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Viral Hemorrhagic Fever (VHF)

Viral Hemorrhagic Fever (VHF) is a group of severe viral illnesses that can cause fever, vascular dysfunction, bleeding, and multi-organ involvement. Important causes include Ebola, Marburg, Lassa, and Crimean-Congo hemorrhagic fever

Also called

Hemorrhagic viral infection

ICD-10

A99

Specialty

Infectious

Onset

Acute

Reviewed

August 2026
On This Page

Overview

–Viral Hemorrhagic Fever (VHF) is a syndrome caused by viruses from several families.

 

-Important examples include:

  • Ebola and Marburg viruses
  • Lassa virus
  • Crimean-Congo hemorrhagic fever virus
  • Some arenaviruses
  • Dengue and yellow fever viruses

 

-Transmission varies and may occur through mosquitoes or ticks, infected animals, contaminated food or materials, or direct contact with infected body fluids

 

Etiology & Risk Factors

-Etiology

–The viruses causing Viral Hemorrhagic Fever (VHF) have different reservoirs and transmission routes:

  • Mosquito or tick exposure
  • Contact with infected rodents, bats, or livestock
  • Exposure to infected blood or body fluids
  • Contact with infected patients or contaminated materials

 

-Risk Factors

  • Residence or travel in an endemic area
  • Contact with infected animals
  • Healthcare exposure
  • Laboratory exposure
  • Close contact with infected patients

Pathophysiology

Viral infection → systemic viral replication → endothelial and immune dysfunction → increased vascular permeability + coagulation abnormalities → tissue hypoperfusion and organ injury → bleeding in some patients → shock and multi-organ failure

Clinical Presentation

-Symptoms:

Early Viral Hemorrhagic Fever (VHF) is often nonspecific:

  • Fever
  • Severe headache
  • Myalgia
  • Weakness and fatigue
  • Nausea and vomiting
  • Diarrhea
  • Abdominal pain

 

-Signs:

  • Fever
  • Rash in some infections
  • Dehydration
  • Hypotension
  • Tachycardia
  • Petechiae or mucosal bleeding

 

-Severe Disease

  • Hemorrhagic manifestations
  • Shock
  • Acute Kidney Injury (AKI)
  • Liver dysfunction
  • Encephalopathy
  • Disseminated Intravascular Coagulation (DIC)
  • Respiratory failure
  • Multi-organ failure
Viral Hemorrhagic Fevers (VHF) Overview
Viral Hemorrhagic Fever (VHF) Overview

Types of VHF Viruses

Viral Haemorrhagic Fevers · Types by Virus Family

Filoviridae
ssRNA (−) · Filamentous
Ebola · Marburg · Cueva
Bunyaviridae
ssRNA (−) · Segmented
CCHF · Hantavirus · Rift Valley · SFTS
Arenaviridae
ssRNA (±) · Segmented
Lassa · Junin · Machupo · Lujo · Sabia
Flaviviridae
ssRNA (+) · Enveloped
Yellow Fever · Dengue · Kyasanur · Omsk
Filoviridae — Filamentous RNA Viruses
VirusSpecies / StrainsReservoirTransmissionMortalityEndemic region
Ebola virus 5 species: Zaire (most lethal), Sudan, Bundibugyo, Taï Forest, Reston (non-pathogenic in humans) Fruit bats (Pteropodidae) — probable. Spillover via bushmeat. Direct contact — blood, body fluids, secretions. No airborne transmission. 25–90%
(Zaire highest)		 Sub-Saharan Africa (DRC, Guinea, Sierra Leone, Uganda)
Marburg virus Single species — Marburg marburgvirus. Two strains: Marburg + Ravn. Egyptian fruit bat (Rousettus aegyptiacus) — confirmed reservoir Direct contact with blood/fluids. Bat caves (miners, tourists). Healthcare nosocomial. 24–88% Central/East Africa (Uganda, DRC, Angola, Guinea). Linked to bat caves.
Filovirus hallmark: Distinctive filamentous "shepherd's crook" shape on EM. Longest incubation among VHFs (up to 21 days). Approved treatment: REGN-EB3 / mAb114 for Ebola Zaire only. Marburg — supportive only. Vaccine: rVSV-ZEBOV (Ervebo) for Ebola Zaire.
Bunyaviridae (Phenuiviridae / Nairoviridae / Hantaviridae)
VirusTransmissionReservoirClinical hallmarkMortalityRegion
CCHF
Crimean-Congo HF		 Hyalomma tick bite — primary. Livestock blood/tissue. Nosocomial (healthcare workers). Hyalomma ticks + livestock (cattle, sheep, goats) — amplifying hosts 3 phases: pre-haemorrhagic → haemorrhagic (petechiae, ecchymoses, GI bleed) → convalescence. Hepatitis common. 5–40% Africa, Middle East (Iraq), Balkans, Central/South Asia
Hantavirus
HFRS / HPS		 Rodent aerosol — inhalation of infected urine/faeces/saliva. No person-to-person (except Andes virus). Rodents — species-specific: Hantaan (Apodemus), Seoul (Rattus), Sin Nombre (deer mouse) HFRS (Old World): fever + renal failure + haemorrhage. HPS (New World): severe pulmonary oedema — "hantavirus pulmonary syndrome" HFRS: 1–15%
HPS: 30–40%		 HFRS: Asia, Europe. HPS: Americas
Rift Valley Fever Mosquito bite (Aedes, Culex). Contact with infected animal blood/abortion material. Aerosol from slaughterhouses. Livestock (sheep, cattle, goats) — amplifying hosts. Mosquitoes — vector. Most mild febrile illness. Severe (<2%): retinitis, encephalitis, haemorrhagic fever. High mortality in neonatal animals (abortion storms). <1% overall
Up to 50% severe		 Sub-Saharan Africa, Egypt, Arabian Peninsula
SFTS
Severe Fever with Thrombocytopenia		 Haemaphysalis tick bite. Limited person-to-person via blood/fluids. Ticks (Haemaphysalis longicornis). Hedgehogs, wild animals — suspected reservoir. Fever + thrombocytopenia + leukopenia + GI symptoms. CNS involvement in severe cases. 12–30% China, South Korea, Japan
Bunyavirus key: All segmented ssRNA (3 segments: L, M, S). Ribavirin effective for CCHF and HFRS (early). No specific treatment for HPS or RVF. CCHF most relevant in Iraq and Middle East.
Arenaviridae — Rodent-Borne RNA Viruses
VirusReservoirTransmissionClinical hallmarkMortalityRegion
Lassa virus Mastomys natalensis (multimammate rat) Rodent urine/faeces contaminating food. Person-to-person via blood/fluids. Nosocomial. 80% asymptomatic/mild. Severe: facial oedema, pleural effusion, haemorrhage, deafness (30% survivors). Ribavirin effective. 1–15% overall
50% hospitalised		 West Africa (Nigeria, Sierra Leone, Guinea, Liberia)
Junin virus
Argentine HF		 Calomys musculinus (corn mouse) Rodent aerosol/contact during harvest. Occupational — farm workers. Haemorrhage + neurological signs (tremor, seizures). Seasonal — harvest time. 15–30%
(untreated)		 Argentina (pampas region)
Machupo virus
Bolivian HF		 Calomys callosus (vesper mouse) Rodent contact. Limited person-to-person. Similar to Junin — haemorrhage + neurological features. 25–35% Bolivia
Lujo virus Unknown rodent reservoir Person-to-person nosocomial (high efficiency — index case → 4 secondary cases) Severe VHF with rash. Fatal in 4/5 of initial outbreak. 80% Southern Africa (Zambia, South Africa)
Sabia virus
Brazilian HF		 Unknown reservoir Unknown natural transmission. Lab accidents documented. Severe haemorrhagic fever. Very few cases described. High Brazil
Arenavirus treatment: Ribavirin — effective for Lassa and South American arenaviruses (Junin, Machupo, Lujo) if given early. Junin: convalescent plasma very effective (reduces mortality from 30% → 1%). Vaccine for Junin (Candid#1) — licensed in Argentina.
Flaviviridae — Mosquito & Tick-Borne RNA Viruses
VirusVectorReservoirClinical hallmarkMortalityRegion
Yellow Fever Aedes aegypti (urban), Haemagogus (sylvatic) Primates (jungle cycle). Humans — urban cycle amplifying host. Remission phase (deceptive recovery) → Intoxication phase (jaundice + haemorrhage + Faget's sign). Black vomit (haematemesis). Mild: <5%
Severe: 20–50%		 Sub-Saharan Africa, South America. Preventable by 17D vaccine.
Dengue virus
Severe dengue		 Aedes aegypti, Aedes albopictus Humans are the primary amplifying host (urban). Primates (sylvatic cycle). 4 serotypes. Secondary infection (different serotype) → antibody-dependent enhancement → severe dengue: plasma leak, haemorrhage, shock (dengue shock syndrome). Tourniquet test positive. <1% (treated)
Up to 20% untreated		 Tropical/subtropical worldwide. Most common arboviral disease.
Kyasanur Forest Disease (KFD) Haemaphysalis tick Hard ticks + small mammals (rodents, monkeys) Biphasic illness: fever + haemorrhage → remission → neurological phase (meningitis, tremors). Monkey deaths = sentinel event. 3–5% India (Karnataka state). Vaccine available.
Omsk HF Dermacentor tick. Contact with muskrats. Muskrats, water voles, ticks Biphasic: fever + haemorrhage → neurological features (encephalitis). Milder than KFD. 0.5–3% Western Siberia (Russia)
Alkhurma HF Tick bite (Ornithodoros). Sheep/camel slaughter. Camels, sheep — amplifying hosts. Ticks — vector. Fever + haemorrhage + encephalitis. Related to KFD. ~25% Saudi Arabia
Flavivirus key: No specific antivirals for any flavivirus VHF — all supportive care. Yellow fever: 17D vaccine = one of the most effective vaccines ever made (single dose, lifelong). Dengue: Dengvaxia vaccine (seropositive only). Avoid aspirin/NSAIDs in all — worsen bleeding via platelet inhibition.

History Taking

-Ask about:

  • Fever onset and progression
  • Bleeding or bruising
  • Headache and myalgia
  • Vomiting or diarrhea
  • Travel or residence in endemic regions
  • Mosquito or tick exposure
  • Contact with rodents, bats, livestock, or primates
  • Contact with suspected or confirmed cases
  • Healthcare or laboratory exposure

Physical Examination

-General Examination

  • Temperature
  • Blood pressure
  • Heart rate
  • Respiratory rate and oxygen saturation
  • Mental status
  • Hydration and perfusion

 

-System-Specific Examination:

  • Inspect skin and mucosa for bleeding
  • Assess the abdomen and neurological status
  • Look for shock and organ dysfunction

 

Investigations

-Complete Blood Count

Useful for assessing:

  • Thrombocytopenia

  • Leukopenia or leukocytosis

  • Anemia

 

-Biochemistry / Specific Tests

  • Serum electrolytes

  • Urea and creatinine

  • Liver function tests

  • Coagulation profile

  • Serum lactate

  • Blood cultures when bacterial sepsis is a differential

  • Virus-specific PCR or serology when appropriate

 

-Imaging

Imaging is guided by symptoms and suspected complications.

  • Chest imaging for respiratory involvement

  • Ultrasound or CT for suspected bleeding or organ complications

 

-Special / Confirmatory Tests

Reverse Transcription Polymerase Chain Reaction (RT-PCR) is an important diagnostic method for many VHFs. Antigen detection and serology may also be used depending on the suspected virus.

Laboratory specimens require strict biosafety and infection-control procedures.

Diagnosis

  • Hemorrhage
  • Shock
  • Acute Kidney Injury (AKI)
  • Disseminated Intravascular Coagulation (DIC)
  • Encephalitis
  • Respiratory failure
  • Multi-organ failure
  • Death
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Related Topics

Management

Viral Haemorrhagic Fevers · Overview & Key VHFs

Ebola
Filoviridae
25–90%
Atoltivimab (mAb) / supportive
Marburg
Filoviridae
24–88%
Supportive only
Lassa
Arenaviridae
1–15% overall
up to 50% hospitalised
Ribavirin (early)
Crimean-Congo (CCHF)
Nairoviridae
5–40%
Ribavirin
Yellow Fever
Flaviviridae
20–50% (severe)
Supportive — vaccine preventable
General Principles — All VHFs
Common mechanism
Endothelial dysfunction → capillary leak → bleeding diathesis
Cytokine storm → multi-organ failure
DIC — consumption of clotting factors + thrombocytopenia
Death from shock, not blood loss — plasma leak more than haemorrhage
Transmission routes
Direct contact — blood, body fluids (Ebola, Marburg, Lassa)
Tick bite — CCHF (Hyalomma tick)
Mosquito bite — Yellow fever (Aedes), Dengue
Rodent contact — Lassa (Mastomys rat urine/faeces), Hantavirus
Aerosol — Lassa, Hantavirus (limited)
Immediate actions on suspicion
Isolate immediately — single room, negative pressure if available
Full PPE — gown, gloves, goggles, FFP3 mask
Notify public health authority immediately
Travel + exposure history — essential
Minimise invasive procedures until diagnosis confirmed

Viral Haemorrhagic Fevers · Supportive Care & Infection Control

Supportive Management — All VHFs
ProblemManagementNotes
Fluid loss / shock IV crystalloid (normal saline / Ringer's lactate) — aggressive replacement matching losses. Oral rehydration if tolerated. Central line if massive losses — use ultrasound guidance, minimise trauma. Lassa: cautious — pulmonary oedema risk. Ebola: 5–10L/day losses common.
Electrolyte imbalance Monitor K⁺, Na⁺, Mg²⁺, Ca²⁺ — correct aggressively. Hypokalaemia + hypomagnesaemia common from diarrhoea. Electrolyte correction improves outcomes significantly
Haemorrhage / DIC Fresh frozen plasma (FFP) — replenish clotting factors. Platelet transfusion if <50,000 + active bleeding. Cryoprecipitate for fibrinogen <1g/L. Tranexamic acid — consider for severe mucosal bleeding. Avoid aspirin, NSAIDs, heparin. Packed RBC if Hb <7 + haemodynamically compromised.
Fever / pain Paracetamol — antipyretic + analgesia. Avoid NSAIDs / aspirin — inhibit platelet function, worsen bleeding. Morphine PO/IV for severe pain if needed
Nausea / vomiting Ondansetron IV/PO. Metoclopramide — caution if CNS involved. Maintain NG feeding if oral route lost. Anti-emetics critical — GI losses are primary driver of shock
Secondary infections Empirical broad-spectrum antibiotics if bacterial sepsis suspected. Treat malaria — always co-test in endemic areas (malaria + VHF can co-exist). Malaria rapid test on all febrile patients from endemic regions
Renal failure Monitor urine output. Avoid nephrotoxic drugs. Dialysis — if AKI refractory. Fluid balance strict monitoring. AKI common in Yellow fever, Hantavirus, severe Ebola
Encephalopathy Correct metabolic causes (hypoglycaemia, electrolytes). Seizure management: benzodiazepines. Avoid LP if coagulopathic — bleeding risk. Common in Lassa, severe Ebola
Infection Control & Healthcare Worker Protection
PPE requirements
Full PPE — double gloves, waterproof gown, apron, boot covers
FFP3 respirator — for aerosol-generating procedures
Eye protection — goggles or face shield
Trained donning + doffing — observer mandatory
Buddy system — never work alone in PPE
Limit staff rotation — reduce exposure numbers
Isolation + decontamination
Negative pressure room — if available (mainly Ebola, Lassa)
Dedicated equipment — no sharing between patients
Chlorine-based disinfectant (0.5–1%) — all surfaces, spills
Safe body handling — corpses highly infectious (Ebola)
Contact tracing — all contacts within 21 days (Ebola incubation)
Notify WHO under International Health Regulations (IHR 2005)
Antiviral summary: Ribavirin — Lassa + CCHF (early, within 6 days). Monoclonal antibodies (REGN-EB3, mAb114) — Ebola Zaire only. No antivirals — Marburg, Yellow fever, Dengue. Supportive care is the backbone for ALL VHFs.

Complications

  • Encephalitis
  • Meningitis
  • Pneumonitis
  • Hepatitis
  • Retinitis
  • Neonatal infection
  • Disseminated infection
  • Malignancy

Prognosis

The prognosis varies with the virus, disease severity, comorbidities, and access to early supportive care. Some VHFs are self-limited, whereas Ebola, Marburg, and severe Crimean-Congo hemorrhagic fever can be highly fatal. Early recognition and supportive care improve outcomes

Key Points / Clinical Pearls

  • Viral Hemorrhagic Fever (VHF) is a syndrome caused by several different viruses.
  • Important causes include Ebola, Marburg, Lassa, and Crimean-Congo hemorrhagic fever.
  • Transmission differs between viruses.
  • Exposure history is essential in suspected cases.
  • Early symptoms are usually nonspecific.
  • Fever, headache, myalgia, vomiting, and diarrhea are common.
  • Bleeding may occur but is not always present.
  • Thrombocytopenia and coagulation abnormalities may occur in severe disease.
  • RT-PCR is important for many VHFs.
  • Suspected cases require immediate infection-control precautions.
  • Public-health notification is essential.
  • Treatment is mainly supportive for many VHFs.
  • Some VHFs have disease-specific therapies or vaccines.
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  • Paessler S, Walker DH. Pathogenesis of the Viral Hemorrhagic Fevers. Annu Rev Pathol. 2013;8:411-440. PubMed .
  • Fauci AS, Lane HC. Viral Hemorrhagic Fevers. In: Harrison's Principles of Internal Medicine.
  • National Library of Medicine (NIH). Viral Hemorrhagic Fevers . StatPearls.