Tularemia: Symptoms, Types, Causes and Treatment

Tularemia, sometimes called “rabbit fever,” is a rare but potentially serious infectious disease caused by the bacterium Francisella tularensis. While it may not make daily headlines, tularemia is an important public health concern due to its diverse clinical presentations, its potential for severe illness, and its status as a possible bioterrorism agent. Understanding tularemia’s symptoms, forms, causes, and treatment options is crucial for both healthcare professionals and the general public—especially in regions where the disease is re-emerging.

Symptoms of Tularemia

Tularemia is notorious for its wide range of symptoms, which can easily be confused with other illnesses. Early recognition is key to effective treatment, but the disease’s variability means it can sometimes go unrecognized—even by experienced clinicians. Let’s break down the main symptoms you might encounter.

Symptom	Form(s) Affected	Notable Features	Source(s)
Fever	All	Often abrupt, high	1 3 4 7
Chills & malaise	All	Generalized, flu-like	3 4 7
Lymphadenopathy	Ulceroglandular, Glandular	Swollen, tender lymph nodes	1 9
Skin ulcer	Ulceroglandular	At site of infection	1 6 9
Sore throat	Oropharyngeal	With or without ulcers	2 7
Eye symptoms	Oculoglandular	Redness, pain, discharge	7 9
Cough/chest pain	Pneumonic	May resemble pneumonia	4 6 8
GI symptoms	Typhoidal, Oropharyngeal	Abdominal pain, diarrhea	2 3 7
Hepatomegaly	Typhoidal, Rare	Enlarged liver, rare	2

Table 1: Key Symptoms

Overview of Tularemia’s Symptom Spectrum

Tularemia can appear suddenly, often starting with fever and general malaise. However, the specific set of symptoms depends on the route of infection and the form of the disease.

Common Symptoms Across All Forms

• Fever and chills are nearly universal, often appearing early and abruptly. This can be accompanied by profound fatigue and muscle aches 1 3 4 7.
• Malaise (a general feeling of illness) is also common, making tularemia easy to mistake for flu or other infections at first.

Distinctive Symptoms by Disease Form

• Ulceroglandular: The classic form, typically features a skin ulcer at the site of bacterial entry (often a tick or insect bite), along with swollen, tender lymph nodes nearby 1 6 9.
• Glandular: Like ulceroglandular but without the skin ulcer—only the lymph nodes are affected 7.
• Oculoglandular: Infection through the eye causes redness, pain, and swelling of nearby lymph nodes 7 9.
• Oropharyngeal: Results from eating or drinking contaminated food or water; presents with sore throat, mouth ulcers, and swollen neck glands 2 7.
• Pneumonic: Caused by inhaling bacteria; symptoms include cough, chest pain, and sometimes pneumonia-like lung infiltrates 4 6 8.
• Typhoidal: The least specific but often most severe; features high fever, abdominal pain, diarrhea, cough, and sometimes enlarged liver or spleen. It may progress to sepsis or meningitis 1 2 3 7.

Symptom Variability and Diagnostic Challenges

Symptoms can overlap or change over time. For example, a patient may start with a general fever and malaise and only later develop the more obvious signs (like skin ulcers or swollen nodes) 1 3 4. Because of this, tularemia can be missed unless the clinician considers it in the differential diagnosis, especially in endemic areas during tick season or after exposure to wild animals 1 3 7.

Types of Tularemia

Tularemia is not a one-size-fits-all disease. Its clinical “types” are defined by the route of infection and the organs most affected, each with its own set of symptoms and severity.

Type	Route of Infection	Key Features	Source(s)
Ulceroglandular	Arthropod bite, contact	Skin ulcer, lymphadenopathy	1 5 6 9
Glandular	Arthropod bite, contact	Lymphadenopathy only	5 7
Oculoglandular	Eye contamination	Eye inflammation, lymph nodes	7 9
Oropharyngeal	Ingestion (food/water)	Sore throat, GI symptoms	2 5 7
Pneumonic	Inhalation	Cough, chest symptoms	4 6 8
Typhoidal	Any/unknown	Systemic illness, sepsis	1 2 3 7

Table 2: Tularemia Types

Ulceroglandular Tularemia

This is the most common and classic presentation. It usually follows a tick or deer fly bite, or direct contact with infected animals. A skin ulcer appears at the entry site, followed by swelling of the regional lymph nodes. It’s generally less severe than other forms, especially when promptly treated 1 6 9.

Glandular Tularemia

Similar to ulceroglandular, but without a visible skin ulcer. Only the lymph nodes are involved. This form can be harder to recognize since the entry wound is missing 5 7.

Oculoglandular Tularemia

This rare form results from the bacterium entering through the eye, usually by touching the eye with contaminated fingers or fluids. Symptoms include painful, swollen, and red eyes, sometimes with discharge, plus swelling of nearby lymph nodes 7 9.

Oropharyngeal Tularemia

Acquired by eating or drinking contaminated food or water. It manifests as sore throat, mouth ulcers, tonsillitis, and sometimes abdominal pain or diarrhea. Swelling of the neck lymph nodes is common. This form is frequently linked to waterborne outbreaks 2 5 7 12.

Pneumonic Tularemia

Results from inhalation of F. tularensis—either from environmental sources or, rarely, as a result of bioterrorism. Symptoms include cough, chest pain, difficulty breathing, and signs of pneumonia. This form is particularly severe and associated with higher mortality rates 4 6 8 9.

Typhoidal Tularemia

A systemic form that does not fit into the other categories. It may develop after any route of infection and is characterized by generalized symptoms such as prolonged fever, severe malaise, abdominal pain, diarrhea, and sometimes sepsis or meningitis. Typhoidal tularemia is often the most severe, with the highest rates of hospitalization and death 1 2 3 7.

Causes of Tularemia

The causes of tularemia go beyond a single bacterium—they involve complex ecological cycles, multiple transmission routes, and a wide range of animal hosts. Understanding how people get tularemia is crucial for prevention.

Cause	Transmission Route	Example Scenario	Source(s)
Francisella tularensis	All forms	Main bacterial agent	5 7 9 10
Arthropod vectors	Bite (tick, fly, mosquito)	Tick bite in forest	1 5 11 12
Animal contact	Direct/indirect	Handling rabbits, rodents	5 9 11
Contaminated water	Ingestion/skin contact	Drinking or wading in streams	5 12
Inhalation	Aerosol, dust	Mowing grass, lab accident	4 5 8
Foodborne	Ingestion	Eating undercooked game	5 7 12

Table 3: Causes and Transmission Routes

The Bacterial Culprit: Francisella tularensis

Tularemia is caused by Francisella tularensis, a small, highly infectious Gram-negative bacterium. There are several subspecies, but the two most important for human disease are F. tularensis subsp. tularensis (Type A, more virulent, mainly in North America) and subsp. holarctica (Type B, milder, found across the Northern Hemisphere) 5 9 10.

Transmission Pathways

• Arthropod vectors: The most common route is through the bite of infected ticks (e.g., Dermacentor), deer flies, or, in some areas, mosquitoes. These insects acquire the bacteria from feeding on infected animals and later transmit them to humans 1 5 11 12.
• Animal contact: Direct handling or skinning of infected wildlife—especially rabbits, rodents, and hares—can lead to skin or mucous membrane infection 5 9 11.
• Contaminated water: Outbreaks have occurred following exposure to water contaminated by animal carcasses or excreta. Infection can happen through drinking, swimming, or even using water for food preparation 5 12.
• Inhalation: Breathing in dust or aerosols contaminated with F. tularensis (e.g., during farming, landscaping, or laboratory work) can cause pneumonic tularemia, which is particularly severe 4 5 8.
• Foodborne infection: Eating undercooked meat from infected animals or contaminated produce can result in oropharyngeal or gastrointestinal tularemia 5 7 12.

Reservoirs and Ecology

F. tularensis infects a wide variety of animals, including wild rodents, rabbits, hares, and even birds. The bacterium can persist in water and soil, contributing to its environmental resilience. The complex ecology makes tularemia difficult to control and contributes to local outbreaks 5 9 11 12.

Treatment of Tularemia

Prompt and effective treatment is crucial for tularemia—delays can result in severe illness or death. Over the years, antibiotic therapy has evolved, but challenges remain, including drug side effects, relapse rates, and the lack of a licensed vaccine.

Drug/Class	Indication/Severity	Route/Duration	Notes/Efficacy	Source(s)
Streptomycin	Severe/systemic cases	Intramuscular, 10+ days	High cure, few relapses	14 7 9
Gentamicin	Severe/systemic cases	IV/IM, 10+ days	Acceptable alternative	14 7 9
Doxycycline	Mild-moderate	Oral, 14+ days	Higher relapse risk	1 14 7 5
Ciprofloxacin	Mild-moderate	Oral, 10–14 days	Effective, esp. in Type B	13 15 17
Tetracyclines	Mild-moderate	Oral, 14+ days	Risk of relapse if short	1 14 17
Quinolones	Mild-moderate	Oral	Valuable for Type B	15 17
No vaccine	All	—	Research ongoing	5 9 7

Table 4: Treatment Options

Mainstay Antibiotic Therapies

• Aminoglycosides: Streptomycin has long been the gold standard, especially for severe cases, with high cure and low relapse rates. Gentamicin is an acceptable alternative, especially when streptomycin is unavailable 14 7 9.
• Tetracyclines and Doxycycline: Used in less severe cases or when aminoglycosides are contraindicated. They are effective but require longer courses (at least 14 days) to minimize relapse 1 14 7.
• Fluoroquinolones (e.g., Ciprofloxacin): Increasingly used for mild to moderate tularemia, especially in children and for outpatient therapy. Clinical studies have shown good efficacy, particularly for infections caused by Type B strains 13 15 17.

Duration and Relapse Risk

Relapse is a concern, particularly if treatment is too short (less than 14 days) or with lower antibiotic doses. Aminoglycosides are generally more reliable at preventing relapse, while shorter courses of tetracyclines or fluoroquinolones may result in recurrence 1 4 14.

Special Considerations

• Children and Pregnancy: Aminoglycosides are the traditional choice, but oral quinolones like ciprofloxacin are now considered safe and effective alternatives in children, with low risk of side effects 13 17.
• Severe or Complicated Cases: Hospitalization is often required for intravenous antibiotics and supportive care, especially in typhoidal or pneumonic forms 1 4 7.
• Novel Approaches: Research is ongoing into new antibiotics, liposomal delivery systems, immune modulation, and monoclonal antibodies, but these are not yet standard care 17.

Lack of a Licensed Vaccine

Despite decades of research, there is currently no commercially available vaccine for tularemia. A live attenuated vaccine exists for laboratory workers but is not widely licensed. Preventive strategies focus on avoiding exposure and prompt post-exposure antibiotic prophylaxis when risk is high 5 7 9.

Conclusion

Tularemia is a multifaceted disease with a complex ecology and a range of clinical presentations. It challenges clinicians with its variable symptoms and demands rapid, appropriate treatment to prevent severe outcomes. Here’s a recap of the main points:

• Tularemia can present with a variety of symptoms, from flu-like illness to severe pneumonia or sepsis, often making diagnosis tricky 1 3 4 7.
• Six main types of tularemia are recognized, each associated with different routes of infection and symptom patterns 1 5 7 9.
• The disease is caused by Francisella tularensis, transmitted through arthropod bites, animal contact, contaminated water, inhalation, or ingestion 5 7 9 11 12.
• Antibiotics are highly effective when started promptly, with aminoglycosides, tetracyclines, and fluoroquinolones as the main options; relapse is a risk if treatment is too short 1 7 13 14 15.
• No licensed vaccine is available, so prevention depends on environmental management and awareness in endemic areas 5 7 9.

Tularemia may be rare, but its impact can be significant. Awareness, early recognition, and timely treatment are key to improving outcomes in both routine cases and potential outbreaks.