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“Epidemiology of Rickettsial Infections”

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6/19/2019 I have got 45 min…… First 15 min… •A travel medicine physician… •Evolution of epidemiology of rickettsial diseases in brief “Epidemiology of rickettsial •Expanded knowledge of rickettsioses vs travel medicine infections” •Determinants of Current epidemiology of Rickettsialinfections •Role of returning traveller in rickettsial diseaseepidemiology Ranjan Premaratna •Current epidemiology vs travel health physician Faculty of Medicine, University of Kelaniya Next 30 min… SRI LANKA •Clinical cases 12 Human Travel & People travel… Human activity Regionally and internationally Increased risk of contact between Bugs travel humans and bugs Deforestation Regionally and internationally Habitat fragmentation Echo tourism 34 This man.. a returning traveler.. down Change in global epidemiology with fever.. What can this be??? • This is the greatest challenge faced by an infectious disease / travel medicine physician • compared to a physician attending to a well streamlined management plan of a non-communicable disease……... 56 1 6/19/2019 Rickettsial diseases • A travel medicine physician… • Represent some of the oldest and most recently recognizedinfectious • Evolution of epidemiology of rickettsial diseases in brief diseases • Expanded knowledge of rickettsioses vs travel medicine • Determinants of Current epidemiology of Rickettsialinfections • Athens plague described during 5th century BC……? Epidemic typhus • Role of returning traveller in rickettsial diseaseepidemiology • Current epidemiology vs travel health physician • Clinical cases 78 In 1916.......... By 1970s-1980s four endemic rickettsioses; a single agent unique to a given geography !!! • R. prowazekii was identified as the etiological agent of epidemic typhus • Rocky Mountain spotted fever • Mediterranean spotted fever • North Asian tick typhus • Queensland tick typhus Walker DH, Fishbein DB. Epidemiology of rickettsial diseases. Eur J Epidemiol 1991 910 Family Rickettsiaceae Transitional group between SFG and TG Genera Rickettsia • R. australis • R. akari Spotted Fever Group (SFG) • R. felis Typhus Group (TG) • (evolutionary genetic relationships) 11 12 2 6/19/2019 Transmitted by…..ticks, mites, fleas and lice.. Genera Orientia • SFG: mainly ticks, also fleas (R. felis), mites (R. akari) [Separated from Genera Rickettsia in1995; antigenically diverse spp] • TG: R. prowazekii • Human body louse (Epidemic louse-borne typhus, recrudescent typhus) • flying squirrel ecto parasites (Flying squirrel associatedtyphus) (Amblyomma ticks) R. typhi (Murine typhus) –Fleas • Orientia (Scrub typhus) • Larval mite (chigger) …??Leeches • (Thomas Weitzel) 13 14 Eg: Rickettsia conorii complex (2005)….. (based on epidemiological and clinical differences) • R. conorii-conorii /Malish strain): Mediterranean spotted fever (MSF): Mediteranian and Africa • R. conorii-Astrakhan strain: Astrakhan fever, Southern Russia Identification of rickettsial spp from pathogenicto • R. conorii-Israeli: Israeli spotted fever non-pathogenic potential across the globe... • R. conorii-Indica: Indian tick typhus: India, Sri Lanka and Pakistan • Rhipicephalus spp. ticks 15 16 Rickettsia spp.. • 30 validated species, incl. 17 pathogens Effect of global warming? • > 100 unclassified rickettsial isolates • Major human pathogens 17 18 3 6/19/2019 Global warming linked to changing epidemiology of MSF 2003 heat wave • Effect of on tick behavior •(↑ incidence of Rh. Sanguineus (Brown Dog Tick)-transmitted • Fatal MSF in France diseases) • one man; 22 attached ticks • Multiple eschars • ↑ period of activity • 2 – 6% fatality reaching 30% in hospitalized patients • ↑ aggressiveness • ↑ biting of unusual hosts (humans) (Socolovschi et al. 2009. Parola et al. 2008) • Multiple eschars, severe forms 19 20 TBR: has become a worldwide disease (Parola et al. Orientia tsutsugamushi (Scrub typhus) 2014) • More than 20 antigenically distinct strains • Originally, 3 prototype strains; Gilliam, Karp and Kato • Later, additional antigenic types: Kawasaki, Kuroki, Shimokoshi etc and other distinct serotypes in the tsutsugamushitriangle • Novel orientia species being described outside the tsutsugamushi triangle; Dubai (O. chuto) and • in Chile (proved novel: “Named”, yet to be published (ThomasWeitzel) 21 22 This Antigenic heterogeneity of Orientia tsutsugamushi reason for • frequent outbreaks and reinfection • Differences in Virulence among the strains • Variation in the general course of the disease and the prognosis dependingon the endemic strain 23 24 4 6/19/2019 Today........ Many Organisms / Serotypes / Strains 25 26 Historically • A travel medicine physician… • Evolution of epidemiology of rickettsial diseases in brief • Different species of prokaryotic pathogens were defined based • Expanded knowledge of rickettsioses vs travel medicine • Determinants of Current epidemiology of Rickettsialinfections • on the diseases they caused • regardless of other ecological or evolutionary considerations • Role of returning traveller in rickettsial diseaseepidemiology • Current epidemiology vs travel health physician • Clinical cases Walker DH, Ismail N. Nature Reviews: 2008 27 28 • Novel Rickettsia isolates •Clinical manifestations of most rickettsioses are neither specific to a •Vary much less from one another • Is an overenthusiastic designation of many new particular agent nor to a geographic species distribution Walker DH, Ismail N. Nature Reviews: 2008 Walker DH, Ismail N. Nature Reviews: 2008 29 30 5 6/19/2019 • A travel medicine physician… • Evolution of epidemiology of rickettsial diseases in brief •R. africae and R. parkeri • Expanded knowledge of rickettsioses vs travel medicine •R. japonica and R. helongjiangiensis • Determinants of Current epidemiology of Rickettsialinfections • Role of returning traveller in rickettsial diseaseepidemiology • Current epidemiology vs travel health physician show minimal differences • Clinical cases Walker DH, Ismail N. Nature Reviews: 2008 31 32 Epidemiology of Tick borne Rickettsioses Most prevalent rickettsioses is 1. Is based mainly on Rickettsia isolated in Ticks • Based on • “Priority agents” for survaillance 2. Reporting error vs rickettsial epidemiology • Reportable rickettsial diseases • Rickettsioses which require medical attention • Rickettsioses that standout for their morbidityand mortality 33 34 “Reporting error”; RMSF in the Americas “cases” • May reflect an unrelated exposure to a vector bearing a Rickettsial agent that caused an immune response rather than the occurrence of a true Most Rickettsial disease diagnosis rickettsiosis is based on IFA Is still the primary tool in thediagnosis Has a marked cross-reactivity within the SFG 35 36 6 6/19/2019 IFA crossreactivity… • This fact led to the change in reporting of “RMSF” cases in the United States • Low pathogenic agents may have contribute to the apparent • Now classified as “SPOTTED FEVER Gr oup” Rickettsioses overall increased incidence of RMSF in Americas? 37 38 In most resource poor countries… Does this really mean… which are important for TravelMedicine… • Rickettsial disease diagnosis is mainly on History and examination… • “In your clinical practice.. you do not want to know what the organism is..??” • Ix facilities are not widely available • Evenif available, its mainly serology based; “will not identify” the causative organism.. Will end up with an umbrella term“SFG” • But simply know that the illness is one ofRickettsial ?? 39 40 Perspective of apragmatist “The laboratory diagnosis of rickettsioses can appear an academic exercise: Is it really necessary to identify thecausative agent For each of > 25 ecologically, epidemiologically, and aetiologically distinct disease comprising ‘the rickettsioses’ responds to thesafe, in a returning traveler? inexpensive, widely distributed, and highly effective antibiotic doxycycline” Paddock CD 41 42 7 6/19/2019 • ….newly described syndromes are a result of………… • A travel medicine physician… • Evolution of epidemiology of rickettsial diseases in brief • a single physician’s curiosity….. • Expanded knowledge of rickettsioses vs travel medicine • introduction of new diagnostictools • Determinants of Current epidemiology of Rickettsialinfections • improved knowledge of diseaseepidemiology • Role of returning traveller in rickettsial diseaseepidemiology • demonstration of pathogenic roles forhumans of • Current epidemiology vs travel health physician rickettsiae previously found only inarthropods • Clinical cases Raoult D, Roux V. Clinical Microbiology Reviews1997 43 44 Newer Rickettsioses: are they really low in numbers? Will their impact be alwayssmall? We have questions needing clarification.. • Low pathogenicity? • Low vector carriage? • Low transmission potential? 45 46 • A travel medicine physician… • Evolution of epidemiology of rickettsial diseases in brief • Expanded knowledge of rickettsioses vs travel medicine Are we planning on preventive measures in travelers? • Determinants of Current epidemiology of Rickettsialinfections • Role of returning traveller in rickettsial diseaseepidemiology • Current epidemiology vs travel health physician • Clinical cases 47 48 8 6/19/2019 Clinical syndrome Exposure risk Fever in this returning traveler: Can this be rickettsial ??... Incubation period Manageable DD • Epidemiology • Clinical judgement 49 50 Expected clinical syndrome of rickettsioses… Important:.. !! Aneruptive fever • Mostly a short incubation (6-7 days) • R. helvetica (although the pathogenic role isunclear) (Ixodes ricinus ticks) European and Asian countries Clinical
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  • Mechanisms of Rickettsia Parkeri Invasion of Host Cells and Early Actin-Based Motility

    Mechanisms of Rickettsia Parkeri Invasion of Host Cells and Early Actin-Based Motility

    Mechanisms of Rickettsia parkeri invasion of host cells and early actin-based motility By Shawna Reed A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Microbiology in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Matthew D. Welch, Chair Professor David G. Drubin Professor Daniel Portnoy Professor Kathleen R. Ryan Fall 2012 Mechanisms of Rickettsia parkeri invasion of host cells and early actin-based motility © 2012 By Shawna Reed ABSTRACT Mechanisms of Rickettsia parkeri invasion of host cells and early actin-based motility by Shawna Reed Doctor of Philosophy in Microbiology University of California, Berkeley Professor Matthew D. Welch, Chair Rickettsiae are obligate intracellular pathogens that are transmitted to humans by arthropod vectors and cause diseases such as spotted fever and typhus. Spotted fever group (SFG) Rickettsia hijack the host actin cytoskeleton to invade, move within, and spread between eukaryotic host cells during their obligate intracellular life cycle. Rickettsia express two bacterial proteins that can activate actin polymerization: RickA activates the host actin-nucleating Arp2/3 complex while Sca2 directly nucleates actin filaments. In this thesis, I aimed to resolve which host proteins were required for invasion and intracellular motility, and to determine how the bacterial proteins RickA and Sca2 contribute to these processes. Although rickettsiae require the host cell actin cytoskeleton for invasion, the cytoskeletal proteins that mediate this process have not been completely described. To identify the host factors important during cell invasion by Rickettsia parkeri, a member of the SFG, I performed an RNAi screen targeting 105 proteins in Drosophila melanogaster S2R+ cells.