Hemorrhagic Fevers

 

(hĕm'ərăj'ĭk) , any of a group of viral diseases characterized by sudden onset, muscle and joint pain, fever, bleeding, and shock from loss of blood. Bleeding occurs in the form of leakage from capillaries in the internal organs and the skin and mucous membranes. The causative viruses may be transmitted to humans by insects, ticks, or rodents, but in the case of the African hemorrhagic fevers, Ebola and Marburg, the animal carrier is unknown. In addition to Ebola and Marburg, well-known hemorrhagic fevers include hantavirus, Lassa fever, yellow fever, and a severe form of dengue called dengue hemorrhagic fever (see dengue fever; see also Ebola virus).

Ebola and Marburg are closely related, newly emergent viruses that have in recent years caused epidemics in central Africa, with very high rates of mortality. Hantavirus occurs in many different parts of the world and is spread to humans from field rodents via microscopic bits of their excretions that get into the air and are inhaled. It was originally known as a disease of Asia and Europe that primarily attacked the kidneys, but a more deadly pulmonary form of hantavirus infection has more recently caused numerous fatalities in the United States, Chile, and other countries. Lassa fever, also spread to humans from rodent excretions, occurs primarily in W Africa. Closely related to the Lassa virus are the Junin and Machupo viruses, which have caused outbreaks of hemorrhagic fever in South America. Yellow fever, transmitted by the bite of a mosquito, still occurs in tropical areas despite largely successful control efforts. Dengue hemorrhagic fever, also spread by mosquitoes, has in recent years caused many fatalities among children in tropical countries.

There is usually no specific treatment to combat the viruses that cause hemorrhagic fevers. An exception is the drug ribavirin, which has been effective in treating Lassa fever. Treatment generally consists of such supportive measures as the replacement of lost blood, the maintainence of fluid balance, and the alleviation of symptoms. Survival depends largely upon the virulence of the virus strain and the quality of treatment.

Bibliography

See R. Reston, The Hot Zone (1994).

Viral hemorrhagic fever
Classification & external resources

ICD-10	A96-A99

The viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses that are caused by four distinct families of RNA viruses: the Arenaviridae, Filoviridae, Bunyaviridae 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.

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.

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 only 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 VHF 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 influencial 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.

See also

• Biological agent
• Biopreparat is a leader in the development of bioweapons.
• Bioterrorism
• Fever
• List of viruses
• Dr. Matthew Lukwiya (1957-2000)

Sources

1. ^ Woods, Lt Col Jon B. (ed.) (April 2005). USAMRIID’s Medical Management of Biological Casualties Handbook, 6th ed., U.S. Army Medical Institute of Infectious Diseases, Fort Detrick, Maryland, 143-144. 
2. ^ Woods, Op. cit., pg 145.

• Health Protection Agency
• This article includes information that originally came from US Government publications and websites and is in the public domain.

Viral diseases (A80-B34, 042-079)
Viral infections of the CNS	Poliomyelitis (Post-polio syndrome) - Subacute sclerosing panencephalitis - Progressive multifocal leukoencephalopathy - Rabies - Encephalitis lethargica - Lymphocytic choriomeningitis - Tick-borne meningoencephalitis - Tropical spastic paraparesis
Arthropod-borne viral fevers and viral haemorrhagic fevers	Dengue fever - Chikungunya - Rift Valley fever - Yellow fever - Argentine hemorrhagic fever - Bolivian hemorrhagic fever - Lassa fever - Crimean-Congo hemorrhagic fever - Omsk hemorrhagic fever - Kyasanur forest disease - Marburg hemorrhagic fever - Ebola
Viral infections characterized by skin and mucous membrane lesions	Herpes simplex - Chickenpox - Herpes zoster - Smallpox - Monkeypox - Measles - Rubella - Plantar wart - Cowpox - Vaccinia - Molluscum contagiosum - Roseola - Fifth disease - Hand, foot and mouth disease - Foot-and-mouth disease
Viral hepatitis	Hepatitis A - Hepatitis B - Hepatitis C - Hepatitis E
Viral infections of the respiratory system	Avian influenza - Acute viral nasopharyngitis - Infectious mononucleosis - Influenza - Severe acute respiratory syndrome - Viral pneumonia
Other viral diseases	Cytomegalovirus - Mumps - Bornholm disease
Sexually transmitted	HIV (AIDS, AIDS dementia complex) - Genital warts - Adult T-cell leukemia

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