Viral Haemorrhagic Fevers

Viral haemorrhagic fever (VHF) is not one disease but a clinical syndrome shared by a group of unrelated RNA viruses. Each is an enveloped, single-stranded RNA virus, almost all are zoonotic, and each can produce the same core picture: fever and malaise giving way to increased vascular permeability, falling blood pressure, coagulation failure and, in the most severe infections, shock and multi-organ failure. The agents come from four groups of viruses, the Arenaviridae, the Filoviridae, the order Bunyavirales and the Flaviviridae, and it is their shared pathophysiology rather than their taxonomy that unites them.

What separates these viruses from commoner causes of fever is their capacity to spread from person to person, above all in hospitals and at funerals, together with the high case fatality of the most dangerous among them, which is why the most lethal are handled only at maximum laboratory containment. A suspected case sets a defined clinical, laboratory and public-health response in motion: recognising the possibility from a compatible exposure, excluding malaria, isolating early, and sampling safely. The articles below cover both the virological and clinical picture of the agents and the pathway that response follows.

→ See Viral Haemorrhagic Fevers: an Overview for the VHF syndrome, the four virus families and their agents, the shared pathophysiology of vascular leak and coagulopathy, the clinical spectrum, the structured approach to a suspected case and the malaria differential, and the biosafety levels used to contain these viruses.

→ See Arenaviruses: New World and Old World for the rodent-borne arenaviruses, the split between the Old World agents (Lassa, Lujo, lymphocytic choriomeningitis virus) and the New World haemorrhagic fevers (Junin, Machupo, Guanarito, Sabia), and the clinical meaning of that divide.

→ See Filoviruses: Ebola and Marburg for the Ebola species and Marburg virus: their bat reservoir, transmission, biphasic clinical course, survivor persistence, and the species-specific vaccine and therapeutic landscape.

→ See South African VHF Guidelines for the operational pathway a suspected case follows: risk assessment and the case definition, safe specimen collection and transport, the reference laboratory, isolation and personal protective equipment, contact management, and notification.

The four families of viral haemorrhagic fever

Family or order	Representative VHF agents	Reservoir and main route	Principal regions
Arenaviridae	Lassa, Lujo, Junin, Machupo	Rodents; contact with excreta and body fluids	West Africa, southern Africa, South America
Filoviridae	Ebola (including Bundibugyo), Marburg	Bats; direct contact with body fluids	Sub-Saharan Africa
Bunyavirales	Crimean-Congo haemorrhagic fever, Rift Valley fever, hantaviruses	Ticks, mosquitoes, rodents	Africa, Europe, Asia, the Americas
Flaviviridae	Yellow fever, severe dengue	Mosquitoes	Tropical Africa, the Americas, Asia

Key terms

Term	Meaning
Viral haemorrhagic fever	A clinical syndrome of fever with increased vascular permeability and coagulopathy, caused by several unrelated RNA viruses.
Zoonosis	An infection maintained in animals that spills over into people.
Reservoir host	The animal population that maintains a virus in nature, usually without severe disease.
Spillover	Transmission of a virus from its animal reservoir into a human host.
Capillary leak	Increased vascular permeability, the core lesion of severe VHF, which drains intravascular volume and drives shock.
Disseminated intravascular coagulation	Widespread activation of clotting that consumes platelets and clotting factors and produces bleeding.
Cytokine storm	An excessive release of inflammatory mediators that drives vascular and organ injury.
Nosocomial transmission	Spread of infection within a healthcare setting, a hallmark risk of several VHFs.
Case fatality ratio	The proportion of diagnosed cases that die of the disease.
Biosafety level 4	The highest level of laboratory containment, required for the most dangerous VHF agents.
Ring vaccination	Vaccinating the contacts of a case, and their contacts in turn, to contain spread.
Post-exposure prophylaxis	Treatment given after a known exposure to prevent disease developing.

References and recommended reading

• Carson G, Bray M, Roth C. Viral Haemorrhagic Fevers. In: Clinical Virology, 4th edition, Chapter 9. ASM Press; 2016. The comparative account of the VHF syndrome across its causative families.
• Hewson R. Understanding Viral Haemorrhagic Fevers: Virus Diversity, Vector Ecology, and Public Health Strategies. Pathogens. 2024;13(10):909. The current reference for VHF virus family taxonomy, vector ecology and control.
• National Institute for Communicable Diseases. Viral Haemorrhagic Fever: guidelines for the management and prevention of infection in South Africa. NICD; 2015, with 2024 to 2026 updates. The South African operational baseline.