TULAREMIA

Caused by Francisella tularensis, a small, pleomorphic, gram-negative coccobacillus found naturally in the northern hemisphere and throughout the United States.  Transmission to humans usually occurs through a tick bite or direct contact with infected animals.

·        Naturally occurring tularemia in humans most commonly involves the skin and lymph nodes (ulceroglandular or glandular tularemia); pneumonic tularemia and other forms of tularemia are not as common.

·        Pneumonic tularemia, caused by inhaling aerosolized bacteria, would be the most likely outcome of an intentional (bioterrorist) aerosol release of F. tularensis.

·     Person-to-person transmission does NOT occur with pneumonic or other forms of    

      tularemia.

PNEUMONIC tularemia

Incubation: commonly 3-5 days (range 1-21 days)

Clinical Illness:

·        Fever, non- to minimally productive cough, sub-sternal tightness, pleuritic chest pain, occasional hemoptysis (though uncommon), as well as chills, headache, malaise, anorexia, and fatigue.

·        May be primary pneumonia or secondary due to bacteremic spread from other tularemia syndromes.

·        Chest X-ray may show infiltrates without symptoms.

-         Other CXR findings include: subsegmental/lobar infiltrates, hilar adenopathy, pleural effusion, or miliary infiltrates resembling tuberculosis (TB). 

-         Caseating granulomas can be seen on lung biopsy which may also lead to confusion with TB.

·        Can manifest as a community acquired pneumonia.

IF YOU HAVE REASON TO SUSPECT TULAREMIA, ALERT YOUR LABORATORY PERSONNEL IMMEDIATELY Culturing F. tularensis can result in exposure of laboratory personnel if proper procedures are not taken.

Laboratory Clues to F. tularensis:

• Pleural fluid usually exudative with more than 1000 leukocytes/mm³.

• Granulomas may develop (and occasionally caseate) and thus may be confused with TB.

Laboratory Confirmation of Diagnosis:

• Culture takes several days to become positive and MUST be done in a bio-safety level 2 or greater laboratory setting for protection of workers.  IF TULAREMIA IS SUSPECTED – INFORM LABORATORY IMMEDIATELY SO PROPER LABORATORY SAFETY PRECAUTIONS MAY BE TAKEN.  Once confirmed, specimens should be transferred to a Bio-Safety Level 3 facility such as the DPH Public Health Laboratories.

• Serologic diagnosis is usually made with microagglutination; however it may take up to two weeks for acute serologies to become positive.  An acute titer of 1:128 is presumptive for tularemia, with a 4-fold rise in titers four weeks later being diagnostic.

• PCR technology is being developed but this technology is not readily available.  If rapid detection is desired, please contact the DOH Public Health Laboratories for availability of immunofluorescence, antigen detection,  PCR and other rapid testing procedures that are under development.

TREATMENT OF PNEUMONIC TULAREMIA

• If untreated, fatality rate may be as high as 35%.

POST-EXPOSURE PROPHYLAXIS

• Antibiotic prophylaxis is not commonly used to prevent naturally-acquired tularemia.  In the case of a suspected bioterrorist release prophylaxis may be indicated.

• Initiation of prophylaxis with oral medications, especially in children, should be coordinated with the local health jurisdiction or the State DPH.

• Oral prophylaxis should continue for at least 14 days if the exposure is confirmed.

RECOMMENDATIONS¹ FOR THE TREATMENT OF PATIENTS WITH TULAREMIA IN THE CONTAINED AND MASS CASUALTY SETTINGS AND FOR POST EXPOSURE PROPHYLAXIS² 

1.      These are adapted from consensus recommendations of the Working Group on Civilian Biodefense and are not necessarily approved by the Food and Drug Administration.  In non-bioterrorism response situations, routine treatment guidelines should be followed.  Please refer to original publication (Dennis DT, Inglesby TV, Henderson DA, et al. Tularemia as a Biological Weapon: Medical and Public Health Management JAMA. 2001; 285: 2763-2773) for explanations and further discussion.

2.     One antimicrobial agent should be selected.  Persons beginning treatment with parenteral doxycycline, ciprofloxacin, or chloramphenicol can be switched to PO when clinically indicated. 

3.      Aminoglycosides must be adjusted according to renal function.  Neonates up to 1 week of age and premature infants should receive gentamicin, 2.5 mg/kg IV twice daily.

4.     Concentration should be maintained between 5 and 20 mg/mL.  Concentrations greater than 25 mg/mL can cause reversible bone marrow suppression.  Children younger than 2 years should not receive chloramphenicol.

5.      In children, ciprofloxacin dose should not exceed 1 g daily, chloramphenicol should not exceed 4 g daily. Children younger than 2 years should not receive chloramphenicol. In neonates, gentamicin loading dose of 4 mg/kg should be given initially. 

6.       Alternatives to breastfeeding may be required while mother is taking certain antibiotics, see specific antibiotic package insert for information on breastfeeding

SYSTEMIC TULAREMIA

• Febrile illness caused by F. tularensis without typical clinical features of other forms of tularemia.

• May be more common in persons with chronic illnesses and lead to rapid death or protracted illness.

• Nondescript symptoms: fever with chills, headache, myalgias, sore throat, anorexia, nausea, vomiting, diarrhea, abdominal pain, cough.

• Patients may develop sepsis with complication of bleeding and organ failure.

• Treatment is the same as for pneumonic tularemia (see Pneumonic Tularemia Treatment Protocol). 

OROPHARYNGEAL, ULCEROGLANDULAR or GLANDULAR TULAREMIA (possible, though unlikely, outcomes of a terrorist aerosol release of F. tularensis)

·        Pharyngeal form results from direct invasion of oral pharynx (contaminated food/water) causing sore throat with exudative tonsillitis/pharyngitis with one or more ulcers. Also, may involve cervical, preparotid and retropharyngeal lymph nodes with possible abscess formation.

·        Ulceroglandular form usually recognized as tularemia:

-   Enlarged, local tender lymph nodes.

-   Skin lesion (can appear before, simultaneously or after lymphadenopathy) starts as red, painful papule that progresses to necrotic painful draining ulcer with raised borders.

-   Multiple lesions may occur.

-   Glandular form is as above without skin lesions.

• Systemic symptoms and pneumonic symptoms (see pneumonic tularemia for both) may be present.

• Oculoglandular tularemia is a rare form resulting from inoculation of bacterium in eye with photophobia, excessive lacrimation, swollen eyelids, painful infected conjunctiva with small, yellowish conjunctival ulcers.

• Inhalation or inoculation of the eye from an aerosolized release may results in pharyngeal or ocular tularemia.

• Treatment is the same as for pneumonic tularemia.

Infection Control

·      Standard (Universal) Precautions for care and transport of patients and during post-mortem care.

·       Wound Precautions for patients with cutaneous tularemia.

·       Isolation of patients is NOT necessary.

·      After an invasive procedure, instruments and the area used should be autoclaved or decontaminated with 0.5% hypochlorite (a 1:10 dilution of household bleach).

·      Contaminated clothing/bedding should be placed in labeled, plastic bags for later incineration, steam sterilization, or laundry with hot water and bleach.

·      Surfaces contaminated during post-mortem procedures should be decontaminated with 0.5% hypochlorite (a 1:10 dilution of household bleach).

·      Any material used in cleaning must be autoclaved or incinerated.

·         Spills of potentially infected body fluid or tissue:

-      Allow aerosol to settle.

-     Gently cover, then liberally apply 0.5% hypochlorite (a 1:10 dilution of household bleach).

-     Let sit for at least 20 minutes before cleaning up (work from perimeter to center).

Contamination of personnel:

-        Remove outer clothing where spill occurred and place in a labeled, plastic bag for later incineration or steam sterilization.

-         Remove rest of clothing in the locker room and place in a labeled, plastic bag for later incineration or steam sterilization.

-         Shower thoroughly with soap and water.

·        If exposure to contaminated sharps occurs:

-       Follow standard reporting procedures for sharps exposures.

-         Notify the local or state department of health.

-         Thoroughly irrigate site with soap and water and apply a disinfectant solution such as 0.5% hypochlorite solution.  DO NOT SCRUB AREA.

-         Use a decontamination solution such as 0.5% hypochlorite (a 1:10 dilution of household bleach) for surfaces.

-         Let sit for at least 20 minutes before cleaning up (work from perimeter to center).

-         Routinely clean non-sterilizable equipment with a sterilizing solution.