Diagnosis Synopsis
Viral hemorrhagic fevers (VHFs) refer to clinical illnesses associated with fever and a bleeding diathesis caused by a virus belonging to the Filoviridae, Arenaviridae, Bunyaviridae, or Flaviviridae families

VHFs are contracted through the bite of an infected arthropod, via aerosol generated from infected rodent excreta, ingestion of contaminated foods, or by direct contact with infected animal carcasses. Yellow fever is an exception; it is contracted through the bite of an infected mosquito. Rift Valley Fever can also be contracted by mosquitoes in addition to the aforementioned modes. At present the vectors or reservoirs for Ebola and Marburg viruses are not understood.

Except for members of the Flaviviridae family, which lack human to human transmission, VHFs are highly contagious and spread easily from person to person via inhalation of aerosolized particles, mucosal exposure or physical contact with a patient or corpse. As such, VHFs are categorized as Category A bioterrorism agents due to their high infectivity rate and mortality rates; which can be as high as 90% (Ebola). The most likely mode of transmission would be an aerosol attack.

The incubation periods of these diseases range from 2 to 21 days with a prodrome of one week or less. Symptoms typically include fever, headache, malaise, arthralgia, myalgia, nausea, abdominal pain, and nonbloody diarrhea. Filoviruses and Flaviviruses typically exhibit an abrupt onset whereas arenaviruses are slower.

Early signs of infection include fever, hypotension, relative bradycardia, tachypnea, conjunctivitis, and pharyngitis. Some may have an accompanying rash. Petechiae, mucous membrane and conjunctival hemorrhage, hematuria, melena and hematemesis may be indicators of a progressing hemorrhagic diathesis. Advanced stages may demonstrate CNS findings such as delirium, convulsions, or coma. Recovery may be complicated by fatigue, anorexia, cachexia, alopecia and arthralgia. Sequelae include hearing or vision loss, impaired motor coordination, transverse myelitis, uveitis, pericarditis, orchitis, parotitis, and pancreatitis.

With the exception of Yellow Fever, there are no vaccines for the VHFs. All suspected cases should be immediately reported to state and local health departments. Practice strict infection control measures including airborne and contact. It is recommended that clinicians use either an N-95 mask or a powered air-purifying respirator (PAPR) when caring for VHF patients.

Look For
Filoviridae:
Ebola: Red eyes and a petechial skin rash accompanying an abrupt onset of fever, malaise, myalgia, headache, sore throat and nausea followed by vomiting, diarrhea and stomach pain. Hiccups and internal and external bleeding may also be seen.
Marburg: Fever, cough, headache, conjunctivitis, petechiae, purpura and hemorrhage.

Arenaviridae:
Lassa Fever: Flushing of the face and trunk. Facial edema and neck swelling may also be seen as well as cervical adenopathy, axillary petechiae and hemorrhages in the setting of a severe, febrile illness.
New World Arenavirus (e.g., Bolivian Hemorrhagic Fever): Facial and upper trunk flushing, conjunctival redness and axillary petechiae accompanied by fever, dizziness, muscle/chest/back/abdominal pain, headache, sore throat, lymphadenopathy, vomiting, cough and photophobia lasting about 7 days. May progress to include petechiae and/or vesicles on the back of the throat and facial edema, mucosal hemorrhaging and pulmonary edema.

Bunyaviridae:
Rift Valley Fever: Fever, headache, backache, generalized weakness, nausea, and vomiting, which may or may not be associated with partial or complete loss of vision, and/or hemorrhage. In patients with disease that has developed into hemorrhagic fever look for jaundice, purpura, gingival bleeding, bloody vomit and rectal bleeding.

Flaviviridae:
Yellow Fever: Facial flushing, conjunctival redness and prominent low-back pain in conjunction with the sudden onset of a flu-like illness. Within days jaundice and other signs of liver involvement as well as hemorrhaging may be seen in about 15% of patients.
Omsk Hemorrhagic Fever: Vesicles on soft palate, upper body flushing (no rash), conjunctival erythema, petechiae, mucosal bleeding and GI hemorrhage.
Kyasanur Forest Disease: The sudden onset of fever, chills, headache, severe prostration, arthralgia, generalized lymphadenopathy, myalgia and facial flushing, followed in 72 hours by nausea, vomiting, diarrhea and hemorrhage.

Diagnostic Pearls
Early diagnosis and practicing the proper precautions are imperative.

Differential Diagnosis & Pitfalls
Influenza
Hepatitis
Staphylococcal sepsis
Gram negative sepsis
Toxic shock syndrome
Meningococcemia
Salmonellosis
Shigellosis
Rickettsial infections (Rocky Mountain spotted fever)
Leptospirosis
Borreliosis
Psittacosis
Dengue
Hantavirus pulmonary syndrome
Malaria
Trypanosomiasis
Septicemic plague
Rubella
Measles
Hemorrhagic smallpox
Idiopathic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Hemolytic uremic syndrome
Acute leukemia
Collagen vascular diseases

Best Tests
Contact your local health department and/or CDC for transport instructions of laboratory specimens.
CBC
Urinalysis
Liver Function
Coagulation abnormalities

Therapy
Supportive, especially fluid and electrolyte balance, circulatory volume, and blood pressure.
Ribavirin (off-label) has been shown to have some activity against Arenaviridae and Bunyaviridae.

Medical Disclaimer:
The information contained in this web page is intended to be an adjunct to traditional medical information sources. It is not intended to be a substitute for professional medical judgment.

Authors and Editors:
Tener Goodwin Veenema PhD, MPH, MS, CPNP