Description

Viral hemorrhagic fever (VHF) is caused by a distinct group of viruses. The initial phase resembles influenza-like illness, while later stages (the hemorrhagic stage and convalescence) comprise a significant minority of critically ill patients. Later stages evolve into multisystem organ dysfunction, shock, and death. Most VHFs are not endemic in the US.

There are no rapid diagnostic assays; diagnosis requires a high index of suspicion and a targeted/detailed history

Etiology

• Important VHF vectors:
  • Hantaviridae (HV): Rodent reservoir, aerosolized rodent excreta (Southwest US):
    • Hemorrhagic fever with renal syndrome
    • Hantavirus pulmonary syndrome
  • Filoviruses: Fruit bat reservoir, unclear mode of transmission (sub-Saharan Africa):
    • Ebola
    • Marburg
  • Arenaviruses: Rodent reservoir, aerosolized rodent excreta (sub-Saharan Africa):
    • Lassa
    • South American hemorrhagic fevers
  • Flaviviruses: Human reservoir, via mosquito (tropics, increasingly worldwide):
    • Dengue (most common cause of VHF)
    • Yellow fever
    • Alkhurma (tick-borne, Saudi Arabia)
  • Bunyaviridae: Rodent reservoir, via tick or mosquito (Europe, South Asia, Africa):
    • Rift Valley fever
    • Crimean–Congo hemorrhagic fever (CCHF)
• RNA viruses that have zoonotic life cycles in specific geographic areas

Pathophysiology

• VHFs generally cause cytokine storm similar to septic shock, wherein later stages of the disease display multisystem organ dysfunction, derangements in microvasculature function, and membrane/capillary permeability
• VHF shock state is both hypovolemic and distributive; often difficult to reverse. Hypotension can progress swiftly and is associated with high mortality
• DIC appears to be a regular feature of Marburg and CCHF, but is less frequent with Arenavirus infections
• Dengue hemorrhagic fever is immune-complex mediated and is usually the result of secondary infection. It is among the most common causes for VHF
• Variable incubation period (2–21 d), patients may not develop symptoms until after travel