Hantaviruses. Objectives. Hantaviruses and Hantavirus Pulmonary Syndrome (HPS)

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1 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 RNA viruses Hantaviruses Asian, European, and American species Renal syndrome in Asia, Europe (Milder form in Europe) Respiratory syndrome in Americas Bunyavirus family with three subfamilies 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 Identification of Hantaviruses Subfamily Murinae associated viruses (HFRS) Virus Host Location Disease Hantaan Apodemus agrarius Asia, Far East Russia HFRS Dobrava Apodemus flavicollis Balkans HFRS Apodemus agrarius Europe Seoul Rattus norvegicus Worldwide HFRS Rattus rattus Subfamily Arvicolinae associated viruses Virus Host Location Disease Puumala Clethrionomys glareolus Europe *Numerous other hantaviruses have been identified but not linked to human 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 milder variant in Scandinavia Hantaviruses in the Americas Subfamily Sigmodontinae associated viruses (HPS) Virus Host Location Disease Sin Nombre Peromyscus maniculatus West/Central HPS U.S. & Canada Monongahela Peromyscus maniculatus Eastern U.S. & HPS Canada New York Peromyscus leucopus Eastern U.S. HPS Bayou Oryzomys palustris Southeastern U.S. HPS Black Cr. Sigmodon hispidus Florida HPS Andes Oligoryzomys longicaudatus Argentina & HPS Chile Oran Oligorozomys longicaudatus Northwestern HPS Argentina Lechiguanas Oligoryzomys flavescens Central Argentina HPS Hu39694 Unknown Central Argentina HPS Laguna Negra Calomys laucha Paraguay & HPS Bolivia Juquitiba Unknown Brazil HPS Etc. * Numerous other hantaviruses have been identified but not linked to human disease 1

2 Sin Nombre Virus Circular single stranded; RNA Total genome nucleotides long 100 (80-120) nm in diameter Surface projections of envelope distinct; spikes (of about 10 nm) 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-B8- DR3 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 Unexplained Adult Respiratory Distress Syndrome (ARDS) Bacterial: plague, tularemia, anthrax, Legionella, Chlamydia, Mycoplasma, Brucella, Q fever, RMSF, relapsing fever Viral: influenza, adenovirus, parvovirus coxsackie, RSV, hemorrhagic fevers Environmental: paraquat, phosphene, phosgene, DNP, metal fumes, polymer fumes, toxic oil syndrome 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% 2

3 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 Broad spectrum antibiotics until HPS proven Intensive care management: monitor electrolytes, pulmonary, and hemodynamics Fluids (eg crystalloid) to get PAOP mm Inotropic agents for myocardial contractility Dobutamine 5-20 micrograms/kg/min? adult ECMO Supportive Treatment 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 and Deer Mice Seasonality hypotheses Virus overwinters in older adult mice with high prevalence Young mice dilute prevalence Young mice progressively infected through summer Increased rainfall can increase populations Mild winter could increase overwinter survival and prevalence (1993 outbreak) Hantavirus Infection of Deer Mice Trapping in Colorado Prevalence 9.5% Range 0-43% for trapping periods Males more likely to be infected Wound were associated with infection at only one of two trapping sites Calisher Emerg Inf Dis Jan-Mar 1999 Mills Emerg Inf Dis Jan-Mar

4 Hantavirus Infection of Deer Mice Trapping in Montana ,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 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 Douglass J Wildlife Dis :12-22 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 Washington HPS Cases 28 cases reported as of Jan cases reported annually /28 (32%) fatal Age range years, 21 (75%) male 14 exposed in eastern Washington counties, 11 in western Washington counties, 3 in multiple counties a/o out of state Lazaro Emerg Inf Dis Jan 2007 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 4

5 SECOND HANDOUT Purpose determine personal and environmental risk factors for HPS Case-control study Case finding from clinicians, medical examiners, infection control practitioners: fax, mail, newsletter, media Case definition during Jan 1 July 19, 1993 a resident of NM, AZ, UT, or CO with: unexplained ARDS or unexplained bilateral infiltrates with low O 2 or compatible autopsy AND lab confirmed recent hantavirus infection Case-control study with three matched controls: uninfected member of case household uninfected member of closest household agreeing to participate randomly selected household > 24 km Matched by location (urban/rural, reservation) Controls without recent acute illness Controls tested for hantavirus Standard questionnaire by interview; surrogate interview for deceased case Rodent trapping (adjusted for sprung traps) Hypotheses at time of study (June-July 1993) Demographics Rodent-human contact Peridomestic activities with potential rodent contact Host factors Agricultural activities Occupation Pulmonary Syndrome Results 17/21 cases participated (81%) 251/282 controls participated (89%) 236 tested negative 12 not tested 3 with detectable IgG were excluded 5

6 Pulmonary Syndrome Results Not associated with HPS: Age and gender Non-mouse animal exposures Mechanical farming, rancher, construction Insect or ectoparasite Recreational activities Specific foods Associated with HPS: Disabling medical condition Certain rodent exposures: trapping or observing mice, peridomestic cleaning, hand plowing Childs et. al. P. maniculatus as Reservoir Design Determine reservoir of hantavirus Cross-sectional survey of rodents in the Four Corners region June-August 1993 Primarily piñon-juniper forest Traps around houses and visited sites for confirmed cases Personal protection respirator, gown, gloves, booties; traps disinfected ELISA serum antibody (Prospect Hill virus) as evidence of past infection to hantaviruses PCR viral RNA in rodent tissue Childs et. al. P. maniculatus as Reservoir Results 1687 rodents of 29 species Deer mouse was 47.9% of rodents Peromyscus species were 67.8% of total Genetic analysis New hantavirus group Viral sequences genetically similar Deer mice is major rodent reservoir Deer mice with highest prevalence for hantavirus Conclude deer mice most likely reservoir with spill over to other species 6

Ecology of Zoonotic Diseases Figuring out the What, Where and When of Disease Outbreaks

The Ecological Society of America Ecology of Zoonotic Diseases Figuring out the What, Where and When of Disease Outbreaks Bob Parmenter, Director, Scientific Services Division, USDA Valles Caldera National