PATHOGENESIS AND CLINICAL PRESENTATION OF TULAREMIAFrancisella tularensis, the causative agent of tularemia, is an aerobic, gram-negative coccobacillus. Tularemia is a zoonotic disease that humans may acquire through diverse environmental exposures and can develop into a severe and sometimes fatal illness. Voles, mice, squirrels, rabbits, and hares are natural reservoirs of infection. Humans may acquire infection in various ways:- Bite from an infected arthropod (tick, deerfly, mosquito)- Handling infectious animal tissues- Ingestion of contaminated foods or liquids- Inhalation of infected aerosolsTransmission from person to person has not been documented. An aerosol release would be the most likely route used in a bioterrorist event.
PathogenesisAfter F. tularensis is inoculated into the skin, mucous membranes, gastrointestinal tract, or lungs, the organisms are taken up by macrophages, where they multiply and spread to regional lymph nodes. The bacteria can then disseminate to organs throughout the body, particularly targeting the lymph nodes, spleen, liver, lungs, and kidneys. Bacteremia may be present during dissemination. F. tularensis can remain viable in the environment for weeks and is able to resist temperatures below freezing. However, it is easily killed by heat and disinfectants.
Clinical PresentationClinical illness due to tularemia occurs after an incubation period of 1 to 21 days (average, 3 to 5 days), and as few as 10 to 50 organisms may cause disease. The onset of tularemia is abrupt and is characterized by fever, headaches, rigors, and generalized body aches (especially low back). Patients occasionally complain of abdominal pain, diarrhea, and vomiting. Pulmonary symptoms include a dry or slightly productive cough, substernal chest discomfort, dyspnea, and pleurisy. A pulse-temperature deficit is found in less than half of patients. The overall case-fatality rate is approximately 2%.Tularemia can appear in one of six forms in humans, depending on the route of inoculation:Ulceroglandular tularemia usually occurs following an infected arthropod bite but may also be acquired after the inoculation of skin with infected blood or body fluids. A papule usually appears at the inoculation site, becomes pustular, and then ulcerates. Fever, chills, headaches, and malaise accompany the cutaneous findings. Regional lymphadenitis occurs within days of the appearance of the papule.Oculoglandular tularemia follows inoculation of the conjunctiva by contaminated hands, infected tissue fluids, or infectious aerosols. Patients have painful, purulent conjunctivitis with preauricular or cervical lymphadenopathy. Fever, chemosis, periorbital edema, and pinpoint conjunctival ulcers may also be noted.Glandular tularemia is characterized by fever and tender lymphadenopathy, without ulceration.Oropharyngeal tularemia may be acquired by ingesting contaminated foods or liquids or by inhaling infectious aerosols. Patients typically develop an acute exudative pharyngotonsillitis with cervical or retropharyngeal lymphadenopathy.Typhoidal tularemia occurs mainly after inhalation of infectious aerosols but can occur after intradermal or gastrointestinal inoculation. This is a systemic illness characterized by fever, headaches, weight loss, and malaise without lymphadenopathy. Abdominal tenderness and he-patosplenomegaly may be present on physical examination. Patients may develop shock, delirium, or coma.Pneumonic tularemia may occur after the inhalation of organisms (primary disease) or following the hematogenous spread of any form of tularemia to the lungs (secondary disease). Disease onset is abrupt, with high fevers, dyspnea, nonproductive cough, and pleuritic chest pain. Patients may rarely develop mucopurulent sputum or hemoptysis. On examination, inspiratory crackles may be heard in the involved areas of the lungs, and pleural friction rubs are common.*215/348/5*
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