University at Albany Prevention Research Center

VIRAL HEMORRHAGIC FEVERS

Infectious Agent

Several different viruses can cause a hemorrhagic fever syndrome and hence are designated as Hemorrhagic Fever Viruses.
Hemorrhagic fever viruses belong to four taxonomic families:
- Filoviridae - Ebola Virus, Marburg Virus
- Arenaviridae - Old World Arenaviruses e.g. Lassa Virus & New World Arenaviruses that cause disease in humans e.g. Junin Virus, Machupo Virus, Guanarito Virus, Sabia Virus, Whitewater Arroyo Virus
- Bunyaviridae - Phlebo Virus, Hanta Virus, Nairo Virus
- Flaviviridae - Yellow Fever Virus, Kyasanur Forest Disease Virus, Omsk Hemorrhagic Fever Virus, Dengue virus
More Information On Infectious Agent at CIDRAP , NYSDOH & CDC
Images at CIDRAP

Clinical Symptoms

Incubation Period
- Ebola Hemorrhagic Fever: 2-21 days
- Marburg Hemorrhagic Fever: 2-14 days
- Lassa Fever: 5-16 days
- Newworld Hemorrhagic Fever: 7-16 days
- Riftvalley Fever: 2-6 days
- Yellow Fever: 3-6 days
- Kyasanur Forest Disease Fever: 2-9 days
- Omsk Hemorrhagic Fever: 2-9 days

Although Clinical Features vary somewhat for the various hemorrhagic fever viruses, the clinical presentations overlap substantially. All of the agents cause a febrile prodrome characterized by fever, varying degrees of prostration, headache, myalgia, abdominal pain, diarrhea etc.

Other Notable Features
- Bleeding manifestations occur in variable proportions of patients (eg, in about 30% of patients with Ebola or Marburg hemorrhagic fever and in only about 1% of patients with Rift Valley fever).
- A maculopapular rash may be noted early in the clinical course in some forms of VHF (notably in Ebola and Marburg hemorrhagic fevers).
- Severe exudative pharyngitis is a characteristic early feature of Lassa fever.
- Several agents cause meningoencephalitis in addition to VHF (eg, Rift Valley fever, Kyasanur Forest disease, Omsk hemorrhagic fever).
- Jaundice may be a prominent feature in some infections (eg, Ebola and Marburg hemorrhagic fevers, Lassa fever, Rift Valley fever, yellow fever).
More Information On Clinical Symptoms at CIDRAP , NYSDOH & CDC
Images at CIDRAP

Epidemiology

Reservoir:

Ebola Virus & Marburg Virus: Unknown
- Lassa Virus: Multimammate Mice (mastomys species)
- Rift Valley Fever Virus: Vertebrates (e.g. cattle, sheep)
- Yellow Fever Virus: Primates
- Kyasanur Forest Disease Virus: Rodents and other small mammals; Monkeys
- Omsk hemorrhagic Fever Virus: Rodents (including muskrats and voles)
- New World Arenaviruses: Calomys musculinus (drylands vesper mouse) for Junin Virus, Calomys callosus (large vesper mouse) for Machupo Virus, Zygodontomys brevicauda (cane mouse) for Guanarito Virus, Neotoma species (woodrats) for Whitewater Arroyo Virus & probably an unknown rodent for Sabia Virus

Arthropod Vectors:
- Ebola Virus & Marburg Virus: None
- Lassa Virus & New World Arenaviruses: Unknown
- Rift Valley Fever Virus: Aedes mosquitoes
- Yellow Fever Virus: Predominantly Aedes and Haemagogus mosquito species; Aedes aegypti is most important vector for urban yellow fever
- Kyasanur Forest Disease Virus: Ticks (Haemaphysalis spinigera)
- Omsk hemorrhagic Fever Virus: Ticks (Dermacentor pictus, Dermacentor reticulatus)

Modes of Transmission:
- Person-to-Person (most likely through contact with blood or body fluids): Ebola Virus, Marburg Virus, Lassa Virus, New World Arenavirus (e.g. Machupo Virus)
- Percutaneous (through reuse of needles or accidental needle sticks): Ebola Virus, Marburg Virus, Lassa Virus
- Contact with cadavers during burial: Ebola Virus
- Direct contact with infected non-human primates/animals or their blood, tissues or carcasses:

Ebola Virus, Marburg Virus, Omsk Hemorrhagic Fever Virus, Rift Valley Fever Virus
- Airborne: Ebola Virus, Marburg Virus, Lassa Virus, New World Arenavirus, Omsk Hemorrhagic Fever Virus, Rift Valley Fever Virus, Kyasanur Forest Disease Virus
- Sexual: Ebola Virus, Marburg Virus, Lassa Virus
- Mucosal contact through infectious droplets or direct contact: Ebola Virus, Marburg Virus
- Bite of an infected mosquito: Rift Valley Fever Virus, Yellow Fever Virus
- Bite of an infected tick: Omsk Hemorrhagic Fever Virus, Kyasanur Forest Disease Virus
More Information On Epidemiology at CIDRAP & CDC

Hemorrhagic Fever Viruses as Bioterrorism Agents

Animal studies using nonhuman primates have demonstrated that clinical infection can be caused by aerosolized preparations of some hemorrhagic fever viruses, including Ebola, Marburg, Lassa, and yellow fever viruses as well as New World arenaviruses. Additional viruses (Rift Valley fever virus and flaviviruses) have been shown to cause aerosol infections in the laboratory setting.

These viruses are considered potentially suitable as biological weapons because:
--They can be disseminated through aerosols
- They have a low infectious dose
- They cause high morbidity and mortality c
- They cause fear and panic in the general public
- Effective vaccines are not available or supplies are limited
- These pathogens are available and most can be readily produced in large quantities
- Research on weaponizing various hemorrhagic fever viruses has been conducted in the past despite the lack of treatment options or protective vaccines

Countries that have either weaponized hemorrhagic fever viruses or conducted biological weapons research on these viruses include the Soviet Union, United States & North Korea.

In 2000, CDC published a list of Category A agents (ie, those that are most likely to cause mass casualties if deliberately disseminated, can be released as small aerosols, and require broad-based public health preparedness). The list included New World arenaviruses and Ebola, Marburg, and Lassa viruses.

According to the Working Group on Civilian Biodefense, hemorrhagic fever viruses that pose serious threats as potential biological weapons include the following:
- Ebola virus
- Marburg virus
- Lassa virus
- New World arenaviruses
- Machupo (Bolivian hemorrhagic fever)
- Junin (Argentine hemorrhagic fever)
- Guanarito (Venezuelan hemorrhagic fever)
- Sabia (Brazilian hemorrhagic fever)
- Rift Valley fever virus
- Yellow fever virus
- Kyasanur Forest disease virus
- Omsk hemorrhagic fever virus

The Working Group determined that several important hemorrhagic fever viruses are less likely than those mentioned above to be used as biological weapons; they include:
- Dengue virus (is not transmissible by small-particle aerosol, requires mosquito-vector transmission, and primary dengue infection only rarely causes hemorrhagic fever)
-Crimean-Congo hemorrhagic fever virus (does not replicate to high concentrations in currently available systems [a barrier to mass production])
- Hantaviruses (do not replicate to high concentrations in currently available systems)
More Information On VHF as a Bioterrorism Weapon at CIDRAP & CDC

Prevention & Control

- Nosocomial Transmission Prevention
- Isolation Precautions
- Environmental Decontamination
More Information on Prevention & Control Of VHF at CIDRAP , NYSDOH & CDC
Infection Control for VHF in the African Health Care Setting at CDC

Click here for Information on

Naturally Occurring VHF at CIDRAP

Laboratory Diagnosis at CIDRAP & NYSDOH
Treatment Information at CIDRAP , NYSDOH & CDC

Additional Sources of Information

- Visit the Centers for Disease Control & Prevention (CDC) VHF Home Page
- Visit Infectious Disease Society of America (IDSA) for VHF Information


Category A Anthrax Botulism Plague Smallpox Tularemia Viral Hemorrhagic Fevers Category B Brucellosis Glanders Melioidosis Psittacosis Q Fever Typhus Fever Viral Encephalitis Toxins Food Safety Water Safety Category C Nipah Hanta Virus Other Important Zoonotic Diseases Transmissible Spongiform Encephalopathy Rift Valley Fever Virus Handra Virus West Nile Fever	VIRAL HEMORRHAGIC FEVERS Infectious Agent Several different viruses can cause a hemorrhagic fever syndrome and hence are designated as Hemorrhagic Fever Viruses. Hemorrhagic fever viruses belong to four taxonomic families: - Filoviridae - Ebola Virus, Marburg Virus - Arenaviridae - Old World Arenaviruses e.g. Lassa Virus & New World Arenaviruses that cause disease in humans e.g. Junin Virus, Machupo Virus, Guanarito Virus, Sabia Virus, Whitewater Arroyo Virus - Bunyaviridae - Phlebo Virus, Hanta Virus, Nairo Virus - Flaviviridae - Yellow Fever Virus, Kyasanur Forest Disease Virus, Omsk Hemorrhagic Fever Virus, Dengue virus More Information On Infectious Agent at CIDRAP , NYSDOH & CDC Images at CIDRAP Clinical Symptoms Incubation Period - Ebola Hemorrhagic Fever: 2-21 days - Marburg Hemorrhagic Fever: 2-14 days - Lassa Fever: 5-16 days - Newworld Hemorrhagic Fever: 7-16 days - Riftvalley Fever: 2-6 days - Yellow Fever: 3-6 days - Kyasanur Forest Disease Fever: 2-9 days - Omsk Hemorrhagic Fever: 2-9 days Although Clinical Features vary somewhat for the various hemorrhagic fever viruses, the clinical presentations overlap substantially. All of the agents cause a febrile prodrome characterized by fever, varying degrees of prostration, headache, myalgia, abdominal pain, diarrhea etc. Other Notable Features - Bleeding manifestations occur in variable proportions of patients (eg, in about 30% of patients with Ebola or Marburg hemorrhagic fever and in only about 1% of patients with Rift Valley fever). - A maculopapular rash may be noted early in the clinical course in some forms of VHF (notably in Ebola and Marburg hemorrhagic fevers). - Severe exudative pharyngitis is a characteristic early feature of Lassa fever. - Several agents cause meningoencephalitis in addition to VHF (eg, Rift Valley fever, Kyasanur Forest disease, Omsk hemorrhagic fever). - Jaundice may be a prominent feature in some infections (eg, Ebola and Marburg hemorrhagic fevers, Lassa fever, Rift Valley fever, yellow fever). More Information On Clinical Symptoms at CIDRAP , NYSDOH & CDC Images at CIDRAP Epidemiology Reservoir: Ebola Virus & Marburg Virus: Unknown - Lassa Virus: Multimammate Mice (mastomys species) - Rift Valley Fever Virus: Vertebrates (e.g. cattle, sheep) - Yellow Fever Virus: Primates - Kyasanur Forest Disease Virus: Rodents and other small mammals; Monkeys - Omsk hemorrhagic Fever Virus: Rodents (including muskrats and voles) - New World Arenaviruses: Calomys musculinus (drylands vesper mouse) for Junin Virus, Calomys callosus (large vesper mouse) for Machupo Virus, Zygodontomys brevicauda (cane mouse) for Guanarito Virus, Neotoma species (woodrats) for Whitewater Arroyo Virus & probably an unknown rodent for Sabia Virus Arthropod Vectors: - Ebola Virus & Marburg Virus: None - Lassa Virus & New World Arenaviruses: Unknown - Rift Valley Fever Virus: Aedes mosquitoes - Yellow Fever Virus: Predominantly Aedes and Haemagogus mosquito species; Aedes aegypti is most important vector for urban yellow fever - Kyasanur Forest Disease Virus: Ticks (Haemaphysalis spinigera) - Omsk hemorrhagic Fever Virus: Ticks (Dermacentor pictus, Dermacentor reticulatus) Modes of Transmission: - Person-to-Person (most likely through contact with blood or body fluids): Ebola Virus, Marburg Virus, Lassa Virus, New World Arenavirus (e.g. Machupo Virus) - Percutaneous (through reuse of needles or accidental needle sticks): Ebola Virus, Marburg Virus, Lassa Virus - Contact with cadavers during burial: Ebola Virus - Direct contact with infected non-human primates/animals or their blood, tissues or carcasses: Ebola Virus, Marburg Virus, Omsk Hemorrhagic Fever Virus, Rift Valley Fever Virus - Airborne: Ebola Virus, Marburg Virus, Lassa Virus, New World Arenavirus, Omsk Hemorrhagic Fever Virus, Rift Valley Fever Virus, Kyasanur Forest Disease Virus - Sexual: Ebola Virus, Marburg Virus, Lassa Virus - Mucosal contact through infectious droplets or direct contact: Ebola Virus, Marburg Virus - Bite of an infected mosquito: Rift Valley Fever Virus, Yellow Fever Virus - Bite of an infected tick: Omsk Hemorrhagic Fever Virus, Kyasanur Forest Disease Virus More Information On Epidemiology at CIDRAP & CDC Hemorrhagic Fever Viruses as Bioterrorism Agents Animal studies using nonhuman primates have demonstrated that clinical infection can be caused by aerosolized preparations of some hemorrhagic fever viruses, including Ebola, Marburg, Lassa, and yellow fever viruses as well as New World arenaviruses. Additional viruses (Rift Valley fever virus and flaviviruses) have been shown to cause aerosol infections in the laboratory setting. These viruses are considered potentially suitable as biological weapons because: --They can be disseminated through aerosols - They have a low infectious dose - They cause high morbidity and mortality c - They cause fear and panic in the general public - Effective vaccines are not available or supplies are limited - These pathogens are available and most can be readily produced in large quantities - Research on weaponizing various hemorrhagic fever viruses has been conducted in the past despite the lack of treatment options or protective vaccines Countries that have either weaponized hemorrhagic fever viruses or conducted biological weapons research on these viruses include the Soviet Union, United States & North Korea. In 2000, CDC published a list of Category A agents (ie, those that are most likely to cause mass casualties if deliberately disseminated, can be released as small aerosols, and require broad-based public health preparedness). The list included New World arenaviruses and Ebola, Marburg, and Lassa viruses. According to the Working Group on Civilian Biodefense, hemorrhagic fever viruses that pose serious threats as potential biological weapons include the following: - Ebola virus - Marburg virus - Lassa virus - New World arenaviruses - Machupo (Bolivian hemorrhagic fever) - Junin (Argentine hemorrhagic fever) - Guanarito (Venezuelan hemorrhagic fever) - Sabia (Brazilian hemorrhagic fever) - Rift Valley fever virus - Yellow fever virus - Kyasanur Forest disease virus - Omsk hemorrhagic fever virus The Working Group determined that several important hemorrhagic fever viruses are less likely than those mentioned above to be used as biological weapons; they include: - Dengue virus (is not transmissible by small-particle aerosol, requires mosquito-vector transmission, and primary dengue infection only rarely causes hemorrhagic fever) -Crimean-Congo hemorrhagic fever virus (does not replicate to high concentrations in currently available systems [a barrier to mass production]) - Hantaviruses (do not replicate to high concentrations in currently available systems) More Information On VHF as a Bioterrorism Weapon at CIDRAP & CDC Prevention & Control - Nosocomial Transmission Prevention - Isolation Precautions - Environmental Decontamination More Information on Prevention & Control Of VHF at CIDRAP , NYSDOH & CDC Infection Control for VHF in the African Health Care Setting at CDC Click here for Information on Naturally Occurring VHF at CIDRAP Laboratory Diagnosis at CIDRAP & NYSDOH Treatment Information at CIDRAP , NYSDOH & CDC Additional Sources of Information - Visit the Centers for Disease Control & Prevention (CDC) VHF Home Page - Visit Infectious Disease Society of America (IDSA) for VHF* Information*
Created by the School of Public Health University at Albany Updated July 2004