Tularemia

1
Tularemia

• Agent
• Francisella tularensis
• Named for Sir Edward Frances (did original work
  on disease) and Tulare, CA (where disease agent
  was first isolated)
• Other names of human disease
• rabbit fever
• deer-fly fever

2
Tularemia

• Microbiological features
• Gram-negative, coccobacillus
• non-motile, unencapsulated
• Two subtypes differ based on virulence
• Type A (biogroup tularensis)
• highly virulent for humans and rabbits
• found in North America
• Type B (biogroup palearctica)
• less virulent for humans, found in aqautic
  animals
• found in Asia and Europe

3
Tularemia

• Microbiological features
• no growth on routine media (requires cysteine or
  cystine)
• special culture media - thioglycolate,
  glucose-cysteine blood agar, chocolate agar
• addition of CO2 may enhance growth

4
Tularemia

• Pathogenesis
• intracellular growth, therefore cell-mediated
  immunity directed against protein antigens is
  responsible for resistance and recovery
• infectious dose depends on site of entry
• few organisms (10-50) required for intradermal
  injection or inhalation
• large number (108) if ingested

5
Tularemia

• Epidemiology
• Occurrence
• common throughout North America
• more common in US prior to 1950, steadily
  declining incidence since 1965
• Incidence 0.05-0.15/100,000
• 50 of cases from AR, OK, MO
• over 75 in men
• more common in gt30 years of age
• recent studies indicate pediatric population can
  represent up to 28 of cases in certain areas

6
Tularemia

• Epidemiology
• Route of transmission
• bite of arthropod vector
• inoculation of skin, mucous membranes with
  contaminated water, blood, tissue
• ingestion of insufficiently cooked meat or
  contaminated water
• inhalation of dust from soil, grain, hay
• animal bite (rare) from animal eating on infected
  carcass

7
Tularemia

• Vectors
• Amblyomma americanum - lone star tick
• Dermacentor variabilis - American dog tick
• D. andersoni - American wood tick
• Chrysops discalis - deer fly
• Aedes cinereus (Sweden)

8
Tularemia

• Clinical features
• Incubation period
• relates to virulence, size of inoculum, location
• 1 - 14 days (3-5 days average)
• Symptoms based on six classic forms of disease
• ulceroglandular
• glandular
• oculoglandular
• oropharyngeal
• typhoidal
• pneumonic

9
Tularemia

• Clinical features
• Symptoms
• abrupt onset of fever, chills, headache,
  anorexia, fatigue
• ulceroglandular (50-75)
• enlarging, painful lymphadenopathy
• large red papule that becomes ulcerative and
  tender
• may have multiple cutaneous lesions (musk-rat
  associated outbreak in Vermont)
• glandular (15-20)
• like ulceroglandular without cutaneous lesions
• oculoglandular (1-4)
• edematous, inflamed eyelid with ulceration of
  conjunctiva and sclera

10
Tularemia

• Clinical features
• Symptoms
• oropharyngeal (4-18)
• pharyngitis ranging from mild to strep or
  mono-like
• local lymphadenopathy
• typhoidal (8-18)
• acute bacteremia
• skin manifestations (exanthems, erythema nodosum)
• diarrhea (bloody)
• pulmonary - infiltrates and pleural effusion can
  be seen with other forms of disease

11
Tularemia
Lymphoglandular lesion - eschar
12
Tularemia
Lymphoglandular lesion - ulcer
13
Tularemia
Lymphoglandular lesion - necrotic lymph node
14
Tularemia
Typhoid form - x-ray of pulmonary inflitrates
15
Tularemia
Typhoid form - pulmonary inflitrates (CT scan)
16
Tularemia
Oculoglandular lesion
17
Tularemia
Lesions in liver from infected rabbit (white
spotted liver)
18
Tularemia

• Clinical features
• Diagnosis
• accurate history, with attention to epidemiologic
  features
• culture and identification
• type A ferment glycerol and converts citrulline
  to ornithine
• agglutination test - most commonly available
• can cross react with Brucella
• agglutinating antibodies with first couple of
  weeks, peak in four weeks
• a single titer gt1160 or four-fold rise in titer
• titers may remain elevated for 10 years
• PCR useful, but only available for research
  purposes

19
Tularemia

• Clinical features
• Treatment
• streptomycin - drug of choice but limited supply
  in some areas
• gentamycin - when streptomycin not available
• doxycycline - 21 days preferred
• Case fatality ratio
• up to 60- inhaled form leading to pneumonia and
  septicemia (typhoidal form) if untreated

20
Tularemia

• Prevention and control
• education
• avoid exposure
• proper handling during skinning, processing
  protective gloves, eye wear
• tick (and other arthropod) control
• proper cooking of meat
• live attenuated vaccines for certain occupations