History
Obtain a detailed travel history, paying particular attention to recent travel to tropical or rural areas, such as Central or South America (yellow fever, arenaviruses), West Africa (Lassa fever), or to endemic portions of Central Africa (Ebola, Marburg, Rift Valley fever [RVF], Crimean-Congo hemorrhagic fever [CCHF]). Ask about contact with potential arthropod or rodent reservoirs.
Although several species of fruit bat have been implicated as the natural reservoir for Ebola and Marburg virus, contact with infected animals or humans is not a prerequisite for transmission of infection. Direct contact with rodents infected with hemorrhagic fever viruses (eg, arenaviruses, hantaviruses) is not necessary for transmission of infection, since aerosolized excreta may transmit infection. Aerosol transmission of some viral hemorrhagic fever infections is reported among nonhuman primates and likely is a mode of transmission in patients with severe infection.
Contacts of patients with known viral hemorrhagic fever (VHF), especially family members or health care workers caring for infected patients, are at risk for infection if appropriate barrier precautions are not used. Transmission of VHF has occurred from the reuse of unsterile needles and syringes used for treatment of infected patients. Transmission of VHF also has occurred to individuals handling the deceased in preparation for burial or to individuals involved in the slaughter of infected livestock (as in RVF or CCHF).
Because of their extreme pathogenicity and potential for transmission by fine-particle aerosol, VHF viruses are considered potential biological warfare agents. In addition, Dr Ken Alibek, the former Deputy Director of the once massive Soviet bioweapons program, Biopreparat, claims Soviet scientists successfully had produced a stable Marburg virus biological weapon that could be delivered as an aerosol. Large numbers of military personnel with VHF symptoms would suggest such an attack. An outbreak of VHF in a nonendemic area would also suggest a biological warfare attack.
Incubation periods for VHF vary from 2-21 days. The initial symptoms correspond to development of viremia and include the following:
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High fever
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Headache
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Fatigue
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Abdominal pain
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Myalgias
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Prostration
In more advanced disease, signs and symptoms include the following:
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Hematemesis and bloody diarrhea
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Generalized mucous membrane hemorrhage
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Rash
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Altered mental status and cardiovascular collapse (preterminal events)
Physical Examination
Depending on the progress of the disease, patients with viral hemorrhagic fever (VHF) initially may present with minimal signs, suggesting a more benign viral syndrome. Maintain a high index of suspicion.
As the disease progresses, more classic findings are present as follows:
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Fever
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Pharyngitis
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Conjunctival injection
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Nondependent edema
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Petechial or ecchymotic rash
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GI bleeding
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Hypotension and/or shock
Most hemorrhagic fevers, except Rift Valley fever, can produce a variety of cutaneous findings that are principally caused by vascular instability and bleeding abnormalities. Such findings include flushing, petechiae, purpura, ecchymoses, and edema.
The Old World arenavirus causing Lassa fever results in the greatest amount of edema of any of the hemorrhagic fever viruses. Additionally, no bleeding abnormalities are present.
The New World arenaviruses (Junin, Machupo, Sabia, and Guanarito) cause less edema and variable amounts of petechiae, purpura, ecchymoses, palatal hyperemia, and mucosal hemorrhage.
The most severe hemorrhage from a hemorrhagic fever virus follows infection with the Congo Crimean hemorrhagic fever (CCHF) virus (see the image below).
Bunyavirus infection. Ecchymoses encompassing left upper extremity one week after onset of CCHF. Ecchymoses often are accompanied by hemorrhage in other locations: epistaxis, puncture sites, hematemesis, melena, and hematuria. Image provided by Robert Swaneopoel, PhD, DTVM, MRCVS, National Institute of Virology, Sandringham, South Africa.
Hantaviruses can cause a relatively distinctive eruption with a petechial eruption around the neck and on the anterior and posterior axillary folds, arms, and trunk. A sunburn-like flush is seen on the head, neck, and upper chest and back and may be accompanied by facial edema (see the image below). Sometimes, a morbilliform eruption occurs. Oral and conjunctival surfaces may develop severe hemorrhages.
Bunyavirus infection - Hantaan virus. Patient with Korean hemorrhagic fever caused by Hantaan virus demonstrating typical 'sunburn flush' of cheeks, chin, and base of neck. Photo courtesy of John Huggins, PhD.
The filoviruses (Marburg and Ebola) exhibit characteristic exanthems that are best seen in fair-skinned patients. Soft palatal hyperemia accompanies the flu-like prodrome and is followed between days 5 and 7 by a nonpruritic, centripetal, pinhead-sized papular, erythematous exanthem. Within 24 hours, this can develop into large and coalescent, well-demarcated, sometimes hemorrhagic macules and papules. In severe cases, hemorrhage exudes from mucous membranes, venipuncture sites, and body orifices.
Dengue virus causes a characteristic erythematous exanthem with striking islands of sparing (see the image below).
Patient with morbilliform exanthem of dengue fever. Note islands of sparing, which is characteristic for dengue. Photo courtesy Duane Gubler, PhD.
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Ebola virus. Electron micrograph courtesy of the Centers for Disease Control and Prevention.
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Marburg virus. Negative stain image courtesy of the Centers for Disease Control and Prevention.
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Mastomys rodent, natural host of Lassa virus. Image courtesy of the Centers for Disease Control and Prevention.
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Bunyavirus infection. Ecchymoses encompassing left upper extremity one week after onset of CCHF. Ecchymoses often are accompanied by hemorrhage in other locations: epistaxis, puncture sites, hematemesis, melena, and hematuria. Image provided by Robert Swaneopoel, PhD, DTVM, MRCVS, National Institute of Virology, Sandringham, South Africa.
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Apodemus agrarius, the vector of Korean hemorrhagic fever caused by a hantavirus. Photo courtesy of David McClain, MD.
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Bunyavirus infection - Hantaan virus. Patient with Korean hemorrhagic fever caused by Hantaan virus demonstrating typical 'sunburn flush' of cheeks, chin, and base of neck. Photo courtesy of John Huggins, PhD.
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Bunyavirus infection. A patient with Korean hemorrhagic fever demonstrating conjunctival hemorrhages, facial petechiae, and "sunburn flush" of the cheeks. Photo courtesy of John Huggins, PhD.
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Filovirus disease - Ebola fever. Patient with Ebola hemorrhagic fever during 1976 outbreak in Zaire demonstrating palatal petechiae and hemorrhage. Photo courtesy of Joel Breman.
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Patient with morbilliform exanthem of dengue fever. Note islands of sparing, which is characteristic for dengue. Photo courtesy Duane Gubler, PhD.
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Patient with dengue hemorrhagic fever complicated by ecchymoses. Photo courtesy of Duane Gubler, PhD.
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Dengue Virus Notice posted outside Maracanã Stadium, Rio de Janeiro, Brazil, 2012. Translation: This site is a strategic point for controlling Dengue.
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Mastomys natalensis, natural host of Lassa virus. Photo courtesy of BioMed Central, originally published in Kelly JD, Barrie MB, Ross RA, Temple BA, Moses LM, Bausch DG. Housing equityfor health equity: a rights-based approach to the control of Lassa fever inpost-war Sierra Leone. BMC Int Health Hum Rights. 2013 Jan 2;13:2.
Tables
Virus Family |
Disease (Virus) |
Natural Distribution |
Usual Source of Human Infection |
Incubation (Days) |
Arenaviridae |
|
|
|
|
Arenavirus |
Lassa fever |
Africa |
Rodent |
5-16 |
|
Argentine HF (Junin) |
South America |
Rodent |
7-14 |
|
Bolivian HF (Machupo) |
South America |
Rodent |
9-15 |
|
Brazilian HF (Sabia) |
South America |
Rodent |
7-14 |
|
Venezuelan HF (Guanarito) |
South America |
Rodent |
7-14 |
Bunyaviridae |
|
|
|
|
Phlebovirus |
Rift Valley fever |
Africa |
Mosquito |
2-5 |
Nairovirus |
Crimean-Congo HF |
Europe, Asia, Africa |
Tick |
3-12 |
Hantavirus |
Hemorrhagic fever with renal syndrome, Hantavirus pulmonary syndrome |
Asia, Europe, worldwide |
Rodent |
9-35 |
Filoviridae |
|
|
|
|
Filovirus |
Marburg and Ebola |
Africa |
Fruit bat |
2-216 |
Flaviviridae |
|
|
|
|
Flavivirus |
Yellow fever |
Tropical Africa, South America |
Mosquito |
3-6 |
|
Dengue HF |
Asia, Americas, Africa |
Mosquito |
Unknown for dengue HF, 5-7 for dengue |
