Viral haemorrhagic fevers

Origin of viral haemorrhagic fevers

History

Yellow fever is a centuries-old example of a viral haemorrhagic fever (VHF).⁶ Ancient China, Manchuria in 1930, countries in north-western Europe in 1934 and Korea in the 1950s experienced, under various names, an acute epidemic viral haemorrhagic fever associated with acute kidney injury.⁶ In 1962, Gajdusek grouped these clearly related infections together under the term haemorrhagic fever with renal syndrome (HFRS), caused by viruses belonging to the same genus, Hantavirus, within the Bunyaviridae family.⁶

It subsequently became apparent that VHFs form a heterogeneous group of viral diseases involving different virus families.⁶˒⁷ The emergence and re-emergence of viral haemorrhagic fevers are a growing global concern.⁸

Over the past 20 years, the Eastern Mediterranean Region has experienced major outbreaks and sporadic cases of yellow fever, Rift Valley fever, severe dengue and Crimean–Congo haemorrhagic fever in more than 12 countries.⁸ The Ebola epidemic that occurred in West Africa in 2015 resulted in more than 29,000 cases and approximately 11,000 deaths.⁹

The biology of the viruses responsible for VHFs, their epidemiology and their case fatality rates vary considerably: 1% for Lassa fever,¹ 50% for Ebola²˒³ and Marburg haemorrhagic fever,⁴ and 40% for Crimean–Congo fever.⁵

The viruses

Different virus families are involved in the development of VHFs:⁶˒⁷

• The Flaviviridae, whose viruses of the genus Flavivirus cause yellow fever and dengue haemorrhagic fever
• The Bunyaviridae, including Hantavirus, Phlebovirus, which causes Rift Valley fever, and Nairovirus, which causes Crimean–Congo haemorrhagic fever
• The Arenaviridae, whose arenaviruses, including Lassa fever virus, are associated with Lassa fever
• The Filoviridae, whose genus Filovirus includes Ebola virus and Marburg virus

Transmission

VHFs have multiple modes of transmission.⁸ Transmission may occur through contact with carrier animals, such as carcasses or fluids from infected animals in the case of Lassa, Marburg or Ebola fevers; through insect bites, including mosquitoes and ticks in the case of Crimean–Congo and Rift Valley fevers; and through human-to-human transmission involving blood, secretions and other bodily fluids.⁷˒⁸ In the vast majority of cases, person-to-person transmission occurs through direct contact with symptomatic patients or with contaminated blood or bodily fluids. Lassa fever may also be transmitted through the respiratory route.⁷˒⁸

The risk of importation of viruses responsible for VHFs differs according to the type of virus, the incubation period and the speed at which haemorrhagic signs develop.⁷

Focus on Filoviruses

The filovirus life cycle takes place in wild animal reservoir species, possibly bats.¹⁰ Occasional transmission to humans through a breach of the species barrier is possible. It occurs through contact with tissues or blood from infected wild animals, either directly or indirectly through the handling of an incidental host.¹⁰ Great apes frequently play a major role in the transmission of Ebola virus as intermediate hosts, as they are hunted as bushmeat.¹⁰

Zoonotic transmission of Marburg virus often results from contact between Egyptian fruit bats, the natural reservoir of the virus, and humans.¹⁰

Human-to-human transmission of filoviruses occurs mainly:

• Through direct contact with a symptomatic patient shedding the virus or with a deceased person
• Through contact with infected bodily fluids and excreta, including blood, faeces, vomit, semen and breast milk
• Through contaminated and impregnated environmental surfaces

Transmission of the virus occurs via the hands, with the ocular mucosa providing a possible portal of entry.¹⁰ Sexual transmission from men to women is also possible for the Ebola and Marburg viruses.¹⁰˒¹² Human-to-human transmission may be increased in hospital settings through nosocomial infection involving contact with viraemic blood, potentially triggering deadly outbreaks of Marburg or Ebola fever.⁶˒⁷

Diagnosis

During the early stages of an outbreak, it is difficult to distinguish a VHF from other common infections such as malaria, typhoid fever, other bacterial infections or acute gastroenteritis.¹⁴

It subsequently remains very difficult to distinguish the different VHFs from one another. However, certain features are associated with particular diseases. Ebola is characterised by a predominance of gastrointestinal symptoms, Rift Valley fever by ophthalmological involvement and Crimean–Congo fever by rhabdomyolysis**.⁷

** massive destruction of skeletal muscle tissue cells.

ANRS Emerging infectious diseases research initiatives on viral haemorrhagic fevers and filoviruses

Leadership of the CORC on filoviruses

In early 2025, ANRS MIE was appointed to lead the CORC (Collaborative Open Research Consortium) on filoviruses and is set to become a WHO Collaborating Centre.

CORCs are international networks of research institutions whose mission is to strengthen global pandemic preparedness through collaborative research, knowledge sharing and the rapid development of countermeasures. An initial meeting held on 13 February 2025 focused on therapeutic trials and research priorities concerning medical countermeasures. Within the CORC, research priorities were defined by ANRS MIE and WHO. Work is under way with all experts from the “Filovirus CORC” to update the research priorities and gaps identified in the MARVAC consortium roadmap.

References

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4. WHO: Marburg virus disease (accessed 8 August 2025).
5. WHO: Crimean–Congo haemorrhagic fever (accessed 8 August 2025).
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13. Avis portant sur la conduite à tenir face à des patients suspects de fièvre hémorragique virale (FHV) dont la maladie à virus Ebola (MVE). Haut Conseil de la santé publique, 20 October 2021. Available online (accessed 8 August 2025).
14. Clinical management of patients with viral haemorrhagic fever: a pocket guide for front-line health workers. Interim emergency guidance for country adaptation. World Health Organization, 2016. Available online (accessed 8 August 2025).