Summary Of Exposure |
A) CAUSATIVE ORGANISM: Francisella tularensis is gram-negative, nonmotile, nonsporulating coccobacillus, and is a fastidious and slow growing bacterium. It consists of 4 subspecies: tularensis (also known as Type A and the most virulent subspecies with the highest morality rate), holarctica (also known as Type B produces a milder form of illness and rarely fatal), novicida (this subspecies is most often associated with immunocompromised humans) and mediasiatica (produces a milder infection). The organism can survive for long periods in soil, plants and water leading to contamination. It can survive in acidic environments but has limited tolerance for high temperatures compared to other enteric bacterial pathogens.
B) EPIDEMIOLOGY: Humans are highly susceptible to F tularensis infection and it can produce severe, life-threatening illness. The form of tularemia can include: pulmonary, gastrointestinal, oropharyngeal, typhoidal, oculoglandular and ulceroglandular. The type of infection that occurs is highly dependent on the strain, dose and route of inoculation. Pulmonary tularemia can result in the highest mortality, if left untreated.
C) TARGET POPULATION: All individuals are susceptible to tularemia.
D) MECHANISM: The organism can invade, survive, and multiply with various host cells, particularly macrophages. The bacterium can limit the macrophages's ability to digest and eliminate the bacterium which allows for the replication and progression of the infection.
E) TIME TO ONSET: 3 to 6 days; symptoms may occur within 1 day or up to a few weeks in some cases depending on the dose, route and the virulence of the strain of F tularensis.
F) DURATION: Varies depending on the type and virulence of a particular strain.
G) ROUTE OF ENTRY: Oral, inhalation, insect bite, or direct contact with a contaminated object.
H) WITH POISONING/EXPOSURE
1) MILD TO MODERATE TOXICITY: The following events are likely to produce mild to moderate toxicity, but may lead to more severe events: a) OROPHARYNGEAL: Ingestion of bacteria that colonizes in the throat leading to stomatitis, pharyngitis or tonsillitis and cervical lymphadenopathy.
b) INTESTINAL: Abdominal pain, vomiting, and diarrhea and in severe cases bowel injury.
c) GLANDULAR: Regional lymphadenopathy with no ulcer; most commonly involves axillary nodes.
d) ULCEROGLANDULAR (most common form; 70% to 80% of cases): Cutaneous ulcer at site of inoculation (ie tick or deer fly bite) with painful regional lymphadenopathy. Symptoms include a sudden onset of chills, fever, and headaches. The bacteria can harbor in the lymphatics or spread systemically to the CNS, liver, kidneys, lungs, and spleen.
e) OCULOGLANDULAR: Conjunctivitis with preauricular lymphadenopathy.
2) SEVERE TOXICITY: The following serious events can develop: a) PNEUMONIC: Primary pleuropulmonary disease can develop. Onset is usually abrupt and characterized by high fever with or without relative bradycardia, severe chills, dyspnea, nonproductive cough, pleuritic chest pain, and profuse sweating.
b) MENINGEAL: Rare occurrence; appears to arise from hematogenous spread. Typically, preceded by ulceroglandular, pharyngeal, or pneumonic involvement. It can lead to permanent brain injury in some cases.
c) TYPHOIDAL: Febrile illness without early localizing signs and symptoms (ulcerative skin lesion and lymphadenopathy absent); patients usually appear extremely toxic; complicated by pneumonia in up to 40% of cases.
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Vital Signs |
3.3.1) SUMMARY
A) Increased temperature and pulse rate are common.
3.3.3) TEMPERATURE
A) Tularemia presents as an acute febrile illness, regardless of specific syndrome; fever present in >85% of patients (Uhari et al, 1990; Jacobs & Narain, 1983; Evans et al, 1985). 1) Fever begins abruptly; often associated with chills; usually continuous or mildly remittent pattern with elevations of 40 to 41.7 C reported; typically higher (greater than 40 degrees C) in typhoidal form and is poor prognostic sign (Uhari et al, 1990; Giddens et al, 1957; Dienst, 1963; Jacobs & Narain, 1983; Evans et al, 1985; Christenson, 1984).
2) When present, a pulse-temperature dissociation (relative bradycardia) should increase clinical suspicion of typhoidal tularemia (Liles & Burger, 1993).
3) May persist for weeks to months in untreated cases (Anon, 2005; Jacobs et al, 1985) (Francis, 1925)(Evans et al, 1985).
3.3.5) PULSE
A) Pulse rate increases, but not as high as expected in a febrile illness (Dienst, 1963). When present, a pulse-temperature dissociation should increase clinical suspicion of typhoidal tularemia (Liles & Burger, 1993).
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Heent |
3.4.3) EYES
A) OCULOGLANDULAR tularemia may present with any of the following clinical manifestations - 1) PHOTOPHOBIA: Present occasionally in typhoidal tularemia; typical symptom in oculoglandular form (Hughes, 1965; Jacobs & Narain, 1983; Dienst, 1963; Billings et al, 1998; Steinemann et al, 1999).
2) EYE PAIN: Primary symptom of oculoglandular tularemia (Halperin et al, 1985; Jacobs & Narain, 1983) (Francis, 1925) (Guerrant et al, 1976a; Hughes, 1965; Chappell et al, 1981) (Steinemann et al, 1999).
3) LACRIMATION: Typical symptom of oculoglandular tularemia (Dienst, 1963; Billings et al, 1998; Steinemann et al, 1999).
4) EYE DISCHARGE: Mucopurulent or watery ocular discharge may occur in oculoglandular form (Halperin et al, 1985; Hughes, 1965; Billings et al, 1998; Steinemann et al, 1999).
5) EYE LESION: Small, multiple, yellowish nodules with shallow necrotic ulcers in palpebral conjunctivae or sclerae characteristic of oculoglandular tularemia (Jacobs & Narain, 1983; Halperin et al, 1985) (Francis, 1925)(Hughes, 1965; Chappell et al, 1981; Billings et al, 1998; Steinemann et al, 1999).
6) CONJUNCTIVAL INJECTION: Conjunctiva typically reddened in oculoglandular form (Christenson, 1984; Guerrant et al, 1976a; Hughes, 1965; Chappell et al, 1981; Dienst, 1963; Billings et al, 1998; Steinemann et al, 1999).
3.4.6) THROAT
A) THROAT PAIN: Presenting symptom in 15% to 40% of patients; more common in children (Evans et al, 1985; Christenson, 1984; Jacobs et al, 1985). May be presenting symptom of oropharyngeal, typhoidal, or ulceroglandular tularemia; throat may not be clinically inflamed (Caruso et al, 1983; Evans et al, 1985; Jacobs et al, 1985; Parkhurst & San Joaquin, 1990; Everett & Templer, 1980; Luotonen et al, 1986; Dienst, 1963). Pharyngeal ulcers may accompany aerosol-induced tularemia (McGovern et al, 1999). 1) In oropharyngeal tularemia, patients may complain of "choking" and excruciating pain on swallowing (Everett & Templer, 1980; Nordahl et al, 1993a).
B) TONSILLAR EXUDATE: In oropharyngeal tularemia, tonsils often markedly reddened and swollen and covered by thick, gray exudate, which may extend onto lateral pharyngeal walls. The pharyngitis is unresponsive to penicillin, and routine cultures are negative (Caruso et al, 1983; Parkhurst & San Joaquin, 1990; Everett & Templer, 1980) (Markowitz, 1985) (Luotonen et al, 1986; Wills et al, 1982; Dienst, 1963; Nordahl et al, 1993a). |
Cardiovascular |
3.5.2) CLINICAL EFFECTS
A) PERICARDITIS 1) WITH POISONING/EXPOSURE a) Pericarditis is uncommon; associated with pericardial friction rub and ECG abnormalities such as ST and T wave changes (Evans et al, 1985).
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Respiratory |
3.6.2) CLINICAL EFFECTS
A) PNEUMONIA 1) WITH POISONING/EXPOSURE a) Inhalation of Francisella tularensis organisms may result in a septicemic typhoidal disease or a primary pneumonia, which may be rapidly fatal. In a biologic terrorist attack, pneumonic tularemia is a primary concern. Clinical manifestations include fever, cough, minimal or no sputum production, and pleuritic chest pain. Physical findings are similar to those of an atypical pneumonia and may include rales, pleural friction rubs, and signs of consolidation or effusions (McGovern et al, 1999; Gill & Cunha, 1997; Garrett, 1995; Langley & Campbell, 1995). 1) Radiographic findings are variable and nonspecific, but may include infiltrates, cavitation, hilar adenopathy, pleural effusions, pneumothorax, and ARDS.
2) Clinical course may be rapidly progressive and fulminant. Without antibiotic treatment, mortality rates range from 30% to 60%. With therapy, mortality drops to 1% to 2.5%.
3) Tularemia presenting as a solitary pulmonary nodule following syngeneic peripheral blood stem cell transplantation has been reported (Naughton et al, 1999).
b) PNEUMONIC TULAREMIA 1) CASE SERIES: In the summer of 2000, 15 cases of confirmed tularemia were reported on Martha's Vineyard. Of those cases, 11 had primary pneumonic tularemia, 2 had ulceroglandular disease (fever with skin ulcers and lymphadenopathy) and 2 had fever and malaise, but no localizing signs. All cases were male except one with a median age of 43 years (range, 13 to 59). One death was reported in a 43-year-old man of primary pneumonic tularemia following a delay in seeking care. Francisella tularensis type A was cultured from blood and lung tissue. Risk factors associated with this outbreak were found to be lawn mowing and brush cutting (Feldman et al, 2001). The authors suggested that F. tularensis was shed in animal excreta, and persisted in the environment, and infected individuals via inhalation after mechanical aerosolization.
B) COUGH 1) WITH POISONING/EXPOSURE a) Cough is present in one third of patients overall and in two thirds of those with pneumonia; more commonly it is dry, hacking, and nonproductive of sputum (Evans et al, 1985; Dienst, 1963) (Syrjala, 1985). Dry cough and retrosternal chest pain may be only clues to respiratory involvement in typhoidal form (Penn, 1995).
C) CHEST PAIN 1) WITH POISONING/EXPOSURE a) Pleuritic chest pain or retrosternal discomfort present in 20% of patients overall and in 40% to 45% of patients with pneumonia (Evans et al, 1985) (Syrjala, 1985). Dry cough and retrosternal pain may be only clues to respiratory involvement in typhoidal form (Penn, 1995).
D) DYSPNEA 1) WITH POISONING/EXPOSURE a) Dyspnea is a complaint in 25% of patients with pneumonia (Syrjala, 1985)(Evans et al, 1985; Dienst, 1963).
E) SPUTUM ABNORMAL - AMOUNT 1) WITH POISONING/EXPOSURE a) Cough is typically nonproductive; increased sputum production occurs in about one third of cases (Evans et al, 1985).
F) DISORDER OF RESPIRATORY SYSTEM 1) WITH POISONING/EXPOSURE a) Signs of pulmonary infection may be diffuse (moist rales throughout lung; 55% to 60%) or localized (rales, dullness, bronchial breathing, increased vocal fremitus, friction rubs; 40% to 45%) (Dienst, 1963).
G) HEMOPTYSIS 1) WITH POISONING/EXPOSURE a) Hemoptysis is present in about 10% of patients with pneumonia (Evans et al, 1985).
H) ACUTE LUNG INJURY 1) WITH POISONING/EXPOSURE a) Acute respiratory distress syndrome is a rare, life-threatening complication of tularemia pneumonia; it is characterized by extensive bilateral pulmonary infiltration on chest films and severe hypoxia; it may require a high concentration of oxygen with PEEP during initial 72 hours for adequate oxygenation (Sunderrajan et al, 1985).
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Neurologic |
3.7.2) CLINICAL EFFECTS
A) INCREASED MUSCLE TONE 1) WITH POISONING/EXPOSURE a) NUCHAL RIGIDITY may be present in typhoidal tularemia (Dienst, 1963; Giddens et al, 1957).
B) HEADACHE 1) WITH POISONING/EXPOSURE a) Occurs in 45% to 75% of patients; often frontal and usually severe (Evans et al, 1985; Christenson, 1984). Less common in children (5% to 10%) (Uhari et al, 1990; Giddens et al, 1957; Jacobs et al, 1985; Dienst, 1963).
C) ALTERED MENTAL STATUS 1) WITH POISONING/EXPOSURE a) Delirium, stupor, and marked restlessness are common in patients with acute toxemia even without CNS infection (Dienst, 1983) (LeDoux, 2000).
D) ATAXIA 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 61-year-old man developed a 2-day history of difficulty walking and was admitted with slight delirium and mild ataxia on finger-to-nose, heel-to-shin, and rapid-alternating-movement testing. The patient also had moderate to severe gait ataxia and marked truncal ataxia in both the seated and standing position. Blood cultures were positive for Francisella tularensis and the patient was treated successfully with doxycycline, gentamicin, and ciprofloxacin with complete resolution of symptoms (LeDoux, 2000). It was suspected the infection was due to the consumption of deer meat approximately 2 weeks prior to symptoms.
E) MENINGITIS 1) WITH POISONING/EXPOSURE a) Meningeal tularemia is a rare occurrence. It appears to arise from hematogenous spread, and is typically preceded by ulceroglandular, pharyngeal, or pneumonic involvement. It may occur with no documented history of tick bite or other animal contact (Rodgers, 1998) (Tarnvik et al, 1997) (Lovell, 1986)(Hutton & Everett, 1985; Harper et al, 1986) (Hill, 1990) (Alfes & Ayers, 1990).
b) Diagnosis is often missed or delayed, and is characterized by headache, neck stiffness, and delirium. The majority of patients have multisystem involvement at the time diagnosis of meningitis is made (Rodgers, 1998) (Tarnvik et al, 1997; Hutton & Everett, 1985; Harper et al, 1986) (Lovell, 1986) (Hill, 1990)(Alfes & Ayers, 1990).
c) CSF findings are nonspecific and include less than 1000 WBC/mm(3), with mononuclear pleocytosis; protein level greater than 100; glucose level less than 30 mg/mL; may be bloody (Rodgers, 1998) (Hutton & Everett, 1985; Harper et al, 1986) (Lovell, 1986)(Alfes & Ayers, 1990).
d) Meningitis may not respond to standard courses of streptomycin or gentamicin; combination therapy with doxycycline or chloramphenicol may be required (Rodgers, 1998)(Hutton & Everett, 1985; Alfes & Ayers, 1990).
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Gastrointestinal |
3.8.2) CLINICAL EFFECTS
A) VOMITING 1) WITH POISONING/EXPOSURE a) GI symptoms, including vomiting, occur in 15% to 20% of patients; more common in typhoidal form (Evans et al, 1985; Christenson, 1984; Jacobs & Narain, 1983; Giddens et al, 1957).
B) DIARRHEA 1) WITH POISONING/EXPOSURE a) Presenting symptom in 10% of patients (Evans et al, 1985).
b) Frequent symptom in typhoidal tularemia; may be presenting sign; usually loose and watery but may be bloody (Jacobs & Narain, 1983; Giddens et al, 1957; Dienst, 1963).
c) Gastrointestinal tularemia associated with acute watery diarrhea (Harrell & Whitaker, 1985); rarely, bloody diarrhea or acute bleeding with minimal diarrhea may occur secondary to superficial colonic ulcerations (Penn, 1995).
C) ABDOMINAL PAIN 1) WITH POISONING/EXPOSURE a) Presenting symptom in 10% of cases (Evans et al, 1985; Giddens et al, 1957).
b) Gastrointestinal tularemia associated with cramping abdominal pain (Harrell & Whitaker, 1985).
D) DYSPHAGIA 1) WITH POISONING/EXPOSURE a) Marked difficulty in swallowing typical symptom of oropharyngeal tularemia (Everett & Templer, 1980).
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Hepatic |
3.9.2) CLINICAL EFFECTS
A) LARGE LIVER 1) WITH POISONING/EXPOSURE a) In one study, 2 of 73 patients had evidence of enlarged liver by percussion; extension of liver below costal margin noted in additional 18 patients (Evans et al, 1985).
b) More common in children; palpation usually painful (Evans et al, 1985; Jacobs et al, 1985).
B) SPLENOMEGALY 1) WITH POISONING/EXPOSURE a) Present in about 15% of cases; more common in children; palpation usually painful (Evans et al, 1985; Jacobs et al, 1985). b) Tularemia should be considered in any patient with a febrile illness and splenomegaly (Garver et al, 1994). c) COMPLICATIONS 1) Splenic abscess may be associated with disseminated infection, particularly in children. Tularemia should be considered in any patient with a febrile illness and splenomegaly, or CT or US findings suggestive of splenic abscess (Garver et al, 1994).
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Genitourinary |
3.10.2) CLINICAL EFFECTS
A) ACUTE RENAL FAILURE SYNDROME 1) WITH POISONING/EXPOSURE a) Acute renal failure is rare; it may occur secondary to tubular necrosis, exudative glomerulonephritis, interstitial nephritis; frequently important contributing factor to death in fatal cases (Giddens et al, 1957; Dienst, 1963).
b) Typhoidal tularemia with renal failure is associated with poor prognosis (Penn & Kinasewitz, 1987; Giddens et al, 1957).
c) CASE REPORT: A 64-year-old man with a history of training dogs was found comatose in his home, and was admitted with evidence of acute renal failure. The patient was treated for acute renal failure and given intravenous ceftriaxone. However, the patient's condition deteriorated and he died 13 days after admission. Two weeks after his death, F. tularensis was isolated from blood cultures by the State laboratory (Centers for Disease Control and Prevention, 2001).
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Dermatologic |
3.14.2) CLINICAL EFFECTS
A) BITE - WOUND 1) WITH POISONING/EXPOSURE a) Inoculation through tick bites often produces lesions on lower extremities, head, back, abdomen, or in concealed body areas such as axilla, groin, or intergluteal region (Lopez, 1982) (Evans et al, 1985; Pullen & Stuart, 1945; Guerrant et al, 1976a).
b) History of tick exposure often absent in patients with pneumonic tularemia (McChesney & Narain, 1983).
B) DERMATITIS 1) WITH POISONING/EXPOSURE a) SUMMARY 1) LOCATION: Hand and fingers following contact with infected animals. Inoculation through bites often produces lesions on lower extremities, abdomen, back, head, or in concealed body areas such as axilla, groin, or intergluteal area (Evans et al, 1985)( Lopez, 1982) (Francis, 1925)(Giddens et al, 1957).
2) COURSE: Macular, erythematous lesion appears at site of inoculation 48 hours after entry of organism; rapidly becomes pruritic papule that enlarges and ulcerates (Francis, 1925 )(Giddens et al, 1957; Dienst, 1963).
b) MACULOPAPULAR RASH 1) Initial lesion macular, erythematous lesion at site of inoculation that rapidly becomes pruritic papule; papule becomes painful and swollen, causing skin to become taut, thick, shiny, and, rarely, fluctuant before ulcerating (Francis, 1925) (Giddens et al, 1957; Dienst, 1963).
c) SKIN ULCERATION 1) Occurs about 96 hours after inoculation; papule suppurates in center, leaving dirty, shallow ulcer 3 to 5 mm in diameter with grey necrotic base, irregular undermined firm edges, and small erythematous border; occasionally may be multiple. Eschar formation is common at the bite site (Giddens et al, 1957)(Francis, 1925)(Dienst, 1963; Evans et al, 1985; Senol et al, 1999; Kodama et al, 1994). Skin sloughing at the bite site occurred a week after a 3-year-old boy developed tularemia after he was bitten on the left ring finger by a pet hamster (Anon, 2005).
d) CELLULITIS 1) CASE REPORT: An 11-year-old girl developed cellulitis of the forearm which did not improve with an oral cephalosporin. The child recovered after doxycycline therapy was started for suspected tularemia; paired serum titers showed an increase in antibodies against F. tularensis. A week before becoming ill the child had been exposed to a rabbit that she had skinned and tanned herself, that had been killed by the family dog (Centers for Disease Control and Prevention, 2001).
e) RASH 1) Present in up to 20% of cases; located on hands, arms, legs; primarily occurs in typhoidal form; may be macular, maculopapular, pustular, or blotchy; usually bilateral and distributed symmetrically (Wills et al, 1982; Evans et al, 1985; Christenson, 1984; Jacobs & Narain, 1983; Pullen & Stuart, 1945).
C) BUBO 1) WITH POISONING/EXPOSURE a) Buboes may occur in untreated or misdiagnosed cases, particularly those infected with type A strains, lymph nodes become caseous and form suppurative buboes (Tarnvik et al, 1997; Penn, 1995).
b) A high incidence of late suppuration (following antibiotic therapy) in children is reported. It occurred in a third of pediatric patients in one series (Jacobs et al, 1985).
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Musculoskeletal |
3.15.2) CLINICAL EFFECTS
A) MUSCLE PAIN 1) WITH POISONING/EXPOSURE a) Generalized muscle aches are a presenting symptom in one third to one half of cases; more common in children (Evans et al, 1985; Jacobs & Narain, 1983; Christenson, 1984; Dienst, 1963).
b) Muscle pain is characteristic symptom of typhoidal tularemia(Evans et al, 1985; Jacobs & Narain, 1983; Christenson, 1984; Dienst, 1963).
B) JOINT PAIN 1) WITH POISONING/EXPOSURE a) Joint pain is present in 8% to 15% of cases (Evans et al, 1985; Christenson, 1984).
C) RHABDOMYOLYSIS 1) WITH POISONING/EXPOSURE a) Rhabdomyolysis may occur in severely ill patients. Pathology of muscle injury not elucidated but may be caused by direct involvement of skeletal muscle (Kaiser, 1985) (Klotz et al, 1987).
b) Tularemia associated with the triad of bacteremia, pneumonia, and rhabdomyolysis has been described (Klotz et al, 1987; Provenza et al, 1986).
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Immunologic |
3.19.2) CLINICAL EFFECTS
A) LYMPHADENOPATHY 1) WITH POISONING/EXPOSURE a) Cutaneous multiplication of organisms can allow the organism to spread to lymph nodes, and then to the blood. Cervical lymphadenopathy is a presenting manifestation in 50% of patients; more common in children; multiple nodes are usually involved (Jacobs et al, 1985; Evans et al, 1985) (Markowitz, 1985) (McGovern et al, 1999; Fisher, 1996). b) Direct invasion of pharynx from ingestion of contaminated meat produces tender, enlarged cervical lymph nodes (Everett & Templer, 1980; Caruso et al, 1983; Parkhurst & San Joaquin, 1990; Luotonen et al, 1986; Wills et al, 1982). c) Typical presenting feature of occuloglandular tularemia; nodes may be exquisitely tender (Francis, 1925) (Halperin et al, 1985; Guerrant et al, 1976a; Hughes, 1965; Pullen & Stuart, 1945). d) CASE REPORT: A week after a 3-year-old boy was bitten on the left ring finger by a pet hamster, he developed fever, malaise, painful left axillary lymphadenopathy, and skin sloughing at the bite site. Serologic test was positive for Francisella tularensis at a titer of 4,096 and the isolate was identified by CDC as type B (Anon, 2005). e) PREAURICULAR LYMPHADENOPATHY 1) Preauricular lymphadenopathy is a presenting sign in 8% of patients (Evans et al, 1985). It is a common finding in oculoglandular syndrome; nodes may be exquisitely tender (Halperin et al, 1985; Guerrant et al, 1976a; Pullen & Stuart, 1945; Chappell et al, 1981; Billings et al, 1998).
f) COMPLICATIONS 1) BUBOES: It may occur in untreated or misdiagnosed cases, particularly those infected with type A strains, lymph nodes become caseous and form suppurative buboes (Tarnvik et al, 1997; Penn, 1995).
2) A high incidence of late suppuration (following antibiotic therapy) in children is reported. It has been noted in one third of pediatric cases in one series (Jacobs et al, 1985).
3) Ulceroglandular infection may result in a lymphadenopathy that can persist for several months (Billings et al, 1998).
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