VA Medical Center, Boston, MA, USA; Boston University School of Medicine, Boston, MA, USA
Mycobacterial infections are common among humans. Of these, infection with Mycobacterium tuberculosis (TB) is the most common and of the greatest concern. Non-tuberculous species of mycobacteria may also cause infections in man, especially among immunosuppressed individuals. Human TB is typically acquired by inhalation of aerosols carrying tubercle bacilli following exposure to a person with active pulmonary infection; non-tuberculous species of mycobacteria are acquired from environmental sources. Since zoonotic transmission of TB does occur, the identification of acid-fast bacilli (AFB) in clinical specimens from animals is a cause of concern, unease, and occasionally misconception for animal care handlers and zoo personnel.
M. tuberculosis Complex
1. Epidemiology, Pathogenesis, and Diagnosis
M. tuberculosis complex organisms include M. tuberculosis and M. bovis, as well as M. africanum and M. microti and infection with any of these species is appropriately termed as “tuberculosis.” These organisms are genetically related, grow slowly on artificial media, and have no known environmental niches.
M. tuberculosis and M. bovis infection is limited to warm blooded animals, although there is one report of M. tuberculosis infection in a turtle.1 In general, while both M. tuberculosis and M. bovis should be considered equally pathogenic, animal related differences in susceptibility to the two species have been reported. Thus, the incidence of infection parallels the frequency of exposure.
Mammals, excluding humans, are most commonly infected with M. bovis although there have been numerous cases of human disease.2 Humans are more commonly infected with M. tuberculosis, which may represent a “humanosis” with infection documented in elephants, rhinoceros, dogs, and nonhuman primates.3 Further, M. tuberculosis may also infect birds, especially parrots and other common pet species.3
Primary infection is usually acquired via tubercle laden droplets generated by coughing or sneezing. The droplets settle into the alveoli where the bacteria begin to multiply. Macrophages engulf the bacteria and while most of the organisms are killed, some survive intracellularly. Groups of macrophages form granulomas around the bacteria that may grow large enough to be detected visually.
Active disease occurs in two situations:
1. Immediately following primary infection; or, more commonly, by
2. Reactivation from a latent source of infection
Clinical disease is primarily pulmonary although extra-pulmonary infection may occur alone or concurrent with pulmonary disease. In both humans and other animals any organ system may be infected.
In both humans and other mammals, skin testing detects only TB infection, not active disease. Active disease in humans is diagnosed either by:
1. Recovery of the organisms by culture or smear, or
2. Identification of thoracic radiographic lesions consistent with active TB
Polymerase chain reaction (PCR) and other amplification methods detect organisms and can thus be used to diagnose active disease. Other indirect methods, such as antibody detection (ELISA) and lymphocyte transformation (Blood Tuberculosis [BTB] test), cannot discriminate infection from active disease.
2. Zoonotic Transmission of Tubercle Bacilli
The primary route of transmission of TB to humans is primarily through aerosols. The most common source of these aerosols is coughing, which generates small droplets that can settle in the alveoli. Only animals with active disease are at risk to spread infection to humans and other animals. The major risk factors for animal to human transmission are the same as those for human-to-human spread of the disease and are listed below.
Risk factors for TB transmission
Number of bacilli being actively shed
Droplet size carrying tubercle bacilli
Total time of exposure
Proximity to an infected animal
Immune status of the person exposed
Other sources of exposure include aerosols created 1) from tuberculous abscesses, 2) during necropsy, and 3) during handling of infected carcasses. Fecal-oral spread is not as important for humans as for animals. The fecal-oral route should be considered when children or animal workers are exposed to infected animals and their excreta. Because their cell wall lipids protect mycobacteria from drying they remain viable in the environment for prolonged time spans. In contrast, sun-exposed bacteria are rapidly killed (see section on control measures).
3. Zoonotic Outbreaks of M. bovis and M. tuberculosis
Transmission of M. bovis from cattle to humans via infected milk accounted for ∼20% of the cases of tuberculosis in the early part of the century. In large part due to pasteurization and TB control programs in domestic hoofstock, milk has been eliminated essentially as a source of infection in the United States. Unfortunately, the same cannot be said for other countries.
In August 1996 two circus elephants died of M. tuberculosis. A third elephant has subsequently been diagnosed with active disease by culture. The state health department is currently conducting skin testing of the animal handlers and other workers for evidence of recent PPD skin conversions. M. tuberculosis was documented in an elephant in this herd in 19834 and thus highlights the risk of possible animal to animal spread of M. tuberculosis.
In the mid-1970s, two of three foxes housed in the primate building at the Duluth Zoo died of M. bovis.5 All 13 primates housed in the same building subsequently tested skin test positive. Two animals were euthanatized because of wasting, and at autopsy were discovered to have disseminated TB. Of 34 animal handlers tested, 4 (11%) were skin test positive. Skin testing of the public was also performed; of 674 individuals tested, 23 (3.4%) were PPD-positive. It is unknown whether any of the positives in the public represented new conversions.
In 1991 a male white rhinoceros died at the Audubon Zoo of M. bovis.6,7 Postmortem examination of the animal was performed “on a dark and stormy night” in a closed building adjacent to the rhinoceros’ compound. Subsequently, two colobus monkeys housed downwind from the building were skin test positive; both were later euthanatized and found to have disseminated M. bovis infection. Of 24 animal handlers exposed to the rhinoceros, seven demonstrated PPD conversions: six were zoo-keepers exposed during routine husbandry; one person converted following exposure during the necropsy.
In 1986 three seals died at a marine park in Western Australia of M. bovis.8 Three years later, one of the seal trainers developed active pulmonary tuberculosis with M. bovis of the same strain as that cultured from the seals. No data was reported for the other trainers.
After an epizootic of M. bovis was identified in domestic elk herds in Alberta, Canada, testing of exposed humans was commenced.9 Of 446 human contacts, 391 had skin tests. Of these, 81 (20.7%) tested positive, 50 with known contact with infected animals. One person developed active pulmonary infection with M. bovis.
M. bovis infections between 1953–1988 among 87 persons from Queensland Australia were reviewed.10 Of 87 cases, isolated pulmonary disease occurred in 67 individuals, extrapulmonary disease was found in eight; in 12 cases both pulmonary and extrapulmonary disease were identified. Work-related exposure to cattle was documented for 57 persons including 40 meatworkers. Thirteen persons were exposed by drinking unpasteurized milk. One person developed disease after exposure to an M. bovis infected human.
4. Control Measures to Minimize and Prevent TB Exposure and Transmission
The most important factor in preventing exposure to animals with TB is a high index of suspicion for infection. In many cases, the diagnosis is considered only when caseous lesions are detected at necropsy. Since the signs and symptoms of TB infection are nonspecific, TB should be included in the differential diagnosis of all animals, regardless of exposure history, that present with wasting, poor feeding, and especially respiratory signs, such as coughing.
All mammals should be considered as potential sources of M. bovis. Ideally, all captive mammals maintained in groups or in close proximity should be evaluated for TB. Unfortunately, TB testing has not been validated for many animal species. Furthermore, differentiating latently infected from actively shedding animals is difficult. For animals considered at high risk for infection, contact time should be limited and personnel should wear masks (HEPA masks, if possible). Protective covering (disposable coveralls, boots) and foot baths are beneficial in limiting potential spread to other animals which may ingest infected particulate matter. Gloves should be used for routine care to minimize fecal-oral transmission to humans. Careful handwashing is mandatory, regardless of glove usage. Showering is not necessary.
Other measures to decrease exposure risks to humans include limiting contact with infected animals to well-ventilated areas (such as open pens), and areas with access to ultraviolet (UV) radiation (direct sunlight or UV ceiling lights).11 The latter exploits TBs exquisite sensitivity to UV radiation. If possible, rooms used for animal care should be HEPA filtered with >6 air exchanges/minute.
To put these recommendations into context, humans admitted to the hospital with a suspicion of TB (cough, sputum production, and consistent chest radiogram) are immediately placed into isolation. Isolation rooms are under negative pressure and have 6 air changes/per minute through a HEPA filter. No non-filtered air is vented to the outside. Patients are removed from isolation when three successive sputum exams are negative for AFB. If the sputum is acid fast positive, isolation is canceled after 2 weeks of treatment if no AFB are detected on repeat sputum exams.
Infection with any of the non-tuberculous mycobacteria should not be considered “tuberculosis.” While any of these organisms may cause granulomatous, TB-like disease, the risk and mode of transmission from animal to animal and from animal to human differs drastically from that for TB. Further, labeling an animal as having “tuberculosis” immediately raises the specter of exposure to handlers and is a cause for alarm.
M. avium Complex
Organisms of the M. avium complex (MAC - M. avium and M. intracellulare) are the second most common mycobacterial species to cause infection in both animals and man. Because of a preference of these bacteria for higher growth temperatures, warm blooded animals are at risk. Marsupials are especially susceptible to disseminated M. avium infection.12
Animal to animal spread of M. avium may be possible through the fecal-oral route, especially when it is considered that M. avium may survive desiccation for periods greater than 1.5 years (J Maslow, unpublished data). DNA typing of isolates has not been able to show animal to animal spread between tree kangaroos, although ducks housed together have been found to be infected with common strains (J Maslow, unpublished data).
Human disease due to MAC infection includes lymphadenitis (scrofula), osteomyelitis, and a TB-like pulmonary infection.13-15 Disseminated disease is common among individuals with defects in cell mediated immunity, especially AIDS patients. Animal disease due to MAC, similar to that in humans, includes lymphadenitis, abscesses, hepatic and splenic infections, and osteomyelitis. To date there have been no documented cases of transmission from animals to humans. It is unknown whether isolates pathogenic for animals are pathogenic to humans. Further, environmental exposure is a more likely source of disease for humans because M. avium is ubiquitous in the environment.
M. fortuitum-M. chelonae Complex
M. fortuitum is a common mycobacterial infection among fish causing abscesses, scale disease, and gill infections. M. chelonae has been observed among reptiles including snakes and turtles.
Disseminated disease, with M. fortuitum has been reported for patients with AIDS.16 Immunocompetent hosts can develop skin abscesses and tendonitis following puncture injuries17 and may occasionally develop disseminated infection.18 No documented cases of animal to human transmission have been recorded.
Human infection with M. marinum is limited to cooler body sites (such as the hands and feet) because of the growth requirements of the organism. The best described infection is “fish handler’s disease,” a localized nodular swelling that develops at the site of trauma (puncture wounds and abrasions).19 Modes of inoculation include puncture by fish spines and abrasions sustained while cleaning fish tanks. Affected animals include fish and snakes. Disease may be disseminated in both species.
Snakes housed together may be infected with the same strains, that may represent either animal to animal spread through the environment or common source exposure (R Wallace, J Maslow, unpublished data).
M. ulcerans can cause an indolent, necrotizing skin disease endemic in some tropical countries. One report documents osteomyelitis, gangrene, and subsequent dissemination of M. ulcerans infection in a West African child following a snakebite (unknown species of snake).20
M. xenopi, a cause of mycobacterial infections among amphibians that is found in many aquatic environments, has been documented as a cause of disseminated infection among patients with AIDS.21
Zoonotic transmission of mycobacteria is well described, although essentially limited to organisms of the M. tuberculosis complex. While M. bovis is the most common species to be transmitted from animals to humans, M. tuberculosis may also be transmitted zoonotically. For the non-tuberculous mycobacteria, only M. marinum in animals has been documented as an immediate infectious disease risk to humans. Any measure that limits the time and level of exposure to infected animals will decrease the risk of transmission of TB and other mycobacteria.
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