1. Name and nature of infecting organism
Francisella tularensis, a gram-negative intracellular bacterium (family Francisellaceae, order Thiotrichales, class Gammaproteobacteria), is the agent of tularaemia.
Francisella tularensis is largely distributed to the Northern hemisphere and is not normally found in the tropics or the southern hemisphere. There are currently four subspecies known: tularensis (Type A) (the most virulent and only occurring in North America), holarctica (Type B) (the most widespread), mediasiatica (present in central Asia), and novicida (the least virulent).
In Europe natural foci of tularaemia are situated in three large ecological areas: (a) boreal forest taiga; (b) temperate broadleaf and mixed forest; (c) temperate grassland and shrubland. For instance, a very typical habitat for F. tularensis is the floodplain forest-meadow ecosystem in central Europe where lagomorphs (hares, wild rabbits) and rodents are the principal vertebrate hosts, and the tick Dermacentor reticulatus is the principal enzootic vector and reservoir.
In Europe, the number of human cases is approximately 800 annually. Sweden and to a lesser extend Finland are the countries reporting the highest notification rate in the European Union/European Economic Area region. There are several European countries where tularaemia does not occur (Iceland, Ireland, United Kingdom).
2. Clinical features
The incubation period of tularaemia is usually 3–5 days but may range from 1-21 days depending on the mode of infection and the infective dose.
Tularemia is often a long and debilitating disease. Early signs of the disease are influenza-like (e.g. fever, fatigue, chills, headache). There are several clinical forms of the disease that are function of the entry route of the bacteria:
- oropharyngeal form with chronic pharyngitis, following ingestion of contaminated water or food;
- glandular and ulcero-glandular forms with local lymphadenopathy and for the latter skin inoculation ulcer; those forms follow the bacteria inoculation via arthropod vector with a primary ulcer at the infection site;
- oculo-glandular form with conjunctivitis and local lymphadenopathy, following conjunctival contamination;
- pneumonic form with lung infection following inhalation of the bacteria or systemic infection;
- typhoidal form with severe systemic symptoms; this form can be the result of any entry route of the bacteria.
A range of wild and domestic animals such as hares or rodents may function as the reservoir for tularaemia, as well as ticks.
3.2 Transmission mode
There are five routes of F. tularensis transmission to humans:
- ingestion of contaminated food or water;
- handling of infected wild or domestic animals;
- haematophagous arthropod bites (e.g. ticks, mosquitoes);
- aerosol from contaminated dust;
- accidental inoculation, ingestion or exposure to aerosol or infectious droplets in laboratory setting.
Francisella tularensis can survive for weeks in cold, moist environments including water, soil, hay, straw and decaying animal carcasses. Due to the ease of aerosolization and the very low infective dose of infection, F. tularensis has been classified as a potential biowarfare agent.
In Europe, ingestion of contaminated water from streams, ponds, lakes and rivers is the main mode of infection. Dermacentor reticulatus, Haemaphysalis concinna and Ixodes ricinus ticks are the tick species most commonly infected by F. tularensis in Europe and act as biological vectors. In Sweden and Finland, bites of infected mosquitoes, especially of the Aedes cinereus species, play a relevant role in the transmission of the bacteria. Some other blood‑sucking arthropods (e.g. deer flies) have occasionally been reported as possible mechanical carriers and vector of F. tularensis in certain wetland or floodplain habitats of northern and eastern Europe during intense epizootics. Human-to-human transmission by aerosol or via arthropods has not been documented.
3.3 Risk groups
People involved in hunting, wildlife management, hiking and camping should be aware of the different modes of transmission of the disease.
4. Prevention measures
Tularaemia is a typical zoonosis being non-transmissible from man to man.
Prevention measures consist in avoiding ingestion, breathing and inoculation of the bacteria. This includes: avoiding drinking untreated surface water; using insect repellent and clothes covering legs and arms to avoid tick and mosquito bites; avoiding contact with dead animals, using gloves when handling wild animals especially skinning of diseased hares, wild rabbits and rodents; not mowing over sick or dead animals, cooking thoroughly game meat before eating; handling biological samples potentially contaminated with F. tularensis in biosafety level-3 (BSL-3) laboratories.
There is currently no effective and safe vaccine available against F. tularensis.
As the disease is relatively rare and the symptoms non-specific, tularemia can easily be misdiagnosed.
Laboratory confirmation of tularemia consists in detecting the bacteria in a biological sample or a specific antibody response. Cultivation of the bacterium is rarely used for the diagnosis as the bacteria are slow growing and require a BSL-3 laboratory. Molecular methods (i.e. PCR) are rapid and allow identification of the subspecies. Serological methods are routinely used for diagnosis and are considered highly specific despite cross-reactions with Brucella, Yersinia, Proteus, Legionella and Mycoplasma species may occur. They usually require two samples taken a minimum of two weeks apart. Early antibiotic treatment can sometimes suppress the production of antibodies and lead to a misdiagnosis.
6. Management and treatment
The antibiotics of choice are aminoglycosides, (i.e. streptomycin or gentamicin), fluoroquinolones (i.e. ciprofloxacin) and tetracyclines (i.e. doxycycline). Most patients under treatment will recover completely but some patients, particularly those infected with the subspecies holarctica, may require a long period of convalescence.
The case fatality rate for infection with the F. tularensis subspecies tularensis is 5–15% without antibiotic treatment, and decreases to 2% with appropriate antibiotic treatment. Fatal cases due to the other F. tularensis subspecies are rare.
7. Key areas of uncertainty
A better understanding of specific variables that affect the activity of natural foci of tularaemia in Europe is needed to improve the monitoring of this disease.
Desvars A, Furberg M, Hjertqvist M, Vidman L, Sjostedt A, Ryden P, et al. Epidemiology and ecology of tularemia in Sweden, 1984-2012. Emerg Infect Dis. 2015 Jan;21(1):32-9.
Dwibedi C, Birdsell D, Lärkeryd A, Myrtennäs K, Öhrman C, Nilsson E, et al. Long-range dispersal moved Francisella tularensis into Western Europe from the East. Microb Genom. 2016 Dec 12;2(12):e000100. doi: 10.1099/mgen.0.000100
Forminska K, Zasada AA, Rastawicki W, Smietanska K, Bander D, Wawrzynowicz-Syczewska M, et al. Increasing role of arthropod bites in tularaemia transmission in Poland - case reports and diagnostic methods. Ann Agric Environ Med. 2015;22(3):443-6.
Hestvik G, Warns-Petit E, Smith LA, Fox NJ, Uhlhorn H, Artois M, et al. The status of tularemia in Europe in a one-health context: a review. Epidemiol Infect. 2015 Jul;143(10):2137-60. doi: 10.1017/S0950268814002398
Hubalek Z, Rudolf I. Francisella tularensis prevalence and load in Dermacentor reticulatus ticks in an endemic area in Central Europe. Med Vet Entomol. 2017 Jun;31(2):234-9.
Maurin M, Gyuranecz M. Tularaemia: clinical aspects in Europe. Lancet Infect Dis. 2016 Jan;16(1):113-24.
Rossow H, Ollgren J, Klemets P, Pietarinen I, Saikku J, Pekkanen E, et al. Risk factors for pneumonic and ulceroglandular tularaemia in Finland: a population-based case-control study. Epidemiol Infect. 2014 Oct;142(10):2207-16.
WHO. World Health Organization Guidelines on Tularaemia. Geneva: WHO 2007. (http://www.who.int/csr/resources/publications/WHO_CDS_EPR_2007_7.pdf?ua=1)