Hantavirus

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Hantavirus : 

Hantavirus

Overview: 

Overview Organism History Epidemiology Transmission Disease in Humans Disease in Animals Prevention and Control

The Organism: 

The Organism

Hantaviruses: 

Hantaviruses Family Bunyaviridae RNA virus Genus Hantavirus Only genus not arthropod-borne Transmitted by murid rodents More than 25 hantavirus species

Hantaviruses: 

Hantaviruses Lipid envelope Deactivated by ordinary disinfectants A “viral hemorrhagic fever” Hantavirus Pulmonary Syndrome (HPS) Hemorrhagic Fever with Renal Syndrome (HFRS)

Hantaviruses in the Old World: 

Hantaviruses in the Old World

Hantaviruses in the New World: 

Hantaviruses in the New World

Hantaviruses in the New World: 

Hantaviruses in the New World *Numerous other hantaviruses have been identified but not linked to human disease

Slide9: 

Sin Nombre Peromyscus maniculatus Rio Segundo Reithrodontomys mexicanus El Moro Canyon Reithrodontomys megalotis Andes Oligoryzomys longicaudatus Bayou Oryzomys palustris Black Creek Canal Sigmodon hispidus Rio Mamore Oligoryzomys microtis Laguna Negra Calomys laucha Muleshoe Sigmodon hispidus New York Peromyscus leucopus Juquitiba Unknown Host Orán Oligoryzomys longicaudatus Caño Delgadito Sigmodon alstoni Isla Vista Microtus californicus Bloodland Lake Microtus ochrogaster Prospect Hill Microtus pennsylvanicus Bermejo Oligoryzomys chacoensis

History: 

History

Hantaviruses in Our Past: 

Hantaviruses in Our Past American Civil War World Wars I and II 1913, 1932 Russia reported cases 1934 Sweden - Nephropathia Endemica 1950’s Reports of Korean Hemorrhagic Fever

Hemorrhagic Fever with Renal Syndrome (HFRS): 

Hemorrhagic Fever with Renal Syndrome (HFRS) 1951-1954: Korean War 3,200 U.N. troops develop disease Hantaan River separated N. & S. Korea 1977 Hantaan agent isolated and characterized 1990: 94% of serum samples from soldiers in 1950’s had antibodies 1979 Seoul virus found in Japan and Europe

U.S.: Four Corners Outbreak: 

U.S.: Four Corners Outbreak

The Four Corners Outbreak: 

The Four Corners Outbreak May 1993 First clinical case Abrupt fever, myalgia, pulmonary edema June 1993 12 fatalities Unexplained Adult Respiratory Distress Syndrome (ARDS) Sera cross-reacted with Hantaan, Seoul, Puumala virus Rodents trapped - deer mouse main reservoir

The Four Corners Outbreak: 

The Four Corners Outbreak Winter and spring 1993 Drought for several years followed by snow and rain Vegetation blossomed and rodent population grew tenfold Virus isolated and named Sin Nombre Virus (SNV) Newly emerging virus has been present since 1959 38 year old Utah man

Epidemic Curve of Four Corners Outbreak: 

Epidemic Curve of Four Corners Outbreak

Recent Cases: 

Recent Cases May 2003: Montana Three cases Two deaths Contracted virus from rodents in home First cases since fall of 2001 Overall cases in Montana Virus first appeared in state in 1993 20 cases 5 deaths

Epidemiology: 

Epidemiology

Common Rodent Reservoirs: 

Common Rodent Reservoirs United States, except the Southeast Deer mouse (Peromyscus maniculatus) Southeast United States Cotton rat (Sigmodon hispidus) Rice rat (Oryzomys palustris) Eastern White-footed mouse (Peromyscus leucopus) House mouse not a carrier!

Slide20: 

Cotton Rat Sigmodon hispidus Deer Mouse Peromyscus maniculatus House Mouse Mus musculus L.L. Masters

Hantaan Virus Reservoir: 

Striped field mouse Apodemus agrarius Hantaan Virus Reservoir

Location of HPS Cases by Virus Types: July 6, 2004: 

Although serologically confirmed as HPS, sequence data are not available for all cases. For non-sequenced cases, the specific infecting hantavirus is assumed to be that corresponding with the known rodent reservoir in the area of probable exposure. Location of HPS Cases by Virus Types: July 6, 2004 Total Cases (N=366 in 31 States)

Distribution* of Peromyscus maniculatus and HPS Cases as of July 6, 2004: 

Distribution* of Peromyscus maniculatus and HPS Cases as of July 6, 2004 Total Cases (N=366 in 31 States) *Rodent distributions from: Burt WH, Grossenheider RP. A Field Guide to the Mammals. 3rd ed. New York, New York. Houghton Mifflin Company. 1980

Distribution* of Oryzomys palustris and Location of HPS Cases as of July 6, 2004: 

Distribution* of Oryzomys palustris and Location of HPS Cases as of July 6, 2004 *Rodent distributions from: Burt WH, Grossenheider RP. A Field Guide to the Mammals. 3rd ed. New York, New York. Houghton Mifflin Company. 1980 Total Cases (N=366 in 31 States)

Distribution* of Peromyscus leucopus and HPS Cases as of July 6, 2004: 

*Rodent distributions from: Burt WH, Grossenheider RP. A Field Guide to the Mammals. 3rd ed. New York, New York. Houghton Mifflin Company. 1980 Distribution* of Peromyscus leucopus and HPS Cases as of July 6, 2004 Total Cases (N=366 in 31 States)

Distribution* of Sigmodon hispidus and HPS Cases as of July 6, 2004: 

Distribution* of Sigmodon hispidus and HPS Cases as of July 6, 2004 *Rodent distributions from: Burt WH, Grossenheider RP. A Field Guide to the Mammals. 3rd ed. New York, New York. Houghton Mifflin Company. 1980 Total Cases (N=366 in 31 States)

HPS Cases by State of Residence U.S.: July 6, 2004: 

HPS Cases by State of Residence U.S.: July 6, 2004 Total Cases (N=366 in 31 States)

HPS Case Count: 

HPS Case Count North & South America 1500 cases United States and Canada Sin Nombre Virus Majority of cases Others implicated Andes, Monongahela, Black Creek Canal, Bayou, and New York viruses Rodent-to-human transmission

HPS Case Count, U.S.: 

HPS Case Count, U.S. United States 31 states have reported cases Occur throughout the year More common in spring-summer 75% of patients reside in rural areas 62% male; 38% female Mean age of confirmed case is 37 Mortality rate 38% Notifiable disease

Non-Sin Nombre HPS Viruses: 

Non-Sin Nombre HPS Viruses Black Creek Canal Virus Cotton rat (Sigmodon hispidus) One case in a Florida man Bayou Virus Rice rat (Oryzomys palustris) 4 cases in Louisiana, Texas New York-1 Virus Deer mouse (P. maniculatus), white footed mouse (P. leucopus) 2 cases in New York

Rodent Exposures and HPS 70 confirmed HPS cases: 

Armstrong, L.R. et al., JID 1995; 172 (October) Rodent Exposures and HPS 70 confirmed HPS cases

Risk of Contracting HPS: 

Risk of Contracting HPS Relatively low Contact with rodent excrement puts you at greatest risk Cleaning a rodent infested dwelling Opening or cleaning buildings that have been closed for a while Especially over winter

Risk of Contracting HPS: 

Risk of Contracting HPS Work, play, or live in closed spaces where rodents are actively living Hikers and campers Construction and utility workers Enter crawl spaces under buildings No serological evidence in 522 samples Traveling to and within hantavirus areas is not a risk factor

HPS U.S. Descriptive Demographic Statistics: July 6, 2003: 

N Male Female 366 (100%) 227 (62%) 139 (38%) White 284 (78%) American Indian 71 ( 19%) Black Asian 3 ( 1%) Hispanic 45 (12%) Dead 135 (37%) Age (years) 6 ( 2%) HPS U.S. Descriptive Demographic Statistics: July 6, 2003 Mean=37 [10-75]

Slide36: 

1995 1996 1997 1998 1999 2000 2001 2002 60 55 50 45 40 35 30 25 20 15 10 5 0 Reported Cases Year

Slide37: 

November 1998

HFRS: 

HFRS Worldwide 150,000–200,000 cases/yr Korean Hemorrhagic Fever South Korea 300-700 cases annually Eastern China ~100,000 cases annually Outbreaks linked to contact with field rodents during planting and harvesting of crops

Transmission: 

Transmission

Transmission of Hantaviruses: 

Chronically infected rodent Virus is present in aerosolized excreta, particularly urine Horizontal transmission of infection between same species by contact Secondary aerosols, mucous membrane contact, and skin breaches are also a consideration Transmission of Hantaviruses

Transmission of Hantaviruses: 

Transmission of Hantaviruses Non-rodent animals may test positive Do not excrete viral particles Some species may introduce rodents into domestic setting Person-to-person transmission rare Not through blood transfusion or vectors Southern Argentina case Lab acquired (several cases)

Disease in Humans: 

Disease in Humans

Clinical Signs of HPS : 

Clinical Signs of HPS Incubation period 14-17 days Early stage Fatigue, fever, myalgia, headache Lasts 3-5 days Half of the patients experience headaches, dizziness, chills, nausea, vomiting, diarrhea, abdominal pain

Clinical Signs of HPS: 

Clinical Signs of HPS Later stage 4 to 10 days after initial signs Coughing and shortness of breath Rapidly progressive, non-cardiogenic pulmonary edema and severe hypotension Hospitalization and ventilation required usually within 24 hours

Clinical Signs of HPS: 

Clinical Signs of HPS Tachypnea, tachycardia Hypotension Crackles or rales on lung examination Lowered albumin, elevated hematocrit Elevated WBC count Platelet count below 150,000 units

HPS Radiographic Findings: 

HPS Radiographic Findings Bilateral interstitial infiltrates Moderate to rapid progression Bilateral alveolar infiltrates Pleural effusion Normal heart size

Radiographic Progression of HPS: 

May 27, 1993 May 30, 1993 May 31, 1993 Source: Dr. L. Ketai Radiographic Progression of HPS

HPS National Surveillance Inclusion Criteria: 

HPS National Surveillance Inclusion Criteria Healthy person with febrile illness; Unexplained acute respiratory distress syndrome OR bilateral interstitial lung infiltrates Supplemental oxygen OR death from unexplained respiratory illness AND noncardiogenic pulmonary edema at autopsy AND no identifiable, specific cause of death

HPS National Surveillance Exclusion Criteria: 

HPS National Surveillance Exclusion Criteria Predisposing underlying medical condition Acute illness that explains the respiratory disease

HPS National Surveillance: 

HPS National Surveillance Confirmation requires meeting all inclusion and exclusion criteria Plus laboratory confirmation Positive serology Positive PCR Positive IHC

Clinical Signs of HFRS: 

Clinical Signs of HFRS Febrile phase Abrupt onset of chills, lethargy, sustained high fever Headache, myalgia, vomiting, diarrhea Thrombocytopenia, petechial hemorrhages Hypotensive phase Increased hematocrit Sinus bradycardia

Clinical Signs of HFRS: 

Clinical Signs of HFRS Oliguric phase Lowered urine output Increased serum urea and creatinine Death due to circulatory or renal failure Diuretic phase Spontaneous Convalescent phase Unable to concentrate urine

Other HFRS Clinical Signs: 

Other HFRS Clinical Signs Hantaan, Seoul, Dobrava viruses Severe hemorrhagic complications Puumala virus Nephropathia Epidemica Acute febrile disease with renal involvement Transient thrombocytopenia

Diagnosis: 

Diagnosis Serology ELISA used by CDC IgM, IgG Immunohistochemistry Detects viral antigen in tissues Virus isolation Various others

HPS Treatment: 

HPS Treatment Early, aggressive intensive care Avoidance of hypoxia Assisted ventilation Electrolyte balance Maintaining normal blood pressure Ribavirin has questionable efficacy Careful monitoring

HPS Prognosis : 

HPS Prognosis Patients can recover With early supportive care Grave prognosis If undiagnosed or do not seek treatment Chronic lung and heart damage Can result depending on the type and aggressiveness of supportive care

Case: 

Case February 2000 61 year old rural Vermont resident Episodes of fever, chills, syncope Hospitalized Swollen lymph node, sore knee Abnormal CBC, normal lung radiographs Progressed to respiratory failure Interstitial edema, mechanical ventilation

Case: 

Case Renal insufficiency, DIC Released after 23 days Initial diagnosis Adult Respiratory Distress Syndrome with sepsis Further Investigation Contact with rodent excrement Paired serum samples positive for SNV 5% of HPS cases occur east of Mississippi River

Disease in Animals: 

Disease in Animals

Disease in Animals: 

Disease in Animals Rodents Reservoir Asymptomatic carriers Antigen present in virtually all organs Infectious for life Other mammals seronegative

Prevention and Control: 

Prevention and Control

HPS Prevention: 

HPS Prevention Limit exposure to mouse excrement Control rodents indoors Control rodents outdoors Use safety precautions when cleaning rodent infested areas Minimize your exposure when enjoying outdoor activities

Control Mice Indoors: 

Control Mice Indoors Prevent access to food sources Keep food preparation and cooking areas clean Cover pet and human food overnight Store garbage in tightly covered or elevated container Rodent trapping

Prevent Entry Indoors: 

Prevent Entry Indoors Seal holes with steel wool or use sheet metal around foundation Clear away brush from foundation

Control Mice Outside: 

Control Mice Outside Eliminate nesting sites Elevate woodpiles and garbage cans Eliminate food sources Store in tight containers Cover uneaten food at night Encourage natural predators Non-poisonous snakes, owls, hawks

Safely Clean Up Rodent Areas: 

Safely Clean Up Rodent Areas Wear rubber gloves Avoid sweeping or vacuuming initially Spray contaminated materials with disinfectant Seal dead rodents and excrement in bags and dispose Disinfect gloves before removal and Wash Hands!

Minimizing Outdoor Exposure: 

Minimizing Outdoor Exposure Avoid contact with rodents Do not camp near rodent burrows Keep campsite clean Tightly seal all food Air out unused cabins before entering Avoid sleeping on the bare ground

Other Measures: 

Other Measures Use N-100 (HEPA) filters on respirators Effective in removing virus particles less than 5 microns Not tested in transmission of HPS

Internet Resources: 

Internet Resources CDC All About Hantavirus www.cdc.gov/ncidod/diseases/hanta/hps/noframes/phys/clinical.htm CDC Infectious Disease Pathology Activity www.cdc.gov/ncidod/diseases/hanta/hps/noframes/printgenlsection.htm

Acknowledgments: 

Acknowledgments Development of this presentation was funded by a grant from the Centers for Disease Control and Prevention to the Center for Food Security and Public Health at Iowa State University.

Acknowledgments: 

Acknowledgments Author: Co-author: Reviewer: Radford Davis, DVM, MPH Danelle Bickett-Weddle, DVM, MPH Stacy Holzbauer, DVM