Approach Considerations
Most patients with viral hemorrhagic fever (VHF) are viremic at the time of presentation (Hantavirus is an exception). Specific viral diagnosis can be made using serologic tests, including enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). Difficult cases may require viral isolation in tissue culture.
Following the 2014 West Africa Ebola outbreak, reverse transcriptase PCR (RT-PCR) emerged as the most common method for detecting Ebola virus in patient serum, plasma, and whole blood. Novel antigen-capture ELISA techniques have also been developed in response to this outbreak.
Real-time reverse-transcription polymerase chain reaction (RT-PCR) remains the gold standard for quantitative, sensitive, and specific detection of Crimean-Congo hemorrhagic fever (CCHF) virus; however, these assays have sensitivity issues due to the genetic diversity of different CCHF viral strains. [1]
Because of the need for specialized microbiologic containment and handling of these viruses, initiate contact with the Centers for Disease Control and Prevention (CDC; Atlanta, GA) as soon as possible and prior to transport of specimens for virus-specific diagnosis. Specific state and federal statutes govern the shipment of highly infectious disease agents.
The CDC and the US Army Medical Research Institute for Infectious Diseases (USAMRIID; Frederick, MD) are among the 10 Biosafety Level 4 (BSL-4) laboratory facilities in the US with such diagnostic facilities.
Report all suspected cases of VHF immediately to local and state public health departments and to the CDC.
Laboratory Studies
Because of risks associated with handling infectious materials, perform the minimum necessary laboratory testing for diagnostic evaluation and patient care.
A complete blood count often indicates leukopenia and thrombocytopenia (these findings may not be present in Lassa fever). Significant electrolyte and metabolic disturbances have been reported in the recent Ebola virus disease outbreak, including hypokalemia, hypocalcemia, hyponatremia, elevated creatinine and elevated anion gap acidosis. [24]
Elevated hepatic transaminases are observed in viral hemorrhagic fever (VHF) and are predictive of high mortality in Lassa fever infection.
Prothrombin time, activated partial thromboplastin time, international normalized ratio, and clotting times are prolonged. A disseminated intravascular coagulation profile including fibrinogen level, fibrin degradation products, and platelet count may be useful.
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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 |
