Francisella tularensis causes potentially severe zoonotic disease in humans. It is sometimes referred to as rabbit fever or deer-fly fever. Serology is the preferred means of confirmation. Clinicians may want to consider testing for other similar disorders, including Rickettsia rickettsii (Rocky Mountain spotted fever), Rickettsia typhi (typhus fever), Brucella spp, and Pasteurella multocida (pasteurellosis).
Diagnosis
Indications for Testing
A history of contact with rabbits, ticks, dogs, cats, or skunks along with nonspecific febrile illness with prominent lymphadenopathy
- Negative history of animal contact does not rule out diagnosis
Laboratory Testing
- CDC diagnostic testing for tularemia
- Serology – acute and convalescent phase titers
- Preferred means of confirmation; retrospective in nature
- Fourfold increase between acute and convalescent serology or >1:160 on acute titer
- Cross-reactivity between Brucella, Salmonella, Yersinia, and Legionella antigens
- Culture – frequently negative
- Difficult to culture – fastidious organism
- Select agents – confirmed positive culture requires approval before transfer
- PCR – not widely available but very sensitive
- Consider testing for other disorders such as Rickettsia rickettsii (Rocky Mountain spotted fever), Rickettsia typhi (typhus fever), Brucella spp, and Pasteurella multocida (pasteurellosis)
Imaging Studies
Chest x-ray for patients presenting with signs and symptoms of pneumonia – demonstrates infiltrates
Differential Diagnosis
Ulceroglandular/glandular
- Streptococcal/staphylococcal skin infection
- Bacillus anthracis (anthrax)
- Pasteurella multocida (pasteurellosis)
- Atypical mycobacteria
- HIV
- Cytomegalovirus
- Toxoplasmosis
- Epstein-Barr virus
- Rickettsia
- Rickettsia rickettsii (Rocky Mountain spotted fever)
- Rickettsia typhi (typhus fever)
- Yersinia pestis (plague)
- Lymphoma (B-cell)
- Fungal disorder
Pneumonic
- Hantavirus
- Influenza virus
- Mycoplasma pneumoniae
- Brucella spp
- Legionella pneumophila
- B. anthracis
- Severe acute respiratory syndrome
- Chlamydophila pneumoniae or psittaci
- Coxiella burnetii (Q–fever)
- Mycobacterium tuberculosis
- Streptococcus pneumoniae
- Respiratory syncytial virus
Oropharyngeal
- Streptococcal disease, Group A
- Adenovirus
- Epstein-Barr virus
- HIV
Typhoidal
- Sepsis
- Salmonella typhi
- Brucella
- Endocarditis
- Coxiella burnetii
Oculoglandular
- Viral – adenovirus
- Bacterial
Background
Epidemiology
- Incidence – <1/100,000 in U.S.
- Most cases occur in the west-central and mountain regions – 56% of total cases from 1990-2000 occurred in Arkansas, Oklahoma, Missouri, and South Dakota
- Transmission – blood-sucking arthropods, contact with infected animals via inapparent abrasions, consumption of contaminated water, airborne spread of contaminated materials
- Primarily a disease of wild animals, especially rabbits
- Risk groups – farmers, veterinarians, hunters, landscapers, meat handlers, lab workers
- In U.S., human vectors are primarily ticks and deer flies
- Tick vectors include Amblyomma americanum, Dermacentor andersoni, Dermacentor variabilis
- Peak seasons – spring and summer
- Historical peaks during fall and early winter (hunting season)
Organism
Gram-negative, aerobic, nonspore forming, fastidious coccobacillus
- Two main biovars are F. tularensis subsp. tularensis (type A) and F. tularensis subsp. holarctica (formerly subsp. palearctica, type B)
- Type A found predominantly in U.S.
- Type B found predominantly in Europe and Asia
- F. tularensis subsp. novicida (type C) – low-virulence strain in North America
Clinical Presentation
- Average incubation – 3-5 days (range 1-21 days)
- Disease often begins with the sudden onset of flu-like symptoms, including chills, fever, headache, generalized aches
- Forms of tularemia (mostly depends on portal of entry)
- Ulceroglandular
- Most common form in adults
- Direct contact with animal or insect bite
- Starts as small, painful papule that becomes an ulcer at entry portal with associated lymphadenopathy
- Glandular – similar presentation to ulceroglandular but lacking ulcer
- Most common form in children
- Progresses to fever, chills, myalgia, possibly septicemia
- Oculoglandular – Parinaud syndrome
- Conjunctival entry via contaminated fingers, splashes, aerosols
- Unilateral intense conjunctivitis, preauricular, submandibular, cervical lymphadenopathy
- Sequelae of corneal perforation and iris prolapse
- Oropharyngeal and gastrointestinal
- Ingestion of contaminated food or water
- Oral – exudative pharyngitis; deep, cervical lymphadenopathy
- Gastrointestinal – ulcerative gastrointestinal lesions, diarrhea
- Pneumonic
- Inhalational exposure or extension from systemic disease (typically ulceroglandular form)
- Pneumonia with dry cough and pleuritic chest pain
- Often occupational exposure (sheep shearing, animal husbandry, farming, lawn/brush cutting, laboratory workers)
- Typhoidal
- Rare in U.S.
- May occur from any portal of entry
- Usually associated with bacterial gastrointestinal or pneumonic disease and consumption of poorly cooked wild game
- High fever, headache, diarrhea, sore throat, anorexia
- Ulceroglandular
- Complications – septicemia, meningitis, endocarditis, hepatitis, renal failure
ARUP Laboratory Tests
Preferred test for detecting antibodies during acute or convalescent phase
Convalescent sera may be required for diagnosis
Cross-reactions with Brucella or Yersinia antibodies may occur; results should be interpreted with caution and correlated with clinical information; the best evidence for current infection is significant change on two appropriately timed specimens
Repeat testing in 10-14 days may be helpful if results are equivocal
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Reference method for identification of most bacterial species
16S rDNA Sequencing
Identify aerobic bacterial isolates
For suspected agents of bioterrorism, notify state department of health and refer isolates to state laboratory for identification; susceptibilities on agents of bioterrorism are not performed at ARUP
For identification by 16s rDNA sequencing only, refer to organism identification by 16s rDNA sequencing; for identification AND susceptibility testing, refer to aerobic organism identification with reflex to susceptibility
Identification. Methods may include biochemical, mass spectrometry, or sequencing.
Confirm presence of Rickettsia typhi
Panel test (IgG and IgM) is preferred
Require comparison of acute- to convalescent-phase serology
Semi-Quantitative Indirect Fluorescent Antibody
Detects antibodies during convalescent phase
Semi-Quantitative Indirect Fluorescent Antibody
Recommended serology test to detect recent infection from Brucella in the context of a clinically compatible illness and exposure history
Cross-reactions may occur between Brucella and F. tularensis antigens and antisera; therefore, parallel tests should be run with these antigens; a fourfold rise in titer is considered diagnostic
Semi-Quantitative Agglutination
Detects antibodies during convalescent phase
Convalescent sera may be required for diagnosis
Cross-reactions with Brucella or Yersinia antibodies may occur; results should be interpreted with caution and correlated with clinical information; the best evidence for current infection is significant change on two appropriately timed specimens
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Detects antibodies during acute phase; paired concurrent specimen with IgG reduces false-positive rate
Convalescent sera may be required for diagnosis
Cross-reactions with Brucella or Yersinia antibodies may occur; results should be interpreted with caution and correlated with clinical information; the best evidence for current infection is significant change on two appropriately timed specimens
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Medical Experts
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