Viral Hemorrhagic Viral Hemorrhagic FeverFever

OverviewOverview OrganismOrganism HistoryHistory EpidemiologyEpidemiology TransmissionTransmission Disease in HumansDisease in Humans Disease in AnimalsDisease in Animals Prevention and ControlPrevention and Control

What is Viral Hemorrhagic What is Viral Hemorrhagic Fever?Fever?

Severe multisystem syndrome   Severe multisystem syndrome   Diffuse Damage to overall vascular Diffuse Damage to overall vascular

systemsystem Symptoms often accompanied by Symptoms often accompanied by

hemorrhagehemorrhage Rarely life threatening in itselfRarely life threatening in itself Includes conjunctivitis, petechia, echymosisIncludes conjunctivitis, petechia, echymosis

Relatively high mortalityRelatively high mortality

Quick Overview: Who are Quick Overview: Who are they?they? VHFs are:VHFs are:

Enveloped Lipid-encapsulated Single-strand RNASingle-strand RNA Zoonotic (animal-borne) Zoonotic (animal-borne) Geographically restricted by hostGeographically restricted by host Persistent in nature (rodents, bats, mosquitoes, Persistent in nature (rodents, bats, mosquitoes,

ticks, livestock, monkeys, and primatesticks, livestock, monkeys, and primates)) Survival dependent on an animal or insect Survival dependent on an animal or insect

host, for the natural reservoirhost, for the natural reservoir

Quick Overview: Who are Quick Overview: Who are they?they?

ArenaviridaArenaviridaee Lassa FeverLassa 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)

BunyaviridaBunyaviridaee Rift Valley Fever (RVF)Rift Valley Fever (RVF) Crimean Congo HF (CCHF)Crimean Congo HF (CCHF) Hantavirus (Hemorrhagic Fever Hantavirus (Hemorrhagic Fever

with Renal Syndrome (HFRS))with Renal Syndrome (HFRS)) Hantavirus Pulmonary Hantavirus Pulmonary

Syndrome (HPS)Syndrome (HPS)

FiloviridaeFiloviridae MarburgMarburg EbolaEbola

FlaviviridaeFlaviviridae Yellow FeverYellow Fever Dengue FeverDengue Fever Omsk HFOmsk HF Kyasanur Forest DiseaseKyasanur Forest Disease

Quick Overview: How do we Quick Overview: How do we get infected?get infected?

Rodents & Arthropods, both reservoir & Rodents & Arthropods, both reservoir & vectorvector

Bites of infected mosquito or tickBites of infected mosquito or tick Inhalation of rodent excretaInhalation of rodent excreta Infected animal product exposureInfected animal product exposure

Person-to-PersonPerson-to-Person Blood/body fluid exposureBlood/body fluid exposure Airborne potential for some arenaviridae, Airborne potential for some arenaviridae,

filoviridaefiloviridae

ArenaviridaeArenaviridae

• Junin virusJunin virus• Machupo virusMachupo virus• Guanarito virusGuanarito virus• Lassa virusLassa virus• Sabia virusSabia virus

Arenaviridae HistoryArenaviridae History First isolated in 1933First isolated in 1933 1958: Junin virus - Argentina 1958: Junin virus - Argentina

First to cause hemorrhagic feverFirst to cause hemorrhagic fever Argentine hemorrhagic feverArgentine hemorrhagic fever

1963: Machupo virus – Bolivia1963: Machupo virus – Bolivia Bolivian hemorrhagic feverBolivian hemorrhagic fever Guanarito (Venezuela)Guanarito (Venezuela)

Sabia (Brazil)Sabia (Brazil) 1969: Lassa virus – Nigeria1969: Lassa virus – Nigeria

Lassa feverLassa fever

Arenavirus StructureArenavirus Structure

Single-stranded, bi-segmented Single-stranded, bi-segmented RNA genomeRNA genome

Large segment (7200nt), small Large segment (7200nt), small one (3500nt)one (3500nt)

Lipid envelope with Lipid envelope with

8-10nm club-shaped 8-10nm club-shaped

projectionsprojections

Arenaviridae TransmissionArenaviridae Transmission Virus transmission and amplification Virus transmission and amplification

occurs in rodentsoccurs in rodents Shed virus through urine, feces, and Shed virus through urine, feces, and

other excretaother excreta Human infection Human infection

Contact with excretaContact with excreta Contaminated materialsContaminated materials Aerosol transmissionAerosol transmission

Person-to-person transmissionPerson-to-person transmission

Arenaviridae in HumansArenaviridae in Humans

Incubation period 10–14 daysIncubation period 10–14 days Fever and malaise 2–4 daysFever and malaise 2–4 days Hemorrhagic stageHemorrhagic stage

Hemorrhage, leukopenia, Hemorrhage, leukopenia, thrombocytopeniathrombocytopenia

Neurologic signsNeurologic signs

Arenaviridae: Lassa FeverArenaviridae: Lassa Fever First seen in Lassa, Nigeria in 1969. First seen in Lassa, Nigeria in 1969. Now in all countries of West AfricaNow in all countries of West Africa

5-14% of all hospitalized febrile illness5-14% of all hospitalized febrile illness Rodent-borne (Rodent-borne (Mastomys natalensisMastomys natalensis)) Interpersonal transmissionInterpersonal transmission

Direct ContactDirect Contact SexSex Breast FeedingBreast Feeding

Lassa Fever VirusLassa Fever Virus

BackgroundBackground Discovered in 1969 Discovered in 1969

when two missionary when two missionary nurses died in Lassa, nurses died in Lassa, Nigeria, W. AfricaNigeria, W. Africa It expands to Guinea, It expands to Guinea,

Liberia, Sierra LeoneLiberia, Sierra Leone 100 to 300 thousand 100 to 300 thousand

cases per year with cases per year with approx. 5,000 deathsapprox. 5,000 deaths

Lassa FeverLassa Fever

Distinguishing FeaturesDistinguishing Features Gradual onsetGradual onset Retro-sternal painRetro-sternal pain Exudative pharyngitisExudative pharyngitis Hearing loss in 25% may be Hearing loss in 25% may be

persistentpersistent Spontaneous abortionSpontaneous abortion

Mortality 1-3% overall (up to 50% in Mortality 1-3% overall (up to 50% in epidemics)epidemics)

Therapy: RibavirinTherapy: Ribavirin

BunyaviridaeBunyaviridae• Rift Valley Fever virusRift Valley Fever virus

• Crimean-Congo Hemorrhagic Fever Crimean-Congo Hemorrhagic Fever virusvirus

• HantavirusHantavirusL-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).

BunyaviridaeBunyaviridae Rift Valley Fever (RVF)Rift Valley Fever (RVF) Crimean-Congo Hemorrhagic Fever Crimean-Congo Hemorrhagic Fever

(CCHF)(CCHF) HantavirusHantavirus

Old World: Hemorrhagic fever with renal Old World: Hemorrhagic fever with renal syndrome (HFRS)syndrome (HFRS)

New World: Hantavirus pulmonary New World: Hantavirus pulmonary syndrome (HPS)syndrome (HPS)

5 genera with over 350 viruses5 genera with over 350 viruses

Bunyaviridae TransmissionBunyaviridae Transmission Arthropod vectorArthropod vector

Exception – HantavirusesException – Hantaviruses RVF – RVF – AedesAedes mosquito mosquito CCHF – Ixodid tickCCHF – Ixodid tick Hantavirus – RodentsHantavirus – Rodents Less commonLess common

AerosolAerosol Exposure to infected animal tissue Exposure to infected animal tissue

BunyaviridaeBunyaviridae Transmission to humansTransmission to humans

Arthropod vector (RVF, CCHF)Arthropod vector (RVF, CCHF) Contact with animal blood or Contact with animal blood or

products of infected livestockproducts of infected livestock Rodents (Hantavirus)Rodents (Hantavirus) Laboratory aerosolLaboratory aerosol Person-to-person transmission with Person-to-person transmission with

CCHFCCHF

Rift Valley FeverRift Valley Fever

Predominantly a disease of sheep and Predominantly a disease of sheep and cattlecattle

1930: First identified in an infected 1930: First identified in an infected newborn lamb in Egyptnewborn lamb in Egypt

In livestock:In livestock: ~100% abortion~100% abortion 90% mortality in young90% mortality in young 5-60% mortality in adults5-60% mortality in adults

Rift Valley FeverRift Valley Fever Asymptomatic or mild illness in Asymptomatic or mild illness in

humanshumans Distinguishing CharacteristicsDistinguishing Characteristics

Hemorrhagic complications rare Hemorrhagic complications rare (<5%)(<5%)

Vision loss (retinal hemorrhage, Vision loss (retinal hemorrhage, vasculitis) in 1-10%vasculitis) in 1-10%

Overall mortality 1%Overall mortality 1% Therapy: Ribavirin?Therapy: Ribavirin?

Crimean-Congo Hemorrhagic Crimean-Congo Hemorrhagic FeverFever

Distinguishing featuresDistinguishing features Abrupt onset Abrupt onset Most humans infected will Most humans infected will

develop hemorrhagic feverdevelop hemorrhagic fever Profuse hemorrhageProfuse hemorrhage

Mortality 15-40%Mortality 15-40% Therapy: RibavirinTherapy: Ribavirin

Bunyaviridae: Bunyaviridae: Crimean-Congo Crimean-Congo HFHF

Transmission to humans:Transmission to humans: Ixodid, HyalommaIxodid, Hyalomma spp. ticks spp. ticks Contact with animal Contact with animal

blood/productsblood/products Person-to-personPerson-to-person Laboratory aerosolsLaboratory aerosols

Extensive geographical Extensive geographical distributiondistribution

Bunyaviridae: HantavirusesBunyaviridae: Hantaviruses

Transmission to humans:Transmission to humans: Exposure to rodent saliva and excretaExposure to rodent saliva and excreta InhalationInhalation BitesBites Ingestion in contaminated food/water (?)Ingestion in contaminated food/water (?) Person-to-person (Andes virus in Person-to-person (Andes virus in

Argentina)Argentina)

Hemorrhagic Fever with Hemorrhagic Fever with Renal Syndrome (HFRS)Renal Syndrome (HFRS)

Distinguishing FeaturesDistinguishing Features Insidious onsetInsidious onset Intense headaches, Intense headaches, Blurred visionBlurred vision kidney failure kidney failure

(causing severe fluid overload)(causing severe fluid overload)

Mortality: 1-15%Mortality: 1-15%

Bunyaviridae HumansBunyaviridae Humans RVF RVF

Incubation period – 2-5 daysIncubation period – 2-5 days 0.5% - Hemorrhagic Fever0.5% - Hemorrhagic Fever

CCHF CCHF Incubation period – 3-7 daysIncubation period – 3-7 days Hemorrhagic Fever - 3–6 days Hemorrhagic Fever - 3–6 days

following clinical signsfollowing clinical signs Hantavirus Hantavirus

Incubation period – 7–21 daysIncubation period – 7–21 days HPS and HFRSHPS and HFRS

Ebola

Marburg

EbolaEbola Ebola-ZaireEbola-Zaire Ebola-SudanEbola-Sudan Ebola-Ivory CoastEbola-Ivory Coast Ebola-BundibugyoEbola-Bundibugyo (Ebola-Reston)(Ebola-Reston)

MarburgMarburg

Filoviridae

Filoviridae HistoryFiloviridae History 1967: Marburg, Frankfurt, Belgrade1967: Marburg, Frankfurt, Belgrade

European laboratory workersEuropean laboratory workers 1976: Ebola virus1976: Ebola virus

Ebola ZaireEbola Zaire Ebola SudanEbola Sudan

1989 and 1992: Ebola Reston1989 and 1992: Ebola Reston USA and ItalyUSA and Italy Imported macaques from PhilippinesImported macaques from Philippines

1994: Ebola Côte d'Ivoire 1994: Ebola Côte d'Ivoire

Filoviridae Transmission Filoviridae Transmission

Reservoir is UNKNOWNReservoir is UNKNOWN Bats implicated with MarburgBats implicated with Marburg

Intimate contactIntimate contact Nosicomial transmissionNosicomial transmission

Reuse of needles and syringesReuse of needles and syringes Exposure to infectious tissues, excretions, Exposure to infectious tissues, excretions,

and hospital wastesand hospital wastes Aerosol transmissionAerosol transmission

PrimatesPrimates

Filoviridae: EbolaFiloviridae: Ebola

Rapidly fatal febrile hemorrhagic illnessRapidly fatal febrile hemorrhagic illness Transmission:Transmission:

bats implicated as reservoirbats implicated as reservoir Person-to-personPerson-to-person NosocomialNosocomial

Five subtypesFive subtypes Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Ebola-Zaire, Ebola-Sudan, Ebola-Ivory

Coast, Ebola-Bundibugyo, Ebola-RestonCoast, Ebola-Bundibugyo, Ebola-Reston Ebola-Reston imported to US, but only Ebola-Reston imported to US, but only

causes illness in non-human primatescauses illness in non-human primates Human-infectious subtypes found only in Human-infectious subtypes found only in

AfricaAfrica

Filoviridae: EbolaFiloviridae: Ebola

Distinguishing features:Distinguishing features: Acute onsetAcute onset Weight loss/protrationWeight loss/protration

25-90% case-fatality25-90% case-fatality

Filoviridae: MarburgFiloviridae: Marburg Transmission:Transmission:

Animal host unknownAnimal host unknown Person-to-personPerson-to-person infected animal blood/fluid exposureinfected animal blood/fluid exposure

Indigenous to AfricaIndigenous to Africa UgandaUganda Western KenyaWestern Kenya ZimbabweZimbabwe Democratic Republic of CongoDemocratic Republic of Congo AngolaAngola

Filoviridae: MarburgFiloviridae: Marburg Distinguising featuresDistinguising features

Sudden onsetSudden onset Chest painChest pain Maculopapular rash on trunkMaculopapular rash on trunk PancreatitisPancreatitis JaundiceJaundice

21-90% mortality21-90% mortality

Filoviridae HumansFiloviridae Humans Most severe hemorrhagic feverMost severe hemorrhagic fever Incubation period: 4–10 daysIncubation period: 4–10 days Abrupt onsetAbrupt onset

Fever, chills, malaise, and myalgiaFever, chills, malaise, and myalgia Hemorrhage and DICHemorrhage and DIC Death around day 7–11Death around day 7–11 Painful recoveryPainful recovery

FlaviviridaeFlaviviridae

• Dengue virusDengue virus

• Yellow Fever virusYellow Fever virus

• Omsk Hemorrhagic Fever Omsk Hemorrhagic Fever virusvirus

• Kyassnur Forest Disease Kyassnur Forest Disease virusvirus

Flaviviridae HistoryFlaviviridae History 1648 : Yellow Fever described1648 : Yellow Fever described 1717thth–20–20thth century century

Yellow Fever and Dengue outbreaksYellow Fever and Dengue outbreaks 1927: Yellow Fever virus isolated1927: Yellow Fever virus isolated 1943: Dengue virus isolated1943: Dengue virus isolated 1947 Omsk Hemorrhagic Fever virus 1947 Omsk Hemorrhagic Fever virus

isolatedisolated 1957: Kyasanur Forest virus isolated1957: Kyasanur Forest virus isolated

Flaviviridae TransmissionFlaviviridae Transmission Arthropod vectorArthropod vector Yellow Fever and Dengue virusesYellow Fever and Dengue viruses

Aedes aegyptiAedes aegypti Sylvatic cycleSylvatic cycle Urban cycleUrban cycle

Kasanur Forest VirusKasanur Forest Virus Ixodid tickIxodid tick

Omsk Hemorrhagic Fever virusOmsk Hemorrhagic Fever virus Muskrat urine, feces, or bloodMuskrat urine, feces, or blood

Flaviviridae EpidemiologyFlaviviridae Epidemiology Yellow Fever Virus – Africa and AmericasYellow Fever Virus – Africa and Americas

Case fatality rate – variesCase fatality rate – varies Dengue Virus – Asia, Africa, Australia, and Dengue Virus – Asia, Africa, Australia, and

AmericasAmericas Case fatality rate – 1-10%Case fatality rate – 1-10%

Kyasanur Forest virus – IndiaKyasanur Forest virus – India Case fatality rate – 3–5%Case fatality rate – 3–5%

Omsk Hemorrhagic Fever virus – EuropeOmsk Hemorrhagic Fever virus – Europe Case fatlity rate – 0.5–3%Case fatlity rate – 0.5–3%

Flaviviridae HumansFlaviviridae Humans Yellow Fever Yellow Fever

Incubation period – 3–6 days Short Incubation period – 3–6 days Short remissionremission

Dengue Hemorrhagic FeverDengue Hemorrhagic Fever Incubation period – 2–5 daysIncubation period – 2–5 days Infection with different serotypeInfection with different serotype

Kyasanur Forest DiseaseKyasanur Forest Disease Omsk Hemorrhagic Fever Lasting Omsk Hemorrhagic Fever Lasting

sequelasequela

Yellow FeverYellow Fever Distinguishing featuresDistinguishing features

Biphasic infectionBiphasic infection Common hepatic Common hepatic involvement & jaundice involvement & jaundice

Mortality: 15-50%Mortality: 15-50%

Flaviviridae: DengueFlaviviridae: Dengue Dengue Fever (DF) /Fatality:Dengue Fever (DF) /Fatality: <1% <1% Dengue Hemorrhagic Fever (DHF)/ Fatality:Dengue Hemorrhagic Fever (DHF)/ Fatality: 5-6% 5-6% Dengue Shock Syndrome (DSS)Dengue Shock Syndrome (DSS) /Fatality 12- /Fatality 12-

44%44%

Four distinct serotypesFour distinct serotypes DEN-1, DEN-2, DEN-3, DEN-4DEN-1, DEN-2, DEN-3, DEN-4

Distinguishing FeaturesDistinguishing Features Sudden onsetSudden onset Eye painEye pain RashRash Complications/sequelae uncommonComplications/sequelae uncommon Illness less severe in younger childrenIllness less severe in younger children

Omsk Hemorrhagic FeverOmsk Hemorrhagic Fever

Distinguishing FeaturesDistinguishing Features Acute OnsetAcute Onset Biphasic infectionBiphasic infection ComplicationsComplications

Hearing lossHearing loss Hair lossHair loss Psycho-behavioral difficultiesPsycho-behavioral difficulties

Mortality: 0.5 – 3%Mortality: 0.5 – 3%

Flaviviridae: Kyanasur ForestFlaviviridae: Kyanasur Forest

Distribution: limited to Distribution: limited to Karnataka State, IndiaKarnataka State, India

Distinguishing FeaturesDistinguishing Features Acute onsetAcute onset BiphasicBiphasic

Case-fatality: 3-5% (400-500 Case-fatality: 3-5% (400-500 cases annually)cases annually)

Symptoms/Signs vary Symptoms/Signs vary with the type of VHFwith the type of VHF

Common PathophysiologyCommon Pathophysiology Small vessel involvementSmall vessel involvement

Increased vascular permeabilityIncreased vascular permeability Multiple cytokine activationMultiple cytokine activation

Cellular damageCellular damage Abnormal vascular regulation:Abnormal vascular regulation:

Early -> mild hypotensionEarly -> mild hypotension Severe/Advanced -> ShockSevere/Advanced -> Shock

ViremiaViremia Macrophage involvementMacrophage involvement

Inadequate/delayed immune Inadequate/delayed immune responseresponse

Common PathophysiologyCommon Pathophysiology Multisystem InvolvementMultisystem Involvement

Hematopoietic Hematopoietic NeurologicNeurologic PulmonaryPulmonary Hepatic (Ebola, Marburg, RVF, CCHF, Yellow Fever)Hepatic (Ebola, Marburg, RVF, CCHF, Yellow Fever) Renal (Hantavirus)Renal (Hantavirus)

Hemorrhagic complicationsHemorrhagic complications Hepatic damageHepatic damage Consumptive coagulopathyConsumptive coagulopathy Primary marrow injury to megakaryocytesPrimary marrow injury to megakaryocytes

Common Clinical Features: Common Clinical Features: Early/Prodromal SymptomsEarly/Prodromal Symptoms

FeverFever MyalgiaMyalgia MalaiseMalaise Fatigue/weaknessFatigue/weakness HeadacheHeadache

DizzinessDizziness ArthralgiaArthralgia NauseaNausea Non-bloody Non-bloody

diarrheadiarrhea

Common Clinical Features: Common Clinical Features: Progressive SignsProgressive Signs

ConjunctivitisConjunctivitis Facial & thoracic Facial & thoracic

flushingflushing PharyngitisPharyngitis ExanthemsExanthems Periorbital edemaPeriorbital edema Pulmonary edemaPulmonary edema

HemorrhageHemorrhage Subconjunctival Subconjunctival

hemorrhagehemorrhage EcchymosisEcchymosis PetechiaePetechiae But the But the

hemorrhage itself hemorrhage itself is rarely life-is rarely life-threatening.threatening.

SymptomsSymptoms Incubation period of 6-21 daysIncubation period of 6-21 days 80% of human infections are asyptomatic 80% of human infections are asyptomatic Onset is slow: fever, weakness, & malaiseOnset is slow: fever, weakness, & malaise Few days: headache, pharyngitis, muscle pain, retrostinal Few days: headache, pharyngitis, muscle pain, retrostinal

& abdominal pain, nausea, vomiting, conjunctivitis, & abdominal pain, nausea, vomiting, conjunctivitis, diarrhea, cough, & proteinuriadiarrhea, cough, & proteinuria

Severe casesSevere cases: : facial swelling, lung cavity fluid, hemorrhaging, hyopotension,facial swelling, lung cavity fluid, hemorrhaging, hyopotension, Neurological problems: tremors, encephalitis, hair loss, gait Neurological problems: tremors, encephalitis, hair loss, gait

disturbance, deafnessdisturbance, deafness 95% death rate among pregnant women & spontaneous 95% death rate among pregnant women & spontaneous

abortionabortion

Common Clinical Features: Common Clinical Features: Severe/End-stageSevere/End-stage

Multisystem compromiseMultisystem compromise Profuse bleedingProfuse bleeding Consumptive coagulopathy/DICConsumptive coagulopathy/DIC EncephalopathyEncephalopathy Shock Shock DeathDeath

Clinical SymptomsClinical Symptoms

More severe Bleeding under skinBleeding under skin

Petechiae, echymoses, conjunctivitisPetechiae, echymoses, conjunctivitis Bleeding in internal organsBleeding in internal organs Bleeding from orificesBleeding from orifices Blood loss rarely cause of deathBlood loss rarely cause of death

< 2 days after viral infection1.Cytolysis by perforin-granzyme2.IFN γ: protect uninfected cells and activate macrophages3.Mediate ADCC

1. Phagocytosis of virus and virus-infected cells2. Kill virus-infected cells3. Produce antiviral molecules: TNFα, NO, IFNα

Plasmcytoid DC21.A major IFNα producer after viral infection2. Toll-like receptor -3

IFNγ

Major antiviral cells in early phrase

ProtectionKilling

Adaptive (specific) immune response to viral infection

Neighboring uninfected

cells

IFNγ IFNα and IFNβ

1

2

34

5

6

7

8

9

Cambridge University Immunology Lectures (www)

Innate & Adaptive Immunity Timeline

Lab studiesLab studies Complete Blood CountComplete Blood Count

Leucopenia, leucocytosis, thrombocytopenia, Leucopenia, leucocytosis, thrombocytopenia, hemoconcentration, DIChemoconcentration, DIC

Liver enzymesLiver enzymes AlbAlb Proteinuria universalProteinuria universal Serological tests – Ab not detected acute phase; Serological tests – Ab not detected acute phase;

Direct examination blood/tissues for viral Ag Direct examination blood/tissues for viral Ag enzyme immunoassay.enzyme immunoassay. Immunohistochemical staining liver tissueImmunohistochemical staining liver tissue Virus isolation in cell cultureVirus isolation in cell culture RT-PCR sequencing of virusRT-PCR sequencing of virus

Electron microscopy specific and sensitiveElectron microscopy specific and sensitive

TreatmentTreatment Supportive care:Supportive care:

• Fluid and electrolyte managementFluid and electrolyte management• Hemodynamic monitoringHemodynamic monitoring• Ventilation and/or dialysis supportVentilation and/or dialysis support• Steroids for adrenal crisisSteroids for adrenal crisis• Anticoagulants, IM injectionsAnticoagulants, IM injections, , • Treat secondary bacterial infectionsTreat secondary bacterial infections

TreatmentTreatment

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 No evidence to support use in Filovirus or Flavivirus

infectionsinfections

Prevention and Prevention and ControlControl

PreventionPrevention Nosocomial: Complete equipment sterilization Nosocomial: Complete equipment sterilization

& protective clothing& protective clothing House to house rodent trappingHouse to house rodent trapping Better food storage & hygieneBetter food storage & hygiene Cautious handling of rodent if used as food Cautious handling of rodent if used as food

source source If human case occurs If human case occurs

Decrease person-to-person transmissionDecrease person-to-person transmission Isolation of infected individualsIsolation of infected individuals

Prevention and ControlPrevention and Control Avoid contact with host speciesAvoid contact with host species

RodentsRodents Control rodent populationsControl rodent populations Discourage rodents from entering or living in Discourage rodents from entering or living in

human populationshuman populations Safe clean up of rodent nests and droppingsSafe clean up of rodent nests and droppings

InsectsInsects Use insect repellentsUse insect repellents Proper clothing and bed netsProper clothing and bed nets Window screens and other barriers to insectsWindow screens and other barriers to insects

VaccinationVaccination Argentine and Bolivian HFArgentine and Bolivian HF

• PASSIVE IMMUNIZATIONPASSIVE IMMUNIZATIONTreat with convalescent serum containing Treat with convalescent serum containing

neutralizing antibody or immune globulinneutralizing antibody or immune globulin Yellow FeverYellow Fever

• ACTIVE IMMUNIZATIONACTIVE IMMUNIZATIONTravelers to Africa and South AmericaTravelers to Africa and South America

Experimental vaccines under studyExperimental vaccines under study Argentine HF, Rift Valley Fever, Argentine HF, Rift Valley Fever,

Hantavirus and Dengue HFHantavirus and Dengue HF

VHF Personal Protective EquipmentVHF Personal Protective Equipment

Airborne and Contact isolation for patients with respiratory symptoms• N-95 or PAPR mask• Negative pressure isolationNegative pressure isolation• GlovesGloves• GownGown• Fitted eye protection and shoe covers if going to be exposed to Fitted eye protection and shoe covers if going to be exposed to

splash body fluidssplash body fluids Droplet and Contact isolationDroplet and Contact isolation for patients for patients without respiratorywithout respiratory

symptomssymptoms• Surgical maskSurgical mask• GlovesGloves• GownGown• Fitted eye protection and shoe covers if going to be exposed to Fitted eye protection and shoe covers if going to be exposed to

splash body fluidssplash body fluids Environmental surfacesEnvironmental surfaces

• Cleaned with hospital approved disinfectantCleaned with hospital approved disinfectant• Linen incinerated, autoclaved, double-bagged for washLinen incinerated, autoclaved, double-bagged for wash

Why do VHFs make good Why do VHFs make good Bioweapons?Bioweapons?

Disseminate through aerosolsDisseminate through aerosols Low infectious doseLow infectious dose High morbidity and mortalityHigh morbidity and mortality Cause fear and panic in the publicCause fear and panic in the public No effective vaccineNo effective vaccine Available and can be produced in large quantityAvailable and can be produced in large quantity Research on weaponization has been conductedResearch on weaponization has been conducted