OVERVIEW OF HANTAVIRUS ACTIVITY AND THE OCCURRENCE OF HANTAVIRUS PULMONARY SYNDROME IN CANADA Harvey Artsob, L. Robbin Lindsay, Michael Drebot, David Safronetz, Daryl Dick and Heinz Feldmann Zoonotic Diseases and Special Pathogens, National

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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
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Hantaviruses - History

• Korean War, 1951-54 gt3,200 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)

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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
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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
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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.

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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 lt1 to 15

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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

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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
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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
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8
16
2
1
10


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524 HPS cases contracted in North America
Total cases 64 including Male
64.1 Female 35.9
As of January 1, 2007
As of January 17, 2007
Total cases 460 including Male
63 Female 37
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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
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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
14

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HPS contracted in Canada (as of Jan 1, 2007)
Mean age 41.9 Median age 42.0
Mean age 38
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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)
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HPS contracted in Canada (as of January 1, 2007)
BY MONTH
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Different approaches used to understand
hantaviruses in Canada

• Passive surveillance
• Active surveillance / case investigations
• Field studies on transmission dynamics

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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
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Typical sampling localities
Abandoned/Isolated
Farm
Natural
Rural Domestic
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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
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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
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1
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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

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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 lt W
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Clinical description of previously reported HPS
cases due to the eastern clade of Sin Nombre virus
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- 1
Estimated fatality rate from eastern clade of
Sin Nombre virus gt3/11 27.3?
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Previously reported HPS cases due to the eastern
clade of Sin Nombre virus
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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
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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?

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2 Deer Mice Subspecies 2 Sin Nombre-Like
Hantavirus Genotypes ?
Grassland subspecies Forest subspecies
(Western Sin Nombre Genogroup)
(Eastern Sin Nombre Genogroup)
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Canadian Deer Mouse Phylogeny
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34
Virus/Host Biology Factors

• What are the relative virus shedding patterns
  of the western and eastern clades of Sin Nombre
  viruses ?

35
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.