Hemorrhagic Fever Viruses

Hemorrhagic fever viruses are a diverse group of RNA viruses that cause viral hemorrhagic fever, a severe systemic illness marked by fever, vascular dysfunction, and, in many cases, bleeding. They include filoviruses (Ebola and Marburg), arenaviruses (Lassa), bunyaviruses (Crimean-Congo hemorrhagic fever, Rift Valley fever, hantaviruses), and flaviviruses (yellow fever, dengue).

Definition

Hemorrhagic fever viruses are enveloped RNA viruses from several families that cause viral hemorrhagic fever (MeSH: Hemorrhagic Fevers, Viral), a syndrome of fever and increased vascular permeability that can progress to coagulopathy, bleeding, shock, and multiorgan failure.

Scope

This topic covers the major families of hemorrhagic fever viruses, the shared clinical syndrome of viral hemorrhagic fever, their animal reservoirs and routes of transmission, their epidemic potential, and the public-health and biosafety considerations they raise. It is reference-educational and does not provide individualized clinical or outbreak-management instructions.

Core questions

• Which virus families cause viral hemorrhagic fever, and what reservoirs and vectors maintain them?
• What unifies the clinical syndrome of viral hemorrhagic fever across these diverse viruses?
• Why do several of these viruses pose major epidemic and biosafety threats?
• How are viral hemorrhagic fevers transmitted to and among humans?

Key concepts

• Viral hemorrhagic fever syndrome
• Filoviruses (Ebola, Marburg)
• Arenaviruses (Lassa)
• Bunyavirales (Crimean-Congo HF, Rift Valley fever, hantaviruses)
• Flaviviruses (yellow fever, dengue)
• Zoonotic reservoirs and vectors
• Increased vascular permeability and coagulopathy
• Epidemic potential and biosafety (BSL-4)

Mechanisms

Hemorrhagic fever viruses are maintained in animal reservoirs (such as bats and rodents) or arthropod vectors and reach humans through contact with infected animals, vectors, or, for some viruses, infected body fluids enabling human-to-human spread. After infection these viruses cause systemic disease in which a combination of direct cellular injury, dysregulated immune and inflammatory responses, endothelial dysfunction, and coagulation abnormalities leads to increased vascular permeability, bleeding, and shock; for Ebola, infection of immune and endothelial cells with intense inflammatory activation is central to severe disease (feldmann-2020; geisbert-jahrling-2004).

Clinical relevance

Viral hemorrhagic fevers are among the most feared infectious diseases because several are highly lethal, capable of person-to-person transmission, and prone to causing explosive outbreaks that strain health systems. Recognition and isolation are critical public-health concerns, and many of these agents require high-level biocontainment. This entry describes the disease category and its epidemiology and is not a basis for individual patient management.

Epidemiology

Most hemorrhagic fever viruses are geographically restricted to regions where their reservoirs or vectors occur, producing sporadic cases and periodic outbreaks; Ebola virus has caused recurrent African outbreaks including the very large West African epidemic of 2014-2016 (feldmann-2020). Because of their lethality and epidemic potential, several hemorrhagic fever viruses appear on the World Health Organization's list of priority pathogens for research and preparedness (who-vhf-priority).

History

Yellow fever was the first hemorrhagic fever virus shown, in the early twentieth century, to be a filterable, mosquito-borne agent. Marburg virus emerged in 1967 and Ebola virus in 1976, defining the filoviruses, while Lassa fever and the Crimean-Congo and hantavirus diseases were characterized in subsequent decades. Recurrent outbreaks, culminating in the 2014-2016 West African Ebola epidemic, drove major advances in countermeasures and preparedness (feldmann-2020; geisbert-jahrling-2004).

Seminal works

• feldmann-2020
• geisbert-jahrling-2004

Frequently asked questions

Do all viral hemorrhagic fevers cause heavy bleeding?

No; bleeding is a feature of severe cases but is not universal. Many infections present mainly with fever and increased vascular permeability, and overt hemorrhage is variable across the different viruses and disease stages.

Why do hemorrhagic fever viruses require such strict containment?

Several are highly lethal, can spread between people through body fluids, and have no widely available specific treatment or vaccine, so the most dangerous agents are handled in maximum-containment (BSL-4) laboratories and managed with strict isolation precautions.