Rocky Mountain Spotted Fever

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Rocky Mountain Spotted Fever 23.03.2013 CHYPRE «Emerging Rickettsioses» © by author ESCMID Online Lecture Library Didier Raoult Marseille - France [email protected] www.mediterranee-infection.com Gram negative bacterium Strictly intracellular Transmitted by arthropods: ticks, fleas, lice,© mites by author ESCMIDMosquitoes? Online Lecture Library U R 2 Louse borne disease - typhus Tick borne : the big killer - RMSF Other: less severe Flea borne - Murine typhus (Maxcy 1925 and Mooser 1921 ) Mite borne diseases - Scrub typhus (tsutsugamushi disease) Rickettsial pox (Huebner 1946© ) by author OtherESCMID rickettsia: non Online pathogenic Lecture Library Any Gram negative intracellular bacteria= Rickettsiales U R 3 NEW RICKETTSIAL DISEASES Many new diseases comparable to Arboviruses New clinical features no rash but adenopathy (R. slovaca, R. raoultii ) no rash, no inoculation eschar (R. helvetica ) others? Several species involved in a same area R. conorii and R. africae - Africa R. conorii, R. mongolotimonae© by author- France R. conorii, R. aeschlimannii - Spain, North Africa R. typhi and R. felis - USA ESCMID R. honei and R.Online australis - Australia Lecture Library R. rickettsii and R. parkeri - USA R. conorii and R. helvetica, R. slovaca - Switzerland U R 4 SITUATION DURING THE XXTH CENTURY One tick borne rickettsiosis per geographical area R. rickettsii agent of RMSF in the USA – other found in ticks: non pathogenic rickettsia (such as Coxiella burnetii or Legionella pneumophila) R. conorii alone in Europe© byand author Africa ESCMID Online Lecture Library Diagnostic provided by unspecific tools never contradict this! U R 5 TICK BORNE DISEASES IN THE 80 ties R. conorii R. sibirica R. rickettsii © by author ESCMID Online Lecture R.Library australis Anything else : non pathogenic U 6 R END XXTH BEGINNING XXITH CENTURY Molecular Biology 16S rRNA: first revolution Rickettsia specific genes: second revolution: Diagnostic PCR New Rickettsia and rickettsial disease © by author Genotyping rickettsiae correlation: ESCMID Genotype: epidemiology,Online Lecture pathotype? Library U R 7 R. rickettsii MOLECULAR BIOLOGY Rickettsia rickettsii R. prowazekii R. prowazekii Orientia tsutsugamushi R. tsutsugamushi R. quintana Ehrlichia chaffeensis E. ewingii C. burnetii E. canis E. ruminantium E. canis Anaplasma E. phagocytophila phagocytophilum E. sennetsu WolbachiaA. marginale pipientis C. ruminantium N. helminthoeca Neorickettsia sennetsu N.helminthoeca Bartonella quintana W. pipientis B. henselae B. talpae W. persica a B. bacilliformis R. grylli Brucella melitensis © by authorCoxiella burnetii Rickettsiales B. bacilliformis Rickettsiella grylli G. talpae Legionella pneumophila «Wolbachia persica» g Francisella tularensis ESCMIDA. marginale Online Lecture Library E. ovis Eperythrozoon ovis Hemobartonella felis H. felis Mycoplasma pneumoniae Gram + 8 Ureaplasma urealyticum a 1984 c b NOW END XXTH BEGINNING XXITH CENTURY Molecular Biology 16S rRNA: first revolution Rickettsia specific genes: second revolution: Diagnostic PCR New Rickettsia and rickettsial disease © by author Genotyping rickettsiae correlation: ESCMID Genotype: epidemiology,Online Lecture pathotype? Library U R 9 SKIN BIOPSY IS THE KEY OF DISCOVERY OF NEW RICKETTSIAL DISEASES © by author ESCMID Online Lecture Library U R 10 SWABING Bechah Y, Socolovschi C, Raoult D. Identification of rickettsial infections by using cutaneous swab specimens and PCR. Emerg Infect Dis. 2011 Jan;17(1):83-6. Mouffok N, Parola P, Raoult D. Murine typhus, Algeria. Emerg Infect Dis. 2008 Apr;14(4):676-8. © by author ESCMID Online Lecture Library 11 DIAGNOSTIC: PCR Tested R. prowazekii B. quintana B. recurrentis Ants 40 0 0 0 Lice 44 16 (36%) 5 (11%) 0 Tested gene Citrate synthase Citrate synthase 16srRNA © by authorITS Negative controls are critical ESCMIDTwo different genes Online for confirmation Lecture of atypical/unique Library case Avoid “open” nested PCR and positive controls U R 12 RAPID ID OF A TICK FROM PATIENT BY MALDI-TOF October 2-2012 Symtoms EPIDEMIOLOGY Travel place / date : Date of symtoms : Fever X Morphological identification: Ixodes ricinus Eschar only/ localisation : Eschar multiples / localisation : X mass spectrometry: I.ricinus score 1,5 Adenopathy / localisation : Single bite/ localisation : multiple bite / localisation : Rash : Maculo-papulus Purpuric Vesiculus Animals contact: => Identify risk factor X Other manifestation: erythematous lesions © by author ESCMID Online Lecture Library Date smarlab Bartonella C. burnetii Rickettsies Coxiella-like Borrelia A. phagoc 08/10/2012 1279089 neg neg neg neg neg ec 13 TICK-BORNE RICKETTSIOSES R. PA4 R. monacensis R. massiliae R. conorii caspia R. sibirica R. sibirica R. parkerii R. helvetica sibirica mongolitimonae R. mongolotimonae R. heilongjiangensis R. amblyommii R. conorii indica R.slovaca R. conorii R. 364D conorii R. conorii israeli R. japonica R. rickettsii © by author R. conorii conorii ESCMID Online LectureR. australis Library R. aeschlimannii R. africae R. honei 14 HOW TO FIND NEW (RICKETTSIAL) DISEASE 1. Anything atypical is a candidate (seasonal variation, severity, atypical clinical symptoms, atypical host) Exemple in France - R.conorii summer, mild to severe, fever generalized rash, 1 inoculation escar on the body. - R.massiliae South est, adultes males no difference, co-infection with R.conorii - R.sibirica mongolitimonae Spring, mild, several inoculation escars, rope like lymphangitis, adenitis, generalized rash and fever - R.slovaca/R.raoultii Cold season, children and women, scalp inoculation, neck adenitis© , bypost infection author fatigue, no fever or rash - R.africae Traveler, very mild, no or low fever, several inoculation eschars, rash in 50 % (vesicular in half case) ESCMID Online Lecture Library - R.helvetica fever, no rash, spring no escar 2. Swab escar or vesicule => PCR 15 What’s new? In Europe P. Parola, C.D. Paddock, D. Raoult. Tick-Borne Rickettsioses around the World: Emerging diseases challenging old concepts. © by authorClin Microbiol Rev. 2005; 18(4):719-56. ESCMID Online LectureFrom Library 1 to 9: Tick borne spotted fever since 1997. U 16 R Mediterranean Spotted Fever Rickettsia conorii Known since 1909 More common More severe (2-10% mortality rate in Portugal) More multiple escars Transmitted by Rhipicephalus sanguineus (world wide dog tick) Restricted to the old world: WHY!!!! © by author ESCMID Online Lecture Library U R 17 R.SANGUINEUS AGRESSIVITY INCREASE WITH TEMPERATURE R. sanguineus © by author ESCMIDWarmer weather linked Online to tick attack andLecture emergence of severeLibrary rickettsioses. Parola P, Socolovschi C, Jeanjean L, Bitam I, Fournier PE, Sotto A, Labauge P, Raoult D. PLoS Negl Trop Dis. 2008;2(11):e338. Epub 2008 Nov 18. May be true for RMSF 18 (Tibola-Debonel) Scalp Escar and Neck lymphadenopathy after tick bite - R. slovaca, R. raoultii Lymphangitis Associated Rickettsiosis - R. sibirica mongolitimonae Aneruptive rickettsiosis:© by author R. helvetica ESCMID Online Lecture Library U R 19 DERMACENTOR TICKS IN EUROPE R. SLOVACA Ambush strategy: • waits, falls • bites head • children © by author • cold season ESCMID Online Lecture Library U R 20 DERMACENTOR SEEKING HAIR © by author ESCMID Online Lecture Library U R 21 R. slovaca infection (compared to MSF) Based on 17 PCR confirmed cases More tick bite found Lesion in the hair Less fever More cervical lymph node Sequels : residual asthenia, localised alopecia Low death rate © by author Young age Females > males LowESCMID serological titres Online Lecture Library (Raoult D, et al. Clin Infect Dis. 2002 ;34:1331-6.) U 22 R U R Cases very closely related to TIBOLA Clinical cases identical to that caused by R. slovaca Present in Dermacentor, ¼ of that of R. slovaca Less pathogenic © by author Present in all Eurasia ESCMID Online Lecture Library 23 Scalp eschar and neck lymphadenopathy caused by Bartonella henselae after Tick Bite. Angelakis E, Pulcini C, Waton J, Imbert P, Socolovschi C, Edouard S, Dellamonica P, Raoult D. Clin Infect Dis. 2010 Feb 15;50(4):549-51. Abstract Rickettsia slovaca and Rickettsia raoultii have been associated with a syndrome characterized by scalp eschar and neck lymphadenopathy following tick bites. However, in many cases, the causative© by agentauthor remains undetermined. We report 3 cases of this syndrome caused by Bartonella henselae,ESCMID and Onlinewe propose Lecture the term Library "SENLAT" to collectively describe this clinical entity. 24 OTHERS AGENTS MORE COMMON IN COLD MONTHS AND SCALP ESCAR • Bartonella henselae • Francisella tularensis © by author Borrelia? ESCMID• Online Lecture Library U R 25 LYMPHANGITIS ASSOCIATED RICKETTSIOSIS (LAR) R.sibirica mongolitimonae Lymphadenopathy Fever, rash in spring Lymphangitis (5/10 cases) 2 “taches noires” (3/10 cases) Lymphadenitis Lymphangitis Clustered cases © by author Eschar Lymphangitis-associatedESCMID rickettsiosis, Online a new Lecture rickettsiosis caused Library by Rickettsia sibirica mongolotimonae: seven new cases and review of the literature. Fournier PE, Gouriet F, Brouqui P, Lucht F, Raoult D. U Clin Infect Dis. 2005 May 15;40(10):1435-44. 26 R ‘‘RICKETTSIA SIBIRICA MONGOLITIMONAE’’ HISTORICAL ASPECTS 1993 : First isolation from Hyalomma asiaticum ticks from Inner Mongolia Yu X, et al. J Clin Microbiol. 1993;31: 83-8. 1996 - 2003: – 9 cases in Marseilles, from France and Algeria Raoult D, et al. Lancet. 1996 ;348:412 Fournier PE, et al. Emerg Infect Dis. 2000;6:290-2. 2000 found
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