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Mediterranean Spotted Fever & Q Fever © by author ESCMID Online LectureDr. LibraryFigen KULOĞLU Trakya University Faculty of Medicine Infectious Diseases Department EDİRNE Species of Rickettsia Small rod-shaped bacteria Obligately intracellular bacteria of the α-Proteobacteria Gram negative cell wall structure that contains lipopolysaccharide, peptidoglycan, outer membrane protein B, a 17-kDa© lipoprotein by author and for SFG rickettsiae outer membrane protein A ESCMID Online Lecture Library Giemsa and Gimenez stain Species of Rickettsia Rickettsia spp. reside in an arthropod host for at least a part of their life cycle tick, mite, louse, flea etc. Transovarian transmission Cycles involving horizontal transmission to mammalian hosts© by author ESCMID Online Lecture Library Species of Rickettsia Target cells = vascular endotelium Rickettsiae multiply in endothelial cells of small vessels, causing a vasculitis Cell-to- cell spread Vascular injury and subsequent host lymphohistiocytic response A perivascular lymphohistiocytic© by author infiltrate in the skin, brain, lung, kidneys, liver, etc. ESCMID Online Lecture Library Species of Rickettsia Divided into two main groups The typhus group R. prowazekii, R. typhi The spotted fever© groupby author R. conorii, R.rickettsii, R. akarii etc. ESCMID Online Lecture Library Etiology, epidemiology and ecology of rickettsial diseases Organism Disease Geographic ditribution Mode of transmission Natural cycle Spotted fever group R. rickettsii Rocky Mountain spotted Western Hemisphere Tick bite Transovarian in ticks and fever rodent-tick cycles R. akari Rickettsialpox USA, Ukraine, Crotia, Korea Mite bite Transovarian in mites and mite-mouse cycles R. conorii Mediterranean spotted fever Southern Europe, Africa, Tick bite Transovarian in ticks Middle East R. africae African tick bite fever Sub-Saharan Africa, Tick bite Transovarian in ticks Caribbean R. parkeri American tick bite fever North and South America Tick bite Transovarian in ticks R. sibirica North Asian tick typhus Asia, Europe, Africa Tick bite Transovarian in ticks R. japonica Japon spotted fever Japan Tick bite Ticks R. australis Queensland tick typhus Australia Tick bite Ticks R. honei Flinders Island spotted fever Australia, Thailand Tick bite Transovarian in ticks R. slovaca Tick-borne lymphadenopathy Eurasia Tick bite Unknown R. felis Flea-borne spotted fever North and South America, Not known Transovarian in cat fleas Europe, Africa Typhus group R. prowazekii Primary louse-borne typhus© Worldwide by authorInfected louse feces Human-louse cycle rubbed into broken skin / mucous membranes R. prowazekii Brill-Zinsser disease Worldwide Recrudescence years after primary attack of ESCMID Online Lecturelouse-borne Library typhus R. typhi Murine typhus Worldwide Infected flea feces Rat-flea cycle rubbed into broken skin / mucous membranes Scrub typhus group O. tsutsugamushi Scrub typhus Japan, eastern Asia, Chigger bite Transovarian in mites northern Australia, west and southwest Pasific Mediterranean Spotted Fever (MSF) “Boutonneuse fever” because of a papular rash Generally in spring and summer High fever, headache, maculopapular rash ± a black eschar at the tick bite site R. conorii is transmitted© by authorby the brown dog tick bite ESCMID R. conorii has Online a natural Lecturecycle between Library its athropod and vertebrate hosts, dogs Maculopapular Rash © by author ESCMID Online Lecture Library Maculopapular Rash © by author ESCMID Online Lecture Library Plantar Rash © by author ESCMID Online Lecture Library Eschar or “Tache noire” © by author ESCMID Online Lecture Library Eschar or “Tache noire” © by author ESCMID Online Lecture Library Eschar or “Tache noire” © by author ESCMID Online Lecture Library Eschar or “Tache noire” © by author ESCMID Online Lecture Library Eschar or “Tache noire” © by author ESCMID Online Lecture Library Diagnosis Serological methods Isolation of rickettsiae: cultivation Immunodetection Polymerase chain reaction-based detection 16S rRNA gene 17 kDa protein encoding gene Citrate synthase© by encoding author gene The outer membrane proteins rOmpA ESCMIDand rOmpBOnline encoding Lecture genes Library Serological Assays Weil-Felix test P. vulgaris OX2, SFG P. vulgaris OX19, TG and Rocky Mountain Spotted Fever P. mirabilis OXK, Orientia tsutsugamushi © by author Weil-Felix test is positive if: ESCMIDA fourfold or Onlinegreater increase Lecture in antibody Library titer A single antibody titer cut-off value of 1/320 Serological Assays Indirect immunofluorescence assay (IFA) The most commonly used technique for the dignosis IFA is positive if: (i) A seroconversion (ii) A fourfold or greater© increase by author in antibody titers (iii) A single antibody titer ≥ cut-off values of 1:128 for IgG ESCMID Online Lecture Library and 1:64 for IgM © by author ESCMID Online Lecture Library Mediterranean spotted fever (MSF) caused by a tick-borne pathogen, Rickettsia© conorii by subsp.author conorii Belongs to the spotted fever group (SFG) rickettsiae ESCMID Online Lecture Library Mediterranean spotted fever in the Trakya region of Turkey Aim: To evaluate the cases with confirmed diagnosis of MSF from 2003 to 2009 in the Trakya region of Turkey Patients with high fever+ maculopapular rash (involving the palms or soles) ± a black inoculation eschar at the site of the tick bite (tache noire) were included in the study There were 128 patients© withby confirmed author MSF diagnosis Before doxycycline treatment, skin biopsy specimens, ESCMIDpreferably from theOnline eschar or fromLecture the maculopapular Library rash, were obtained for DNA extraction Mediterranean spotted fever in the Trakya region of Turkey © by author ESCMID Online Lecture Library Mediterranean spotted fever in the Trakya region of Turkey © by author ESCMID Online Lecture Library Mediterranean spotted fever in the Trakya region of Turkey IFA was performed to detect antibodies against R. conorii in acute and convalescent sera Seroconversion or a 4 fold or greater rise in titre in 97 (77%) patients A single high titre in 16 (12.7%) patients A standard PCR reaction using primers suitable for hybridisation within the conserved region of genes coding for ompA and citrate synthase (gltA) According to PCR analysis,© by58 (73%) author of 79 biopsy specimens from the eschar and 19 (70%) of 27 specimens from the maculopapular rash showed positive results (totally 77 (72.6%) of 106 biopsy ESCMIDsamples) Online Lecture Library No significant difference was found between the rate of positive skin biopsies taken from the eschar and the maculopapular rash (chi-square: 0,094; p: 0,759) Mediterranean spotted fever in the Trakya region of Turkey 14 (10.9%) patients presented with a severe course of disease 5 had pneumonia, 4 had meningoencephalitis, 1 had both pneumonia and meningoencephalitis, 3 had multiple organ dysfunction, and 1 had pneumonia and multiple organ dysfunction Two (1.6%) old patients with multiple organ dysfunction died Doxycycline was administered for 7–14 days Quinolones were used only in 2 patients In the MSF cases, the mean© byduration author of high fever was 2.5 ± 1.4 days after doxycycline therapy Since 2007, we had 3 patients in whom a differentiation between ESCMIDCrimean Congo haemorrhagic Online fever Lecture and SFG rickettsiosis Library could not be made according to clinical characteristics Later these cases were serologically diagnosed as SFG rickettsioses Mediterranean spotted fever in the Trakya region of Turkey DNA sequence analysis was performed R. conorii conorii (type strain: Malish, ATCC VR-613) MSF is a potentially severe and even fatal disease resembling viral haemorrhagic fevers While IFA allows for retrospective diagnosis in MSF Advanced molecular© techniques by author provide the rapid detection of rickettsia in all skin samples, including eschar ESCMIDand maculopapular Online rash Lecture Library Patients and methods: Epidemiological, clinical characteristics and risk factors for severe MSF cases were analysed retrospectively A patient with two or more organ dysfunctions or patient death was defined as a severe case Results: From January 1999 to December 2009, 161 MSF cases were referred and 26 cases (16.1%)© by were authorconsidered severe Doxycycline administration prior to deterioration of disease (in 31 patients) protected patients from development of severe MSF ESCMIDFluoroquinolone treatment Online (in 21 patients)Lecture was significantly Library and independently associated with MSF severity Conclusions: Fluoroquinolone treatment was associated with increased MSF disease severity They retrospectively studied 339 patients, diagnosed with MSF between 2000 and 2011 All patients presented with fever (99.4%), rash (98.2%), and 57.9% had evidence of a tick bite There were no recorded deaths Serologic diagnosis was© made by by author IFA MSF is endemic in southeastern Romania Travel-associated MSF should be suspected in patients with ESCMIDcharacteristic symptoms Online returning Lecture from this endemic Library area Hindawi Publishing Corporation, BioMed Research International, Volume 2013, Article ID 395806, http://dx.doi.org/10.1155/2013/395806 The first cases of MSF were described in Tunisia in 1909 As characteristic skin eruptions were papular rather than macular, the disease was referred to as ‘boutonneuse’ fever The eschar at the site of the tick bite, the hallmark of rickettsial diseases, was described in Marseille in 1925 by Boinet and Pieri © by author In the 1930s,
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