Consensus statement ularemia, a bacterial zoono

PATHOGENESIS AND CLINICAL MANIFESTATIONS

Pathogenesis

Francisella tularensis can infect hu- mans through the skin, mucous mem- branes, gastrointestinal tract, and lungs. It is a facultative intracellular bacte- rium that multiplies within macro- phages.68,69 The major target organs are the lymph nodes, lungs and pleura, spleen, liver, and kidney.19,20,49,70-72 Un- treated, bacilli inoculated into skin or mucous membranes multiply, spread to the regional lymph nodes and further multiply, and may then disseminate to organs throughout the body. Bactere- mia may be common in the early phase of infection. The initial tissue reaction to infection is a focal, intensely suppu- rative necrosis consisting largely of accumulations of polymorphonuclear leukocytes, followed by invasion of macrophages, epithelioid cells, and lym- phocytes. Suppurative lesions become granulomatous, and histopathological examination of the granulomas shows a central necrotic, sometimes caseat- ing zone surrounded by a layer of epi- thelioid cells, multinucleated giant cells, and fibroblasts in a radial arrange-

Table 1. Diagnosis of Inhalational Tularemia Following Use of a Biological Weapon

Clinical Findings

Sudden onset of acute febrile illness, progressing in some patients to pharyngitis, bronchiolitis, pneumonitis, pleuritis, hilar lymphadenitis. Complications of overwhelming untreated infection may lead to sepsis and inflammatory response syndrome.

Epidemiology

Point-source outbreak pattern; likely urban, nonagricultural setting. Unexpected severe respiratory illness in otherwise healthy persons. Risk related to degree of exposure with no differences in susceptibility by age or sex.

Microbiology

Small, gram-negative coccobacilli in direct stain of respiratory secretions. Sputum, tracheobronchial secretions, and blood should be cultured using cysteine-enriched medium. Antimicrobial susceptibility of isolates should be determined. Direct fluorescent antibody stain is first-line, rapid identification procedure at reference laboratories. Polymerase chain reaction and antigen detection procedures may also provide rapid identification. Microagglutination assay can detect serum antibodies beginning 10 days after illness onset. Virulence testing and molecular genetic characterizations are performed at specialized laboratories.

Pathology

Histological findings of acute suppurative necrosis followed by granulomatous reactions. Target organs include lungs, lymph nodes, spleen, liver, and kidney.

Radiology

Peribronchial infiltrates leading to bronchopneumonia in 1 or more lobes, often accompanied by pleural effusion and enlarged hilar nodes. Signs may be absent or minimal, with only 1 or several small, discrete pulmonary infiltrates, or scattered granulomatous lesions of lung parenchyma or pleura.

MANAGEMENT OF TULAREMIA AS A BIOLOGICAL WEAPON

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