Basics
Description
Tularemia is an infection caused by Francisella tularensis, a small, fastidious, nonmotile, gram-negative coccobacillus; 4 distinct subspecies have been described:
- tularensis (type A): found primarily in North America; causes the most severe cases of tularemia in humans
- holarctica (type B): subspecies found primarily in Europe and Asia; less virulent than tularensis
- novicida: rarely isolated but can be found worldwide
- mediasiatica: recovered from ticks and animals in Central Asia; not associated with disease in immunocompetent humans
- An additional species, Francisella philomiragia (formerly Yersinia philomiragia), has also been reported. This is a rare cause of human disease and is possibly associated with salt water exposure.
- Tularemia typically presents with fever, myalgias, and headache 3 " 6 days after initial exposure. The extent of the illness depends on infecting dose, subspecies, and route of entry.
- 6 clinical forms are typically described:
- Ulceroglandular tularemia
- Constitutes 75% of all cases
- A papule, which ruptures and ulcerates, occurs at the site of entry.
- Glandular tularemia
- Identical to the ulceroglandular form
- However, does not have an identified primary skin lesion
- Oculoglandular tularemia
- Occurs when the organism gains access via the conjunctival sac
- Usually from the patient rubbing the eyes with contaminated fingers
- Yellow nodules and ulcers may appear on the palpebral conjunctiva associated with enlarged preauricular nodes.
- Oropharyngeal tularemia
- Occurs after the ingestion of contaminated food or water
- An ulcerative or membranous tonsillitis accompanies a painful sore throat.
- Lower GI tract involvement with vomiting, diarrhea, and abdominal pain may be associated.
- Typhoidal tularemia
- Presents with fever of unknown origin, without localizing lymphadenopathy or skin findings
- Shock, pleuropulmonary findings, odynophagia, diarrhea, and bowel necrosis are often associated.
- Pneumonic tularemia
- Occurs after inhalation of the organism
- It can also be present in association with ulceroglandular and typhoidal tularemia.
- Pulmonary tularemia is the most fulminant and lethal form.
- Symptoms include fever, dry cough, and pleuritic chest pain.
- Tularemia in this form is a feared potential biologic weapon because an exposure to only 1 " 10 colony-forming units can result in infection. Although not transmitted person to person, laboratory workers working with organism on an agar plate are at risk for this form of disease.
Alert
- F. tularensis is currently listed as a class A bioterrorism agent because of its potential ease for dissemination and infection as well as potential for high case fatality rates.
- In the past, resistant forms of F. tularensis have been engineered, but the actual use of this organism as a bioterrorism agent has not been documented.
- The diagnosis of inhalation tularemia should raise the suspicion of bioterrorism.
Epidemiology
- F. tularensis is found primarily in the Northern hemisphere from the 30 " 70-degree latitudes. Wild mammals (e.g., rabbits, hares, squirrels, beavers, deer, and rodents) may be infected as well as invertebrates (e.g., ticks, deerflies, horseflies, and mosquitoes).
- Humans acquire tularemia after a bite by an infected arthropod or through contact with tissues or body fluids of an infected animal. The subspecies holarctica has been shown to persist in various water sources, and waterborne transmission to humans has been reported.
- Inhalational exposure can happen in the laboratory setting or after the organism is aerosolized during meat preparation.
- Most commonly reported during the summer months in children between 5 and 9 years of age and those >75 years old
Risk Factors
- Most frequently infected groups include hunters, trappers, farmers, and veterinarians.
- Activities involving wild animals or exposure to various arthropod vectors
- Infection has been linked to landscapers using lawn mowers and brush cutters.
- Laboratory personnel working with samples known to be or potentially infected with Francisella
General Prevention
- Isolation of the hospitalized patient
- Standard precautions are recommended for protection against secretions. Human-to-human transmission has not been reported.
- Control measures
- Protective clothing and insect repellent should be used to minimize insect bites.
- Inspection for ticks and their immediate removal should be routine after outdoor activity in endemic areas.
- Rubber gloves should be worn while handling or cooking wild animals (e.g., rabbits, lemmings) possibly contaminated with Francisella.
- Laboratory workers should wear rubber gloves and masks in a biosafety level 3 environment when working with specimens potentially containing Francisella.
- Vaccine
- Significant research into various vaccine techniques continues to evolve given concerns of F. tularemia as an agent of bioterrorism.
Pathophysiology
- Entry into the human is via skin, mucous membranes, or inhalational.
- A primary lesion develops at the site of exposure.
- Local tender lymph node swelling ensues.
- After skin inoculation or inhalation, the organism can spread via the bloodstream to various organs.
Etiology
Human infection can result from various modes of entry:
- Skin contact with infected animals
- Vector-borne infection described after the bite of a tick, mosquito, horsefly, or deerfly
- Inhalation of aerosolized organism seen in laboratory workers, crop harvesting, disturbance of contaminated hay, and grass cutting
- Ingestion of contaminated food products or water
Diagnosis
History
- In the right clinical setting, a history that elicits any occupational exposure or recreational activity previously noted as risk factors should raise suspicion for tularemia.
- History of a recent tick or fly bite may be recalled among affected patients.
- A history of a papule that became ulcerated is classic for the ulceroglandular form.
- Fever >101 °F for 2 " 3 weeks is common, with associated weight loss.
Physical Exam
- A papule or ulcer may be seen at the inoculation site.
- Skin lesions should be sought, especially when lymphadenopathy is present.
- Lymph node swelling is typically tender with overlying erythema.
- After a 3 " 6-day incubation period, symptoms may include fever, myalgias, and headache.
- Hepatosplenomegaly, purulent conjunctivitis, adenopathy, an ulcerative skin lesion, and tonsillitis are other localized findings.
Diagnostic Tests & Interpretation
Lab
- Serum tube agglutination titers of 1:160 or greater are generally considered positive.
- A 4-fold rise in titers over a 2-week period is necessary to define a current infection.
- Cultures of blood, skin, ulcers, lymph nodes, gastric washings, and respiratory secretions require special media containing cysteine.
- Laboratory personnel should be made aware of the infection risk from specimens. Growth of the organism requires a biosafety level 3 laboratory.
- Polymerase chain reaction (PCR) tests are available in some laboratories. They are more sensitive than culture and can be performed on tissue samples. Current PCR techniques do not differentiate subspecies, but such techniques are under development.
- Fluorescent in situ hybridization techniques have been used in the research setting to differentiate subspecies and may be clinically useful in the future.
Differential Diagnosis
Depending on the form of tularemia, the infection can mimic other illnesses such as streptococcal or staphylococcal infection, cat-scratch disease, mononucleosis, cutaneous anthrax, pasteurellosis, Q fever, legionellosis, typhoid fever, or mycobacterial disease. In general, tularemia should be considered in the following differential diagnoses:
- Fever of unknown origin
- Fever with purulent conjunctivitis
- Fever with hepatosplenomegaly
- Fever with skin ulcer
Treatment
Medication
- IV/IM antibiotic therapy with gentamicin is considered 1st-line therapy.
- 2nd-line therapeutic options include streptomycin, ciprofloxacin, or doxycycline. Relapses have been associated with the latter two, and they are generally only used in adults or in specific situations.
- Duration of treatment is typically 7 " 10 days. In severe disease, some experts recommend combination therapy such as gentamicin with ciprofloxacin or doxycycline.
Inpatient Considerations
Initial Stabilization
- If respiratory compromise is present, oxygen supplementation and/or assisted ventilation must be rapidly addressed.
- Recognition and prompt aggressive treatment of shock should be a major priority.
Prognosis
- When recognized and treated with appropriate antibiotics, the course is generally <1 month.
- Mortality is low, except in cases of fulminant disease or are otherwise immunocompromised.
- The subspecies tularensis is thought to be more virulent than the others.
- Both typhoidal and pneumonic forms of tularemia are associated with the highest risk for mortality.
Complications
- Lymph node suppuration, meningitis, endocarditis, hepatitis, and renal failure have all been associated with tularemia. Lymph node suppuration despite adequate therapy may occur in up to 25% of patients with ulceroglandular or glandular disease.
- Infection with F. tularensis may be complicated by necrotic and granulomatous lesions in the liver and spleen as well as parenchymal degeneration.
- A sepsis syndrome with shock, fever, myalgias, and severe headache can be seen. Recognition and prompt aggressive treatment of shock should be a major priority.
- Skin manifestations, including vesiculopapular rash, erythema nodosum, and erythema multiforme have been associated with tularemia.
Additional Reading
- Barry EM, Cole LE, Santiago AE. Vaccines against tularemia. Hum Vaccin. 2009;5(12):832 " 838. [View Abstract]
- Cross JT Jr, Schutze GE, Jacobs RF. Treatment of tularemia with gentamicin in pediatric patients. Pediatr Infect Dis J. 1995;14(2):151 " 152. [View Abstract]
- Eliasson H, Broman T, Forsman M, et al. Tularemia: current epidemiology and disease management. Infect Dis Clin N Am. 2006;20(2):289 " 311. [View Abstract]
- Nigrovic LE, Wingerter SL. Tularemia. Infect Dis Clin North Am. 2008;22(3):489 " 504. [View Abstract]
- Snowden J, Stovall S. Tularemia: retrospective review of 10 years ' experience in Arkansas. Clin Pediatr (Phila). 2011;50(1):64 " 68. [View Abstract]
- Tarnvik A, Chu MC. New approaches to diagnosis and therapy of tularemia. Ann N Y Acad Sci. 2007;1105:378 " 404. [View Abstract]
Codes
ICD09
- 021.9 Unspecified tularemia
- 021.0 Ulceroglandular tularemia
- 021.3 Oculoglandular tularemia
- 021.8 Other specified tularemia
- 021.1 Enteric tularemia
- 021.2 Pulmonary tularemia
ICD10
- A21.9 Tularemia, unspecified
- A21.0 Ulceroglandular tularemia
- A21.1 Oculoglandular tularemia
- A21.8 Other forms of tularemia
- A21.3 Gastrointestinal tularemia
- A21.2 Pulmonary tularemia
- A21.7 Generalized tularemia
SNOMED
- 19265001 Tularemia (disorder)
- 37722001 Ulceroglandular tularemia (disorder)
- 73363000 Oculoglandular tularemia (disorder)
- 398575000 Oropharyngeal tularemia
- 398599000 Enteric tularemia
- 21857006 Glandular tularemia (disorder)
- 45556008 Pulmonary tularemia
FAQ
- Q: If a tick is removed from my child, should antibiotics be started?
- A: No. Empiric antimicrobial therapy will not prevent tularemia.
- Q: Can my child get tularemia again?
- A: No. It appears once infection has occurred, the patient is protected from further new infections.