TULAREMIA ALL SUSPECT CASES OF TULAREMIA MUST BE REPORTED IMMEDIATELY TO THE HEALTH AND HUMAN SERVICES COMMUNICABLE DISEASE CONTROL: During business hurs: (916) 875-5881 After hurs (Health Officer On call): (916) 875-5000 Epidemilgy: Highly infectius after aerslizatin Infectius dse can be as lw as 10-15 rganisms Persn-t-persn transmissin des nt ccur Clinical: Incubatin perid is 3-6 days (ranges 1-21 days) Aerslizatin wuld mst likely result in typhidal tularemia, with pneumnic invlvement Typhidal tularemia is a nnspecific illness, with fever, headache, malaise and nn-prductive cugh (mrtality rates can be as high as 30-60%) Diagnsis requires high index f suspicin given nnspecific presentatin Labratry Diagnsis: Bacterial cultures shuld be handled in a Bisafety Level 3 facility; islatin f rganism can therwise put labratry wrkers at risk. Organism is difficult t culture and grws prly n standard media; cysteine-enriched media is required. Serlgy is mst cmmnly used fr diagnsis. Cntact the Sacrament Cunty Public Health Labratry fr assistance. Patient Islatin: Treatment: Prphylaxis: Standard precautins. Respiratry islatin nt required. Streptmycin (7.5 mg/kg IM q 12 hurs x 10-14 days) r gentamicin (3-5 mg/kg/day IV r IM qd in 3 divided dses x 10-14 days) are the preferred antibitics Tetracyclines are alternative chices, althugh they are bacteristatic and assciated with higher relapse rates and must be cntinued fr at least 14 days Antibitic prphylaxis is mst effective if begun within 24 hurs after expsure t aersl Tetracyclines are recmmended fr 14 days
SACRAMENTO COUNTY HEALTH AND HUMAN SERVICES COMMUNICABLE DISEASE CONTROL Medical Treatment and Respnse t Suspected Tularemia: Infrmatin fr Health Care Prviders During Bilgic Emergencies I. Key Summary Pints II. Intrductin/Epidemilgy III. Significance as a Ptential Biterrrism Agent IV. Clinical Manifestatins V. Labratry Diagnsis VI. Handling Labratry Specimens VII. Treatment VIII. Islatin f Patients IX. Dispsal f Infectius Waste X. Autpsy and Handling f Crpses XI. Management f Expsed Persns XII. Reprting During Business Hurs After Business Hurs XIII. References ALL SUSPECT CASES OF TULAREMIA MUST BE REPORTED IMMEDIATELY TO THE SACRAMENTO COUNTY HEALTH AND HUMAN SERVICES, COMMUNICABLE DISEASE CONTROL: During Business Hurs: (916) 875-5881 After Hurs (Nights, Weekends and Hlidays): Health Officer On call, at (916) 875-5000
I. KEY SUMMARY POINTS Epidemilgy: Highly infectius after aerslizatin Infectius dse can be as lw as 10-15 rganisms Persn-t-persn transmissin des nt ccur Clinical: Incubatin perid is 3-6 days (ranges 1-21 days) Aerslizatin wuld mst likely result in typhidal tularemia, with pneumnic invlvement Typhidal tularemia is a nnspecific illness, with fever, headache, malaise and nn-prductive cugh (mrtality rates can be as high as 30-60%) Diagnsis requires high index f suspicin given nnspecific presentatin Labratry Diagnsis: Bacterial cultures shuld be handled in a Bisafety Level 3 facility; islatin f rganism can therwise put labratry wrkers at risk Organism is difficult t culture and grws prly n standard media; cysteine-enriched media is required Serlgy is mst cmmnly used fr diagnsis Cntact Sacrament Cunty Public Health Labratry at (916) 874-9231 fr assistance. Patient Islatin: Standard precautins. Respiratry islatin nt required. Treatment: Streptmycin (7.5 mg/kg IM q 12 hurs x 10-14 days) r gentamicin (3-5 mg/kg/day IV r IM qd in 3 divided dses x 10-14 days) are the preferred antibitics Tetracyclines are alternative chices, althugh they are bacteristatic and assciated with higher relapse rates and must be cntinued fr at least 14 days Prphylaxis: Antibitic prphylaxis is mst effective if begun within 24 hurs after expsure t aersl Tetracyclines are recmmended fr 14 days ALL SUSPECT CASES OF TULAREMIA MUST BE REPORTED IMMEDIATELY TO THE SACRAMENTO COUNTY HEALTH AND HUMAN SERVICES, COMMUNICABLE DISEASE CONTROL: During Business Hurs: (916) 875-5881 After Hurs (Nights, Weekends and Hlidays): Health Officer On call, at (916) 875-5000
II. III. IV. Intrductin/Epidemilgy Tularemia is a zntic disease caused by Francisella tularensis, a gram-negative intracellular cccbacillus. F. tularensis has several bivars; F. tularensis bivar tularensis is the mst cmmn naturally-ccurring islate in the United States. The rganism is primarily recvered frm lagmrphs (rabbits), rdents and arthrpds (ticks and deer flies) in the United States and frm water, msquites and aquatic mammals utside the United States. The rabbit is the vertebrate mst cmmnly assciated with tularemia in Nrth America. In recent years, the reprted incidence f tularemia has declined t less than 200 cases per year in the United States. Tularemia is acquired under natural cnditins by direct inculatin (such as an arthrpd bite), animal cntact such as skinning r eating infected animals, r via the airbrne rute. (Dmestic cats have ccasinally transmitted tularemia by bites r scratches.) F. tularensis may survive fr prlnged perids in water, mud and animal carcasses; even if frzen Francisella tularensis is highly infectius. After aerslizatin, 10-50 virulent rganisms given by aersl can cause infectin in humans, and as few as 10 rganisms can cause infectin when administered percutaneusly. In the event f a biterrrist attack, aerslizatin wuld be the mst likely rute f infectin. Tularemia transmissin frm patient-t-patient has never been reprted, even amng patients with tularemia pneumnia. Persns expsed t an aersl f Francisella tularensis d nt present a risk fr secndary infectin f thers r fr re-aerslizatin f the rganism. Significance as a Ptential Biterrrist Agent Weapnized by the United States military during the bilgic ffensive prgram in the 1950s-1960s. Highly infectius after aerslizatin; infectius dse can be as lw as 10 t 50 micrrganisms if inhaled. Aerslized F. tularensis wuld cause typhidal tularemia (a nnspecific, febrile illness), with high mrtality rates (30-60%) if untreated. Clinical Manifestatins During an act f biterrrism, release f an aersl will be the mst likely rute f transmissin with typhidal tularemia the mst likely clinical presentatin. There are several different classificatin systems fr clinical tularemia. The mst straightfrward classifies tularemia int ulcerglandular (75% f patients) and typhidal (25% f patients). Ulcerglandular disease invlves lesins n the skin r mucus membranes (including cnjunctiva), lymph ndes larger than 1 cm, r bth. In typhidal tularemia, the lymph ndes are usually smaller than 1 cm and n skin r mucus membrane lesins are present--this frm is mre cmmnly assciated with pneumnia and has a higher mrtality rate. A. Typhidal Tularemia -- An acute, nnspecific febrile illness assciated with F. tularensis that is nt assciated with prminent lymphadenpathy. Typhidal tularemia is mainly due t inhalatin f infected aersls. Mst likely frm during an act f biterrrism. Incubatin perid: 3-6 days (range 1-21 days)
Symptms - prminent symptms include: fever with chills headache myalgias sre thrat anrexia nausea vmiting diarrhea (can be a majr cmpnent f illness, generally watery stl nt bldy) abdminal pain cugh Patients may develp a sepsis syndrme with hyptensin, adult respiratry distress syndrme, renal failure, disseminated intravascular cagulatin and shck. Pleurpulmnary disease (pneumnic tularemia) is cmmn with pulmnary infiltrates r pleural effusins seen in up t 45% f typhidal tularemia cases. A patchy, alvelar prcess is mst ften seen n chest x-ray. Patients may develp acute respiratry distress syndrme and require mechanical ventilatin. B. Ulcerglandular Tularemia -- generally due t inculatin f the rganism int the skin r mucus membranes. Incubatin perid: 3-6 days (range 1-21 days) Symptms - Lcal papule develps at the inculatin site, with prgressin t a pustule then an ulcer within several days. Lymphadenpathy develps in 85% f patients. Ndes are usually tender and 0.5-10 cm in diameter (mean 2 cm). Enlarged ndes may becme fluctuant, drain spntaneusly r persist fr mnths t years. A cutaneus ulcer ccurs in 60% f cases. Ulcers are usually singular and 0.4-3.0 cm in diameter, with heaped-up brders. Ulcers are almst always accmpanied by reginal lymphadenpathy. In additin, the fllwing symptms may be present (in decreasing rder f likelihd f appearance): fever (present in 85% f patients) chills headache cugh myalgia chest pain vmiting arthralgia sre thrat abdminal pain diarrhea dysuria back pain stiff neck Ulcerglandular tularemia can als be cmplicated by pleurpulmnary disease r pharyngeal invlvement. Pharyngeal tularemia (via ingestin f cntaminated fd, water r drplets) is assciated with severe thrat pain, exudative pharyngitis and ften pharyngeal ulceratins.
V. Labratry Diagnsis Rutine labratry wrk must be dne in Bisafety Level 2 facilities. Hwever, handling f bacterial cultures nce the rganism is identified shuld be dne in Bisafety Level 3 facilities If tularemia is suspected, please call the Sacrament Cunty Public Health Labratry at (916) 874-9231 t arrange fr submissin f specimens fr testing. After hurs, please call Health Officer On call, at (916) 875-5000. The diagnsis f tularemia requires a high index f suspicin since the disease ften presents with very nnspecific symptms. The diagnsis can be made by recvery f the rganism frm bld, ulcers, cnjunctival exudates, sputum, pleural fluid, lymph ndes, gastric washings and pharyngeal exudates. Since the rganism is difficult t islate and cnstitutes a ptential danger t labratry persnnel, serlgic evidence f infectin in a patient with a cmpatible clinical syndrme is cmmnly used fr diagnsis. Culture F. tularensis grws prly n standard media. It frms small, smth, paque clnies when grwn n media cntaining cysteine r ther sulfhydryl cmpunds (e.g., glucse cysteine bld agar r thiglycllate brth) at 37C. The rganism has als been islated frm autmated radimetric detectin systems if the media is subcultured n chclate agar. The bacteria grws slwly; sme strains may require up t 2-3 weeks t develp visible clnies. Ntify the clinical labratry in advance f submitting specimens fr culture which may cntain F. tularensis, since islatin f the rganism can put labratry wrkers at risk fr infectin. Serlgy Antibdy detectin assays include tube agglutinatin, micragglutinatin and ELISA. Significant antibdy des nt appear until the end f the secnd week f illness, peaks at 4-5 weeks, and can persist fr mre than a decade. A single titre (by tube agglutinatin) f > 1:160 is a presumptive psitive; a fur-fld rise is required fr a definitive serlgic diagnsis. ELISA and micragglutinatin tests may be mre sensitive than tube agglutinatin. Antibdies may crss-react with Brucella spp., Prteus 0X19 and Yersinia spp. but dithithreitl treatment f the serum will eliminate mst f these reactins. Serlgy testing is available thrugh natinal reference labratries. VI. Handling Labratry Specimens Tularemia is the third mst cmmnly reprted labratry-assciated bacterial infectin. Cases have ccurred amng clinical labratrians wrking with bacterial cultures. Labratry staff handling specimens frm persns wh are suspected f having tularemia must wear face masks with eye prtectin, surgical glves, prtective gwns, and she cvers --- especially when wrking with pure bacterial cultures. Labratry tests (such as serlgical examinatins and staining f impressin smears) can be perfrmed in Bilgical Safety Level 2 cabinets. Bld cultures shuld be maintained in a clsed system and clinical islates frm bld r any ther site shuld be handled in Bilgical Safety Level 3 cabinets. Every effrt shuld be made t avid splashing r creating an aersl. Bisafety Level 3 practices and facilities shuld be used fr inculatin, incubatin, centrifugatin and harvesting f cell cultures and the manipulatin f infected tissues.
VII. VIII. IX. Accidental spills f ptentially cntaminated material shuld be decntaminated immediately by cvering liberally with a disinfectant slutin (0.1% sdium hypchlrite r sdium hydrxide (0.1N)). All bihazardus waste shuld be decntaminated by autclaving. Cntaminated equipment r instruments may be decntaminated with a hypchlrite slutin, hydrgen perxide, peracetic acid, 1% glutaraldehyde slutin, frmaldehyde, ethylene xide, cpper irradiatin, r ther O.S.H.A. apprved slutins, r by autclaving r biling fr 10 minutes. Treatment The treatment f chice fr all frms f tularemia except meningitis is streptmycin; gentamicin is an acceptable alternative. Fr bth drugs, dsages must be adjusted fr renal insufficiency. Gentamicin is safe during pregnancy; avid streptmycin due t its assciatin with irreversible deafness in children expsed in uter. (1) Streptmycin: Adult dsage is 0.5-1.0 gm (7.5 mg/kg) intramuscularly every 12 hurs fr 10-14 days. In very sick patients, streptmycin may be give at 15 mg/kg intramuscularly every 12 hurs fr 10-14 days. Pediatric dse: 15 mg/kg intramuscularly every 12 hurs fr 10-14 days. Alternatives: (2) Gentamicin: 3-5 mg/kg/day intravenusly r intramuscularly in three divided dses, with a peak serum level f at least 5 ug/ml desirable. Cntinue fr 10-14 days. Pediatric dse: 2.5 mg/kg intravenusly r intramuscularly every 8 hurs fr 10-14 days (3) Tetracycline and chlramphenicl are bacteristatic and assciated with high relapse rates. These agents must be cntinued fr a minimum f 14 days. Tetracycline: 2 grams /day IV r rally in fur divided dses r dxycycline 100 mg IV r rally twice a day fr at least 14 days. Pediatric dse: [Nt recmmended fr children less than 9 years, pregnant r lactating wmen] If > 45 kg, give adult dsage f dxycycline; if less than 45 kg, give 2.2 mg/kg twice a day. Tetracycline at 30 mg/kg/day rally, t a maximum f 2 grams/day, in fur divided dses fr at least 14 days. Chlramphenicl shuld generally nt be used due t the availability f effective alternatives with fewer serius side effects. (4) Additinal agents with favrable in vitr susceptibility tests but limited clinical data n efficacy include: flurquinlnes (except cinxacin), erythrmycin (resistant strains f F. tularensis have been identified), and rifampin. Penicillin and cephalsprins are nt effective and shuld nt be used t treat tularemia. Meningitis A rare cmplicatin f tularemia, meningitis requires special attentin with regard t therapy as the penetratin f streptmycin r gentamicin int the CSF is subptimal. The treatment f meningeal infectin shuld include cmbinatin therapy with chlramphenicl plus streptmycin r pssibly a third-generatin cephalsprin plus streptmycin (limited data available n efficacy). Islatin f Patients Tularemia is nt transmissible frm persn-t-persn. Standard precautins shuld be fllwed fr all patients -- respiratry islatin rms are nt required. Ulcers r wunds in patients with tularemia shuld be cvered and cntact islatin maintained as F. tularensis can be islated frm such lesins fr ne mnth r lnger. Dispsal f Infectius Waste Use f tracking frms, cntainment, strage, packaging, treatment and dispsal methds shuld be based upn the same rules as all ther regulated medical wastes.
X. Autpsy and Handling f Crpses All pstmrtem prcedures are t be perfrmed using Respiratry Precautins. Effrts shuld be made t avid aerslizatin. All persns perfrming r assisting in pstmrtem prcedures must wear mandated P.P.E. (persnal prtective equipment) as delineated by O.S.H.A. guidelines. Instruments shuld be autclaved r sterilized with a 10% bleach slutin r ther slutins apprved by O.S.H.A. Surfaces cntaminated during pstmrtem prcedures shuld be decntaminated with an apprpriate chemical germicide such as 10% hypchlrite r 5% phenl (carblic acid). XI. XII. Management f Expsed Persns An expsed persn is defined as a persn wh has been expsed t the release f a Francisella tularensis-cntaining aersl. Pst-expsure prphylaxis: Antibitic prphylaxis shuld begin as sn as pssible after expsure and is mst effective if begun within 24 hurs. Limited data suggests that tetracyclines may be effective: Tetracycline 500 mg rally in 4 divided dses fr 14 days Dxycycline 100mg rally twice daily fr 14 days Pediatric patients and pregnant wmen: Althugh tetracyclines are nt generally recmmended fr children under age 9 r fr pregnant wmen, the risk f develping tularemia may utweigh these limitatins. Flrquinlnes are a ptential alternative fr prphylaxis. Dxycycline: If > 45 kg - 100 mg rally every 12 hurs If < 45 kg - 2.2 mg/kg rally every 12 hurs If antibitic prphylaxis is nt started within 24 hurs f expsure, then expsed persns shuld be instructed t begin a fever watch and seek medical care if temperature exceeds 38.5 C. Reprting t the Health Department Tularemia is a reprtable cnditin in Califrnia. Cnfirmed r suspect tularemia cases must be reprted immediately: During business hurs Sacrament Cunty Health and Human Services Cmmunicable Disease Cntrl at (916) 875-5881 After business hurs Sacrament Cunty Health Officer On call, at (916) 875-5000
XIII. References Enderlin G, Mrales L, Jacbe RF, Crss JT. Streptmycin and alternative agents f r the treatment f tularemia: review f the literature. Clin Infect Dis. 1994;19:42-47. Evans ME, Friedlander AM. Tularemia. In: Sidell FR, Takafuji ET, Franz DR, eds. Medical Aspects f Chemical and Bilgical Warfare. Part I. Washingtn, DC: Office f the Surgen General at TMM Publicatins;1997:503-512. Evans ME, Gregry DW, Schaffner W, McGee ZA. Tularemia: A 30-year experience with 88 cases. Medicine. 1985;64:251-269. Fleming DO, Richardsn JH, Tulis JJ, Vesley D, eds. Labratry Safety Principles and Practices. 2nd ed. Washingtn, DC: American Sciety fr Micrbilgy;1995:324. Franz DR, Jahrling PB, Friedlander AM, et al. Clinical recgnitin and management f patients expsed t bilgical warfare agents. JAMA. 1997;278:399-411. Penn RL. Francisella tularensis (Tularemia). In: Mandell GL, Bennett JE, Dlin R, eds. Principles and Practice f Infectius Diseases. 4th ed. New Yrk, NY: Churchill Livingstn Inc; 1995:2060-2068. Sawyer WD, Dangerfield HG, Hgge AL, Crzier D. Antibitic prphylaxis and therapy f airbrne tularemia. Bacteril Rev. 1966;30:542-548. Turnbull PCB, Kramer JM. Bacillus. In: Balws A, Haulser WJ, Herrman KL, Shadmy HJ, eds. Manual f Clinical Micrbilgy 5th ed. Washingtn, DC: American Sciety fr Micrbilgy; 1991:298-299. Octber 2001 Used with permissin and adapted frm the New Yrk City Health Department/Bureau f Cmmunicable Diseases