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Viral Hemorrhagic Fevers

Viral Hemorrhagic Fevers. Or The Viruses that you Desperately want to Avoid Eric Gorgon Shaw, MD, FACEP, FAAEM, FAWM. Objectives. Describe the relevance of Viral Hemorrhagic Fevers (VHF) to Wilderness Medicine Describe geographical distribution of VHFs

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Viral Hemorrhagic Fevers

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  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. 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… Quick Overview: Who are they?

  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 -> mild hypotension • Severe/Advanced -> 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. Fever Myalgia Malaise Fatigue/weakness Headache Dizziness Arthralgia Nausea Non-bloody diarrhea Common Clinical Features: Early/Prodromal Symptoms

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

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

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

  15. Symptoms/Signs vary with the type of VHF

  16. Quick Overview: Mortality • Case-Fatality • <10%: 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. 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 Lassa Fever

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

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

  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 • >200 cases • 10% case-fatality • Maintained in livestock, but unapparent/subclinical 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 • >3000 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. Distinguishing features: Acute onset Weight loss/protration 25-89% case-fatality Filoviridae: Ebola

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

  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. 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 < 5y/o 82% of hospitalized patients were adults Case-Fatality: DF: <1% DHF: 5-6% DSS: 12-44% Dengue

  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. 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) Flaviviridae: Kyanasur Forest

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

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