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Tularaemia is a zoonosis - an infection which can be spread from animals to humans to cause an acute, febrile, granulomatous infection. It is caused by the bacterium Francisella tularensis which can infect many animals, especially small rodents, rabbits and hares. F. tularensis is very infectious and requires as few as ten organisms to initiate human infection.
Attempts have been made to develop tularaemia for biological warfare and these have focused on the airborne dispersal route.
- F. tularensis is distributed across the Northern Hemisphere.
- There are two types of the bacterium, both of which can infect humans:
- Type A infections occur naturally only in North America. Type A infects animals and ticks and can be fatal in humans.
- Type B causes milder symptoms than type A and does not cause fatal infections. Type B occurs in animals throughout the northern hemisphere, including North America.
- In Europe, the number of human cases is approximately 1,200 each year.
- Countries with the highest incidence rates in Europe include Finland, Sweden, Hungary, the Slovak Republic, Serbia, Montenegro, the Czech Republic and Bulgaria.
- In Europe, tularaemia has not occurred in Iceland, Ireland or Great Britain. There are some countries where the disease has not been reported, although probably does occur, including Albania, Greece, Romania, Belgium, Luxembourg and Portugal.
- Tularaemia is primarily a disease of a wide variety of wild mammals and birds. Humans become infected mainly:
- Through the bite of arthropods, particularly ticks and mosquitoes.
- Through the skin, conjunctival sac or oropharyngeal mucosa, by direct contact with infected animals or animal materials.
- By ingestion of contaminated food or water or inhalation of contaminated dust or aerosols.
- F. tularensis is easily transmitted by aerosols and inhalation of only a few organisms is likely to cause infection. Person-to-person transmission has not been documented.
There are six well-recognised clinical forms:
- Approximately 80% of cases.
- Infection is usually via a scratch or abrasion which causes an ulcerated skin lesion at the site of entry and is associated with painful regional lymphadenopathy.
Similar to the ulceroglandular form except for the absence of the characteristic skin lesion.
- Accounts for 1-2% of patients.
- The organism enters via the conjunctivae, causing a unilateral, painful, purulent conjunctivitis with submandibular, preauricular, and cervical lymphadenopathy.
- This is a rare form; infection occurs from eating poorly cooked meat of an infected rabbit.
- It usually presents with a sore throat (pharyngotonsillitis with regional adenopathy), abdominal pain (mesenteric lymphadenopathy), nausea, vomiting, diarrhoea and occasionally frank gastrointestinal bleeding from intestinal ulcerations.
- Primary lung infection is rarely acquired naturally but may develop in laboratory workers.
- However, pneumonia may develop after haematogenous spread in 10-15% of patients with ulceroglandular tularaemia and in 30-80% of those with typhoidal tularaemia.
- It usually presents with a dry cough, dyspnoea and pleuritic chest pain.
- Chest examination may be normal.
- Lobar pneumonia and/or adult respiratory distress syndrome may develop.
Typhoidal (septicaemic) tularaemia
- This accounts for 10-15% of tularaemia cases.
- It is more severe and patients present with fever, chills, myalgia, malaise and weight loss.
- Those affected often have pneumonia. Ulcers and lymphadenopathy are usually absent.
Other possible manifestations
These include acute kidney injury, abnormal LFTs, and rhabdomyolysis.
These include osteomyelitis, pericarditis, peritonitis, endocarditis, and meningitis.
Symptoms usually develop 2-5 days after infection but the incubation period can be as short as one day or as long as three weeks. Natural infection can result in a variety of symptoms:
- Ulcers: these are common and occur either at the site of an infected insect bite, or sometimes on the surface of the eye following exposure to airborne bacteria. The ulcers may be accompanied by swollen lymph nodes, general aches and fevers.
- Sore throat, pharyngitis or tonsillitis: after consumption of contaminated food or water.
- Less commonly, acute flu-like illness, often with diarrhoea and vomiting, can occur following inhalation or ingestion of bacteria.
- Pneumonia and blood poisoning: these are the most serious (and least common) natural forms of the disease (but the most likely to occur following deliberate airborne release). Symptoms would include sudden onset of high fever, chills, muscle aches, dry cough and weakness.
- Rash: as many as 20% of patients may have a blotchy, macular, maculopapular, or pustular rash.
- Patients have fever and possibly tender hepatosplenomegaly.
- Otherwise, physical findings vary with the clinical form of disease presentation.
- Similar bioterrorism agents such as plague, pulmonary anthrax or Q fever.
- Tick-borne diseases - eg, Colorado tick fever.
- Systemic fungal infections.
- Blood tests show abnormal LFTs in approximately half of all patients.
- Diagnosis is usually based on serology: detection by polymerase chain reaction allows early diagnosis. Tularaemia serology tests may cross-react with Salmonella, Brucella, Yersinia and Legionella species.
- F. tularensis can be isolated from blood, biopsy samples, or other bodily fluids and tissues. A specific culture medium is required to grow this organism in the laboratory.
- F. tularensis is highly infectious to laboratory staff, so infection control precautions are required.
- Skin testing may detect a cellular immune response and is both sensitive and specific (but skin test antigens are not commercially available).
- Symptomatic and supportive care for accompanying conditions (eg, osteomyelitis, pericarditis, peritonitis) as clinically indicated.
- Antibiotic eradication: recommended treatment for tularaemia is either a ten-day course of streptomycin (drug of choice) or gentamicin.
- Other antibiotics used to treat tularaemia include doxycycline, and ciprofloxacin .
- Lung abscess
- Respiratory failure
- Acute kidney injury
- Type B generally causes a milder illness, which can occasionally be symptom-free.
- Type A causes more severe disease, causing death in 5-7% of untreated patients.
- Although symptoms may last for several weeks, most patients who receive appropriate treatment recover completely.
- Prevention of naturally occurring disease depends largely on:
- Avoiding tick bites: wear trousers and long-sleeved shirts; use tick repellents and frequent inspection for evidence of ticks. Remove ticks promptly but take care not to squeeze the body because tick secretions may be infectious.
- Wear gloves when exposure to dead or wild animals is necessary (eg, skinning or eviscerating a rabbit carcass).
- Wild animal meats must be cooked thoroughly before consumption.
- Frequent and thorough hand washing is also advised.
- Streptomycin, gentamicin, doxycycline or ciprofloxacin are recommended for post-exposure prophylaxis and must be taken for at least 14 days.
- A vaccine could be the most efficient way to prevent infection in the event of bioterrorism but an officially approved vaccine with both efficacy and safety has not yet been developed.
Further reading and references
Zoonotic diseases (zoonoses): guidance, data and analysis; Public Health England
Bossi P, Tegnell A, Baka A, et al; Bichat guidelines for the clinical management of tularaemia and bioterrorism-related tularaemia. Euro Surveill. 2004 Dec 159(12):E9-10.
Pohanka M, Skladal P; Bacillus anthracis, Francisella tularensis and Yersinia pestis. The most important bacterial warfare agents - review. Folia Microbiol (Praha). 200954(4):263-72. doi: 10.1007/s12223-009-0046-1. Epub 2009 Oct 14.
Gurcan S; Epidemiology of tularemia. Balkan Med J. 2014 Mar31(1):3-10. doi: 10.5152/balkanmedj.2014.13117. Epub 2014 Mar 1.
Tularaemia; World Health Organization
Tarnvik A, Berglund L; Tularaemia. Eur Respir J. 2003 Feb21(2):361-73.
Tularaemia; DermNet NZ
Johansson A, Forsman M, Sjostedt A; The development of tools for diagnosis of tularemia and typing of Francisella tularensis. APMIS. 2004 Nov-Dec112(11-12):898-907.
Generali JA, Cada DJ; Ciprofloxacin: Tularemia (Adults). Hosp Pharm. 2015 Apr50(4):274-6. doi: 10.1310/hpj5004-274. Epub 2015 Apr 8.
Hong KJ, Park PG, Seo SH, et al; Current status of vaccine development for tularemia preparedness. Clin Exp Vaccine Res. 2013 Jan2(1):34-9. doi: 10.7774/cevr.2013.2.1.34. Epub 2013 Jan 15.