Clinical Features of Disease

Tularemia classically presents as one of six clinical syndromes, depending on the route of infection and biotype of the infecting organism. Both inoculum size and host immune status influence the severity and extent of disease. Onset of infection is usually acute and is heralded by fever, chills, headache and myalgias. Following a deliberate airborne release the most likely presentation would be pneumonic or septicaemic tularemia.

Pneumonic tularemia

This usually results from the direct inhalation of contaminated aerosols but can also follow haematogenous spread from another site. In primary inhalation the disease commonly presents as an acute flu-like illness with or without clinical pneumonia/ pneumonitis. Features include fever, non-productive cough, pharyngitis, pleuritic chest pain and hilar lymphadenopathy. This can progress to a severe pleuropneumonitis with moderate sized pleural effusions. When consolidation occurs this is usually nonlobar, with patchy infiltrates. Chest signs may, however, be minimal or absent. Volunteers challenged with aerosols of virulent F. tularensis type A regularly developed systemic symptoms of acute illness 3-5 days following exposure and 25-50% showed radiological evidence of pneumonitis early in the infection. In the largest airborne outbreak involving type B organisms, which occurred in Sweden in 1966-1967, only 10% of serologically confirmed cases had symptoms suggestive of pneumonia. In most cases of established pulmonary disease, progression tends to be less dramatic than that seen with anthrax or plague, although mortality rates in excess of 30% may occur.

Septicaemic tularemia

The patient presents as an acute Gram-negative sepsis with fever, abdominal pain, diarrhoea, and vomiting which may be prominent early in the course of illness. The patient typically appears toxic and may progress to septic shock, disseminated intravascular coagulation, haemorrhage, acute respiratory distress, confusion and coma.

Ulceroglandular tularemia

Naturally occurring ulceroglandular tularemia usually arises from handling a contaminated carcass or following an arthropod bite. Typically a local papule arises at the site of inoculation accompanied by generalised symptoms including fever and aches. The lesion may be pruritic and enlarges to form a pustule, which ruptures and develops into a painful, indolent ulcer. This may or may not be accompanied by eschar formation. Differential diagnoses include cutaneous anthrax (surrounding oedema is usually not as prominent as in cutaneous anthrax), plague, lymphogranuloma venereum, granuloma inguinale, and cat-scratch fever. A localised vesiculopapular eruption may also occur. As the lesion progresses it is accompanied by tender enlargement of one or more regional lymph nodes, which may become fluctuant and rupture releasing caseous material. Local disease often continues to progress despite appropriate antibiotic therapy.

Glandular tularemia may occur in the absence of an obvious site of inoculation.

Click here for clinical pictures of tularemia ulcers 

Oculoglandular tularemia

This follows airborne exposure, autoinoculation or after cleaning infected animal carcasses. Ulceration of the cornea produces chemosis and pain and is accompanied by tender preauricular lymphadenopathy.

Oropharyngeal tularemia

This is acquired by drinking contaminated water or food, direct inoculation from the hands to the mouth and sometimes by inhaling contaminated droplets or aerosols. Affected persons may develop a stomatitis, but more commonly an exudative pharyngitis or tonsillitis ensues with or without painful mucosal ulceration.

Typhoidal tularemia

An acute flu-like illness, often with diarrhoea and vomiting may follow ingestion or inhalation of F. tularensis. Pneumonic changes, mucocutaneous lesions and regional lymphadenopathy are usually absent.

Mortality

Untreated, the overall mortality for all types of tularemia is 8%, 4% for ulceroglandular and 30-50% for typhoidal, septicaemic and pneumonic types. With appropriate treatment, mortality is reduced to 1%.

Antimicrobial Susceptibilities

Aminoglycoside antibiotics (eg gentamicin), are bactericidal against F. tularensis and are currently the treatment of choice for pneumonic or typhoidal tularemia (and severe forms of glandular disease). Fluoroquinolones have shown promise because of their low toxicity and potential for oral therapy. Chloramphenicol and tetracyclines are associated with high relapse rates. The beta-lactams, except for carbapenems, are considered ineffective. Macrolide antibiotics are not recommended. If doxycycline or ciprofloxacin are given 48 hours before challenge and continued for 5 days after challenge in a murine model, these antibiotics protected against intraperitoneal infection. However all mice succumbed once the antibiotics were stopped. If treatment was continued for 10 days after challenge, then fewer relapses occurred.

Last reviewed: 9 November 2009