“Viral hemorrhagic fever”的意思、由来-开放百科全书

Viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses in which fever and hemorrhage are caused by a viral infection. VHFs may be caused by five distinct families of RNA viruses: the families Arenaviridae, Filoviridae, Bunyaviridae, Flaviviridae, and Rhabdoviridae. 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.

Signs and symptoms

Signs and symptoms of VHFs include (by definition) fever and bleeding. Manifestations of VHF often also include flushing of the face and chest, small red or purple spots (petechiae), bleeding, swelling caused by edema, low blood pressure (hypotension), and shock. Malaise, muscle pain, headache, vomiting, and diarrhea occurs frequently. 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 filovirus 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, Rift Valley fever, and Lassa fever.

Causes

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

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 for pathogensis. 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 macrophages, 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.

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.

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.

Prevention

With the exception of yellow fever vaccine neither vaccines nor experimental vaccines are readily available. Prophylactic (preventive) ribavirin may be effective for some bunyavirus and arenavirus infections (available only as an investigational new drug (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 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.^[4]

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).

Epidemiology

Biowarfare potential

The VHF viruses are spread in a variety of ways. Some may be transmitted to humans through a respiratory route. According to Soviet defector Ken Alibek, Soviet scientists concluded China may have tried to weaponize a VHF virus during the late 1980s but discontinued to do so after an outbreak.^[13] 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.^[14]^[15]

See also

References

1. ^{{cite journal |vauthors=Grard G, Fair JN, Lee D, etal |title=A novel rhabdovirus associated with acute hemorrhagic fever in central Africa |journal=PLoS Pathog. |volume=8 |issue=9 |pages=e1002924 |date=September 2012 |pmid=23028323 |pmc=3460624 |doi=10.1371/journal.ppat.1002924 }}
2. ^¹{{cite journal |vauthors=Acuna-Soto R, Stahle DW, Cleaveland MK, Therrell MD |title=Megadrought and megadeath in 16th century Mexico |journal=Emerging Infect. Dis. |volume=8 |issue=4 |pages=360–62 |date=April 2002 |pmid=11971767 |pmc=2730237 |doi=10.3201/eid0804.010175 |url=https://www.cdc.gov/ncidod/EID/vol8no4/01-0175.htm}}
3. ^https://www.theguardian.com/world/2018/jan/16/mexico-500-years-later-scientists-discover-what-killed-the-aztecs
4. ^{{cite book |editor-last=Woods |editor-first=Lt Col Jon B. |url=http://www.usamriid.army.mil/education/bluebookpdf/USAMRIID%20BlueBook%206th%20Edition%20-%20Sep%202006.pdf |title=USAMRIID's Medical Management of Biological Casualties Handbook |edition=6th |publisher=U.S. Army Medical Institute of Infectious Diseases |location=Fort Detrick MA |year=2005 |pages=143–44 |format=PDF |ref=harv |access-date=2007-06-09 |archive-url=https://web.archive.org/web/20070609104204/http://www.usamriid.army.mil/education/bluebookpdf/USAMRIID%20BlueBook%206th%20Edition%20-%20Sep%202006.pdf |archive-date=2007-06-09 |dead-url=yes |df= }}
5. ^{{Cite web |url=http://usmex.ucsd.edu/assets/022/10129.pdf |title=Was the Huey Cocoliztli a Haemorrhagic Fever? |access-date=2010-07-25 |archive-url=https://web.archive.org/web/20100617183040/http://usmex.ucsd.edu/assets/022/10129.pdf |archive-date=2010-06-17 |dead-url=yes |df= }}
6. ^Indigenous Hemorrhagic Fever and The Spanish Conquest
7. ^{{cite journal |vauthors=Acuna-Soto R, Romero LC, Maguire JH |title=Large Epidemics of Hemorrhagic Fevers in Mexico 1545–1815 |journal=Am J Trop Med Hyg |volume=62 |issue=6 |pages=733–39 |date=June 2000 |format=PDF |url=http://www.ajtmh.org/cgi/reprint/62/6/733.pdf |pmid=11304065 |access-date=2006-12-04 |archive-url=https://web.archive.org/web/20070320023728/http://www.ajtmh.org/cgi/reprint/62/6/733.pdf |archive-date=2007-03-20 |dead-url=yes |df= }}
8. ^Epidemics in New Spain
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10. ^{{cite journal |vauthors=Olson PE, Hames CS, Benenson AS, Genovese EN |title=The Thucydides syndrome: Ebola déjà vu? (or Ebola reemergent?) |journal=Emerging Infect. Dis. |volume=2 |issue=2 |pages=155–56 |year=1996 |pmid=8964060 |pmc=2639821 |doi=10.3201/eid0202.960220 }}
11. ^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}}.
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13. ^{{Cite book|url=https://www.nlm.nih.gov/nichsr/esmallpox/biohazard_alibek.pdf|title=Biohazard: the chilling true story of the largest covert biological weapons program in the world, told from the inside by the man who ran it|last=Alibek|first=Ken|last2=Handelman|first2=Steven|publisher=Random House New York|year=1999|isbn=978-0-375-50231-6|location=|pages=286}}
14. ^{{harvnb|Woods|2005|p=145}}
15. ^{{cite book |last=Peters |first=C. |chapter=Are Hemorrhagic Fever Viruses Practical Agents for Biological Terrorism? |title=Emerging Infections |year=2000 |volume=4 |pages=201–09 |editor1-first=W. M. |editor1-last=Scheld |editor2-first=W. A. |editor2-last=Craig |editor3-first=J. M. |editor3-last=Hughes |publisher=ASM Press |location=Washington, DC |isbn=978-1555811976 }}