Viral Hemorrhagic Fevers: Facts & Information
Hemorrhagic fever viruses (HFVs) are a diverse group of organisms, each of which belong to one of four distinct families:
1. Filoviridae: Ebola and Marburg viruses
2. Arenaviridae: Lassa fever virus and a group of viruses referred to as the New World arenaviruses
3. Bunyaviridae: Crimean Congo hemorrhagic fever virus, Rift Valley fever virus, and a group of viruses known as the 'agents of hemorrhagic fever with renal syndrome'
4. Flaviviridae: dengue, yellow fever, Omsk hemorrhagic fever, and Kyasanur Forest disease virus
Hemorrhagic fever viruses are all capable of causing a clinical diseases associated with fever and bleeding disorder, classically referred to as viral hemorrhagic fever (VHF). None of these viruses occurs naturally in the United States. Risk factors for these diseases include travel to certain geographic areas where these diseases may naturally occur (such as certain areas of Africa, Asia, the Middle East, and South America), handling of animal carcasses, contact with sick animals or people with the disease, and arthropod bites. The Working Group for Civilian Biodefense identified a subset of these viruses that pose particularly serious threats as biological weapons, based on, among other characteristics, their infectious properties, morbidity and mortality, transmissibility by way of aerosol dissemination, and prior research and development as biological weapons. Specifically, these viruses are: Ebola, Marburg, Lassa fever, New World arenaviruses, Rift Valley fever, yellow fever, Omsk hemorrhagic fever, and Kyasanur Forest disease. The history and characteristics of these viruses are described in detail in the full consensus statement.
An understanding of the epidemiology, clinical presentation, and the recommended medical and public health response following a biological attack with any of the HFVs of greatest concern could substantially decrease the morbidity and mortality of such an event.
There is the potential for significant morbidity and mortality if hemorrhagic fever viruses were disseminated by aerosol dispersal, given the lack of readily available therapy and vaccines. Some of these viruses (namely, Ebola, Marburg, Lassa fever, New World arenaviruses, and Crimean-Congo hemorrhagic fever viruses) are also transmissible from person-to-person; this characteristic has the potential to amplify disease outbreaks.
Most of what is known regarding the epidemiology of these diseases is derived from naturally occurring outbreaks. Rift Valley fever and the Flaviviridae are not transmissible from person-to-person. For the remaining HFVs of concern, the major mode of transmission appears to be from direct contact with a sick person or contaminated items, such as syringes. Transmission via the airborne route appears to be rare but cannot be conclusively ruled out. All of these viruses, including Rift Valley fever and the Flaviviridae, may be transmitted to laboratory personnel by way of aerosol generated during specimen processing. For that reason, attempts to culture these viruses must be conducted in high containment (BSL-4) laboratories. There are two such labs in the US; one is located at the Centers for Disease Control and Prevention, and the other at the United States Army Medical Research Institute of Infectious Diseases.
Following an aerosol dissemination of any of these HFVs of concern, cases would likely appear 2-21 days following exposure. Patients would present with fever, rashes, body aches, headaches, and fatigue, and bleeding manifestations could occur later in the disease course. Suspected cases of viral hemorrhagic fevers should be immediately reported to local or state health department. These illnesses are not endemic in the U.S.; thus, were a case of VHF to be detected domestically in a person who does not have any of the risk factors for the disease, bioterrorism should be considered as a potential cause.
Health-care workers caring for patients with suspected or confirmed VHF should take special protective measures. The Working Group recommends adherence to strict hand hygiene and the donning of double-gloves, impermeable gowns, leg and shoe coverings, face shields or goggles for eye protection, and either N-95 masks or powered air-purifying respirators (for airborne precautions). In addition, if resources are available, patients should be cared for in a negative pressure isolation room (used for the care of patients with tuberculosis).
Prophylaxis & Treatment
Currently, there is no approved antiviral medication for the treatment of any of these diseases. Ribavirin, an antiviral medication which, when used in combination with interferon, is approved for the treatment of chronic hepatitis C, is active against some of these viruses (the Arenaviridae and Bunyaviridae). Unfortunately, no antiviral medications have been shown to be useful in the treatment of the other families of viruses (the Filoviridae and Flaviviridae).
A vaccine exists for only one of these viruses: yellow fever. The vaccine is very effective in protecting travelers to areas where the disease is endemic from acquiring yellow fever. This vaccine would not be useful following a bioterrorist attack because yellow fever has a very short incubation period, so that even if victims were vaccinated subsequent to a known exposure, they would likely develop the disease before they develop protective antibodies.
The Working Group recommends that ribavirin be administered to individuals believed to have VHF after a bioterrorist attack, and to those who develop symptoms after a VHF contact with other sick persons. However, if the causative virus is ultimately identified as a Filoviridae or a Flaviviridae, ribavirin will not be useful and should not be continued. Persons who may have been infected by a bioweapon disseminating HFVs should be followed closely by a designated medical expert or public health official so they may be immediately treated if they develop symptoms. There is an urgent need for the development of rapid diagnostic tests, effective vaccines and drug therapy for the HFVs of greatest concern