Tularemia is an infectious disease caused by the bacterium Francisella tularensis. It is a hardy and highly infectious organism, meaning that exposure to a very small number of the bacteria can be enough to cause disease. It primarily affects mammals, especially rodents, rabbits, and hares, but it can be transmitted to humans through a variety of environmental exposures.

Once the bacteria enter the human body, they are taken up by immune cells called macrophages. The F. tularensis bacterium is particularly adept at surviving and multiplying inside these immune cells, effectively using them as a Trojan horse to hide from the wider immune system and spread throughout the body.

• A helpful analogy is to think of the Francisella tularensis bacterium as a highly specialized secret agent designed to infiltrate a fortress (your body).
• Instead of fighting the fortress’s security guards (your immune cells) head-on, this agent has a “master key” that allows it to be willingly captured and taken inside the main security offices (the macrophages).
• Once inside, instead of being neutralized, it takes over the office, multiplies its forces, and then uses the fortress’s own internal transportation system (the lymphatic system) to travel to other critical command centers, like the lymph nodes, lungs, and spleen.
• This allows the infection to establish itself deeply within the body before a full-blown immune response is mounted, leading to the symptoms of the disease.

In my experience, tularemia often masquerades as a common flu or local skin infection until exposure history reveals a potential contact with rabbits, ticks, or contaminated water.

Tularemia is caused by infection with the bacterium Francisella tularensis. There are several subspecies of this bacterium, but the one most associated with severe disease in North America is F. tularensis subspecies tularensis (Type A). The subspecies found more commonly in Europe and Asia, F. tularensis subspecies holarctica (Type B), typically causes a milder form of the illness.

Clinically, tularemia is caused by infection with Francisella tularensis, a highly infectious, gram-negative bacterium often transmitted through tick or deer fly bites, handling infected animals, or inhaling contaminated particles.

It is very important to understand that tularemia is not spread from person to person. It is a disease that a person acquires from the environment through contact with infected animals or through the bite of an infected insect.

The bacteria are maintained in a cycle in nature between various animals and arthropod vectors. Humans become accidental hosts when they enter this cycle. The most common routes of transmission include:

• Bites from Infected Arthropods: This is a very common mode of transmission. In the United States, this includes bites from several types of ticks (such as the dog tick, the wood tick, and the lone star tick) and from the deer fly.
• Handling Infected Animals: Direct contact with the tissue or body fluids of an infected animal is another major route. This is most classically associated with skinning or dressing rabbits or hares, which is why the disease is often called “rabbit fever.” Bacteria can enter the body through small cuts or scrapes in the skin.
• Ingestion of Contaminated Food or Water: Eating undercooked meat from an infected wild animal or drinking water from a source that has been contaminated by the urine of an infected animal can cause the disease.
• Inhalation of Aerosolized Bacteria: This is a rare route of transmission in nature but is the one that causes the most severe form of the disease. It can occur when dust from contaminated soil or hay is stirred up by activities like farming or landscaping, or when handling the hide of an infected animal. Because the bacteria are so infectious when inhaled, F. tularensis is classified as a potential agent of bioterrorism.

In my experience, most patients contract tularemia through insect bites, especially from ticks, or through skin contact with infected animals like rabbits.

The signs and symptoms of tularemia can vary widely depending on how the bacteria entered the body. The incubation period is typically 3 to 5 days but can range from 1 to 14 days. The onset of illness is almost always sudden.

There are six main clinical forms of the disease:

1. Ulceroglandular Tularemia

This is the most common form, accounting for about 75% of all cases. It typically results from a tick bite or handling an infected animal.

• A skin ulcer develops at the site where the bacteria entered the body. It starts as a red papule that then ulcerates, often with a black base.
• The lymph nodes that drain that area become very swollen, tender, and painful. This is known as regional lymphadenopathy. For example, a tick bite on the arm would lead to swollen lymph nodes in the armpit.

2. Glandular Tularemia

This is similar to the ulceroglandular form but without the skin ulcer. The person has swollen and painful lymph nodes but no identifiable entry wound on the skin.

3. Oculoglandular Tularemia

This rare form occurs when the bacteria enter the body through the eye, for example, by rubbing the eyes with contaminated hands.

• It causes a very painful, red, and irritated eye (conjunctivitis).
• It is also accompanied by swelling of the lymph nodes in front of the ear.

4. Oropharyngeal Tularemia

This form results from eating or drinking contaminated food or water.

• It causes a severe sore throat (pharyngitis), mouth ulcers, and tonsillitis.
• The lymph nodes in the neck become very swollen.

5. Typhoidal Tularemia

This is a serious, systemic form of the disease where the bacteria have spread throughout the bloodstream.

• It is characterized by high fever, chills, and a general state of illness (prostration) without the localized signs of a skin ulcer or swollen lymph nodes.
• Because it lacks localizing signs, it can be very difficult to diagnose and can be mistaken for other severe illnesses like typhoid fever or sepsis.

6. Pneumonic Tularemia

This is the most severe and life-threatening form of tularemia. It can occur either primarily, from inhaling the bacteria, or secondarily, from the bacteria spreading to the lungs from another site in the body.

• It causes a severe pneumonia with symptoms of cough, chest pain, and difficulty breathing.

Clinically, I pay close attention to abrupt fever, fatigue, and localized pain following animal or arthropod exposure. The wide range of symptoms often delays diagnosis.

Because it is a rare disease with non-specific symptoms, diagnosing tularemia can be very challenging. The most important clue is the patient’s history. A doctor must have a high index of suspicion, which is usually raised by asking about recent activities and potential exposures. A history of a recent tick bite, hiking or camping in an endemic area, or contact with wild rabbits is a major red flag that should prompt a doctor to consider tularemia.

The diagnosis is confirmed with laboratory tests.

• Serology (Antibody Tests): This is the most common and safest way to confirm a diagnosis. A blood sample is tested for the presence of antibodies that the body has produced against the F. tularensis bacteria. A diagnosis is typically confirmed by showing a four-fold or greater rise in the antibody titer between a blood sample taken early in the illness and a second sample taken two to three weeks later.
• Culture: The bacteria can be grown from a sample of an ulcer, a lymph node aspirate, or other body fluids. However, F. tularensis is very difficult to grow in a standard lab and is highly infectious and dangerous for laboratory personnel. Any suspected tularemia sample must be handled with extreme care in a specialized, high-safety level laboratory.
• PCR (Polymerase Chain Reaction): This is a molecular test that can quickly detect bacteria DNA in a clinical sample.

In my experience, I’ve found that early testing is key, especially when patients present with nonhealing ulcers, lymphadenopathy, or atypical pneumonia after outdoor or animal exposure.

Tularemia is a serious bacterial infection that requires prompt treatment with antibiotics. With early and appropriate treatment, most patients make a full recovery.

Antibiotic Therapy

• First-Line Treatment: The antibiotics of choice for treating tularemia, especially severe forms, are the aminoglycosides. This includes streptomycin (given by intramuscular injection) or gentamicin (given intravenously). Treatment is typically for 10 days.
• Alternatives: For less severe cases, or once a patient is improving, oral antibiotics can be used. The most common alternatives are doxycycline and ciprofloxacin. These are typically given for 14 days.

Supportive Care

Patients with severe forms of tularemia, such as the typhoidal or pneumonic forms, will require hospitalization for IV antibiotics, IV fluids, and other supportive measures to manage the complications of the severe infection. In some cases, a large, pus-filled lymph node may need to be surgically drained.

Prevention

Prevention is focused on reducing your exposure risk in areas where the disease is present.

• Use Insect Repellent: When hiking or in wooded areas, use an insect repellent containing DEET on your skin and treat clothing with permethrin.
• Check for Ticks: After being outdoors, perform a thorough body check for ticks and remove any promptly and carefully.
• Avoid Sick or Dead Animals: Never handle sick or dead animals, especially rabbits, hares, or rodents. If you must handle them (e.g., hunters), wear gloves and protective eyewear.
• Cook Game Meat Thoroughly.
• Ensure Safe Drinking Water: Do not drink from untreated ponds, streams, or wells.

Clinically, I emphasize early antibiotic therapy. Delayed treatment can lead to prolonged illness or complications like sepsis, especially in pulmonary forms.

Tularemia is a rare but serious bacterial disease that humans can contract from tick bites or through contact with infected animals, particularly rabbits. It is a “great imitator,” capable of presenting in many different ways, from a simple skin ulcer with swollen glands to a severe, life-threatening pneumonia. Because it is so uncommon, the key to a successful outcome lies in a doctor having a high index of suspicion based on a patient’s history of outdoor or animal exposure. While the disease can be severe, it is important to remember that it is treatable. Clinically, I’ve seen that with prompt antibiotic treatment, most patients recover fully, awareness and prevention in endemic areas remain the best strategy.

Centers for Disease Control and Prevention (CDC). (2022). Tularemia. Retrieved from https://www.cdc.gov/tularemia/index.html

The World Health Organization (WHO). (2021). Tularemia. Retrieved from https://www.who.int/news-room/fact-sheets/detail/tularemia

The Merck Manual Professional Version. (2023). Tularemia. Retrieved from https://www.merckmanuals.com/professional/infectious-diseases/gram-negative-bacilli/tularemia