Viral hemorrhagic fever
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The viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses that are caused by five distinct families of RNA viruses: the Arenaviridae, Filoviridae, Bunyaviridae, Togaviridae, and Flaviviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in extreme cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian nephropathia epidemica, whilst others, such as the African Ebola virus, can cause severe, life-threatening disease.
Also known as:
- Crimean-Congo hemorrhagic fever (CCHF)
- Ebola hemorrhagic fever
- Hantavirus Pulmonary Syndrome
- Hemorrhagic fever with renal syndrome (HFRS)
- Lassa Fever
- Marburg hemorrhagic fever
References
http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/vhf.htm
http://www.cdc.gov/ncidod/diseases/virlfvr/virlfvr.htm
Etiologic agents
The Arenaviridae include the viruses responsible for Lassa fever and Argentine, Bolivian, and Venezuelan hemorrhagic fevers. The Bunyaviridae include the members of the Hantavirus genus that cause hemorrhagic fever with renal syndrome (HFRS), the Crimean-Congo hemorrhagic fever (CCHF) virus from the Nairovirus genus, and the Rift Valley fever (RVF) virus from the Phlebovirus genus. The Filoviridae include Ebola and Marburg viruses. Finally, the Flaviviridae include dengue, yellow fever, and two viruses in the tick-borne encephalitis group that cause VHF: Omsk hemorrhagic fever virus and Kyasanur Forest disease virus.
Risk Factors
VHF should be suspected in febrile persons who, within 3 weeks before onset of fever, have either 1) traveled in the specific local area of a country where VHF has recently occurred; 2) had direct unprotected contact with blood, other body fluids, secretions, or excretions of a person or animal with VHF; or 3) had a possible exposure when working in a laboratory that handles hemorrhagic fever viruses. The likelihood of acquiring VHF is considered low in persons who do not meet any of these criteria. Even following travel to areas where VHF has occurred, persons with fever are more likely to have infectious diseases other than VHF (e.g., common respiratory viruses, endemic infections such as malaria or typhoid fever). Clinicians should promptly evaluate and treat patients for these more common infections while awaiting confirmation of a VHF diagnosis.
In Africa, transmission of VHF in healthcare settings has been associated with reuse of contaminated needles and syringes and with provision of patient care without appropriate barrier precautions to prevent exposure to virus-containing blood and other body fluids (including vomitus, urine, and stool). The transmission risks associated with various body fluids have not been well defined because most caregivers who have acquired infection had contacts with multiple fluids.
The risk for person-to-person transmission of hemorrhagic fever viruses is greatest during the latter stages of illness when virus loads are highest; latter stages of illness are characterized by vomiting, diarrhea, shock, and, in less than half of infected patients, hemorrhage. No VHF infection has been reported in persons whose contact with an infected person occurred only during the incubation period (i.e., before onset of fever). The incubation period for VHF ranges from 2 days to 3 weeks, depending on the viral agent. There are reports of Ebola virus transmission occurring within a few days after onset of fever; however, the presence of other symptoms in the source patients and the level of exposure to body fluids among secondary cases are unknown in these instances (CDC, unpublished data, 1995). In studies involving three monkeys experimentally infected with Ebola virus (Reston strain), fever and other systemic signs of illness preceded detection of infectious virus in the animals’ pharynx by 2-4 days, in the conjunctivae and on anal swabs by 5-6 days, and in the nares by 5-10 days.
References
http://www.cdc.gov/ncidod/dhqp/bp_vhf_interimGuidance.html
Pathophysiology
VHFs are caused by viruses of four distinct families: arenaviruses, filoviruses, bunyaviruses, and flaviviruses. Each of these families share a number of features:
- They are all RNA viruses, and all are covered, or enveloped, in a fatty (lipid) coating.
- Their survival is dependent on an animal or insect host, called the natural reservoir.
- The viruses are geographically restricted to the areas where their host species live.
- Humans are not the natural reservoir for any of these viruses. Humans are infected when they come into contact with infected hosts. However, with some viruses, after the accidental transmission from the host, humans can transmit the virus to one another.
- Human cases or outbreaks of hemorrhagic fevers caused by these viruses occur sporadically and irregularly. The occurrence of outbreaks cannot be easily predicted.
- With a few noteworthy exceptions, there is no cure or established drug treatment for VHFs.
- In rare cases, other viral and bacterial infections can cause a hemorrhagic fever; scrub typhus is a good example.
Viruses associated with most VHFs are zoonotic. This means that these viruses naturally reside in an animal reservoir host or arthropod vector. They are totally dependent on their hosts for replication and overall survival. For the most part, rodents and arthropods are the main reservoirs for viruses causing VHFs. The multimammate rat, cotton rat, deer mouse, house mouse, and other field rodents are examples of reservoir hosts. Arthropod ticks and mosquitoes serve as vectors for some of the illnesses. However, the hosts of some viruses remain unknown -- Ebola and Marburg viruses are well-known examples.
How are hemorrhagic fever viruses transmitted?
Viruses causing hemorrhagic fever are initially transmitted to humans when the activities of infected reservoir hosts or vectors and humans overlap. The viruses carried in rodent reservoirs are transmitted when humans have contact with urine, fecal matter, saliva, or other body excretions from infected rodents. The viruses associated with arthropod vectors are spread most often when the vector mosquito or tick bites a human, or when a human crushes a tick. However, some of these vectors may spread virus to animals, livestock, for example. Humans then become infected when they care for or slaughter the animals.
Some viruses that cause hemorrhagic fever can spread from one person to another, once an initial person has become infected. Ebola, Marburg, Lassa and Crimean-Congo hemorrhagic fever viruses are examples. This type of secondary transmission of the virus can occur directly, through close contact with infected people or their body fluids. It can also occur indirectly, through contact with objects contaminated with infected body fluids. For example, contaminated syringes and needles have played an important role in spreading infection in outbreaks of Ebola hemorrhagic fever and Lassa fever.
References
http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/vhf.htm
Clinical and treatment aspects
Signs and symptoms of VHFs include (by definition) fever and bleeding diathesis. Manifestations of VHF often also include flushing of the face and chest, petechiae, frank bleeding, edema, hypotension, and shock. Malaise, myalgias, headache, vomiting, and diarrhea occur frequently. Definitive diagnosis is usually made at a reference laboratory with advanced biocontainment capabilities.
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 a US FDA approved investigational new drug (IND). Convalescent plasma may be effective in Argentine or Bolivian hemorrhagic fevers (also available only as IND). The only licensed vaccine for a VHF is the 17D yellow fever vaccine. Experimental vaccines for other VHFs are not readily available.
Prophylactic (preventive) ribavirin may be effective for some Bunyaviridae and Arenaviridae infections (again, available only as IND).
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 faceshield 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 N-95 mask), a battery-powered, air-purifying respirator, or a positive pressure supplied air respirator to be worn by personnel coming within six feet of a VHF patient. Multiple 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 or phenolic disinfectants. [1]
Pathophysiology
The diversity of clinical features seen among the VHF infections probably originates from varying mechanisms of pathogenesis. An immunopathogenic mechanism, for example, has been identified for dengue hemorrhagic fever, which usually occurs among patients previously infected with a heterologous dengue serotype. An influential theory explaining this phenomenon is called “antibody-dependent enhancement.” In contrast, disseminated intravascular coagulation (DIC) is thought to underlie the hemorrhagic features of Rift Valley, Marburg and Ebola fevers. In most VHFs, however, the etiology of the coagulopathy is most likely multifactorial (e.g., hepatic damage, consumptive coagulopathy, primary marrow dysfunction, etc).
The reasons for variation among patients infected with the same virus are unknown but stem from a complex system of virus-host interactions. Moreover, why some infected persons develop full-blown VHF while others do not also remains an unresolved issue. Virulence of the infecting agent clearly plays an important role. The “VHF syndrome” (capillary leak, bleeding diathesis and hemodynamic compromise leading to shock) occurs in a majority of patients manifesting disease from filoviruses, CCHF and the South American hemorrhagic fever viruses, while it occurs in a small minority of patients with dengue, RVF and Lassa fever.
Biowarfare/bioterrorism potential
The VHF viruses are spread in a variety of ways. Some may be transmitted to humans through a respiratory route. Although evidence for a history of “weaponization” (development into a biological weapon) does not exist for many of these viruses, all 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. [2]
Notable VHF outbreaks
- Mékambo in Gabon is the site of several outbreaks of Ebola hemorrhagic fever.
- Orientale, Congo villages of Durba and Watsa were the epicenter of the 1998–2000 outbreak of Marburg hemorrhagic fever.
- Uige Province in Angola is the site of world's worst haemorrhagic fever epidemic, which occurred in 2005.
- The ongoing VHF outbreak in the village of Mweka, Democratic Republic of the Congo (DRC) that started in August, 2007, and that has killed 103 people (100 adults and three children), has been shown to be caused (at least partially) by the Ebola virus.
- Some experts believe that the Black Death of the Middle Ages may have been caused by a VHF and not by the bubonic plague.[3]
See also
- Biological agent
- Biopreparat
- Bioterrorism
- Fever
- List of viruses
- Dr. Matthew Lukwiya (1957-2000)
Sources
- ↑ Woods, Lt Col Jon B. (ed.) (April 2005). USAMRIID’s Medical Management of Biological Casualties Handbook (6th ed. ed.). U.S. Army Medical Institute of Infectious Diseases, Fort Detrick, Maryland. pp. 143–144. External link in
|title=(help) - ↑ Woods, Op. cit., pg 145.
- ↑ "Black Death did not kill indiscriminately." January 29, 2008, Will Dunham. Reuters.
- Health Protection Agency
- This article includes information that originally came from US Government publications and websites and is in the public domain.
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