BACTERIA MAINTAINED BY HOSTS WITH CLINICALLY ACTIVE INFECTIONS

Bacteria in this reservoir type depend upon an unbroken series of clinically active infec­tions among susceptible hosts. This reservoir type is reported relatively uncommonly among bacteria.

Bacteria in this life history group typically are passed by direct transmission. For myco- bacteriae, clinical disease develops slowly and persistently. Sometimes infection leads to domination by the bacteria and death of the host; in other cases the host survives and slowly eliminates the parasite. In many cases the host may die from other causes before the disease balance is resolved. Many bacte­ria using other reservoirs, such as recovered carriers or soil and water, can be transmitted directly from clinically ill animals to other susceptible hosts; however, these bacteria do not rely on a continuous sequence of new susceptible hosts for their survival.

mycobacterium spp. The mycobacteriae include a few obligate and facultative parasites along with a much larger number of free-living saprophytes feeding on dead and decaying matter in the environment (Grange 1996, Clifton-Hadley et al. 2001). Many species of Mycobacterium have a capacity to function as free-living opportunistic pathogens in the envi­ronment (Mitscherlich and Marth 1984, Grange 1996, Metchock et al. 1999). Further, because of the chronic and slow-developing nature of myco­bacterial infections, many infected animals also function as carriers, and can shed mycobacte- riae for extended periods before succumbing to clinical illness (Clifton-Hadley et al. 2001, Williams 2001, Fulton and Thoen 2003). This versatility in life history patterns is a character­istic that greatly complicates control strategies with mycobacteriae.

Most mycobacteriae of concern in wildlife diseases have the capacity to produce chronic, long-term diseases, and some also are obligate parasites. Mycobacteriae of the M. tuberculosis complex use diseased tissue ofclinically infected hosts of warm-blooded animals as their primary niche. In contrast, members of the Mycobacte­rium avium complex seem less dependent on a parasitic lifestyle; they are ubiquitous in nature and have been isolated from water, soil, plants, and other environmental sources (Metchock et al. 1999). Because many of these strains can be sustained solely by ongoing transmission from animals with active clinical infection to other susceptible hosts, we address the genus as a whole in the clinically active reservoir type. Further, we recognize that some of mycobac- teriae have a capacity to function as free-living opportunistic pathogens in the environment (Grange 1996, Metchock et al. 1999).

causative agent Members of Mycobac­terium spp. are aerobic, non-spore-forming, non-motile, acid-fast, rod-shaped bacteria (Family Mycobacteriaceae; App. 1: Table 7) that often have a filamentous growth (Metchock et al. 1999). Although considered gram posi­tive, the high lipid content of their cell wall excludes many of the usual dyes from being taken up (Metchock et al. 1999). Growth generally is slow for mycobacteriae, with gen­eration times ranging from 2 to >20 hours (Metchock et al. 1999).

The genus Mycobacterium contains many potentially pathogenic species. The most important mammalian pathogens are mem­bers of the M. tuberculosis complex and include M. bovis, M. tuberculosis, M. microti, and M. africanum (Thoen and Williams 1994). Most species within the M. avium complex infect birds, especially M. avium; to a lesser extent they are infected by M. genavense, M. intracellulare, M. fortuitum, M. tuberculosis, M. gordonae, and M. nonchromogenicum (Converse 2007). Until recently, the M. avium complex comprised 28 serotypes of two distinct species: M.

host range and geographic distribution Members of the M. tuberculosis complex have a worldwide distribution and are commonly reported in wildlife, domes­tic animals, and humans. Mycobacterium tuberculosis itself is most commonly associated with humans and is considered uncommon as a wildlife problem, though it has occurred in a number of captive nonhuman primates, elephants, and psittacine birds (Isaza 2003). Mycobacterium bovis is a significant pathogen of domestic cattle and also has been reported from at least 70 species of nondomestic mammals (de Lisle et al. 2001), including many cervids and bovids; it regularly affects antelope, camelids, equids, nonhuman primates, carnivores such as European badger (Meles meles) and ferrets (Mus- tela putorius furo), as well as marsupials such as the Australian brushtail possum (Trichosurus vulpecula) (Clifton-Hadley et al. 2001, Isaza 2003). Mycobacterium microti occurs in voles and other rodents, while M. africanum, first iso­lated in Africa, is a rare cause of tuberculosis in humans (Clifton-Hadley et al. 2001).

Members of the M. avium complex also have a worldwide distribution, but occur most frequently in north temperate regions; they have been isolated from a wide variety of wild birds, including upland birds, passerine spe­cies, and aquatic species (Gale 1971). A wide range of free-living and captive birds among at least 15 orders have been diagnosed with avian tuberculosis; there are no reports of avian species resistant to all mycobacteriae (Converse 2007).

Although most members of the M. avium complex infect birds, some can infect marsupi­als and humans. In particular, M. avium para­tuberculosis is a parasite of wild and domestic ruminants (Sweeney 1996, Williams 2001, Isaza 2003) and has been reported from at least 24 species of nondomestic mammals, primar­ily among the bovids and cervids, as well as some camelids, the European rabbit (Orycto- lagus cuniculus), and stump-tailed macaques (Macaca arctoides) (Williams 2001). Most members of the M. tuberculosis complex and some of the M. avium complex are infective to humans (Fraser and Mays 1986).

reservoirs and transmission The major ecological niche for members of the M. tuber­culosis complex, including M. bovis, is diseased tissue of warm-blooded mammals (Metchock et al. 1999). While these mycobacteriae can survive in the environment for variable lengths of time (Wray 1975), they tend to rely on the continual availability of susceptible hosts for parasite transmission.

While members of the M. avium complex are commonly associated with long-term, chronic infections, many also can be free living in soil and water or use carrier animals with­out evidence of disease (Metchock et al. 1999). Many members of the M. avium complex are considered ubiquitous in nature and have been isolated from water, soil, plants, and other envi­ronmental sources (Metchock et al. 1999). Sur­vival in the environment has been reported up to 2 years when buried in the soil and 4 years in poultry litter and soil (Schalk et al. 1935, Wray 1975, Mitscherlich and Marth 1984). This suc­cess in the environment may be enhanced by the ability of some M. avium to use amebae as environmental hosts (Cirillo et al. 1997, Steinert et al. 1998) and the possible use of earthworms as vectors (Fischer et al.

Mycobacterium avium paratuberculosis is able to use silent carriers, in which infected animals may shed organisms and serve as sources of infection of susceptible herd mates for years and yet never develop clinical disease (Williams 2001). These organisms have been isolated from feces of clinically healthy free-ranging fallow deer (Dama dama) and axis deer (Axis axis) (Riemann et al. 1979), tule elk (Cervus elaphus nannodes) (Cook et al. 1997), and white-tailed deer (Odocoileus virginianus) (Chiodini and vanKruiningen 1983). Among one elk popula­tion, the organisms persisted over a 13-year period, including a 6-year absence of observed clinical signs (Cook et al. 1997). In contrast to most other members of the M. avium complex, M. avium paratuberculosis generally survived less than 5 months in soil after removal of infected animals (Whittington et al. 2003). Scaven­ger animals also are regularly infected with M. avium paratuberculosis (Anderson et al. 2007).

Mycobacterium bovis and other members of the M. tuberculosis complex typically are trans­mitted by inhalation of droplet nuclei or inges­tion of contaminated food or water (Thoen and Williams 1994, Clifton-Hadley et al. 2001). Among birds, M. avium is spread most com­monly by infected birds with advanced lesions excreting the organism in their feces; suscep­tible birds subsequently ingest the bacteria from contaminated food or water (Rankin and McDiarmid 1969, Converse 2007). Preda­tors and cannibalistic flock mates may become infected by ingesting portions of carcasses (Gale 1971, Fraser and Mays 1986, Friend 1999d) Mycobacteriae also can be spread by aerosol from lesions in the respiratory tract of infected birds (Thoen 1997). There is also evidence that M. avium can be spread mechanically by arthro­pods, including ticks (Argas persicus) (Kovalev 1983). Factors that appear to enhance transmis­sion of M. avium paratuberculosis include the age and immune competence of the host, strain of the bacterium, and factors affecting available bac­terial inoculum such as degree of contamination, humidity, and exposure to sunlight (Williams 2001).

CLINICAL EFFECTS AND DIAGNOSIS Two clinical syndromes commonly are associated with tuberculosis: a respiratory disease associ­ated with inhalation as a means of transmis­sion, and nodular infections of internal organs such as liver and spleen associated with inges­tion of mycobacteriae (Clifton-Hadley et al. 2001). The virulence of the mycobacteriae is linked to lipids in the bacterial cell wall that may protect the bacterium from phagocytosis and that incite a granulomatous response from the host (Tell et al. 2001).

For respiratory infections involving M. bovis, there typically is an initial focus in the lung, followed by dissemination of the bacteria to regional lymph nodes; following ingestion, a similar process occurs in the pharynx or intes­tine (Clifton-Hadley et al. 2001). In avian tuber­culosis from M. avium, typical signs involve emaciation, lethargy, and weakness; granulo­mas are commonly found in the liver, spleen, and gastrointestinal tract (Friend 1999d, Isaza

2003). Birds with avian tuberculosis usually are sick for a few weeks to several months; death is the usual outcome (Converse 2007).

Paratuberculosis, M. avium paratuberculosis infection, is a chronic intestinal infection that leads to a thickening of the intestine. Lymphoid tissue replaces intestinal tissue, and animals waste away because they cannot properly absorb food or water (Williams 2001). Emaciation and a variable occurrence of diarrhea characterize clinical signs of infection. There also may be associated bone fractures, deformed antlers, and a light, brittle hair coat (Williams 2001).

Presumptive diagnoses often can be based on finding acid-fast bacilli in smears prepared from lesions or in feces. Enzyme-linked immu­nosorbent assays (ELISAs) also are available (Converse 2007). Polymerase chain reaction tests have been used for identification of some mycobacteriae (Miller et al. 1999). However postmortem examination combined with bac­terial culture from tissues is the most sensi­tive method for diagnosis (Clifton-Hadley et al. 2001, Converse 2007). There are reliable molecular tests using nucleic acid hybridization probes to detect genetic fingerprints among isolated strains (Thorel 2004).

population effects Mycobacterial infec­tions most commonly cause ongoing chronic diseases among infected host populations for both mammals (Riemann et al. 1979, de Vos et al. 1995, Joly et al. 1998, Clifton-Hadley et al. 2001) and birds (Plum 1942, Mitchell and Duthie 1950, McDiarmid 1956, MacNeill and Barnard 1978, Smit et al. 1987). Although extrapolating prevalences among birds found dead to likely prevalences in live populations is difficult, tuberculosis generally appears as a chronic infection of low to moderate prevalence. There are no clear cases of mycobacteriae limit­ing wild populations or causing significant pop­ulation reductions, although there is a concern about the possible effects of wildlife-transmitted tuberculosis among Iberian lynx (Lynx pardi- nus), a highly endangered species susceptible to bovine tuberculosis (Gortazar et al. 2008).

special problems Because of the per­ceived risk of infected wildlife to eradication programs for domestic cattle, some cases of M. bovis-infected wildlife populations have drawn considerable attention, including infec­tions among badgers (Meles meles) in Europe, brushtail possums (Trichosurus vulpecula) in Australia, feral ferrets (Mustelaputorius furo) in New Zealand, and white-tailed deer (Odocoileus virginianus) in Michigan (Clifton-Hadley et al. 2001, Schmitt et al. 2002), as well as several wildlife species in Spain (Aranaz et al. 2004, Gortazar et al. 2008). Mycobacterium bovis, in combination with anthrax, has become part of a difficult biological and political issue in Wood Buffalo National Park, Canada.

One special problem is the M. bovis infec­tion of the Michigan white-tailed deer herd, documented in 1994 (Schmitt et al. 1997); this may be the first self-sustaining epizootic of this bacterium in free-ranging North American cer- vids (O'Brien et al. 2002). Under experimental conditions, the mycobacteriae can be transmit­ted among deer, as well as from deer to cattle, through nasal secretions, saliva, or contami­nated feed (Palmer et al. 2001, 2004a, 2004b). Once tuberculosis was present, supplemental feeding by local residents appeared to exacer­bate the risk of infection to susceptible animals (Miller et al. 2003). More recently, infections have been found among carnivores associated with the infected deer herd, including coyotes (Canis latrans) (Bruning-Fann et al. 1998), rac­coons (Procyon lotor), red foxes (Vulpes vulpes), and black bears (Ursus americanus); one bob­cat (Lynx rufus) also was positive by PCR for M. bovis (Bruning-Fann et al. 2001). Deer are believed to be the likely source of M. bovis for the carnivores (Bruning-Fann et al. 1998). Two human cases have been linked to deer of the region (Wilkins et al. 2008).

High deer densities and focal concentrations caused by hunting deer that have been attracted to feed, as well as general supplemental feed­ing, probably were important contributors to establishing this reservoir (Schmitt et al. 2002). The epizootic is characterized by broad areas of very low prevalence surrounding focal areas of higher prevalence; the tuberculosis may be maintained at very low prevalence in matriar­chal groups, with primary dissemination of the mycobacteriae attributed to dispersal of males (O'Brien et al. 2002). Estimated prevalence of active M. bovis infection among Michigan deer in the affected region is about 3.6% (O'Brien et al. 2004). These deer have been identified as a reservoir host of bovine tuberculosis and are perceived as a potential threat to the tubercu­losis control and eradication programs that are now in their final stages in the United States (Payeur et al. 2002).

Paratuberculosis among elk and cattle at Point Reyes National Seashore, California, is another special problem. Tule elk (Cervus ela- phus nannodes) were introduced to Point Reyes in 1978 as part of a program to protect and relocate tule elk into historic ranges. Follow­ing their contact with infected cattle on Point Reyes, the elk became infected with M. avium paratuberculosis (Jessup et al. 1981). The elk probably maintain paratuberculosis due to high animal density as well as conditions favorable for survival of the bacteria in the environment (Cook et al. 1997, Jessup and Williams 1999). Mycobacterium avium paratuberculosis has been isolated from asymptomatic axis deer (Axis axis) and fallow deer (Dama dama) on Point Reyes (Riemann et al. 1979), with cattle and elk serving as susceptible hosts (Jessup et al. 1981, Williams 2001); however, elk also can serve as silent carriers (Cook et al. 1997). Once estab­lished at a site, the mycobacteriae are difficult to eradicate; isolations of M. avium paratuber­culosis from the feces of free-ranging elk on Point Reyes in one study were made at least 13 years after known infections were present and after a 6-year absence of any observed clinical cases (Cook et al. 1997). As a protected subspe­cies, the tule elk cannot be culled. In 1999, 45 elk were transplanted from the isolated herd to other parts of Point Reyes as a temporary solution to overpopulation of the infected herd; 17 animals ELISA-positive for M. avium para­tuberculosis were euthanized. However, the remaining elk were released into free-ranging conditions within the park and have a potential to mingle with cattle. A primary concern is that the free-ranging infected elk can enhance the cycle among domestic cattle in enzootic areas and even expand infections to new populations through their movements.

Paratuberculosis also has been observed among the endangered Florida Key deer (Odocoileus virginianus clavium) (Quist et al. 2002). However, at this time, the disease occurs in a low prevalence and in a relatively small geographic area within the Key deer range (Pedersen et al. 2008).

control High deer densities and increased focal deer concentrations at artificial feeding stations, as well as general supplemental feed­ing by local residents, may have been impor­tant contributing factors in establishing the tuberculosis reservoir among deer of Michigan (Schmitt et al. 2002). Because of these con­cerns, baiting and feeding have been banned since 1998 in counties with the disease. Also, the deer herd has been reduced by an estimated 50% through use of unlimited antlerless per­mits. Correlated to these management steps, there is evidence of reduced M. bovis prevalence (O'Brien et al. 2002, Schmitt et al. 2002).

Michigan white-tailed deer also appear to give a strong cellular immune response to M. bovis following subcutaneous vaccination (Waters et al. 2004). Oral administration of M. bovis vaccine also resulted in effective immu­nity among white-tailed deer (Nol et al. 2008). Thus vaccine use could be a future potential tool.

Avian tuberculosis among ring-necked pheasants (Phasianus colchicus), chukar par­tridges (Alectoris chukar), and wild turkeys (Meleagris gallopavo) was eradicated from the Yountville Game Farm (Napa County, CA) after a 20-year occurrence. This followed the applica­tion of three steps: not keeping birds for more than 18 months, allowing pens to remain idle in alternate years, and not exchanging eggs or birds with other facilities (Rosen and Platt 1949).

In eradicating bovine tuberculosis among feral cattle and buffalos (Bubalus bubalis) in the Northern Territory of Australia, intensive cull­ing of buffalo and cattle populations was under­taken, with whole areas depopulated (Lehane 1996, Clifton-Hadley et al. 2001). Tracking radio-collared buffalos that rejoined their herds was used to find and destroy the few remain­ing pockets of animals (Clifton-Hadley et al. 2001). Restocking of these areas was done with animals from tuberculosis-free populations (Clifton-Hadley et al. 2001). Test and slaughter techniques were not determined to be practical in this case (Lehane 1996).

For the Wood Buffalo National Park bison in Canada, a test and slaughter procedure initially was used to remove tuberculin reac­tors (Choquette et al. 1961). More recently, the Federal Environmental Assessment Review Panel recommended that all of the diseased introduced bison be destroyed and replaced with tuberculosis-free wood bison from the Mackenzie Sanctuary; the Bison Research and Containment Program was established for this purpose (Clifton-Hadley et al. 2001). There has been little apparent progress on this proposal.

In an effort to reduce the transmission of bovine tuberculosis from badgers (Meles meles) to cattle in the United Kingdom, a program was initiated in 2006 to vaccinate badgers against M. bovis. Once the safety and efficacy of the vaccine is established, badgers eventually will be vaccinated by mixing microcapsules of vac­cine with peanuts (Anonymous 2006). Past programs based on culling badgers have not proven effective (Woodroffe et al. 2006). How­ever, in one recent study, prevalence of cattle tuberculosis inside an area from which badgers had been culled declined significantly after the badger-culling program was completed (Jenkins et al. 2008).

In a study among wildlife of Donana Bio­sphere Reserve of Spain, a high prevalence of bovine tuberculosis was maintained among wild boar (Sus scrofa), red deer (Cervus elaphus), and fallow deer (Dama dama) in the absence of cattle as well as of artificial feeding of wildlife. The implication was that a feeding ban alone would have a limited effect on wildlife M. bovis prevalence among wildlife in this system.