Tularemia: causes, symptoms, diagnosis, treatment, prognosis, and prevention

Tularemia, also known as deer fly fever, deer fly disease, deer fly malady, Pahvant Valley fever, Pahvant Valley plague, rabbit fever, tularaemia, or Ohara disease, is an acute febrile infection caused by Francisella tularensis and is a natural focal zoonosis predominantly affecting rodents and rabbits. The main clinical symptoms are fever, skin ulcers, local lymphadenopathy, conjunctival congestion, inflammation of the respiratory and digestive tract, and septicemia.


Francisella tularensis is a short asporogenic Gram-negative coccobacillus parasitizing in the mononuclear phagocytes of humans and animals. The bacterium has strong ability to survive in water, can survive in tap water or well water at 13 - 17 °C for 3 months, survive in water at 4 °C for more than 5 months, and can withstand low temperatures of -30 °C. The bacterium can survive for 3 months in frozen meat and 1 month in bacon. The physical sterilization effect can be achieved by direct sunlight for 30 minutes, heating at 56 °C for 30 minutes, or heating at 60 °C for 10 to 20 minutes. The bacterium is sensitive to disinfectants, and can be killed in 0.1% sublimate solution or 1% saponated cresol solution for 30 seconds.

According to the virulence of the bacterium strain to rabbits and the ability to decompose glycerol, the known bacterium strains around the world are divided into three geographical variants: Franicisellatularensis nearctica that can decompose glycerol and has strong virulence, Franicisellatularensis palaearctica that can merely decompose glycerol and has weak virulence, and Franicisellatularensis mediaasiatica that can decompose glycerol but has weak virulence.

Source of infection includes mammals, contaminated water sources, haystacks, animal fur, and prey, as well as vectors such as ticks and horseflies, mostly wild rabbits and rodents.

The disease has a variety of modes of transmission. The breached skin directly exposing to the prey with bacteria, the process of stripping and processing the fur and meat, agricultural activities such as transporting grass, moving stacks, and threshing, ingestion of semi-cooked meat and contaminated raw water, contact with contaminated water, and inhalation of infectious aerosols can cause infection. Infections caused by bloodsucking bites of arthropods such as ticks and horseflies are also common. Routes of infection that the bacteria invade humans include skin, oral and ocular mucosa, respiratory tract, and digestive tract.


After the pathogen invades the human body through the skin or mucous membrane, most patients can develop localized primary ulcers. The bacteria reach the local lymph nodes along the lymphatic vessels, causing inflammatory reactions, resulting in swollen lymph nodes. Some bacteria are engulfed by phagocytic cells, and other bacteria invade the blood circulation, causing bacteremia. The bacteria disseminate to various organs along with blood circulation, causing a series of lesions in organs such as heart, liver, lung, spleen, and kidney. Ulcers occur in the invaded local skin, and caseous necrosis may be present if the deep tissue is involved. Polymorphonuclear leukocytes and epithelioid cells usually aggregate around the ulcer, and the bacteria can be detected in monocytes, macrophagocytes, and polymorphonuclear leukocytes by fluorescent antibody staining. Deep and shallow lymph nodes connected to the ulcers are mostly invaded and are with focal necrosis and suppuration, but paradenitis is absent. Pulmonary lesions present with parenchymal lesions and fusion of focal subpleural necrosis, and abscess can occur. The liver, spleen, and adrenal glands may be swollen. Granuloma can occur in many organs such as the throat, esophagus, stomach, colon, ileum, appendix, kidney, adrenal gland, pericardium, brain, meninges, and bone marrow. Occasionally, central necrosis or suppuration can occur.

Signs and Symptoms

The incubation period is usually 1 week, as short as only few hours, as long as 2 - 3 weeks.

Sudden onset is present, the body temperature rises rapidly to 39 - 40 °C, and general malaise, chills, headache, back pain, and generalized muscle pain are present, progressing into systemic symptoms such as deliration, lethargy, and dysphoria. Hyperthermia lasts for 2 - 5 days, and then slowly drops. Local lymph nodes in the site of bacterial invasion may be painful, and primary lesions occur mostly in the hands or fingers within 2 days. Initial skin lesions are red papules, developing into pustules, forming central necrosis after rupture, evolving into ulcers with hard edges. The enlarged local lymph nodes can also rupture. The course of the disease is usually 3 - 4 weeks, and the recovery period is about 2 - 3 months or longer.

There are different types of tularemia with various symptoms and signs.

Ulceroglandular tularemia is the most common tularemia, often in the fingers and neck, and is infected by contact with tissues or body fluids of infected animals. Primary papules or nodules occur at the site of infection and rapidly rupture, forming painless ulcers, with hard edges, persisting for about 6 weeks, leaving scars after healing. In the cases of transmission by tick and deer fly bites, primary lesions are usually in the legs or perineum. Lymphangitis spreads outward from the primary lesion, and local lymph nodes are swollen and painful and tend to rupture, forming subcutaneous suppurative nodules, resembling sporotrichosis. During the course of the disease, other skin lesions are visible, but are not characteristic. Other skin lesions include macules, papules, vesicles, and petechiae.

Glandular tularemia is also common. Although the bacteria mostly invade the skin, there is no primary lesion in the skin. Lymphadenopathy and fever are usually present, and systemic symptoms are generally mild.

Oculoglandular tularemia is caused by invasion of the conjunctiva. Symptoms include conjunctivitis, local obvious contestation, palpebral edema, photophobia, epiphora, and amblyopia. In severe cases, keratohelcosis is present and can lead to blindness. Preauricular glands and cervical lymph nodes may be swollen.

Oropharyngeal tularemia is characterized by exudative pharyngitis, pseudomembrane and pus on the tonsils, cervical lymph nodes enlargement, dysphagia, and high fever. In severe cases, tracheal obstruction can result in death, more common in children.

Intestinal tularemia often occurs suddenly and is characterized by hyperthermia, spasmodic colic, and watery diarrhea. Occasionally, peritonitis, hematemesis, and melena can occur.

Pneumonic tularemia is caused by the inhalation of dust from the respiratory tract or hematogenous infections. Dry cough and substernal pain are present, and septic shock may occur. X-ray examination reveals increased lung markings or infiltrating lesions, occasionally pulmonary abscess and cavitation, often accompanied by pleural involvement and hilar lymphadenopathy.

Typhoidal tularemia usually has no primary lesion and local lymphadenopathy. The bacteria enter the bloodstream and cause sepsis, so the systemic symptoms are serious, resembling typhoid fever clinically. Sometimes, severe pleural and pulmonary infection and diarrhea may occur. The mortality can reach 30% if untreated.


According to a history of contact with rabbits, wild rodents, or arthropod vectors, sudden onset, and characteristic primary lesions, the disease can be considered.

Specific fluorescent antibodies found in the exudate smear in the fluorescent staining can assist in the definitive diagnosis. The pathogenic bacteria can be cultured in the blood dextrose cystine agar medium or other selective medium. Agglutination test is a reliable diagnostic method. After 2 weeks of illness, the agglutination titer in most patients is elevated. If the titer is elevated fourfold, definitive diagnosis can be provided.


For moderate to severe infections, treatment regimen is streptomycin 1g intramuscularly once every 12 hours in adults and 15mg/kg intramuscularly once every 12 hours in children for 7 - 10 days.

If meningitis is present, chloramphenicol 12.5 - 25mg/kg intravenously once every 6 hours or doxycycline 100mg twice daily for 14 - 21 days is added.

Alternatives to streptomycin as follows:

  • Gentamicin 1 - 2mg/kg IM or IV q8h for moderate to severe infection
  • Doxycycline 100mg PO q12h for mild infection
  • Chloramphenicol 12.5 - 25mg/kg IV q6h for only meningitis
  • Ciprofloxacin 500mg PO q12h for mild infection

In the case of large-scale casualties, oral administration of doxycycline or ciprofloxacin may be given to adults and children if intravenous administration is not possible. However, recurrences are occasionally present and lymph node suppuration can be prevented.

Continuous wet compress with saline gauze is beneficial for primary skin lesions and can reduce the severity of lymphangitis and lymphadenitis. Drainage may be necessary in large abscesses, but unless treatment is delayed, there is very little need for drainage.

For ocular tularemia, wet compress with warm saline gauze and dark glasses can alleviate symptoms. In severe cases, 2% homatropine eye drops once every 4 hours can relieve symptoms.

For severe headache, oral painkillers such as oxycodone and hydrocodone can be administered.


The duration is 3 - 4 weeks, and the recovery period is 2 months or longer. Patients can acquire persistent immunity after healing. Oculoglandular tularemia may cause blindness, oropharyngeal tularemia can cause tracheal obstruction, resulting in death, and the mortality rate is as high as 30% in typhoidal tularemia.


When entering the epidemic area, protective clothes and insect repellents are necessary, and prevention of bites of ticks or flies is important.

When processing rabbits and rodents, especially in endemic areas, protective clothes, including rubber gloves and face masks, should be worn. Wild birds and prey must be thoroughly cooked before ingestion.

Water that may be contaminated must be disinfected before use.

There are currently no vaccines available. Oral doxycycline or ciprofloxacin for 14 days is recommended for high risk post-exposure prophylaxis.