Tularemia (Rabbit Fever): Symptoms, Causes & Treatment

What Is Tularemia and How Do You Get It?

Tularemia is a bacterial infection caused by Francisella tularensis, a highly infectious organism found in small mammals, particularly rabbits and rodents. You can contract tularemia through tick or deer fly bites, handling infected animals, drinking contaminated water, or inhaling contaminated dust or aerosols. The disease is also called rabbit fever or deer fly fever.

Tularemia is a zoonotic disease, meaning it primarily affects animals and can spread to humans under certain circumstances. The bacterium Francisella tularensis is remarkably infectious - as few as 10 to 25 organisms can cause disease in humans, making it one of the most infectious bacterial pathogens known to science. This extreme infectivity is one reason why it has been classified as a Category A bioterrorism agent by the Centers for Disease Control and Prevention (CDC).

The disease occurs throughout the Northern Hemisphere, including North America, Europe, and parts of Asia. In the United States, naturally occurring infections have been reported from all states except Hawaii. The highest incidence occurs in the south-central states, particularly Arkansas, Missouri, Oklahoma, and Kansas. Globally, certain regions of Scandinavia, Japan, and Russia also report significant numbers of cases.

There are two main subspecies of Francisella tularensis that cause disease in humans. Type A (subspecies tularensis) is found primarily in North America and causes more severe illness with higher mortality rates. Type B (subspecies holarctica) occurs across Europe and Asia and typically produces milder disease. Understanding these geographic patterns helps clinicians predict disease severity and guides treatment decisions.

How Tularemia Spreads to Humans

The routes of transmission for tularemia are diverse, and understanding them is crucial for both prevention and diagnosis. The method of infection often determines which clinical form of the disease develops, making exposure history essential for medical evaluation.

Arthropod bites represent one of the most common transmission routes, particularly in endemic areas. Ticks (especially the dog tick, wood tick, and Lone Star tick) and deer flies can transmit the bacteria when they feed on humans after previously biting infected animals. The bite creates an entry point for bacteria, often leading to the ulceroglandular form of tularemia with a characteristic skin ulcer at the bite site.

Direct contact with infected animals accounts for many cases, particularly among hunters, trappers, and those who handle wildlife. Rabbits, hares, and rodents are especially susceptible to tularemia and often die in large numbers during outbreaks. Handling infected carcasses, skinning animals, or cleaning game can allow bacteria to enter through small cuts or abrasions in the skin. Even intact skin may not provide complete protection against this highly infectious organism.

Ingestion of contaminated water or food can cause oropharyngeal or gastrointestinal tularemia. Drinking untreated water from streams, ponds, or wells that have been contaminated by infected animals poses a significant risk. Eating undercooked meat from infected animals can also transmit the disease. These routes of infection tend to affect the throat, tonsils, and gastrointestinal tract.

Inhalation of contaminated aerosols or dust can lead to pneumonic tularemia, the most severe form of the disease. This can occur during activities that disturb environments where infected animals have died or left excrement, such as mowing lawns, handling hay, or agricultural work. Laboratory workers handling F. tularensis cultures are also at risk of respiratory infection. Pneumonic tularemia carries the highest mortality rate among all forms of the disease.

Who Is at Risk for Tularemia?

While anyone can contract tularemia given the right exposure circumstances, certain groups face elevated risk due to their occupations or activities. Understanding these risk factors helps target prevention efforts and increases clinical suspicion when evaluating patients with compatible symptoms.

Hunters and trappers have frequent contact with wild animals, particularly rabbits and rodents that serve as primary reservoirs for F. tularensis. The process of field dressing game creates numerous opportunities for skin exposure to infected tissues and blood. Studies have shown that hunters in endemic areas have higher rates of antibodies to tularemia, indicating past exposure even without recognized clinical illness.

Agricultural workers and landscapers face risk through environmental exposure. Activities like mowing, brush cutting, or handling hay can aerosolize bacteria from contaminated soil or decomposing animal carcasses. Farmers in endemic regions may encounter infected rodents in barns, grain storage facilities, or fields.

Laboratory personnel working with F. tularensis require strict biosafety precautions. The organism's high infectivity means that even brief, minor exposures during routine laboratory procedures can cause infection. Historically, laboratory-acquired infections were common before modern biosafety protocols were established.

Veterinarians and wildlife biologists who work with wild animals, particularly during disease outbreaks in animal populations, may encounter infected specimens. Proper personal protective equipment and awareness of tularemia's presence in local wildlife populations are essential safeguards for these professionals.

What Are the Symptoms of Tularemia?

Tularemia symptoms typically appear 3-5 days after exposure and include sudden high fever (up to 104°F/40°C), severe headache, chills, muscle aches, and profound fatigue. Additional symptoms depend on how you were infected: skin ulcers with swollen lymph nodes (ulceroglandular), eye inflammation (oculoglandular), sore throat (oropharyngeal), cough and chest pain (pneumonic), or widespread systemic illness (typhoidal).

The clinical presentation of tularemia varies considerably depending on the route of infection, the dose of bacteria, and the subspecies involved. However, nearly all forms share certain early symptoms that reflect the body's systemic response to infection. Recognizing these symptoms and connecting them to potential exposures is crucial for early diagnosis and treatment.

The incubation period - the time between exposure and symptom onset - typically ranges from 3 to 5 days but can extend from 1 to 21 days. During this time, the bacteria multiply at the site of entry and begin spreading through the lymphatic system. Patients often feel completely well during incubation, then experience sudden, dramatic onset of illness.

Fever is the hallmark symptom of tularemia, occurring in virtually all patients. The fever typically rises rapidly, often reaching 104°F (40°C) or higher. Patients frequently describe feeling fine one moment and severely ill the next. The fever pattern may be continuous or may fluctuate, with chills and drenching sweats occurring cyclically.

Headache accompanies fever in most patients and is often described as severe and persistent. The headache may be frontal, generalized, or throbbing in character. Pain medication may provide only partial relief until specific antibiotic treatment begins.

Fatigue and malaise are typically profound, far exceeding what patients expect from ordinary infections. Many patients report complete exhaustion, difficulty performing even basic activities, and a general sense of being very unwell. This severe fatigue may persist for weeks or months even after successful treatment.

Muscle aches (myalgia) affect many patients and may be generalized or localized to the back and legs. Joint pain (arthralgia) can also occur. These symptoms contribute to the overall sense of illness and may be mistaken for influenza in early stages.

The Six Clinical Forms of Tularemia

Medical professionals classify tularemia into six distinct clinical forms based on the primary site of infection and symptom pattern. Understanding these forms helps guide diagnostic testing and provides insight into the likely route of exposure.

Ulceroglandular Tularemia

Ulceroglandular tularemia is the most common form, accounting for approximately 75% of all cases. It typically develops after a tick or deer fly bite or through handling of infected animals. The characteristic presentation includes both a skin ulcer at the site of bacterial entry and enlargement of regional lymph nodes.

The skin lesion begins as a painful, red papule (bump) at the site where bacteria entered the body. Over several days, this evolves into a pustule, then breaks down to form an ulcer with raised, sharply defined edges. The ulcer base is typically covered with a dark eschar (scab) and may drain pus or clear fluid. Without treatment, these ulcers can persist for weeks or months.

Regional lymphadenopathy (swollen lymph nodes) accompanies the skin ulcer and represents the spread of bacteria through lymphatic channels. The affected nodes become markedly enlarged, often reaching several centimeters in diameter. They may be exquisitely tender and can eventually suppurate (fill with pus), sometimes requiring surgical drainage.

Pneumonic Tularemia

Pneumonic tularemia represents the most serious form of the disease, with mortality rates of 30-60% without treatment. It can result from primary inhalation of contaminated aerosols or as a secondary complication when bacteria spread to the lungs through the bloodstream from another site of infection.

Symptoms of pneumonic tularemia include cough (which may be dry or productive), chest pain, and progressive difficulty breathing. Chest X-rays typically show bilateral pneumonia, often with pleural effusions (fluid around the lungs). Patients may deteriorate rapidly, developing acute respiratory distress syndrome (ARDS) if treatment is delayed.

How Is Tularemia Diagnosed?

Tularemia is diagnosed through a combination of clinical evaluation, exposure history, and laboratory tests. Serologic testing (blood tests for antibodies) is most commonly used, with initial titers greater than 1:160 or a four-fold rise between acute and convalescent samples confirming diagnosis. Blood cultures and PCR testing can also identify the bacteria directly, though these require specialized laboratory facilities.

Diagnosing tularemia requires a high index of clinical suspicion because its symptoms overlap with many other infectious and non-infectious conditions. Healthcare providers must actively consider tularemia when evaluating patients with compatible symptoms and relevant exposure histories, particularly in endemic areas or during known outbreaks.

The clinical history provides crucial diagnostic clues. Physicians will ask detailed questions about recent outdoor activities, animal contact, tick bites, water sources, and occupational exposures. A history of hunting, trapping, or handling wild animals in the weeks preceding illness onset significantly increases the probability of tularemia. Geographic location and time of year also inform diagnostic considerations.

Physical examination focuses on identifying the characteristic findings of different tularemia forms. For ulceroglandular disease, careful inspection of the skin for ulcers and palpation of lymph nodes are essential. Eye examination may reveal conjunctivitis in oculoglandular cases. Throat examination can identify the exudative pharyngitis and tonsillar enlargement of oropharyngeal tularemia. Lung examination and chest imaging are critical for suspected pneumonic cases.

Laboratory Testing for Tularemia

Serologic testing remains the most widely used method for confirming tularemia diagnosis. These blood tests detect antibodies produced by the immune system in response to F. tularensis infection. A single serum sample showing an antibody titer of 1:160 or higher suggests tularemia, but definitive diagnosis typically requires demonstrating a four-fold rise in antibody levels between acute (early illness) and convalescent (2-4 weeks later) samples.

An important limitation of serologic testing is that antibodies may not be detectable early in the illness. During the first week of symptoms, antibody levels may be too low to measure, potentially leading to false-negative results. For this reason, negative early serologic tests do not exclude tularemia, and repeat testing is often necessary.

Culture of F. tularensis from blood, lymph node aspirates, wound drainage, sputum, or other clinical specimens provides definitive diagnosis. However, the organism is difficult to grow, requiring specialized media and extended incubation periods. More importantly, F. tularensis poses significant biosafety risks to laboratory workers, so cultures must be handled in biosafety level 3 (BSL-3) facilities. Many clinical laboratories are not equipped for this level of containment.

Polymerase chain reaction (PCR) testing can detect F. tularensis DNA in clinical specimens and offers advantages over culture. PCR is faster, does not require viable organisms, and can be performed more safely than culture. However, PCR testing for tularemia is not universally available and may need to be sent to reference laboratories.

Routine laboratory tests in tularemia patients often show nonspecific abnormalities. The white blood cell count may be normal, elevated, or decreased. Inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are typically elevated. Liver function tests may show mild abnormalities, and electrolyte imbalances can occur in severe cases.

How Is Tularemia Treated?

Tularemia is treated with antibiotics, typically for 7-14 days depending on disease severity. First-line treatment is intravenous gentamicin or streptomycin. For milder cases or oral therapy, ciprofloxacin or doxycycline may be used. With appropriate antibiotic treatment, the mortality rate drops from 10-50% (untreated) to less than 4%. Swollen lymph nodes that develop abscesses may require surgical drainage.

Prompt antibiotic treatment is the cornerstone of tularemia management and dramatically improves outcomes. Before antibiotics became available, tularemia mortality reached 60% in severe cases. Modern treatment has reduced this to less than 4% overall, though pneumonic and typhoidal forms still carry higher risk even with therapy.

The choice of antibiotic depends on the severity of illness, the clinical form of tularemia, patient factors, and practical considerations such as the route of administration and duration of hospitalization. Healthcare providers consider all these factors when designing treatment regimens.

First-Line Antibiotic Treatment

Aminoglycoside antibiotics (gentamicin and streptomycin) are considered first-line treatment for tularemia based on decades of clinical experience and consistent efficacy. These antibiotics work by interfering with bacterial protein synthesis and are bactericidal (they kill bacteria rather than just stopping their growth).

Gentamicin is the preferred aminoglycoside in most clinical settings due to its wider availability and familiarity among healthcare providers. It is administered intravenously, typically for 7-14 days depending on disease severity and clinical response. Patients receiving gentamicin require monitoring of kidney function and drug levels to prevent toxicity.

Streptomycin was historically the treatment of choice and remains highly effective. However, its use has declined due to limited availability, the need for intramuscular injection, and concerns about toxicity. When available, streptomycin is an excellent option, particularly for severe cases.

Alternative Antibiotic Options

Fluoroquinolones such as ciprofloxacin have emerged as important alternatives to aminoglycosides. They can be administered orally, making them attractive for outpatient treatment of milder cases or for completing therapy after initial intravenous treatment. Studies have shown good efficacy, though some experts express concern about their use for the more virulent Type A strains found in North America.

Doxycycline is another oral option that can be considered for mild cases. However, as a bacteriostatic antibiotic (one that stops bacterial growth rather than killing bacteria), doxycycline has been associated with higher relapse rates than aminoglycosides or fluoroquinolones. It may be most appropriate for patients who cannot tolerate other options.

Supportive Care and Complications

Beyond antibiotics, supportive care plays an important role in tularemia management. Patients with severe illness may require hospitalization for intravenous fluids, pain management, and close monitoring. Those with pneumonic tularemia may need supplemental oxygen or, in severe cases, mechanical ventilation.

Suppurative lymphadenopathy - lymph nodes that become filled with pus despite antibiotic treatment - is a common complication that may require surgical intervention. Incision and drainage can provide symptom relief and may promote faster resolution. Some abscessed nodes eventually drain spontaneously.

How Can You Prevent Tularemia?

Prevent tularemia by using insect repellent containing DEET, wearing long sleeves and pants in tick-prone areas, performing tick checks after outdoor activities, wearing gloves when handling wild animals, avoiding drinking untreated water, and thoroughly cooking wild game. There is currently no vaccine available to the general public.

Prevention of tularemia focuses on reducing exposure to the bacteria through protective measures against ticks and deer flies, safe handling of animals, and avoiding environmental contamination. While no strategy provides complete protection, combining multiple preventive measures significantly reduces risk.

Protection Against Ticks and Biting Flies

Arthropod bite prevention is crucial in endemic areas, particularly during warmer months when tick and deer fly activity peaks. Effective strategies include both personal protective measures and environmental modifications.

Insect repellent containing DEET (20-30% concentration) provides effective protection against ticks and flies when applied to exposed skin. Permethrin-treated clothing offers additional protection by killing ticks on contact. Combining both methods provides optimal defense during outdoor activities.

Protective clothing creates a physical barrier against arthropod bites. Wear long-sleeved shirts and long pants, tucking pants into socks or boots to prevent ticks from reaching skin. Light-colored clothing makes it easier to spot ticks. Wide-brimmed hats can help deter deer flies, which are attracted to the head and upper body.

Tick checks should be performed promptly after spending time outdoors in tick-prone areas. Carefully examine all body areas, paying special attention to the scalp, behind the ears, underarms, groin, and backs of knees. Showering within two hours of coming indoors can help wash away unattached ticks and provides an opportunity for thorough inspection.

Safe tick removal, if a tick is found attached, is important to minimize infection risk. Use fine-tipped tweezers to grasp the tick as close to the skin as possible, then pull upward with steady, even pressure. Clean the bite area and hands with rubbing alcohol or soap and water. Never crush a tick with bare fingers.

Safe Animal Handling

Those who hunt, trap, or otherwise handle wild animals should take specific precautions to prevent tularemia transmission through direct contact.

• Wear protective gloves (rubber or latex) when handling wild animals, especially rabbits, hares, and rodents
• Avoid handling visibly sick animals or those found dead, as they may have died from tularemia
• Process game meat outdoors or in well-ventilated areas to reduce inhalation risks
• Cook all wild game thoroughly to an internal temperature of at least 165°F (74°C)
• Wash hands and equipment thoroughly after handling animals, even with gloves
• Keep pets away from wild animal carcasses, as they can become infected and potentially transmit bacteria to humans

Environmental Precautions

Water safety is important because contaminated water can transmit tularemia. Never drink untreated water from streams, ponds, wells, or other natural sources in endemic areas. Boiling water for at least one minute or using appropriate water purification methods eliminates the risk.

Lawn and yard maintenance can inadvertently expose individuals to tularemia. Avoid mowing over dead animals, which can aerosolize bacteria. Wear a dust mask when mowing in areas where rodents may be present, particularly after die-offs have been reported.

What Is the Prognosis for Tularemia?

With prompt antibiotic treatment, the prognosis for tularemia is excellent, with mortality rates below 4%. Most patients recover completely within weeks to months. Without treatment, mortality ranges from 6% for ulceroglandular disease to 30-60% for pneumonic forms. Some patients experience prolonged fatigue, and complications like scarring or chronic lymph node problems can occur.

The outlook for tularemia patients depends heavily on two factors: the clinical form of disease and the timing of treatment. Early recognition and appropriate antibiotic therapy dramatically improve outcomes across all forms of tularemia.

For ulceroglandular and glandular tularemia, the prognosis with treatment is excellent. These forms have the lowest mortality even without therapy (approximately 6%), and with antibiotics, fatal outcomes are rare. The skin ulcer typically heals within 3-4 weeks of starting treatment, though scarring may occur. Lymph node swelling resolves more slowly and may persist for weeks to months.

Pneumonic and typhoidal tularemia carry more serious prognoses. Without treatment, mortality can reach 30-60% for pneumonic disease and 35-50% for typhoidal forms. Even with appropriate antibiotics, these patients require close monitoring and may need intensive care support. Survivors may have residual lung damage or prolonged recovery periods.

Long-term effects of tularemia can persist beyond acute illness resolution. Many patients report fatigue, weakness, and malaise lasting weeks to months after completing treatment. Some develop chronic lymphadenopathy or recurring lymph node abscesses. Pneumonic tularemia survivors may have persistent lung abnormalities on imaging studies.

Frequently Asked Questions About Tularemia