Tularemia incubation period Six different clinical forms Common to all ulceroglandular form

Transcription

1 Tularemia First described in Japan in 1837 Francisella tularensis: facultative, intracellular, aerbic, gram-negative, nnmtile, plemrphic, and primarily rd-shaped cccbacillus. F tularensis is an extremely virulent rganism. Althugh rabbits, rdents, and ticks are the mst well-knwn surces fr transmissin f the disease t humans, F tularensis has been identified in ver 100 species (cats, fxes, squirrels, muskrats, beavers ). Methds f transmissin include inhalatinal, ingestinal, and vectr-assciated expsure. the primary mde f transmissin is cntact with infected animals r their carcasses. transmissin can fllw cnsumptin f inadequately cked game meats the bite f a tick r deerfly disease can als result frm direct cntact with r ingestin f cntaminated sil, water, r fmites by inhalatin f water aersls r dust frm sil, grains, r cntaminated pelts Persn-t-persn transmissin is nt characteristic. After inculatin, F tularensis is ingested by and multiplies within macrphages The initial tissue reactin t infectin is a fcal, intensely suppurative necrsis cnsisting largely f accumulatins f plymrphnuclear leukcytes, fllwed by invasin f macrphages, epitheliid cells, and lymphcytes. Suppurative lesins becme granulmatus, and histpathlgical examinatin f the granulmas shws a central necrtic, smetimes caseating, zne surrunded by a layer f epitheliid cells, multinucleated giant cells, and fibrblasts, typical f ther granulmatus cnditins such as tuberculsis and sarcidsis. Cell-mediated immunity cnstitutes the majr prtective mechanism The humral immune respnse plays a limitedrle in the hst defense against naturally acquired infectin The incubatin perid is dependent n the size f the inculum but generally ranges frm 1-21 days (usually 2-6 d). Six different clinical frms f tularemia have been described: ulcerglandular, glandular, culglandular, rpharyngeal, pneumnic, typhidal. Cmmn t all are the fllwing : abrupt nset f fever (38 C 40 C) and chills (typically last fr several days, remit fr a brief interval, and then recur) headache, myalgias, malaise and fatigue r prstratin anrexia, vmiting, diarrhea pharyngitis, cugh, chest pain arthralgia, back pain abdminal pain secndary pneumnitis (may ccur in 45-83% f patients with the typhidal frm) The ulcerglandular frm (in sme series f patients, as many as 87% f cases f tularemia [>75% f adult cases, 44% f pediatric cases]) results in the fllwing: Small erythematus papule ccurs at site f inculatin; papule enlarges and ulcerates 2-3 days later. Ulcers are tender with raised edges and a jagged flr.

2 Tick-brne tularemia usually is in the grin and lwer extremities, the trunk, and the axillae. The rabbit-assciated frm is usually n hands r fingers. Lymphadenpathy/lymphadenitis may ccur with tender suppurative lcal enlargement reflecting site f entry. Reginal lymph ndes may becme fluctuant, ulcerate and drain spntaneusly Systemic adenpathy may ccur. In the glandular frm (3-20% f cases, secnd mst cmmn frm in adults), tender lymphadenpathy ccurs withut evidence f lcal cutaneus lesins. The bacterium presumably gains entry via micrscpic abrasins. In the culglandular frm (0-5% f cases, secndary t tuching r rubbing eyes with cntaminated hands), The rganism enters thrugh the cnjunctiva frm either a splash f infected bld r rubbing the eyes after cntact with infectius materials (eg, bld frm a rabbit carcass). incubatin perid f 3-5 (range 1-14) days, unilateral cnjunctivitis (with injectin and chemsis), ften with purulent exudate. lid edema, itching, lacrimatin, phtphbia ulceratins r papules n cnjunctivae painful preauricular and/r cervical lymphadenpathy The rpharyngeal frm r gastrintestinal tularemia via ingestin f cntaminated fd, undercked meat, cntaminated water r drplets, and ral inculatin frm the hands after cntact with cntaminated material. rpharyngeal tularemia presents either as: acute pharyngitis (may ccasinally develp a membrane resembling unilateral diphtheria) with ulcer(s), with cervical lymphadenpathy r ulcerative gastrintestinal lesins with abdminal pain, diarrhea, nausea, vmiting, mesenteric lymphadenpathy and gastrintestinal bleeding. The pneumnic frm (uncmmn): This frm ccurs when the rganism is inhaled. This frm is bserved in labratry wrkers and, ccasinally ccurs naturally. Pneumnia als ccurs in 10-15% f patients with ulcerglandular tularemia and in ne-half f thse patients with typhidal tularemia. Initial presentatin as atypical cmmunity-acquired pneumnia (CAP) unrespnsive t typical antibitic therapy fr CAP Illness may prgress rapidly t severe disease OR may be indlent with prgressive debilitatin ver several mnths Prminent symptms: abrupt nset f fever, nnprductive cugh, dyspnea, pleuritic chest pain, myalgias Hilar adenpathy, pleural effusin, pleural adhesins, brnchilitis, and/r pharyngitis may be present Nausea, vmiting, diarrhea may ccur 20% may have generalized maculpapular rash with prgressin t pustules r erythemandsum type rash Cmplicatins: Lung abscess r cavitary lesins, Respiratry failure, ARDS Chest radigraphy: Cmmn findings include bilateral patchy infiltrates, lbar, segmental, r subsegmental lbar infiltrates, cavitary lesins, r a pleural effusin. The typhidal (septicemic) frm (5-30% f cases) results in the fllwing: Fever, chills, malaise, weakness, myalgias, arthralgias

3 Prstratin GI symptms (watery diarrhea, vmiting, abdminal pain) Hepatmegalia Skin findings may include generalized maculpapular rash with prgressin t pustules r erythema-ndsum type rash Other symptms similar t thse f typhid fever In general, tularemia wuld be expected t have a slwer prgressin f illness and a lwer casefatality rate than either inhalatinal plague r anthrax Lab Studies: Standard labratry test results are nnspecific. Serum transaminases are mildly elevated in abut ne half f patients. Urinalysis may shw a sterile pyuria in as many as ne furth f patients. Cmplete bld cell cunt may shw an elevated WBC cunt, but results are ften within the reference range. Mild thrmbcytpenia may be present. Elevatin f creatine kinase may be bserved and is assciated with rhabdmylysis. Cerebrspinal fluid may shw a mild elevatin f prtein r plecytsis. Althugh the rganism has been cultured frm sputum, pleural fluid, wunds, bld, lymph nde bipsies, and gastric washings, the yield is extremely lw and culture pses a danger t labratry persnnel. Bld cultures have a pr sensitivity. Pr sensitivity is prbably due t the specific medium (cysteine-glucse-bld agar) needed t culture this rganism. Serlgic studies reveal the fllwing: Antibdies may be measured by agglutinatin and enzyme-linked immunsrbent assay (ELISA). An agglutinatin titer greater than 1:160 is cnsidered presumptively psitive, and treatment may be started if this result is btained. A secnd titer demnstrating a 4-fld increase in 2 weeks cnfirms the diagnsis. Nte that althugh titers begin t rise within 7-10 days after expsure, early titers in the first 2 weeks f illness may be negative in the setting f infectin. Indirect flurescent antibdy test f suppurative material is rapid and specific. Plymerase chain reactin (PCR) has been used t detect F tularensis even after initiatin f antibitics. It is nt yet available in mst labratries. Capture ELISA is a mre recent advancement that is based n mnclnal antibdies specific fr lipplysaccharide f the virulent frms f F tularensis. In animal studies, the capture ELISA has prven mre sensitive and specific than rutine ELISA and in fact rivals PCR withut the time and expense assciated with PCR. Histlgic Findings: Caseating granulmas may be fund n histlgic examinatin f lymph ndes. Treatment: Treatment shuld be cntinued fr days. Adults Preferred chices: - Streptmycin, 1g IM twice daily - Gentamicin, 5 mg/kg IM r IV nce daily Alternative chices: - Dxycycline, 100 mg IV twice daily - Chlramphenicl, 15 mg/kg IV 4 times daily - Ciprflxacin, 400 mg IV twice daily Children

4 Preferred chices: - Streptmycin, 15 mg/kg IM twice daily (shuld nt exceed 2 gm/d) - Gentamicin, 2.5 mg/kg IM r IV 3 times daily Alternative chices: - Dxycycline, If weight >= 45 kg, 100 mg IV If weight < 45 kg, give 2.2 mg/kg IV twice daily - Chlramphenicl, 15 mg/kg IV 4 times daily - Ciprflxacin, 15 mg/kg IV twice daily Pregnant Wmen Preferred chices: - Gentamicin, 5 mg/kg IM r IV nce daily - Streptmycin, 1 g IM twice daily Alternative chices: - Dxycycline, 100 mg IV twice daily - Ciprflxacin, 400 mg IV twice daily Mass Casualty Setting and Pstexpsure Prphylaxis expsed persns shuld be prphylactically treated with 14 days Adults Preferred chices: Dxycycline, 100 mg rally twice daily Ciprflxacin, 500 mg rally twice daily Children Preferred chices: Dxycycline, and If >=45kg give 100 mg rally twice daily If <45 kg then give 2.2 mg/kg rally twice daily Ciprflxacin, 15 mg/kg rally twice daily Pregnant Wmen Preferred chices: Ciprflxacin, 500 mg rally twice daily Dxycycline, 100 mg rally twice daily Cmplicatins: Suppurative lymphadenitis Pneumnitis, respiratry failure Renal failure Rhabdmylysis Pericarditis, endcarditis Meningitis Peritnitis, appendicitis Perisplenitis Ostemyelitis Guillain-Barre syndrme Prgnsis: Untreated typhidal tularemia can have a mrtality rate as high as 30%, but the verall mrtality rate fr tularemia is less than 10%. Treated tularemia has a mrtality rate f less than 1%. Special Cncerns:

5 A tularemia vaccine is available. This is a live vaccine but des nt prvide cmplete immunity and has the ptential f inducing the illness.