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Tularemia: Epidemiology, Diagnosis, and Treatment Nada S FEATURE Tularemia: Epidemiology, Diagnosis, and Treatment Nada S. Harik, MD ularemia is a rare zoonosis caused ETIOLOGY AND EPIDEMIOLOGY by Francisella tularensis. Al- Tularemia is a zoonotic infection Tthough many animals may be caused by F. tularensis, a small, fastidi- infected with tularemia, human infection ous, aerobic gram-negative coccobacillus. most commonly occurs via an insect vec- There are four distinct subspecies of F. tu- tor such as a tick or deer fly. In the US, larensis; however, disease is mainly caused most cases of tularemia occur in the sum- by F. tularensis subspecies tularensis (type mer in the south-central states, specifically A) and F. tularensis subspecies holarctica Missouri, Arkansas, and Oklahoma. There (type B).1 Type A is more virulent and is are six major tularemia clinical syndromes primarily found in North America.1 Type each with different clinical presentations: B is found throughout the Northern Hemi- ulceroglandular tularemia (42%-75% of sphere, mainly in Europe and Asia, and all tularemia cases), glandular tularemia causes milder infection than type A.1 F. tu- (15%-44% of all tularemia cases), oro- larensis is highly contagious; only a small pharyngeal tularemia, oculoglandular inoculum is needed to produce disease.1 tularemia, typhodial tularemia, and pneu- More than 100 species of mammals monic tularemia. The diagnosis of tula- have been noted to be infected with tulare- remia is typically made clinically, taking mia. This includes rabbits, hares, muskrats, into account exposure history and clinical prairie dogs, skunks, raccoons, rats, voles, manifestations and confirmed by serologic squirrels, sheep, cattle, and cats.1 Disease © Shutterstock testing. Aminoglycosides are the drugs of transmission can occur via handling the in laboratories where F. tularensis is pres- choice for the treatment of tularemia. Tu- carcass of an infected animal, via the bite ent. The disease can also be transmitted by laremia prevention is best accomplished by of a infected animal, or via ingestion of drinking water contaminated with F. tula- keeping away from dead or infected ani- meat from a diseased animal. rensis; this organism can survive in water mals and avoiding ticks. The bite of an insect vector such as a and animal carcasses for long periods. tick, deer fly, or flea can also transmit tula- Frozen rabbit meat has remained infective Nada S. Harik, MD, is Assistant Professor, De- remia to humans. Insects become infected for greater than 3 years.3 Person-to-person partment of Pediatrics, Division of Pediatric when they feed on an infected animal; ticks transmission of tularemia does not occur. Infectious Diseases, University of Arkansas for can also become infected by transovarian In the US, 90 to 154 cases of tularemia Medical Sciences. passage.2 In the United States, ticks are the have been reported yearly to the Centers Address correspondence to: Nada S. Harik, most common and important insect vector for Disease Control and Prevention (CDC) MD, Department of Pediatrics, Division of Pediat- of tularemia.2 Tick species that transmit from 2001 to 2010.4 Tularemia has been ric Infectious Diseases, University of Arkansas for tularemia to humans include Amblyomma reported by every state except Hawaii.4 Ar- Medical Sciences, 1 Children’s Way, Slot 512-11, americanum (lonestar tick), Dermacentor kansas, Oklahoma, and Missouri account Little Rock, AR 72202-36591; email: hariknada@ andersoni (wood tick), and Dermacentor for approximately 50% of the cases of tula- uams.edu. variabilis (dog tick). remia reported in the US each year.5 Figure Disclosure: The author has no relevant finan- Tularemia can also be caused by con- 1 (see page 289) is a CDC map detailing cial relationships to disclose. tact with aerosolized bacteria from mow- the locations of reported cases of tularemia doi: 10.3928/00904481-20130619-13 ing lawns, working on farms, or working from 2001 to 2010.4 288 | Healio.com/Pediatrics PEDIATRIC ANNALS 42:7 | JULY 2013 FEATURE Tularemia presents most commonly TABLE 1. in the summer, due to high tick activity, in the south-central US and peaks in the Common Characteristics of the Six Tularemia winter, the primary hunting season, in the Clinical Syndromes northeastern US.1 Individuals at risk for Tularemia Syndrome Characteristics Portal of Entry developing infection include hunters, trap- Ulceroglandular Skin papule followed by ulcer, tender lymph- Skin pers, taxidermists, grounds maintenance adenopathy, fever workers, sheep herders/shearers, labora- Glandular Tender lymphadenopathy, fever Unknown (likely skin) tory workers, those with tick exposure, and Oropharyngeal Severe pharyngitis, cervical lymphadenitis, fever Oropharyngeal mucosa those living in or traveling to areas where Oculoglandular Conjunctivitis, Parinaud’s oculoglandular Conjunctiva tularemia is endemic. The highest inci- syndrome dence of tularemia occurs in children (and Typhodial Fever of unknown cause, sepsis, myalgia, headache Oropharyngeal mucosa in adults older than age 75 years); boys or respiratory tract have a higher incidence of infection than Pneumonic Pneumonia, fever Respiratory tract girls.5 The higher incidence in boys is most likely due to their greater participation in activities such as hunting that increase exposure to tularemia. Figure 2 (see page 290) shows the age and gender of reported tularemia cases from 2001 to 2010.4 CLINICAL SYNDROMES AND MANIFESTATIONS The incubation period of tularemia is 1 to 21 days, with an average of 2 to 5 days. There are six major tularemia clinical syn- dromes, which are classified by the portal of entry of the infection (see Table 1). Ulceroglandular Tularemia The most common syndrome, account- Figure 1. Reported cases of tularemia, United States, 2001 to 2010. One dot placed randomly within ing for between 42% and 75% of all cases county of residence for each confirmed case. (From US Centers for Disease Control and Prevention4) of tularemia, is ulceroglandular tulare- mia.6-8 This syndrome is characterized by malaise. The most common sites of lymph younger than 6 years and had ulceroglan- a painful swollen papule at the portal of en- node involvement in a recent review of dular or glandular disease.8 try of the infection (skin) that becomes an pediatric tularemia in Arkansas were head ulcer. Tender lymphadenopathy is present and neck (33%), followed by inguinal ad- Oropharyngeal Tularemia proximal to the papule/ulcer (see Figure 3, enitis (30%).8 Traditionally representing less than page 291). Fever and malaise are common- In 50% of untreated cases of ulcero- 5% of cases of tularemia, infection with ly seen with ulceroglandular tularemia. glandular or glandular tularemia, lymph oropharyngeal tularemia is established nodes suppurate and drain.1 Lymph node through the oropharyngeal mucosa, most Glandular Tularemia suppuration can occur even in the setting of commonly by eating undercooked meat Glandular tularemia, representing 15% appropriate antibacterial therapy. Glandu- from an infected animal.6,7 The hallmarks to 44% of all cases of tularemia,6-8 presents lar tularemia is more common in children of oropharyngeal tularemia are severe with tender lymphadenopathy. Involved than adults; 44% of children compared pharyngitis (out of proportion to pharyn- lymph nodes are most commonly axillary, with 16% of adults had primary glandular geal appearance), cervical lymphadenitis, inguinal, or cervical. The portal of entry tularemia in a Missouri study of tularemia.7 and fever. Oral ulcers and/or an oropha- with glandular tularemia is unknown but Likewise, in a review of 30 cases of pediat- ryngeal pseudomembrane may be pres- most likely is through the skin. Common ric tularemia from 1996 through 2006 from ent. Cervical lymph nodes may suppurate additional symptoms include fever and Arkansas, the majority of children were and drain. PEDIATRIC ANNALS 42:7 | JULY 2013 Healio.com/Pediatrics | 289 FEATURE TABLE 2. Differential Diagnoses for the Various Clinical Syndromes of Tularemia Ulceroglandular and Oropharyngeal Tularemia Oculoglandular Typhodial Tularemia Pneumonic Tularemia Glandular Tularemia Tularemia Staphylococcus aureus Streptococcal pharyngitis Bartonella Bacterial sepsis Typical and atypical bacterial pneumonia lymphadenitis Staphylococcus pyogenes Diphtheria Sporotrichosis Malaria Tuberculosis lymphadenitis Tuberculosis Viral pharyngitis Tuberculosis Brucellosis Legionnaire’s disease Non-tuberculous mycobacterium Syphilis Q fever Q fever Bartonella Coccidioidomycosis Rickettsial diseases Fungal pneumonia Anthrax HSV Ehrlichiosis Viral pneumonia HIV Typhoid fever Psittacosis Infectious mononucleosis Disseminated Plague tuberculosis Sporotrichosis Disseminated Lymphoma histoplasmosis Lymphogranuloma venereum Lymphoma Oculoglandular Tularemia Oculoglandular tularemia was noted 80 to cause 4% of all cases of tularemia in 70 Missouri from 2000 to 2007.7 Nodular conjunctivitis, conjunctival inflammation, 60 and edema are typically seen and corneal Male ulcers may occur. Regional lymphadeni- 50 Female tis is also seen. Oculoglandular tularemia 40 can manifest as Parinaud’s oculoglandular Cases syndrome (conjunctivitis and painful ip- 30 silateral preauricular lymphadenopathy). The conjunctiva is the portal of entry for 20 oculoglandular tularemia and infection is 10 usually caused by direct inoculation from infected fingers. 0 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 5 year age group Typhodial Tularemia Figure 2. Reported tularemia cases in the United States
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