Diseases / List of Bacterial Diseases / Tularemia / Detailed Disease Description:

< > Reports of PATHOLOGICAL FINDINGS - (Necropsy/Post Mortem) for Tularemia:

Liver of hare with tularemia, showing miliary pale foci. Click here for full-page view with caption. Liver necrosis, European brown hare with tularemia. Click here for full-page view with caption Immunohistochemical staining with monoclonal antibody, liver of hare with tularemia. Click here for full-page view with caption. Fluorescent staining with poly antibody, liver of hare with tularemia. Click here for full-page view with caption.

OVERALL PATHOLOGICAL FINDINGS - Editorial Comment
(Text Replicated on Overall Disease page - Tularemia))

Editorial Overview (Editorial Overview Text Replicated on Overall Disease page - Tularemia)
GROSS PATHOLOGY
  • Gross lesions are variable both within and between species, and are not always found in individuals which have died from acute tularemia.
  • Usually this is an acute infection and the affected individual is in good body condition.
  • Enlargement of lymph nodes (regional or generalised) is a common finding.
  • The spleen may be enlarged and/or contain pale (necrotic) foci.
  • The liver may contain pale foci and is sometimes swollen.
  • The bone marrow may contain pale foci.
  • The lungs may be congested and oedematous, sometimes with areas of consolidation, and may contain necrotic foci.
  • Sometimes intestinal lesions are present.
  • With more chronic infection, poor body condition and granulomatous lesions may be found.
HISTOLOGY
  • Lesions developing depend on the degree of susceptibility of the host and thus the time course of infection. 
  • In highly susceptible species with an acute course of disease, foci of coagulative necrosis are found in the liver, spleen and bone marrow (e.g. in hares), and, in infection occurred by the respiratory route, there may be congestion. oedema, areas of consolidation or lungs.
  • In species which are less sensitive, chronic inflammatory changes may be present, with chronic granulomas present in the spleen, liver, lungs and kidneys and proliferative changes (macrophages, epithelioid cells and giant cells) in lymph nodes.
AGENT DETECTION
  • Immunohistochemistry confirms antigen of Francisella tularensis particularly in organs with necrotic lesions. This has been used successfully not only on sections from fresh tissues but also on deparaffinized and rehydrated formalin-fixed, paraffin-embedded tissue sections.
  • The organism can be cultured on appropriate media, then typed.
Gross/ General Pathological Findings)

Liver of hare with tularemia, showing miliary pale foci. Click here for full-page view with caption.

Note:  

  • Necropsy findings are variable. (W31.Apr09.w1)
  • Gross lesions are not always visible following death from acute infection. (J64.11.w9)

  • Usually good body condition. Signs of septicaemia: pale foci (variable in size, may not be visible with the naked eye) in liver, bone marrow and spleen. Often splenomegaly. Lungs often congested and oedematous, sometimes with areas of consolidation, fibrinous pneumonia or pleuritis. In the abdominal cavity, fibrin may be noted. In one or more lymph nodes, particularly those draining the extremities and those in the abdominal cavity, there are often caseous necrotic foci. (W31.Apr09.w1)
  • In species which are less sensitive, following more chronic infection, necropsy findings may resemble those of tuberculosis, with chronic granulomas present in the spleen, liver, lungs and kidneys. (B209.18.w18, W31.Apr09.w1)
  • Typically:
    • Spleen and liver: may be blueish-red, enlarged. (B282.18.w18)
    • Spleen, liver and lymph nodes: nodules, pinpoint to irregular conglomerations of several millimetres diameter. (B282.18.w18)
    • Lungs: small necrotic foci or white plaques. (B282.18.w18)
    • Bone marrow: small white nodules (may not be visible grossly). (B282.18.w18)
  • Sensitive species:
    • Usually good body condition. In the abdominal cavity, fibrin may be noted. 
    • Signs of septicaemia: pale foci (variable in size, may not be visible with the naked eye) in liver, bone marrow and spleen. Often splenomegaly. 
    • Lungs: often congested and oedematous, sometimes with areas of consolidation, fibrinous pneumonia or pleuritis.
    • Lymph nodes, particularly those draining the extremities and those in the abdominal cavity: often caseous necrotic foci. (W31.Apr09.w1)
  • Less sensitive species:
    • Spleen, liver, lungs and kidneys, chronic granulomas (similar to those seen with tuberculosis). (W31.Apr09.w1)
Rodents

In naturally and experimentally infected ground squirrels. [1911] (N42.43.w1)

  • General: Occasionally slight jaundice. 

  • Lymph nodes: normal structure replaced by a firm, caseous mass (bubo), with a dry, yellowish or blood-stained surface. This may be the only lesion. Often only a single affected lymph node (inguinal, axillary, cervical or pelvic) but sometimes more than one e.g. inguinal and pelvic. Occasionally a purulent lymph node. 

  • Spleen: splenomegaly, reaching 4-5 times normal size. Firm consistency, dark, slate blue or nearly black, with white to yellowish caseous granules, pinpoint to 1 mm diameter, from e.g. a dozen to very numerous, throughout the parenchyma and projecting slightly on the surface.

  • Hepatic: caseous granules, often greyish, in the liver; may be numerous.

  • Lungs: usually normal, rarely (e.g. in 1/32 cases of natural infection), caseous granules similar to those in the spleen and liver. 

  • In experimentally infected ground squirrels: at the sight of inoculation, a slight scab and moderate thickening. (N42.43.w1)

In a naturally infected, clinically normal Spermophilus franklinii - Franklin's ground squirrel: (J4.175.w3)

  • Hepatic tiny pale foci, uniformly distributed through the liver. (J4.175.w3)

In experimentally infected guinea pigs: [1911] (N42.43.w1)

  • Lymph nodes: enlarged and necrotic; normal structure replaced by a firm, caseous mass (bubo), with a dry, yellowish or blood-stained surface; this often appears waxy. Following inoculation on the abdomen, both inguinal nodes may be affected, also in the pelvic lymph nodes, fine pearly-white granules. If the organism is introduced via the nose, the main lymph node lesion is present in the cervical nodes, while if induced by feeding, the cervical or abdominal lymph nodes are affected.  

  • Spleen: large, dark, friable, with white caseous granules, varying in size up to 1 mm diameter, usually very numerous.

  • Liver: numerous granules; sometimes irregular yellow-green areas.

  • Lungs: often patchy congestion, occasionally punctate haemorrhages and rarely fine white granules. Occasionally a serous pleural effusion. 

In experimentally infected guinea pigs (J330.34.w1)

  • Hepatic: Small necrotic foci throughout. (J330.34.w1)

  • Splenic: Small necrotic foci throughout. (J330.34.w1)

  • Lymph nodes: Caseated. (J330.34.w1)

In guinea pigs experimentally infected by scarification of the abdomen. (J240.24.w1)

  • Hepatic: liver enlarged and congested, with necrotic foci (less numerous than in the spleen). (J240.24.w1)

  • Splenic: spleen enlarged, hard and dark, with numerous grey-yellow necrotic foci. (J240.24.w1)

  • Body cavities: In the peritoneal, pleural and pericardial cavities, haemorrhagic exudate. (J240.24.w1)

  • Note: lesions were more pronounced in guinea pigs taking longer to die after inoculation. (J240.24.w1)

In experimentally infected mice, after subcutaneous inoculation: (J119.37.w1)

  • Inoculation site: subcutaneous hyperaemia and infiltrate. (J119.37.w1)

  • Lymph nodes: Regional lymph nodes enlarged. (J119.37.w1)

  • Hepatic: Liver enlarged. (J119.37.w1)

  • Splenic: Spleen enlarged. (J119.37.w1)

  • GIT: Intestines and mesentery hyperaemic. (J119.37.w1)

  • Renal: Kidneys sometimes pale. (J119.37.w1)

  • Adrenals: Sometimes hyperaemic. (J119.37.w1)

In naturally infected wild Microtus pennsylvanicus - meadow mouse: USA; diagnosed by culture. (J100.76.w1)

  • Splenic: Slight splenomegally (2 cm x 0.87 cm); this was often the only finding. (J100.76.w1)
  • Lymph nodes: in one individual, enlarged lymph nodes. (J100.76.w1)
  • Respiratory: In one individual, bilateral lobar pneumonia. (J100.76.w1)
  • Infection confirmed by culture from the individual with multiple lesions and from a pool of tissues from six others. (J100.76.w1)

In pen-reared Castor canadensis - American beavers: (J13.23.w1)

  • General: subcutaneous tissues congested.

  • Hepatic: enlarged liver, with numerous necrotic foci.

  • Splenic: enlarged spleen, with numerous necrotic foci.

In experimentally infected Cricetus cricetus - common hamsters (Muridae - Rats, mice, voles, gerbils etc. (Family)). (J1.46.w1)

  • Splenic: Enlarged, congested. In one of the two animals, pinpoint white foci both on the serosal surface and the cut surface. (J1.46.w1)

In naturally infected Ondatra zibethica - Musk rat (Muridae - Rats, mice, voles, gerbils etc. (Family)), on Walpole Island, Lake St Clair, Ontario, Canada in 1955. (J240.24.w1)

  • Spleen: enlarged, with many yellow-white necrotic foci. (J240.24.w1)

Lagomorphs
  • Typical lesions in hares include acellular necrosis in the liver, spleen and (most frequently) bone marrow. (J307.22.w1)

In experimentally infected laboratory rabbits (J330.34.w1, D392.II.w2)

  • Hepatic:

    • Small necrotic foci throughout. (J330.34.w1)

    • Hepatic enlargement (swelling). (D392.II.w2)

  • Splenic:

    • Small necrotic foci throughout. (J330.34.w1)

    • Splenic swelling. (D392.II.w2)

  • Lymph nodes:

    • Caseated. (J330.34.w1)

    • Lymphadenopathy. (D392.II.w2)

In Lepus timidus - Mountain hare

  • General:  
    • In six hares dying December to March in Sweden, poor nutritional condition. (J1.24.w14)
    • In Lepus timidus - Mountain hares in Sweden in the 1967 outbreak, subcutaneous petechiae or larger haemorrhages were noted occasionally. (J33.21.w1)
    • In a young male from Stora Karlsö, an island off the coast of Sweden, in an outbreak killing about 150 hares, poor nutritional state. (J33.36.w1)
  • Splenic:
    • Moderate enlargement of the spleen, and pinpoint white foci. (J1.24.w14)
    • In Lepus timidus - Mountain hares in Sweden in the 1967 outbreak, only moderate enlargement of the spleen (4 - 5 cm long versus normal 3 - 4 cm, and 2.8 g versus normal 0.3 - 0.5 g, compared with 8 - 11 cm and 20g or larger in some other diseases such as pseudotuberculosis), which did not show rounded edges and was generally greyish-brown or greyish-lilac in colour, more rarely dark red. Disseminated pinpoint grey-white foci were found in about 75% of spleens. (J33.21.w1)
    • In a young male from Stora Karlsö, an island off the coast of Sweden, in an outbreak killing about 150 hares, moderate enlargement and multiple grey-white foci. (J33.36.w1)
  • Hepatic:
    • Pinpoint white foci in the liver. (J1.24.w14)
    • In Lepus timidus - Mountain hares in Sweden in the 1967 outbreak, the liver was often normal, sometimes slightly yellower or slightly darker red than normal, with pinpoint grey-white foci seen in about 14%. (J33.21.w1)
    • In a young male from Stora Karlsö, an island off the coast of Sweden, in an outbreak killing about 150 hares, multiple grey-white foci. (J33.36.w1)
  • Digestive system:  
    • In six hares dying December to March, haemorrhagic enteritis and typhlitis, with congestion and necrosis of mucosa in the jejunum and caecum. (J1.24.w14)
    • In Lepus timidus - Mountain hares in Sweden in the 1967 outbreak, the mucosa of the GIT was usually hyperaemic. (J33.21.w1)
  • Respiratory:
  • Bone Marrow: 
    • Pinpoint white foci. (J1.24.w14)
    • In Lepus timidus - Mountain hares in Sweden in the 1967 outbreak, multiple pinpoint grey-white foci were seen in about 80% of cases. (J33.21.w1)
    • In a young male from Stora Karlsö, an island off the coast of Sweden, in an outbreak killing about 150 hares, multiple grey-white foci. (J33.36.w1)
  • Lymph nodes:
    • In a young male from Stora Karlsö, an island off the coast of Sweden, in an outbreak killing about 150 hares, moderate enlargement. (J33.36.w1)

In a naturally infected Lepus europaeus - Brown hare from Thuringia, Germany: (J238.123.w1)

  • Splenic: Moderate splenomegaly. (J238.123.w1)
  • Lymph nodes: Swollen. (J238.123.w1)
  • Kidneys: Swollen. (J238.123.w1)
  • Respiratory: Tracheal mucosa diffusely reddened and with petechiae. (J238.123.w1)
  • GIT: In the colon, mucoid inflammation. (J238.123.w1)

In 50 naturally infected Lepus europaeus - Brown hare from Hungary: (J26.47.w1)

  • In 47 shot or found-dead hares which were found to be seropositive (no similar lesions were found in seronegative hares): (J26.47.w1)
    • General: Body condition good (24%), moderate (22%) or weak (54%). (J26.47.w1)
    • In 88% of the hares, variable numbers of necrotic foci in various organs, either in one organ (24 hares) two organs (13 hares) or multiple organs (seven hares). Foci were white, grey-white or yellow-white, 1 - 5 mm diameter, often with a hyperaemic ring around the focus. In the lungs and kidneys, foci often coalesced to form nodules up to 1 cm diameter. (J26.47.w1)
    • Pulmonary: (Lesions in 40 hares, 80% of hares) Foci were commonly present and often coalesced to form nodules up to 1 cm diameter. Those on the serosal surface were raised, domed or flattened, with a dry, granular serosal surface (focal serositis). (J26.47.w1)
    • Cardiac: (Pericardial lesions in 14 hares, 28%) Pericardial foci were raised, domed or flattened, with a dry, granular serosal surface (focal serositis). (J26.47.w1)
    • Renal: (lesions in 10 hares, 20%) Foci often coalesced to form nodules up to 1 cm diameter. Those on the serosal surface were raised, domed or flattened, with a dry, granular serosal surface (focal serositis). (J26.47.w1)
    • Reproductive: (lesions in two hares, 4%) Testes enlarged in some cases, and the cut surface revealed several yellow-white foci or nodules. (J26.47.w1)
    • Bone marrow: (lesions in two hares, 4%)Small numbers of foci. (J26.47.w1)
    • Mammary glands: (lesions in one hare, 2%)Small numbers of foci. (J26.47.w1)
    • Hepatic: (lesions in one hares, 2%). Foci.
    • In two of the three male hares which had died naturally and were seropositive: (J26.47.w1)
      • General: Poor body condition. (J26.47.w1)
      • Pulmonary: Lungs swollen. Petechial haemorrhages and large numbers of greyish-white or yellowish-white foci. (J26.47.w1)
      • Cardiac: large numbers of greyish-white or yellowish-white foci. (J26.47.w1)
      • Splenic: Spleens swollen. (J26.47.w1)
      • Hepatic: liver swollen. (J26.47.w1)
      • Renal: Kidneys swollen. (J26.47.w1)
      • Reproductive: In one hare, large numbers of greyish-white or yellowish-white foci in the testes. (J26.47.w1)

In two Lepus europaeus - Brown hares experimentally inoculated subcutaneously with 2.6 x 109 CFU of a wild strain of Francisella tularensis isolated from a wild hare: (J307.53.w1)

  • Splenic: Splenomegaly. (J307.53.w1)
  • Note: Three hares survived infection and were euthanased at 35 dpi. There were no gross lesions in these hares. (J307.53.w1)

In seven experimentally infected Lepus californicus - Black-tailed jackrabbit (D392.III.w3)

  • Hepatic: numerous small white foci. (D392.III.w3)
  • Splenic: enlargement (slight to moderate) of the spleen, and diffuse pinpoint white foci, fewer in animals dying sooner. (D392.III.w3)
  • Lymph nodes: slight to moderate enlargement of regional (inguinal and pelvic) lymph nodes in hares dying after five days (not in those dying earlier) and caseation on the same hares; also enlargement and caseation of pelvic lymph nodes in one hare dying on day four. (D392.III.w3)
  • Bone marrow: red and soft, with variable numbers of pinpoint white foci in most animals; no lesions in two hares. (D392.III.w3)

In six experimentally infected Sylvilagus floridanus - Eastern cottontail (D392.IV.w4)

  • Respiratory: Congestion and induration in 1/6. (D392.IV.w4)
  • Hepatic: numerous small white necrotic foci in all rabbits. (D392.IV.w4)
  • Splenic: slight to substantial enlargement; no foci in one but variable numbers of miliary foci in the other rabbits. (D392.IV.w4)
  • Lymph nodes: no to slight enlargement of regional lymph nodes. (D392.IV.w4)
  • Bone marrow: very red and soft, with numerous small white foci. (D392.IV.w4)
Primates

In experimentally infected [species unspecified] monkeys:

  • Site of inoculation: whitish necrotic area

  • Lymph nodes: draining lymph node(s) caseous.

  • Spleen: swollen, and in two of three individuals, containing numerous granules, pinpoint to  mm diameter.

(N42.43.w1)

In a naturally infected Pongo pygmaeus - Orang-utan (J2.40.w1)

  • Pulmonary: Lung congestion and oedema.
  • Hepatic: congestion, rounded edges, multiple white foci throughout the parenchyma and on the surface. (J2.40.w1)
  • Splenic: congestion, rounded edges, multiple white foci throughout the parenchyma and on the surface. (J2.40.w1)

In a one-year-nine-months-old Callithrix jacchus - Common marmoset in Switzerland. (J238.61.w1, P6.2.w12)

  • General: Organs congested. (P6.2.w12)
  • Respiratory: Diffuse acute alveolar emphysema. (P6.2.w12)
  • Hepatic: Throughout the liver, numerous white foci, up to 1 mm diameter. (J238.61.w1, P6.2.w12)
  • Renal: In both the cortex and medulla of the kidneys, numerous white foci, up to 1 mm diameter. (J238.61.w1, P6.2.w12)
  • Splenic: Spleen enlarged and containing numerous white foci, up to 1 mm diameter. (J238.61.w1, P6.2.w12)
  • Lymph nodes: Enlarged, hyperplastic, with small white foci (< 1 mm diameter) visible on the cut surface of the mandibular, retropharyngeal, cervical and mesenteric lymph nodes. (J238.61.w1, P6.2.w12)

In Callithrix jacchus - Common marmosets experimentally infected by inhalation of Francisella tularensis SCHU S4: (J127.90.w1)

  • Pulmonary: haemorrhage, sometimes discrete firm nodules. (J127.90.w1)
  • Splenic: Splenomegaly, sometimes pale areas or small lesions in the spleen. (J127.90.w1)
  • Hepatic: sometimes liver lesions. (J127.90.w1)

Leontopithecus chrysomelas - Golden-headed lion tamarin

In a two-year old female golden-headed lion tamarin at a Swiss zoo. (J3.155.w5)

  • Splenic: Throughout the spleen, including on the surface under the capsule, 2 mm yellowish foci. (J3.155.w5)

In naturally infected Saimiri sciureus - Squirrel monkeys (J238.127.w1)

  • General: cachexic state. (J238.127.w1)
  • Hepatic: liver swollen; surface slightly marbled. (J238.127.w1)
  • Splenic: spleen swollen; surface slightly marbled. (J238.127.w1)
  • Pulmonary: pulmonary oedema and congestion with miliary areas of consolidation. (J238.127.w1)

In a naturally infected five year old male Saimiri sciureus - Squirrel monkey (Cebidae - New-world monkeys (Family))(P1.1988.w10)

  • Head: Cellulitis, including the orbits, and multifocal extensive ulcerative stomatitis. (P1.1988.w10)
  • Lymph nodes: cervical and submandibular lymph nodes, lymphadenitis. (P1.1988.w10)

In two naturally infected female squirrel monkeys. (J495.47.w2)

  • General: Cutaneous haemorrhages, particularly around the eyes and on the perineum and medial thighs. In the peritoneal cavity, bloody fluid and blood clots. (J495.47.w2)
  • Pulmonary: lungs haemorhagic. (J495.47.w2)
  • Hepatic: pale liver with an enhanced lobular pattern; in one monkey, multiple 1mm diameter white necrotic foci. (J495.47.w2)
  • Splenic: enlarged spleen in both cases; in one monkey, multiple 1mm diameter white necrotic foci. (J495.47.w2)
  • Lymph nodes: Enlarged. (J495.47.w2)
  • Adrenals: haemorrhages noted (J495.47.w2)
  • GIT: Haemorrhages present. (J495.47.w2)
  • Cardiac: Petechiae on the epicardial surface; in one monkey, multiple 1mm diameter white necrotic foci. (J495.47.w2)
  • CNS: along the dorsal midline of the brain, meningeal haemorrhages. (J495.47.w2)

In naturally infected Saguinus nigricollis - Black and red tamarin (J4.175.w3)

  • General: 
    • Slightly excessive abdominal fluid. (J4.175.w3)
    • Fibrinous exudate on serosal and pleural surfaces. (J4.175.w3)
  • Hepatic: pinpoint white foci throughout the liver. (J4.175.w3)
  • Splenic: pinpoint white foci throughout the spleen. (J4.175.w3)
  • Lymph nodes: mesenteric lymph nodes enlarged and oedematous. (J4.175.w3)
  • GIT: in the intestines, mild intraluminal haemorrhage. (J4.175.w3)

In a naturally infected Miopithecus (Cercopithecus) talapoin - Talapoin (J4.175.w3)

  • General: 
    • Slightly excessive abdominal fluid. (J4.175.w3)
    • Fibrinous exudate on serosal and pleural surfaces. (J4.175.w3)
  • Hepatic: pinpoint white foci throughout the liver. (J4.175.w3)
  • Splenic: pinpoint white foci throughout the spleen. (J4.175.w3)
  • Lymph nodes: mesenteric lymph nodes enlarged and oedematous. (J4.175.w3)
  • GIT: in the intestines, mild intraluminal haemorrhage. (J4.175.w3)

Primates - Lemur catta - Ring-tailed lemur, Cercopithecus nictitans nictitans - Greater spot-nosed guenon, Hylobates lar - White-handed gibbon

  • Respiratory: In the Cercopithecus nictitans nictitans - Greater spot-nosed guenon, no gross abnormality. In the others, mainly in the dorsal aspects of the lung lobes, pale tan areas, variable in extent. In one Lemur catta - Ring-tailed lemur fibrinous adhesions of the lungs to the pleura and in the Hylobates lar - White-handed gibbon, fibrous adhesions. (J2.24.w9)
  • Splenic: Markedly enlarged spleen, dark red to purplish, firm to turgid, with the capsular surface rough and multiple 1-2 mm foci through the parenchyma. (J2.24.w9)
  • Hepatic: Liver pale tan, some friable; the margins of some were blunt/rounded. (J2.24.w9)
  • GIT: Hylobates lar - White-handed gibbon, GIT haemorrhage; Cercopithecus nictitans nictitans - Greater spot-nosed guenon duodenal haemorrhage and gastric lymphoid tissue enlarged. (J2.24.w9)
  • Lymph nodes: Hylobates lar - White-handed gibbon, pharyngeal lymphoid tissue enlarged. (J2.24.w9)

In naturally infected Macaca fascicularis - Crab-eating macaque (Cynomolgus monkeys) in Germany

  • Oral: Oral cavity and pharynx, severe inflammatory alterations in all six monkeys, with pharyngeal lymphoid tissue enlarged and inflamed, with multiple focal abscesses. On the tongues of two individuals, oligofocal ulcers., and in one of these, also severe gingivitis. (J26.44.w5)
  • Splenic: markedly enlarged spleen in all six individuals. Throughout the parenchyma, numerous white foci (maximum 1 mm diameter). (J26.44.w5)
  • Hepatic: mild enlargement of the liver, and blunted margins; friable. Throughout the parenchyma, numerous white foci (maximum 1 mm diameter). (J26.44.w5)
  • Pulmonary: In three of six individuals, numerous granulomatous lesions in the lungs (severe multifocal subacute granulomatous bronchopneumonia). (J26.44.w5)
  • Lymph nodes: gross enlargement of submandibular lymph nodes. (J26.44.w5)
Experimentally in Macaca mulatta - Rhesus macaques:
  • Head: In macaques exposed to large particles, 12.5 - 24 µm, nasopharyngeal mucosal congestion. (J267.5.w1)
  • Pulmonary: 
    • In macaques exposed to small-sized aerosol particles (2.1 or 7.5 µm), pulmonary consolidation with necrotic foci on the surface of the lungs. (J267.5.w1)
    • In macaques exposed to large particles, 12.5 - 24 µm, small numbers (average 3 - 5 per monkey) of small foci were found in the lungs. (J267.5.w1)
  • Hepatic: 
    • In macaques exposed to small-sized aerosol particles (2.1 or 7.5 µm) the liver was firm with multiple small foci. (J267.5.w1)
  • Splenic: In macaques exposed to small-sized aerosol particles (2.1 or 7.5 µm) the liver was firm with multiple small foci. (J267.5.w1)
  • Lymph nodes: 
    • In macaques exposed to small-sized aerosol particles (2.1 or 7.5 µm) the bronchial lymph nodes were firm and yellow (J267.5.w1)
    • In macaques exposed to large particles, 12.5 - 24 µm, the cervical and mandibular lymph nodes were swollen, with abscess formation. (J267.5.w1)

Chlorocebus aethiops - Savanna monkey

In African green monkeys experimentally infected with Francisella tularensis subsp. tularensis SCHU S4 by inhalation: (J26.46.w4)

  • Pulmonary: In all lung lobes, multiple white raised lesions, up to 1 cm diameter and coalescing. Over lesions, the pleura was dry and granular in appearance (pleuritis). Between lesions, the lungs were dark red and non-collapsing, with oedema and congestion and/or haemorrhage. Sometimes also lesions in the trachea. (J26.46.w4)
  • Hepatic: In most individuals, one or a few scattered foci. (J26.46.w4)
  • Splenic: Rounded edges to the spleen (congestion) and multiple 0.1 - 0.5 cm, sometimes coalescing, white raised lesions. (J26.46.w4)
  • Lymph nodes: In tracheobronchial and mediastinal lymph nodes, multiple irregular raised pale lesions. (J26.46.w4)
  • Cardiac: Sometimes white foci.  (J26.46.w4)
  • Urogenital: Sometimes white foci on the urinary bladder and urethra. (J26.46.w4)
  • Other: Other locations in which white foci were sometimes present included the mediastinum, the mesentery and the diaphragm. (J26.46.w4)

In a naturally infected Chlorocebus aethiops - Savanna monkey (Vervet monkey) (J212.21.w1)

  • Pulmonary: multiple purulent 1 - 5 mm grey-white foci throughout the parenchyma, with surrounding dark, hyperaemic tissue. (J212.21.w1)
  • Hepatic: liver mildly  enlarged, friable, and containing multiple 1mm greyish foci. (J212.21.w1)
  • Splenic: spleen enlarged and dark, containing multiple necrotic foci. (J212.21.w1)
  • Lymph nodes: enlarged, with several 1 mm greyish-white foci. (J212.21.w1)

Erythrocebus patas - Patas monkey

In a naturally infected Erythrocebus patas - Patas monkey (J212.21.w1)

  • Pulmonary: multiple purulent 1 - 5 mm grey-white foci throughout the parenchyma, with surrounding dark, hyperaemic tissue. (J212.21.w1)
  • Hepatic: liver mildly  enlarged, friable. (J212.21.w1)
  • Splenic: spleen enlarged and dark, containing multiple necrotic foci. (J212.21.w1)
  • Renal: multiple greyish 1mm foci. (J212.21.w1)
  • Lymph nodes: enlarged, with several 1 mm greyish-white foci. (J212.21.w1)
Carnivores

Canis latrans - Coyote

  • Canis latrans - Coyote cubs experimentally infected by being fed tissues from rabbits and guinea pigs dying of tularemia showed no gross lesions at necropsy. (J330.41.w1)

In Felis catus - Domestic cat

  • Lymph nodes:  
    • In two cats on Nantucket Island, Massachusetts, USA, enlarged mesenteric lymph nodes containing irregular white raised foci, multifocal to coalescing.. (J212.6.w2)
    • Caseous necrosis in all cases. (J212.14.w2)
  • Splenic:
    • In two cats on Nantucket Island, Massachusetts, USA,the spleens contained irregular white raised foci, multifocal to coalescing. (J212.6.w2)
    • Caseous necrosis in nine of ten cases. (J212.14.w2)
  • Hepatic:  
    • In two cats on Nantucket Island, Massachusetts, USA, the livers contained scattered pale yellow/white foci, 1-2 mm diameter, or had no visible lesions [one of each?]. (J212.6.w2)
    • Lesions often present in the liver. (J212.14.w2)
  • Pulmonary:
    • Lesions often present in the lungs. (J212.14.w2)
  • GIT:
    • Lesions often present in the small intestines. (J212.14.w2)

In naturally infected Urocyon cinereoargenteus - Grey fox (J100.56.w1)

  • General: Thin/emaciated with soiling of the fur with diarrhoea over the buttocks and tail. Heavy flea burdens and in some cases also ticks. (J100.56.w1)
  • Respiratory: "tubercle-like lesions" in the lungs. (J100.56.w1)
  • Lymph nodes: visceral lymph nodes congested. (J100.56.w1)
  • Hepatic: large numbers of white miliary foci in one fox, a few such lesions in another, none in the other eight foxes. (J100.56.w1)
  • Splenic: large numbers of white miliary foci in one fox, a few such lesions in another, none in the other eight foxes. (J100.56.w1)
  • GIT: In one fox, slight thickening of the intestinal mucosa, with occasional ulceration. (J100.56.w1)

In experimentally infected Vulpes vulpes - Red fox [1936](D392.XII.w12)

  • Respiratory:
    • In one fox, in the right lung, red hepatisation of upper lobes; in both lungs lower lobe consolidation and in the right lung the start of abscessation. In another fox, diffuse pulmonic consolidation, pale and firm with a few nodules; in a third, described as "soft red and moist", while a fourth showed no lung lesions. (D392.XII.w12)
  • Hepatic: No lesions in three, but numerous necrotic foci in one fox. (D392.XII.w12)
  • Splenic: Numerous necrotic foci in one fox, a few foci in another and none in two others. (D392.XII.w12)
Perissodactylids

Equus caballus - Domestic horse

  • Liver: markedly swollen, with small necrotic areas.
  • Spleen: markedly swollen with small necrotic areas.
  • Kidneys: markedly swollen with small necrotic areas.
  • Pulmonary: In one of two foals, lobular consolidation and multiple necrotic foci.
  • Cardiac: heart dilated, with epicardial petechiae.
(J538.78.w1)
Artiodactylids
Sheep:  
  • Variable findings. (D392.X.w10)
  • Subcutaneous: areas of congestion, dark red, up to 3cm diameter, at tick attachment sites. (B496)
  • Lymph nodes: 
    • Enlarged lymph nodes. (J196.56.w1)
    • Nodes draining the areas of greatest tick attachment may be enlarged and congested. (B496)
  • Pulmonary: sometimes lung oedema, congestion or consolidation. (B496)
Pigs: 
  • Pulmonary: pleuritis and pneumonia. (B496)
  • Lymph nodes: submaxillary and parotid lymph nodes abscessed. (B496)
Birds
  • In birds, splenic enlargement may be the only finding, or there may be no abnormalities evident. Necrotic foci, e.g. in the liver, have been found only rarely with Francisella tularensis infection in birds. (B576.19.w19)

In a naturally infected Strix uralensis - Ural owl: (J1.19.w19)

  • General: emaciated, anaemic.
  • Splenic: Moderately enlarged spleen [this was thought to be the only lesion directly related to the infection, the other findings being typical of starvation).
  • Hepatic: Liver reddened.
  • Respiratory: Lungs reddened.
  • Renal: Kidneys reddened.
In a naturally infected Buteo lagopus - Rough-legged buzzard (Rough-legged hawk) (J1.19.w19)
  • General: good nutritional condition. (J1.19.w19)
  • Splenic: moderate enlargement of the spleen. (J1.19.w19)
  • Positive for Francisella tularensis by FAT on impression smears from the liver and spleen. (J1.19.w19)

In experimentally infected Colinius virginianus - Bobwhite quail (J330.44.w1, D392.XIII.w13)

  • No gross lesions were found in two quail dying three days after inoculation (except some whitening of muscle at the inoculation site), one dying 14 days after feeding, or 10 which remained well despite multiple intramuscular or oral inoculations. (D392.XIII.w13)
  • Splenic: Enlargement of the spleen, possibly foci in the spleen. (D392.XIII.w13)
  • Respiratory: deep red colour of the lungs in two of five birds inoculated orally (note: infection was confirmed in all five birds by guinea pig inoculation). (J330.44.w1)
  • Hepatic:  
    • In two of five birds inoculated orally (not the ones with respiratory lesions), small necrotic foci scattered over the liver (note: infection was confirmed in all five birds by guinea pig inoculation). (J330.44.w1)
    • In one quail dying 15 days after infection by feeding, two small white spots on the liver. (D392.XIII.w1I3)
In a Buteo borealis borealis - Eastern red-tailed hawk (Buteo jamaicensis borealis) experimentally infected by  feeding with viscera from infected rodents.  (D392.XIV.w14)
  • On the costal surface of the left lung, three caseous nodules were found; these were the only gross lesions and were not thought related to tularemia. (D392.XIV.w14)

In apparently healthy wild Corvus corax - Common ravens in Sweden

  • Spleen: enlarged (in all three birds in which Francisella tularensis was detected using IFAT); necrotic foci in one of these ravens. (J33.31.w1)
  • Other, variable, findings in these and four other ravens included necrotic foci in the liver, degenerative fatty changes in the liver, and degenerative fatty changes in skeletal muscle. (J33.31.w1)
Histological, Immuno- histochemistry and Electron- microscopical Findings

Liver necrosis, European brown hare with tularemia. Click here for full-page view with caption Immunohistochemical staining with monoclonal antibody, liver of hare with tularemia. Click here for full-page view with caption. Fluorescent staining with poly antibody, liver of hare with tularemia. Click here for full-page view with caption.

General:  
  • Focal or diffuse caseous foci, with central caseous necrosis surrounded by mononuclear and epithelioid cells. In acute cases, focal necrosis and suppuration; with subacute disease, granulomatous lesions, sometimes with giant cells. (B282.18.w18)
  • Lesions seen depend on the degree of susceptibility of the host and thus the time course of infection. In highly susceptible species with an acute course of disease, coagulative necrosis is found in the liver, spleen and bone marrow (e.g. in hares). In species which are less sensitive, chronic inflammatory changes are seen, with proliferative changes (macrophages, epithelioid cells and giant cells) in lymph nodes. (J64.11.w9)
  • Organism can be isolated in guinea pigs (J196.56.w1); adequate containment is required. (B47)
Rodents

In ground squirrels and guinea pigs [1911] (N42.43.w1)

  • Lymph nodes: extensive mononuclear and polynuclear leucocyte infiltration; evidence of disintegration of nuclei in some araes.
  • Spleen: Scattered aggregations of mononuclear and polynuclear cells.
  • Liver: Focal necrosis and formation of minute abscesses, particularly in the portal triads, with the aggregations of mononuclear and polynuclear cells often replacing normal liver architecture.

(N42.43.w1)

In mice inoculated with Francisella tularensis LVS by the intraperitoneal route: (J267.59.w1)

  • Spleen: Necrotic foci in the spleen, and inflammatory infiltrates consisting mainly of neutrophils and monocytes. (J267.59.w1)
  • Hepatic: Necrotic foci in the liver, and inflammatory infiltrates consisting mainly of neutrophils and monocytes. (J267.59.w1)
  • Culture: Francisella tularensis cultured from the spleen, liver and lungs, with a logarithmic increase in the number of viable organsims present over time. No organisms cultured from the heart, kidneys or stomach. (J267.59.w1)

In mice inoculated with Francisella tularensis LVS by the intravenous route: (J267.59.w1)

  • Spleen, liver and lungs: acute inflammatory lesions initially, progressing to necrotising, then by seven days to granulomatous. (J267.59.w1)
  • Culture: Organisms in the spleen and liver by day one and in the lungs by day 2-3. (J267.59.w1)

In mice inoculated with Francisella tularensis LVS by the intranasal route: (J267.59.w1)

  • Pulmonary: Bronchopneumonia by three days, necrotising lesions by six dpi. (J267.59.w1)
  • Hepatic: By six days, foci of acute inflammation with necrosis; by eight days, granulomatous lesions. (J267.59.w1)
  • Splenic: Spleen enlarged by six days; in the periarteriolar lymphoid sheaths, significant mononuclear cell proliferation. (J267.59.w1)
  • Culture: Organisms in the lungs by two dpi and in the liver and spleen by three dpi. Not found in kidney, stomach or heart. (J267.59.w1)

In experimentally infected mice, after subcutaneous inoculation: (J119.37.w1)

  • Spleen, liver, blood: on Giemsa stained smears, lymphocytosis, and numerous very small cocci/short rods (0.3 - 0.5 x 0.5 - 1.0 um), mainly in clusters. (J119.37.w1)

In mice challenged intranasally with a virulent Francisella tularensis biovar A strain (NMFTA1): (J267.73.w1)

  • Pulmonary: "moderate multifocal to coalescing, pyogranulomatous and lymphocytic to necrotizing peribrochovascular inflammation, often with neutrophilic to necrotizing vasculitis, and moderate, multifocal pyogranulomatous to necrotizing bronchopneumonia." (J267.73.w1)
  • Splenic: areas of multifocal to coalescing neutrophilic to pyogranulomatous splenitis; necrosis involved the splenic red pulp. Apoptosis of splenic lymphocytes was noted. (J267.73.w1)
  • Hepatic: multifocal neutrophilic and lymphohistiocytic hepatitis. Hepatocellular necrosis was prominent. Numerous small colonies of extracellular bacteria were present. (J267.73.w1)

In naturally infected wild-caught commercially-traded Cynomys ludovicianus - Prairie dogs (J212.16.w3)

  • Hepatic: multifocal necrosis, associated mixed inflammatory infiltrate (mainly neutrophils and macrophages). (J212.16.w3)
  • Splenic: necrosis of lymphoid follicles, associated mixed inflammatory infiltrate (mainly neutrophils and macrophages). (J212.16.w3)
  • Lymph nodes: necrosis of lymphoid follicles, associated mixed inflammatory infiltrate (mainly neutrophils and macrophages). (J212.16.w3)
  • Lung: multifocal peribronchiolar inflammation; in the bronchiolar-associated lymphoid tissue, necrosis and infiltration of neutrophils, macrophages and mature lymphocytes. (J212.16.w3)
  • GIT: In the ileum, mucosal infiltration of neutrophils and macrophages from the epithelial surface through to the submucosa. In gut-associated lymphoid tisues (GALT), extensive necrosis and inflammatory infiltrate. (J212.16.w3)
  • Other organs: No lesions detected (heart, kidney, bladder, pancreas, stomach, large intestine, brain). (J212.16.w3)
  • Immunohistochemical analysis of fixed tissue sections from Cynomys ludovicianus - Prairie dogs mainly detected free Francisella tularensis lipopolysaccharide (LPS) antigen in necrotic areas, with intracellular LPS antigen in necrotic foci and phagocytic cells only, and not in any epithelial cells. In mandibular lymph nodes, necrotic foci associated with cortex follicular areas showed intense staining, while in intact follicles, only phagocytic cells were stained while mature lymphoid cells were not stained. In the spleen, staining was found in necrotic foci of lymphoid follicles, antigen-presenting cells within intact follicles, and in the white and red pulp, infiltrating inflammatory cells (macrophages, neutrophils). In the liver, Kupffer cells lining the sinusoids were stained, also infiltrating inflammatory cells (tissue macrophages, neutrophils) also free antigen or bacteria were stained within the sinusoids; it was noted that hepatocytes, even those which were becoming necrotic, did not stain. In the lung, areas of necrosis and inflammation showed intense staining; within the bronchiolar-associated lymphoid tissue, staining was limited to antigen-presenting cells in intact follicles, and there was no staining of pulmonary epithelial cells. In the small intestine, in the superficial and deep mucosa, macrophages and neutrophils were stained, as well as extracellular antigen in necrotic areas; no staining of ileal enterocytes was noted. (J212.16.w3)

In experimentally infected Cricetus cricetus - Common hamsters (Muridae - Rats, mice, voles, gerbils etc. (Family)). (J1.46.w1)

  • Splenic: Severe acute necrosis. Bacterial emboli were found. (J1.46.w1)

  • Hepatic: Acute focal/multifocal necrosis of the liver. Bacterial emboli were found in the sinusoids and blood vessels in one of the two hamsters. (J1.46.w1)

  • Lymph nodes: Acute focal/multifocal necrosis. (J1.46.w1)

  • Bone marrow: Acute focal/multifocal necrosis. (J1.46.w1)

  • Respiratory: acute multifocal haemorrhage in the lungs, also moderate lymphohistiocytic interstitial bronchopneumonia. Bacterial emboli were found in pulmonary blood vessels in one of the two hamsters. (J1.46.w1)

  • Renal: Severe acute glomerulonephrosis and tubulonephrosis. Bacterial emboli were found in the glomeruli and in interstitial blood vessels. (J1.46.w1)

  • Immunohistochemistry: In all organs examined, antigens of Francisella tularensis were detected either as small dots or large aggregates in blood vessels or sinusoids. (J1.46.w1)

In pen-reared Castor canadensis - American beavers: (J13.23.w1)

  • Organism isolation: Infection confirmed by mouse and guinea pig inoculation followed by culture. (J13.23.w1)

Lagomorphs
  • Typical lesions in hares include acellular necrosis in the liver, spleen and (most frequently) bone marrow. (J307.22.w1)

In experimentally infected rabbits (Oryctolagus cuniculus)

  • Hepatic: focal fibrinocasoeus necrosis. (D392.II.w2)

  • Splenic: focal fibrinocaseous necrosis. (D392.II.w2)

  • Lymph nodes: fibrinocaseous necrosis (D392.II.w2)

  • Respiratory: foci of fibrinocaseous necrosis. (D392.II.w2)

  • Bone marrow: foci of fibrinocaseous necrosis. (D392.II.w2)

In Lepus timidus - Mountain hare

  • Typical lesions in hares include acellular necrosis in the liver, spleen and (most frequently) bone marrow; in 28 hares, such lesions were visible in all the bone marrow sections examined, 88% of spleens and 81% of livers. (J307.22.w1)
  • In Lepus timidus - Mountain hares in Sweden in the 1967 outbreak, multiple miliary necrosis of the liver, spleen and bone marrow. (J33.21.w1)
  • Hepatic: 
    • Acute coagulative necrosis of the liver. (J1.24.w14)
    • In six hares dying December to March in Sweden, usually but not always acute coagulative necrosis. (J1.24.w14)
    • In Lepus timidus - Mountain hares in Sweden in the 1967 outbreak, miliary necrosis: focal, intense non-cellular coagulative necrosis without any associated signs of inflammatory reaction. (J33.21.w1)
    • In a young male from Stora Karlsö, an island off the coast of Sweden, in an outbreak killing about 150 hares, acellular necrosis. (J33.36.w1)
  • Splenic: 
    • Acute coagulative necrosis of the red pulp. (J1.24.w14)I
    • In six hares dying December to March in Sweden, usually but not always acute coagulative necrosis. (J1.24.w14)
    • In Lepus timidus - Mountain hares in Sweden in the 1967 outbreak, mainly in the red pulp, miliary necrosis: focal, intense non-cellular coagulative necrosis. Foci were often confluent; there was an associated intense hyperaemia but very few neutrophils were found. In the splenic nodules, an acute inflammatory reaction was found with central regressive lesions while cellular debris was phagocytosed by reticular macrophages. (J33.21.w1)
    • In a young male from Stora Karlsö, an island off the coast of Sweden, in an outbreak killing about 150 hares, acellular necrosis. (J33.36.w1)
  • Digestive:
    • In six hares dying December to March in Sweden, haemorrhagic enteritis and typhlitis, with congestion and necrosis of mucosa in the jejunum and caecum. This was the main lesion in these hares. (J1.24.w14)
  • Bone marrow: 
    • Acute coagulative necrosis. (J1.24.w14)
    • In six hares dying December to March in Sweden, usually but not always acute coagulative necrosis. (J1.24.w14)
    • In Lepus timidus - Mountain hares in Sweden in the 1967 outbreak, miliary necrosis: focal, intense non-cellular coagulative necrosis without any associated signs of inflammatory reaction. There were also degenerative cells with pyknotic nuclei and sometimes lysis of nutrophils and megakaryocytes. (J33.21.w1)
    • In a young male from Stora Karlsö, an island off the coast of Sweden, in an outbreak killing about 150 hares, acellular necrosis. (J33.36.w1)
  • Lymph nodes:
    • In six hares dying December to March in Sweden, usually but not always acute coagulative necrosis. (J1.24.w14)
  • CNS:
  • Immunohistochemistry: 
    • FAT showed the highest concentrations of bacteria in the necrotic foci of the spleen, liver and bone marrow, but bacteria were also found in the lymph nodes, lungs, brain and kidneys, usually in intravascular spaces. (J1.24.w14)
    • In six hares dying December to March in Sweden, FAT demonstrated the organism in all organs, and not concentrated in necrotic foci. It was found in the kidneys (in the interstitial tissue) and in the intestines (mucosa, crypts and lumen). (J1.24.w14)
    • In a young male from Stora Karlsö, an island off the coast of Sweden, in an outbreak killing about 150 hares, positive for Francisella tularensis by FAT on both fresh and formalin fixed sections. (J33.36.w1)
  • Electron Microscopy: 
  • Organism isolation: Francisella tularensis biovar palearctica was isolated on cystein agar. (J1.24.w14)

In 50 naturally infected Lepus europaeus - Brown hare from Hungary: (J26.47.w1)

  • In 47 shot or found-dead hares which were found to be seropositive (no similar lesions were found in seronegative hares): (J26.47.w1)
    • General: In sites corresponding to those in which gross lesions were seen, randomly distributed focal or coalescing granulomatous inflammatory lesions replacing the normal organ tissues. The main cell type was macrophages, with occasional lymphocytes, heterophil granulocytes, multinucleate giant cells, and fibrocytes. In the centre of the lesions, necrotic foci were commonly found. (J26.47.w1)
      • Pulmonary: Lesions in 40 hares, 80% of hares. These lesions often did not contain necrotic areas, or had only minor necrotic areas; remnants of blood vessels and bronchioles sometimes were visable. In alveoli away from granulomatous inflammation, sometimes there was inflammatory exudate and debris in bronchioles, and associated alveolar oedema. (J26.47.w1)
      • Cardiac: (Pericardial lesions in 14 hares, 28%). The granulomatous inflammatory lesions had extensive central necrosis, while the overlying serosal surface showed obvious fibrinous inflammation. (J26.47.w1)
      • Renal: (lesions in 10 hares, 20%). In the cortex and the medulla, multiple granulomatous inflammatory foci were present; tubules in these areas were filled with necrotic debris and were variably necrotic. In the suburethral area of the renal pelvis also multifocal granulomatous inflammation was present with necrotic exudate in the adjacent lumen. (J26.47.w1)
      • Reproductive: (lesions in two hares, 4%). In large areas of the testes and epididymis, the intertubular connective tissue lining was expanded by the granulomatous inflammation; tubules were variably necrotic and filled with necrotic inflammatory exudate.  (J26.47.w1)
      • Bone marrow: granulomatous inflammatory lesions with central necrosis were found in three hares (gross lesions had been found in two) (J26.47.w1)
      • Mammary glands: granulomatous inflammatory lesions with central necrosis in one hare, 2%. (J26.47.w1)
      • Hepatic: granulomatous inflammatory lesions with central necrosis were found in three hares (gross lesions were found in only one of these hares).
      • Splenic: granulomatous inflammatory lesions with central necrosis were found in two hares. (J26.47.w1)
    • Lymph nodes: granulomatous inflammatory lesions with central necrosis were found in mediastinal lymph nodes in 12/35 hares.  (J26.47.w1)
    • Note: 
      • Two hares without any gross lesions nevertheless had granulomatous inflammatory lesions on histopathological examination. (J26.47.w1)
      • Four of 50 seropositive hares and none of 20 seronegative hares (control) had no histopathological lesions. (J26.47.w1)
    • Immunohistochemistry: In all 46 cases with lesions in the tissues, Francisella tularensis antigen was present, clearly associated with lesions seen histologically, mainly extracellularly, but also within macrophages, giant cells and less commonly in other cells (bronchiolar and renal pelvis epithelial cells, renal, testis and epididimal tubular epithelial cells and hepatocytes, as well as both within and outside cells in the inflammatory exudate within airways. In the hares found dead, antigen was detected in lung, liver and spleen in areas where no lesions were found, with extracellular labelling in blood vessels as well as antigen in intact alveolar epithelial cells, hepatocytes and intravascular macrophages. Four of the seropositive hares were negative on immunohistochemistry (giing 100% sensitivity but only 83% specificity for the slide agglutination test compared to the IHC assay: seronegative hares were always negative on IHC and there was a 92% chance of a seropositive hare being IHC positive).
    • Culture: From 35/50 hares, Francisella tularensis was isolated by culture, with greyish-white 1 mm colonies visible after four days inclubation on modified Francis agar (chocolate agar with 0.1% cysteine and 1% glucose). The Gram-negative coccoid rods were less than 1 um long, non-motile, weakly catalase positive, oxidase negative, and unable to utilise glycerol, which indicated they were Francisella tularensis ssp. holarctia. PCR and amplification of the partial 16S rRNA gene showed 100% identity with a reference Francisella tularensis ssp. holarctia isolate (accession no. CP000608 in GenBank). Compared with IHC, culture gave 100% specificity and 76.1% sensitivity. (J26.47.w1)

In five experimentally inoculated Lepus timidus - Mountain hares and Lepus europaeus - Brown hare inoculated intramuscularly: (J1.24.w14) 

  • At the inoculation site, purulent dermatitis and myositis. In the subcutaneous tissues, many neutrophils, macrophages, plasma cells and lymphocytes; no giant cells were found. Often hyperplasia of the lymph nodes and spleen. (J1.24.w14)
    • Immunohistochemistry: FAT positive only at the inoculation site. (J1.24.w14) 

In two Lepus europaeus - Brown hares experimentally inoculated subcutaneously with 2.6 x 109 CFU of a wild strain of Francisella tularensis isolated from a wild hare: (J307.53.w1)

  • Splenic: Diffuse necrosis. (J307.53.w1)
  • Hepatic: Multifocal necrosis of the liver, also moderate hepatocyte vacuolation. (J307.53.w1)
    • Culture: Francisella tularensis was cultured from liver, lung, spleen, kidney and tissue of the hare dying 5 dpi and from spleen and bone marrow of the hare dying 9 dpi. (J307.53.w1)
  • Note: Three hares survived infection and were euthanased at 35 dpi. There were no microscopic lesions in these hares. (J307.53.w1)

In experimentally infected Black-tailed jack rabbits (Lepus sp.) (D392.III.w3)

  • Pulmonary: moderate to marked congestion; in the alveoli, slight to moderate serous exudate. In septal capillaries, small hyaline thrombi (few to numerous), often with clumps of very small coccoid organisms and sometimes with a few cells showing swelling or karyorrhexis, occasionally septal coagulation necrosis. (D392.III.w3) In the capillaries and in cells of the alvelolar septa, minute coccoid organisms; these were frequently found in swollen epithelial cells of the alveoli, particularly in areas with serous exudation.

  • Hepatic: coagulative to caseous necrotic foci (usually 0.1 - 0.2 mm, sometimes reaching 0.5 mm), hyaline thrombosis of capillaries, and large numbers of the organism in liver calls and sometimes in Kuppfer cells. (D392.III.w3)

  • Splenic: severe congestion, also numerous 0.1 - 0.2 mm necrotic foci, containing central masses of pyknotic nuclei and outer finely granular (occasionally fibrillar) material, in all but one hare. (D392.III.w3)

  • Bone marrow: moderate to marked congestion, with numerous necrotic foci, 0.2 - 0.5 mm. In the blood sinuses, small hyaline thrombi. Large numbers of minute coccoid organisms present, both inside and outside cells; staining reveals large numbers in the necrotic foci. (D392.III.w3)

  • Lymph nodes (inguinal, pelvic) in the one individual in which these were examined, confluent areas of caseous necrosis, with ocasional clumps of the organisms as well as nuclear and cellular debris present.

  • Renal: moderate parenchymous degeneration, a few dilated tubules containing foamy albuminous exudate or casts, and in about 50% of individuals, a few small hyaline thrombi in one or more glomerular loops, with clusters of minute coccoid organisms.

  • Adrenal: Single or clumped cortex cells full of minute coccoid organisms; cytoplasms finely vacuolated, hyaline or swollen and hydropic. Sometimes also small foci of coagulation necrosis and isolated coagulated necrotic cells in the cortex. Where necrotic foci are present, and sometimes elsewhere, hyaline thrombi may be found in capillaries, often with clusters of organisms. Medulla: moderate vacuolation and fraying of cells. (D392.III.w3)

  • On tissue smears organisms morphologically typical for Francisella tularensis were found in heart blood (2/4), liver (usually few organisms), spleen (moderate to man bacteria) and bone marrow (many Vascular epithelial cells, pulmonary aorganisms). (D392.III.w3)

In a naturally-infected wild rabbit in Missouri [probably Sylvilagus floridanus - Eastern cottontail]

  • Hepatic: acute, multifocal necrotising hepatitis. (J84.16.w3)
    • Note: Concurrent hepatic coccidiosis was present, as indicated by biliary hyperplasia and the presence of numerous intraepithelial coccidia. (J84.16.w3)
    • The presence of Francisella tularensis was confirmed by culture and PCR. (J84.16.w3)

In six experimentally infected Sylvilagus floridanus - Eastern cottontails (D392.IV.w4)

  • Summary: In the liver, spleen, bone marrow, intestinal mucosa, lymph nodes and sometimes the renal glomeruli and adrenals, acute caseous necrotic foci without any marginal inflammatory reaction. In vascular endothelial cells, hepatocytes, pulmonary alveolar epithelium reticuloendothelial cells of the liver, spleen and lymph nodes, extensive bacterial colonisation; in the spleen, also extensive thrombonecrosis. Free organisms numerous in the blood and tissue spaces. Scattered thrombi (hyaline, cellular and caseous) in capillaries and veins (D392.IV.w4)
  • Respiratory: marked congestion and oedema in 1/5 rabbits, serous exudation in two, focal alveolar haemorrhage in one, scattered capillary foci in four, focal alveolar septal swelling with karyorrhexis in two. Francisella tularensis organisms were found in all the rabbits: in the capillary endothelial cells (3/5), swollen alveolar epithelial cells (4/5), in caseous thrombi in capillaries (2/5) and in the lumen of blood vessels. (D392.IV.w4)
  • Cardiac: muscle fibres noted to be cloudy, and containing fine oxyphilic granules; striations were still visible. In 1/2 examined, scattered swollen capillary endothelial cells contained clumps of minute bacilliform organisms; in the other rabbit, hyaline capillary thrombi were found and vessels occasionally contained clumps of organisms. (D392.IV.w4)
  • Hepatic: congestion, numerous thrombi in capillaries and sometimes larger veins. Swelling of hepatocytes and Kupffer cells, containing large numbers of minute organisms (coccoid and bacillary). Scattered oxyphilic and karyolytic hepatocytes. Numerous small foci of coagulation necrosis with caseous capillary thrombi, containing organisms, separating cords of coagulated liver hepatocytes. Also necrotic foci with marginal oxyphil granular material or fibrin and central pyknotic nuclear debris. (D392.IV.w4)
  • Splenic: congestion, foci of acute caseous necrosis in all but one rabbit. Also extensive hyaline or fibrous thrombosis, consideable cell degeneration, patchy karyolysis and karyorrhexis. Variable karyorrhexis of follicles; sometimes conpletely necrotis. Numerous organisms in thrombosed and degenerating spleen pulp as well as in thrombi and outside cells.. (D392.IV.w4)
  • Lymph nodes: variable from moderate swelling of reticuloendothelial cells (organisms present) to caseous necrosis of the periphery or of the entire lymph node. In the later cases, organisms were found in cells of the capsule and in dilated capillaries, but not in necrotic tissue. (D392.IV.w4)
  • Bone marrow: congestion, multiple small hyaline thrombi and 0.2 mm diameter caseous necrotic foci as well as diffuse cellular degeneration andkaryorrhexis; coccoid and coccobacillary organisms were numerous in the thrombi, necrotic foci, littoral cells and diffusely in one rabbit. (D392.IV.w4)
  • GIT: In the single individual examined, in the stroma of the villi (duodenum and jejunum), minute to small foci of karyorrhectic necrosis, and hyaline to necrotic thrombi in capillaries, with organisms in clusters in thrombi and at the margins of the foci. (D392.IV.w4)
  • Renal: Moderate parenchymatous degeneration, with more severe degeneration of the convoluted tubules in some individuals, and casts in the collecting tubules. In glomerular loops, scattered swollen endothelial cells were present, containing coccoid and bacilliform organisms; in about 50% of the rabbits, individual loops were affected by caseous thrombosis, sometimes with coagulative necrosis of part of the glomerulus. In some cases, in the cortex there were similar changes in the intertubular capillaries, and in the rabbit with the most severe lesions, foci of lymphocytic infiltration, sometimes with partial caseous necrosis, were present. (D392.IV.w4)
  • Adrenal: swollen and distended capillary endothelial cells, in the cortex and medulla,  containing clumps of coccoid organisms, sometimes smaller numbers of the organisms in foamy cortical cells. Also in both the cortex and medulla, caseous cellular thrombi with coccoid organisms present. In about 50% of cases, in the cortex, small foci of coagulative or caseous necrosis, with the organisms seen on the periphery of these lesions; in two rabbits these foci were present in the medulla. Variable cell vacuolation and fraying in the medulla. (D392.IV.w4)
  • Skin: In rabbits inoculated via shaved/abraded skin, superficial necrosis, ulceration and crusting, with foci of fragmented cells and nuclei in the corium, apparently occluding capillaries or lymphatics and containing minute organisms, which were also found in connective tissue and capillary endothelial cells. (D392.IV.w4)
  • Other organs: In the limited number of individuals in which other organs were studies (one rabbit per organ, mainly), occasional thrombi containing minute organisms were found. (D392.IV.w4)
Primates

In a naturally infected Pongo pygmaeus - Orang-utan (J2.40.w1)

  • Hepatic: Severe hepatitis; small foci of necrosis, and microabscesses. (J2.40.w1)
  • Splenic: Severe splenitis; small foci of necrosis, and microabscesses. (J2.40.w1)
  • Indirect fluorescent antibody assay (IFA) on unfixed spleen confirmed Francisella tularensis and this was cultured from the spleen. PCR, glycerol fermentation and pulsed-field gel electrophoresis identified Francisella tularensis type A. (J2.40.w1)

In Callithrix jacchus - Common marmosets 

In a one-year- nine-months-old common marmoset in Switzerland. (J238.61.w1, , P6.2.w12)

  • Respiratory: Acute necrosis (J238.61.w1). Acute alveolar emphysema, with multifocal acute peribronchial and perivascular necrosis, with a mainly macrophage infiltrate. (P6.2.w12)
  • Hepatic: Acute coagulative parenchymal necrosis. (J238.61.w1,  P6.2.w12)
  • Renal: Acute coagulative interstitial necrosis with a predominantly macrophage infiltrate. Some renal tubules contained proteinaceous casts(P6.2.w12)
  • Splenic: Acute coagulative parenchymal necrosis (P6.2.w12)
  • GIT: Acute jejunal necrosis (J238.61.w1); in the jejunal crypts, multifocal acute epithelial necrosis and a mild effusion of neutrophils into the lumen.
  • Lymph nodes: Mandibular, retropharyngeal, cervical and mesenteric lymph nodes were hyperaemic, with severe infiltration of both subcortical and medullary sinuses by neutrophils, while in the cortical and paracortical region, multiple acute necrotic foci were present. (J238.61.w1)
  • Bone marrow: Haematopoetic bone marrow filing the marrow cavity; in the femurs, decreased fat content, highly cellular, and haemorrhages. Reduced numbers of megakaryocytes and underrepresentation of granulocytes but overrepresentation of the erythroid line. (P6.2.w12)
  • Immunofluorescence: In the liver, in small necrotic foci and in leucocytes, and in the mesenteric lymph node, in leucocytes, fluorescent antibody-positive bacteria were detected. (P6.2.w12)
  • Culture: Cultures developed after five days on sheep's-blood agar and after 48 hours on chocolate agar. Using 16s rRNA analysis of a 1.4 kb PCR fragment the organism showed 100% match with Francisella tularensis var. tularensis vaccine strain. (J238.61.w1, P6.2.w12)

In a group of common marmosets in Germany in 2004: (J19.135.w1)

  • Hepatic: mild multifocal necrotising (1/5) or necrotising and granulomatous(4/5) hepatitis. Panlobular fat droplet accumulation was noted in hepatocytes. (J19.135.w1)
  • Splenic: Splenitis in 3/5. (J19.135.w1)
  • GIT: severe multifocal haemorrhagic enteritis in 2/5). (J19.135.w1)
  • Lymph nodes: Lymphadenitis of the axillary and submandibular lymph nodes in 1/5. (J19.135.w1)
  • Organism isolation:  
    • Positive on antigen capture-ELISA, and by PCR, and culture of Francisella tularensis holarctica, from spleen or liver homogenates. In three cases there was contamination with mixed bacterial flora, while the other two grew pure cultures. (J19.135.w1)

In Callithrix jacchus - Common marmosets experimentally infected by inhalation of Francisella tularensis SCHU S4: (J127.90.w1)

  • Pulmonary: mainly severe suppurative bronchopneumonia with necrosis and haemorrhage and/or foci of pyogranulomatous pneumonia with neutrophils, macrophages and lymphocytes infiltrating; degeneration of neutrophils noted. In one individual only mild interstitial pneumonia. (J127.90.w1)

  • Splenic: Splenitis - severe multifocal pyogranulomatous. Infiltration of neutrophils, macrophages and lymphocytes into the parenchyma; degeneration of neutrophils noted. (J127.90.w1)

  • Hepatic: Hepatitis - severe multifocal pyogranulomatous.bInfiltration of neutrophils, macrophages and lymphocytes into the parenchyma; degeneration of neutrophils noted.(J127.90.w1)

  • Lymph nodes: Severe multifocal pyogranulomatous lymphadenitis. mInfiltration of neutrophils, macrophages and lymphocytes into the parenchyma; degeneration of neutrophils noted. (J127.90.w1)

In common marmosets experimentally infection by inhalation of Francisella tularensis SCHU S4. (J626.59.w1)

  • By 48 hours post-exposure, splenomegaly was present, also slight hepatomegaly in one of two marmosets and slight lung enlargement in the other marmoset. (J626.59.w1)

  • By 48 hours post-exposure, in the lungs there were small areas of emphysema. (J626.59.w1)

  • By 72 hours, the lung, liver, spleen and lymph nodes showed pyogenic foci. (J626.59.w1)

  • By 96 hours, pyogranulomatous pneumonia, interstitial pneumonia, pulmonary oedema, lymphadenitis (necrosis) in lymph nodes draining the lungs, hepatitis, and splenitis were evident. Neutrophils were the main infiltrating cells; lymphocytes, macrophages and plasma cells were present also. Other findings included the presence of giant cells and thrombosis. (J626.59.w1)

Leontopithecus chrysomelas - Golden-headed lion tamarin

In a two-year old female golden-headed lion tamarin at a Swiss zoo. (J3.155.w5)

  • Splenic: severe acute suppurative to necrotising, multifocal to confluent splenitis. (J3.155.w5)

  • Culture: slow growth of colonies (four days) on blood agar, containing very small, Gram-negative non-motile coccobacilli, nonhaemolytic, cytochrome oxidase reaction negative, mederately positive catalase reaction, weak acidic reaction with maltose but not with sucrose. Specific agglutination in a slide agglutination test using polyclonal Francisella tularensis antiserum. Typical Francisella tularensis colonies (greenish white, round, smooth, slightly mucous colonies up to 4 mm diameter) on cysteine heart agar with 10% heated sheep's blood. 

  • Sequencing: PCR on a 900 bp fragment containing the FopA gene follwed by nucleotide analysis gave 99.1% homology to Francisella tularensis fopA gene; 16S rDNA amplification using universal primers produced a sequence with 99.8% homology with the Francisella tularensis LVS vaccine strain; at position 1153 the nucleotide A strongly suggested Francisella tularensis subsp. holarctica. (J3.155.w5)

Leontopithecus chrysomelas - Golden-headed lion tamarin, Leontopithecus rosalia - Golden lion tamarin, Saguinus midas - Redhanded tamarin, Saguinus oedipus - Cotton-top tamarin and Callimico goeldii - Goeldi's monkey

In seven individuals at Phoenix Zoo, Arizona, in May 2000: (P1.2002.w9)

  • Hepatic: necrosuppurative hepatitis. (P1.2002.w9)

  • Splenic: necrosuppurative splenitis. (P1.2002.w9)

  • GIT: necrosuppurative enteritis. (P1.2002.w9)

In naturally infected Saguinus nigricollis - Black and red tamarin (J4.175.w3)

  • Pulmonary: pneumonitis. (J4.175.w3)
  • Hepatic: foci of caseous necrosis in the liver. (J4.175.w3)
  • Splenic: foci of caseous necrosis in the spleen. (J4.175.w3)
  • Renal: acute glomerulitis
  • GIT: enteritis. (J4.175.w3)
  • Lymph nodes: lymphadenitis. (J4.175.w3)
  • Culture: heavy pure growth of small colonies developed on chocolate agar after five days of incubation at 35 C, and on blood agar, pinpoint colonies were seen after seven days. The organism was Gram-negative, pleomorphic, cytochrome oxidase negative and catalase positive, and showed a positive agglutination with Francisella tularensis antiserum. (J4.175.w3)

In a naturally infected Miopithecus (Cercopithecus) talapoin - Talapoin (J4.175.w3)

  • Pulmonary: pneumonitis. (J4.175.w3)
  • Hepatic: foci of caseous necrosis in the liver. (J4.175.w3)
  • Splenic: foci of caseous necrosis in the spleen. (J4.175.w3)
  • Renal: acute glomerulitis
  • GIT: enteritis. (J4.175.w3)
  • Lymph nodes: lymphadenitis. (J4.175.w3)
  • Culture: heavy pure growth of small colonies developed on chocolate agar after five days of incubation at 35 C, and on blood agar, pinpoint colonies were seen after seven days. The organism was Gram-negative, pleomorphic, cytochrome oxidase negative and catalase positive, and showed a positive agglutination with Francisella tularensis antiserum. (J4.175.w3)

In naturally infected Saimiri sciureus - Squirrel monkeys (J238.127.w1)

  • Hepatic: multifocal acute hepatic necrosis with associated rod-shaped bacilli. (J238.127.w1)
  • Splenic: severe splenic congestion and multifocal acute necrosis with associated rod-shaped bacilli. (J238.127.w1)
  • Pulmonary: multifocal acute necrosis with alveolar fibrin accumulation, early microthrombi formation and sometimes associated rod-shaped bacilli. (J238.127.w1)
  • Renal: In one of two monkeys, rod-shaped bacilli in clusters in the capillaries of the glomeruli and in the lumen of vessels of the cortex and medulla. (J238.127.w1)
  • CNS: In one monkey, gliosis in the cortex. (J238.127.w1)
  • Culture & PCR: Francisella tularensis cultured from one, only E. coli from the other, but Francisella tularensis subsp. holarctica confirmed in both by PCR. (J238.127.w1)

In two naturally infected female Saimiri sciureus - Squirrel monkeys. (J495.47.w2)

  • Pulmonary: Acute multifocal haemorrhage. Occasional small blood vessels showed fibrinoid degeneration of the wall. In the second monkey, multiple alveolar septal necrotic foci; in the adjacent alveolar spaces, macrophages, both viable and degenerate neutrophils, fibrin and haemorrhage. (J495.47.w2)
  • Hepatic: multiple necrotic foci in the liver, particularly adjacent to portal triads and blood vessels. Some hepatic veins were necrotic, the walls infiltrated by neutrophils. (J495.47.w2)
  • Splenic: multiple necrotic foci in the spleen. (J495.47.w2)
  • Lymph nodes: Diffuse necrosis of the cervical lymph nodes. (J495.47.w2)
  • Adrenals: acute multifocal haemorrhage and, in the second monkey, multiple necrotic foci (J495.47.w2)
  • GIT: in the lamina propria, acute multifocal haemorrhage. (J495.47.w2)
  • Skin: In the dermis, acute multifocal haemorrhage. (J495.47.w2)
  • Bacteriology: Francisella tularensis was cultured from the liver of each monkey. For the first case, typing confirmed Francisella tularensis subsp. holarctica (type B); typing was not carried out in the second case. (J495.47.w2)

Primates - Lemur catta - Ring-tailed lemur, Cercopithecus nictitans nictitans - Greater spot-nosed guenon, Hylobates lar - White-handed gibbon

  • Respiratory: Pulmonary hyperaemia and haemorrhage in all species. In the Lemur catta - Ring-tailed lemurs also acute multifocal bronchopneumonia and sometimes distention of alveoli withexudate (fibrinopurulent), while theHylobates lar - White-handed gibbon, had pleural pulmonary fibrosis. (J2.24.w9)
  • Splenic: In all species, acute diffuse necrotising splenitis with focal, occasionally coalescing, microabscesess. Other common findings were hyperaemia, haemorrhage and macrophages filled with haemosiderin. (J2.24.w9)
  • Hepatic: In all (except one Lemur catta - Ring-tailed lemur), hyperaemia and necrosis, with acute microabscesses.. (J2.24.w9)
  • GIT: 
    • Cercopithecus nictitans nictitans - Greater spot-nosed guenon gastric ulceration (J2.24.w9)
    • Hylobates lar - White-handed gibbon, acute necrotising ulcerative pharyngitis. (J2.24.w9)
  • Renal: Hylobates lar - White-handed gibbon, acute glomerulonephritis. (J2.24.w9)
  • Lymph nodes: 
    • Cercopithecus nictitans nictitans - Greater spot-nosed guenon, acute necrotising lymphadenitis (mesenteric and gastric lymphoid tissue). (J2.24.w9)
    • Hylobates lar - White-handed gibbon, Pharyngeal lymphoid tissue abscessation and necrosis. (J2.24.w9)
  • Culture: Francisella tularensis was cultured from livers, spleens and lungs, with growth at 48 hours on chocolate agar and at 72 hours on blood agar, at 35 C, aerobic with 7% carbon dioxide. Gram-negative, oxidase negatice coccobacilli. The Francisella tularensis was identified as type B (not glycerol-fermenting)(J2.24.w9)

In naturally infected Macaca fascicularis - Crab-eating macaque (Cynomolgus monkeys) in Germany.

  • Oral: Oral cavity and pharynx, severe inflammatory alterations in all six monkeys, with pharyngeal lymphoid tissue enlarged and inflamed, with multiple focal abscesses. On the tongues of two individuals, oligofocal ulcers., and in one of these, also severe gingivitis. (J26.44.w5)
  • Splenic: Both the white and red pulm affected by granulomatous inflammation. (J26.44.w5)
  • Hepatic: moderate acute multifocal necrosis. Amorphous cellular debris, hepatocyte necrosis, activated Kuppfer cella and a degree of initration by lymphocytes and neutrophils. (J26.44.w5)
  • Pulmonary: In three of six individuals, severe multifocal subacute granulomatous bronchopneumonia with diffusely distributed granulomas associated with large pulmonary vessels. The granulomas had central nectrotic areas, haemorrhage, mild inflammatory cell infiltrate and sharp borders. (J26.44.w5)
  • Renal: in two monkeys, severe multifocal pyogranulomatous tubulonephritis. (J26.44.w5)
  • Lymph nodes: necrosis, varying from well-defined zones of necrosis and acute inflammation mainly affecting the outer cortex, to generalised necrosis of the whole lymph node, and in some cases granulomatous inflammation. (J26.44.w5)
  • CNS: In one inidividual, suppurative leptomeningitis and granulomatous encephalitis. (J26.44.w5)
  • GIT: In one individual, necrotising oesophagitis with mucosal ulcerated areas containing neutrophils and mixed bacteria, and overlying necrotic debris. (J26.44.w5)
  • Immunohistochemistry: widespread positive findings using specific monoclonal anti-Francisella tularensis antibody, widespread in the affected organs, and particularly in oropharyngeal tissues and regional lymph nodes., while many splenic, pulmonary and hepatic lesions (granulomatous) were negative (only peracute changes such as peracute perivescular lesions in the lungs were antigen-positive).
  • ELISA: Positive capture-ELISA for Francisella tularensis LPS. (J26.44.w5)
  • PCR: positive using real-time PCR against the 16 SrDNA and tul4 genes. (J26.44.w5)
  • Culture: Positive on cysteine agar using material from four of six monkeys. Partial sequencing of the16 SrDNA genes confirmed Francisella tularensis subsp. holarctica. (J26.44.w5)

Chlorocebus aethiops - Savanna monkey

In a naturally infected Chlorocebus aethiops - Savanna monkey (Vervet monkey) (J212.21.w1)

  • Pulmonary: throughout the lung parenchyma, "severe, multifocal, purulent, pyogranulomatous to granulomatous penumonia" with central necrotic areas surrounded by haemorrhage with histiocytes and smaller numbers of neutrophils, and demarcated by connective tissue. (J212.21.w1)
  • Hepatic: Granulomatous inlammation of the liver. (J212.21.w1)
  • Splenic: Granulomatous infiltration and necrotic foci. (J212.21.w1)
  • Lymph nodes: Granulomatous infiltration and necrotic foci. (J212.21.w1)
  • Culture: Francisella tularensis cultured (grey-white 1mm colonies after four days of incubation, containing small (< 1 um) non motile Gram-negative cocco-bacilli, oxidase negative, weakly catalase positive and unable to use glycerol as a sole carbon source. Identity of Francisella tularensis subsp. holarctica was confirmed by PCR and identification of part of the 16s rRNA gene, giving 100% identity with sequences deposited in GenBank. (J212.21.w1)

In African green monkeys experimentally infected with Francisella tularensis subsp. tularensis SCHU S4 by inhalation: (J26.46.w4)

  • Pulmonary: areas of necrosis, with airways, alveolar septa, alveolar spaces and pleura replaced by cellular and karyorrhectic debris, fibrin, oedema, haemorrhage, both viable and degenerate neutrophils and many macrophages with abundant cytoplasm. In areas where the lesions were less extensive it could be seen that they were associated with small to medium-sized airways. Blood vessels in affected areas showed necrotising vasculitis: disruption of the tunica intima, while the tunica media and tunica adventitia were expanded with necrotic debris, fibrin, oedema, haemorrhage necrotic neutrophils and macrophages. Around the necrotic areas, the lung parenchyma showed moderate to marked congestion and frequently flooding of alveoli with oedema or haemorrhage, as well as increased numbers of alveolar macrophages with foamy cytoplasm. Marked multifocal pleuritis was present, with necrotising and pyogranulomatous inflammation, oedema and occasionally haemorrhage. In four of five monkeys there was tracheitis and laryngotracheitis with degeneration, necrosis and loss of the surface epithelium, while the subepithelium was expanded with eosinophilic cellular and karyorrhectic debris forming domed lesions. (J26.46.w4)
  • Hepatic: a few to many scattered necrotic and inflammatory foci disrupting the hepatic cords.(J26.46.w4)
  • Splenic: Disruption of the normal splenic architecture and replacement by necrosis, macrophages with abundant cytoplasm, and small numbers pf neutrophils. Marked congestion in areas o the red pulp which were less severely affected. (J26.46.w4)
  • Lymph nodes: Mediastinal lymph nodes showed lymphoid depletion; mediastinal lymph nodes contained multiple necrotising lesions disrupting at least 50% of the nodes, sometimes the whole node. Other lymph nodes sometimes showed inflammation (lymphadenitis). (J26.46.w4)
  • Cardiac: myocarditis was sometimes seen.(J26.46.w4)
  • Urogenital: cystitis and urethritis were sometimes present.  (J26.46.w4)
  • Other: Tonsillitis, mediastinitis, peritonitis, enteritis, adrenalitis and osteomyelitis were sometimes present. (J26.46.w4)
  • Immunohistochemistry:
    • Francisella tularensis immunoreactivity was noted in multiple cell types, in the cytoplasm. In particular, strong reactions were seen associated with macrophages in the tonsils, lymph nodes (mandibular, maxillary, mediastinal, axillary, inguinal) and in alveolar macrophages, as well as pleural mesothelial cells, respiratory epithelial cells of the larynx, trachea, bronchi and bronchioles, degenerating hepatocytes, splenic macrophages and reticuloendothelial cells, glomerular mesangial and/or endothelial cells, bone marrow (various cell types), adrenals (cortical cells), urinary bladder and urethra (epithelial cells) and in numerous tissue, in macrophages and neutrophils. (J26.46.w4)
  • Electron microscopy: (tissues from one individual). Oval to elongated 0.4 - 0.5 um wide organisms were found within membrane-bound vacuoles in the cytoplasm of cells, adjacent to the nucleus. The central cytoplasm of the bacteria was pale, becoming darker near to the thin cell wall; around some organisms an outer wavy membrane was seen. (J26.46.w4)

Erythrocebus patas - Patas monkey

In a naturally infected Erythrocebus patas - Patas monkey (J212.21.w1)

  • Pulmonary: throughout the lung parenchyma, "severe, multifocal, purulent, pyogranulomatous to granulomatous penumonia" with central necrotic areas surrounded by haemorrhage with histiocytes and smaller numbers of neutrophils, and demarcated by connective tissue. (J212.21.w1)
  • Splenic: Granulomatous infiltration and necrotic foci. (J212.21.w1)
  • Lymph nodes: Granulomatous infiltration and necrotic foci. (J212.21.w1)
  •  (J212.21.w1)
  • Renal: multifocal pyogranulomatous tubulonephritis. (J212.21.w1)
  • Culture: Francisella tularensis cultured (grey-white 1mm colonies after four days of incubation, containing small (< 1 um) non motile Gram-negative cocco-bacilli, oxidase negative, weakly catalase positive and unable to use glycerol as a sole carbon source. Identity of Francisella tularensis subsp. holarctica was confirmed by PCR and identification of part of the 16s rRNA gene, giving 100% identity with sequences deposited in GenBank. (J212.21.w1)
Carnivores

Canis latrans - Coyote

  • Organism isolation: In Canis latrans - Coyote cubs experimentally infected by being fed tissues from rabbits and guinea pigs dying of tularemiahe presence of the organism was confirmed by animal inoculation, including from the salivary glands. (J330.41.w1)

In experimentally infected Vulpes vulpes - Red fox [1936](D392.XII.w12)

  • Respiratory:
    • In one fox, bronchopneumonia, partially purulent, partially haemorrhagic, with masses of bacilli. Also areas where alveoli were filled with large foamy mononuclear cells; this was thought possibly related to subacute tularemia, since the organism was confirmed. (D392.XII.w12)
    • In one fox, small foci of bronchopneumonia,; in the alveoli, necrotising purulent exudate or monocytes and phagocytic macrophages, also some interstitial epithelioid cell proliferation. In another fox, necrotising confluent nodular purulent pneumonia. In a third fox, haemorrhagic consi=olidation and nodules, m exudate of monocytes, epithelial cells, multinucleate giant cells a few leucocytes and lymphocytes.  (D392.XII.w12)
  • Lymph nodes:
    • In one fox, oedema. In others, "sinus dilatation, macrophage exudation, reticuloendothelial proliferation, sunus area necrosis and caseation, solid epithelioid cell nodules, margination of necrotic areas by foamy epithelioid cells and intramarginal fibrin exudation." (D392.XII.w12)
  • Liver: scattered small foci of acute caseous necrosis, sometimes with margins of vacuolated epithelial cells; some lesions non-caseous. (D392.XII.w12)
  • Renal: variously a few foci of infiltration by lymphocytes, congestion of the pelvis, pelvis ulcers and suppurating pyramidal abscesses, plasma cell infiltration and intraepithelial pustules.
  • Spleen: foci of necrosis. (D392.XII.w12)
  • GIT: in the colon, patchy infiltration of the submucosa by lymphocytes and degenerating macrophagesin one; in another, focal necroses in lymphoid follicles and small mucosal ulcers. (D392.XII.w12)

In Felis catus - Domestic cat

  • Splenic:
    • In two cats on Nantucket Island, Massachusetts, USA, particularly in the white pulp, caseous necrosis, multifocal to focally extensive, with degenerated neutrophils and macrophages bordering these areas. (J212.6.w2)
    • Caseous necrosis, multifocal to coalescing, also granulomatous inflammation. (J212.14.w2)
  • Hepatic:
    • In two cats on Nantucket Island, Massachusetts, USA, randomly scattered necrotic areas with neutrophil infiltration and macrophages bordering the areas; affected areas varied from a few hepatocytes to whole lobule. (J212.6.w2)
  • Lymph nodes:
    • In two cats on Nantucket Island, Massachusetts, USA, caseous necrosis, multifocal to focally extensive, with degenerated neutrophils and macrophages bordering these areas. The cortical lymphoid follicles were most severely affected. (J212.6.w2)
    • Caseous necrosis, multifocal to coalescing, also granulomatous inflammation. (J212.14.w2)
  • GIT:
    • In two cats on Nantucket Island, Massachusetts, USA, in the small intestine, submucosal lymphoid folicles showed marked necrosis, with the the lesions extending into the mucosa overlying the follicles and the muscular tunics below. (J212.6.w2)
  • Culture:  
    • In two cats on Nantucket Island, Massachusetts, USA,  large mucoid grey colonies developed on chocolate blood agar after three days, while on Schaedler blood agar, 2-3 mm colonies surrounded by alpha haemolysis zones were grown after four days (both media contain cysteine). The organisms were confirmed as Francisella tularensis using a slide agglutination test with specific antiserum. (J212.6.w2)
    • Francisella tularensis cultured on cystein heart agar where dew-drop colonies formed, and blood agar where either no colonies grew or small colonies appeared 24-48 hours later than those on cysteine blood agar. Four of the isolates were sent for typing and confirmed as Francisella tularensis subsp. tularensis. (J212.14.w2)
  • Immunohistochemistry:  
    • Positive staining was confirmed in at least one tissue of all 10 cats with culture-confirmed infection, and in nine additional cats using a fluorescent antibody test on deparaffinized and rehydrated formalin-fixed, paraffin-embedded tissue sections. (J212.14.w2) 
Perissodactylids

Equus caballus - Domestic horse

  • Organism isolation: Infection confirmed by culture and guinea pig inoculation: from lungs, liver, spleen and kidneys, isolation of a bacterium "morphologically and biochemically indistinguishable from P. tularensis and highly pathogenic for guinea pigs." (J538.78.w1)
Birds
  • Splenic enlargement may be the only finding, or there may be no abnormalities evident. Necrotic foci, e.g. in the liver, have been found only rarely with Francisella tularensis infection in birds. (B576.19.w19)

In a naturally infected Strix uralensis - Ural owl: (J1.19.w19)

  • Splenic: congestion.
  • Hepatic: congestion.
  • Respiratory: Lungs congested.
  • Renal: Kidneys congested.
  • Cardiac: congestion.
  • Francisella tularensis biovar holarctica, not growing on medium containing citrillin, highly sensitive to erythromycin. (J1.19.w19)

Colinus virginianus - Bobwhite quail

In quail infected orally (contaminated feed): (J330.44.w1)

  • Lungs: In 2/5, lungs deep red.
  • Liver: In 2/6 (not the same as those with lung changes) scattered necrotic foci.

In five experimentally infected Colinius virginianus - Bobwhite quail which died after inoculation (D392.XIII.w13)

  • Respiratory: 
    • In one bird dying 14 days after the start of oral inoculation, no lesions. (D392.XIII.w13)
    • In four birds, pulmonary congestion; in two of these, also haemorrhages, one bird further showing perivascular oedema and in the bronchi and air tubules, serocellular exudate containing epithelial cells, red blood cells, and detritus, plus large numbers of long, slender bacilli; it was considered that the exudate was not due to the tularemia. A single caseous necrotic focus under the epithelium of a bronchus was thought to be due to tularemia. (D392.XIII.w13) 
  • Cardiac: In the quail which died after four days "slightly cloudy muscle fibres and a few small focal haemorrhages." No lesions in the other birds. (D392.XIII.w13) 
  • GIT:  
    • In the quail which died after four days, infiltration of the mucosa by lymphocytes, and hyperplasia of lymphoid follicles. (D392.XIII.w13)
    • In a quail dying 14 days after infection by feeding, in the small intestine, small ulcers as well as patchy lymphocyte infiltration.In the colon, multiple ulcerated caseous necrotic areas containing fibrin, nuclear debris and large numbers of short, wide bacilli 9not Francisella tularensis); a zone of proliferating epithelioid cells bordered these lesions. (D392.XIII.w13)
  • Hepatic:
    • In quail dying 3-4 dpi following intramuscular inoculation, isolated liver cells were necrotic; there were small yaline thrombi present and diffuse fatty degeneration, finely vacuolar. Additionally, in those dying at 3 dpi, scattered liver cells were full of cocci and diplococci. In one quail, in the hyaline thrombi and in Kupffer cells, organisms were present. (D392.XIII.w13)
    • In the birds dying 14 - 15 dpi after feeding on infected material, no lesions other than moderate haemosiderois of Kupffer cells in one bird. (D392.XIII.w13)
  • Splenic: 
    • In quail dying 3-4 dpi following intramuscular inoculation, in the pulp, around ellipsoids and follicles, hyaline thrombonecrosis. Variable cytoplasmic oxyphilia and reticulum cell karyorrhexis, with hyaline oyxphil intracellular deposit, also in the necrotic areas of one quail, small clumps of cocci. (D392.XIII.w13)
    • In the birds dying 14 - 15 dpi after feeding on infected material, moderate lymphocyte infiltration, haemosiderosis of the pulp, also prominent ellipsoid. (D392.XIII.w13)
  • Renal:
    • In three birds, in the secreting tubules, finely granular changes and moderate swelling. In one quail dying 3 dpi following intramuscular inoculation, glomerular distension, hyaline thrombosis (partial to complete), severe secreting tubule degeneration with granular and hyaline droplet degeneration, vacuolation, desquamation of epithelium cytoplasmic oxyphilia and some coagulation necrosis. (D392.XIII.w13)
  • Skeletal muscle:
    • In the birds inoculated intramuscularly, at the site of inoculation, severe degenerative changes to the muscle, with fibres replaced by vacuolated masses of round/oval hyaline bodies, other fibres showing hyaline degeneration and necrosis, with blood vessels containing caseous and necrotic cellular thrombi. (D392.XIII.w13)

In a Buteo borealis borealis - Eastern red-tailed hawk (Buteo jamaicensis - Red-tailed hawk) experimentally infected by feeding with viscera from infected rodents. (D392.XIV.w14)

  • Pulmonary: Caseous abscesses not thought to be related to the experimental infection. (D392.XIV.w14)
  • Hepatic: local interstitial infiltration by lymphocytes. (D392.XIV.w14)
  • Adrenal: increased interstitial lymphoid tissue. (D392.XIV.w14)
  • Renal: Slight cloudy swelling of the kidneys. (D392.XIV.w14)

In two Buteo lineatus lineatus - Red-shouldered hawk juveniles (six-weeks old at the start of the trial) experimentally infected by feeding with viscera from infected rodents. (D392.XIV.w14)

  • Hepatic: local periportal infiltraion by lymphocytes. (D392.XIV.w14)
  • Splenic: "large ellipsoids, pulp moderately filled with blood and lymphocytes and small follicles, containing a few swollen phagocytic reticulum cells with a little ingested nuclear debris. (D392.XIV.w14)
  • Organism isolated by guinea pig inoculation from the liver of one bird. (D392.XIV.w14)

In apparently healthy wild Corvus corax - Common ravens in Sweden

  • Francisella tularensis was detected by an indirect fluorescent antibody test in tissue smears from the spleen (which was enlarged in these three birds), but not liver or muscle, of three of four birds tested. (J33.31.w1)
Overall Typical-Indicative Findings
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Authors & Referees

Authors Debra Bourne MA VetMB PhD MRCVS (V.w5)
Referee Gete Hestvik (V.w166)

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