Vol. 17, No. 20
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER
Monday, May 18, 1998
A. Provided by Marguerite-Hawkins, Epidemiology and Disease Control Program, Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene.
From May 8, 1998 through May 14, 1998, 4 outbreaks have been reported to the Maryland Department of Health and Mental Hygiene. They are as follows: 3 food-related gastroenteritis and 1 presumed viral gastroenteritis
B. The Johns Hopkins Hospital. Information provided by Dr. Edward Weir, Dept. of Pathology.
Case History: A 54-year-old furnace repairman presented to his primary care physician with complaints of fever, chills, fatigue, and generalized myalgias of several days duration. He reported a sudden onset of these symptoms during one afternoon while at work. On presentation, the patient was diaphoretic, tachypnic, slow to respond, and in mild-to moderate distress. Physical examination was remarkable for a fever of 40.2 C and right-sided axillary and cervical adenopathy. He also had multiple superficial cuts and abrasions on his fingers, hands, and elbows bilaterally. Bandages on the proximal interphalangeal knuckles of the 2nd and 3rd digits of his right hand were covering erythematous, purulent, ulcerating lesions, each measuring less than 0.5cm in diameter. The patient reported the finger sores were work-related cuts that became infected. He also reported returning from a successful hunting trip 10 days prior to initial presentation.
Organism: Francisella tularensis is the causative agent of tularemia in animals and humans. F. tularensis is a very small (0.2 x 0.2 to 0.7 um), faintly staining, gram-negative coccobacillus. The organism is nonmotile and nonpiliated, is surrounded with a thin lipid capsule, and has fastidious growth requirements. Francisella species are strictly aerobic and require enriched media and incubation for a minimum of 3 days. F. tularensis is an intracellular parasite that can survive for prolonged periods in macrophages of the RES because the organism inhibits phagosome-lysosome fusion. Pathogenic strains possess an antiphagocytic capsule, and loss of the capsule is associated with decreased virulence. Like all gram-negative bacilli, this organism has an endotoxin.
Clinical Disease: The symptoms of tularemia develop abruptly after a 3- to 5-day incubation period and include fever, chills, headache, and generalized aching. The disease is classified clinically on the basis of the site of infection and the presence of skin ulcers and lymphadenopathy. The ulceroglandular form of tularemia is the most common (80%) presentation and is characterized initially by a painful skin papule at the site of inoculation associated with enlarged local lymph nodes. The papule may eventually ulcerate and necrotize. Ulcers on the upper extremities usually result from exposure to infected mammals and occur mostly on hunters and ranchers. Lesions on the lower extremities, head, and back are usually from the bite of a blood-sucking arthropod such as a tick, deerfly, or mosquito. Oculoglandular tularemia is a specialized form of the disease and results from direct contamination of the eye via exposure to contaminated fingers, aerosols, or water. The conjuctiva are usually painfully inflamed and may show numerous yellowish nodules and pinpoint ulcers. The painful preauricular adenopathy that develops is unique to tularemia and separates it from cat scratch disease, tuberculosis, sporotrichosis, and syphilis. Oropharyngeal tularemia usually manifests as painful pharyngitis in children. The buccal and pharyngeal mucosa is considered the portal of entry because the classic ulcer is frequently found there. The tonsils may enlarge and become covered with a white pseudomembrane similar to that described for diphtheria. Typhoidal tularemia is a systemic illness characterized by sepsis with multiorgan involvement. It has a mortality rate of 30 to 60% and is usually associated with a massive inoculation or a patient who is otherwise compromised. Gastrointestinal and pleuropulmonary tularemia result from consumption of contaminated food or inhalation of aerosolized organisms, respectively. When fatal cases of these forms of the disease have been autopsied, extensive ulceration throughout the bowel and respiratory mucosa has been found, suggesting a massive inoculum.
Lab Diagnosis: The detection of F. tularensis in gram-stained smears of lymph node aspirates or ulcers is almost always unsuccessful because the organism is extremely small and stains faintly. A more sensitive and specific approach is direct staining of the clinical specimen with fluorescein-labeled antibodies directed against the organism. Positive culture requires growth on a chocolate blood agar plate supplemented with cysteine. F. tularensis grows slowly and may be overlooked if the cultures are not incubated for a prolonged period. Blood cultures are generally negative for the organism, but cultures of sputum and aspirates of lymph nodes are usually positive. The organism is weakly catalase positive and oxidase negative. The results of most biochemical tests are negative, so identification is confirmed by demonstrating the bacteria's reactivity with specific antiserum. Serology results usually show a fourfold or greater rise in the titer of antibodies during the illness or a single titer of 160 or greater. However, antibodies can persist for many years making it difficult to differentiate between past and current disease.
Treatment: Streptomycin is the antibiotic of choice for all forms of tularemia. Gentamicin is an acceptable alternative. Penicillins and cephalosporins are ineffective because F. tularensis strains produce beta-lactamase. Bacteriostatic agents such as tetracycline and chloramphenicol have been used with some success but are associated with high rates of relapse. The mortality rate of tularemia is <1% in patients treated promptly with appropriate antibiotics. Live, attenuated vaccines, recommended for those at increased risk of exposure to the organism, are not completely effective in preventing disease but can lessen the severity of the disease.
References
1. Capellan J, Fong I: Tularemia from a cat bite: case report and review of feline-associated tularemia, Clin Infect Dis, 16:472-75, 1993.
2. Koneman EW, et al.: Color Atlas & Textbook of Diagnostic Microbiology. JB Lippincott Company, 4th edition, 338-40, 1992.
3. Halperin S, Gast T, and Ferrieri P: Oculoglandular syndrome caused by Francisella tularensis. Clin Pediatr, 24:520-22, 1985.