eMedicine Specialties > Infectious Diseases > Lower Respiratory Tract Infections

Tularemia

Author: Kerry O Cleveland, MD, Associate Professor of Medicine, University of Tennessee College of Medicine; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Methodist Healthcare of Memphis
Coauthor(s): Michael Gelfand, MD, FACP, Chief, Professor, Department of Internal Medicine, Division of Infectious Diseases, Methodist Healthcare of Memphis, University of Tennessee; Gregory J Raugi, MD, PhD, Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle
Contributor Information and Disclosures

Updated: Feb 4, 2009

Introduction

Background

Tularemia is an acute, febrile, granulomatous, infectious zoonosis caused by the aerobic gram-negative pleomorphic bacillus Francisella tularensis. Although tularemia has likely existed since ancient times,¹ the disease was first described in Japan in 1837. In 1911, a plaguelike disease in ground squirrels was described in Tulare County, California (tulare is an Aztec word for the tule reed, a marsh plant commonly found in that area), and was later found to be caused by the bacterium now known as F tularensis. Edward Francis studied the causative organism further, named the disease, and, in 1928, described his experience.²

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Worldwide, more than 100 species of animals, birds, amphibians, and arthropods host F tularensis. The bacillus may also be found in mud and water. F tularensis produces acute infectious illness in humans. The mode of transmission and factors related to the host and organism influence the clinical presentation (ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, typhoidal).

Pathophysiology

Humans become infected with F tularensis after introduction of the bacillus by inhalation, intradermal injection, or oral ingestion. The clinical form of tularemia reflects the mode of transmission. Some authors classify the disease as typhoidal (predominance of systemic symptoms), pneumonic (pulmonary findings), or ulceroglandular (regional symptoms).

To cause tularemia in humans via intradermal injection or inhalation, 10-50 bacilli are required. To transmit the disease orally, 100 million organisms are required.

Ulceroglandular tularemia (80% of reported cases) usually occurs after F tularensis enters through the skin. Reportedly, bacilli can penetrate intact skin, but an abrasion (which may be clinically inapparent), a tick bite, or an insect bite is more likely to allow entry. Inoculation of the oral mucosa or conjunctiva may follow (1) contact with hands or fingers contaminated with tissue fluids or (2) contact with infectious aerosols.

Following an incubation period of 3-5 days (range, 1-14 d), a papule develops. In 2-4 more days, the papule may ulcerate, usually accompanied by fever and regional lymphadenopathy. Humans are probably bacteremic during this phase. The bacilli become entrapped in the reticuloendothelial system, where they may survive for a prolonged period. Caseating granulomata, with or without multinucleated giant cells, may develop.

Many animals and arthropods may carry F tularensis; however, ticks (especially Dermatocentor and Amblyomma species) and rabbits are the most common vectors implicated in cases of human tularemia. Domestic cats are increasingly recognized as associated with human tularemia. The deer fly is also a classic vector, although a less commonly reported one.

Inhalation of F tularensis may lead to pulmonic tularemia, while oral ingestion may cause oropharyngeal tularemia. Conjunctival inoculation may follow contact with contaminated tissue fluids. The portal of entry is unknown in most cases of typhoidal tularemia.

Frequency

United States

A few hundred cases of tularemia are reported annually. Many cases are probably undiagnosed, misdiagnosed, or unreported. Tularemia has been reported in all states except Hawaii. Most reported cases occur in Arkansas, Tennessee, Texas, Oklahoma, Kansas, Utah, and Missouri.

In the past, tularemia infections reportedly occurred more frequently during the cold-weather months (eg, rabbit-associated disease); however, recently, tularemia has been reported more frequently during warm-weather months (eg, tick-associated disease).

International

Tularemia occurs throughout the Northern Hemisphere, except for in the United Kingdom. Cases have been reported in the United States, the former Soviet Union, Japan, Canada, Mexico, and Europe. Tularemia has not been reported in Africa and South America.

Mortality/Morbidity

Overall, untreated tularemia carries a mortality rate of approximately 8%. The mortality rate of untreated typhoidal tularemia is 2-3 times higher. With early diagnosis and appropriate treatment, the mortality rate is less than 1%.

Race

All races are equally susceptible to tularemia.

Sex

Both sexes are equally susceptible to tularemia; however, societal activities common to young men may predispose them to F tularensis exposure.

Age

People of all ages are susceptible to the tularemia; however, young-to-middle-aged people are more likely to participate in activities that predispose them to exposure.

Clinical

History

Most patients with tularemia experience an abrupt onset of fever, chills, malaise, and fatigue and develop 1 of 6 well-recognized clinical forms: ulceroglandular tularemia, glandular tularemia, oculoglandular tularemia, oropharyngeal tularemia, pneumonic tularemia, and typhoidal (septicemic) tularemia.

• Ulceroglandular tularemia
  • This form accounts for approximately 80% of tularemia cases.
  • F tularensis usually gains entry into the body via a scratch or abrasion and then spreads lymphatically, usually causing painful regional lymphadenopathy and an ulcerated skin lesion. Rarely, lymphangitis or nodular sporotrichoid lesions develop proximal to the ulcer.
  • In rabbit-associated disease, the ulcer is located on a finger or hand in more than 90% of patients.
    
    

    

    Eschar on thumb and under thumbnail at the site of a rabbit bite in a patient with tularemia.

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    Eschar on thumb and under thumbnail at the site of a rabbit bite in a patient with tularemia.

  • In tick-borne tularemia, the ulcer is found on a lower extremity or the perineal area in 50% of patients, the trunk in 30%, and the head in 5-10%.
• Glandular tularemia
  • This form is similar to ulceroglandular tularemia except for the absence of the characteristic skin lesion.
  • F tularensis is presumed to enter via an inapparent abrasion and then to spread lymphatically or via the bloodstream.
    
    

    

    Axillary bubo in a patient with tularemia.

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    Axillary bubo in a patient with tularemia.

• Oculoglandular tularemia
  • In this form (1-2% of patients), F tularensis enters via the conjunctivae after inoculation from either splashing of blood or rubbing of eyes after contact with contaminated tissue fluids.
  • Clinical manifestations are usually unilateral.
  • Painful purulent conjunctivitis with preauricular or cervical lymphadenopathy may develop. Some patients experience chemosis, periorbital edema, and small nodular or ulcerative lesions of the palpebral conjunctivae.
• Oropharyngeal tularemia
  • This is a rare form that may occur after consumption of poorly cooked meat of an infected rabbit.
  • Patients with oropharyngeal tularemia usually report a sore throat, abdominal pain (due to mesenteric lymphadenopathy), nausea, vomiting, diarrhea, and, occasionally, frank gastrointestinal bleeding (caused by intestinal ulcerations).
• Pneumonic tularemia
  • Primary tularemia pneumonia is uncommon and occurs after inhalation of the F tularensis.
  • Rarely acquired naturally, pneumonic tularemia may develop in laboratory workers.
  • Pneumonia develops after hematogenous spread in 10-15% of patients with ulceroglandular tularemia and in 30-80% of those with typhoidal tularemia.
  • Patients with this form of tularemia usually report a dry cough, dyspnea, and pleuritic-type chest pain.
  • Chest radiography may reveal patchy ill-defined infiltrates in one or more lobes. Frank lobar pneumonia may also develop. Bilateral hilar adenopathy may be present. Bloody pleural effusions are characteristic and demonstrate a mononuclear cellular response.
  • Adult respiratory distress syndrome (ARDS) develops in some patients.
• Typhoidal (septicemic) tularemia
  • This form accounts for 10-15% of tularemia cases.
  • It is more severe and probably represents F tularensis bacteremia.
  • Patients with this form of tularemia present with fever, chills, myalgias, malaise, and weight loss. They often have pneumonia.
  • Diagnosis is difficult because ulcers and lymphadenopathy are usually absent.
• Clinical symptoms
  • Clinical symptoms correspond to the type of tularemia.
  • As many as 20% of patients with tularemia have a blotchy, macular, maculopapular, or pustular rash.
  • Erythema nodosum and erythema multiforme are rare.
• Other forms
  • Rare manifestations of tularemia include osteomyelitis, pericarditis, peritonitis, endocarditis, and nervous system abnormalities, including meningitis, abscesses,³ and optic neuritis.⁴
  • Other possible manifestations include acute renal failure, hepatomegaly, abnormal liver function, and rhabdomyolysis.

Physical

Physical findings of tularemia vary based on the clinical form disease presentation. Patients have fever and possibly tender hepatosplenomegaly.

• Ulceroglandular tularemia
  • This form is characterized by an ulcer at the site of F tularensis entry through the skin. The ulcer varies with the vector. It usually begins as a tender papule that eventually ulcerates and has a sharply demarcated border with a yellowish exudate. Initially, the base of the ulcer also has a yellowish exudate that turns to black.
  • Regional lymphadenopathy develops. The lymph nodes are usually edematous and tender. They can become fluctuant and may drain spontaneously.
• Oculoglandular tularemia
  • Ocular findings are usually unilateral.
  • Painful conjunctivitis with purulent exudate may be present.
  • Nodules or ulcerations may develop on the palpebral conjunctivae.
  • Submandibular, preauricular, and cervical adenopathy are common.
  • Corneal ulcerations may develop.
• Oropharyngeal tularemia: Exudative or membranous pharyngotonsillitis with regional adenopathy may be observed.
• Pneumonic tularemia: Chest examination findings may be normal in tularemic pneumonia, or rales may be present in the affected lung fields.
• Clinical symptoms: As many as 20% of patients with tularemia have a rash that may begin as blotchy, macular, or maculopapular and that may progress to pustular lesions. Erythema nodosum and erythema multiforme rarely occur.
• Less-common clinical forms of tularemia: In these forms of the disease (eg, meningitis, pericarditis, peritonitis, osteomyelitis), physical findings are the same as those commonly found in the clinical forms described above.

Causes

• Tularemia is caused by infection with the bacterium F tularensis.

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