Gram Positive Bacteria and Other Infectious Agents

Last modified on August 22, 2010

The recommended Animal Biosafety Level is indicated in the table below.{3950}

Gram positive organisms

Clostridium

Members of the genus Clostridium are long, anaerobic, Gram positive sporeforming rods{3953} (except Clostridium piliforme, the cause of Tyzzer's disease). The species that cause disease in laboratory animals are:

Antibiotics incriminated in causing outbreaks in guinea pigs include clindamycin, lincomycin, erythromycin, penicillin, bacitracin, dihydrostreptomycin and ampicillin within 1-5 days of treatment. Safer antibiotics in these animals are chloramphenicol, enrofloxacin, trimethoprim-sulfa, and aminoglycosides.{3775} In one experiment attempting to evaluate the effects of administering probiotics (mixtures of Lactobacillus, Bifidobacteria and Streptococcus) to guinea pigs receiving a single injection of 125 mg/kg clindamycin, there were no differences in weight loss, feed and water intake, or rectal temperature between probiotic and untreated groups. All guinea pigs given clindamycin developed lethargy and depression with varying levels of weight loss and decreased feed intake. C. difficile was not cultured from these young male Hartley guinea pigs; in only a few animals were they able to culture organisms such as Klebsiella pneumoniae, Cardiobacterium, or C. perfringens.{4136}

An outbreak of C. difficile in tamarins (S. oedipus) was thought to be due to antibiotic treatment for diarrhea caused by Corynebacterium. Four cases occurred in the same room and fifth in another room, suggesting possible fecal spread. At necropsy pseudomembranous colitis was diagnosed in two cases, and clostridial toxin was identified.{3892}

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Corynebacterium

These are small, pleomorphic (diphtheroid), Gram positive non-sporeforming rods. They are facultative anaerobes. They are usually of no pathogenic significance when found on the skin or mucous membranes, but may cause opportunistic infections. Gram-stained smears may have organisms that resemble streptococci, staphylococci and Listeria due to pleomorphism. The organism grows on blood agar and has a "Chinese letter" or "palisade" configuration.{3953}

C. hoffmani is a common cause of conjunctivitis in mice, probably as an opportunist. C. bovis causes pseudodiphtheriticum sporadically in nude mouse colonies, which is a dermatitis with high mortality in younger animals.{3763}

It is not known whether Corynebacterium is virulent for macaques or is a commensal organism; however, strains that produce toxins (either diphtheria toxin, DT, or phospholipase D, PLD) are associated with pathology. PLD production is a virulence factor for caseous lymphadenitis caused by C. pseudotuberculosis in small ruminants. In a colony of macaques (mostly rhesus) with cephalic implants for recordings, the three most commonly isolated bacteria were Staphylococcus aureus, Corynebacterium ulcerans, and Streptococcus pyogenes. In other reports, Enterococcus, Candida and Trichosporon have also been cultured from either the dental acrylic headsets or the recording cylinders. All were sensitive to amoxicillin, bacitracin, enrofloxacin, cephalothin, erythromycin, gentamicin, and trimethoprim-sulfamethoxazole. PLD was detected by PCR and also by coculture with Rhodococcus equi, in which hemolysis occurs only if PLD is produced by the Corynebacterium. The Rhodococcus produces cholesterol oxidase or "equi factor". In a survey of all the macaques, all but one had multiple bacterial species from skin cultures near the implants.{4109}

C. pseudotuberculosis causes caseous lymphadenitis in ruminants. Any presentation of abscessed draining lymph nodes should be assumed to be caused by this until proven otherwise. Diagnosis is based on clinical signs and ELISA testing. Antibiotics are not helpful; abscesses should be lanced and flushed and sanitation methods improved in the housing area.

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Listeria monocytogenes

This Gram positive, motile, non-spore-forming coccobacillus has a tropism for the uterus and placenta. Occasional epizootics in rabbits are characterized by fever, abortions and sudden death of does in late gestation. Potential sources of infection are contaminated feed and water. The infection can also be transplacental, causing stunting or meningoencephalitis in kits. Gross lesions are multiple necrotic foci of coagulative necrosis in the liver and spleen, lymphadenopathy, ecchymoses, acute metritis, hydrothorax, ascites and anasarca.{3768} In NHPs the mother is usually normal but the infant dies with purulent placentitis, meningoencephalitis, pneumonia and focal liver necrosis.{3770} In the guinea pig the organism causes conjunctivitis which may progress to ulcerative keratoconjunctivitis.{3775} Chinchillas are very susceptible to listeriosis, with malaise, depression, derangement, abortion and/or sudden death{3560}{3997}.

The disease in sheep, goats, and cattle occurs in one of three forms: (1) CNS involvement, (2) abortion or stillbirth, and (3) in the young, septicemia from in utero infection. There are no gross lesions in the CNS form; histologically there is meningoencephalomyelitis. The organism is thought to enter by invasion of oral epithelium, and from there into the trigeminal nerve causing a peripheral neuritis. Listeriolysin is a virulence factor required for intracellular multiplication. Both cell-mediated and humoral immunity play a role in resistance.{4105}

It is a Level 2 biosafety agent that kills nearly 100% of infected human fetuses. Sources of infection for humans include soft cheese, meat and unwashed vegetables.

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Staphylococcus

S. aureus is common in mice, in which it causes abscesses particularly in the cervical lymph nodes. Nude mice get furunculosis. It is often a secondary invader in mice with hypersensitivity to mite infestation, causing ulcerative dermatitis. Rats develop ulcerative dermatitis over the nape of the neck and shoulders, and/or mastitis. Ulcerative dermatitis is likely associated with epidermolytic strains.{3763}

Outbreaks of staphylococcosis occur sporadically in rabbit colonies. Transmission is via direct contact or by aerosols. S. aureus are common bacteria, but only the b-hemolytic, coagulase-positive strains are considered pathogenic. Infection usually is initiated through skin abrasions or the umbilicus. From there the organisms spread locally or hematogenously causing either localized lesions, embolic lesions, or generalized septicemia. Gross lesions include pyoderma, purulent mastitis, internal abscesses, septicemia, purulent bronchopneumonia and pododermatitis. On histologic sections stained with Gram stain, colonies of Gram positive cocci should be seen. The differential in rabbits includes pasteurellosis, Tyzzer’s disease and listeriosis.{3768}

Guinea pigs generally develop either pododermatitis (bumblefoot) or dermatitis (strain 13 pigs) of the ventrum.{3775}

NHPs carry Staphylococcus as well. If it invades the skin it causes pustular dermatitis, especially in the young. Another common syndrome is vegetative myocardial valvulitis with septic embolism or infarction of other organs. Monkeys may also develop secondary immune complex glomerulonephritis. Meningeal abscesses can mimic TB.{3770}

S. aureus produces a number of enterotoxins, classified in nine groups signified SEA-SEJ. The toxins bind to class-II MHC where they stimulate T cell proliferation. Fever, hypotension and endotoxic shock are the result of increased pro-inflammatory cytokines. The enterotoxins are significant in toxic shock syndrome, food poisoning, pseudomembranous enterocolitis, and autoimmune diseases such as rheumatoid arthritis and Kawasaki disease. In mice, SEB toxin induces rapid weight loss, hypoglycemia, thymic atrophy and immune suppression in a dose- and strain-dependent fashion. These effects are potentiated with other modifiers such as LPS, D-galactosamine or actinomycin D; and also by adrenalectomy or infection with non-lethal influenza virus. SEB values are measured with the Limulus amebocyte lysate assay. Unlike NHPs and rabbits, mice do not have an initial fever increase before developing hypothermia. Profound hypothermia can be used in these experiments as an alternative to death as an endpoint.{4088}

S. aureus and S. epidermidis are frequent causes of implant or catheter-associated infection (see Corynebacterium ulcerans). For example, weanling pigs implanted with vascular access ports developed high incidence of staphylococcal catheter infections. Related factors included expertise level of the surgeon, presence of pre-operative skin lesions, and failure to use antibiotics{4117}.

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Streptococcus

The CAMP test is used for presumptive identification of Streptococcus agalactiae, which is able to complete the partial lysis of RBCs produced by Staphylococcus. A streak of Staph is placed on a blood agar plate, and the species for testing is streaked at right angles to it. If the test species is Streptococcus agalactiae there will be a distinctive arrow or triangle shape of clear hemolysis at the intersection of the two streaks. {3953} 

Mice: Beta-hemolytic Streptococcus agalactiae serotype V was identified as the cause of an infection in commercial laboratory mice. Principally, the organism induced fatal septicemia in DBA/2 breeding-age mice. The syndrome originated as an ascending pyelonephritis, which progressed to septicemia. Microscopic lesions were found in the heart, kidneys, spleen, and liver, and less commonly in the uterus, thoracic cavity, lymph nodes, and lungs. The epizootic was controlled by eradication of the breeding colonies, disinfection of the barrier, and autoclaving of all equipment. The source was suspected to be a human worker; the vendor switched to handling mice only with forceps during cage change.{4146}

A few outbreaks of ulcerative dermatitis in mice have been caused by b-hemolytic strep.{3763} Pneumonia in Swiss mice used to study S. pneumoniae pneumonia was exacerbated by halothane or methoxyflurane anesthesia prior to intranasal inoculation, compared to IP pentobarbital.{4147}

Rats: In rats, outbreaks of disease can occur but are usually asymptomatic. Subclinical carriers are very common (80%). Disease and abscesses are found in the respiratory tract, ear, and reproductive tract of the rat caused by Streptococcus pneumoniae, also called diplococcus or pneumococcus. Beta-hemolytic streptococci, divided into Lancefield groups, rarely cause disease in rats.{3763}{4757}

NHPs: Streptococcus pneumoniae (formerly called Diplococcus) causes fibrinopurulent serositis and pneumonia, the most devastating respiratory pathogen in NHPs. Some animals are found dead. Signs are pneumonia, meningitis, arthritis, depression and dehydration. There are numerous thrombi and infarcts which may result in CNS damage if the animal survives. Diplococci can be seen in Gram-stained smears of the exudates, providing a presumptive diagnosis. Gross lesions are engorgement of the meningeal vasculature and purulent exudate. The lungs may be congested, edematous, and have acute purulent bronchopneumonia with gray hepatization of the ventral lobes. There may also be suppurative peritonitis with adhesions in chronic cases, suppurative arthritis and panophthalmitis.{3770, 4762} On blood agar the bacteria are a-hemolytic.{3775}  

Guinea pigs: Cervical lymphadenitis in guinea pigs is characterized as a chronic ADR with systemic signs, rhinitis and otitis. The causative organism is S. zooepidemicus, a b-hemolytic, encapsulated bacterium. "Lumps" can also be caused by Streptobacillus moniliformis, Yersinia pseudotuberculosis, Salmonella, other streptococci, zygomycetes and cavian leukemia. Systemic antibiotics such as chloramphenicol or enrofloxacin are effective.{3775}  

Guinea pigs may also be affected by S. pneumoniae, due to predisposing factors related to poor sanitation and stress. In addition to respiratory disease (bronchopneumonia), it causes metritis with abortions and stillbirths, fibrinopurulent pericarditis, and otitis media. An optochin disk on blood agar inhibits growth, a feature used for identification.{3775}{3984}

Dogs: Streptococcus zooepidemicus can cause acute pneumonia which may result in peracute death without premonitory signs. Some dogs will have moist rales with purulent nasal discharge and tonsillitis. Lesions include diffuse hemorrhagic pneumonia and septic thrombi in various organs.{3776}

Farm animals: S. suis is associated with outbreaks of meningitis, arthritis, pneumonia, endocarditis, abortions, and abscesses in swine; it also causes pneumonia, meningitis and abscesses in other species including horses, cattle, sheep and cats. Fatal meningitis and endocarditis has been reported in humans. Swine and ruminants can be carriers; 80% of piglets may carry it in their tonsils. It is a commensal organism in the intestine of ruminants. It is generally susceptible to penicillins, gentamicin, and cephalosporins, and is highly susceptible to ceftiofur in vitro. In a case report, Strep suis colonized an implanted cardiac annuloplasty ring device, causing endocarditis and meningitis. In this case the bacteria showed only intermediate susceptibility to chloramphenicol.{4560}

Fish: An outbreak of zoonotic infections of S. iniae occurred in 1997 in people who had received minor skin wounds from tilapia purchased live for food. A variety of fish in closed aquaculture systems have been infected. The disease is hemorrhagic enteritis with hemorrhage also observed at the base of the fins.{3779, 4780}

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Spirochetes

Borrelia burgdorferi (Lyme disease)

Spirochetes in the cardiac papillary muscle connective tissue of a C3H mouse 15 days after intradermal inoculation with B. burgdorferi (N40). Modified Dieterle silver stain. Magnification, x370. {4015}

Borrelia burgdorferi is a tick-borne (Ixodes dammini) spirochete. Many species other than humans can be infected, i.e. rhesus macaques, dogs, rabbits, guinea pigs, gerbils, hamsters, rats and mice. The natural reservoir is Peromyscus {4579}. Mice are a good model because of their size, genetically defined status, and disease similarity. Disease severity is genetically determined in both humans and mice; in mice, C3H/He are most affected, BALB/c are intermediate and C57BL/6 seem to be only mildly affected.

The organism has a predilection for connective tissues of the heart, joints, skin and serosa. Arthritis begins to develop as soon as 4 days after inoculation in mice. By 2 weeks, C3H/He mice have grossly visible edema of the tibiotarsal joints. During this acute phase, mice also develop cardiovascular disease. Inflammation is found at the base of the heart, and organisms can be seen with silver stains or by immunohistochemistry.

After the acute phase, protective antibody develops in mice and humans. However, a few organisms remain and can cause periodic flare-ups of disease. Since SCID mice also develop disease (and have NK cells and WBCs), the disease is not immune-mediated. Beige mice lack NK cells and granulocytes (the Chediak Higashi mutation) and are fully susceptible to borreliosis. It turns out that it's the leukocytes that are the cause of disease susceptibility, as mice with functional NK cells that are WBC-depleted with cyclophosphamide develop disease.

Differences between mouse and human disease include the lack of neurologic, dermatologic or chronic unremitting arthritic lesions in mice.{4015}

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Other Infectious Agents

Chlamydophila

C. trachomatis is also called the Nigg agent after Clara Nigg who discovered it while trying to isolate influenza virus from human throat washings inoculated into mice. It is experimentally transmitted to NHPs but is not naturally transmissible from man to animals.{4780}

The guinea pig develops inclusion conjunctivitis and possibly abortions. It is widespread and common in guinea pigs, with most adults seropositive. The disease is self-limiting in a few weeks, so no treatment is usually needed.{3775}

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Mycoplasma

These are the smallest free-living organisms, and unlike bacteria have a cell membrane instead of a cell wall. Therefore, they are pleomorphic and can appear in rings, small coccobacilli, or filaments. They have been placed in the class Mollicutes, order Mycoplasmatales. 

Murine respiratory mycoplasmosis, caused by Mycoplasma pulmonis, causes chronic respiratory disease in mice and rats, with disease more severely affecting rats. There is a distinct strain susceptibility, with Lewis rats more susceptible than F344.{4354} Disease is often subclinical and rats can remain seronegative for months. They develop a characteristic sneezing and snorting, then rhinitis, otitis, laryngitis, tracheitis, bronchiolitis, bronchopneumonia with bronchiolectasis and lymphoid hyperplasia (because it is a B cell mitogen). Treatment in rodents is depopulation.{3763}{3953} At left is an image of mycoplasmosis in a rat; a hallmark characteristic of the inflammation induced by M. pulmonis is accumulation of large numbers of lymphocytes and plasma cells, particularly around the bronchi, bronchioles, and adjacent vessels, where such accumulations can become quite extensive. In this case, the rats were part of a study of chemical carcinogenesis (aspartame and MTBE), and the lesions were misinterpreted as those of lymphoma, when in fact the rats probably had mycoplasmosis.{4774} At the contract facility that initially performed the study, rats were housed 5/cage with 200cm² per rat, less than the ETS123 guidelines require; overcrowding probably contributed to the high death losses from respiratory disease.

Genital mycoplasmal infection may lead to various outcomes, again depending on the strain. Lewis and F344 females are more resistant to development of genital disease than are Wistar and Sprague-Dawley. Females (especially Sprague-Dawley) develop endometritis, salpingitis and peri-oophoritis. Pregnancies result in lower birth weight, smaller litter size, stillbirths and fetal resorption, particularly in Sprague-Dawleys.{4354}

Macaques are frequently infected with urogenital mycoplasmas (M. genitalium, M. hominis, or Ureaplasma urealyticum); a total of 29% of 166 animals tested positive by PCR. Prevalence was higher in chimpanzees than in cynos, rhesus, baboons or pigtails. Many of the mycoplasmas were unidentified, but were picked up with a "generic" PCR, indicating that there are probably unknown mycoplasmas in laboratory primates. Whether these organisms are a significant cause of abortion, infertility, urethritis and/or salpingitis is yet to be determined.{3895} 

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Rickettsia

Ehrlichia

This organism causes ehrlichiosis in dogs (E. canis and others) and humans (human granulocytic ehrlichiosis or HGE, caused by members of the E. phagocytophila complex). Both are transmitted by ticks. Ixodes scapularis, the black-legged or deer tick, ranges in the NE and upper Midwest and is the reservoir for both Lyme disease and HGE. Rhipicephalus sanguineus is the vector for canine ehrlichiosis.{4580} 

Eperythrozoon

E. coccoides is spread by Polyplax serrata and causes anemia, splenomegaly and reticuloendothelial cell proliferation in the mouse. It is diagnosed on blood smears. Its significance is as a contaminant of biological products.{3763} E. ovis causes extravascular hemolysis in sheep and goats due to immune-mediated destruction of parasitized RBCs.{4514}

Hemobartonella

H. muris is rare in the rat and is transmitted by Polyplax spinulosa. Disease, if present, consists of transient anemia and splenomegaly.{3763}

Coxiella burnetii

This organism causes Q fever in ungulates and humans. Dogs, cats, domestic fowl and chickens can also be infected. The disease has two self-perpetuating cycles: one in wild animals where it is spread by ticks, and the other in domestic cattle, sheep and goats. Infection is widespread among US sheep.{3964} A Canadian study suggested that the major reservoirs of infection in Ontario were goats and dairy cattle rather than sheep. Sheep could carry the organisms on their fleece, so clipping it short could help control the spread of disease.{2202} It can also be transmitted by the mite Ornithonyssus bacoti. Dairy goats were implicated in an outbreak in goat workers in Nova Scotia, in which 37% of the people seroconverted; there were no deaths, generally only acute febrile illness.{4241}

Q fever is of concern in research facilities. Most human infections are asymptomatic, but some outbreaks have occurred that underscore the organism's ability to infect by aerosol and persist in the environment for many months. In one outbreak, many individuals seroconverted who had no animal contact, but were located along the path of sheep transport carts. In another outbreak, laundry workers exposed to soiled linens also became seropositive.{3964} Next to brucellosis, Q fever is the second most common lab-acquired infectious disease. ABSL3 precautions are needed when handling embryonated eggs (the only way to culture it), infected guinea pigs, ewes, or when performing necropsy on infected animals.{3950}

In ungulates, which do not develop clinical disease, organisms are shed in urine, feces, milk and especially placental fluids and tissues. Aerosol transmission to man is the most common route of zoonotic exposure. After a 2-4 week incubation, people develop acute febrile illness. Those with pre-existing cardiac valvular disease may develop subacute endocarditis. There are no skin signs such as those commonly seen in other rickettsial infections. Fever, chills, sweating, malaise, anorexia, myalgia, nausea, severe frontal headache, pharyngitis and possibly encephalitis are characteristic in man. Liver function may be affected. Most cases resolve within a few weeks, but the elderly may have protracted or even relapsing symptoms.{3964} Chronic symptoms include either atypical pneumonia or GI signs such as vomiting and anorexia. Death usually results from either hepatitis or endocarditis.{4206}

SCID-bo mice are C.B-17 scid-bg mice with sections of fetal bovine liver, lymph node and thymus implanted in the abdomen. The mice (xenochimeras) develop primary and secondary bovine humoral immune responses to T-cell-dependent antigens. In two groups of such implanted mice, a few were found dead or rough-looking. The liver had irregular surfaces and white depressed foci, and enlarged but normal-looking spleens. Histologically there was chronic active hepatitis and basophilic cytoplasmic inclusions in Kupffer cells and macrophages. PCR using a sort of general bacterial 16S ribosome yielded 100% identity with Coxiella burnetii. Unfortunately, the bovine donor tissues (from a slaughterhouse) did not test positive, but that is the presumed source of the infection. Inoculation of naive C.B-17 scid-bg mice caused lethargy and rough coats before 14 days, with identical histologic signs. Note that necropsy of animals infected with this organism should be conducted at ABSL-3 (although in this case they used a "biosafety level 2 hood").{4583}

If sheep must be used for research, males or non-pregnant females are safest. If pregnant ewes must be kept, physical separation from humans is the best method of prevention. Failing that, air handling must be addressed as well as restricting animal movements and disinfection of waste materials before disposal.  Bleach (1:100), hydrogen peroxide (5%) or Lysol (1:100) are effective.{3964}

There are vaccines available that are effective in humans, prepared from the phase I cellular antigen. However, if people have been previously sensitized, vaccination can induce abscesses. Therefore, vaccination candidates must be screened prior to vaccination. A study in guinea pigs showed that an extracted vaccine (chloroform/methanol extracted TSI-GSD vaccine) caused fewer abscess problems in previously-sensitized animals.{4070} Both rhesus and cynomolgus macaques have been experimentally infected. Cynos develop radiographic signs that more closely mimic human Q fever, although the duration of fever was longer in rhesus.{4197}

Serologic testing is available, but sensitivity and specificity are unclear. Interpretation for a single animal is more difficult than for an entire herd or flock.{4206}

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Mycobacteria

Although there are many saprophytic species of mycobacteria, tubercle bacilli (M. bovis, M. avium-intracellulare, and M. tuberculosis) are the most clinically significant. Host response includes humoral components and neutrophils, but the macrophage is the most important cell in protecting the host. Macrophages process the antigens and present them to T cells, the key recognition unit in the immune response to mycobacteria. Progressive disease is related to complex lipids in the cell walls and production of toxic lipids.{3953}

Positive acid-fast smears will usually indicate the presence of infection, but false negatives are common. Direct smears should be stained with the Kinyoun modification of the Ziehl-Neelson stain because it requires no heat. Auramine (yellow) and rhodamine (red) methods using UV light have also been used. Confirmation requires culture. Tissues are usually treated with sodium borate to kill contaminants during shipment.{3953}

M. bovis

This organism causes tuberculosis in cattle, swine, cats, humans, NHPs and hoofed exotic animals.{3953} In rhesus monkeys TB is a rapidly progressive disease. Although caged animals often are asymptomatic, those severely affected exhibit wasting, coughing, enlarged lymph nodes, splenomegaly and hepatomegaly. New World monkeys appear to be more resistant. Mammalian Old Tuberculin (1500 units) is used for diagnosis. Gross lesions are disseminated caseous yellow-white granulomas in the lung, with secondary spread to lymph nodes, spleen, liver and elsewhere. Tuberculoid granulomas are layered, with organisms found in the caseous centers, then epithelioid spindle cells and macrophages, then giant cells and finally a layer of lymphocytes. Pott’s paraplegia in humans is the result of osteomyelitis causing vertebral collapse.{3770, 4762} Dr. Baskin successfully treated fifteen rhesus macaques with tuberculosis using 12 months of combination therapy with rifampin, isoniazid and ethambutol.{4201}

A recent case report involved an imported cyno which developed lethargy, weakness, incoordination, and weight loss. Test results included anemia, monocytosis, neutrophilia with left shift, increased asparagine transaminase, alk phos, globulins and total protein, with decreased ALT and albumin. Due to previous cases of melioidosis, the monkey was euthanatized. He had had two negative TB tests up to this time. The left kidney was obliterated by a large purulent mass containing thick yellow fluid. Tissues were sent to NVSL since the monkey was in import quarantine. Histology revealed mild interstitial pneumonia. Five months later, positive culture results for M. tuberculosis complex were received, and all the cohort animals were euthanatized. Of the five other animals, two tested positive in renal tissues for M. avium. In humans, disease caused by M. bovis is indistinguishable from that caused by M. tuberculosis, except that M. bovis more often causes non-pulmonary disease. M. bovis is principally transmitted in milk. There may also be a relationship between SRV-2 infection in macaques and mycobacterial infection, similar to that noted in HIV patients.{4551}

M. tuberculosis

The human tubercle bacillus causes pulmonary disease also in monkeys, baboons, some hoofed animals, dogs, and parrots.{3953} Common growth media includes Middlebrook (which is not egg-based), Lowenstein-Jensen, Petragnami and Herrold’s. Studies of M. tuberculosis or M. bovis in NHPs must be conducted using ABSL3 precautions, as the human infectious dose is only a few organisms.

M. avium-intracellulare complex (MAIS)

There are many different serotypes in this complex. Some have been isolated from human AIDS patients. It is the most common cause of tuberculosis in swine and chickens. {3953}

There has been a single report of M. avium-intracellulare from C57BL/6 mice with granulomas in the lungs, liver and mesenteric lymph nodes.{3763}

In NHPs, M. avium and M. pseudotuberculosis cause intestinal lesions with a thickened firm mucosa caused by histiocytic infiltrates. Animals are usually immunodeficient, as with SIV or SRV infection{3770, 4762}.

Rapidly growing mycobacteria: M. chelonae, M. fortuitum, M. marinum

Closed aquaculture systems are often infected with mycobacteria, which are zoonotic (fish tank granuloma or swimming pool granuloma){4780}. M. marinum, M. fortuitum, and M. chelonae have all infected fish. Diagnosis is made by examining acid-fast stains of granulomas.{3779} An outbreak of disease in two Danio rerio aquaculture systems was caused by infection with M. fortuitum, an atypical organism. Signs in the fish were decreased reproductive performance and increased mortality. Upon examination, several fish had hyperemic gills, petechial hemorrhages on the opercula, abdominal distention and emaciation. The liver was inflamed and necrotic. In a second zebrafish colony at the same institution, fish had skin ulcers. Granulomas were present in gonads, liver and peritoneum. M. abscessus and M. chelonae were isolated. Specific PCR was used to provide rapid screening.{4198} M. chelonae also caused weight loss and non-healing skin ulcers in a colony of Xenopus laevis frogs, the first report of this organism in captive Xenopus.{4199}

M. chelonae was also cultured from tails of mice housed in open caging with non-autoclaved bedding. Granulomatous swellings were noted. The mice were immunocompromised transgenics. This was the first report of this organism in laboratory mice.{4200}

Other Mycobacteria

These are Level 2 organisms, with no cases of lab-associated transmission.

M. kansasii can induce positive mammalian TB skin tests. It has been found in pulmonary and other lesions in humans, and from the lymph nodes of cattle, swine and some exotic animals.{3770}  It was isolated from a rhesus macaque with a positive tuberculin skin test and pulmonary lesions, picked up at the regular semi-annual test.{4202} M. marinum causes swimming pool granuloma and has been isolated from cold-blooded animals. M. scrofulaceum comes from pigs and is zoonotic. M. fortuitum is the cause of pulmonary disease in humans, thoracic granulomas in dogs, skin granulomas in cats, and mastitis in cattle. It has also caused outbreaks of mortality in Japanese medaka (Oryzias latipes) with multi-organ granulomatous inflammation.{4592} M. lepraemurium is the rat leprosy bacillus.{3770} 

M. leprae, the cause of leprosy (Hansen’s disease), causes naturally occurring disease in armadillos and possibly in cats. Natural infection has also been reported in the chimpanzee and sooty mangabey (Cercocebus torquatus atys). Whether NHPs become diseased depends on their ability to mount a cell-mediated immune response. Lesions in the nerves are pathognomonic. Acid-fast bacteria may be demonstrable with Fite-Faraco acid fast stain.{3770} 

M. paratuberculosis, the cause of Johne’s disease, has been isolated from ruminants.{3953}

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Nocardia

Nocardia is an aerobic actinomycete found normally in soil and decaying vegetation. Nocardia asteroides infects NHPs via skin wounds, inhalation or ingestion. Monkeys get dyspnea, epistaxis, weight loss with abdominal distension and pain, and chronic intermittent diarrhea. They may also have draining cutaneous tracts or subcutaneous nodules filled with sulfur granules. On a radiograph, Nocardia cannot be distinguished from tuberculosis. There are no reports of successful treatment.{4762}

Unclassified diseases

Rabbit mucoid enteropathy

The etiology is thought to be multifactorial, with bacteria, toxins and a dietary component or intestinal obstruction. The disease can be reproduced experimentally by ligating sections of the large intestine. Mucoid enteropathy is a major disease of young rabbits 7-10 weeks of age. They pass copious quantities of gelatinous mucous with their feces. The disease is frequently fatal. It is thought that the mucous results from stimulation of the goblet cells of the jejunum, ileum and colon. An undetermined bacterium is thought to secrete an inciting molecule of some sort in the cecum, which is then transported to the colon. Grossly, the stomach is distended with fluid and gas, the jejunum is distended with translucent watery fluid, the cecum is impacted with dry contents, and the sacculated colon is distended with clear gelatinous mucus. Around the hyperplastic goblet cells there is no inflammation.{3768}  

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©1999, Janet Becker Rodgers, DVM, MS, DipACLAM, MRCVS

All rights reserved.

Comments? Send an email to janet.rodgers@vet.ox.ac.uk