American College of Physicians: Internal Medicine — Doctors for Adults ®



From the May ACP Observer, copyright 2004 by the American College of Physicians.

As the name implies, viral hemorrhagic fevers target the vascular bed, causing microvascular damage and changes in vascular permeability that result in a bleeding diathesis.

Viral hemorrhagic fevers (VHFs) are caused by four viral families. For more detailed information on these families and the viruses they include, see "Hemorrhagic fever viruses."

All the viruses that cause VHF are zoonotic RNA viruses. Most are hosted primarily by rodents and arthropods, although the reservoir and vector for Ebola and Marburg viruses are unknown.

Humans are incidentally infected when they make contact with excreta of infected rodents or vector-infected livestock, or are bitten by infected mosquitoes or ticks. Some VHFs can also be transmitted from person to person.

Ebola virus.

Each VHF is restricted mainly to the habitat of its primary host, although travelers can spread the disease to outlying areas.

Scientists in both the former Soviet Union and the United States developed several hemorrhagic viruses as bioweapons, including Marburg, Ebola, Lassa, Junin, yellow fever and Rift Valley fever. Consider the possibility of a bioterrorist attack if you see VHF in a patient not known to have traveled to an endemic area.

Clinical presentation and diagnosis

All VHFs are characterized by high fever, headache, arthralgias, myalgias, abdominal pain and fatigue. Signs of bleeding range from only conjunctival hemorrhage, mild hypotension, flushing and petechiae, to shock and generalized mucous membrane hemorrhage and evidence of pulmonary, hematopoietic and neurologic dysfunction.

Renal insufficiency is proportional to cardiovascular compromise, except in hemorrhagic fever with renal syndrome, in which it is an integral part of the disease. Patients often die from multi-organ failure.

It can be difficult to distinguish one VHF from another, although some viral hemorrhagic fevers do present with suggestive clinical syndromes:

  • Jaundice and hepatitis dominate the clinical presentation in some cases of Rift Valley, Congo-Crimean, Marburg and Ebola hemorrhagic fevers, and yellow fever.
  • Biphasic illnesses with pulmonary symptoms followed by central nervous system manifestations are characteristics of Kyasanur Forest disease and Omsk hemorrhagic fever.
  • Severe peripheral edema without significant hemorrhage suggests Lassa fever.
  • Severe hemorrhage and nosocomial transmission suggest Congo-Crimean hemorrhagic fever.
  • Fever, hemorrhage, shock, renal failure and polyuria mark the classic presentation of hemorrhagic fever with renal syndrome.

A number of laboratory findings indicate VHFs. Thrombocytopenia is common to most viral hemorrhagic fever infections, with the exception of Lassa fever. Leukopenia is common to most viral hemorrhagic fever infections except Lassa, Hantaan and some cases of Congo-Crimean hemorrhagic fevers.

Rapid enzyme immunoassays and viral cultures are available for VHFs, but only at the CDC and the U.S. Army Medical Research Institute of Infectious Diseases in Maryland. Because no viral hemorrhagic fevers are endemic in North America, any suspected cases should immediately be reported to local public health officials and the CDC.

Differential diagnosis

Malaria is the major entity in the differential diagnosis. Other entities that mimic viral hemorrhagic fevers include typhoid fever, leptospirosis, shigellosis, relapsing fever, fulminant hepatitis and meningococcemia.

Noninfectious mimics include acute leukemia, systemic lupus erythematosus, immune thrombocytopenic purpura, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

In naturally occurring VHF cases, patients are likely to have risk factors such as travel to an endemic area and handling of animal carcasses, exposure to sick people or arthropod bites within 21 days of the illness. In a bioterrorist attack, a high index of suspicion is required to make the correct diagnosis and distinguish VHF from its many mimics.

Suggestive clues that warrant immediate notification of local and state public health agencies include an outbreak of a severe disease characterized by a fever greater than 38.3 C (101 F) and any two of the following: hemorrhagic or purpuric rash, epistaxis, hematemesis, hemoptysis, blood in the stool or any other hemorrhagic symptom.


Ribavirin reduces morbidity in hemorrhagic fever with renal syndrome. It also reduces morbidity and mortality in Lassa fever. There is some evidence ribavirin may be effective in Argentine hemorrhagic fever when given within seven days of onset.

Physicians also use convalescent plasma experimentally to treat Argentine hemorrhagic fever. But for most viral hemorrhagic fevers, there is no proven effective treatment.

Avoid intramuscular injections, antiplatelet drugs and anticoagulant agents when treating patients with VHFs. Corticosteroids are not beneficial, and fatality rates—which vary by virus—can be as high as 90%.

Post-exposure containment

The incubation period varies according to virus, but it ranges from two to 21 days. Viral hemorrhagic fever patients often have significant infectious virus in their blood and body secretions.

Barrier and contact precautions must be meticulous. While aerosol transmission of hemorrhagic fever viruses is infrequent, respiratory isolation should be used for all patients.

Isolate patients in negative-pressure rooms and use gowns, gloves, eye protection and N95 masks when treating them. Note that for some VHFs, secondary transmission occurs by contact with objects contaminated with infected body fluids.

The risk of person-to-person transmission of VHFs is highest during the later stages of illness, which are characterized by vomiting, diarrhea, shock and often hemorrhage. VHF infections have not been reported in persons whose contact with an infected patient occurred only during the incubation period, or before the patient became febrile.

Prophylaxis following exposure to arenavirus may be attempted with ribavirin, although the effectiveness of this measure is not known. Individuals with potential exposure should be instructed to check their temperature twice a day and monitor themselves for any symptoms.

A licensed vaccine is available only for yellow fever. In addition, an experimental vaccine for Argentine hemorrhagic fever is currently under investigation.


Hemorrhagic fever viruses


  • Argentine hemorrhagic fever
  • Bolivian hemorrhagic fever
  • Sabia-associated hemorrhagic fever
  • Lassa fever
  • Lymphocyctic choriomeningitis
  • Venezuelan hemorrhagic fever


  • Ebola hemorrhagic fever
  • Marburg hemorrhagic fever


  • Crimean-Congo hemorrhagic fever
  • Rift Valley fever (Hantaan fever)
  • Hemorrhagic fever with renal syndrome


  • Tick-borne encephalitis
  • Kyasanur Forest disease
  • Omsk hemorrhagic fever


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