Tularemia: Symptoms, Treatments, Medications and Prevention

Tularemia is a rare but potentially serious infectious disease caused by the bacterium Francisella tularensis. Also known as rabbit fever or deer fly fever, Tularemia primarily affects small mammals such as rabbits, rodents, and hares, but it can also infect humans. It is a zoonotic disease, meaning it is transmitted from animals to humans, and it can be acquired through various modes, including direct contact with infected animals, bites from infected insects, ingestion of contaminated food or water, or inhalation of contaminated aerosols.

While Tularemia is treatable with antibiotics, it can cause severe illness or even be fatal if not promptly treated.

What is Tularemia?

The Causative Agent: Francisella tularensis

Tularemia is caused by the bacterium Francisella tularensis, a highly infectious and pathogenic microorganism. F. tularensis is a Gram-negative bacterium that is divided into several subspecies, each with varying degrees of virulence:

• F. tularensis tularensis (Type A): Found mainly in North America, this subspecies is highly virulent and responsible for the most severe cases of Tularemia.
• F. tularensis holarctica (Type B): Found in Europe, Asia, and North America, this subspecies is less virulent than Type A but can still cause significant illness.
• F. tularensis mediasiatica and F. tularensis novicida: These are less common and less virulent subspecies found in Central Asia and the western United States, respectively.

F. tularensis is an intracellular pathogen, meaning it can live and multiply inside the host’s cells. This allows it to evade the immune system, contributing to its virulence. The bacterium can infect a wide range of animals, including rabbits, hares, rodents, and even birds, and it can persist in the environment for weeks or months, especially in water, soil, or animal carcasses.

Modes of Transmission

Humans can acquire Tularemia through various routes:

• Direct Contact: Handling infected animals or their tissues can transmit the bacterium, especially through cuts, wounds, or breaks in the skin.
• Insect Bites: Bites from infected ticks, mosquitoes, or deer flies can transmit the bacteria.
• Inhalation: Inhalation of contaminated dust or aerosols, such as during mowing or farming activities, can lead to pulmonary Tularemia.
• Ingestion: Drinking contaminated water or eating undercooked meat from infected animals can lead to oropharyngeal Tularemia.
• Laboratory Exposure: Tularemia is classified as a Category A bioterrorism agent, meaning it has the potential to be weaponized. Laboratory workers handling the bacterium are at risk of accidental exposure.

Human-to-human transmission of Tularemia is extremely rare, and it is primarily an occupational or environmental hazard.

Who is at Risk of Tularemia?

Although anyone can develop Tularemia if exposed to the bacterium, certain populations and behaviors increase the risk of contracting the disease.

Occupational and Environmental Risk Factors

Individuals who work or engage in activities that bring them into close contact with wildlife or environments where the bacterium is present are at higher risk. This includes:

1. Hunters and Trappers

People who hunt or trap wild animals, especially rabbits, hares, and rodents, are at increased risk of direct contact with infected animal tissues. Skinning or handling these animals without protective equipment can expose hunters to the bacterium.

2. Farmers and Agricultural Workers

Agricultural workers, particularly those involved in activities like cutting grass, mowing, or harvesting crops, may be exposed to aerosolized bacteria from contaminated soil, animal carcasses, or hay.

3. Laboratory Workers

Individuals working in laboratories where F. tularensis is handled are at risk of accidental exposure, particularly if proper biosafety protocols are not followed.

4. Landscapers and Gardeners

People working in landscaping or gardening may come into contact with contaminated soil, water, or plants, especially in regions where Tularemia is prevalent.

5. Tick and Mosquito Exposure

People who spend time outdoors in areas with high tick or mosquito populations, such as hikers, campers, and outdoor enthusiasts, are at risk of contracting Tularemia through insect bites.

Geographic Risk Factors

Tularemia occurs naturally in certain parts of the world, with specific regions having higher rates of infection:

• North America: Particularly in the central United States (Arkansas, Missouri, and Oklahoma), where Type A Tularemia is more common.
• Europe: Particularly in Scandinavia, Eastern Europe, and parts of Russia.
• Asia: Countries like Turkey and Japan have reported cases of Tularemia.

Symptoms of Tularemia

The symptoms of Tularemia vary widely depending on the route of infection and the form of the disease. There are several clinical forms of Tularemia, each with distinct features. However, all forms share some common symptoms.

General Symptoms of Tularemia

Regardless of the form, Tularemia usually begins with the sudden onset of flu-like symptoms, including:

• Fever (can be high, up to 104°F/40°C)
• Chills
• Headache
• Fatigue
• Muscle aches
• Joint pain

These general symptoms are often accompanied by more specific manifestations depending on the type of Tularemia. The disease has six major clinical forms:

1. Ulceroglandular Tularemia

This is the most common form of Tularemia and results from direct contact with infected animals or insect bites.

Symptoms:

• Skin ulcer: A painful ulcer forms at the site of infection, typically where an insect bite or contact with an animal occurred.
• Swollen lymph nodes: Nearby lymph nodes become enlarged, often in the armpit or groin area, and can become painful.

2. Glandular Tularemia

This form is similar to ulceroglandular Tularemia but without the skin ulcer.

Symptoms:

• Swollen lymph nodes: Lymph nodes become swollen and painful, usually near the site of infection (insect bite or skin contact).

3. Oculoglandular Tularemia

This form occurs when the bacteria enter the body through the eyes, usually from touching the eyes after handling infected materials.

Symptoms:

• Eye pain and redness: Inflammation and irritation of the eyes (conjunctivitis).
• Swollen eyelids: The eyelids may become swollen and tender.
• Swollen lymph nodes: Lymph nodes near the eyes (preauricular) may become enlarged.

4. Oropharyngeal Tularemia

This form results from ingesting contaminated food or water, leading to infection in the throat and digestive system.

Symptoms:

• Sore throat: Pain and swelling in the throat, often accompanied by difficulty swallowing.
• Mouth ulcers: Sores may form inside the mouth.
• Gastrointestinal symptoms: Nausea, vomiting, and abdominal pain may occur.
• Swollen lymph nodes: Lymph nodes in the neck and throat may become enlarged.

5. Pneumonic Tularemia

Pneumonic Tularemia is the most serious form of the disease and occurs when the bacteria are inhaled. This form can lead to severe respiratory illness.

Symptoms:

• Cough: Often dry, but it may become productive with phlegm.
• Chest pain: Sharp pain in the chest, particularly when coughing or breathing deeply.
• Shortness of breath: Difficulty breathing, which can worsen as the infection progresses.
• Respiratory failure: In severe cases, the infection can lead to pneumonia and respiratory failure.

6. Typhoidal Tularemia

Typhoidal Tularemia is a rare form that results in systemic infection without localized symptoms.

Symptoms:

• High fever: Persistent fever, often with chills and sweats.
• Weight loss: Unexplained weight loss over time.
• Severe fatigue: Profound weakness and malaise.
• Abdominal pain: Pain in the abdomen, often with nausea or vomiting.

Diagnosis of Tularemia

Diagnosing Tularemia can be challenging because the symptoms resemble those of other infectious diseases, such as plague, brucellosis, and Q fever. A combination of clinical assessment, laboratory tests, and patient history is necessary to make a definitive diagnosis.

Clinical Evaluation

Doctors will conduct a thorough examination and ask about the patient’s recent activities, such as hunting, outdoor exposure, or travel to endemic areas. Noting any history of tick or insect bites or contact with wildlife is crucial for identifying potential exposure.

Laboratory Tests

1. Blood Cultures

Blood cultures can be used to isolate Francisella tularensis from the bloodstream. However, this bacterium is difficult to grow in standard laboratory conditions, and results may take time.

2. Serology

Serological tests can detect antibodies to F. tularensis in the patient’s blood. The presence of IgM and IgG antibodies indicates an immune response to the bacterium. A fourfold rise in antibody levels over time is considered diagnostic of Tularemia.

3. Polymerase Chain Reaction (PCR)

PCR testing is a more rapid and sensitive method for detecting F. tularensis DNA in clinical samples, such as blood, sputum, or tissue biopsies. PCR can confirm the presence of the bacteria within hours.

4. Chest X-rays

In cases of suspected pneumonic Tularemia, a chest X-ray may show signs of pneumonia or lung infiltrates.

5. Tissue Biopsy

In cases of ulceroglandular Tularemia, a biopsy of the ulcer or swollen lymph node may be taken and tested for the presence of the bacteria.

Treatments for Tularemia

Tularemia is treatable with antibiotics, and early intervention is crucial for preventing complications or death. The choice of antibiotic depends on the severity and form of the disease, but most cases respond well to therapy.

Antibiotic Treatment

The following antibiotics are commonly used to treat Tularemia:

1. Streptomycin

Streptomycin is considered the gold standard for treating Tularemia, particularly in severe cases. It is an aminoglycoside antibiotic that is highly effective at killing F. tularensis. Streptomycin is usually administered intramuscularly and is especially effective for treating ulceroglandular, pneumonic, and typhoidal Tularemia.

2. Gentamicin

Gentamicin is another aminoglycoside antibiotic that can be used as an alternative to streptomycin. It is often preferred for patients who cannot tolerate streptomycin due to side effects. Gentamicin is also administered intramuscularly or intravenously, and it is effective in treating most forms of the disease.

3. Doxycycline

Doxycycline is a tetracycline antibiotic that can be used to treat milder cases of Tularemia. It is administered orally and is often prescribed for glandular and oropharyngeal Tularemia. However, doxycycline is less effective than aminoglycosides for severe forms of the disease and is usually reserved for mild cases or for patients who cannot receive aminoglycosides.

4. Ciprofloxacin

Ciprofloxacin, a fluoroquinolone antibiotic, is also an option for treating Tularemia. Like doxycycline, it is taken orally and is effective in mild to moderate cases. Ciprofloxacin is often used for prophylaxis in individuals who have been exposed to the bacterium but have not yet developed symptoms.

5. Chloramphenicol

In some cases of meningitis caused by Tularemia, chloramphenicol may be used. This antibiotic has good penetration into the central nervous system and can help treat infections of the brain and spinal cord.

Duration of Treatment

The typical duration of antibiotic treatment for Tularemia is 10 to 21 days, depending on the severity of the infection and the antibiotic used. Streptomycin and gentamicin treatments generally last 10 to 14 days, while doxycycline and ciprofloxacin treatments may last longer, often 14 to 21 days.

Supportive Care

In addition to antibiotics, patients with Tularemia may require supportive care, especially in severe cases. This can include:

• Intravenous fluids to treat dehydration or maintain blood pressure in critically ill patients.
• Oxygen therapy or mechanical ventilation in cases of severe respiratory distress or pneumonia.
• Pain management for patients with painful ulcers or swollen lymph nodes.

Most Common Medications for Tularemia

The most commonly prescribed medications for treating Tularemia include:

1. Streptomycin

As the first-line treatment for Tularemia, streptomycin is used to treat both mild and severe forms of the disease. It is administered intramuscularly and is effective against F. tularensis, making it the treatment of choice.

2. Gentamicin

Gentamicin is often used as an alternative to streptomycin, especially for patients who may not tolerate streptomycin. It is also administered intramuscularly or intravenously.

3. Doxycycline

Doxycycline is a common oral treatment for less severe cases of Tularemia. It is used when the patient’s condition is not life-threatening, such as in mild ulceroglandular or glandular forms of the disease.

4. Ciprofloxacin

Ciprofloxacin is another oral antibiotic that is effective in treating milder cases of Tularemia. It is often used in prophylactic treatment for individuals who may have been exposed to the bacterium but have not yet developed symptoms.

5. Chloramphenicol

Chloramphenicol is used in rare cases of central nervous system involvement, such as meningitis caused by Tularemia.

Where is Tularemia Most Prevalent?

Tularemia occurs in several parts of the world, but its prevalence varies depending on the geographic region and the presence of animal reservoirs and insect vectors.

North America

Tularemia is most commonly reported in the United States, particularly in the central and western regions, including states such as Arkansas, Missouri, Oklahoma, South Dakota, and Montana. The Type A strain of F. tularensis is more prevalent in North America, and it is associated with severe forms of the disease.

Europe

In Europe, Tularemia is reported primarily in Scandinavia, Eastern Europe, and Russia. The Type B strain of F. tularensis is more common in Europe and tends to cause milder forms of the disease. Countries such as Sweden, Finland, and Norway have experienced significant outbreaks, particularly related to contact with hares and other wildlife.

Asia

Tularemia is also present in parts of Asia, including Turkey, Kazakhstan, and Japan. The Type B strain is more common in Asia, and cases are often associated with contaminated water or animal exposure.

Other Regions

Tularemia has been reported sporadically in other parts of the world, including Australia, where it was first identified in 2011, and Africa, though it is rare in these regions.

Prevention of Tularemia

Preventing Tularemia involves reducing the risk of exposure to F. tularensis, particularly in areas where the bacterium is endemic. Preventive measures focus on avoiding contact with infected animals, protecting against insect bites, and practicing good hygiene when handling wildlife or working in environments where the bacterium may be present.

Avoiding Contact with Infected Animals

1. Hunters and Trappers

• Wear gloves when handling or skinning wild animals, particularly rabbits, hares, and rodents.
• Cook wild game thoroughly to kill any potential bacteria.
• Avoid touching or handling dead animals without protection, especially in areas known to have Tularemia outbreaks.

2. Pet Owners

• Prevent pets, especially cats and dogs, from hunting or eating wild animals that may be infected with Tularemia.
• If a pet becomes ill after exposure to wildlife, seek veterinary care promptly.

Insect Bite Prevention

1. Use of Insect Repellents

• Apply insect repellents containing DEET or permethrin when spending time outdoors in areas with high tick or mosquito populations.

2. Wear Protective Clothing

• Wear long-sleeved shirts, long pants, and closed shoes to reduce the risk of insect bites when hiking, camping, or engaging in outdoor activities.

3. Tick Checks

• Perform regular tick checks after spending time outdoors, especially in areas where Tularemia is known to occur. Remove ticks promptly and carefully using tweezers.

Safe Water and Food Practices

• Avoid drinking untreated water from streams, lakes, or ponds that may be contaminated with F. tularensis.
• Wash hands thoroughly after handling animals or working with soil or water in areas where Tularemia is endemic.
• Cook food, especially wild game, thoroughly to prevent the ingestion of bacteria.

Vaccination and Laboratory Safety

Although no Tularemia vaccine is widely available for the general public, a vaccine has been developed for individuals at high risk, such as laboratory workers handling F. tularensis. Laboratory personnel should follow strict biosafety protocols to avoid accidental exposure, including wearing protective clothing and working in biosafety cabinets when handling the bacteria.