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 diseases. Viral means a health problem is caused by a virus, which is a type of infection. To hemorrhage means to bleed. In the case of VHFs, bleeding is a very common sign or symptom. Another common sign is fever, which means an unusually high body temperature. Both humans and non human animals can be infected. There are five known families of RNA viruses which causes VHFs: Arenaviridae , Filoviridae , Flaviviridae , Hantaviridae , and Rhabdoviridae . Some VHFs are usually mild, such as nephropathia epidemica (within the family Hantaviridae). But some are usually severe and have a high death rate, such as Ebola virus (within the family Filoviridae). All VHFs can potentially cause severe blood loss, high fever, and death.

Contents

Signs and symptoms

The following are signs and symptoms of most or all VHFs.

The severity of symptoms varies with the type of virus. The "VHF syndrome" causes bleeding diathesis, capillary leak, and circulatory shock. It happens to most people who have Filoviridae infections (such as Ebola virus or Marburg virus), Crimean–Congo hemorrhagic fever (CCHF), or the South American hemorrhagic fevers (which are caused by Arenaviridae')'. VHF syndrome only happens to a small minority of people who have dengue fever or Rift Valley fever.

Causes

Five families of RNA viruses have been recognized 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 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 ]

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 VHFs are generally not available. If a person is exposed to CCHF (such as a health care provider taking care of somebody who has the infection), they can take ribavirin as post-exposure prophylaxis (PEP). [4] In other words, the ribavirin makes it less likely the person who was exposed will become infected. It might also help in exposure to Lassa fever. [5]

Any person who is taking care of a patient with any VHF (except dengue fever) 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. 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. [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 ]

Potential Therapies

A potential novel treatment, the NMT inhibitor, has been shown to completely inhibit lassa (LAS) and Junín (JUN) viral infections in cells based assays. [7]

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 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. [16] [17]

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

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> Mosquito-borne disease

Dengue fever is a mosquito-borne disease caused by dengue virus, prevalent in tropical and subtropical areas. It is frequently asymptomatic; if symptoms appear they 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 severe dengue with bleeding, low levels of blood platelets, blood plasma leakage, and dangerously low blood pressure.

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

Marburg virus disease (MVD), formerly Marburg hemorrhagic fever (MHF) 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 illness caused by respiratory syncytial virus (RSV) and hepatitis C virus (HCV) infections, as well as some viral hemorrhagic fevers. For HCV, it is used in combination with other medications, such as simeprevir, sofosbuvir, peginterferon alfa-2b or peginterferon alfa-2a. It can also be used for viral hemorrhagic fevers—specifically, for Lassa fever, Crimean–Congo hemorrhagic fever, and Hantavirus infections. Ribavirin is usually taken orally or inhaled. Despite widespread usage, it has faced scrutiny in the 21st century because of lack of proven efficacy in treating viral infections for which it has been prescribed in the past.

<i>Filoviridae</i> Family of viruses in the order Mononegavirales

Filoviridae is a family of single-stranded negative-sense RNA viruses in the order Mononegavirales. Two members of the family that are commonly known are Ebola virus and Marburg virus. Both viruses, and some of their lesser known relatives, cause severe disease in humans and nonhuman primates in the form of viral hemorrhagic fevers.

<i>Ebolavirus</i> Genus of virus

The genus Ebolavirus is a virological taxon included in the family Filoviridae, order Mononegavirales. The members of this genus are called ebolaviruses, and encode their genome in the form of single-stranded negative-sense RNA. The six known virus species are named for the region where each was originally identified: Bundibugyo ebolavirus, Reston ebolavirus, Sudan ebolavirus, Taï Forest ebolavirus, Zaire ebolavirus, and Bombali ebolavirus. The last is the most recent species to be named and was isolated from Angolan free-tailed bats in Sierra Leone. Each species of the genus Ebolavirus has one member virus, and four of these cause Ebola virus disease (EVD) in humans, a type of hemorrhagic fever having a very high case fatality rate. The Reston virus has caused EVD in other primates. Zaire ebolavirus has the highest mortality rate of the ebolaviruses and is responsible for the largest number of outbreaks of the six known species of the genus, including the 1976 Zaire outbreak and the outbreak with the most deaths (2014).

<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, mostly in boa constrictors. 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 due to loss of net saline of basal cells, 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.

<i>Chapare mammarenavirus</i> Species of virus

Chapare mammarenavirus or Chapare virus is a virus from the family Arenaviridae which causes a hemorrhagic fever in humans known as Chapare hemorrhagic fever. It was first described after an outbreak of a novel zoonotic mammarenavirus infection occurred in the village of Samuzabeti, Chapare Province, Bolivia, in January 2003. A small number of people were infected and one person died.

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.

The species Bundibugyo ebolavirus is the taxonomic home of one virus, Bundibugyo virus (BDBV), that forms filamentous virions and is closely related to the infamous Ebola virus (EBOV). The virus causes severe disease in humans in the form of viral hemorrhagic fever and is a Select agent, World Health Organization Risk Group 4 Pathogen, National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogen, Centers for Disease Control and Prevention Category A Bioterrorism Agent, and is listed as a Biological Agent for Export Control by the Australia Group.

<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 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.

Ravn virus is a close relative of Marburg virus (MARV). RAVV causes Marburg virus disease in humans and nonhuman primates, a form of viral hemorrhagic fever. RAVV is a Select agent, World Health Organization Risk Group 4 Pathogen, National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogen, Centers for Disease Control and Prevention Category A Bioterrorism Agent, and listed as a Biological Agent for Export Control by the Australia Group.

<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

Orthoebolavirus zairense or 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">Prevention of viral hemorrhagic fever</span>

Viral hemorrhagic fevers (VHFs) are a diverse group of diseases. Prevention methods are very similar for the different viruses. The vast majority of the information in this article is from the document "Infection Control for Viral Hemorrhagic Fevers in the African Health Care Setting", which was published in December 1998. It was prepared by the Centers for Disease Control and Prevention (CDC) (part of the national government in the United States of America) and the World Health Organization (WHO) (a non-governmental organization).

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

The 1967 Marburg virus disease 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.

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