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Hantaviruses - History

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Hantaviruses - History

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  1. OVERVIEW OF HANTAVIRUS ACTIVITY AND THE OCCURRENCE OF HANTAVIRUS PULMONARY SYNDROME IN CANADAHarvey Artsob,L. Robbin Lindsay,Michael Drebot, David Safronetz, Daryl Dick and Heinz FeldmannZoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada and Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada Presented to Animal Determinants of Emerging Diseases (ADED) National Zoonoses Rounds, February 20, 2007

  2. Hantaviruses - History • Korean War, 1951-54: >3,200 cases “Korean Hemorrhagic Fever” • Fever, shock, ARF, pulmonary edema • 10% case-fatality rate • Tents “overrun with rodents” • Rodent-association established in 1978 • Virus isolated in 1981from rodents collected along Hantaan River in Korea (=Hantavirus)

  3. Rodent-associated viruses World-wide: Two lineages of hantaviruses Old World - 9 species, 4 which cause disease New World - 23 species, 11 which cause disease

  4. General cycle of transmission of Hantaviruses Chronically infected rodent Horizontal transmission of infection by intraspecific aggressive behavior Virus also present in throat swab and feces Virus is present in aerosolized excreta, particularly urine Secondary aerosols, mucous membrane contact, and skin breaches are also sources of infection * * possible human-to-human in some South American HPS cases

  5. Hantavirus Transmission Viruses are transmitted to humans via inhalation of infected particles or food contaminated with urine, saliva or faeces of rodents. Once infected, animals excrete virus for a long time. There is a close connection between the specific hantavirus and species of rodent that forms the reservoir.

  6. Hantaviruses and disease in humans • Hemorrhagic Fever with Renal Syndrome (HFRS) • Restricted to Asia and Europe • Annually 200,000 HFRS cases in Europe and Asia • Mortality rate ranges from <1 to 15%

  7. Hantaviruses and disease in humans • Hantavirus Pulmonary Syndrome (HPS) • First identified in 1993 in the southwest “Four Corners” region of the US • Now reported in Canada, the United States, South America (Argentina, Bolivia, Brazil, Chile, Paraguay, Peru, Uruguay & Venezuela) and Panama • More than 700 cases of HPS have been confirmed, predominantly in Argentina and the US • Mortality rate approx. 40%

  8. New World Hantaviruses New York Peromyscus leucopus Sin Nombre Peromyscus maniculatus Prospect Hill Microtus pennsylvanicus Muleshoe Sigmodon hispidus Bloodland Lake Microtus ochrogaster Isla Vista Microtus californicus Bayou Oryzomys palustris Black Creek Canal Sigmodon hispidus El Moro Canyon Reithrodontomys megalotis Rio Segundo Reithrodontomys mexicanus Calabazo Zygodontomys brevicauda Juquitiba Unknown Host Laguna Negra Calomys laucha Caño Delgadito Sigmodon alstoni Choclo Oligoryzomys fulvescens Maciel Necromys benefactus Rio Mamore Oligoryzomys microtis Hu39694 Unknown Host Orán Oligoryzomys longicaudatus Lechiguanas Oligoryzomys flavescens Bermejo Oligoryzomys chacoensis Pergamino Akodon azarae Andes Oligoryzomys longicaudatus

  9. Virus Type Sin Nombre (470) New York (2) Bayou (3) Black Creek Canal (1) Location of North American HPS Cases by Virus Type as of February, 2006 Total Cases: USA-416 in 30 States; Canada-60 in 5 provinces 33 8 16 2 1

  10. 524 HPS cases contracted in North America As of January 1, 2007 Total cases – 64 including: Male – 64.1% Female – 35.9% As of January 17, 2007 Total cases – 460 including: Male – 63% Female – 37%

  11. HPS contracted in North America By Outcome: 20/64 (32.3%) fatalities as of January 1, 2007 162/460 (36%) fatalities as of January 17, 2007

  12. HPS contracted in Canada (as of January 1, 2007) Total cases – 64 Infecting hantavirus In all instances where PCR testing was undertaken, Sin Nombre was shown to be the infecting virus. Quebec case – eastern clade of Sin Nombre virus. All other Canadian HPS cases for which PCR was undertaken correlated with the western clade

  13. HPS contracted in Canada (as of Jan 1, 2007) Mean age – 41.9 Median age – 42.0 Mean age – 38

  14. HPS contracted in Canada (as of January 1, 2007) BY YEAR (average 4.7 cases/year) * * An additional 3 retrospective cases were diagnosed: 1989(1), 1990 (1), 1992(1)

  15. HPS contracted in Canada (as of January 1, 2007) BY MONTH :

  16. Different approaches used to understand hantaviruses in Canada • Passive surveillance • Active surveillance / case investigations • Field studies on transmission dynamics

  17. Passive surveillance Collaborators across Canada including: Public health inspectors, pest control personnel, wildlife biologists, University facility, private contractors, etc., Rodents collected using: Snap traps & various live traps Whole carcasses, Nobuto strips (or blood samples) shipped to lab Screen for antibodies by ELISA, lungs Harvested from selected positives for PCR

  18. Typical sampling localities Abandoned/Isolated Farm Natural Rural Domestic

  19. Seronegative rodents Seropositive rodents Serological survey for hantaviruses in deer mice from across Canada Sin Nombre virus YT-107 (8.4) NT-184 NF-62 (3.2) BC-627 (3) AB-2065 (7.9) QC-503 (6.2) MB-1490 (3.6) PE-122 SK-887 (4) ON-1898 (2.9) NS-287 NB-232 (5.6) 380/7,891 (4.8%) deer mice with antibodies

  20. Canadian Sin Nombre Virus Phylogeny (M Segment, G1 sequencing) SK 94 MB 97 Yukon 95 West CC107 SNV AB 97 Distinct amino acid markers, Not serological distinct ! BC 95 NY1 ON 95 MGL East NF 96 QC 96 NB 95

  21. HPS and Hantaviruses in Canada SN-like virus YT NT NF BC AB SK MB QC PE 9 ON NB 34 NS 18 2 Seronegative rodents Number of HPS cases as of January 1, 2007(64) Seropositive rodents 1

  22. HPS contracted in Canada Infecting Sin Nombre clade: 63/64 of the Canadian HPS cases have occurred within the range of the western clade of Sin Nombre virus The 64th case in the province of Quebec occurred within the range of the eastern clade Studies were undertaken to better understand HPS risk from the eastern clade

  23. Why are there so many more cases of HPS due to the western clade of Sin Nombre virus? Differences in virus virulence? Epidemiological Factors ? Virus/host biology as factors? East --West Genotypes Differ In Virulence ? Could Virus/Host Biology Be A Key Factor ? Environmental, Occupational, E < W

  24. Clinical description of previously reported HPS cases due to the eastern clade of Sin Nombre virus

  25. - 1 Estimated fatality rate from eastern clade of Sin Nombre virus >3/11 = 27.3%?

  26. Previously reported HPS cases due to the eastern clade of Sin Nombre virus

  27. Possible locations of exposure Domestic 34.4% Farm 25.0% Wildlife Surveys 3.1% Recreational 3.1% Ranch 3.1% Military 3.1% Lumber Mill 15.6% Unknown 3.1% Domestic and Additional Risk Factors 9.4%

  28. Epidemiological/Ecological Factors • Are people exposed to more Peromyscus species in the west versus the eastern part of North America? 2. Is the seroprevalence rate higher in infected Peromyscus species in the west versus the east?

  29. 2 Deer Mice Subspecies =2 Sin Nombre-Like Hantavirus Genotypes ? Grassland subspeciesForest subspecies (Western Sin Nombre Genogroup) (Eastern Sin Nombre Genogroup)

  30. ON1 ON2 QC1 QC2 NF1 NF2 Canadian Deer Mouse Phylogeny AB-K1 T G A C A A A C C C C A A A A G C A T G G A A C C C A A T T C A G G C T T T T A C G C A T T C T A G AB-K2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AB-W . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . W E AB-S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . MB1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . MB2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . MB3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . T . . . . . T . . . . C . C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . T . . . . . T . . . . C . C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . T . . . . . T . . . . C . C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . T . . . . . T . . . . C . C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . T . . . . . T . . . . C . C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . T . . . . . T . . . . C . C . . . . . . . . . . . .

  31. Virus/Host Biology Factors What are the relative virus shedding patterns of the western and eastern clades of Sin Nombre viruses ?

  32. Summary • As of January 1, 2007, 64 cases of HPS have been diagnosed in Canada in individuals with no histories of recent travel. 2. 63 cases contracted in Canada have occurred within the range of the western clade of Sin Nombre virus and 1 within the range of the eastern clade. 3. Two clades of Sin Nombre virus have been demonstrated in a discontinuous distribution in deer mice from British Columbia to Newfoundland. 4. Canadians are considered to be at low risk for contracting hantaviral disease across the country with the risk higher within the distribution of the western clade of Sin Nombre virus for reasons yet to be determined.

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