To the Editor—Tularemia, a potentially life-threatening zoonosis, is caused by the Gram-negative bacterium Francisella tularensis that occurs naturally in the Northern Hemisphere.Reference Hornick 1 At least 6 distinct clinical syndromes have been described, and ulceroglandular tularemia is the most frequent disease manifestation in North America and Central Europe.Reference Hestvik, Warns-Petit and Smith 2 Recently, outbreaks in the United States, Turkey, and some European countries have led to the recognition of tularemia as an emerging infectious disease.Reference Dixon 3 F. tularensis is a highly infectious agent; a quantity of just 10–25 bacteria can infect a human and cause severe clinical disease. Hence, F. tularensis is considered a ‘category A’ bioterrorism agent. Transmission may occur through inhalation of infectious aerosols, direct contact with infected animals (eg, rodents), arthropod bites, or oral ingestion of contaminated tissues or water.Reference Hornick 1 Similar to other bacterial zoonotic pathogens like Bacillus anthracis and Brucella melitensis, the causative agents of anthrax and brucellosis, respectively, person-to-person transmission of tularemia does generally not occur and infected patients do not need to be isolated. However, biological specimens from patients with tularemia may constitute a significant threat to healthcare workers. Indeed, F. tularensis ranks among the 5 most frequently reported laboratory-acquired infections, and inhalation of infectious aerosols is considered a major transmission route in these cases.Reference Singh 4 After a recent case of ulceroglandular tularemia at our hospital, we investigated the possibility of tularemia as an airborne healthcare-associated infection in the operating room.
A 48-year-old male patient presented with painless cervical swelling on the right side accompanied by occasional fever and night sweats during the preceding 2 months. The patient worked as a falconer and reported having frequent contact with raptors and other wild animals. On clinical examination, cervical lymphadenopathy was noted. Ultrasound examination and subsequent magnetic resonance imaging (MRI) showed multiple enlarged, partially necrotic lymph nodes. Infectious and neoplastic etiologies were considered, and 1 enlarged lymph node was surgically removed. Histopathology showed a phlegmonous and abscess-forming inflammation with no signs of malignancy. Culture and polymerase chain reaction (PCR) assays for bacteria, mycobacteria, and fungi were negative. The patient’s symptoms worsened despite antibiotic treatment with cefuroxime. A second surgical lymph node excision was performed 4 weeks later, showing a necrotizing granulomatous inflammation with epithelioid cell granulomas. Bacterial cultures were negative, but PCR revealed F. tularensis as the causative agent. The serology report revealed a markedly increased titer of F. tularensis-specific IgM, thus confirming the diagnosis. Antibiotic treatment with doxycycline (200 mg/day for 3 weeks) was started and led to a rapid decrease of lymphadenitis and resolution of all clinical symptoms. After the diagnosis had been established, one of the surgeons reported to the infection prevention team that he had had painful, unilateral tonsillitis some days after the first surgery. Concerns arose regarding whether the anesthesiologist, the surgeons, and the nurses involved in the 2 surgical procedures might have been at risk of acquiring tularemia through infectious aerosols. Overall, 5 healthcare workers who had close contact with the infected tissue specimens were serologically screened for tularemia 21 days after exposure, but all tested negative.
The tularemia guidelines issued by the World Health Organization (WHO) recommend monitoring the body temperature of an incidentally exposed individual for 14 days after the event and initiating post-exposure prophylaxis with ciprofloxacin or doxycycline in case of fever or any arising clinical symptoms. 5 In the case presented here, however, none of the exposed individuals reported an acute feverish illness, and all tested negative on serology 3 weeks after exposure, thus excluding tularemia.Reference Splettstoesser, Tomaso, Al Dahouk, Neubauer and Schuff-Werner 6 To minimize the risk of healthcare-associated infections, WHO recommends that clinicians report any suspicion of tularemia to the diagnostic laboratory. However, even in endemic areas, tularemia is rarely taken into account by clinicians, resulting in a low notification rate to the laboratory. Human infections with F. tularensis had never before been reported from the federal state of Germany where the patient lives (Saarland); thus, tularemia was not initially considered in the differential diagnosis.
Human-to-human transmission of tularemia has never been unambiguously documented, but a literature review concluded that aerosolized F. tularensis bacteria remain viable for prolonged time periods and may be inhaled by others.Reference Jones, Nicas, Hubbard, Sylvester and Reingold 7 Various factors need to be taken into consideration to predict the risk of infection via aerosols, ie, the actual number of viable bacterial cells within a handled specimen, the size of droplets arising from the aerosol, and the intensity of an individual’s exposure.Reference Tang, Li, Eames, Chan and Ridgway 8 While tularemia is commonly acquired via inhalation by hunters when handling infected animals, it remains to be elucidated whether this transmission route may also occur during exposure to infected human specimens. The pathogen load in human lymph nodes is probably much lower than in organs from infected rodents, and F. tularensis is mainly located inside macrophages, which might decrease the potential infectivity of human specimens. Yet, given the very low infectious dose of F. tularensis, it may be speculated that aerosols generated during surgical procedures on bacteria-containing specimens in the operating room constitute a significant risk of infection for the medical staff who are directly involved. For brucellosis, this exceptional route of transmission has recently been confirmed.Reference Mesner, Riesenberg and Biliar 9
We conclude that there is a need for an increased awareness of the various transmission routes of F. tularensis and the potentially arising implications for infection control and prevention in hospital settings. Further research is warranted to accurately assess the significance of aerosols as vectors of infectious diseases in the operating room.
Financial support. No financial support was provided relevant to this article.
Potential conflicts of interest. All authors report no conflicts of interest relevant to this article. All authors submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest, and the conflicts that the editors consider relevant to this article are disclosed here.