Francisella
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Francisella is a genus of pathogenic, Gram-negative bacteria.They are small coccobacillary or rod-shaped, non motile organisms, which are also facultative intracellular parasites of macrophages.[1] Strict aerobes, Francisella colonies bear a morphological resemblance to those of the genus Brucella.[2]
Causative Agent
- F. tularensis is found in widely diverse animal hosts and habitats and can be recovered from contaminated water, soil, and vegetation.
- A variety of small mammals, including voles, mice, water rats, squirrels, rabbits, and hares are natural reservoirs of infection.
- They acquire infection through tick, fly, and mosquito bites and by contact with contaminated environments.
- Epizootics with sometimes extensive die-offs of animal hosts may herald outbreaks of tularemia in humans.
- Humans can become incidentally infected through diverse environmental exposures: bites by infected arthropods; handling infectious animal tissues or fluids; direct contact with or ingestion of contaminated food, water, or soil; and inhalation of infective aerosols.
- Humans can develop severe and sometimes fatal illness, but do not transmit the disease to others.
Pathophysiology
The type species, F. tularensis, causes the disease tularemia or rabbit fever.[3] F. novicida and F. philomiragia (previously Yersinia philomiragia) are associated with septicemia and invasive systemic infections. It should be noted that the taxonomy of the genus is somewhat uncertain, especially in the case of F. novicida (may be a subspecies of F. tularensis). In general, identification of species is accomplished by biochemical profiling or 16S rRNA sequencing.
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.[4][5][6]
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.[7]
- 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.
Diagnosis
Laboratory Findings
Francisella can survive for several weeks in the environment; paradoxically, they can be difficult to culture and maintain in the lab.[8] Growth is slow (though increased by CO2 supplementation) and the organisms are fastidious, with most Francisella strains requiring cystine and cysteine media supplementation for growth. Growth has been successful on several media types, including chocolate agar and Thayer-Martin medias with appropriate additives as noted above. Attempted isolation on MacConkey agar is not reliable or generally successful.[3]
After 24 hours of incubation on appropriate solid media, Francisella colonies are generally small (1 to 2 mm), opaque, and white-gray to bluish-gray in color. Colonies are smooth, with clean edges and, after a 48 hours of growth, tend to have a shiny surface.
References
- ↑ Allen LA (2003). "Mechanisms of pathogenesis: evasion of killing by polymorphonuclear leukocytes". Microbes Infect. 5 (14): 1329–35. PMID 14613776.
- ↑ Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed. ed.). McGraw Hill. pp. 488&ndash, 90. ISBN 0-8385-8529-9.
- ↑ 3.0 3.1 Collins FM (1996). Pasteurella, Yersinia, and Francisella. In: Baron's Medical Microbiology (Baron S et al, eds.) (4th ed. ed.). Univ of Texas Medical Branch. ISBN 0-9631172-1-1.
- ↑ http://www.bt.cdc.gov/agent/tularemia/facts.asp
- ↑ http://www.asm.org/ASM/files/LEFTMARGINHEADERLIST/DOWNLOADFILENAME/0000000525/tularemiaprotocol%5B1%5D.pdf
- ↑ http://www.bt.cdc.gov/agent/tularemia/tularemia-biological-weapon-abstract.asp#2
- ↑ http://www.cidrap.umn.edu/cidrap/content/bt/tularemia/biofacts/tularemiafactsheet.html#_Overview_1
- ↑ Ellis J, Oyston P, Green M, Titball R (2002). "Tularemia". Clin Microbiol Rev. 15 (4): 631–46. PMID 12364373.