漢他病毒感染 衛生署疾病管制局 中區傳染病防治醫療網 王任賢指揮官
Overview Organism History Epidemiology Transmission Disease in Humans Disease in Animals Prevention and Control
The Organism
Hantaviruses Family Bunyaviridae RNA virus Genus Hantavirus Only genus not arthropod-borne Transmitted by murid rodents More than 25 hantavirus species
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 Serotype Host Location Hantaan Dobrava Seoul Apodemus agrarius (striped field mouse) A. agrarius, A. flavicollis (yellow neck mouse) Rattus norvegicus, R. rattus (Norway brown rat, roof rat) Asia, Far East Russia Europe Balkans Worldwide Puumala Clethrionomys glareolus (red bank vole) Europe
Hantaviruses in the New World Serotype Host Location Sin Nombre Monongahela New York Bayou Black Creek Canal Peromyscus maniculatus (deer mouse) Peromyscus maniculatus (deer mouse) Peromyscus leucopus (whitefooted mouse) Oryzomys palustris (rice rat) Sigmodon hispidus (cotton rat) Central & West U.S., Canada Eastern U.S., Canada Eastern U.S., Canada SE U.S. SE U.S.
Hantaviruses in the New World Serotype Host Location Andes Oligoryzomys longicaudatus (long-tailed pygmy rice rat) Argentina/Chile Oran O. longicaudatus NW Argentina Lechiguanas O. flavescens Central Argentina Hu39694 Unknown Central Argentina Laguna Negra Calomys laucha Paraguay/ Bolivia Juquitiba Unknown Brazil *Numerous other hantaviruses have been identified but not linked to human disease
New World Hantaviruses Sin Nombre Peromyscus maniculatus Muleshoe Sigmodon hispidus Isla Vista Microtus californicus El Moro Canyon Reithrodontomys megalotis Caño Delgadito Sigmodon alstoni Juquitiba Unknown Host Rio Mamore Oligoryzomys microtis Orán Oligoryzomys longicaudatus Bermejo Oligoryzomys chacoensis Andes Oligoryzomys longicaudatus New York Peromyscus leucopus Prospect Hill Microtus pennsylvanicus Bloodland Lake Microtus ochrogaster Bayou Oryzomys palustris Black Creek Canal Sigmodon hispidus Rio Segundo Reithrodontomys mexicanus Laguna Negra Calomys laucha Maciel Necromys benefactus Hu39694 Unknown Host Lechiguanas Oligoryzomys flavescens Pergamino Akodon azarae
History
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) 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
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 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
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
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!
Deer Mouse Peromyscus maniculatus House Mouse Mus musculus L.L. Masters Cotton Rat Sigmodon hispidus
Hantaan Virus Reservoir Striped field mouse Apodemus agrarius
Location of HPS Cases by Virus Types: July 6, 2004 Total Cases (N=366 in 31 States) 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.
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 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 Peromyscus leucopus 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 Sigmodon hispidus 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
HPS Cases by State of Residence U.S.: July 6, 2004 Total Cases (N=366 in 31 States)
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. 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 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 Peridomestic exposure Peridomestic & occupational exposure Peridomestic & recreational exposure Occupational exposure Entering/cleaning rodent-infested structures 69% (48/70) 19% (13/70) 9% (6/70) 4% (3/70) 9% (6/70) Armstrong, L.R. et al., JID 1995; 172 (October)
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 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 Characteristics Gender Race Ethnicity Case Fatality Age (years) N Male Female Total 366 (100%) 227 (62%) 139 (38%) White 284 (78%) American Indian 71 (19%) Black Asian 6 ( 2%) 3 ( 1%) Hispanic 45 (12%) Dead 135 (37%) Mean=37 [10-75]
0 Reported Cases 5 10 15 20 25 30 35 40 45 50 55 60 1995 1996 1997 1998 1999 2000 2001 2002 Year
November 1998
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 of Hantaviruses Chronically infected rodent Horizontal transmission of infection between same species by contact Virus is present in aerosolized excreta, particularly urine Secondary aerosols, mucous membrane contact, and skin breaches are also a consideration
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
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 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 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 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
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 Predisposing underlying medical condition Acute illness that explains the respiratory disease
HPS National Surveillance Confirmation requires meeting all inclusion and exclusion criteria Plus laboratory confirmation Positive serology Positive PCR Positive IHC
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 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 Hantaan, Seoul, Dobrava viruses Severe hemorrhagic complications Puumala virus Nephropathia Epidemica Acute febrile disease with renal involvement Transient thrombocytopenia
Diagnosis Serology ELISA used by CDC IgM, IgG Immunohistochemistry Detects viral antigen in tissues Virus isolation Various others
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 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 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 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 Rodents Reservoir Asymptomatic carriers Antigen present in virtually all organs Infectious for life Other mammals seronegative
Prevention and Control
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 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 Seal holes with steel wool or use sheet metal around foundation Clear away brush from foundation
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 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 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 Use N-100 (HEPA) filters on respirators Effective in removing virus particles less than 5 microns Not tested in transmission of HPS
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