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Surveillance of RickettsialLecture Diseases: do we need aauthor lab for it? Onlineby Marina© E. Eremeeva Centers for Disease Control and Prevention, Atlanta, USA

Post Graduate Educational Course: Intracellular – from biology to clinic ESCMID2-5 November 2010, Sousse-Tunisia Outline Library

• What is disease surveillance? • What types of surveillanceLecture are used? • Surveillance of rickettsiosesauthor in the USA • Laboratory basedOnline surveillanceby ©

ESCMID Definition and Terminology • Disease surveillance is an epidemiologicalLibrary practice in which the spread of disease is monitored to establish patterns of progression • Disease surveillance isLecture conducted to a. predict, observe, and minimize the harm caused by outbreak, epidemic, and pandemicauthor situations b. increase knowledge about factors that might contribute to disease outbreaksOnline by • Disease surveillance© is the practice of disease case reporting

ESCMID Mandatory Disease Case Reporting Library • Mandatory reporting imposed by

a.World Health Organization b.National GovernmentsLecture c.Regional Governmentsauthor Onlineby ©

ESCMID Reportable Infectious Diseases WHO mandate GovernmentLibrary mandate • Since 1965 a. Tuberculosis a. b. HIV b. Lecturec. Botulism c. Yellow fever d. Hantavirus d. Smallpox authore. Anthrax e. Relapsing feverOnlineby f. Rabies f. © g. RMSF • Since 2005 h. Lyme disease a. SARS b.ESCMIDPolio Challenges of Disease Reporting Library • Political issues a.Global health needs vs. state secret (tourism, business) • Communication issues Lecture a.Public and government official alerts vs. rumors and news reporting author b.ProMed, Harvard EID project • Technical challengesOnlineby © a.Differential testing b.Test and infrastructure availability c.Proficiency, standards, cold chain, technology transfer ESCMID Types of Disease Surveillance Library •Active surveillance and immediate notification •Passive surveillance •Special surveillance projectsLecture •Short-term surveillance: to detect additional cases following initial identificationauthor of an unusual caseOnline by •Research projects:© specifically looking for a disease in a define region through multidisciplinary studies ESCMID Reporting Library • Public health officials rely on health providers, diagnostic laboratories, and other public health personnelLecture to report the occurrence of notifiable diseases • Requires universal caseauthor definitions Onlineby ©

ESCMID Chain of Reporting in the USA

Local Health Care Providers Library

Cities Lecture Counties author StatesOnlineby © CDC

MortalityESCMID and Morbidity Weekly Reports New Case Definition Development

CSTE approves new case definition Library

Health State New case definition is Departments adapt new presented to the CSTE Lecture case definition author by CDC and State sponsor Online Health State develop and propose Departments report new case definition © the cases

CDC conducts national surveillance, analyses ESCMID trends and discovers new pathogens and diseases Case Definition Library • Compatible clinical presentation (rash, headache, myalgia, anemia, thrombocytopenia, or any hepatic transaminase elevation)Lecture • Epidemiological clues (potential exposure to vectorsauthor and reservoirs within 14- 21 days prior to onset),Online clusters,by seasonality • Laboratory evidence© (confirmed, probable and suspect cases) ESCMID Classification of Clinically Compatible CasesLibrary

• Confirmed • Probable a. 4-fold IgG IFA titer rise a. Elevated single antibody b. PCR positive Lecturetiter by any serologic assay c. Immunohistochemistry author d. Culture isolation Onlineby © Suspect: only clinical and epi data, no laboratory data ESCMID Inoculation of rickettsiae

Library

Specific host immune response detection Lecture author Onlineby ©

IHC PCR Culture Acute + Convalescent Convalescent ESCMID sera serum Confirmed case Probable case Disease Reporting Library • National Electronic Disease Surveillance System (NEDSS) • National Notifiable DiseaseLecture Surveillance System (NNDSS) author • Case report forms (CRF) Onlineby ©

ESCMID Passive Surveillance

• Reports are received passively Libraryon notifiable diseases • Physicians may or may not report cases, although it is mandatedLecture by state law (voluntary report to CDC)author • State health departments must spend time Onlineby educating physicians© and encourage reporting • State reporting is not identical ESCMID Limitations of Data Library • Passive data is biased in many ways • Passive data is retrospective only • Passive data providesLecture only a fuzzy snapshot of points in timeauthor and space Onlineby ©

ESCMID Common Reporting Artifacts Library • Non-cases may be reported as cases • Test results on non-ill patients are not cases (must be ill) Lecture • Interpretation of commercial laboratory test results does not matchauthor case definitions • Not all cases Onlineare followedby up to obtain epidemiologic, clinical,© and laboratory data and provide a complete story – Time &$$ ESCMID CSTE-CDC Case Definitions for Rickettsial Diseases Library • Spotted fever group (including Rocky Mountain spotted fever) • due to E.Lecture chaffeensis • Ehrlichiosis due to E. authorewingii • Unspecified (undetermined)Onlineby ehrlichiosis • due© to A. phagocytophilum • () www.cdc.gov/ncphi/disss/nndss/casedef/index.htmESCMID Q Fever Reporting Library 180

160

140

120 Lecture

100 Acute

Number of cases Number Chronic 80 author Total number 60 Onlineby 40 © 20 Year 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 ESCMID NNDSS Q Fever Seroprevalence Library Seroprevalence Mexican American 7.4% Non-Hispanic black 1.4% Non-Hispanic Lecturewhite 2.8% Total 3.1% author USA born 2.3% BornOnline abroadby 7.4% ©

ESCMID Anderson et al. 2009 Significant Potential for C. burnetii Exposure

Coxiella DNA in environmental samples CoxiellaLibraryDNA in raw cow milk

Region % Positive Rocky 44.6 Mountains South-central 36.1 Lecture Upper Midwest 24.7 West Coast 13.7 author East Coast 6.0 by Deep South 16.3Online Total 23.8 ©

ESCMID Kersh et al. 2010, Loftis et al. 2010 Reporting of Ehrlichioses and

AnaplasmosisNational Ehrlichiosis Incidencein 1996the-2005 USA Library 3

2.5 HGA HME Other 2 Lecture 1.5 author 1 Onlineby 0.5

Incidence per 1,000,000 Population US 1,000,000 per Incidence © 0 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 Year ESCMID Courtesy of J. Openshaw Geographic Distribution of Human Cases and

Human monocytic ehrlichiosis Human granulocytic anaplasmosis Library

Lecture

0 0-3 3-15 15+ author0 0-3 3-15 15+ Onlineby ©

ESCMID Courtesy of J. McQuiston E.ewingii and Unspecified Ehrlichioses

Library

Lecture author Onlineby Disproportionally high numbers of unspecified ehrlichioses have been reported from northern states based© on positive serology to E. chaffeensis : • Travel cases? • Changes in vector range distribution? • Emergence of new pathogens? • Ordering inadequate tests? • ConfusionsESCMID about the names of diseases and etiological agents? Historical and current range of Amblyomma americanum Library

Lecture author Onlineby

Historical range of A. americanum© Area of A. americanum expansion

E. chaffeensis – 10.4% (0-40%) E. ewingii -- 3.5% (0-18.6%) Panola Mountain Ehrlichia sp. – 4.5% (0-27.3%) ESCMIDR. amblyommii –41.2% (0-84%) Yabsley, 2010 Emerging Ehrlichia Pathogens • Ehrlichia muris like agent a. 10 cases identified in 2009-2010, LibraryMN and WI b. Found in Ixodes scapularis and Peromyscus mice • Panola Mountain Ehrlichia a. 1 case identified in 2008,Lecture GA b. Found in Amblyomma americanum in 10 States (0.27-27.3% prevalence)author c. Infects white Onlinetail deerby • Ehrlichia canis © a. 6 cases identified in 2006, Venezuela b. All patients had contacts with dogs All casesESCMID were diagnosed by PCR, serology was not contributing and clinical manifestations non-specific RMSF Historical Reporting Trend Library

Lecture author Onlineby ©

ESCMIDIncidence Case fatality rate Courtesy of J. McQuiston Decreased Reporting of Confirmed RMSF Cases Library

Lecture author Onlineby ©

ESCMID Number of cases % Confirmed cases RMSF Case Fatalities, 2000-2007 Library

Lecture author

Case fatality fatality rate Case Onlineby

(% N died/Number of cases) of cases) N died/Number(% ©

ESCMID * Includes confirmed and probable cases, Case report forms Current Status of RMSF Reporting Library Reported RMSF incidence has increased > 300% over the past 8 years But case fatality rate and Lecturenumber of fatal cases have shown a dramatic decrease during the same period author Onlineby ©

ESCMID Increasing Incidence • Changing climate, ecology and etiology Library a. Increase in populations and disease transmission b. Changes in tick and animal geography c. Identification of new rickettsial pathogens Lecture • Changing diagnostic tools and approaches a. New assays of differing sensitivity/specificityauthor b. Non-standardizedOnline interpretationby of test results © • Changing surveillance activities a. Changes in detection at state and local levels b. ESCMIDChanges in physician recognition and reporting National RMSF Incidence 2000-2007 Library

Lecture author Onlineby ©

ESCMID

* Includes confirmed and probable cases Changing Ecology •Identification of new tick vectors Library Rhipicephalus sanguineus a. rickettsii in Arizona, California and Georgia b. Rickettsia massiliae in Arizona and California Lecture Dermacentor occidentalis a. Rickettsia sp. 364D and in Californiaauthor Onlineby Amblyomma© maculatum a. in states that border the Gulf and southern Atlantic coasts ESCMID Changing or New Etiology

•Emerging rickettsial pathogens Library

Pathogen Description, yr Human Disease, yr Rickettsia parkeri 1939 2004 Rickettsia sp. 364D 1973Lecture 2009 Rickettsia massiliae 1992 2005* Rickettsia ammblyommii 1981authorNo confirmed cases •New clinical manifestations:Onlineby eschar, erythema migrains © •New diagnostic challenges: cannot be differentiated serologically ESCMID *Have not been diagnosed in the USA yet Changing Diagnostic Tools: RMSF Cases Diagnosed by Serologic Methods other than IFA Library

2004Lecture New RMSF Case Definition author Onlineby ©

ESCMID Year Latex agglutination assay ELISA Surveillance of Zoonotic Diseases Library What else can be done? •Surveillance of wild life •Surveillance of domesticLecture and companion animals author •Surveillance of arthropods Onlineby •Surveillance of© environmental samples

ESCMID Non-Human Surveillance Library • Benefits a. More lead time for preventive measures b. No patient contacts Lecture c. More data points d. More variables author e. More controlOnline by • Potential Problems© a. Data interpretation b. Follow up action ESCMID Canine Serosurveillance Library Survey of dogs in RMSF Survey of dogs outside of endemic outbreak area area Number County % Seropositive Lectureof dogs Coconino 53 0 Greenleeauthor 40 17.5 Navajo 48 6.3 Onlineby Pinal 26 3.8 © Total 167 7.8

ESCMID McQuiston et al. 2009, Nicholson et al. 2006, Demma et al. 2005, 2006 RMSF in California • 1903-1938: 188 casesLibrary reported, nearly all in Modoc Plateau area with D. andersoni (black) •1950-1973: 16 well- documentedLecture cases reported outsideauthor Modoc Plateau (yellow) Onlineby © •2002-2006: 29 cases reported in CA, none in Modoc Plateau and 14 in S. California (red) http://www.censusfinder.com/_derived/ESCMID mapca.htm_txt_mapca.gif Detection of Spotted Fever Group Rickettsiae in Ticks from California

Location, County Tick PCR positive,Library % SFGR Species So. California D. occidentalis 24% R. rhipicephali 7.7% Rickettsia 364D 0.6% R. bellii 0.1% R. rickettsii D. variabilis Lecture100% R. rhipicephali R. sanguineus author0.3% R. rickettsii No. California D. occidentalis 37% R. rhipicephali Onlineby Rickettsia 364D D. variabilis © 27% R. rhipicephali

D. andersoni 100% R. peacockii

H. leporispalustris 0% NA ESCMID Take Home Message

• Surveillance of rickettsial diseasesLibrary is an import public health task with many challenges • Incidence of rickettsial diseases is greatly under reported Lecture • Accurate case definition authoris necessary requirement • Onlineby Laboratory confirmation© is import for reliable reporting and case recognition

ESCMID Library

Lecture author Onlineby For more information, please, contact Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta GA 30333© Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348 Email:[email protected] Web:www.cdc.gov

[email protected] (404-639-4612)

The findings and conclusions in this report are those of the author and do not necessarily represent the official positionESCMID of the Centers for Disease Control and Prevention