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Background
Francisella tularensis is the agent of tularemia, a serious and occasionally fatal disease of humans and animals. For centuries, this disease was known primarily to veterenarians, animal handlers, and hunters. With the increased attention to bio-terrorism, concern has been raised that this bacteria could be used as an agent of terror.
Ulceroglandular tularemia is the most common form of the disease and is usually a consequence of a bite from an arthropod vector which has previously fed on an infected animal. The pneumonic form of the disease is rarer but has gained noteriety as the form of the disease that may surface as a result of a bioterrorism attack.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION EPIDEMIOLOGIC ASSOCIATIONS JAPAN Clinical manifestations of tularemia in Japan--analysis of 1,355 cases observed between 1924 and 1987.
Ohara Y, Sato T, Fujita H, Ueno T, Homma M.
Dept. of Neurological Sciences, Tohoku University School of Medicine, Sendai, Japan.
Infection. 1991 Jan-Feb;19(1):14-7. Abstract quote
A total of 1,355 cases of tularemia observed between 1924 and 1987 in Japan were viewed on the basis of clinical manifestations and the results were compared with those in the United States. The incubation period varied from one day to over one month.
In 75.5% of cases, the symptoms of illness appeared within seven days with the peak on the third day. A sudden onset of flu-like symptoms was generally observed, and 92% of cases was followed by regional lymph node swelling which mostly appeared in axillary and cubital regions. They were observed predominantly at the left rather than the right side.
In contrast with the cases in the United States, the number of cases of ulceroglandular type in Japan was only one third of those of glandular type. None of the pleuropulmonary cases or fatal tularemia have been reported in Japan. The number of oropharyngeal cases has remarkably increased after World War II, and is still on the rise, presumably because of the change of dietary habits in Japan.
All these characteristics of Japanese tularemia are assumed to be caused by low virulence of Japanese strains of Francisella tularensis.
LABORATORY/
RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC LABORATORY MARKERS PCR
Detection of Francisella tularensis in ulcers of patients with tularemia by PCR.
Sjostedt A, Eriksson U, Berglund L, Tarnvik A.
Department of Microbiology, National Defence Research Establishment, Umea, Sweden.
J Clin Microbiol. 1997 May;35(5):1045-8. Abstract quote
The diagnosis of human cases of tularemia is usually confirmed by the demonstration of an antibody response to Francisella tularensis, which occurs about 2 weeks after the onset of disease.
Due to a high risk of infection in the laboratory, cultivation of the causative agent tends to be avoided. During an outbreak in Sweden, the use of PCR for diagnosing the ulceroglandular form of tularemia was evaluated. Extraction and preparation of F. tularensis DNA from swab samples from the wounds of patients with tularemia involved the use of the nuclease inhibitor guanidine thiocyanate. The DNA was detected by multiplex PCR targeting the 16S rRNA gene and a 17-kDa lipoprotein gene of F. tularensis. In 29 of 40 (73%) patients with serologically confirmed tularemia, F. tularensis DNA was successfully amplified.
Considering the limitations of current diagnostic procedures, PCR may become useful for the early diagnosis of tularemia.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL
Tularemia.
Ellis J, Oyston PC, Green M, Titball RW.
Defence Science and Technology Laboratory, CBS Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom.
Clin Microbiol Rev. 2002 Oct;15(4):631-46. Abstract quote
Francisella tularensis is the etiological agent of tularemia, a serious and occasionally fatal disease of humans and animals. In humans, ulceroglandular tularemia is the most common form of the disease and is usually a consequence of a bite from an arthropod vector which has previously fed on an infected animal. The pneumonic form of the disease occurs rarely but is the likely form of the disease should this bacterium be used as a bioterrorism agent.
The diagnosis of disease is not straightforward. F. tularensis is difficult to culture, and the handling of this bacterium poses a significant risk of infection to laboratory personnel. Enzyme-linked immunosorbent assay- and PCR-based methods have been used to detect bacteria in clinical samples, but these methods have not been adequately evaluated for the diagnosis of pneumonic tularemia. Little is known about the virulence mechanisms of F. tularensis, though there is a large body of evidence indicating that it is an intracellular pathogen, surviving mainly in macrophages. An unlicensed live attenuated vaccine is available, which does appear to offer protection against ulceroglandular and pneumonic tularemia. Although an improved vaccine against tularemia is highly desirable, attempts to devise such a vaccine have been limited by the inability to construct defined allelic replacement mutants and by the lack of information on the mechanisms of virulence of F. tularensis.
In the absence of a licensed vaccine, aminoglycoside antibiotics play a key role in the prevention and treatment of tularemia.
Tularemia as a biological weapon: medical and public health management.
Dennis DT, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Friedlander AM, Hauer J, Layton M, Lillibridge SR, McDade JE, Osterholm MT, O'Toole T, Parker G, Perl TM, Russell PK, Tonat K; Working Group on Civilian Biodefense.
Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, PO Box 2087, Fort Collins, CO 80522, USA
JAMA. 2001 Jun 6;285(21):2763-73. Abstract quote
OBJECTIVE: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals if tularemia is used as a biological weapon against a civilian population.
PARTICIPANTS: The working group included 25 representatives from academic medical centers, civilian and military governmental agencies, and other public health and emergency management institutions and agencies.
EVIDENCE: MEDLINE databases were searched from January 1966 to October 2000, using the Medical Subject Headings Francisella tularensis, Pasteurella tularensis, biological weapon, biological terrorism, bioterrorism, biological warfare, and biowarfare. Review of these references led to identification of relevant materials published prior to 1966. In addition, participants identified other references and sources.
CONSENSUS PROCESS: Three formal drafts of the statement that synthesized information obtained in the formal evidence-gathering process were reviewed by members of the working group. Consensus was achieved on the final draft.
CONCLUSIONS: A weapon using airborne tularemia would likely result 3 to 5 days later in an outbreak of acute, undifferentiated febrile illness with incipient pneumonia, pleuritis, and hilar lymphadenopathy. Specific epidemiological, clinical, and microbiological findings should lead to early suspicion of intentional tularemia in an alert health system; laboratory confirmation of agent could be delayed. Without treatment, the clinical course could progress to respiratory failure, shock, and death. Prompt treatment with streptomycin, gentamicin, doxycycline, or ciprofloxacin is recommended. Prophylactic use of doxycycline or ciprofloxacin may be useful in the early postexposure period.VARIANTS HEAD AND NECK Tularemia of the head and neck: a possible sign of bioterrorism.
Stupak HD, Scheuller MC, Schindler DN, Ellison DE.
Department of Otolaryngology-Head and Neck Surgery, University of California, 400 Parnassus Ave., Suite A717, San Francisco, CA 94143, USA
Ear Nose Throat J. 2003 Apr;82(4):263-5. Abstract quote
Recent bioterror attacks and other world events have focused the medical community's attention on agents that might be used in biological warfare. One of these potential biological weapons is Francisella tularensis, a gramnegative coccobacillus that is one of the most infectious bacteria known. F tularensis can cause severe, even fatal, systemic tularemia.
Under normal circumstances, F tularensis is transmitted by infected ticks, insects, and other animals. As a weapon of terrorism, the bacterium would likely be disseminated as an aerosol and contracted by inhalation. Because many cases of tularemia are characterized by head and neck symptoms, otolaryngologists should be familiar with the diagnosis and management of this disease.
In this article, we describe a case of zoonotic tularemia that manifested as a neck mass, and we review the pathophysiology, diagnosis, and treatment of tularemia. We also summarize what is known about its potential as a biological weapon.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Histologic and molecular diagnosis of tularemia: a potential bioterrorism agent endemic to North America.
Lamps LW, Havens JM, Sjostedt A, Page DL, Scott MA.
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Mod Pathol. 2004 May;17(5):489-95. Abstract quote
Francisella tularensis (FT), a zoonotic bacterium that causes tularemia, has received attention as a possible bioterrorism threat.
We developed a PCR assay for use in fixed, processed tissues, which are safer to handle and allow archival testing. PCR analysis for a 211-bp fragment of the FT lipoprotein gene was performed on tissues from 16 cases of tularemia. In all, 14/15 cases with intact DNA (93%) were positive for FT by PCR. Frequent histologic findings in PCR-positive tissues included irregular microabscesses and granulomas in liver, spleen, kidney, and lymph nodes, and necrotizing pneumonia.
Unusual cases featuring suppurative leptomeningitis and gastrointestinal ulcers were also seen.
As this disease is endemic in North America, and has been identified as a potential bioterroristic threat, awareness of the clinicopathologic spectrum of disease and available detection methods is increasingly important. This PCR assay, the first designed for use in processed tissues, is an excellent method for diagnosis of tularemia.
TREATMENT CHARACTERIZATION GENERAL ANTIBIOTICS Prompt treatment with streptomycin, gentamicin, doxycycline, or ciprofloxacin is recommended. Prophylactic use of doxycycline or ciprofloxacin may be useful in the early postexposure period. VACCINE Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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