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伊波拉出血熱

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伊波拉出血熱
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一幀攝於1976年薩伊的照片。裡面的兩位護士站在一名伊波拉患者(金沙薩第三宗病例)的病床前。幾天後,此同樣從事護士的病人死於嚴重內出血
ICD-10 A98.4
ICD-9 078.89
DiseasesDB 18043
MedlinePlus 001339
eMedicine med/626
MeSH D019142
Ebola」的各地常用別名
大陸 埃博拉
港臺 伊波拉

伊波拉出血熱(又名:伊波拉病毒病;通稱:伊波拉)是一種由伊波拉病毒引起,多出現於靈長動物身上之人畜共患傳染病[1]罹患此病的人會在2天至3週內陸續出現發燒頭痛肌肉疼痛英语Myalgia嘔吐腹瀉出疹病徵。病情後會進一步惡化為英语Liver failure腎衰竭[1]步入此階段,病人或會出現體內、外出血的現象,並可能在首個症狀出現後的6至16天内,因血容量過低多重器官衰竭而死亡。[2][3]

盡可能撇除其他諸如瘧疾霍亂腦膜炎、其他病毒性出血熱等可造成近似病徵的疾病,為診斷伊波拉出血熱的首要工作。血液樣本中之抗病毒體、病毒的核糖核酸或病毒本身均為鑑定的指標。[1]目前尚未有針對性的治療方案,各方亦正致力研發安全、可供廣泛使用的疫苗藥物[1]病人大多接受口服補液治療英语Oral rehydration therapy靜脈注射等,可提高存活率的舒緩性療法,以降低疾病所帶來的傷害及併發症的風險。[1]深切治療則能進一步應付器官衰竭的問題。[4]根據一直以來的疫情,此出血熱可造成高達25-90%(平均約五成)的綜合臨床致死率[1][5]

伊波拉患者多因接觸了帶有病毒的體液(包括血液)、器官,或間接觸摸到最近受污染之器具而染病。[1]目前尚未有足夠證據,顯示病毒能經空氣微粒在靈長動物間傳播。[6]患者的精液母乳在其康復後的數週至數月内,仍可能載有病毒。[1][7]果蝠被認為是伊波拉病原體天然宿主英语Natural reservoir,能在自身不受影響的狀況下將之散播。[1]疫症的控制在乎醫療界以及一定程度的社區配合。前線醫學措施包括了快速的病例偵測、實驗室診斷、接觸者追蹤德语Contact Tracing、正確看護、謹慎處理醫療廢物及妥善安葬或火化屍體[1][8]減少接觸受感染的個體為社區防疫的一大重點。在近距離接觸患者時,應穿著完整的連身型防護衣物,並勤加洗手。[1]叢林肉易沾染病毒,故需在徹底煮熟後方能進食;在處理這類產物時,也需佩戴醫用手套。[1]

此病在1976年首次出現於當時的蘇丹薩伊[註 1][1],並常於非洲撒哈拉以南的地區造成間歇性爆發。直至2013年,世界衛生組織一共公佈了1,716宗確診個案,合計24次爆發。[1][9]最近且最嚴重的一次流行,為仍肆虐利比里亞幾內亞塞拉利昂西非疫症;截至2015年6月29日  (2015-06-29),是次爆發已錄得27,551宗疑似個案,共11,236宗死亡案例。[10][11][12]

病徵[编辑]

伊波拉出血熱病徵一覽圖。[13]

伊波拉出血熱的潛伏期(感染與發病的時間差)為2-21天不等[1][13],但多數為4-10天[2]。一項近期發表的數學模型評估推算,約有5%的病人為多於3週。[14]

罹患此病的早期症狀與普通感冒大同小異,且為突發性。初期病徵為:疲倦乏力英语Weakness食慾不振發燒,以及肌肉、關節、咽喉和頭部疼痛。[13][2][15][16]患者體溫往往超越38.3(101)。[17]腹瀉嘔吐腹痛呼吸困難胸痛英语Chest pain水腫意識下降英语Altered level of consciousness英语Liver failure腎衰竭亦會隨之而來。[16]除此,約有五成的病患者會在發病後的5-7天內起斑丘疹英语Maculopapular rash[2][17]

到了後期,一些病人開始出現體內、外出血的現象[1](多始於第一個病徵顯露後的5-7天內[18]);所有患者均有凝血障礙英语Coagulopathy[17]。出血位置通常為黏膜處(主要為消化道鼻腔牙齦)及針管的穿刺點。[19]這還會導致紅眼吐血咳血便血[20]流血處若伸延至皮膚的話,則會引起瘀點瘀斑紫斑血腫英语Hematoma(尤其是針刺處附近)。[4]可是,大量出血的情況實屬罕見,亦只發生在消化道。[17][21]

若病人能成功抵抗病毒,就會在病發後的7-14天內逐步康復[16];否則會在6-16天內逝世,死因多為血容量過低多重器官衰竭[3][2]。宏觀而言,出血表示了患者的病情較差,因失血過多而死的機會頗高。[15]死者在臨終前均會陷入昏迷狀態。[16]生還者則會產生至少10年有效的天然抗體,但暫不清楚此是否足以抵擋後繼感染。[22]

致病機理[编辑]

伊波拉出血熱致病機理概要。

伊波拉出血熱的病態生理學為醫學界的熱門討論議題之一。伊波拉病毒主要透過粘膜處及表皮傷口入侵宿主身體。[23]它們能在多種細胞內進行高效繁殖,包括:單核細胞巨噬細胞內皮細胞肝細胞英语hepatocytes成纖維細胞腎上腺細胞[24]這一過程會觸發細胞素風暴,導致敗血症[25]巨噬細胞首當其衝受到影響,淋巴細胞後會一併進入細胞凋亡階段。[26]因此,病人往往會出現淋巴細胞缺乏症英语Lymphocytopenia及免疫力衰退。[23]病毒在數天後開始侵襲血管內皮細胞,破壞血管的凝聚。[26]負責處理細胞粘附英语cell adhesion及細胞間結構的整合素,會隨著病毒糖蛋白數量的上升而下降。[2]帶病者的肝臟亦受到破壞。[2]持續的出血會導致水腫低血容量休克[27]彌散性血管內凝血常見於伊波拉病人身上。這是因病毒促使了單核及巨噬細胞分泌過剩的组织因子英语Tissue factor,導致了血液凝固作用級聯。[2][28]

其中,先天性免疫力破壞為伊波拉致病機理的一大重點。[29][30]病毒使患者身體無法對一型干擾素英语Interferon type Iαβ)及二型干擾素伽瑪作出自然反應。[31][32]一般而言,數種位於宿主細胞基質內、外的受體(主要為鐘形受體)會辨認出病原相關分子,並進入活化階段。期間,干擾素控制因子英语Interferon regulatory factors(3及7)觸發通信級聯,令一型干擾素表露並被釋放,使之與鄰近細胞表面的相關受體結合。[31]結合完成後,信使蛋白“STAT1”及“STAT2”被活化並轉移至細胞核刺激干擾素激活性基因英语Interferome,以製造出抗病毒蛋白。[31]伊波拉病毒(模式種)的“V24”及“VP35”蛋白,分別封鎖了“STAT1”的去路及直接阻擋了β干擾素的釋放。[31][32]通過抑制這些免疫反應,病毒能迅速蔓延至全身。[26]

診斷方式[编辑]

患者的病史對診斷伊波拉出血熱極為重要。

實驗室診斷[编辑]

血小板减少症英语Thrombocytopenia、肝細胞谷丙轉氨酶天冬氨酸氨基轉移酶的上升、血凝力失常(多伴隨著彌散性血管內凝血)、白細胞减少症白細胞增生症英语Leukocytosis的先後出現,均為診斷伊波拉出血熱的非針對性指標。[33]

針對性測試方面,若病人血液樣本被驗出含有病毒、病毒的核糖核酸蛋白質、相關抗體的話,即被確診感染伊波拉病毒。細胞培養病毒測試法、聚合酶鏈式反應病毒核糖核酸測試法、酶聯免疫吸附試驗病毒蛋白測試法於早期病患者及屍體身上較為有效,而抗體測試法則適用於後期病人或痊癒者。[34]絲狀病毒(包括伊波拉病毒)因具有獨特蟲狀構造而容易透過電子顯微鏡辨認,惟此無法進一步鑑定具體種類。[35]疾病爆發期間,提取病毒的測試方式不太適用。故聚合酶鏈式反應及酶聯免疫吸附試驗為實地檢查或流動醫院中,最常用之診斷方法。[36]2014年於利比里亞推行的新型流動測試設備,能在樣本呈交後的3-5小時之內給予結果。[37]

鑑別診斷[编辑]

伊波拉出血熱病徵與馬爾堡出血熱英语Marburg virus disease的如出一轍。[38]其亦容易與其他一些常見於非洲赤道地區的疾病混為一談(如:其他的病毒性出血熱瘧疾傷寒志賀桿菌病立克次體病(尤其是斑疹傷寒霍亂革蘭氏陰性菌敗血症)及諸如回歸熱英语Relapsing fever出血性腸道炎等的萊姆病)。除此,鉤端螺旋體病恙蟲病鼠疫Q型流感念珠菌病組織胞漿菌病英语Histoplasmosis錐蟲病英语Trypanosomiasis器官利甚曼病、出血性天花麻疹和急性重症型病毒性肝炎亦位列鑑別診斷的名單上。[39]有機會與伊波拉出血熱混淆的非傳染性疾病英语Non-communicable disease有:急性早幼粒細胞白血病英语Acute promyelocytic leukemia溶血性尿毒綜合症、蛇咬中毒、凝血因子缺乏症/血小板疾病、血栓性血小板減少紫斑症英语Thrombotic thrombocytopenic purpura遺傳性出血性血管擴張症川崎氏病,以及華法林中毒。[40][41][42][43]

病情監控[编辑]

目前尚未有針對性的伊波拉治療方案,所有的措施均旨在舒緩疾病所帶來的傷害及降低併發症的風險。[44]美國食品藥品監督管理局亦呼籲大眾要提防假冒產品。[45][46]

標準看護[编辑]

及早接受口服補液治療英语Oral rehydration therapy靜脈注射等舒緩性療法,有助提升存活率。[1]這包括了痛楚控制英语Pain management、體溫控制、止吐、抗憂鬱。於發病早期注射抗凝劑(如肝素)可減少彌散性血管內凝血的危害;而在後期注射凝固劑則可降低出血的程度。另外,抗生素有助杜絕由細菌真菌(於已受伊波拉病毒破壞之器官)所引起的繼發性感染[47][48][49]世衛呼籲避免使用阿斯匹林布洛芬這兩種容易導致出血的藥物止痛。[50]濃縮紅血球血包英语Packed red blood cells血小板冰凍血漿英语Fresh frozen plasma一類的血液製品,在必要時也可一併使用。[51]

根據世衛指引,提供家中護理者宜使用已吸收氯水的毛巾移動病人或屍體,並以乾淨的毛巾遮掩口鼻。[52]

深切治療[编辑]

已發展國家一般可為病人提供深切治療英语Intensive care medicine[4]首要工作為保持患者體液電解質的平衡,以降低脫水對身體帶來的影響。血液透析體外膜氧合則可分別解決腎衰竭及肺功能下降的問題。[4]

預後[编辑]

罹患伊波拉出血熱的綜合死亡率位於25-90%之間,平均值為五成(模式種病毒的威脅則更高)。[1][5]臨床實例證明,持續感染會造成長期的後遺症,如:睾丸炎關節疼痛英语Arthralgia肌肉疼痛英语Myalgia脫屑英语Desquamation脫髮及多種眼部症狀(畏光英语Photophobia溢淚英语Epiphora (medicine)葡萄膜炎英语Uveitis脈絡膜視網膜炎英语Chorioretinitis,甚至失明)。[1]除此,康復者大多都會出現慢性肌肉與關節疼痛、肝炎、聽力下降以及諸如長期疲勞、胃口下降、無法恢復體重等的全身症狀。[16][25]

病源[编辑]

美國疾病控制與預防中心編制的伊波拉病毒生存週期概覽圖。

伊波拉出血熱的病原體為五種伊波拉病毒屬的成員——本迪布焦病毒(Bundibugyo virus)、雷斯頓病毒(Reston virus)、蘇丹病毒(Sudan virus)、塔伊森林病毒(Taï Forest virus)及舊稱“扎伊爾伊波拉病毒”的伊波拉病毒(Ebola virus)。[53]後者是此屬的模式種且最具危險性,因其造成了最大規模的爆發及最高的死亡率。[54]雷斯頓病毒尚未被發現有感染人類的能力,但已在其他靈長動物身上誘發疾病。[55][56]它們的特徵與馬爾堡病毒相似。[53]

病毒概論[编辑]

伊波拉馬爾堡病毒系統發生樹對照圖。數字顯示有關分支的分類信心率。
電子顯微鏡下的伊波拉病毒。

伊波拉病毒屬的成員為已有數百萬年歷史的絲狀病毒之一。[57]病毒學家利用分子時鐘法英语Molecular clock追索當中的源流,發現伊波拉與馬爾堡病毒雖極為相似,但其實早已於數千年前分化。[58]

如其他絲狀病毒,伊波拉病毒體型修長。它們呈“6”或“U”字狀,有時亦會捲曲成環狀,並帶分支。這類病毒的平均寬度為80納米,長度參差甚大——從974到14,000納米不等。[35]

伊波拉病毒具有線性、非結段型、不具感染性的單鏈核糖核酸基因組。此基因組帶負極性,並具有逆互補性的3'及5'極端。其不含5'端帽、不具多腺苷酸化性,亦並非以共價鍵與蛋白質相連。[59]它們的基因組約有一千個鹼基對,內含7個以“3'-UTR-NP-VP35-VP40-GP-VP30-VP24-L-5'-UTR”次序排列的基因[60]這五種伊波拉病毒的基因組以基因重疊的位置及數量區分。

伊波拉病毒會與宿主體內特定的細胞受體(如:“DC-SIGN英语DC-SIGN”、C-型凝集素整合素)結合進行胞飲作用,開始它們的生命週期[29]成功入侵後,病毒會移動至細胞核內體溶酶體處,使自身含有獨特糖蛋白(“GP1”及“GP2”)的包膜分解,以便和細胞膜內壁的蛋白物融合並釋放病毒核衣殼。[29][31]L 基因編碼的病毒核糖核酸聚合酶解封核衣殼,並將有關基因轉錄為正荷單鏈信使核糖核酸。此核糖核酸後進一步被翻譯為數種結構與非結構性蛋白物,其中以核蛋白的數量最多,它的濃度亦決定著何時從基因轉錄推進至基因組複製。基因組複製會產生完整的抗基因組物質,並被再轉錄為新病毒的基因組。[30]此乃伊波拉病毒自我複製的方式。新產生的病毒組合物,會聚集到細胞膜的內壁將之穿破,沿途亦會奪取適用的合成物以製造自身的包膜。新生病毒繼續襲擊其他細胞,並重複以上週期。伊波拉病毒的特質使研究工作困難重重。[61]

天然宿主[编辑]

目前還未能鐵定伊波拉病毒的天然宿主英语Natural reservoir,但是根據過往的調查,蝙蝠(尤其是錘頭果蝠反曲肩果蝠英语Franquet's epauletted fruit bat小領果蝠英语Little collared fruit bat)的機會最高。[62][63]1996年發表的一份報告指出,在24種植物及19種脊椎動物中,只有蝙蝠受到伊波拉病毒(模式種)的感染,可它們事後並沒有發病,此乃天然宿主的一大特點。[64]1976-98年期間,共有30,000隻哺乳類、鳥類、爬行類、兩棲類及節肢類動物接受檢驗,惟研究者只在六隻中非共和國囓齒動物彼得鼠英语Peters's mouse非洲柔毛鼠)及一隻鼩鼱動物大森林鼩鼱英语Greater forest shrew)的體內找到過病毒的遺傳痕跡,其他均一無所獲。[65][66]2001及2003年疾病爆發期間,人們在一些大猩猩及黑猩猩的屍體中,發現伊波拉病毒(模式種)的構成物。可此病對靈長動物的殺傷力高,故他們作為天然宿主的機會微乎其微。[65][67]一項於2002-03年、涉及1,030隻動物的實驗顯示,679隻加蓬剛果蝙蝠中的13隻,帶有模式種的核糖核酸片段。[68]專家另也於孟加拉國的果蝠身上,找到針對模式種及雷斯頓種的抗體,故伊波拉病原體亦可能存在於亞洲[69]

傳播途徑[编辑]

準備食用的叢林肉(攝於2013年的加納)。人類進食受污染之野味可感染包括伊波拉出血热在内的多種傳染病。[1]

雖只是一知半解,但專家相信與帶病動物或屍體的直接接觸為指示病例出現之因。除了蝙蝠本身,黑猩猩、大猩猩、羚羊等野生動物,亦可因攝取了曾被蝙蝠啃咬的果實而沾染伊波拉病毒。[70][71]豬隻、狗隻等家畜也有機會攜帶病原體。前者被證實有能力將病毒傳染給非人類的靈長動物,但後者卻並無此說且甚少出現病徵。[72]

病毒絕少直接在天然宿主與人類群體間散播,而是通過首批患者的體液傳染給其他人。[23][73]病毒最常從患者的血液糞便嘔吐物,通過鼻腔口腔傷口進入被感染者的體內。只有重症病人的唾液及大體積的呼吸道分泌物(如飛沫)具傳染性,不慎觸摸則有機會染病。[74]接觸到受病毒污染的醫療器具(特別是針管)亦可致病[62],故照顧伊波拉病人的醫護人員為高危人士[22],特別是他們未有正確穿著保護衣物或沒有妥善處理醫療廢物。伊波拉病毒能在乾燥物件表面生存數小時,若伴隨體液的話則可達數天。[22]院內感染的情況於一些醫療體系較不完善的非洲地區見怪不怪[75],特別是他們重用已進行了皮下注射的針管[76][16]。此烈性病潛伏期短,病發時,患者往往無法自由行動,使之易被警覺,故其在有能力進行完善隔離的醫學發達地區展開大規模流行的機會不大。[77]男性患者的精液在其康復後的7週內仍可攜帶病毒,並有機會透過性交將之傳播;女性病人的乳汁亦然,惟暫不清楚何時方能進行安全餵哺。[1][7]除以上兩種情況外,痊癒者不再具傳染性。[22]

伊波拉病人的屍體同樣可傳播病毒。一些傳統的土葬或遺體保存技術,因涉及觸摸屍體故具一定風險。[78]

目前沒有足夠的證據,顯示伊波拉病毒能通過空氣微粒於人類間傳播。[6][23][62]此傳染模式僅曾在設定了多項條件的猴子實驗裡出現。[79][80]另一項研究證實了豬隻能在不接觸的情況下將病毒傳染給猴子,但未能證明同樣的情況出現於猴子之間。[81]不像豬隻,病毒多滋生於靈長動物的血液裡而非呼吸道表面,故後者無法通過咳嗽、打噴嚏的方式隔空傳播大量的病毒給其他個體。[82]

預防措施[编辑]

美國疾病控制與預防中心制定之預防病毒性出血熱措施。

避免接觸患者及帶病屍體的血液與分泌物、及早隔離及觀察帶病者、具備完善的疾病通報機制為基本的防疫條件。[83][84]

個人衛生保護[编辑]

與今不同,昔日的醫護人員在照顧伊波拉病人時,並不經常穿著保護衣物。
今日穿著全套保護衣物工作的伊波拉病毒研究人員。

醫護與研究人員需嚴格遵守個人保護指引。美國疾病控制與預防中心建議,在照顧病人或處理其排泄物時,應先穿著全套保護衣物(包括:連身型防護衣、口罩、手套、保護鏡),不應暴露身體任何的部分。[84][83][註 2]當局亦提出加強對非洲醫護人員在這一方面的訓練。[85]曾接觸患者分泌物的醫療儀器均需一併消毒[84]西非疫症中,當地兒童獲分配保護裝備及消毒用品,以留在家中照顧患病的家人,解決醫院床位不足的問題。[86]故傳授基本看護知識及保證醫療用品的供應成為了無國界醫生的首要任務。[87]於存有生物危害品實驗室工作的人員,需接受嚴格的個人防疫訓練,並需在適當的設施中操作伊波拉樣本。[88]

高溫或化學消毒法能有效清除伊波拉病毒。持續至少30分鐘的60或5分鐘的100℃高溫可將病毒分解。 一些諸如酒精製品、洗潔精、漂白水(次氯酸鈉)及漂白粉(次氯酸鈣)等的表面清潔劑,在適當的濃度下同樣為有效的消毒用品。[89][90]勤加以清水及肥皂洗手也是有效的防疫措施。[15] 叢林肉易沾染病毒且為人類感染伊波拉出血熱的源頭之一,故有關產物需在徹底煮熟後方能進食,亦不宜赤手觸摸。[1]傳統土葬殯儀涉及屍體觸碰,故應被勸阻或由社會人類學家協助改良。[91][83][84][92]

公共衛生政策[编辑]

適當的公共衛生政策也是重要的一環。截至2014年8月,世衛認為旅遊禁令非為有效之防疫政策[93],但飛機機組人員應按照指引,第一時間隔離並上報任何疑似案例[6]。2014年10月,美國疾病預防中心制定了一套四級制的風險評估,衡量相關赴美人士罹患伊波拉出血熱的機會,以決定是否限制其活動。[94][註 3]隔離檢疫(即強制隔離)將具傳染性的個體與正常人群分隔,能有效阻止伊波拉出血熱的擴散。[95][96][97]接触者追踪英语contact trancing旨在尋找与感染者曾有密切接触的人士,並將之隔離以進行醫學測試及相應治療。[98][99]

流行概況[编辑]

1979-2008年,非洲伊波拉出血熱爆發事件的規模與元兇。

伊波拉出血熱常間歇性地出現於非洲撒哈拉以南的地區,走向風裡楊花。從1976年(人類首次發現此病)至2013年為止,世衛一共公佈了1,716宗確診個案,共24次爆發。[1][9]最具規模的一次流行,為仍肆虐幾內亞塞拉利昂西非疫症

1976年[编辑]

一幀攝於1976年薩伊的照片:一名疾病控制與預防中心的工作人員正焚化伊波拉病患者的醫療廢物。

蘇丹[编辑]

人類史上第一宗伊波拉出血熱確診個案,出現於現在的南蘇丹(當時的蘇丹)一個名為“恩扎拉英语Nzara, South Sudan”的村落。[53][100][101]該病人為當地一家棉織廠的主人。他於6月27日發病,三天后入院,並在7月6日死亡。[4][102]引發此次爆發的元兇,為最終奪取了151人性命(總患病人數為284名)的蘇丹病毒。雖然世衛人員知道他們面對的是一種新型疾病,但在相隔數月後的扎伊爾爆發中,病原體才被深入了解及命名。[102]

扎伊爾[编辑]

同年8月26日,現在的剛果民主共和國(當時的扎伊爾)北部蒙加拉省亚布库村莊,爆發了伊波拉出血熱。[103][104]首名患者是當地一所學校的校長。他早前於8月12至22日期間,到伊波拉河接近中非共和國的邊沿地帶旅行,回家後在8月26日出現病徵。[105]起初,有關衛生所對此病例不以為然,列作瘧疾處理,分配了奎寧作治療藥物。可是,他的病情持續惡化,最終於9月5日被送入當地的教會醫院,至發病後的第14天(即9月8日)病逝。[106][107]多名與這位校長有近距離接觸的人士先後出現病徵,並陸續死亡,全村陷入恐慌。[105][108][109][110]當地衛生局及時任扎伊爾總統的蒙博托·塞塞·塞科宣布,將包括國都金沙薩在內的有關地區劃為檢疫區,禁止外人進入,另對水、陸、空運輸實施戒嚴美國疾病控制與預防中心的研究員彼得·皮奧特英语Peter Piot在視察該地時指出,當地的比利時修女使用了未經徹底消毒的針管為孕婦注射多餘的維他命,無意地促成了這次流行。疾病爆發期間,恩戈伊·莫索拉(Ngoy Mushola)醫生首度為此病作出了臨床描述:“罹患這病的典型特徵為:39或以上的高燒、吐血、便血、胸骨下腹痛、關節“重感”、虛脫及以平均三天的速度死亡。”[111]起先,元兇被誤認為是形態相似的馬爾堡病毒,後發現其乃前所未見的新型種,並與早前的蘇丹爆發有所關聯(時下各種伊波拉病毒尚未被劃分)。專家以位於亞布庫(此病最早的爆發確認點)附近的伊波拉河為依據,將此病原體定名為“伊波拉病毒”。[4][註 4]疾病爆發最終在26天後,因隔離檢疫生效及防疫意識上升而結束,檢疫期為時2週。[113]此次的流行由模式種病毒引起,最終在318位感染者中奪取了280人的性命。[114][115]

1979-2012年[编辑]

2000年伊波拉爆發期間,一個位於烏干達古盧的隔離病房。

伊波拉出血熱在相隔多年後死灰復燃。[116]繼1979年再次侵襲蘇丹後,又在1994年首次出現於加蓬[117],2000年蔓延至烏干達[118]。2003年的剛果共和國爆發錄得了至今最高的伊波拉病死率——143名病患者中的128人死亡(致死率為90%)。[119]模式種及蘇丹種病毒其後間歇性地出現於以上各地。[116]另外,一種名為“本迪布焦病毒”的新型伊波拉病毒,在2007年的西烏干達本迪布焦區爆發中首度亮相。[120][121]

2013-2015年[编辑]

西非[编辑]

西非疫症的受感染及死亡人數隨著時間而不斷上升。

西非疫症乃伊波拉出血熱有史以來最嚴重的一次爆發,亦是該病首次登陸西非。[116][122]一名於2013年12月6日死亡的嬰兒或為是次流行的源頭。[123]疫症一發不可收拾。畿內亞於2014年的3月,由世衛確認出現首宗病例;8月底,疾病已蔓延至尼日利亞塞內加爾[124]同年8月8日,世衛宣布此次爆發為“國際突發性公共衛生事件”,並呼籲各國積極及迅速協助受影響地區。[125][126]相關陸軍封鎖了疫區,防止病毒進一步擴散。[127]8月中旬,無國界醫生表示,利比里亞首都蒙羅維亞的情況為“災難性”及“每況愈下”。當地醫療系統運作癱瘓,工作人員處於恐慌之中,很多罹患其他疾病的人士未能得到及時的看護[128];逾百位醫護人員殉職[129]。世衛於9月26日的報告中總結:“西非伊波拉疫症是人類當代最嚴重且緊急的一次公共衛生危機。即便是其他第四類生物危險品亦沒有如此迅速、持續地感染多個地區的人們。”[130]截至2015年6月29日  (2015-06-29),是次爆發已有27,551宗疑似個案被上報,共11,236宗死亡案例被證實[10][11][12],惟此或低於實際情況[131]

除了人命傷亡,疫症亦造成了經濟損失及社會動盪。《金融時報》一篇報告指出,由疾病引發之資源短缺問題造成了比病毒本身更大的負面影響。[132]數以千計的利比里亞、幾內亞和塞拉利昂居民受到檢疫隔離,長時間缺乏足夠的食物,聯合國世界糧食計劃署採取了相應行動。[128]8月16日,蒙羅維亞西點英语West Point, Monrovia的檢疫隔離中心發生了蘇亂。一群示威者大肆破壞以示對政府及醫護人員的不滿,他們稱此次爆發乃當局的鑿空之論。不少正受醫療監護的病人(連帶沾有鮮血的床上用品)逃脫,為疫情雪上加霜。[133]

刚果民主共和国[编辑]

2014年8至11月期間,剛果民主共和國第七度爆發伊波拉出血熱,地點為赤道省博恩区。疫情最終在世衛及联合国儿童基金会等各方的致力幫助下得到控制。[134]此次爆發與西非疫症無直接關係。[135]

其他地区[编辑]

主條目:美國伊波拉出血熱病例英语Ebola virus cases in the United States英國伊波拉出血熱病例西班牙伊波拉出血熱病例英语Ebola virus disease in Spain

受到西非疫症的影響,其他地區亦相繼出現零星個案。英國有一名護士染病,後在倫敦皇家自由醫院英语Royal Free Hospital的高危隔離病房英语Isolation ward接受診治,並成功康復。[136]美國西班牙分別出現四宗(其中一人死亡)及一宗的境外移入案例,患者均為醫護人員。在嚴格的醫療監控下,病毒沒有進一步擴散。[137]

社會文化議題[编辑]

生物武器[编辑]

伊波拉病毒屬的所有成員均被歸入第四類生物危險品美國疾病預防控制中心的甲級生物恐怖主義範疇[24][138];此類病毒具備成為生物武器的潛能[139][140],但因無法長久逗留於空氣中而難以成為大規模殺傷性武器[141]。不過,前蘇聯生化武器研究部副主任肯·阿里貝克英语Ken Alibek相信,伊波拉能與天花結合,成為一種具有大殺傷力及高傳染性的基因重組病毒英语Recombinant virus[142]

大眾文化[编辑]

過去數十年來,多部暢銷小說及電影著作均以伊波拉出血熱為題,以戲劇化或寫實的方式敘述不同年份的爆發。[143][144][145]西非疫症期間,多部以電子或印刷書籍形式對外發表的私人著作,含有誤導成分。世衛及聯合國批評有關資訊助長了疾病的流行。[146]

深入伊波拉疫區工作的医护人員,獲美国《时代杂志》评为2014“年度风云人物”。[147]

其他動物[编辑]

科學家自本世紀初起,密切監察着其他動物的疫情,希望能盡量預防人類感染個案。[148]

靈長類動物[编辑]

伊波拉病毒對其他靈長動物同樣致命。[149]2002至2003年间,在一个名為“Lossi”的保育區,伊波拉疫症使每420平方公里的黑猩猩跟踪率下降了88%。[150]這些動物染病的主因是進食了受污染的肉類,而非為相互觸摸或觸碰到屍體。[151]雷斯頓病毒於初次亮相時,奪取了不少實驗室猴子的性命。1989年末,隸屬黑澤爾頓科研產品公司(Hazelton Research Products)的雷斯頓英语Reston, Virginia檢疫區中,一群由菲律賓運來的食蟹獼猴罹患神秘致命疾病,並被誤診為感染猴出血熱病毒英语Simian hemorrhagic fever virus。動物病理學家後將活組織樣本,寄給了位於馬里蘭德特里克堡英语Fort Detrick美國陸軍傳染病醫學研究所英语United States Army Medical Research Institute of Infectious Diseases酶聯免疫吸附試驗的結果證實了此樣本含有針對伊波拉病毒的抗體[152],結果與電子顯微鏡映像相乎[153]。尚未因病致死的猴子被人道毀滅,屍體交由德特里克堡的病理及病毒學家研究,最終被安全棄置。[152]178名曾接觸這些猴子的工作人員中,有6位出現血清轉換的現象,但沒有出現病徵。[154][27]最後,研究人員獨立出一種出現於亞洲、名為“雷斯頓病毒”的新型伊波拉病毒種。[152]美國疾病預防控制中心總結,雷斯頓種雖與其他伊波拉病毒共被歸入第四類生物危險品,但它對人類的致病性不高。[155]

其他類別[编辑]

伊波拉病毒也出現於其他種類的動物身上。雷斯頓病毒曾感染了賓夕法尼亞州德克薩斯州意大利的豬隻。[72]雖然一項於2012年進行的實驗證實了這類病毒能在沒有接觸的情況下,從豬擴散至其他靈長動物身上,但該測試無法證明病毒能以同樣的方式,於靈長動物間傳播。[156] 在非洲,狗隻經常進食或含有伊波拉病毒的腐肉,但甚少出現病徵。一項2005年的測試顯示,出現在伊波拉爆發地的狗對模式種病毒的血清陽性率英语Seroprevalence為30%,但處於較遠地區的則為9%。[157]另外,羚羊也是主要的帶病動物。[100]

世衛建議使用次氯酸鈉(即漂白水)或其他適當的清潔劑定期消毒農場,並隔離任何疑似感染個案,以防病毒傳染至其他動物群體。[1]

科研概論[编辑]

研究人員正分析多張用以製造單克隆抗體細胞的映像,以找出最可取的一種。

治療方案[编辑]

目前尚未有安全、可供廣泛使用的伊波拉出血熱治療藥物或預防疫苗,各个方向的科研項目仍在进行之中。

藥物治療[编辑]

多種藥物均具備治療伊波拉出血熱的潛質,當中以抗病毒及抗體藥物為主流的研究對象。獲日本官方批准存貨的法匹拉韋日语ファビピラビル在老鼠身上取得理想成效。[15][158]美國 BioCryst 藥廠研發的廣譜分子“BCX4430”及“Brincidofovir”亦為候選者之一:前者獲美國陸軍傳染病醫學研究所英语United States Army Medical Research Institute of Infectious Diseases承認其動物測試結果[159];而後者則獲美國食物安全中心批准進入臨床試驗程序[160]。一名利比里亞醫生在2014年9月,以本用於抑制愛滋病病毒的藥物拉米夫定輔以抗生素(針對機會性細菌感染)及靜脈注射,治愈了15名伊波拉病人中的13人。[161]由於不肯定因素過多及樣本量太少,病毒學家對此療法表示懷疑;美國國立衛生研究院亦未能於初步體外試驗中證實其功效,但表示會繼續研究。[162]由中國四環醫藥公司及中國軍事醫學院合力研製的“JK-05”據稱已成功通過動物測試,並進入了臨床試驗階段。[163]除此,研究者一叩洪鐘,向其他種類的抗病毒物質著手。[164][165]一些天然化合物(如:“Scytovirin”及“Griffithsin”)[166][167]、合成藥(“DZNep”、“FGI-103”、“FGI-104”、“FGI-106”、“dUY11”與“LJ-001”)[168]、不同組合性生化物質均包括在內[169]。名為“ZMapp”的實驗性、含三種單克隆抗體的藥物於獼猴身上取得成效。[170][171]美國衛生及公共服務部促請多個研究中心加快生產,以備不時之需。[172]泰國研究團隊宣佈成功以病毒合成片段製成了一種抗體藥物。世衛及美國國立衛生研究院已經安排測試,惟此藥物仍有待改進。[173]原用以治療不育及乳癌克羅米芬英语clomiphene托瑞米芬英语Toremifene亦見有效[174],它們分別治愈了90%及50%的實驗白鼠[174]。2014年的一項體外測試發現,用以治療心律失常的粒子通道阻滯藥胺碘酮能阻止伊波拉病毒進入細胞。[175]

其他性質[编辑]

反譯治療英语Antisense therapy的技術同樣獲得關注。針對伊波拉病毒(模式種)的核糖核酸聚合酶L蛋白,短干擾核糖核酸嗎啉基兩種化學物質於其他靈長動物身上起到治療的功效。[176][177]現處於第一临床试验階段的實驗性藥物“TKM-Ebola”便含有短干擾核糖核酸的成分。[170][178]由美國研發的薩雷普塔治療英语Sarepta Therapeutics則已經通過第一期临床试验的階段。[179]

1999年的剛果民主共和國爆發中,有7/8接受實驗的病人被輸入了康復者的血液後痊癒[180],但此治療方法具有爭議性[181]靜脈注射免疫球蛋白獲證實能在非人類靈長動物身上能抵禦伊波拉病毒。[182]

預防疫苗[编辑]

目前仍未研發出人類預防疫苗[1][183][44]去氧核糖核酸疫苗英语DNA vaccination[184]及以提取腺病毒[185]水泡性口膜炎病毒英语Vesicular stomatitis virus[186][187][188]或絲狀病毒粒子[189]而製成的疫苗於其他靈長動物身上見效。[190][191][192]伊波拉刺狀蛋白-腺病毒媒介疫苗在食蟹獼猴身上取得過更快的免疫功效。[185]兩年後,一種伊波拉(或馬爾堡)混合水泡性口膜炎病毒的減毒重組疫苗同樣保護了非人類靈長動物。[193][194][195]2011年12月6日,一種成功在老鼠身上建立抗伊波拉免疫能力的疫苗面世。與眾不同的是,這種新製成品能以冷凍乾燥法長時間儲存,以待疫症的爆發。[196]雖說已有部分疫苗進入了人類測試階段[190],但因受到風險監控而不能與實際的感染情況同日而語[197],故仍未能確定它們的實際功效。

附註[编辑]

  1. ^ 此乃伊波拉河的所在地,即伊波拉出血熱病名之由來。
  2. ^ 美國疾病控制與預防中心製作的防護衣物穿著步驟短片:
  3. ^ 此機制分“高風險(High risk)”、“一般風險(Some risk)”、“低風險(Low [but not zero] risk)”及“無風險(No risk)”四大級別,主要根據個人的旅遊史及健康狀況評定。當局建議處於“低風險”或更高級別的人士,接受為期21天的健康監察;處於“一般風險”的病人或會被實施旅遊及戶外活動限制;“高風險”人士則必須遵從有關限制。[94]
  4. ^ 暫不清楚是以卡爾·約翰遜為首的美國疾病中心的團隊,抑或是有關的比利時研究隊才是最初的命名者(兩者均有獲引述)。[112]

參考文獻[编辑]

註:參考語言以英文為主(除特別指明)。

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