Atypical Mycobacteriosis in Swine

Atypical mycobacteriosis is a chronic infectious disease caused by atypical mycobacteria (AM), which are mycobacteria other than those belonging to the Mycobacterium tuberculosis complex that includes M. tuberculosis, M. bovis, M. africanum, M. microti and M. canettii.  Additionally, AM usually do not include M. leprae and M. avium subsp paratuberculosis.  AM are widely distributed in nature, and are potentially pathogenic to a variety of species.  The main pathogenic AM belong to the M. avium complex (MAC).  These are most prevalent among birds and pigs.  MAC infection in pigs occurs worldwide and sometimes leads to serious economic losses at slaughter.  The incidence of disease caused by AM is also increasing among immunodeficient patients such as those with Acquired Immunodeficiency Syndrome (AIDS).

Etiology:  AM are gram-positive, aerobic, slow-growing, acid-fast rods.  They are also known as mycobacteria other than tuberculous mycobacteria (MOTT) or non-tuberculous mycobacteria (NTB).  They are divided into 4 groups (I through IV) by Runyon based on differences in growth rate, colony pigmentation and other characteristics.  MAC, which belong to group III, can be further subdivided into 28 serovars.  The latest classification divided MAC into two species:  M. avium and M. intracellulare.  M. avium contains 4 subspecies: avium, paratuberculosis, silvaticum and hominisuis.  In the U.S., where more than 15 MAC serovars have been isolated, serovars 1, 2, 4 and 8 are the most commonly isolated from lesions in infected pigs.

  AM are found in soil, salt and fresh water, insects, earthworms, sawdust and peat.  Pigs are likely most commonly infected through exposure to contaminated environment (such as sawdust and peat used for bedding) and infected wild birds; sows that excrete MAC are an additional source of infection.

  The infection almost exclusively occurs by ingestion.  An experimental study in which 5-week-old pigs were orally exposed to the bacteria demonstrated the occurrence of gross lesions in mesenteric lymph nodes 10 days post infection.  Respiratory and wound infections are uncommon.  Transmission of the bacteria between humans or from pigs to humans has not been reported to date; therefore, humans are thought to be infected from the environment as well.

Clinical findings:  Most of the infected pigs do not show any specific clinical signs.  Gross lesions are often restricted to lymph nodes, and are incidental findings when pigs are slaughtered or die due to another, unrelated disease.  Generalized lesions, including severe granulomatous enteritis causing chronic diarrhea and wasting, have been reported; however, such cases are rare.

Pathologic findings:  It is thought that MAC usually enter through the mucosa of the pharynx and/or the small intestine, with gross lesions limited to the tonsil and the mandibular, retropharyngeal and mesenteric lymph nodes, particularly the jejunal lymph node.  These lesions are characterized by well-circumscribed, yellowish white nodules.  They range in size from very small (<1mm) up to relatively large, with eventual involvement of the entire node.  Uncommonly, generalized lesions are seen, characterized by small, white, smooth-surfaced nodules in the liver, spleen, lung, kidney and many lymph nodes, indicating hematogenous spread.  These lesions are usually not accompanied by any clinical signs.  In rare cases, the wall of the small intestine may be thickened due to infiltration of the lamina propria by inflammatory cells.

  Histologically, lesions are primarily characterized by granulomatous inflammation, composed of epithelioid macrophages and multinucleate giant cells, sometimes with central caseation necrosis, but without distinct encapsulation.  Special stains such as Ziehl-Neelsen are used to demonstrate the presence of low numbers of intralesional acid-fast bacilli.

Diagnosis:  Intradermal injection of purified protein derivative (PPD) tuberculin into the dorsal surface of the ear is the diagnostic test recommended on a herd basis.  The reading is performed 48 hours later.  Since MAC infection does not cause any specific clinical signs, even if a pig has generalized disease, it is difficult to establish a clinical diagnosis.  Since some tuberculous pigs may fail to react to the tuberculin test, this should be repeated in a herd that previously had animals with positive reactions.  An enzyme-linked immunosorbent assay (ELISA) has also been developed in order to detect antibodies in pigs infected with MAC.  This assay is useful to test replacement animals.  At postmortem examination, the presence of intralesional acid-fast bacilli is usually demonstrated by using an acid-fast stain on smears or sections from tissues with lesions.  Careful interpretation is necessary since other acid-fast bacteria such as Rhodococcus equi can cause tuberculosis-like lymphadenitis in pigs.  Bacterial culture is the gold standard test.  It takes 4-6 weeks to grow visible colonies if solid media are used for culture; if liquid or broth media are used, the growth rate is slightly shorter.  MAC are identified through biochemical and seroagglutination tests and through molecular techniques.  PCR assays can be used to amplify regions of the 165 rRNA gene from MAC.  Insertion sequences (IS), which are species specific, are also used for bacterial identification.  IS elements are identified as IS901, IS1110, IS1245 and IS1311 for M. avium and IS1141 for M. intracellulare.  Finally, restriction fragment length polymorphism (RFLP) analysis of IS elements can be used for strain genotyping.

Treatment and Prevention:  Since infected pigs do not normally have specific clinical signs, it is uncommon to treat pigs.  Thorough cleaning of infected premises using heat and disinfectants such as 3% formalin, 2% Lysol or 2.5% phenol are reportedly effective in eliminating the bacteria, as is the removal of animals that are PPD tuberculin test positive.  It is unknown whether BCG vaccination can protect pigs from MAC infection.  From a public health perspective, MAC infection is a serious problem for immunodeficient patients since MAC is a common opportunistic infectious agent.  The disease tends to be disseminated in these patients, whereas AM in immunocompetent patients affects primarily the lungs.  In the U.S. and Europe, the incidence of tuberculosis in the general population is low; the incidence of AM disease is, however, high in AIDS patients.  Since AM are ubiquitous in nature, it is difficult to control disease caused by these bacteria.  Nonetheless, there is a need to determine potential wildlife and environmental reservoirs in order to reduce the exposure of human and domestic animals to the mycobacteria.

-by Dr. Nozomi Shimonohara, ADDL extern

-edited by Dr. Ingeborg Langohr, former ADDL graduate student

References:

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