Viral hemorrhagic fever

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Viral hemorrhagic fever
Other namesviral haemorrhagic fever
7042 lores-Ebola-Zaire-CDC Photo.jpg
Two nurses standing near Mayinga N'Seka, a nurse with Ebola virus disease in the 1976 outbreak in Zaire. N'Seka died a few days later due to severe internal hemorrhage.
Specialty Infectious disease

Viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses. VHFs may be caused by five distinct families of RNA viruses: the families Filoviridae , Flaviviridae , Rhabdoviridae , and several member families of the Bunyavirales order such as Arenaviridae , and Hantaviridae . All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in many cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian nephropathia epidemica (a hantavirus), while others, such as Ebola virus, can cause severe, life-threatening disease.

Contents

Signs and symptoms

Signs and symptoms of VHFs include (by definition) fever and bleeding:

The severity of symptoms varies with the type of virus. The "VHF syndrome" (capillary leak, bleeding diathesis, and circulatory compromise leading to shock) appears in a majority of people with filoviral hemorrhagic fevers (e.g., Ebola and Marburg virus), Crimean–Congo hemorrhagic fever (CCHF), and the South American hemorrhagic fevers caused by arenaviruses, but only in a small minority of patients with dengue or Rift Valley fever.

Causes

Five families of RNA viruses have been recognised as being able to cause hemorrhagic fevers.[ citation needed ]

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. [2] [3]

Pathophysiology

Different hemorrhagic fever viruses act on the body in different ways, resulting in different symptoms. In most VHFs, it is likely that several mechanisms 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 dissemination of 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 ]

Diagnosis

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 ]

Prevention

With the exception of yellow fever vaccine and Ebola vaccines, vaccines for VHF-associated viruses are generally not available. Post-exposure prophylactic (preventive) ribavirin may be effective for some bunyavirus and arenavirus infections. [4] [5]

VHF isolation guidelines dictate that all VHF patients (with the exception of dengue patients) should be cared for using strict contact precautions, including hand hygiene, double gloves, gowns, shoe and leg coverings, and face shield or goggles. 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 meter (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. [6]

Management

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 ]

Epidemiology

Biowarfare potential

The VHF viruses are spread in a variety of ways. Some may be transmitted to humans through a respiratory route.[ citation needed ] The virus is considered by military medical planners to have a potential for aerosol dissemination, weaponization, or likelihood for confusion with similar agents that might be weaponized. [15] [16]

See also

Related Research Articles

<span class="mw-page-title-main">Lassa fever</span> Viral disease spread by a type of mouse

Lassa fever, also known as Lassa hemorrhagic fever, is a type of viral hemorrhagic fever caused by the Lassa virus. Many of those infected by the virus do not develop symptoms. When symptoms occur they typically include fever, weakness, headaches, vomiting, and muscle pains. Less commonly there may be bleeding from the mouth or gastrointestinal tract. The risk of death once infected is about one percent and frequently occurs within two weeks of the onset of symptoms. Of those who survive, about a quarter have hearing loss, which improves within three months in about half of these cases.

<span class="mw-page-title-main">Dengue fever</span> Tropical disease caused by the dengue virus, transmitted by mosquito

Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin 3 to 14 days after infection. These may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin itching and skin rash. Recovery generally takes two to seven days. In a small proportion of cases, the disease develops into a more severe dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs.

<span class="mw-page-title-main">Marburg virus disease</span> Human viral disease

Marburg virus disease is a viral hemorrhagic fever in human and non-human primates caused by either of the two Marburgviruses: Marburg virus (MARV) and Ravn virus (RAVV). Its clinical symptoms are very similar to those of Ebola virus disease (EVD).

<span class="mw-page-title-main">Ribavirin</span> Antiviral medication

Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, peginterferon alfa-2b or peginterferon alfa-2a. Among the viral hemorrhagic fevers it is sometimes used for Lassa fever, Crimean–Congo hemorrhagic fever, and Hantavirus infection but should not be used for Ebola or Marburg infections. Ribavirin is taken by mouth or inhaled. Despite widespread usage, since the 2010s it has faced scrutiny for a lack of efficacy in treating viral infections it has historically been prescribed for.

Bolivian hemorrhagic fever (BHF), also known as black typhus or Ordog Fever, is a hemorrhagic fever and zoonotic infectious disease originating in Bolivia after infection by Machupo mammarenavirus.

<i>Bunyavirales</i> Order of RNA viruses

Bunyavirales is an order of segmented negative-strand RNA viruses with mainly tripartite genomes. Member viruses infect arthropods, plants, protozoans, and vertebrates. It is the only order in the class Ellioviricetes. The name Bunyavirales derives from Bunyamwera, where the original type species Bunyamwera orthobunyavirus was first discovered. Ellioviricetes is named in honor of late virologist Richard M. Elliott for his early work on bunyaviruses.

<span class="mw-page-title-main">Arenavirus</span> Family of RNA viruses

An arenavirus is a bi- or trisegmented ambisense RNA virus that is a member of the family Arenaviridae. These viruses infect rodents and occasionally humans. A class of novel, highly divergent arenaviruses, properly known as reptarenaviruses, have also been discovered which infect snakes to produce inclusion body disease. At least eight arenaviruses are known to cause human disease. The diseases derived from arenaviruses range in severity. Aseptic meningitis, a severe human disease that causes inflammation covering the brain and spinal cord, can arise from the lymphocytic choriomeningitis virus. Hemorrhagic fever syndromes, including Lassa fever, are derived from infections such as Guanarito virus, Junin virus, Lassa virus, Lujo virus, Machupo virus, Sabia virus, or Whitewater Arroyo virus. Because of the epidemiological association with rodents, some arenaviruses and bunyaviruses are designated as roboviruses.

Venezuelan hemorrhagic fever (VHF) is a zoonotic human illness first identified in 1989. The disease is most prevalent in several rural areas of central Venezuela and is caused by Guanarito mammarenavirus (GTOV) which belongs to the Arenaviridae family. The short-tailed cane mouse is the main host for GTOV which is spread mostly by inhalation of aerosolized droplets of saliva, respiratory secretions, urine, or blood from infected rodents. Person-to-person spread is possible, but uncommon.

<span class="mw-page-title-main">Crimean–Congo hemorrhagic fever</span> Disease of humans and other animals

Crimean–Congo hemorrhagic fever (CCHF) is a viral disease. Symptoms of CCHF may include fever, muscle pains, headache, vomiting, diarrhea, and bleeding into the skin. Onset of symptoms is less than two weeks following exposure. Complications may include liver failure. Survivors generally recover around two weeks after onset.

Clarence James Peters, Jr is a physician, field virologist and former U.S. Army colonel. He is noted for his efforts in trying to stem epidemics of exotic infectious diseases such as the Ebola virus, Hanta virus and Rift Valley fever (RVF). He is an eminent authority on the virology, pathogenesis and epidemiology of hemorrhagic fever viruses.

Lujo is a bisegmented RNA virus—a member of the family Arenaviridae—and a known cause of viral hemorrhagic fever (VHF) in humans. Its name was suggested by the Special Pathogens Unit of the National Institute for Communicable Diseases of the National Health Laboratory Service (NICD-NHLS) by using the first two letters of the names of the cities involved in the 2008 outbreak of the disease, Lusaka (Zambia) and Johannesburg. It is the second pathogenic Arenavirus to be described from the African continent—the first being Lassa virus—and since 2012 has been classed as a "Select Agent" under U.S. law.

<span class="mw-page-title-main">Marburg virus</span> Species of filamentous virus responsible for hemorrhagic fever

Marburg virus (MARV) is a hemorrhagic fever virus of the Filoviridae family of viruses and a member of the species Marburg marburgvirus, genus Marburgvirus. It causes Marburg virus disease in primates, a form of viral hemorrhagic fever. The virus is considered to be extremely dangerous. The World Health Organization (WHO) rates it as a Risk Group 4 Pathogen. In the United States, the National Institute of Allergy and Infectious Diseases ranks it as a Category A Priority Pathogen and the Centers for Disease Control and Prevention lists it as a Category A Bioterrorism Agent. It is also listed as a biological agent for export control by the Australia Group.

Hantaan orthohantavirus (HTNV) is an enveloped, single-stranded, negative-sense RNA virus species of Old World Orthohantavirus. It is the causative agent of Korean hemorrhagic fever in humans. It is named for the Hantan River in South Korea, and in turn lends the name to its genus Orthohantavirus and family Hantaviridae.

<span class="mw-page-title-main">Ebola</span> Viral hemorrhagic fever of humans and other primates caused by ebolaviruses

Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after infection. The first symptoms are usually fever, sore throat, muscle pain, and headaches. These are usually followed by vomiting, diarrhoea, rash and decreased liver and kidney function, at which point some people begin to bleed both internally and externally. It kills between 25% and 90% of those infected – about 50% on average. Death is often due to shock from fluid loss, and typically occurs between six and 16 days after the first symptoms appear. Early treatment of symptoms increases the survival rate considerably compared to late start. An Ebola vaccine was approved by the US FDA in December 2019.

<i>Zaire ebolavirus</i> Species of virus affecting humans and animals

Zaire ebolavirus, more commonly known as Ebola virus, is one of six known species within the genus Ebolavirus. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and other mammals, known as Ebola virus disease (EVD). Ebola virus has caused the majority of human deaths from EVD, and was the cause of the 2013–2016 epidemic in western Africa, which resulted in at least 28,646 suspected cases and 11,323 confirmed deaths.

<span class="mw-page-title-main">FGI-106</span> Chemical compound

FGI-106 is a broad-spectrum antiviral drug developed as a potential treatment for enveloped RNA viruses, in particular viral hemorrhagic fevers from the bunyavirus, flavivirus and filovirus families. It acts as an inhibitor which blocks viral entry into host cells. In animal tests FGI-106 shows both prophylactic and curative action against a range of deadly viruses for which few existing treatments are available, including the bunyaviruses hantavirus, Rift Valley fever virus and Crimean-Congo hemorrhagic fever virus, the flavivirus dengue virus, and the filoviruses Ebola virus and Marburg virus.

<span class="mw-page-title-main">2017 Uganda Marburg virus outbreak</span> Disease outbreak in Uganda

The 2017 Uganda Marburg virus outbreak was confirmed by the World Health Organization (WHO) on 20 October 2017 after there had been an initial fatality due to the virus.

<span class="mw-page-title-main">1967 Marburg virus outbreak</span> Disease outbreak in Germany and Yugoslavia

The 1967 Marburg virus outbreak was the first recorded outbreak of Marburg virus disease. It started in early August 1967 when 30 people became ill in the West German towns of Marburg and Frankfurt and later two in Belgrade, Yugoslavia. The infections were traced back to three laboratories in the separate locations which received a shared shipment of infected African green monkeys. The outbreak involved 25 primary Marburg virus infections and seven deaths, and six non-lethal secondary cases.

<i>Orthornavirae</i> Kingdom of viruses

Orthornavirae is a kingdom of viruses that have genomes made of ribonucleic acid (RNA), including genes which encode an RNA-dependent RNA polymerase (RdRp). The RdRp is used to transcribe the viral RNA genome into messenger RNA (mRNA) and to replicate the genome. Viruses in this kingdom share a number of characteristics which promote rapid evolution, including high rates of genetic mutation, recombination, and reassortment.

References

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  2. 1 2 Acuna-Soto R, Stahle DW, Cleaveland MK, Therrell MD (April 2002). "Megadrought and megadeath in 16th century Mexico". Emerging Infect. Dis. 8 (4): 360–62. doi:10.3201/eid0804.010175. PMC   2730237 . PMID   11971767.
  3. ↑ "500 years later, scientists discover what probably killed the Aztecs". The Guardian . Agence France-Presse. 2018-01-16.
  4. ↑ Ergönül Ö, Keske Ş, Çeldir MG, Kara İA, Pshenichnaya N, Abuova G, et al. (2018). "Systematic Review and Meta-analysis of Postexposure Prophylaxis for Crimean-Congo Hemorrhagic Fever Virus among Healthcare Workers". Emerg Infect Dis. 24 (9): 1642–1648. doi:10.3201/eid2409.171709. PMC   6106438 . PMID   30124196.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ↑ Hadi CM, Goba A, Khan SH, Bangura J, Sankoh M, Koroma S, et al. (2010). "Ribavirin for Lassa fever postexposure prophylaxis". Emerg Infect Dis. 16 (12): 2009–11. doi:10.3201/eid1612.100994. PMC   3294560 . PMID   21122249.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ↑ Woods LC, ed. (2005). USAMRIID's Medical Management of Biological Casualties Handbook (PDF) (6th ed.). Fort Detrick MA: U.S. Army Medical Institute of Infectious Diseases. pp. 143–44. Archived from the original (PDF) on 2007-06-09. Retrieved 2007-06-09.
  7. ↑ "Was the Huey Cocoliztli a Haemorrhagic Fever?" (PDF). Archived from the original (PDF) on 2010-06-17. Retrieved 2010-07-25.
  8. ↑ Indigenous Hemorrhagic Fever and The Spanish Conquest
  9. ↑ Acuna-Soto R, Romero LC, Maguire JH (June 2000). "Large Epidemics of Hemorrhagic Fevers in Mexico 1545–1815" (PDF). Am J Trop Med Hyg. 62 (6): 733–39. doi:10.4269/ajtmh.2000.62.733. PMID   11304065. Archived from the original (PDF) on 2007-03-20. Retrieved 2006-12-04.
  10. ↑ Epidemics in New Spain
  11. ↑ Towner JS, Khristova ML, Sealy TK, Vincent MJ, Erickson BR, Bawiec DA, Hartman AL, Comer JA, Zaki SR, Ströher U, Gomes Da Silva F, Del Castillo F, Rollin PE, Ksiazek TG, Nichol ST (2006). "Marburgvirus Genomics and Association with a Large Hemorrhagic Fever Outbreak in Angola". Journal of Virology. 80 (13): 6497–516. doi:10.1128/JVI.00069-06. PMC   1488971 . PMID   16775337.
  12. ↑ Olson PE, Hames CS, Benenson AS, Genovese EN (1996). "The Thucydides syndrome: Ebola déjà vu? (or Ebola reemergent?)". Emerging Infect. Dis. 2 (2): 155–56. doi:10.3201/eid0202.960220. PMC   2639821 . PMID   8964060.
  13. ↑ Scott, Susan and Duncan, Christopher. (2004). Return of the Black Death: The World's Greatest Serial Killer West Sussex; John Wiley and Sons. ISBN   0-470-09000-6.
  14. ↑ Briese T, Paweska J, McMullan L, Hutchison S, Street C, Palacios G, Khristova M, Weyer J, Swanepoel R, Engholm M, Nichol S, Lipkin W (2009). "Genetic Detection and Characterization of Lujo Virus, a New Hemorrhagic Fever–Associated Arenavirus from Southern Africa". PLOS Pathog. 5 (5): e1000455. doi: 10.1371/journal.ppat.1000455 . PMC   2680969 . PMID   19478873.
  15. ↑ Woods 2005 , p. 145
  16. ↑ Peters C (2000). "Are Hemorrhagic Fever Viruses Practical Agents for Biological Terrorism?". In Scheld WM, Craig WA, Hughes JM (eds.). Emerging Infections. Vol. 4. Washington, D.C.: ASM Press. pp.  201–09. ISBN   978-1555811976.
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