Tularemia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Tularemia is caused by the bacterium Francisella tularensis found in animals (especially rodents, rabbits, and hares). Francisella tularensis (F. tularensis) is a tiny, pleomorphic, nonmotile, gram-negative, facultative intracellular coccobacillus (0.2 to 0.5 μm by 0.7 to 1.0 μm). It is a fastidious organism and may require cysteine supplementation for good growth on general laboratory media.

Pathogenesis

Transmission

• Bacteremia may be common in the early phase of infection.
• The initial tissue reaction to infection is a focal, intensely suppurative necrosis consisting largely of accumulations of polymorphonuclear leukocytes, followed by invasion of macrophages, epithelioid cells, and lymphocytes.
• Suppurative lesions become granulomatous, and histopathological examination of the granulomas shows a central necrotic, sometimes caseating, zone surrounded by a layer of epithelioid cells, multinucleated giant cells, and fibroblasts in a radial arrangement, typical of other granulomatous conditions such as tuberculosis and sarcoidosis.
• Humans with inhalational exposures also develop hemorrhagic inflammation of the airways early in the course of illness, which may progress to bronchopneumonia.
• Histopathological examination of the lungs shows alveolar spaces filled with an exudate of mononuclear cells.
• Pleuritis with adhesions and effusion and hilar lymphadenopathy are common in radiological and pathological findings.
• Primary clinical forms vary in severity and presentation according to virulence of the infecting organism, dose, and site of inoculum.
• The onset of tularemia is usually abrupt, with fever (38oC–40oC), headache, chills and rigors, generalized body aches (often prominent in the low back), coryza, and sore throat. A pulse-temperature dissociation has been noted in as many as 42% of patients. A dry or slightly productive cough and substernal pain or tightness frequently occur with or without objective signs of pneumonia, such as purulent sputum, dyspnea, tachypnea, pleuritic pain, or hemoptysis. Nausea, vomiting, and diarrhea may occur.
• Sweats, fever, chills, progressive weakness, malaise, anorexia, and weight loss characterize the continuing illness.
• In general, tularemia would be expected to have a slower progression of illness and a lower case-fatality rate than either inhalational plague or anthrax. Milder forms of inhalational tularemia would be indistinguishable from Q fever; another potential bioterrorism agent; establishing a diagnosis of either would be problematic without reference laboratory testing.

Mechanism of infection

• Francisella tularensis is one of the most infective bacteria known; fewer than ten organisms can cause disease leading to severe illness.
• The bacteria penetrate into the body through damaged skin and mucous membranes, or through inhalation.
• Humans are most often infected by tick bite or through handling an infected animal. Ingesting infected water, soil, or food can also cause infection.
• Tularemia can also be acquired by inhalation; hunters are at a higher risk for this disease because of the potential of inhaling the bacteria during the skinning process.
• Tularemia is not spread directly from person to person.
• Francisella tularensis is an intracellular bacterium, meaning that it is able to live as a parasite within host cells.
• It primarily infects macrophages, a type of white blood cell. It is thus able to evade the immune system.
• The course of disease involves spread of the organism to multiple organ systems, including the lungs, liver, spleen, and lymphatic system.
• The course of disease is similar regardless of the route of exposure. Mortality in untreated (pre-antibiotic-era) patients has been as high as 50% in the pneumoniac and typhoidal forms of the disease, which however account for less than 10% of cases.
• Overall mortality was 7% for untreated cases, and the disease responds well to antibiotics with a fatality rate of about 2%.
• The exact cause of death is unclear, but it is thought be a combination of multiple organ system failures.