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Educational Workshop Educational Workshop EW14: Pathogenic intracellular bacteria arranged with ESCAR (ESCMID Study Group for Coxiella, Anaplasma, Rickettsia and Bartonella) Convenors: Gilbert Greub (Lausanne, CH) Pierre-Edouard Fournier (Marseille, FR) Faculty: Amel Omezzine Letaief (Sousse, TN) Pierre-Edouard Fournier (Marseille, FR) Achilleas Gikas (Heraklion, GR) Gilbert Greub (Lausanne, CH) Letaief –Spotted fever rickettsiosis Tick-Borne rickettsial pathogens Spotted Fever Group Rickettsioses (SFGR) Amel Omezzine Letaief, MD Farhat Hached Hospital ; Sousse - Tunisia 22/04/2009 ESCAR, 19th ECCMID - Helsinki 1 Session objectives ? True or False ? •There are multiple SFGR •SFGR are of limited geographic distribution •Clinical features are specific of rickettsia species •SFGR are severe diseases •Diagnosis of SFGR is difficult to confirm •Therapy of SFGR has been optimized 22/04/2009 ESCAR, 19th ECCMID - Helsinki 2 Clinical case • A 55-year-old Finnish man, traveled to Africa and south Europe : Cruise on the mediterranean sea for 10 days, on September • 5 days after return : Abrupt onset of fever (40°C) Loss of appetite, Headache Abdominal pain 1 episode of diarrheae • No medical history, no medication 22/04/2009 ESCAR, 19th ECCMID - Helsinki 3 3 Letaief –Spotted fever rickettsiosis Clinical case Continues… _______________________________________ •Physical examination at day 3 : –No signs of severe sepsis –Fever + generalized maculo-papular rash –Purpuric lesions on legs - Biological tests including : –blood smears (-), –blood cell count, normal •And Rickettsioses!!… SFGR ? 22/04/2009 ESCAR, 19th ECCMID - Helsinki 4 22/04/2009 ESCAR, 19th ECCMID - Helsinki 5 Which Rickettsia ? Order : Rickettsiales et Bartonellaceae (Bartonella + Rochalimaea) Tribu : Rickettsiaceae Anasplasmataceae Genus : Orientia Rickettsia O tsutsugamushi Typhus group (Spotted Fever Group) (scrub typhus) Epidemic typhus R.prowazekii R rickettsii RMSF Murine typhus R.typhi R. conorii MSF R. akari vesicular fever R. africae African tick bite rickett Excluded from Rickettsiales : R. felis Cat-flea typhus Coxiella burnetii (Q fever) …. 22/04/2009 ESCAR, 19th ECCMID - Helsinki 6 4 Letaief –Spotted fever rickettsiosis SFG Rickettsial pathogens and diseases • Rickettsia akari Rickettsialpox • Rickettsia felis Flea-borne spotted fever or cat flea typhus • Rickettsia australis Queensland tick typhus • Rickettsia helvetica Aneruptive fever • Rickettsia massiliae Spotted fever • Rickettsia aeschlimannii Spotted fever • Rickettsia rickettsii Rocky mountain spotted fever • Rickettsia sibiricasibirica Siberian tick typhus • Rickettsia sibiricamongolitimonae LAR • Rickettsia slovaca TIBOLA-DEBONEL • Rickettsia africae African tick bite fever • Rickettsia conorii conorii Mediterranean spotted fever • Rickettsia conorii israelensis Israeli spotted fever • Rickettsia conorii caspia Astrakhan fever • Rickettsia conorii indica Indian tick bite typhus • Rickettsia heilongjiangensis Far Eastern tick-borne rickettsiosis • Rickettsia japonica Japanese or oriental spotted fever • Rickettsia parkeri Spotted fever • Rickettsia honei Flinders island spotted fever • Rickettsia raoultii DEBONEL-TIBOLA 22/04/2009 ESCAR, 19th ECCMID - Helsinki 7 A. Renvoisé, D. Raoult / Médecine et maladies infectieuses 39 (2009) SFGR • Most tick - borne rickettsioses !!!! •R. akari (Ricketsialpox) : mite •R. felis : flea • Disease named by geographic distribution •Mediterranean spotted fever •Rocky Mountain spotted fever •Queensland tick typhus •North Asian tick typhus. • Human are incidental host • Natural host are small mammal !! Not all known •wild rodents, mouse, dog 22/04/2009 ESCAR, 19th ECCMID - Helsinki 8 Life cycle- Human contamination Human yes TICK : no non Adult Vector and Adult♀ ♂ Reservoir ouiyes Nymph larva vertebrate Host ? reservoir? 22/04/2009 ESCAR, 19th ECCMID - Helsinki 9 5 Letaief –Spotted fever rickettsiosis ~ 20 SFGRickettsial pathogens… R. C. Astrakhan R. slovaca R. mongolotimonae R. helvetica R. sibirica R. mongolotimonae R. C israëli R. helvetica R. conorii R. aeschlimannii R. C israëli R. japonica R. conorii R. rickettsii R. C. indica R. conorii R. australis R. africae R. honei 22/04/2009 ESCAR, 19th ECCMID - Helsinki 10 Distribution, vector, and main clinical features of the different subspecies of SFGR Symptoms , % patients Fatal forms? Rickettsia Vector tick Geographic repartition Human Disease Inoculation (% patients) Fever Eschar Rash R. conorii Rhipicephalus Mediterraneanarea Mediterranean 91– 20–87 93–100 Yes conorii, sp., Croatia, Slovenia, Kenya, spotted fever 100 (0–18.1) isolates Haemaphysali Somalia, South Africa, Malish, s leachii and surrounding the Moroccan Black Sea Kenyan R. conorii Rh. Israel, Portugal, Sicily Israeli spotted 100 0–46 98–100 Yes israelensis sanguineus fever (0–3. 5) R. conorii Rh. Astrakhan region, Chad, Astrakhan 100 23 94 No caspia sanguineus, R. Kosovo pumilio spotted fever R. conorii Rh. India, Pakistan Indian tick 100 Rare 100 No indica Sanguineus typhus (freq. Boophilus purpuric) microplus, H. leachii R. rickettsii Dermacentor North, Centerand south Rocky 100 Rrare 100 Yes, 5-10 1919 andersoni America mountain purpuric Dermacentor variabilis spotted fever 22/04/2009 ESCAR, 19th ECCMID - Helsinkiadapted from ww.cdc.gov/eid• Vol. 14, No. 9,11 2008 Distribution, vector, and main clinical features of the different subspecies of SFGR Symptoms , % patients Fatal Geographic Rickettsia Vector tick Human Disease forms? repartition Inoculation Fever Eschar Rash (%) R. Slovaca Dermacentor Europe TIBOLA - rare >80, drai- No No marginatus DEBONEL ning ADP R.africae Amblyomma ; Souh Africa, west African tick-bite 88 Yes (55), 50 No Indies fever multiple R. Aeschli- Hyalomma Africa, South Europe Spotted fever 100 Yes, multiple yes No mannii marginatum (rare cases reported) R. akari mite USA, Corea, East Rickettsialpox 97- 90 100 No Europe 100 vesicular R. japonica Haemophysalis Japon, Chine Japanese/ Oriental 100 90 purpiric Severe Dermacentor spotted fever forms up to20% (4) R. sibirica Dermacentor Central Asia, China Siberian tick yes yes yes ? Haemophysalis typhus R. mongo- Hyalomma China, Europe, Spotted fever yes yes Few spots No lotimonae asiaticum Africa R. australis Ixodes Australia Queensland tick yes 50% Yes low holocyclus fever vesicular R. honei Ixodes, Thailand, Australia Flinders Island tick yes rare Yes, ? Aponomma typhus purpuric 22/04/2009 ESCAR, 19th ECCMID - Helsinki 12 6 Letaief –Spotted fever rickettsiosis Epidemiologic and Clinical Features frequent SFGR • Mediterranean Spotted Fever Group (MSF) R.conorii – Hot season – Mediterranean region, south Europ, Africa – Rural area, dogs tick –bite – Eschar inoculation « Tache noire » + fever + Maculo-papular eruption – Rare severe forms • Rocky Mountain Spotted Fever (RMSF) R. rickettsii – America, North – Tick bite, – Fever + purpuric rash, eschar rarely – Frequent severe forms 22/04/2009 ESCAR, 19th ECCMID - Helsinki 13 Epidemiologic and Clinical Features frequent SFGR • African tick-bite fever R. africae – Hot season – Africa, subsaharian – multiple tick –bite – Eschars of inoculation + fever + Maculo-papular eruption – Rare severe forms • TIBOLA : Tick-Borne Lyphadenopathy R.slovaca – Europe – Tick bite, winter, women and children!! – Eschar of the scalp + Fever + Lyphadenopathy – Sequellae : alopecia 22/04/2009 ESCAR, 19th ECCMID - Helsinki 14 Mediterranean Spotted Fever History – 1910 : disease described by CONOR and BRUSH in Tunisia – 1925 : «tache noire» described by PIERI in Marseille – 1930 : role of dog’sTick Rhipicephalus sanguineus – 1932 : R. conorii by Brumpt 22/04/2009 ESCAR, 19th ECCMID - Helsinki 15 7 Letaief –Spotted fever rickettsiosis MSF Clinical features of hospitalized patients Central Tunisia Marseille Clinical findings (%) (%) Fever (100) (100) Headache (76) (56) The clinical triad Chills (46.5) - fever +rash+ Eschar Cough (17.5) (10) 55 - 70% Myalgia (58) (36) Rash (92.5) (97) Eschar lesion (62) (72) Conjunctivitis (12) (9) Gastrointestinal symptoms (20) Hepatomegaly and or (8) (10) splenomegaly 22/04/2009 ESCAR, 19th ECCMID - Helsinki 16 22/04/2009 ESCAR, 19th ECCMID - Helsinki 17 Characteristics of eschar (Tache noire) Central Tunisia (%) Presence of Eschar (62) Number one (95.5) 2 (4.5) Sites of Eschar trunk (16) extremities (33.5) gyrus (9.5) genital organs (24.5) breast (4) others (12.5) 22/04/2009 ESCAR, 19th ECCMID - Helsinki 18 8 Letaief –Spotted fever rickettsiosis Laboratory findings Central Tunisia Marseille (%) (%) Leukopenia and/or (79) (75) normal blood cells Thrombocytopenia (55) (35) Elevation of (60) (39) transaminases Hyponatremia (58) (25) Increased LDH level (94) - Creatinine (µmol) >150 (5) (6) Elevated ESR (> (80) - 30mm/h) ESR: eleva ted erythrocyte sedi mentation rate 22/04/2009 ESCAR, 19th ECCMID - Helsinki 19 Ocular manifestations • Prospective study, 30 patients with MSF underwent complete ophthalmic examination • 25 (83.3%) had unilateral or bilateral posterior segment involvement (white retinal lesions), 9 patients had ocular complaints • Final visual acuity was 20/20 in 93% of affected eyes Khairallah M, Ophthalmology 2004; 111 (3): 529-34 22/04/2009 ESCAR, 19th ECCMID - Helsinki 20 Diagnosis Score Epidemiologic criteria • Endemic area 2 • Hot season (May –September) 2 • Tick bite 2 ≥ 17 Clinical criteria S=85% • Fever exceeding 39°C 5 SPF=30% • Eschar (tache noire) 5 • Maculopapularor purpuricrash 5 • Two (of three) clinical criteria 3 • All three clinical criteria 5 _____ 29 Letaief A. Ann N Y Acad Sci. 2003 (from Raoult’sscore) 22/04/2009
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