Viral hemorrhagic fever

Signs and symptoms of most or all viral hemorrhagic fevers can be divided into "wet" and "dry" symptoms. ^[3] Not all VHFs will include both symptoms.^[4]

Five families of RNA viruses have been recognized as being able to cause hemorrhagic fevers.^{[citation needed]}

• The order Bunyavirales includes the families Arenaviridae, Fimoviridae, and all members of the former family Bunyaviridae, especially Peribunyaviridae.

• The family Arenaviridae include the viruses responsible for Lassa fever (Lassa virus), Lujo virus, Argentine (Junin virus), Bolivian (Machupo virus), Brazilian (Sabiá virus), Chapare hemorrhagic fever (Chapare virus), Venezuelan (Guanarito virus) and Whitewater Arroyo virus hemorrhagic fevers.
• The former family Bunyaviridae includes

• the causative agents of Hantavirus hemorrhagic fever with renal syndrome (HV-HFRS) (Hantaviridae),
• the Crimean-Congo hemorrhagic fever (CCHF) virus from the genus Orthonairovirus (Nairoviridae),
• Garissa virus and Ilesha virus from the genus Orthobunyavirus (Peribunyaviridae), and
• the Rift Valley fever (RVF) virus from the genus Phlebovirus (Phenuiviridae).

• The family Filoviridae (order Mononegavirales) includes Ebola virus and Marburg virus.
• The family Flaviviridae (order Amarillovirales) includes dengue, yellow fever, and two viruses in the tick-borne encephalitis group that cause VHF: Omsk hemorrhagic fever virus and Kyasanur Forest disease virus.
• The family Rhabdoviridae (order Mononegavirales). In September 2012 scientists writing in the journal PLOS Pathogens reported the isolation of a member of the Rhabdoviridae responsible for two fatal and two non-fatal cases of hemorrhagic fever in the Bas-Congo district of the Democratic Republic of Congo. The virus was named Bas-Congo virus. The non-fatal cases occurred in healthcare workers involved in the treatment of the other two, suggesting the possibility of person-to-person transmission.^[5] This virus is related to the Ephemerovirus and Tibrovirus genera.
• The family Togaviridae (order Martellivirales) includes Chikungunya virus which causes Chikungunya fever.

The pathogen that caused the cocoliztli epidemics in Mexico of 1545 and 1576 is still unknown, and the 1545 epidemic may have been bacterial rather than viral.^[6][7]

Different hemorrhagic fever viruses act on the body differently, resulting in variable symptoms. In most VHFs, several mechanisms likely contribute to symptoms, including liver damage, disseminated intravascular coagulation (DIC), and bone marrow dysfunction. In DIC, small blood clots form in blood vessels throughout the body, removing platelets necessary for clotting from the bloodstream and reducing clotting ability. DIC is thought to cause bleeding in Rift Valley, Marburg, and Ebola fevers. For filoviral hemorrhagic fevers, there are four general mechanisms of pathogenesis. The first mechanism is the dissemination of the virus due to suppressed responses by macrophages and dendritic cell (antigen-presenting cells). The second mechanism is prevention of antigen specific immune response. The third mechanism is apoptosis of lymphocytes. The fourth mechanism is when infected macrophages interact with toxic cytokines, leading to diapedesis and coagulation deficiency. From the vascular perspective, the virus will infect vascular endothelial cells, leading to the reorganization of the VE-cadherin catenin complex (a protein important in cell adhesion). This reorganization creates intercellular gaps in endothelial cells. The gaps lead to increased endothelial permeability and allow blood to escape from the vascular circulatory system.^{[citation needed]}

The reasons for variation among patients infected with the same virus are unknown but stem from a complex system of virus-host interactions. Dengue fever becomes more virulent during a second infection by means of antibody-dependent enhancement. After the first infection, macrophages display antibodies on their cell membranes specific to the dengue virus. By attaching to these antibodies, dengue viruses from a second infection are better able to infect the macrophages, thus reducing the immune system's ability to fight off infection.^{[citation needed]}

Definitive diagnosis is usually made at a reference laboratory with advanced biocontainment capabilities. The findings of laboratory investigation vary somewhat between the viruses but in general, there is a decrease in the total white cell count (particularly the lymphocytes), a decrease in the platelet count, an increase in the blood serum liver enzymes, and reduced blood clotting ability measured as an increase in both the prothrombin (PT) and activated partial thromboplastin times (PTT). The hematocrit may be elevated. The serum urea and creatine may be raised but this is dependent on the hydration status of the patient. The bleeding time tends to be prolonged.^{[citation needed]}

Labs can use RT-PCR to detect the genetic material of the virus, or an ELISA test in later stages to detect antibodies produced by the immune system.^[8]

With the exception of yellow fever vaccine and Ebola vaccines, vaccines for VHFs are generally not available. For someone exposed to CCHF, ribavirin is available as post-exposure prophylaxis (PEP).^[9] Ribavirin may also help in exposure to Lassa fever.^[10]

Any person who is taking care of a patient with any VHF should take multiple precautions against exposure and infection. The precautions include hand hygiene, double gloves, gowns, shoe and leg coverings, and face shields or goggles. Treatment of any VHF should involve careful donning (putting on) and doffing (taking off) procedures for PPE. A Trained Observer, or TO, is used to monitor the donning/doffing process. Lassa, CCHF, Ebola, and Marburg viruses may be particularly prone to nosocomial (hospital-based) spread. Airborne precautions should be utilized including, at a minimum, a fit-tested, HEPA filter-equipped respirator (such as an N95 mask), a battery-powered, air-purifying respirator, or a positive pressure supplied air respirator to be worn by personnel coming within 1.8 meters (six feet) of a VHF patient. Groups of patients should be cohorted (sequestered) to a separate building or a ward with an isolated air-handling system. Environmental decontamination is typically accomplished with hypochlorite (e.g. bleach) or phenolic disinfectants.^[11]

Some VHF patients, notably those infected with Marburg and Ebola, are at their most infectious after death. Strict precautions should be taken including the safe transport and disinfection of the body. ^[12]

Medical management of VHF patients may require intensive supportive care. Antiviral therapy with intravenous ribavirin may be useful in Bunyaviridae and Arenaviridae infections (specifically Lassa fever, RVF, CCHF, and HFRS due to Old World Hantavirus infection) and can be used only under an experimental protocol as IND approved by the U.S. Food and Drug Administration (FDA). Interferon may be effective in Argentine or Bolivian hemorrhagic fevers (also available only as IND).^{[citation needed]}

A potential novel treatment, the NMT inhibitor, has been shown to completely inhibit Lassa (LAS) and Junín (JUN) viral infections in cells based assays.^[13] Another host-directed antiviral acts on EPRS1 which in turn acts, in human cells, as a proviral factor in mammarenaviruses infection, including LCMV, JUNV, and LASV, and its inhibition using halofuginon compound, a prolyl domain inhibitor of EPRS1, completely abolishes the viral infection by interrupting viral assembly and budding.^[14] PKR has been shown to act as a proviral factor ^[15] while the inhibition of its kinase activity restricted the virus replication and infectivity.^[16]

The VHF viruses are spread in a variety of ways. Some may be transmitted to humans through a respiratory route.^{[citation needed]} The viruses are considered by military medical planners to have a potential for aerosol dissemination, weaponization, or likelihood for confusion with similar agents that might be weaponized.^[17][18]

Scientific Research Institute of Medicine of the Ministry of Defense in Sergiyev Posad was researching the military use potential of hemorrhagic fever viruses.

• Biosafety
• Jordi Casals-Ariet
• Dr. Matthew Lukwiya (1957–2000)
• C. J. Peters