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Viral Hemorrhagic Fevers

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Viral Hemorrhagic Fevers Or The Viruses that you Desperately want to Avoid Eric Gorgon Shaw, MD, FACEP, FAAEM, FAWM * pronounced den' gee The degree of vascular leak ... – PowerPoint PPT presentation

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Title: Viral Hemorrhagic Fevers


1
Viral Hemorrhagic Fevers
  • Or
  • The Viruses that you Desperately want to Avoid
  • Eric Gorgon Shaw, MD, FACEP, FAAEM, FAWM

2
Objectives
  • Describe the relevance of Viral Hemorrhagic
    Fevers (VHF) to Wilderness Medicine
  • Describe geographical distribution of VHFs
  • Describe common clinical features of VHFs
  • Describe preventative measures for travel with
    potential exposure
  • List therapeutic options for patients with VHF
  • List infection control precautions for healthcare
    providers caring for patients with VHF

3
Lecture Overview
  • Pathophysiology Common Clinical Findings
  • Virus-specific information
  • VHF from the perspective of the traveler
  • VHF from the perspective of the clinician
  • Case Presentation

4
Why Learn about Viral Hemorrhagic Fevers at a WMS
Conference?
  • Remote locations of outbreaks
  • Worldwide distribution
  • Relation to Travel Medicine
  • Fever in a traveler

5
Viral Hemorrhagic FeverWhat is it?
  • An acute viral infection causing
  • Diffuse vascular damage
  • Hemorrhage
  • Multisystem compromise
  • Relatively high mortality

6
Quick Overview Who are they?
  • VHFs are
  • Lipid-encapsulated
  • Single-strand RNA
  • Zoonotic (animal-borne)
  • Geographically restricted by host
  • Persistent in nature (rodents, bats, mosquitoes,
    ticks, livestock, monkeys, primates)

7
Quick Overview Who are they?
  • Arenaviridae
  • Lassa Fever
  • Argentine HF (Junin)
  • Bolivian HF (Machupo)
  • Brazilian HF (Sabia)
  • Venezuelan HF (Guanarito)
  • Bunyaviridae
  • Rift Valley Fever (RVF)
  • Crimean Congo HF (CCHF)
  • Hantavirus (Hemorrhagic Fever with Renal Syndrome
    (HFRS))
  • Hantavirus Pulmonary Syndrome (HPS)
  • Filoviridae
  • Marburg
  • Ebola
  • Flaviviridae
  • Yellow Fever
  • Dengue Fever
  • Omsk HF
  • Kyasanur Forest Disease
  • Not to be confused with

8
Quick Overview How do we get infected?
  • Rodents Arthropods, both reservoir vector
  • Bites of infected mosquito or tick
  • Inhalation of rodent excreta
  • Infected animal product exposure
  • Person-to-Person
  • Blood/body fluid exposure
  • Airborne potential for some arenaviridae,
    filoviridae

9
Common Pathophysiology
  • Small vessel involvement
  • Increased vascular permeability
  • Multiple cytokine activation
  • Cellular damage
  • Abnormal vascular regulation
  • Early -gt mild hypotension
  • Severe/Advanced -gt Shock
  • Viremia
  • Macrophage involvement
  • Inadequate/delayed immune response

10
Common Pathophysiology
  • Multisystem Involvement
  • Hematopoietic
  • Neurologic
  • Pulmonary
  • Hepatic (Ebola, Marburg, RVF, CCHF, Yellow Fever)
  • Renal (Hantavirus)
  • Hemorrhagic complications
  • Hepatic damage
  • Consumptive coagulopathy
  • Primary marrow injury to megakaryocytes

11
Common Clinical Features Early/Prodromal Symptoms
  • Dizziness
  • Arthralgia
  • Nausea
  • Non-bloody diarrhea
  • Fever
  • Myalgia
  • Malaise
  • Fatigue/weakness
  • Headache

12
Common Clinical Features Progressive Signs
  • Hemorrhage
  • Subconjunctival hemorrhage
  • Ecchymosis
  • Petechiae
  • But the hemorrhage itself is rarely
    life-threatening.
  • Conjunctivitis
  • Facial thoracic flushing
  • Pharyngitis
  • Exanthems
  • Periorbital edema
  • Pulmonary edema

13
Common Clinical Features Laboratory Findings
  • Leukopenia
  • Thrombocytopenia (not Lassa)
  • Proteinuria
  • Hepatic inflammation

14
Common Clinical Features Severe/End-stage
  • Multisystem compromise
  • Profuse bleeding
  • Consumptive coagulopathy/DIC
  • Encephalopathy
  • Shock
  • Death
  • BUT

15
Symptoms/Signs vary with the type of VHF
16
Quick Overview Mortality
  • Case-Fatality
  • lt10 Dengue HF, Rift Valley Fever
  • 53 (225/425) Ebola-Sudan in Uganda (2000).
  • 81 (257/317) Ebola-Zaire in Kikwit, Zaire
    (1995). (2/3 of patients were health care workers
    171 health care workers dead!)
  • 90 (227/252) Marburg in Angola (2004-2005)

17
Arenaviridae
  • Spread to humans by rodent contact (virus found
    in urine, feces, and other excreta)
  • Lassa Fever (West Africa)
  • New World HFs
  • Machupo (Bolivia)
  • Junin (Argentina)
  • Guanarito (Venezuela)
  • Sabia (Brazil)
  • Explosive Nosocomial outbreaks with Lassa
    Machupo

18
Arenaviridae Lassa Fever
  • First seen in Lassa, Nigeria in 1969.
  • Now in all countries of West Africa
  • 5-14 of all hospitalized febrile illness
  • Rodent-borne (Mastomys natalensis)
  • Interpersonal transmission
  • Direct Contact
  • Sex
  • Breast Feeding

19
Lassa Fever
  • Distinguishing Features
  • Gradual onset
  • Retro-sternal pain
  • Exudative pharyngitis
  • Hearing loss in 25
  • may be persistent
  • Spontaneous abortion
  • Mortality 1-3 overall (up to 50 in epidemics)
  • Therapy Ribavirin

20
Arenaviridae South American HFs
  • Rodent-borne
  • Potential for person-to-person transmission
  • Junin uncommon
  • Machupo probable
  • Guanarito not-documented
  • Distinguishing characteristics
  • Gradual onset
  • Hyporeflexia, hyperesthesia
  • High mortality (20-30)
  • 70 recovery in 7-8 days without sequelae
  • Therapy Ribavirin (?)

21
Bunyaviridae
  • Rift Valley Fever (RVF)
  • Crimean-Congo Hemorrhagic Fever (CCHF)
  • Hantavirus
  • Old World Hemorrhagic fever with renal syndrome
    (HFRS)
  • New World Hantavirus pulmonary syndrome (HPS)
  • Sin Nombre (1993 outbreak in SW US)
  • 5 genera with over 350 viruses

22
Bunyaviridae
  • Transmission to humans
  • Arthropod vector (RVF, CCHF)
  • Contact with animal blood or products of
    infected livestock
  • Rodents (Hantavirus)
  • Laboratory aerosol
  • Person-to-person transmission with CCHF

23
Bunyaviridae Rift Valley Fever
  • Transmission to humans
  • Aedes mosquito
  • Contact with blood/products of infected livestock
  • Found throughout Africa, not just around the Rift
    Valley

24
Rift Valley Fever
  • Predominantly a disease of sheep and cattle
  • 1930 First identified in an infected newborn
    lamb in Egypt
  • In livestock
  • 100 abortion
  • 90 mortality in young
  • 5-60 mortality in adults

25
Rift Valley Fever
  • Asymptomatic or mild illness in humans
  • Distinguishing Characteristics
  • Hemorrhagic complications rare (lt5)
  • Vision loss (retinal hemorrhage, vasculitis) in
    1-10
  • Overall mortality 1
  • Therapy Ribavirin?

26
Bunyaviridae Crimean-Congo HF
  • Transmission to humans
  • Ixodid, Hyalomma spp. ticks
  • Contact with animal blood/products
  • Person-to-person
  • Laboratory aerosols
  • Extensive geographical distribution

27
Crimean-Congo Hemorrhagic Fever
  • 1940s Crimean Peninsula
  • Hemorrhagic Fever in agricultural workers
  • gt200 cases
  • 10 case-fatality
  • Maintained in livestock, but unapparent/subclinica
    l disease

28
Crimean-Congo Hemorrhagic Fever
  • Distinguishing features
  • Abrupt onset
  • Most humans infected will develop hemorrhagic
    fever
  • Profuse hemorrhage
  • Mortality 15-40
  • Therapy Ribavirin

29
Bunyaviridae Hantaviruses
  • Transmission to humans
  • Exposure to rodent saliva and excreta
  • Inhalation
  • Bites
  • Ingestion in contaminated food/water (?)
  • Person-to-person (Andes virus in Argentina)

30
Hantavirus
  • Worldwide distribution Rodent distribution
  • Old World Hemorrhagic Fever with Renal Syndrome
    (HFRS)
  • Hantaan virus eastern Asia (China, Russia,
    Korea)
  • Seoul virus worldwide
  • Dobrova-Belgrade virus Balkans
  • Puumala virus Scandinavia, western Europe,
    Russia
  • New World Hantavirus Pulmonary Syndrome (HPS)
    (non-hemorrhagic)
  • Sin Nombre virus of US
  • New York virus of US
  • Black Creek Canal virus of US
  • Bayou virus of US
  • Andes virus of Argentina, Chile

31
Hantavirus Hemorrhagic Fever with Renal Syndrome
(HFRS)
  • 1951 Korea Hemorrhagic Fever in UN Troops
  • gt3000 cases of acute febrile illness
  • 33 hemorrhagic manifestations
  • 5-10 case-fatality
  • One of 7 HFs researched by US for biological
    weapons

32
Hemorrhagic Fever with Renal Syndrome (HFRS)
  • Distinguishing Features
  • Insidious onset
  • Intense headaches,
  • Blurred vision
  • kidney failure
  • (causing severe fluid overload)
  • Mortality 1-15

33
Filoviridae
  • Ebola
  • Ebola-Zaire
  • Ebola-Sudan
  • Ebola-Ivory Coast
  • Ebola-Bundibugyo
  • (Ebola-Reston)
  • Marburg

34
Filoviridae Ebola
  • Rapidly fatal febrile hemorrhagic illness
  • Transmission
  • bats implicated as reservoir
  • Person-to-person
  • Nosocomial
  • Five subtypes
  • Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast,
    Ebola-Bundibugyo, Ebola-Reston
  • Ebola-Reston imported to US, but only causes
    illness in non-human primates
  • Human-infectious subtypes found only in Africa

35
Filoviridae Ebola
  • Sporadic Outbreaks (16 from 1976 2008)
  • First described in 1976 along the Ebola River in
    Zaire (now Congo) and Sudan.
  • Ebola River, Zaire, 1976 (Ebola-Zaire)
  • 318 cases, 88 mortality
  • Kikwit, Zaire, 1995 (Ebola-Zaire)
  • 315 cases, 81 mortality
  • Uganda, 2000 (Ebola-Sudan)
  • 425 cases, 53 mortality
  • Congo, 2007 (Ebola-Zaire)
  • 264 cases, 71 mortality
  • Uganda, 2007-8 (Ebola-Bundibugyo)
  • 149 cases, 25 mortality

36
Filoviridae Ebola
  • Distinguishing features
  • Acute onset
  • Weight loss/protration
  • 25-89 case-fatality

37
Filoviridae Marburg
  • Transmission
  • Animal host unknown
  • Person-to-person
  • infected animal blood/fluid exposure
  • Indigenous to Africa
  • Uganda
  • Western Kenya
  • Zimbabwe
  • Democratic Republic of Congo
  • Angola

38
Filoviridae Marburg
  • Sporadic outbreaks (8 from 1967 2008)
  • First seen in 1967, in simultaneous outbreaks of
    laboratories in Marburg, Frankfurt, and Belgrade
  • Marburg, Frankfurt, Belgrade, 1967
  • 32 cases, 21 mortality
  • Durba, DRC, 1998-2000
  • 154 cases, 83 mortality
  • Angola, 2004-2005
  • 252 cases, 90 mortality

39
Filoviridae Marburg
  • Distinguising features
  • Sudden onset
  • Chest pain
  • Maculopapular rash on trunk
  • Pancreatitis
  • Jaundice
  • 21-90 mortality

40
Flaviviridae
  • Yellow Fever
  • Dengue
  • Omsk Hemorrhagic Fever (OHF)
  • Kyanasur Forest

41
Yellow Fever
  • 1649 First reported in Cuba
  • Enormous toll of soldiers during Spanish-American
    War (1898)
  • American
  • 400 Combat deaths
  • 2000 from Yellow Fever
  • Spanish
  • 16,000 deaths from YF between 1895-1898 (out of
    an original force of 230,000)

42
Flaviviridae Yellow Fever
  • Transmission
  • Aedes aegypti mosquito
  • Sylvatic Cycle
  • Infected monkeys
  • Urban Cycle
  • Human host

43
Yellow Fever
  • Distinguishing features
  • Biphasic infection
  • Common hepatic involvement jaundice (thus, its
    name)
  • Mortality 15-50

44
Flaviviridae Dengue
  • Dengue Fever (DF)
  • Dengue Hemorrhagic Fever (DHF)
  • Dengue Shock Syndrome (DSS)
  • Four distinct serotypes
  • DEN-1, DEN-2, DEN-3, DEN-4
  • Infection with one does NOT confer immunity to
    the others
  • A person can become infected multiple times with
    Dengue
  • Counterintuitively increases the risk for DHF
    with subsequent infection
  • Transmission
  • Aedes aegypti, Aedes albopictus mosquito spp.
  • Sylvatic Urban Cycles

45
Dengue Fever History Distribution
  • 1779-1780 First reported epidemic of DF
  • Near simultaneous occurrence in Asia, Africa,
    North America
  • After WWII pandemic began in SE Asia
  • 1950s DHF emergence into the Pacific region
    Americas
  • Since discontinuation of Ae. aegypti eradication
    program, DF/DHF range has expanded

46
Dengue
  • 50-100 million cases of DF/year
  • 300,000 cases of CHF/year
  • Distinguishing Features
  • Sudden onset
  • Eye pain
  • Rash
  • Complications/sequelae uncommon
  • Illness less severe in younger children
  • 2000 Bangladesh epidemic
  • no deaths in pts lt 5y/o
  • 82 of hospitalized patients were adults
  • Case-Fatality
  • DF lt1
  • DHF 5-6
  • DSS 12-44

47
Flaviviridae Omsk Hemorrhagic Fever
  • Transmission
  • Tick bite Dermacentor, Ixodes
  • Host rodents (water vole, muskrat)
  • Infected Animal Contact
  • Milk from infected goats, sheep.
  • 1945-1947 First described in Omsk, Russia
  • Distribution western Siberia regions of Omsk,
    Novosibirsk, Kurgan and Tyumen

48
Omsk Hemorrhagic Fever
  • Distinguishing Features
  • Acute Onset
  • Biphasic infection
  • Complications
  • Hearing loss
  • Hair loss
  • Psycho-behavioral difficulties
  • Mortality 0.5 3

49
Flaviviridae Kyanasur Forest
  • Transmission
  • Tick bite (Haemaphysalis spinigera nymphs, Ixodes
    petauristae)
  • Contact with infected animal
  • Host small rodents, monkeys, shrews, bats,
    porcupines
  • Distribution limited to Karnataka State, India
  • 1957 First identified from a sick monkey
  • Distinguishing Features
  • Acute onset
  • Biphasic
  • Case-fatality 3-5 (400-500 cases annually)

50
VHFs Prevention for the World-travellerVaccinatio
ns
  • Yellow Fever
  • Kyanasur Forest Disease?
  • Investigational/non-FDA-approved
  • Argentine HF
  • Rift Valley Fever
  • Hantavirus
  • Ongoing research
  • All the others
  • Dengue Fever
  • Filoviridae

51
VHFs Prevention for the World-travellerRodent
Exposure Precautions
  • Dont mess with live/dead rodents, or their
    burrows/nests
  • Dont use rodent-infested cabins/shelters
  • Dont pitch tents or sleep near rodent feces,
    burrows, or potential rodent shelters (garbage
    dumps, woodpiles)
  • Avoid sleeping on the ground (cot gt12 inches up,
    or tent w/ floor)
  • Keep food rodent-proof
  • Dispose of waste appropriately

52
VHF Prevention for the World-travellerMosquito
Exposure Precautions
  • DEET (20-30) on exposed skin
  • Permethrine on clothing, bednets
  • Headnets
  • Bednets

53
VHF Prevention for the World-travellerTick
Exposure Precautions
  • DEET (20-30) on exposed skin
  • Permethrine on clothing, bednets
  • Light-colored clothing
  • Routine tick-check

54
VHF Prevention for the World-travellerLivestock
Animal Exposure Precautions
  • Know from where your food is coming
  • Avoid participation in birthing or butchering of
    livestock or game
  • Wild monkeys dont make good pets!

55
VHF for the ClinicianIdentification of
Suspected Cases
  • Temperature gt 101 F (38.3 C) for lt 3 weeks
  • No predisposing factors for hemorrhagic
    manifestations
  • 2 or more of the following
  • Hemorrhagic rash
  • Epistaxis
  • Hematemesis
  • Hemoptysis
  • Hematochezia/melena
  • Other hemorrhagic signs
  • No established alternative diagnosis

56
VHF for the ClinicianExposure Precautions
  • Body Fluid Exposure
  • Gloves (double)
  • Face Eye shields
  • Gowns (impermeable) w/ leg shoe coverings
  • Masks (surgical v. N95)
  • Sharp Instrument Precautions
  • Hand-washing disinfectants
  • Cadaver-exposure
  • Avoid
  • Prompt burial by trained teams

57
VHF for the ClinicianInfection Control
  • CDC Publication "Infection Control for Viral
    Haemorrhagic Fevers in the African Health Care
    Setting
  • Dedicated medical equipment
  • Stethoscopes
  • BP cuffs
  • Etc.
  • Point-of-care analysis of routine labs, if
    available

58
VHF in the lab BSL-4
  • High-level protection required for
  • Laboratory manipulation
  • Mechanical generation of aerosols
  • Concentrated infectious material
  • Viral culture

59
VHF for the ClinicianDifferential Diagnosis
  • Meningococcemia
  • Acute Leukemia
  • Hepatitis
  • Rickettsial Infection
  • Leptospirosis
  • Thrombocytopenia Purpura (ITP or TTP)
  • Fever in a traveller
  • Malaria
  • Typhoid fever
  • VHF
  • Others

60
VHF for the Clinician Distinguishing
Characteristics
  • Signs
  • Eye pain Dengue
  • Exudative Pharyngitis Lassa Fever
  • Jaundice Yellow Fever
  • Anuria RVF
  • Severe ecchymosis CCHF
  • Marked wt. loss/prostration Filoviridae
  • Vision Loss RVF
  • Hearing Loss Omsk
  • Hair Loss Omsk
  • Onset
  • Insidious Arenaviridae
  • Acute Filoviridae, Flaviviridae, RVF
  • Course
  • Incubation period 2-21 days (varies by virus)
  • Biphasic Flaviviridae
  • Laboratory
  • Absence of/minor thrombocytopenia Lassa
  • Convalescence
  • Deafness (20 Lassa)

61
VHF for the ClinicianDiagnostics
  • Isolation of virus from tissue, cell culture
  • Serum antigen detection
  • ELISA
  • RT-PCR
  • Immunohistochemical staining of infected tissue

62
VHF for the ClinicianTreatment
  • Specific Therapy
  • Ribavirin (not FDA-licensed)
  • Lassa Fever
  • New World Arenaviruses
  • Crimean-Congo Hemorrhagic Fever
  • Convalescent-phase plasma
  • Argentine Hemorrhagic Fever (Junin)
  • Non-specific Therapy Supportive Care
  • Fluid electrolyte management
  • Oxygenation
  • Blood pressure support
  • Correct coagulopathies as needed
  • No antiplatelet/anticoagulant drugs, IM therapy

63
VHF for the ClinicianManagement of Exposures
  • Medical surveillance x 21 days
  • Potential exposures
  • Close contacts
  • High-risk exposures (percutaneous/mucocutaneous
    exposure)
  • Percutaneous/mucocutaneous exposure to infected
    individual
  • Percutaneous wash thoroughly with soap water
  • Mucocutaneous flush/irrigate with saline or water
  • Prophylaxis
  • Ribavirin for close contacts
  • Lassa fever
  • Crimean-Congo HF
  • Convalescent abstinence from sex x 3 months (!)
  • Arenaviridae
  • Filoviridae

64
VHF for the ClinicianInfection Control
65
Case Presentation
  • 38 y/o male complains of fever, chills, diarrhea,
    back pain, sore throat
  • (Easy! Viral syndrome. Whos next!)
  • PE Temp 103.6 F, BP 90/60
  • Skin w/ diffuse ecchymosis, maculopapular rash on
    extremities
  • (AwCrap!)
  • Travel History just got back from a 4 month stay
    on his farms in Liberia and Sierra Leone
  • (OhFrick!)

66
Case PresentationHospital Course
  • Day 4
  • Patient developed ARDS
  • Despite empiric antibiotics (incl. antimalarials)
  • Intubated
  • Day 5
  • Local State Health Depts. notified.
  • Investigational New Drug (IND) protocol to
    administer ribavirin
  • Patient died before ribavirin administered

67
Case PresentationPost-mortem
  • Samples sent to CDC
  • Lassa Fever confirmed
  • Serum antigen detection
  • Virus isolation in cell culture
  • RT-PCR sequencing of virus
  • Immunohistochemical staining of liver samples

68
Case PresentationExposure Management/Infection
Control
  • 5 High risk contacts
  • 5 (wife, kids, visitor)
  • 183 Low risk contacts
  • 9 other family members
  • 139 HCW at hospital 42 labworkers, 32 RN, 11 MD
  • 16 labworkers in Virginia and California
  • 19 passengers on flight from London to Newark
  • No additional cases

69
Summary
  • You probably wont be carrying Biohazard Level 4
    gear.
  • If you dont have religion, this might be a good
    time
  • Dont breathe rat poop!
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