埃博拉病毒

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? 編輯 埃博拉病毒
埃博拉病毒的电子显微镜图像（来源：CDC）
分类
域： 病毒域 (-)ssRNA viruses 目： 單股負鏈病毒目 Mononegavirales 科： 纖維病毒科 屬： 埃博拉病毒属
种
象牙海岸埃博拉病毒 Reston埃博拉病毒 苏丹埃博拉病毒 扎伊尔病毒

伊波拉是一個用來稱呼一群屬於纖維病毒科伊波拉病毒屬下數種病毒的通用術語，可導致伊波拉病毒出血熱，^[1]罹患此並可致人於死，包含數種不同程度的症狀，包括噁心、嘔吐、腹瀉、膚色改變、全身痠痛、體內出血、體外出血、發燒等，感染者症狀與同為纖維病毒科的马尔堡病毒極為相似。^[2]具有50%至90%的致死率，^[2]致死原因主要為低血容量休克或多發性器官衰竭。^[3]

此病毒以非洲剛果民主共和國的伊波拉河命名（該國舊稱薩伊），此地接近首次爆發的部落，^[4]剛果民主共合國仍是最近四次爆發的所在地，包括2005年5月的一次大流行。

伊波拉是人畜共通病毒，儘管世界衛生組織煞費苦心研究，至今沒有辨認出任何有能力在爆發時存活的動物儲主，目前認為果蝠是儲存宿主的可能候選。^[5]因為伊波拉的致命力，加上目前尚未有任何疫苗被證實有效，伊波拉被列為生物安全第四級（Biosafety Level 4）病毒劑，也同時被視為生物恐怖主義的工具之一。^[6]

目录 1 結構 1.1 外觀 1.2 基因體 2 品種 2.1 薩伊伊波拉病毒 2.2 蘇丹伊波拉病毒 2.3 雷斯頓伊波拉病毒 2.4 象牙海岸伊波拉病毒 3 病毒複製 4 伊波拉出血熱 4.1 症狀 4.2 Transmission 4.3 Treatments 4.4 疫苗 5 病毒儲主 6 生物戰爭 7 文化影響 7.1 Popular description and representation 8 疫情 8.1 Cultural impact 9 參見 10 參考文獻 11 延伸閱讀 12 外部連結

[编辑] 結構

[编辑] 外觀

伊波拉病毒屬的成員，在電子顯微鏡下呈現線形的結構，病毒粒子也可能出現「U」字、「6」字形、纏繞、環狀或分枝形，不過實驗室純化技術也可能是造成這些形狀產生的因素之一，例如離心機的高速運轉可能使病毒粒子變形。病毒粒子一般直徑約80奈米，但長度可達1400奈米，典型的伊波拉病毒粒子平均長度則接近1000奈米。在病毒粒子中心結構的核殼蛋白由螺旋狀纏繞之基因體RNA與核殼蛋白質以及蛋白質病毒蛋白VP35、VP30、L組成，病毒包含的醣蛋白從表面深入病毒粒子10奈米長，另外10奈米則向外突出在套膜表面，而這層套膜來自宿主的細胞膜，在套膜與核殼蛋白之間的區域，稱為基質空間，由病毒蛋白VP40和VP24組成。

[编辑] 基因體

Each virion contains one molecule of linear, single-stranded, negative-sense RNA, totalling 18900 nucleotides in length. The 3′ terminus is not polyadenylated and the 5′ end is not capped. It codes for seven structural proteins and one non-structural protein. The gene order is 3′ - leader - NP - VP35 - VP40 - GP/sGP - VP30 - VP24 - L - trailer - 5′; with the leader and trailer being non-transcribed regions which carry important signals to control transcription, replication and packaging of the viral genome into new virions. The genomic material by itself is not infectious, because viral proteins, among them the RNA-dependent RNA polymerase, are necessary to transcribe the viral genome into mRNAs, as well as for replication of the viral genome.

[编辑] 品種

[编辑] 薩伊伊波拉病毒

薩伊伊波拉病毒有高達90%的致死率，在流行地區死亡率1976年88%、1977年100%、1994年59%、1995年81%、1996年73%、2001年至2002年80%，2003年則是90%，27年平均為83%，造成大爆發的病毒株通常都以薩伊品系的為主。

1976年8月26日首次於薩伊北邊城鎮爆發，首位個案紀錄為44歲教師Mabalo Lokela，當時他的高燒被診斷為疑似瘧疾感染，並且接受奎寧注射治療，這位病人每日回醫院就診觀察，一週後卻惡化為無法控制的嘔吐，帶血腹瀉、頭痛、暈眩 dizziness伴隨呼吸困難，並開始自口、鼻、直腸等多處開始出血，終於在9月18日過世，病程僅約2週。

不久之後，更多病患帶著相似的症狀就醫，包括發燒、頭痛、肌肉痛、關節痛、疲倦、噁心、暈眩等。這些常發展成帶血腹瀉、嚴重嘔吐和多處自發性出血，初期傳染可能肇因於重複使用Lokela用過卻未消毒之針筒，後續傳染主要則是照顧病患時，在沒有適當安全措施的情況下受到病毒侵襲或傳統埋葬前置作業的清洗過程。

[编辑] 蘇丹伊波拉病毒

Sudan Ebolavirus was the second strand of Ebola reported in 1976. It apparently originated amongst cotton factory workers in Nzara, Sudan. The first case reported was a worker exposed to a potential natural reservoir at the cotton factory. Scientists tested all animals and insects in response to this, however none tested positive for the virus. The carrier is still unknown.

A second case involved a nightclub owner in Nzara, Sudan. The local hospital, Maridi, tested and attempted to treat the patient; however, nothing was successful, and he died. The nurses did not apply safe and practical procedures in sterilizing and disinfecting the medical tools used on the nightclub owner, facilitating the spread of the virus in the hospital.

The most recent outbreak of Sudan Ebolavirus occurred in May 2004. As of May 2004, 20 cases of Sudan Ebolavirus were reported in Yambio County, Sudan, with 5 deaths resulting. The Centers for Disease Control and Prevention confirmed the virus a few days later. The neighbouring countries of Uganda and the Democratic Republic of Congo have increased surveillance in bordering areas, and other similar measures have been taken to control the outbreak. The average fatality rates for Sudan Ebolavirus were 53% in 1976, 68% in 1979, and 53% in 2000/2001. The average case-fatality rate is 53.76%.

[编辑] 雷斯頓伊波拉病毒

主条目：Ebola Reston

1989年11月首次發現在一群of 100 Crab-eating monkeys (Macaca fascicularis) imported from the 菲律賓進口至美國維吉尼亞雷斯頓，受污染的貨物也送到美國費城，此一病毒株對猴子有很高的致死率，但不對人類造成任何影響， Six of the Reston primate handlers tested positive for the virus, two due to previous exposure.

Further Reston Ebolavirus infected monkeys were shipped again to Reston, and Alice, Texas in February of 1990. More Reston Ebolavirus infected monkeys were discovered in 1992 in Siena, Italy and in Texas again in March 1996. A high rate of co-infection with Simian Hemorrhagic Fever (SHF) was present in all infected monkeys. No human illness has resulted from these two outbreaks.

[编辑] 象牙海岸伊波拉病毒

This species of Ebola was first discovered amongst chimpanzees of the Tai Forest in Côte d’Ivoire, Africa. On November 1, 1994, the corpses of two chimpanzees were found in the forest. Necropsies showed blood within the heart to be liquid and brown, no obvious marks seen on the organs, and one presented lungs filled with liquid blood. Studies of tissues taken from the chimps showed results similar to human cases during the 1976 Ebola outbreaks in Zaïre and Sudan. Later in 1994, more dead chimpanzees were discovered, with many testing positive to Ebola using molecular techniques. The source of contamination was believed to be the meat of infected Western Red Colobus monkeys, which the chimpanzees preyed upon.^[7]

One of the scientists performing the necropsies on the infected chimpanzees contracted Ebola. She developed syndromes similar to dengue fever approximately a week after the necropsy and was transported to Switzerland for treatment. After two weeks she was discharged from hospital, and was fully recovered six weeks after the infection.

[编辑] 病毒複製

The viral attachment protein recognizes specific receptors, which may be protein, carbohydrate or lipid, on the outside of the cell. The mechanism of virus entry into host cells is unknown, but it is reasonable to assume that the glycoprotein spikes on the surface of the virion would mediate the process, as they are the only transmembrane protein present on the surface. The two types of GP, the other being sGP, are specific for different cell types.

The virus next activates and releases its own genetic material, causing the host to begin manufacturing the proteins necessary for virus reproduction using its own resources. This replication continues until the cell ruptures and bursts. The virus is then spread to neighboring cells, and continues this chain of reproduction until masses of host cells are damaged. The host then may die soon after. The spread of the virus through the population can be halted if the proper sterilization and quarantine measures are taken, as the only method by which the virus may continue to propagate is via direct contact with body fluids. In order for a successful infection the virus must first evade the immune system. One of the ways it does this is by inhibiting interferon activity. VP24 blocks IFN-α/β and IFN-γ signaling by interacting with karyopherin α1, the nuclear localization signal receptor for tyrosine-phosphorylated STAT1, preventing the formation of an interferon induced antiviral state. Another protein, VP35, blocks the transcription factor interferon regulatory factor 3 (IRF-3), which is important for the expression of IFN-α/β.

[编辑] 伊波拉出血熱

在人类之间，病毒通过与受感染的人的体液，例如血液的直接接触传播。埃博拉发热的潜伏期从两天到三个星期不等。症状也不相同。但是当发病时通常有突然而明显的高烧、虚脱、关节痛、腹部疼痛和头痛的症状。这些症状进一步发展为呕吐、腹泻、结膜炎、器官损坏（特别是肝和肾），蛋白尿、以及内外出血，通常通过肠胃道。在6-10天内，病人就会康复或者死亡。

[编辑] 症狀

Symptoms are varied and often appear suddenly. Initial symptoms include: high fever (at least 38.8°C/101°F), severe headache, muscle, joint, or abdominal pain, severe weakness and exhaustion, sore throat, nausea, and dizziness. Before an outbreak is suspected, these early symptoms are easily mistaken for malaria, typhoid fever, dysentery, influenza, or various bacterial infections, which are all far more common.

Ebola goes on to cause diarrhea, dark or bloody stool, vomiting blood, red eyes from swollen blood vessels, red spots on the skin from subcutaneous bleeding, maculopapular rash, purpura, and bleeding internally and externally from any orifice, including from the nose, mouth, rectum, genitals or needle puncture sites.

Other secondary symptoms include hypotension (less than 90mm Hg), hypovolemia, tachycardia, severe organ damage (especially the kidneys, spleen, and liver) as a result of disseminated systemic necrosis, and proteinuria. The span of time from onset of symptoms to death (usually due to hypovolemic shock and/or multiple organ failure) is usually between 7 and 14 days. By the second week of infection, patients will either defervesce (the fever will lessen) or undergo systemic multiorgan failure.

[编辑] Transmission

Among humans, the virus is transmitted by direct contact with infected body fluids, or to a lesser extent, skin or mucus membrane contact. The incubation period can be anywhere from 2 to 21 days, but is generally between 5 and 10 days.

Although airborne transmission between monkeys has been demonstrated in a laboratory, there is very limited evidence for human-to-human airborne transmission in any reported epidemics. Nurse Mayinga might represent the only possible case. The means by which she contracted the virus remain uncertain.

So far all epidemics of Ebola have occurred in sub-optimal hospital conditions, where practices of basic hygiene and sanitation are often either luxuries or unknown to caretakers and where disposable needles and autoclaves are unavailable or too expensive. In modern hospitals with disposable needles and knowledge of basic hygiene and barrier nursing techniques, Ebola rarely spreads on such a large scale.

In the early stages, Ebola may not be highly contagious. Contact with someone in early stages may not even transmit the disease. As the illness progresses, bodily fluids from diarrhea, vomiting, and bleeding represent an extreme biohazard. Due to lack of proper equipment and hygienic practices, large scale epidemics occur mostly in poor, isolated areas without modern hospitals and/or well-educated medical staff. Many areas where the infectious reservoir exists have just these characteristics. In such environments all that can be done is to immediately cease all needle sharing or use without adequate sterilization procedures, to isolate patients, and to observe strict barrier nursing procedures with the use of a medical rated disposable face mask, gloves, goggles, and a gown at all times. This should be strictly enforced for all medical personnel and visitors.

[编辑] Treatments

Treatment is primarily supportive and includes minimizing invasive procedures, balancing electrolytes, replacing lost coagulation factors to help stop bleeding, maintaining oxygen and blood levels, and treating any complicating infections. Despite some initial anecdotal evidence, blood serum from Ebola survivors has been shown to be ineffective in treating the virus. Interferon is also thought to be ineffective. In monkeys, administration of an inhibitor of coagulation (rNAPc2) has shown some benefit, protecting 33% of infected animals from a usually 100% (for monkeys) lethal infection. In early 2006, scientists at USAMRIID announced a 75% recovery rate after infecting four rhesus monkeys with Ebola virus and administering antisense drugs.^[8]

[编辑] 疫苗

Vaccines have been produced for both Ebola and Marburg that were 100% effective in protecting a group of monkeys from the disease.^[9] These vaccines are based on either a recombinant Vesicular stomatitis virus or a recombinant Adenovirus^[10] carrying the Ebola spikeprotein on its surface. Early human vaccine efforts, like the one at NIAID in 2003, have so far not reported any successes.^[11]

[编辑] 病毒儲主

Despite numerous studies, the wildlife reservoir of Ebolavirus has not been identified. Between 1976 and 1998, from 30,000 mammals, birds, reptiles, amphibians and arthropods sampled from outbreak regions, no Ebolavirus was detected ^[12] apart from some genetic material found in six rodents (Mus setulosus and Praomys species) and a shrew (Sylvisorex ollula) collected from the Central African Republic in 1998.^[13] Ebolavirus was detected in the carcasses of gorillas, chimpanzees and duikers during outbreaks in 2001 and 2003 (the carcasses were the source of the initial human infections) but the high mortality from infection in these species precludes them from acting as reservoirs.^[12]

Plants, arthropods and birds have also been considered as reservoirs, however bats are considered the most likely candidate. Bats were known to reside in the cotton factory in which the index cases for the 1976 and 1979 outbreaks were employed and have also been implicated in Marburg infections in 1975 and 1980.^[12] Of 24 plant species and 19 vertebrate species experimentally inoculated with Ebolavirus, only bats became infected.^[14] The absence of clinical signs in these bats is characteristic of a reservoir species. In 2002-03, a survey of 1,030 animals from Gabon and the Republic of the Congo including 679 bats found Ebolavirus RNA in 13 fruit bats (Hyspignathus monstrosus, Epomops franquetti and Myonycteris torquata).^[15] Bats are also known to be the reservoirs for a number of related viruses including Nipah virus, Hendra virus and lyssaviruses.

[编辑] 生物戰爭

伊波拉病毒被美國CDC歸類為最高等級之生物恐怖主義的工具，也being considered a select agent that has the "potential to pose a severe threat to public health and safety". Ebola was considered in biological warfare research at both Fort Detrick^[16] in the United States and Biopreparat^[17] in the Soviet Union during the Cold War.

Ebola shows potential as a biological weapon because of its lethality but due to its relatively short incubation period it may be more difficult to spread since it may kill its victim before it has a chance to be transmitted. As a result, some developers have considered breeding it with other agents such as smallpox^[18] to create so-called chimera viruses.

As a terrorist weapon, Ebola has been considered by members of Japan's Aum Shinrikyo cult, whose leader, Shoko Asahara led about 40 members to Zaire in 1992 under the guise of offering medical aid to Ebola victims in what was presumably an attempt to acquire a sample of the virus.^[19]

[编辑] 文化影響

[编辑] Popular description and representation

Ebola and marburg have served as a rich source of ideas and plotlines for many forms of entertainment. The infatuation with the virus is likely due to the high mortality rate of its victims, its mysterious nature, and its tendency to cause gruesome bleeding from body orifices.

Much of the representation of the Ebola virus in fiction and the media is considered exaggerated or myth. Many of the stories about Ebola in Preston's book The Hot Zone are refuted in the book Level 4: Virus Hunters of the CDC by Joseph B. McCormick, an employee of the CDC at the time of the early outbreaks. One pervasive myth follows that the virus kills so fast that it has little time to spread. Victims die very soon after contact with the virus. In reality, the incubation time is usually about a week. The average time from onset of early symptoms to death varies in the range 3-21 days, with a mean of 10.1. Although this would prevent the transmission of the virus to many people, it is still enough time for some people to catch the disease.

Another myth states that the symptoms of the virus are horrifying beyond belief. Victims of Ebola suffer from squirting blood, liquefying flesh, zombie-like faces and dramatic projectile bloody vomiting, at times, from even recently deceased. In actual fact, only a fraction of Ebola victims have severe bleeding that would be even somewhat dramatic to witness. Approximately 10% of patients suffer some bleeding, but this is often internal or subtle, such as bleeding from the gums. Ebola symptoms are usually limited to extreme exhaustion, vomiting, diarrhea, abdominal pain, a high fever, headaches and other body pains.

The following is an excerpt from an interview with Philippe Calain, M.D. Chief Epidemiologist, CDC Special Pathogens Branch, Kikwit 1996:

At the end of the disease the patient does not look, from the outside, as horrible as you can read in some books. They are not melting. They are not full of blood. They're in shock, muscular shock. They are not unconscious, but you would say 'obtunded', dull, quiet, very tired. Very few were hemorrhaging. Hemorrhage is not the main symptom. Less than half of the patients had some kind of hemorrhage. But the ones that had bled, died.

[编辑] 疫情

该地区靠近1976年Nhoy Mushola记载的在扎伊尔的Yambuku和苏丹西部的Nzara第一次爆发的地方。在这次爆发中，共有602个感染案例，有397人死亡。其中扎伊尔284例感染，有151例死亡；苏丹有284例感染，151例死亡。

埃博拉共有4种亚型。两种分别命名为EBO-Z（Ebola-Zaire，埃博拉-扎伊尔）和EBO-S（Ebola-Sudan，埃博拉-苏丹）在1976年被确认。相对于扎伊尔亚型的90%的死亡率，在苏丹爆发的埃博拉亚型的死亡率较低，约为50%。1990年，相似的病毒在从菲律宾进口到美国维吉尼亚州赖斯顿的猴子中发现。这种病毒被命名为Ebola-Reston。

更进一步的爆发发生在刚果扎伊尔（1995年和2003年），加蓬（1994年，1995年和1996年）以及在乌干达（2000年）。1994年在象牙海岸人体个别案例上发现一些病毒的变种。

[编辑] Cultural impact

主条目：Ebola inspired entertainment

[编辑] 參見

• Bolivian haemorrhagic fever
• Crimean Congo hemorrhagic fever (CCHF)
• Marburg haemorrhagic fever, the first known disease caused by a filovirus
• Matthew Lukwiya, Ugandan doctor at the forefront of the 2000 outbreak

[编辑] 參考文獻

[编辑] 延伸閱讀

[编辑] 外部連結

• （英文）伊波拉病例和爆發 - 美國疾病管制局
• （英文）伊波拉病毒出血熱
• （英文）Death Called a River - Jason Socrates Bardi, Scripps Research Institute
• （英文）What is the probability of a dangerous strain of Ebola mutating and becoming airborne? ­ Brett Russel
• （英文）WHO Factsheet - 伊波拉概括資訊
• （英文）伊波拉殺死超過五千隻大猩猩 BBC News, 8 December 2006.
• （英文）[1]
• （中文）中国公众科技网：刚果担心新一轮埃博拉病毒感染爆发