Viral Hemorrhagic Fever

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

What is Viral Hemorrhagic Fever? Severe multisystem syndrome Severe multisystem syndrome Diffuse Damage to overall vascular system Diffuse Damage to overall vascular system Symptoms often accompanied by hemorrhage Symptoms often accompanied by hemorrhage Rarely life threatening in itself Rarely life threatening in itself Includes conjunctivitis, petechia, echymosis Includes conjunctivitis, petechia, echymosis Relatively high mortality Relatively high mortality

Quick Overview: Who are they? VHFs are: VHFs are: Enveloped Lipid-encapsulated Single-strand RNA Single-strand RNA Zoonotic (animal-borne) Zoonotic (animal-borne) Geographically restricted by host Geographically restricted by host Persistent in nature (rodents, bats, mosquitoes, ticks, livestock, monkeys, and primates ) Persistent in nature (rodents, bats, mosquitoes, ticks, livestock, monkeys, and primates ) Survival dependent on an animal or insect host, for the natural reservoir Survival dependent on an animal or insect host, for the natural reservoir

Quick Overview: Who are they? Arenavirida e Arenavirida e Lassa Fever Lassa Fever Argentine HF (Junin) Argentine HF (Junin) Bolivian HF (Machupo) Bolivian HF (Machupo) Brazilian HF (Sabia) Brazilian HF (Sabia) Venezuelan HF (Guanarito) Venezuelan HF (Guanarito) Bunyavirida e Bunyavirida e Rift Valley Fever (RVF) Rift Valley Fever (RVF) Crimean Congo HF (CCHF) Crimean Congo HF (CCHF) Hantavirus (Hemorrhagic Fever with Renal Syndrome (HFRS)) Hantavirus (Hemorrhagic Fever with Renal Syndrome (HFRS)) Hantavirus Pulmonary Syndrome (HPS) Hantavirus Pulmonary Syndrome (HPS) Filoviridae Filoviridae Marburg Ebola Flaviviridae Flaviviridae Yellow Fever Dengue Fever Omsk HF Kyasanur Forest Disease

Quick Overview: How do we get infected? Rodents & Arthropods, both reservoir & vector Rodents & Arthropods, both reservoir & vector Bites of infected mosquito or tick Bites of infected mosquito or tick Inhalation of rodent excreta Inhalation of rodent excreta Infected animal product exposure Infected animal product exposure Person-to-Person Person-to-Person Blood/body fluid exposure Blood/body fluid exposure Airborne potential for some arenaviridae, filoviridae Airborne potential for some arenaviridae, filoviridae

Arenaviridae Junin virus Junin virus Machupo virus Machupo virus Guanarito virus Guanarito virus Lassa virus Lassa virus Sabia virus Sabia virus

Arenaviridae History First isolated in 1933 First isolated in : Junin virus - Argentina 1958: Junin virus - Argentina First to cause hemorrhagic fever First to cause hemorrhagic fever Argentine hemorrhagic fever Argentine hemorrhagic fever 1963: Machupo virus – Bolivia 1963: Machupo virus – Bolivia Bolivian hemorrhagic fever Bolivian hemorrhagic fever Guanarito (Venezuela) Guanarito (Venezuela) Sabia (Brazil) Sabia (Brazil) 1969: Lassa virus – Nigeria 1969: Lassa virus – Nigeria Lassa fever Lassa fever

Arenavirus Structure Single-stranded, bi-segmented RNA genome Single-stranded, bi-segmented RNA genome Large segment (7200nt), small one (3500nt) Large segment (7200nt), small one (3500nt) Lipid envelope with Lipid envelope with 8-10nm club-shaped 8-10nm club-shapedprojections

Arenaviridae Transmission Virus transmission and amplification occurs in rodents Virus transmission and amplification occurs in rodents Shed virus through urine, feces, and other excreta Shed virus through urine, feces, and other excreta Human infection Human infection Contact with excreta Contact with excreta Contaminated materials Contaminated materials Aerosol transmission Aerosol transmission Person-to-person transmission Person-to-person transmission

Arenaviridae in Humans Incubation period 10–14 days Incubation period 10–14 days Fever and malaise 2–4 days Fever and malaise 2–4 days Hemorrhagic stage Hemorrhagic stage Hemorrhage, leukopenia, thrombocytopenia Hemorrhage, leukopenia, thrombocytopenia Neurologic signs Neurologic signs

Arenaviridae: Lassa Fever First seen in Lassa, Nigeria in First seen in Lassa, Nigeria in Now in all countries of West Africa Now in all countries of West Africa 5-14% of all hospitalized febrile illness 5-14% of all hospitalized febrile illness Rodent-borne (Mastomys natalensis) Rodent-borne (Mastomys natalensis) Interpersonal transmission Interpersonal transmission Direct Contact Direct Contact Sex Sex Breast Feeding Breast Feeding

Lassa Fever Virus Background Background Discovered in 1969 when two missionary nurses died in Lassa, Nigeria, W. Africa Discovered in 1969 when two missionary nurses died in Lassa, Nigeria, W. Africa It expands to Guinea, Liberia, Sierra Leone It expands to Guinea, Liberia, Sierra Leone 100 to 300 thousand cases per year with approx. 5,000 deaths 100 to 300 thousand cases per year with approx. 5,000 deaths

Lassa Fever Distinguishing Features Distinguishing Features Gradual onset Gradual onset Retro-sternal pain Retro-sternal pain Exudative pharyngitis Exudative pharyngitis Hearing loss in 25% may be persistent Hearing loss in 25% may be persistent Spontaneous abortion Spontaneous abortion Mortality 1-3% overall (up to 50% in epidemics) Mortality 1-3% overall (up to 50% in epidemics) Therapy: Ribavirin Therapy: Ribavirin

Bunyaviridae Rift Valley Fever virus Rift Valley Fever virus Crimean-Congo Hemorrhagic Fever virus Crimean-Congo Hemorrhagic Fever virus Hantavirus Hantavirus L-segment codes for an L- protein (the RNA dependent RNA polymerase); M segment codes for two surface glycoproteins G1 and G2 which form the envelope spikes; S segment codes for an N- protein (nucleocapsid protein).

Bunyaviridae Rift Valley Fever (RVF) Rift Valley Fever (RVF) Crimean-Congo Hemorrhagic Fever (CCHF) Crimean-Congo Hemorrhagic Fever (CCHF) Hantavirus Hantavirus Old World: Hemorrhagic fever with renal syndrome (HFRS) Old World: Hemorrhagic fever with renal syndrome (HFRS) New World: Hantavirus pulmonary syndrome (HPS) New World: Hantavirus pulmonary syndrome (HPS) 5 genera with over 350 viruses 5 genera with over 350 viruses

Bunyaviridae Transmission Arthropod vector Arthropod vector Exception – Hantaviruses Exception – Hantaviruses RVF – Aedes mosquito RVF – Aedes mosquito CCHF – Ixodid tick CCHF – Ixodid tick Hantavirus – Rodents Hantavirus – Rodents Less common Less common Aerosol Aerosol Exposure to infected animal tissue Exposure to infected animal tissue

Bunyaviridae Transmission to humans Transmission to humans Arthropod vector (RVF, CCHF) Arthropod vector (RVF, CCHF) Contact with animal blood or products of infected livestock Contact with animal blood or products of infected livestock Rodents (Hantavirus) Rodents (Hantavirus) Laboratory aerosol Laboratory aerosol Person-to-person transmission with CCHF Person-to-person transmission with CCHF

Rift Valley Fever Predominantly a disease of sheep and cattle Predominantly a disease of sheep and cattle 1930: First identified in an infected newborn lamb in Egypt 1930: First identified in an infected newborn lamb in Egypt In livestock: In livestock: ~100% abortion ~100% abortion 90% mortality in young 90% mortality in young 5-60% mortality in adults 5-60% mortality in adults

Rift Valley Fever Asymptomatic or mild illness in humans Asymptomatic or mild illness in humans Distinguishing Characteristics Distinguishing Characteristics Hemorrhagic complications rare (<5%) Hemorrhagic complications rare (<5%) Vision loss (retinal hemorrhage, vasculitis) in 1-10% Vision loss (retinal hemorrhage, vasculitis) in 1-10% Overall mortality 1% Overall mortality 1% Therapy: Ribavirin? Therapy: Ribavirin?

Crimean-Congo Hemorrhagic Fever Distinguishing features Distinguishing features Abrupt onset Abrupt onset Most humans infected will develop hemorrhagic fever Most humans infected will develop hemorrhagic fever Profuse hemorrhage Profuse hemorrhage Mortality 15-40% Mortality 15-40% Therapy: Ribavirin Therapy: Ribavirin

Bunyaviridae: Crimean-Congo HF  Transmission to humans: Ixodid, Hyalomma spp. ticks Ixodid, Hyalomma spp. ticks Contact with animal blood/products Contact with animal blood/products Person-to-person Person-to-person Laboratory aerosols Laboratory aerosols Extensive geographical distribution Extensive geographical distribution

Bunyaviridae: Hantaviruses Transmission to humans: Transmission to humans: Exposure to rodent saliva and excreta Exposure to rodent saliva and excreta Inhalation Inhalation Bites Bites Ingestion in contaminated food/water (?) Ingestion in contaminated food/water (?) Person-to-person (Andes virus in Argentina) Person-to-person (Andes virus in Argentina)

Hemorrhagic Fever with Renal Syndrome (HFRS) Distinguishing Features Distinguishing Features Insidious onset Insidious onset Intense headaches, Intense headaches, Blurred vision Blurred vision kidney failure kidney failure (causing severe fluid overload) (causing severe fluid overload) Mortality: 1-15% Mortality: 1-15%

Bunyaviridae Humans RVF RVF Incubation period – 2-5 days Incubation period – 2-5 days 0.5% - Hemorrhagic Fever 0.5% - Hemorrhagic Fever CCHF CCHF Incubation period – 3-7 days Incubation period – 3-7 days Hemorrhagic Fever - 3–6 days following clinical signs Hemorrhagic Fever - 3–6 days following clinical signs Hantavirus Hantavirus Incubation period – 7–21 days Incubation period – 7–21 days HPS and HFRS HPS and HFRS

Ebola Marburg Ebola Ebola Ebola-Zaire Ebola-Zaire Ebola-Sudan Ebola-Sudan Ebola-Ivory Coast Ebola-Ivory Coast Ebola-Bundibugyo Ebola-Bundibugyo (Ebola-Reston) (Ebola-Reston) Marburg Marburg Filoviridae

Filoviridae History 1967: Marburg, Frankfurt, Belgrade 1967: Marburg, Frankfurt, Belgrade European laboratory workers European laboratory workers 1976: Ebola virus 1976: Ebola virus Ebola Zaire Ebola Zaire Ebola Sudan Ebola Sudan 1989 and 1992: Ebola Reston 1989 and 1992: Ebola Reston USA and Italy USA and Italy Imported macaques from Philippines Imported macaques from Philippines 1994: Ebola Côte d'Ivoire 1994: Ebola Côte d'Ivoire

Filoviridae Transmission Reservoir is UNKNOWN Reservoir is UNKNOWN Bats implicated with Marburg Bats implicated with Marburg Intimate contact Intimate contact Nosicomial transmission Nosicomial transmission Reuse of needles and syringes Reuse of needles and syringes Exposure to infectious tissues, excretions, and hospital wastes Exposure to infectious tissues, excretions, and hospital wastes Aerosol transmission Aerosol transmission Primates Primates

Filoviridae: Ebola Rapidly fatal febrile hemorrhagic illness Rapidly fatal febrile hemorrhagic illness Transmission: Transmission: bats implicated as reservoir bats implicated as reservoir Person-to-person Person-to-person Nosocomial Nosocomial Five subtypes Five subtypes Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast, Ebola-Bundibugyo, Ebola-Reston Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast, Ebola-Bundibugyo, Ebola-Reston Ebola-Reston imported to US, but only causes illness in non-human primates Ebola-Reston imported to US, but only causes illness in non-human primates Human-infectious subtypes found only in Africa Human-infectious subtypes found only in Africa

Filoviridae: Ebola Distinguishing features: Distinguishing features: Acute onset Acute onset Weight loss/protration Weight loss/protration 25-90% case-fatality 25-90% case-fatality

Filoviridae: Marburg Transmission: Transmission: Animal host unknown Animal host unknown Person-to-person Person-to-person infected animal blood/fluid exposure infected animal blood/fluid exposure Indigenous to Africa Indigenous to Africa Uganda Uganda Western Kenya Western Kenya Zimbabwe Zimbabwe Democratic Republic of Congo Democratic Republic of Congo Angola Angola

Filoviridae: Marburg Distinguising features Distinguising features Sudden onset Sudden onset Chest pain Chest pain Maculopapular rash on trunk Maculopapular rash on trunk Pancreatitis Pancreatitis Jaundice Jaundice 21-90% mortality 21-90% mortality

Filoviridae Humans Most severe hemorrhagic fever Most severe hemorrhagic fever Incubation period: 4–10 days Incubation period: 4–10 days Abrupt onset Abrupt onset Fever, chills, malaise, and myalgia Fever, chills, malaise, and myalgia Hemorrhage and DIC Hemorrhage and DIC Death around day 7–11 Death around day 7–11 Painful recovery Painful recovery

Flaviviridae Dengue virus Dengue virus Yellow Fever virus Yellow Fever virus Omsk Hemorrhagic Fever virus Omsk Hemorrhagic Fever virus Kyassnur Forest Disease virus Kyassnur Forest Disease virus

Flaviviridae History 1648 : Yellow Fever described 1648 : Yellow Fever described 17 th –20 th century 17 th –20 th century Yellow Fever and Dengue outbreaks Yellow Fever and Dengue outbreaks 1927: Yellow Fever virus isolated 1927: Yellow Fever virus isolated 1943: Dengue virus isolated 1943: Dengue virus isolated 1947 Omsk Hemorrhagic Fever virus isolated 1947 Omsk Hemorrhagic Fever virus isolated 1957: Kyasanur Forest virus isolated 1957: Kyasanur Forest virus isolated

Flaviviridae Transmission Arthropod vector Arthropod vector Yellow Fever and Dengue viruses Yellow Fever and Dengue viruses Aedes aegypti Aedes aegypti Sylvatic cycle Sylvatic cycle Urban cycle Urban cycle Kasanur Forest Virus Kasanur Forest Virus Ixodid tick Ixodid tick Omsk Hemorrhagic Fever virus Omsk Hemorrhagic Fever virus Muskrat urine, feces, or blood Muskrat urine, feces, or blood

Flaviviridae Epidemiology Yellow Fever Virus – Africa and Americas Yellow Fever Virus – Africa and Americas Case fatality rate – varies Case fatality rate – varies Dengue Virus – Asia, Africa, Australia, and Americas Dengue Virus – Asia, Africa, Australia, and Americas Case fatality rate – 1-10% Case fatality rate – 1-10% Kyasanur Forest virus – India Kyasanur Forest virus – India Case fatality rate – 3–5% Case fatality rate – 3–5% Omsk Hemorrhagic Fever virus – Europe Omsk Hemorrhagic Fever virus – Europe Case fatlity rate – 0.5–3% Case fatlity rate – 0.5–3%

Flaviviridae Humans Yellow Fever Yellow Fever Incubation period – 3–6 days Short remission Incubation period – 3–6 days Short remission Dengue Hemorrhagic Fever Dengue Hemorrhagic Fever Incubation period – 2–5 days Incubation period – 2–5 days Infection with different serotype Infection with different serotype Kyasanur Forest Disease Kyasanur Forest Disease Omsk Hemorrhagic Fever Lasting sequela Omsk Hemorrhagic Fever Lasting sequela

Yellow Fever Distinguishing features Distinguishing features Biphasic infection Biphasic infection Common hepatic involvement & jaundice Common hepatic involvement & jaundice Mortality: 15-50% Mortality: 15-50%

Flaviviridae: Dengue Dengue Fever (DF) /Fatality: <1% Dengue Fever (DF) /Fatality: <1% Dengue Hemorrhagic Fever (DHF)/ Fatality: 5-6% Dengue Hemorrhagic Fever (DHF)/ Fatality: 5-6% Dengue Shock Syndrome (DSS) /Fatality 12-44% Dengue Shock Syndrome (DSS) /Fatality 12-44% Four distinct serotypes Four distinct serotypes DEN-1, DEN-2, DEN-3, DEN-4 DEN-1, DEN-2, DEN-3, DEN-4 Distinguishing Features Distinguishing Features Sudden onset Sudden onset Eye pain Eye pain Rash Rash Complications/sequelae uncommon Complications/sequelae uncommon Illness less severe in younger children Illness less severe in younger children

Omsk Hemorrhagic Fever Distinguishing Features Distinguishing Features Acute Onset Acute Onset Biphasic infection Biphasic infection Complications Complications Hearing loss Hearing loss Hair loss Hair loss Psycho-behavioral difficulties Psycho-behavioral difficulties Mortality: 0.5 – 3% Mortality: 0.5 – 3%

Flaviviridae: Kyanasur Forest Distribution: limited to Karnataka State, India Distribution: limited to Karnataka State, India Distinguishing Features Distinguishing Features Acute onset Acute onset Biphasic Biphasic Case-fatality: 3-5% ( cases annually) Case-fatality: 3-5% ( cases annually)

Symptoms/Signs vary with the type of VHF

Common Pathophysiology Small vessel involvement Small vessel involvement Increased vascular permeability Increased vascular permeability Multiple cytokine activation Multiple cytokine activation Cellular damage Cellular damage Abnormal vascular regulation: Abnormal vascular regulation: Early -> mild hypotension Early -> mild hypotension Severe/Advanced -> Shock Severe/Advanced -> Shock Viremia Viremia Macrophage involvement Macrophage involvement Inadequate/delayed immune response Inadequate/delayed immune response

Common Pathophysiology Multisystem Involvement Multisystem Involvement Hematopoietic Hematopoietic Neurologic Neurologic Pulmonary Pulmonary Hepatic (Ebola, Marburg, RVF, CCHF, Yellow Fever) Hepatic (Ebola, Marburg, RVF, CCHF, Yellow Fever) Renal (Hantavirus) Renal (Hantavirus) Hemorrhagic complications Hemorrhagic complications Hepatic damage Hepatic damage Consumptive coagulopathy Consumptive coagulopathy Primary marrow injury to megakaryocytes Primary marrow injury to megakaryocytes

Common Clinical Features: Early/Prodromal Symptoms Fever Fever Myalgia Myalgia Malaise Malaise Fatigue/weakness Fatigue/weakness Headache Headache Dizziness Dizziness Arthralgia Arthralgia Nausea Nausea Non-bloody diarrhea Non-bloody diarrhea

Common Clinical Features: Progressive Signs Conjunctivitis Conjunctivitis Facial & thoracic flushing Facial & thoracic flushing Pharyngitis Pharyngitis Exanthems Exanthems Periorbital edema Periorbital edema Pulmonary edema Pulmonary edema Hemorrhage Hemorrhage Subconjunctival hemorrhage Ecchymosis Petechiae But the hemorrhage itself is rarely life- threatening.

Symptoms Incubation period of 6-21 days Incubation period of 6-21 days 80% of human infections are asyptomatic 80% of human infections are asyptomatic Onset is slow: fever, weakness, & malaise Onset is slow: fever, weakness, & malaise Few days: headache, pharyngitis, muscle pain, retrostinal & abdominal pain, nausea, vomiting, conjunctivitis, diarrhea, cough, & proteinuria Few days: headache, pharyngitis, muscle pain, retrostinal & abdominal pain, nausea, vomiting, conjunctivitis, diarrhea, cough, & proteinuria Severe cases: Severe cases: facial swelling, lung cavity fluid, hemorrhaging, hyopotension, facial swelling, lung cavity fluid, hemorrhaging, hyopotension, Neurological problems: tremors, encephalitis, hair loss, gait disturbance, deafness Neurological problems: tremors, encephalitis, hair loss, gait disturbance, deafness 95% death rate among pregnant women & spontaneous abortion 95% death rate among pregnant women & spontaneous abortion

Common Clinical Features: Severe/End-stage Multisystem compromise Multisystem compromise Profuse bleeding Profuse bleeding Consumptive coagulopathy/DIC Consumptive coagulopathy/DIC Encephalopathy Encephalopathy Shock Shock Death Death

Clinical Symptoms More severe Bleeding under skin Bleeding under skin Petechiae, echymoses, conjunctivitis Petechiae, echymoses, conjunctivitis Bleeding in internal organs Bleeding in internal organs Bleeding from orifices Bleeding from orifices Blood loss rarely cause of death Blood loss rarely cause of death

< 2 days after viral infection 1.Cytolysis by perforin-granzyme 2.IFN γ: protect uninfected cells and activate macrophages 3.Mediate ADCC 1.Phagocytosis of virus and virus-infected cells 2.Kill virus-infected cells 3.Produce antiviral molecules: TNFα, NO, IFNα Plasmcytoid DC2 1.A major IFNα producer after viral infection 2. Toll-like receptor -3 IFNγ Major antiviral cells in early phrase

Protection Killing Adaptive (specific) immune response to viral infection Neighboring uninfected cells IFN γ IFN α and IFN β

Cambridge University Immunology Lectures (www)www Innate & Adaptive Immunity Timeline

Lab studies Complete Blood Count Complete Blood Count Leucopenia, leucocytosis, thrombocytopenia, hemoconcentration, DIC Leucopenia, leucocytosis, thrombocytopenia, hemoconcentration, DIC Liver enzymes  Alb  Liver enzymes  Alb  Proteinuria universal Proteinuria universal Serological tests – Ab not detected acute phase; Direct examination blood/tissues for viral Ag enzyme immunoassay. Serological tests – Ab not detected acute phase; Direct examination blood/tissues for viral Ag enzyme immunoassay. Immunohistochemical staining liver tissue Immunohistochemical staining liver tissue Virus isolation in cell culture Virus isolation in cell culture RT-PCR sequencing of virus RT-PCR sequencing of virus Electron microscopy specific and sensitive Electron microscopy specific and sensitive

Treatment  Supportive care: Fluid and electrolyte management Fluid and electrolyte management Hemodynamic monitoring Hemodynamic monitoring Ventilation and/or dialysis support Ventilation and/or dialysis support Steroids for adrenal crisis Steroids for adrenal crisis Anticoagulants, IM injections, Anticoagulants, IM injections, Treat secondary bacterial infections Treat secondary bacterial infections

Treatment   Manage severe bleeding complications Cryoprecipitate (concentrated clotting factors)Cryoprecipitate (concentrated clotting factors) PlateletsPlatelets Fresh Frozen PlasmaFresh Frozen Plasma Heparin for DICHeparin for DIC   Ribavirin in vitro activity vs. Lassa feverLassa fever New World Hemorrhagic feversNew World Hemorrhagic fevers Rift Valley FeverRift Valley Fever No evidence to support use in Filovirus or Flavivirus infectionsNo evidence to support use in Filovirus or Flavivirus infections

Prevention and Control

Prevention Nosocomial: Complete equipment sterilization & protective clothing Nosocomial: Complete equipment sterilization & protective clothing House to house rodent trapping House to house rodent trapping Better food storage & hygiene Better food storage & hygiene Cautious handling of rodent if used as food source Cautious handling of rodent if used as food source If human case occurs If human case occurs Decrease person-to-person transmission Decrease person-to-person transmission Isolation of infected individuals Isolation of infected individuals

Prevention and Control Avoid contact with host species Avoid contact with host species Rodents Rodents Control rodent populations Control rodent populations Discourage rodents from entering or living in human populations Discourage rodents from entering or living in human populations Safe clean up of rodent nests and droppings Safe clean up of rodent nests and droppings Insects Insects Use insect repellents Use insect repellents Proper clothing and bed nets Proper clothing and bed nets Window screens and other barriers to insects Window screens and other barriers to insects

Vaccination  Argentine and Bolivian HF PASSIVE IMMUNIZATION PASSIVE IMMUNIZATION Treat with convalescent serum containing neutralizing antibody or immune globulin Treat with convalescent serum containing neutralizing antibody or immune globulin  Yellow Fever ACTIVE IMMUNIZATION ACTIVE IMMUNIZATION Travelers to Africa and South America Travelers to Africa and South America Experimental vaccines under study Experimental vaccines under study Argentine HF, Rift Valley Fever, Hantavirus and Dengue HF Argentine HF, Rift Valley Fever, Hantavirus and Dengue HF

VHF Personal Protective Equipment Airborne and Contact isolation for patients with respiratory symptoms N-95 or PAPR mask Negative pressure isolation Negative pressure isolation Gloves Gloves Gown Gown Fitted eye protection and shoe covers if going to be exposed to splash body fluids Fitted eye protection and shoe covers if going to be exposed to splash body fluids  Droplet and Contact isolation for patients without respiratory symptoms Surgical mask Surgical mask Gloves Gloves Gown Gown Fitted eye protection and shoe covers if going to be exposed to splash body fluids Fitted eye protection and shoe covers if going to be exposed to splash body fluids  Environmental surfaces Cleaned with hospital approved disinfectant Cleaned with hospital approved disinfectant Linen incinerated, autoclaved, double-bagged for wash Linen incinerated, autoclaved, double-bagged for wash

Why do VHFs make good Bioweapons?  Disseminate through aerosols  Low infectious dose  High morbidity and mortality  Cause fear and panic in the public  No effective vaccine  Available and can be produced in large quantity  Research on weaponization has been conducted