iastate.edu  Email: [email protected] page 6 of 11 Paratuberculosis Vaccine safety Antognoli MC, Hirst HL, Garry FB, Salman MD. Immune Paratuberculosis vaccines, which are oil-based, can response to and faecal shedding of Myobacterium avium subspecies paratuberculosis in young dairy calves, and the cause severe local reactions including tissue sloughing, association between test results in the calves and the infection chronic synovitis and tendonitis, if they are accidentally status of their dams. Zoonoses Public Health. 2007;54:152-9. injected into humans. The severity of the reaction may Arrazuria R, Juste RA, Elguezabal N. Mycobacterial infections in depend on the amount of vaccine injected and amount of rabbits: from the wild to the laboratory. Transbound Emerg tissue damage. Some cases can require surgery. Dis. 2017;64(4):1045-8. Atreya R, Bülte M, Gerlach GF, Goethe R, Hornef MW, Köhler Internet Resources H, Meens J, Möbius P, Roeb E, Weiss S; ZooMAP Consortium. Facts, myths and hypotheses on the zoonotic International Association for Paratuberculosis nature of Myobacterium avium subspecies paratuberculosis. http://www.paratuberculosis.org/ Int J Med Microbiol. 2014;304(7):858-67. Barkema HW, Orsel K, Nielsen SS, Koets AP, Rutten VPMG, et Mycobacterial Diseases of Animals al. Knowledge gaps that hamper prevention and control of http://mycobacterialdiseases.org/ Myobacterium avium subspecies paratuberculosis infection. The Merck Veterinary Manual Transbound Emerg Dis. 2017 Sep 22 [Epub ahead of print]. http://www.merckvetmanual.com/ Beard PM, Daniels MJ, Henderson D, Pirie A, Rudge K, Buxton D, Rhind S, Greig A, Hutchings MR, McKendrick I, University of Wisconsin School of Veterinary Medicine Stevenson K, Sharp JM. Paratuberculosis infection of Johne’s Information Center nonruminant wildlife in Scotland. J Clin Microbiol. http://www.johnes.org/ 2001;39:1517-21. Beard PM, Stevenson K, Pirie A, Rudge K, Buxton D, Rhind SM, World Organization for Animal Health (OIE) Sinclair MC, Wildblood LA, Jones DG, Sharp JM. http://www.oie.int Experimental paratuberculosis in calves following inoculation with a rabbit isolate of Myobacterium avium subsp. OIE Manual of Diagnostic Tests and Vaccines for paratuberculosis. J Clin Microbiol. 2001;39:3080-4. Terrestrial Animals Bolton MW, Pillars RB, Kaneene JB, Mauer WA, Grooms DL. http://www.oie.int/international-standard-setting/terrestrial- Detection of Myobacterium avium subspecies paratuberculosis manual/access-online/ in naturally exposed dairy heifers and associated risk factors. J OIE Terrestrial Animal Health Code Dairy Sci. 2011;94:4669-75. http://www.oie.int/international-standard-setting/terrestrial- Carta T, Álvarez J, Pérez de la Lastra JM, Gortázar C. Wildlife and code/access-online/ paratuberculosis: a review. Res Vet Sci. 2013;94(2):191-7. Clark RG, Griffin JF, Mackintosh CG. Johne's disease caused by Myobacterium avium subsp. paratuberculosis infection in red Acknowledgements deer (Cervus elaphus): an histopathological grading system, and comparison of paucibacillary and multibacillary disease. This factsheet was written by Anna Rovid Spickler, DVM, N Z Vet J. 2010;58(2):90-7. PhD, Veterinary Specialist from the Center for Food Collins DM, De Zoete M, Cavaignac SM. Myobacterium avium Security and Public Health. The U.S. Department of subsp. paratuberculosis strains from cattle and sheep can be Agriculture Animal and Plant Health Inspection Service distinguished by a PCR test based on a novel DNA sequence (USDA APHIS) provided funding for this factsheet through difference. J Clin Microbiol. 2002;40:4760-2. a series of cooperative agreements related to the Collins DM, Gabric DM, de Lisle GW. Identification of two development of resources for initial accreditation training. groups of Mycobacterium paratuberculosis strains by restriction endonuclease analysis and DNA hybridization. J The following format can be used to cite this factsheet. Clin Microbiol. 1990;28:1591-6. Spickler, Anna Rovid. 2007. Paratuberculosis. Retrieved Collins MT. Food safety concerns regarding paratuberculosis. Vet from http://www.cfsph.iastate.edu/DiseaseInfo/ Clin North Am Food Anim Pract. 2011;27(3):631-6, vii-viii. factsheets.php. Corn JL, Manning EJ, Sreevatsan S, Fischer JR. Isolation of Myobacterium avium subsp. paratuberculosis from free- References ranging birds and on livestock premises. Appl Environ Microbiol. 2005;71:6963-7. Aiello SE, Moses MA, editors. The Merck veterinary manual. 11th Crawford GC, Ziccardi MH, Gonzales BJ, Woods LM, Fischer ed. Kenilworth, NJ: Merck and Co; 2016. Paratuberculosis. p. JK, Manning EJ, Mazet JA. Myobacterium avium subspecies 762-4, 2151. paratuberculosis and Myobacterium avium subsp. avium Alvarez J, De Juan L, Briones V, Romero B, Aranaz A, infections in a tule elk (Cervus elaphus nannodes) herd. J Fernández-Garayzábal JF, Mateos A. Mycobacterium avium Wildl Dis. 2006;42:715-23. subspecies paratuberculosis in fallow deer and wild boar in Spain. Vet Rec. 2005;156(7):212-3.

© 2003-2020 www.cfsph.iastate.edu  Email: [email protected] page 7 of 11 Paratuberculosis Dalto AC, Bandarra PM, Pavarini SP, Boabaid FM, de Bitencourt Fecteau ME, Hovingh E, Whitlock RH, Sweeney RW. Persistence AP, Gomes MP, Chies J, Driemeier D, da Cruz CE. Clinical of Myobacterium avium subsp. paratuberculosis in soil, crops, and pathological insights into Johne's disease in buffaloes. and ensiled feed following manure spreading on infected dairy Trop Anim Health Prod. 2012;44(8):1899-904. farms. Can Vet J. 2013;54(11):1083-5. Daniels MJ, Hutchings MR, Beard PM, Henderson D, Greig A, Fecteau ME, Ross J, Tennent-Brown BS, Habecker PL, Stevenson K, Sharp JM. Do non-ruminant wildlife pose a risk Sreevatsan S, Sweeney RW, Whitlock RH. Myobacterium of paratuberculosis to domestic livestock and vice versa in avium ssp. paratuberculosis high shedding in an adult female Scotland? J Wildl Dis. 2003; 39:10-5. alpaca, and its implications for the rest of the herd. Vet Intern Delgado L, Marín JF, Muñoz M, Benavides J, Juste RA, García- Med. 2009;23(6):1311-4. Pariente C. Pathological findings in young and adult sheep Fecteau ME, Whitlock RH. Treatment and chemoprophylaxis for following experimental infection with 2 different doses of paratuberculosis. Vet Clin North Am Food Anim Pract. Myobacterium avium subspecies paratuberculosis. Vet Pathol. 2011;27(3):547-57. 2013;50(5):857-66. Fecteau ME, Whitlock RH, Buergelt CD, Sweeney RW. Exposure Del-Pozo J, Girling S, McLuckie J, Abbondati E, Stevenson K. An of young dairy cattle to Myobacterium avium subsp. unusual presentation of Myobacterium avium spp. paratuberculosis (MAP) through intensive grazing of paratuberculosis infection in a captive tundra reindeer contaminated pastures in a herd positive for Johne's disease. (Rangifer tarandus tarandus). J Comp Pathol. Can Vet J. 2010;51(2):198-200. 2013;149(1):126-31. Fernández M, Benavides J, Sevilla IA, Fuertes M, Castaño P, Dimareli-Malli Z, Mazaraki K, Stevenson K, Tsakos P, Zdragas Delgado L, García Marín JF, Garrido JM, Ferreras MC, Pérez A, Giantzi V, Petridou E, Heron I, Vafeas G. Culture V. Experimental infection of lambs with C and S-type strains phenotypes and molecular characterization of Myobacterium of Myobacterium avium subspecies paratuberculosis: avium subsp. paratuberculosis isolates from small ruminants. immunological and pathological findings. Vet Res. 2014;45:5. Res Vet Sci. 2013;95(1):49-53. Forde T, Pruvot M, De Buck J, Orsel K. A high-morbidity Djønne B, Pavlik I, Svastova P, Bartos M, Holstad G. IS900 outbreak of Johne's disease in game-ranched elk. Can Vet J. restriction fragment length polymorphism (RFLP) analysis of 2015;56(5):479-83. Mycobacterium avium subsp. paratuberculosis isolates from Forde T, Orsel K, De Buck J, Côté SD, Cuyler C, Davison T, goats and cattle in Norway. Acta Vet Scand. 2005;46(1-2):13-8. Elkin B, Kelly A, Kienzler M, Popko R, Taillon J, Veitch A, Dohmann K, Strommenger B, Stevenson K, de Juan L, Stratmann Kutz S. Detection of Myobacterium avium subspecies J, Kapur V, Bull TJ, Gerlach GF. Characterization of genetic paratuberculosis in several herds of Arctic caribou (Rangifer differences between Myobacterium avium subsp. tarandus ssp.). J Wildl Dis. 2012;48(4):918-24. paratuberculosis type I and type II isolates. J Clin Microbiol. Garcia AB, Shalloo L. The economic impact and control of 2003;41:5215-23. paratuberculosis in cattle. J Dairy Sci. 2015;98(8):5019-39. Doré E, Paré J, Côté G, Buczinski S, Labrecque O, Roy JP, Geraghty T, Graham DA, Mullowney P, More SJ. A review of Fecteau G. Risk factors associated with transmission of bovine Johne's disease control activities in 6 endemically Myobacterium avium subsp. paratuberculosis to calves within infected countries. Prev Vet Med. 2014;116(1-2):1-11. dairy herd: a systematic review. J Vet Intern Med. Gilardoni LR, Paolicchi FA, Mundo SL. Bovine paratuberculosis: 2012;26(1):32-45. a review of the advantages and disadvantages of different Dukes TW, Glover GJ, Brooks BW, Duncan JR, Swendrowski M. diagnostic tests. Rev Argent Microbiol. 2012;44(3):201-15. Paratuberculosis in saiga antelope (Saiga tatarica) and Glanemann B, Schönenbrücher H, Bridger N, Abdulmawjood A, experimental transmission to domestic sheep. J Wildl Dis. Neiger R, Bülte M. Detection of Mycobacterium avium 1992;28(2):161-70. subspecies paratuberculosis-specific DNA by PCR in Eisenberg S, Nielen M, Hoeboer J, Bouman M, Heederik D, Koets intestinal biopsies of dogs. J Vet Intern Med. A. Mycobacterium avium ssp. paratuberculosis in bioaerosols 2008;22(5):1090-4. after depopulation and cleaning of two cattle barns. Vet Rec. Grant IR, Hitchings EI, McCartney A, Ferguson F, Rowe MT. 2011;168:587. Effect of commercial-scale high-temperature, short-time Eisenberg SW, Nielen M, Koets AP. Within-farm transmission of pasteurization on the viability of Mycobacterium bovine paratuberculosis: recent developments. Vet Q. paratuberculosis in naturally infected cows' milk. Appl 2012;32(1):31-5. Environ Microbiol. 2002;68:602-7. Elliott GN, Hough RL, Avery LM, Maltin CA, Campbell CD. Greig A, Stevenson K, Henderson D, Perez V, Hughes V, Pavlik I, Environmental risk factors in the incidence of Johne's disease. Hines ME, McKendrick I, Sharp JM. Epidemiological study of Crit Rev Microbiol. 2015;41(4):488-507. paratuberculosis in wild rabbits in Scotland. J Clin Microbiol. Espeschit IF, Schwarz DGG, Faria ACS, Souza MCC, Paolicchi 1999; 37:1746-51. FA, Juste RA, Carvalho IA, Moreira MAS. Paratuberculosis in Greig A, Stevenson K, Perez V, Pirie AA, Grant JM, Sharp JM. Latin America: a systematic review. Trop Anim Health Prod. Paratuberculosis in wild rabbits (Oryctolagus cuniculus). Vet 2017 Sep 7 [Epub ahead of print]. Rec. 1997;140:141-3. Fechner K, Mätz-Rensing K, Lampe K, Kaup FJ, Czerny CP, Haghkhah M, Derakhshandeh A, Jamshidi R, Moghiseh A, Schäfer J. Detection of Myobacterium avium subsp. Karimaghaei N, Ayaseh M, Mostafaei M. Detection of paratuberculosis in non-human primates. J Med Primatol. Myobacterium avium subspecies paratuberculosis infection in 2017;46(5):211-7. two different camel species by conventional and molecular techniques. Vet Res Forum. 2015;6(4):337-41.

© 2003-2020 www.cfsph.iastate.edu  Email: [email protected] page 8 of 11 Paratuberculosis Hendrick SH, Kelton DF, Leslie KE, Lissemore KD, Archambault Liverani E, Scaioli E, Cardamone C, Dal Monte P, Belluzzi A. M, Duffield TF. Effect of paratuberculosis on culling, milk Myobacterium avium subspecies paratuberculosis in the production, and milk quality in dairy herds. J Am Vet Med etiology of Crohn's disease, cause or epiphenomenon? World J Assoc. 2005;227:1302-8. Gastroenterol. 2014;20(36):13060-70. Holstad G1, Sigurdardóttir OG, Storset AK, Tharaldsen J, Nyberg Lybeck KR, Løvoll M, Johansen TB, Olsen I, Storset AK, O, Schönheit J, Djønne B. Description of the infection status Valheim M. Intestinal strictures, fibrous adhesions and high in a Norwegian cattle herd naturally infected by local interleukin-10 levels in goats infected naturally with Mycobacterium avium subsp. paratuberculosis. Acta Vet Mycobacterium avium subsp. paratuberculosis. J Comp Scand. 2005;46(1-2):45-56. Pathol. 2013;148(2-3):157-72. Jorgensen JB. Paratuberculosis in pigs. Experimental infection by Mackintosh CG, Clark RG, Thompson B, Tolentino B, Griffin JF, oral administration of Mycobacterium paratuberculosis. Acta de Lisle GW. Age susceptibility of red deer (Cervus elaphus) Vet Scand. 1969;10: 275-87. to paratuberculosis. Vet Microbiol. 2010;143(2-4):255-61. Julian RJ. A short review and some observations on Johne's Mackintosh CG, Clark RG, Tolentino B, de Lisle GW, Liggett S, disease with recommendations for control. Can Vet J. 1975; Griffin JF. Immunological and pathological responses of red 16(2): 33-43. deer resistant or susceptible genotypes, to experimental Judge J, Kyriazakis I, Greig A, Davidson RS, Hutchings MR. challenge with Myobacterium avium subsp. paratuberculosis. Routes of intraspecies transmission of Myobacterium avium Vet Immunol Immunopathol. 2011;143(1-2):131-42. subsp. paratuberculosis in rabbits (Oryctolagus cuniculus): a Mackintosh C, Clark G, Tolentino B, Liggett S, de Lisle G, Griffin field study. Appl Environ Microbiol. 2006;72:398-403. F. Longitudinal pathogenesis study of young red deer (Cervus Juste RA, Perez V. Control of paratuberculosis in sheep and goats. elaphus) after experimental challenge with Myobacterium Vet Clin North Am Food Anim Pract. 2011;27(1):127-38. avium subsp. paratuberculosis (MAP). Vet Med Int. Kaevska M, Lvoncik S, Slana I, Kulich P, Kralik P. Microscopy, 2012;2012:931948. culture, and quantitative real-time PCR examination confirm Mackintosh CG, Labes RE, Clark RG, de Lisle GW, Griffin JF. internalization of mycobacteria in plants. Appl Environ Experimental infections in young red deer (Cervus elaphus) Microbiol. 2014;80(13):3888-94. with a bovine and an ovine strain of Myobacterium avium Kim JM, Ku BK, Lee HN, Hwang IY, Jang YB, Kim J, Hyun BH, subsp paratuberculosis. N Z Vet J. 2007;55:23-9. Jung SC. Myobacterium avium paratuberculosis in wild boars Mackintosh CG, Labes RE, Thompson BR, Clark RG, de Lisle in Korea. J Wildl Dis. 2013;49(2):413-7. GW, Johnstone PD, Griffin JF. Efficacy, immune responses Klawonn W, Einax E, Pützschel R, Schmidt M, Donat K. Johne's and side-effects of vaccines against Johne's disease in young disease: reliability of environmental sampling to characterize red deer (Cervus elaphus) experimentally challenged with Myobacterium avium subspecies paratuberculosis (MAP) Myobacterium avium subsp paratuberculosis. N Z Vet J. infection in beef cow-calf herds. Epidemiol Infect. 2008;56(1):1-9. 2016;144(11):2392-400. Manning EJ. Paratuberculosis in captive and free-ranging wildlife. Koets AP, Eda S, Sreevatsan S. The within host dynamics of Vet Clin North Am Food Anim Pract. 2011;27(3):621-30, vii. Myobacterium avium ssp. paratuberculosis infection in cattle: Manning EJB, Kucera TE, Gates NB, Woods LM, Fallon- where time and place matter. Vet Res. 2015;46:61. McKnight M. Testing for Myobacterium avium subsp. Kopecna M, Ondrus S, Literak I, Klimes J, Horvathova A, paratuberculosis infection in asymptomatic free-ranging tule Moravkova M, Bartos M, Trcka I, Pavlik I. Detection of elk from an infected herd. J Wildl Dis. 2003;39:323-8. Myobacterium avium subsp. paratuberculosis in two brown Matos AC, Andrade S, Figueira L, Matos M, Pires MA, Coelho bears in the central European Carpathians. J Wildl Dis. AC, Pinto ML. Mesenteric lymph node granulomatous lesions 2006;42:691-5. in naturally infected wild boar (Sus scrofa) in Portugal-- Krüger C, Köhler H, Liebler-Tenorio EM. Sequential development Histological, immunohistochemical and molecular aspects. of lesions 3, 6, 9, and 12 months after experimental infection Vet Immunol Immunopathol. 2016;173:21-6. of goat kids with Myobacterium avium subsp Matos AC, Figueira L, Martins MH, Loureiro F, Pinto ML, Matos paratuberculosis. Vet Pathol. 2015;52(2):276-90. M, Coelho AC. Survey of Myobacterium avium subspecies Kumar S, Singh SV, Singh AV, Singh PK, Sohal JS, Maitra A. paratuberculosis in road-killed wild carnivores in Portugal. J Wildlife (Boselaphus tragocamelus)-small ruminant (goat and Zoo Wildl Med. 2014;45(4):775-81. sheep) interface in the transmission of 'Bison type' genotype of Matos AC, Figueira L, Martins MH, Matos M, Alvares S, Pinto Myobacterium avium subspecies paratuberculosis in India. ML, Coelho AC. Disseminated Myobacterium avium subsp. Comp Immunol Microbiol Infect Dis. 2010;33(2):145-59. paratuberculosis infection in two wild Eurasian otters (Lutra Larsen AB, Moon HW, Merkal RS. Susceptibility of horses to lutra L.) from Portugal. J Zoo Wildl Med. 2013;44(1):193-5. Mycobacterium paratuberculosis. Am J Vet Res. 1972;33: McAloon CG, Whyte P, More SJ, Green MJ, O'Grady L, Garcia 2185-9. A, Doherty ML. The effect of paratuberculosis on milk yield-- Larsen AB, Moon HW, Merkal RS. Susceptibility of swine to A systematic review and meta-analysis. J Dairy Sci. Mycobacterium paratuberculosis. Am J Vet Res. 2016;99(2):1449-60. 1971;32:589-95. Miller MA, Davey SC, Van Helden LS, Kettner F, May SM, Last Li L, Katani R, Schilling M, Kapur V. Molecular epidemiology of R, Grewar JD, Botha L, Van Helden PD. Paratuberculosis in a Myobacterium avium subsp. paratuberculosis on dairy farms. domestic dog in South Africa. J S Afr Vet Assoc. Annu Rev Anim Biosci. 2016;4:155-76. 2017;88(0):e1-e5.

© 2003-2020 www.cfsph.iastate.edu  Email: [email protected] page 9 of 11 Paratuberculosis Mitchell RM, Schukken Y, Koets A, Weber M, Bakker D, Stabel Robbe-Austerman S. Control of paratuberculosis in small J, Whitlock RH, Louzoun Y. Differences in intermittent and ruminants. Vet Clin North Am Food Anim Pract. continuous fecal shedding patterns between natural and 2011;27(3):609-20, vii. experimental Myobacterium avium subspecies Rossiter CA, Hutchinson LJ. Hansen D, Whitlock RH. Prevention paratuberculosis infections in cattle. Vet Res. 2015;46:66. and control of Johne’s disease in dairy herds. A workbook for Mortier RA, Barkema HW, De Buck J. Susceptibility to and veterinarians and producers [online]. 1st ed. United States diagnosis of Myobacterium avium subspecies paratuberculosis Animal Health Association National Johne's Working Group infection in dairy calves: A review. Prev Vet Med. (NJWG) Subcommittee on Education Prevention and Control 2015;121(3-4):189-98. of Johne's Disease in Dairy Herds; 2002 March. Available at: Mortier RA, Barkema HW, Orsel K, Wolf R, De Buck J. Shedding http://www.usaha.org/njwg/jddairym.html.* Accessed 5 Sept patterns of dairy calves experimentally infected with 2003. Myobacterium avium subspecies paratuberculosis. Vet Res. Roussel AJ. Control of paratuberculosis in beef cattle. Vet Clin 2014;45:71. North Am Food Anim Pract. 2011;27(3):593-8, vi. Motiwala AS, Amonsin A, Strother M, Manning EJ, Kapur V, Rubery ED (Judge Institute of Management, University of Sreevatsan S. Molecular epidemiology of Myobacterium Cambridge, UK). A review of the evidence for a link between avium subsp. paratuberculosis isolates recovered from wild exposure to Mycobacterium paratuberculosis (MAP) and animal species. J Clin Microbiol. 2004;42:1703-12. Crohn’s disease (CD) in humans. A report for the Food Nugent G, Whitford EJ, Hunnam JC, Wilson PR, Cross Ml, de Standards Agency [online]. Food Standards Agency, United Lisle GW. Myobacterium avium subsp. paratuberculosis Kingdom; 2002 Jan 22. 52 p. Available at: infection in wildlife on three deer farms with a history of http://www.foodstandards.gov.uk/multimedia/pdfs/mapcrohnr Johne's disease. N Z Vet J. 2011;59(6):293-8. eport.pdf.* Accessed 13 Sept 2003. Palmer MV, Stabel JR, Waters WR, Bannantine JP, Miller JM. Salgado M, Herthnek D, Bölske G, Leiva S, Kruze J. First Experimental infection of white-tailed deer (Odocoileus isolation of Myobacterium avium subsp. paratuberculosis virginianus) with Myobacterium avium subsp. from wild guanacos (Lama guanicoe) on Tierra del Fuego paratuberculosis. J Wildl Dis. 2007;43(4):597-608. Island. J Wildl Dis. 2009;45(2):295-301. Palmer MV, Stoffregen WC, Carpenter JG, Stabel JR. Isolation of Salgado M, Monti G, Sevilla I, Manning E. Association between Myobacterium avium subsp paratuberculosis (Map) from feral cattle herd Myobacterium avium subsp. paratuberculosis cats on a dairy farm with Map-infected cattle. J Wildl Dis. (MAP) infection and infection of a hare population. Trop 2005;41:629-35. Anim Health Prod. 2014;46(7):1313-6. Patton EA. Paratuberculosis vaccination. Vet Clin North Am Food Schukken YH , Whitlock RH, Wolfgang D, Grohn Y, Beaver A, Anim Pract. 2011;27(3):573-80, vi. VanKessel J, Zurakowski M, Mitchell R. Longitudinal data Pithua P, Espejo LA, Godden SM, Wells SJ. Is an individual collection of Myobacterium avium subspecies calving pen better than a group calving pen for preventing paratuberculosis infections in dairy herds: the value of precise transmission of Myobacterium avium subsp paratuberculosis field data. Vet Res. 2015;46:65. in calves? Results from a field trial. Res Vet Sci. Sigurdardóttir OG, Nordstoga K, Baustad B, Saxegaard F. 2013;95(2):398-404. Granulomatous enteritis in a pig caused by Mycobacterium Public Health Agency of Canada [PHAC]. Pathogen Safety Data avium. Vet Pathol. 1994;31(2):274-6. Sheet – Mycobacterium spp. [online]. Pathogen Regulation Singh SV, Singh AV, Singh PK, Kumar A, Singh B. Molecular Directorate, PHAC; 2011 Sept. Available at: identification and characterization of Myobacterium avium https://www.canada.ca/en/public-health/services/laboratory- subspecies paratuberculosis in free living non-human primate biosafety-biosecurity/pathogen-safety-data-sheets-risk- (Rhesus macaques) from North India. Comp Immunol assessment/mycobacterium.html. Accessed 20 Oct 2017. Microbiol Infect Dis. 2011;34(3):267-71. Quist CF, Nettles VF, Manning EJB, Hall DG, Gaydos JK, Wilmers Singh SV, Singh PK, Singh AV, Sohal JS, Kumar N, Chaubey TJ, Roper RR. Paratuberculosis in Key deer (Odocoileus KK, Gupta S, Rawat KD, Kumar A, Bhatia AK, Srivastav AK, virginianus clavium). J Wildl Dis. 2002; 38: 729-37. Dhama K. 'Bio-load' and bio-type profiles of Myobacterium Rademaker JL, Vissers MM, Te Giffel MC. Effective heat avium subspecies paratuberculosis infection in the domestic inactivation of Myobacterium avium subsp. paratuberculosis livestock population endemic for Johne's disease: a survey of in raw milk contaminated with naturally infected feces. Appl 28 years (1985-2013) in India. Transbound Emerg Dis. Environ Microbiol. 2007;73(13):4185-90. 2014;61 Suppl 1:43-55. Rankin JD. Identification of a strain of Mycobacterium johnei Sorge US, Kurnick S, Sreevatsan S. Detection of Myobacterium recovered from a horse. J Path Bact. 1956;72:689-90. avium subspecies paratuberculosis in the saliva of dairy cows: a pilot study. Vet Microbiol. 2013;164(3-4):383-6. Rideout BA, Brown ST, Davis WC, Giannella RA, Huestan WD, Hutchinson LJ. Diagnosis and control of Johne's disease Stabel JR, Bradner L, Robbe-Austerman S, Beitz DC. Clinical [online]. Washington, DC: National Academies Press; 2003. disease and stage of lactation influence shedding of Available at: https://www.nap.edu/catalog/10625/diagnosis- Myobacterium avium subspecies paratuberculosis into milk and-control-of-johnes-disease. Accessed 6 Apr 2007. and colostrum of naturally infected dairy cows. J Dairy Sci. 2014;97(10):6296-304. Rindi L, Garzelli C. Genetic diversity and phylogeny of Myobacterium avium. Infect Genet Evol. 2014;21:375-83. Stevenson K. Genetic diversity of Myobacterium avium subspecies paratuberculosis and the influence of strain type Ringdal G. Johne's disease in pigs. Nord Vet Med. 1963;15: 217-38. on infection and pathogenesis: a review. Vet Res. 2015;46:64.

© 2003-2020 www.cfsph.iastate.edu  Email: [email protected] page 10 of 11 Paratuberculosis Stevenson K, Alvarez J, Bakker D, Biet F, de Juan L, et al. Weber MF, Kogut J, de Bree J, van Schaik G, Nielen M. Age at Occurrence of Myobacterium avium subspecies which dairy cattle become Myobacterium avium subsp. paratuberculosis across host species and European countries paratuberculosis faecal culture positive. Prev Vet Med. with evidence for transmission between wildlife and domestic 2010;97(1):29-36. ruminants. BMC Microbiol. 2009;9:212. Whittington RJ, Marshall DJ, Nicholls PJ, Marsh IB, Reddacliff Stringer LA, Wilson PR, Heuer C, Mackintosh CG.A randomised LA. Survival and dormancy of Myobacterium avium subsp. controlled trial of Silirum vaccine for control of paratuberculosis in the environment. Appl Environ Microbiol. paratuberculosis in farmed red deer. Vet Rec. 2004;70:2989-3004. 2013;173(22):551. Windsor PA. Paratuberculosis in sheep and goats. Vet Microbiol. Sweeney RW. Pathogenesis of paratuberculosis. Vet Clin North 2015;181(1-2):161-9. Am Food Anim Pract. 2011;27(3):537-46, v. Windsor PA, Whittington RJ. Evidence for age susceptibility of Sweeney RW, Collins MT, Koets AP, McGuirk SM, Roussel AJ. cattle to Johne's disease. Vet J. 2010;184(1):37-44. Paratuberculosis (Johne's disease) in cattle and other Witte CL, Hungerford LL, Rideout BA. Association between susceptible species. Vet Intern Med. 2012;26(6):1239-50. Myobacterium avium subsp. paratuberculosis infection among Thoen CO, Jarnagin JL, Richards WD. Isolation and identification offspring and their dams in nondomestic ruminant species of mycobacteria from porcine tissues: a three-year summary. housed in a zoo. J Vet Diagn Invest. 2009;21(1):40-7. Am J Vet Res. 1975;36(9):1383-6. World Organization for Animal Health [OIE]. Manual of Trangoni MD, Gioffré AK, Cerón Cucchi ME, Caimi KC, Ruybal diagnostic tests and vaccines [online]. Paris: OIE; 2017. P, Zumárraga MJ, Cravero SL. LAMP technology: Rapid Paratuberculosis. Available at: identification of Brucella and Myobacterium avium subsp. http://www.oie.int/eng/normes/mmanual/A_00045.htm. paratuberculosis. Braz J Microbiol. 2015;46(2):619-26. Accessed 11 Oct 2017. United States Animal Health Association National Johne's Working World Organization for Animal Health [OIE]. World Animal Group [USAHA NJWG] Subcommittee on Education. Prevention Health Information Database (WAHIS) interface: List of and control of Johne's disease in dairy cattle. USAHA NJWG; countries by disease situation. Paratuberculosis. Available at: 2002 March. Available at: http://www.oie.int/wahis_2/public/wahid.php/Diseaseinformat http://www.usaha.org/njwg/jddairy.html.* Accessed 6 Sept 2003. ion/statuslist. Accessed 19 Oct 2017. U.S. Department of Agriculture, Animal and Plant Health Zanetti S, Bua A, Molicotti P, Delogu G, Mura A, Ortu S, Sechi Inspection Service [USDA APHIS]. Preventing introduction LA. Identification of mycobacterial infections in wild boars in of Johne’s disease [online]. USDA APHIS; 2007 April. Northern Sardinia, Italy. Acta Vet Hung. 2008;56(2):145-52. Available at: http://www.aphis.usda.gov/animal_health/animal_diseases/joh *Link defunct nes/prevent-intro.shtml#prevent.* Accessed 5 Apr 2007. Van Brandt L, Coudijzer K, Herman L, Michiels C, Hendrickx M Vlaemynck G. Survival of Myobacterium avium ssp. paratuberculosis in yoghurt and in commercial fermented milk products containing probiotic cultures, J Appl Microbiol. 2011;110:1252-61. van Roermund HJ, Bakker D, Willemsen PT, de Jong MC. Horizontal transmission of Myobacterium avium subsp. paratuberculosis in cattle in an experimental setting: Calves can transmit the infection to other calves. Vet Microbiol. 2007;122(3-4):270-9. Vansnick E, Vercammen F, Bauwens L, D'Haese E, Nelis H, Geysen D. A survey for Mycobacterium avium subspecies paratuberculosis in the Royal Zoological Society of Antwerp. Vet J. 2005;170(2):249-56. Verin R, Perroni M, Rossi G, De Grossi L, Botta R, De Sanctis B, Rocca S, Cubeddu T, Crosby-Durrani H, Taccini E. Paratuberculosis in sheep: Histochemical, immunohistochemical and in situ hybridization evidence of in utero and milk transmission. Res Vet Sci. 2016;106:173-9. Waddell L, Rajić A, Stärk K, McEwen SA. Myobacterium avium ssp. paratuberculosis detection in animals, food, water and other sources or vehicles of human exposure: A scoping review of the existing evidence. Prev Vet Med. 2016;132:32-48. Waddell LA, Rajić A, Stärk KD, McEwen SA. The zoonotic potential of Myobacterium avium ssp. paratuberculosis: a systematic review and meta-analyses of the evidence. Epidemiol Infect. 2015;143(15):3135-57.

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