Transcript Hantaviruses

Hantaviruses and Hantavirus
Pulmonary Syndrome (HPS)
Objectives
• Describe common hantaviruses in the United
States and their reservoirs
• Know the clinical nature of hantavirus infection
• Understand the epidemiology of hantavirus in
Washington State
Hantaviruses
• RNA viruses
• Asian, European, and American species
– Renal syndrome in Asia, Europe
(Milder form in Europe)
– Respiratory syndrome in Americas
• Bunyavirus family with three subfamilies
Identification of Hantaviruses
• Syndrome reported from Asia as
hemorrhagic fever with renal syndrome
(HFRS) including in Korean War troops
• Virus isolated in 1976 from striped field
mouse trapped near Hantaan River in Korea
• No arthropod vector established
(... unique among genera of Bunyaviridae)
Hantaviruses in Asia and Europe
Subfamily Murinae associated viruses (HFRS)
Virus
Host
Location
Disease
Hantaan Apodemus agrarius
Asia, Far East Russia
HFRS
Dobrava Apodemus flavicollis
Apodemus agrarius
Balkans
Europe
HFRS
Seoul
Worldwide
HFRS
Rattus norvegicus
Rattus rattus
Subfamily Arvicolinae associated viruses
Virus
Host
Location
Puumala Clethrionomys glareolus Europe
*Numerous other hantaviruses have been identified
but not linked to human disease
Disease
HFRS
Hemorrhagic Fever with Renal Syndrome
• Incubation: 5-35 days
• Prodrome: malaise, loss of appetite, nausea,
vomiting, conjunctivitis
• Decreased platelets, vascular permeability
• Hemorrhagic symptoms:
petechiae, conjunctival hemorrhage,
renal failure, GI bleeding
shock with 5-30% fatality rate
Hantaviruses in the Americas
Subfamily Sigmodontinae associated viruses (HPS)
Virus
Host
Location
Sin Nombre
Peromyscus maniculatus
West/Central
U.S. & Canada
Eastern U.S. &
HPS
Eastern U.S.
Southeastern U.S.
Florida
Argentina &
Chile
Northwestern
Argentina
Central Argentina
Central Argentina
Paraguay &
Bolivia
Brazil
HPS
HPS
HPS
HPS
Monongahela
New York
Bayou
Black Cr.
Andes
Peromyscus maniculatus
Canada
Peromyscus leucopus
Oryzomys palustris
Sigmodon hispidus
Oligoryzomys longicaudatus
Oran
Oligorozomys longicaudatus
Lechiguanas
Hu39694
Laguna Negra
Oligoryzomys flavescens
Unknown
Calomys laucha
Juquitiba
Etc.
Unknown
* Numerous other hantaviruses have been identified but not linked to human disease
Disease
HPS
HPS
HPS
HPS
HPS
HPS
Sin Nombre Virus
• Circular single stranded; RNA
• Total genome 10500-22700 nucleotides long
• 100 (80-120) nm in diameter
• Surface projections of envelope distinct;
spikes (of about 10 nm)
www.virology.net/Big_ Virology/BVRNAbunya.html
Hantavirus (Cardio)Pulmonary Syndrome
• Agent: Sin Nombre virus, others
(e.g., Monongahela virus)
• Vector: deer mouse (Peromyscus maniculatus)
mouse exposure may not be recognized
• Regions: western US, Mexico, Canada for SNV;
other viruses throughout Americas
including South American
• Mild or asymptomatic disease rare
HPS Pathophysiology
• Replication primarily in pulmonary endothelial cells
– Found widely in capillary endothelial cells
• Interstitial pneumonitis and mononuclear infiltrates
– Vascular permability and capillary leakage result
• High neutralizing antibody with better outcome
• May be genetic predisposition – HLA
– In some studies Sin Nombre virus associated with
certain HLA types
– Puumala renal syndrome associated with HLA-B8DR3
HPS Presentation
• Incubation 1-6 weeks
• Prodrome: fever, chills, myalgias (aches in
legs and back) lasting 1-7 days
may be nausea, vomiting, diarrhea
• Cough, URI symptoms rapidly progress to
pulmonary edema, hypoxia, ARDS;
cold/flu syndrome without: nasal discharge,
sore throat, sinusitis, ear infection
• Many causes of similar symptoms
HPS Clinical Course
• Shock with hypoxia, alveolar edema fluid
poor oxygenation causes renal failure
• Normal-to-low pulmonary wedge pressure
• Decreased cardiac index
• Increased systemic vascular resistance
• Mortality ~ 30%
HPS Laboratory Testing
• Hematology: low platelets, myelocytes, left
shift, elevated hematocrit, elevated WBC
• Chemistry: low albumin, elevated LDH,
elevated AST (SGOT), elevated ALT (SGPT)
• Serology: specific test for Sin Nombre virus
Asian viruses cross-react
paired IgM and IgG antibody testing
• Immunohistochemistry, PCR
serum, frozen tissue, tissue blocks, BAL
• Culture
Supportive Treatment
•Broad spectrum antibiotics until HPS proven
•Intensive care management: monitor
electrolytes, pulmonary, and hemodynamics
•Fluids (eg crystalloid) to get PAOP 12-15 mm
•Inotropic agents for myocardial contractility
Dobutamine 5 - 20 micrograms/kg/min
•? adult ECMO
Hantavirus Reservoirs
• Rodent hosts: genus (possibly species) specific
• Rodents shed but are not symptomatic
• Disease distribution follows rodent distribution
• No person to person transmission in N. America
• Virus in aerosolized urine, also feces, saliva
• Horizontal transmission among mice by
intraspecific aggressive behavior
Hantavirus and Deer Mice
• Sin Nombre virus throughout range of deer mice
• Difference in prevalence of mouse infection
• Transmission horizontally including aggressive
encounters and bites
• Recently infected most likely to be infectious
Hantavirus Hypotheses
• Seasonal trends
– Virus overwinters in older adult mice with high
prevalence
– Young mice dilute prevalence
– Young mice progressively infected through summer
• Temporal trends
– Increased rainfall can increase food and mouse
populations
– Mild winter could increase winter survival and
prevalence
Mills Emerg Inf Dis Jan-Mar 1999
Hantavirus Infection of Deer Mice
• Trapping in Colorado 1994-1997
• Prevalence 9.5%
– Range 0-43% for trapping periods
– Males more likely to be infected
– Wounds were associated with infection at only
one of two trapping sites
Calisher Emerg Inf Dis Jan-Mar 1999
Hantavirus Infection of Deer Mice
• Trapping in Montana 1994-2004
– 244,600 trap nights of effort
• Multiple captures for 2,747 deer mice
• Found 99 seroconversions between consecutive
trapping sessions
– More likely to be older male, in breeding condition
– Not related to wounds or scars
– Infected mice with less weight gain than seronegative
Douglass J Wildlife Dis 2007 45:12-22
Hantavirus Infection of Deer Mice
• Trapping and fluorescent tagging in Utah 2005
– Study 15 days in Spring and 15 days in Autumn
– Five mice a night tagged and released
– Trapped following night, checked for fluorescence
• Infection prevalence 25-30%
– Mice with more contacts averaged 11 percent heavier
– No effect of gender or breeding condition
• May be higher prevalence of hantavirus in
populations where mice are older
– May reflect better food or cover
Clay Proc. R. Soc. B April 7, 2009
HPS Epidemiology
• Greater number of cases in spring-summer
– Varies by elevation, location, biome
• Rainfall preceding year increases food supply
prompting rodent population growth
• Risks – exposure through rodent excreta
MMWR June 9, 2006
Hantavirus Clusters in Argentina
• Hantavirus endemic in southern Argentina
• Clustering for 39% of cases (vs. 7.5% SNV)
• Eight clusters with > 2 weeks between cases
– Breast fed infant IgG positive, mother died with ARDS
– Wife symptomatic 20 days after husband who handled
mice
– Breast fed child with mild illness and seroconversion
19 days after mother
– Wife symptomatic 40 days after husband who cleared
plants in wilderness
Lazaro Emerg Inf Dis Jan 2007
Washington HPS Cases
•
•
•
•
•
28 cases reported as of Jan 2005
1-5 cases reported annually 1994-2005
9/28 (32%) fatal
Age range 20-75 years, 21 (75%) male
14 exposed in eastern Washington counties,
11 in western Washington counties, 3 in
multiple counties a/o out of state
Washington HPS Cases
• Exposures
– 21/24 cases lived in rural locations or
settings
– 19/24 cases – rodent exposure/signs
reported or found on inspection in/around
home or workplace
– 11/24 cases – lived or worked in agricultural
setting
Hantavirus Outbreak, 1993
• Impact on local community
– Loss of tourism and associated
income
– Prejudice
– Media intrusion
– Disregard for religious observances