Tularemia

OVERVIEW: What every practitioner needs to know

Are you sure your patient has tularemia? What should you expect to find?

• Patients usually present with the abrupt onset of fever, chills, malaise, myalgias, chest discomfort vomiting, abdominal pain and diarrhea. A severe generalized headache is often present.
• Ulcero-glandular fever – In the most common form of tularemia; in this form of tularemia22, a painful ulcer is observed with raised borders at the site where the bacteria were first inoculated into the skin. The lymph nodes draining this region are swollen and painful.
• Glandular fever- Less commonly lymphadenopathy is observed without an ulcerative skin lesion.
• Oculoglandular fever – if contaminated fluid splashes the eye or the eyes are rubbed with contaminated fingers conjunctivitis can develop that can be accompanied by conjunctival ulcers along with lymphadenopathy in the periauricular, submandibular and cervical areas.
• Pharyngeal – contracted during ingestion of contaminated food. Pharyngitis is exudative and extremely painful, accompanied by regional lymphadenopathy.
• Typhoidal form – high fever, hypotension and diarrhea is a third constellation of symptoms and signs. This form of tularemia is frequently mistaken for Salmonella typhoid fever.
• Pneumonic tularemia – is rare in natural disease being rarely seen in sheep shearers, farmers and laboratory workers. Pneumonia caused by Francisella tularensis should always raise the possibility of an aerosol bioterrorist attack. Cough is usually dry, hacking and nonproductive. Respiratory complaints may not be present and the clinical picture may mimic the typhoidal form of disease.

How did the patient develop tularemia? What was the primary source from which the infection spread?

• F. tularensis is a zoonotic pathogen and only incidentally infects humans. The disease is contracted through contact with animals, including rabbits, beaver, muskrats, squirrels, and birds. A case was reported following a hamster bite.

  Hunters develop skin infections after skinning, dressing or eating an infected animal, Rabbits are the most commonly reported animal to spread the infection to humans

• Infection less commonly can be transmitted by ticks, biting flies, and mosquitoes.
• Aerosol droplets from contaminated water or mud can be created by using a lawn mower or while gardening. The organism is able to survive in water for long periods by taking up residence in Acanthamoeba castellanii.
• This infection is seen in temperate climates during the summer months and during hunting season. This infection is most commonly reported in Arkansas, Missouri, Kansas, South Dakota, Oklahoma and Cailfornia. Outside the US it is seen in all of Europe except Great Britain, and also in the former Soviet Union, Turkey, Tunisia, Iran, Israel, China and Japan.

Which individuals are at greater risk of developing tularemia?

• Occupational history is important to obtain along with animal exposures and outdoors activities. Hunters are at highest risk, along with sheep herders and shearers, farmers, landscapers and those spending time in the wilderness.
• No known host defense defect is known to specifically predispose to tularemia.
• Outcome is worse in the elderly and in those with underlying diseases.

Beware: there are other diseases that can mimic tularemia:

• Ulcero-glandular and glandular fever can be mistaken for cat scratch disease, malignancy, atypical and typical mycobacterial infection, toxoplasmosis, fungal infection, herpes simplex infection, syphilis, bubonic plague, anthrax, and rat-bite fever,
• Oculoglandular disease can be misdiagnosed as cat scratch disease, herpes simplex, adenovirus infection, or other forms of pyogenic conjunctivitis.
• Pharyngeal disease can be misdiagnosed as Group A streptococcal pharyngitis, mononucleosis, adenoviral pharyngitis, or diphtheria.
• Typhoidal disease – in addition to mimicking Salmonella tularemia can be mistaken for brucellosis, Q fever and endocarditis.
• Pneumonic disease can be mistaken for Q fever, psittacosis, tuberculosis, pneumonic plague, pulmonary fungal infection, as well as community-acquired pneumonia.
• A failure to respond to conventional antibiotics should raise the possibility of tularemia.

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

• Routine diagnostic testing is usually not helpful.

  The peripheral WBC can be elevated, normal or low in this disease.

  The platelet count is depressed in some patients,

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  A low serum sodium may be observed.

  Abnormal liver function tests

  Elevated CPK may be seen as a consequence of rhabdomyolysis.

  Pyuria can also be observed.

• Aspiration of pleural fluid usually reveals lymphocytes suggesting the diagnosis of tuberculosis.
• Gram stains of the sputum and skin lesions are usually unrevealing.

Results that confirm the diagnosis

• Blood cultures are almost always negative because the organism does not grow on routine media, requiring either cysteine orcystine for growth.

  This organism is dangerous for laboratory workers because an inoculum of 10-50 organisms is all that is required to cause disease.

  When sending samples that may contain this organism the laboratory should be warned.

• Organisms may be identified following sliver staining of lymph node biopsies
• Diagnosis is usually made by testing for anti F. tularensis serum antibody. One of two tests is recommended

  Tube agglutination – requires two weeks to become positive. A single titer of 1:160 or higher is supportive of the diagnosis, but could represent old disease. A rise in titer of 4-fold are greater in convalescent serum is considered diagnostic

  Microagglutination assay – A titer of 1:128 or higher supports the diagnosis and a 4-fold or greater rise in titer in covalescent serum is felt to be diagnostic.

  These tests should only be ordered if tularemia is a strong possibility and should not be used for routine screening.

• A rapid, sensitive and specific PCR test has been reported, but is not widely available.

What imaging studies will be helpful in making or excluding the diagnosis of tularemia?

• CXR may reveal a bronchopneumonia pattern of opacification in 50% of inhalation cases. Pleural effusions are noted in 15% of cases. $

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What consult service or services would be helpful for making the diagnosis and assisting with treatment?

Given the fact that tularemia can mimic many infectious diseases, an infectious disease consultation will generally be helpful. Surgery may be consulted in some cases to obtain a lymph node biopsy.

If you decide the patient has tularemia, what therapies should you initiate immediately?

Key principles of therapy:

F. tularensis is not sensitive to cephalosporins or penicillins. In patients who fail to respond to these empiric antibiotics the possibility of tularemia should be considered. Aminoglycosides are the treatment of choice. Most experience is with streptomycin and many regard this antibiotic as the treatment of choice. However, in most developed countries gentamicin is more readily available. For mild disease oral doxycycline is recommended. Because the organism grows within cells, relapse is quite common following doxycycline treatment. Usually a more prolonged course of doxycycline for 21 days will prove effective. Alternatively treatment with an aminoglycoside can be initiated. There is less experience with the use of fluoroquinolones for the treatment of tularemia; however, of 14 cases recently treated in Missouri with ciprofloxacin, 86% were cured.

Delay in therapy worsens the prognosis. Untreated patients suffer continued weight loss, lassitude and often have prominent lymphadenopathy.

1. Anti-infective agents

Treatment for Tularemia

See Table I.

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