II. Pathophysiology
- Natural host species (e.g. animal carcasses, infected bats) are specific to certain geographic regions
- Natural outbreaks typically start in these regions
 - However, person to person spread may occur in new regions if patients travel
- Responsible for most cases in humans
 
 
 - Transmission
- Natural exposure to body fluids
 - Bioterrorism exposure to aerosolized infectious agent
 
 - Pathogenesis
- All Viral Hemorrhagic Fevers result in vascular endothelial damage
- Results in Flushing, edema, Petechiae, Ecchymosis, Hemorrhage and shock
 
 
 - All Viral Hemorrhagic Fevers result in vascular endothelial damage
 
III. Causes
- Background
- Four families of lipid-enveloped single-stranded RNA Viruses
 
 - Arena Virus (Arenaviridae, Rodent Reservoir)
- Lassa Fever
 - Junin
 - Machupo
 - Lujo
 - Sabia
 - Chapare
 
 - 
                          Bunyavirus (Bunyaviridae)
- Rift Valley Fever
 - Crimean Congo Hemorrhagic FeverVirus
 - Hantavirus Hemorrhagic Fever
 
 - 
                          Flavivirus (Flaviviridae)
- Yellow Fever
 - Dengue Fever
 - Omsk Hemorrhagic Fever
 - Kyasanur Forest Disease
 
 - Filovirus (Filoviridae, Bat Reservoir)
 
IV. Findings
- Incubation: 2-21 days
 - Non-specific symptoms (initial phase)
- Fever
 - Headache
 - Myalgias
 - Arthralgias
 - Rash
 
 - Gastrointestinal symptoms (second phase)
 - Bleeding
- Conjunctival Injection
 - Mucosal Bleeding (gums, Gastrointestinal Tract)
 - Hemoptysis
 - Epistaxis
 - Hemoptysis
 - Bloody Diarrhea
 - Petechiae, Purpura and Ecchymosis
 
 - Other late findings
- Shock with Multisystem organ failure
 - Encephalitis
 
 
V. Diagnosis: Hemorrhagic Fever Syndrome (WHO)
- Fever <3 weeks AND
 - Severely ill patient AND
 - Two hemorrhagic findings (without known host predisposing factors)
- Hemorrhagic or Purpuric rash
 - Epistaxis
 - Hematemesis
 - Hemoptysis
 - Blood in stools
 
 
VI. Labs
- Diagnostic specimens are sent to specialized labs (e.g. CDC or U.S. Army Medical Research Institute of Infectious Diseases)
 
VII. Complications
- Multiorgan Failure
- Hepatic Failure
 - Renal Failure
 
 - Hemorrhagic Shock
 - Septic Shock
 
VIII. Management: General
- See Specific causes
 - Strict patient isolation
 - Supportive care
 - 
                          Antiviral management
- Ribavirin (see below)
 - Monoclonal Antibody treatments have been developed for several hemorrhagic fevers
- See Ebola
 
 
 - 
                          Personal Protective Equipment for care givers
- Transmission from the body fluids (percutaneous, mucosal contact) is common at the end stages of the disease
 - See Personal Protection Equipment for protection against Viral Hemorrhagic Fevers
 - See Donning and Doffing PPE
 
 - Disinfection with dilute bleach
- Use 1:10 bleach solution to disinfect bodies and excretions
 - Use 1:100 bleach solutions to disinfect surfaces, equipment, bedding and reusable PPE
 
 
IX. Management: Ribavirin (Virazole)
- Indications
- Lassa Fever
 - Arenaviridae
 - Bunyaviridae
 - May be used in other Viral Hemorrhagic Fevers (e.g. ebola)
 
 - 
                          Ribavirin Protocol
- Load 30 mg/kg (up to 2 g) IV
 - Then 16 mg/kg (up to 1 g) IV every g hours for 4 days
 - Then 8 mg/kg (up to 500 mg) IV every 8 hours for 6 days
 
 
X. References
- Black, Martin, DeVos (2018) Crit Dec Emerg Med 32(8): 3-12
 - Charbonnet and Mace (2023) Crit Dec Emerg Med 37(4): 4-10
 - Gladwin (2014) Clinical Microbiology, MedMaster, Miami, p.306-7, 398
 - Rathjen (2021) Am Fam Physician 104(4): 376-85 [PubMed]