埃博拉病毒病是一种应予通报的疾病。主要治疗方法是早期发现感染,并在医院环境中进行有效隔离和优化支持性治疗。
高病死率可能与埃博拉病毒感染疫情暴发在资源匮乏的农村地区有关,那里可用的支持性治疗有限,反映这些农村地区的患者难以从超负荷医疗保健机构获得基本医疗服务。[18]WHO Ebola Response Team. Ebola virus disease in West Africa: the first 9 months of the epidemic and forward projections. N Engl J Med. 2014 Oct 16;371(16):1481-95.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411100#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25244186?tool=bestpractice.com
[20]Bah EI, Lamah MC, Fletcher T, et al. Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N Engl J Med. 2015 Jan 1;372(1):40-7.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411249#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25372658?tool=bestpractice.com
输入发达国家的病例情况有所不同,在这些国家,病例可得到全面支持性治疗,包括重症监护病房的器官功能支持。[45]Kreuels B, Wichmann D, Emmerich P, et al. A case of severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med. 2014 Dec 18;371(25):2394-401.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411677#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25337633?tool=bestpractice.com
[134]Wolf T, Kann G, Becker S, et al. Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. Lancet. 2015 Apr 11;385(9976):1428-35.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962384-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25534190?tool=bestpractice.com
尽管如此,即使在能够获得最佳支持性治疗的发达国家/地区,由于缺乏证实有效的特异性疗法,也有死亡病例。[107]Lyon GM, Mehta AK, Varkey JB, et al; Emory Serious Communicable Diseases Unit. Clinical care of two patients with Ebola virus disease in the United States. N Engl J Med. 2014 Dec 18;371(25):2402-9.
https://www.nejm.org/doi/full/10.1056/NEJMoa1409838#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25390460?tool=bestpractice.com
[135]Parra JM, Salmerón OJ, Velasco M. The first case of Ebola virus disease acquired outside Africa. N Engl J Med. 2014 Dec 18;371(25):2439-40.
https://www.nejm.org/doi/full/10.1056/NEJMc1412662
http://www.ncbi.nlm.nih.gov/pubmed/25409262?tool=bestpractice.com
[136]Uyeki TM, Mehta AK, Davey RT Jr, et al. Clinical management of Ebola virus disease in the United States and Europe. N Engl J Med. 2016 Feb 18;374(7):636-46.
https://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
对于将预后不良的晚期疾病患者转移至院内感染危险较高的重症监护病房的适宜性,之前曾存在激烈争论。以前认为,若不为疑似的(但未经确诊的)感染患者提供全面的支持性治疗可能会导致给予这些患者标准以下的治疗,这些患者之后可能被诊断为存在可治愈的疾病(例如疟疾)。现在已经清楚,充分的支持性治疗可以降低死亡率,据报告,在西非地区以外治疗的患者,其存活率为 81.5%,所以应尽可能提供支持性治疗。[137]Zacharowski K, Brodt HR, Wolf T. Medical treatment of an Ebola-infected doctor -ethics over costs? Lancet. 2015 Feb 21;385(9969):685.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60279-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25706208?tool=bestpractice.com
[138]Solano T, Gilbert GL, Kerridge IH, et al. Ethical considerations in the management of Ebola virus disease. Med J Aust. 2015 Aug 17;203(4):193-5e.1.
http://www.ncbi.nlm.nih.gov/pubmed/26268293?tool=bestpractice.com
[139]Jacobs M, Beadsworth M, Schmid M, et al. Provision of care for Ebola. Lancet. 2014 Dec 13;384(9960):2105-6.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62250-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25479694?tool=bestpractice.com
在转移至重症监护病房之前和已经转移至重症监护病房的疑似患者,当地医院的诊疗流程指南应考虑如何处理这种情况。[115]Fowler RA, Fletcher T, Fischer WA 2nd, et al. Caring for critically ill patients with Ebola virus disease. Perspectives from West Africa. Am J Respir Crit Care Med. 2014 Oct 1;190(7):733-7.
https://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
[136]Uyeki TM, Mehta AK, Davey RT Jr, et al. Clinical management of Ebola virus disease in the United States and Europe. N Engl J Med. 2016 Feb 18;374(7):636-46.
https://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
[138]Solano T, Gilbert GL, Kerridge IH, et al. Ethical considerations in the management of Ebola virus disease. Med J Aust. 2015 Aug 17;203(4):193-5e.1.
http://www.ncbi.nlm.nih.gov/pubmed/26268293?tool=bestpractice.com
[140]Decker BK, Sevransky JE, Barrett K, et al. Preparing for critical care services to patients with ebola. Ann Intern Med. 2014 Dec 2;161(11):831-2.
https://annals.org/article.aspx?articleid=1910124
http://www.ncbi.nlm.nih.gov/pubmed/25244048?tool=bestpractice.com
[141]Canadian Critical Care Society; Canadian Association of Emergency Physicians; Association of Medical Microbiology and Infectious Diseases of Canada. Ebola clinical care guidelines: a guide for clinicians in Canada. October 2014 [internet publication].
https://www.canadiancriticalcare.org/resources/Pictures/Ebola%20Clinical%20Care%20Guidelines_ENG.pdf
[Figure caption and citation for the preceding image starts]: 西非地区一所埃博拉病毒感染治疗中心的病区(2014)来自 Chris Lane (MSc) 的个人资料收集;经许可后使用 [Citation ends].
感染预防和控制
感染预防和控制(infection prevention and control, IPC)是当务之急,应遵守当地规程。根据病例定义被确定为有感染风险的患者应立即接受隔离,并使用个人防护装备(personal protective equipment, PPE),直到确认或排除感染。
WHO 建议在医疗环境中遵循以下 IPC 原则。[92]World Health Organization. Infection prevention and control guideline for Ebola and Marburg disease. Aug 2023 [internet publication].
https://www.who.int/publications/i/item/WHO-WPE-CRS-HCR-2023.1
在病例管理期间,建议在医疗机构和社区采用感染预防和控制环围方法。
对疑似或确诊感染患者应进行隔离,最好是用单人病房隔离。
应使用酒精洗手液或采用正确方法使用肥皂和流动水洗手,保持手部卫生。
接触疑似病例或确诊病例时,应穿戴适当的 PPE。
应完全覆盖眼、口、鼻黏膜。应使用面罩或护目镜(然后再将头颈部覆盖)。建议使用防液体喷溅的外科口罩或医用口罩,口罩应采用结构化支撑设计(以免口罩塌陷贴附于口部)。如果操作过程中有气溶胶产生,应使用防液体喷溅、防颗粒物呼吸器。
应穿戴好手套、一次性防护服(或工作服)和围裙,其面料经测试可抵御体液或血液传播病原体渗透。首选丁腈手套而非乳胶手套。
具体 PPE 使用要求取决于与患者接触的程度(即,筛查和分诊等间接接触 vs 直接接触病例)。在筛查过程中,如能保证至少 1 米的距离,并严格遵守不接触原则,则无需 PPE。
在为疑似或确诊感染患者提供诊疗的机构和环境中,应对各种表面进行消毒(使用擦拭法)。
为疑似或确诊感染患者提供诊疗时产生的所有废物均应作为传染性废物处理。
应立即对发生职业暴露的医务工作者员进行暴露风险评估,并采取相应的管理措施。
WHO 提供了更详细的 IPC 指导:
[Figure caption and citation for the preceding image starts]: 世界卫生组织(WHO)应对埃博拉指南中的主要感染防控措施Willet V et al. BMJ 2024; 384 :p2811 doi:10.1136/bmj.p2811; 获准使用 [Citation ends].
CDC 也提供了相关指导:
应根据当地和国家治疗方案采集和运送标本,以进行实验室检查(例如埃博拉病毒 RT-PCR、全血细胞计数、血清肌酐和尿素、肝功能检查、动脉血气、凝血功能检查、血培养和针对其他疾病 [例如疟疾] 的检查)。明智选择检查项目对降低实验室工作人员和其他医疗保健工作人员面临的传播风险至关重要。在患者住院早期给予中心静脉置管(如果可能)有助于采集血液和输液,同时最大限度地降低针刺伤风险。[142]Rees PS, Lamb LE, Nicholson-Roberts TC, et al. Safety and feasibility of a strategy of early central venous catheter insertion in a deployed UK military Ebola virus disease treatment unit. Intensive Care Med. 22015 May;41(5):735-43.
http://www.ncbi.nlm.nih.gov/pubmed/25761540?tool=bestpractice.com
WHO 和 CDC 制定了详细的标本采集指导:
优化支持性治疗
推荐对所有患者给予个体化的优化支持性治疗。[143]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
[144]Centers for Disease Control and Prevention. Clinical guidance for Ebola disease. May 2024 [internet publication].
https://www.cdc.gov/ebola/hcp/clinical-guidance
患者的系统性评估和再评估
评估生命体征、体格检查、容量状态和实验室监测。记录临床或实验室参数改变或异常,并作出应对。
有并发症高风险的患者:至少每 4 小时评估一次。推荐人员配比为,一名医生对最多两名患者。
无并发症高风险的患者:至少每 24 小时评估 3 次(每 8 小时一次)。推荐人员配比为,一名医生对最多四名患者。
在住院时以及住院后,每日评估患者躯体、社会、心理和精神方面的健康状况。
液体复苏
电解质监测和纠正
血糖监测和管理
混合感染患者管理
营养学
对症治疗
并发症的预防和处理
每名患者每日均应采用合适的检查表进行系统性评估。可从 WHO 获取检查表示例。[143]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
关于处理原则的更多信息详见下文。
WHO: optimized supportive care for Ebola virus disease
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补液和补充电解质
呕吐和腹泻频发意味着患者处于脱水和低血容量状态,尤其是在就诊延迟的情况下。这可能是埃博拉病毒感染疫情暴发期间病死率高的原因,因为基本临床监测(即体温、呼吸频率、脉率、血压和液体输入量/排出量)至关重要,但是在资源匮乏的地区往往难以进行基本临床监测。
对于可耐受口服给药且脱水不严重的患者,可以使用口服补液溶液,但大多数患者需要静脉补液,可使用生理盐水或乳酸林格氏液。[20]Bah EI, Lamah MC, Fletcher T, et al. Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N Engl J Med. 2015 Jan 1;372(1):40-7.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411249#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25372658?tool=bestpractice.com
[94]Hunt L, Gupta-Wright A, Simms V, et al. Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study. Lancet Infect Dis. 2015 Nov;15(11):1292-9.
http://www.ncbi.nlm.nih.gov/pubmed/26271406?tool=bestpractice.com
[Figure caption and citation for the preceding image starts]: 西非地区一所埃博拉病毒感染治疗中心提供的口服补液溶液(2014 年)来自 Chris Lane (MSc) 的个人资料收集;经许可后使用 [Citation ends].[Figure caption and citation for the preceding image starts]: 为一名成年埃博拉病毒病患者进行静脉置管(西非)来自 Tom E. Fletcher (MBE, MBChB, MRCP, DTM&H) 收集的资料;经许可后使用 [Citation ends].
有低灌注的标志性表现时可能提示口服液体不良或不充分,患者应立即转为静脉输注。可选择的路径有周围或中心静脉输注、或骨髓腔内输注。[145]Lamontagne F, Fowler RA, Adhikari NK, et al. Evidence-based guidelines for supportive care of patients with Ebola virus disease. Lancet. 2018 Feb 17;391(10121):700-8.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31795-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29054555?tool=bestpractice.com
应根据临床检查情况(例如脱水程度和休克体征)和液体损失量(例如腹泻和/或呕吐量)评估所需的静脉输液量。具有腹泻症状的发热患者可能需要大量补液(高达 10 L/天)。[45]Kreuels B, Wichmann D, Emmerich P, et al. A case of severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med. 2014 Dec 18;371(25):2394-401.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411677#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25337633?tool=bestpractice.com
[146]Perner A, Fowler R, Bellomo R, et al. Ebola care and research protocols. Intensive Care Med. 2015 Jan;41(1):111-4.
http://www.ncbi.nlm.nih.gov/pubmed/25427868?tool=bestpractice.com
[147]Roberts I, Perner A. Ebola virus disease: clinical care and patient-centred research. Lancet. 2014 Dec 6;384(9959):2001-2.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962316-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25483156?tool=bestpractice.com
可能还需要大量补充钾(例如每小时 5-10 mmol/L [5-10 mEq/L] 氯化钾)。[22]Schieffelin JS, Shaffer JG, Goba A, et al; KGH Lassa Fever Program; Viral Hemorrhagic Fever Consortium; WHO Clinical Response Team. Clinical illness and outcomes in patients with Ebola in Sierra Leone. N Engl J Med. 2014 Nov 27;371(22):2092-100.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411680#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25353969?tool=bestpractice.com
[134]Wolf T, Kann G, Becker S, et al. Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. Lancet. 2015 Apr 11;385(9976):1428-35.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962384-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25534190?tool=bestpractice.com
[148]Clay KA, Johnston AM, Moore A, et al. Targeted electrolyte replacement in patients with Ebola virus disease. Clin Infect Dis. 2015 Sep 15;61(6):1030-1.
http://www.ncbi.nlm.nih.gov/pubmed/26056238?tool=bestpractice.com
必须严密监督和频繁监测患者情况,因这对于评价患者对治疗的反应和预防容量超负荷非常重要。应频繁检查患者是否有休克、脱水或水中毒的体征,并相应地对输液速度做出调整。必须每天对生命体征(如心率、血压、尿量、胃肠道液体的丧失)和容量状态进行至少三次的系统性监测,以发现低血容量。[145]Lamontagne F, Fowler RA, Adhikari NK, et al. Evidence-based guidelines for supportive care of patients with Ebola virus disease. Lancet. 2018 Feb 17;391(10121):700-8.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31795-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29054555?tool=bestpractice.com
口服洛哌丁胺可能有助于缓解严重腹泻,但需要进一步的证据以确定口服洛哌丁胺的疗效,世界卫生组织目前并不建议使用口服洛哌丁胺。[149]World Health Organization. Manual for the care and management of patients in Ebola care units/community care centres: interim emergency guidance. January 2015 [internet publication].
https://www.who.int/publications/i/item/manual-for-the-care-and-management-of-patients-in-ebola-care-units-community-care-centres
[150]Kendall RE, Gosser RA, Schulz LT, et al. Anti-diarrheal medication use in the treatment of Ebola virus-induced diarrhea. Travel Med Infect Dis. 2015 Mar-Apr;13(2):205-6.
http://www.ncbi.nlm.nih.gov/pubmed/25682446?tool=bestpractice.com
[151]Chertow DS, Uyeki TM, DuPont HL. Loperamide therapy for voluminous diarrhea in Ebola virus disease. J Infect Dis. 2015 Apr 1;211(7):1036-7.
https://jid.oxfordjournals.org/content/early/2015/02/04/infdis.jiv001.long
http://www.ncbi.nlm.nih.gov/pubmed/25573887?tool=bestpractice.com
[152]World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Feb 2016 [internet publication].
https://apps.who.int/iris/bitstream/10665/205570/1/9789241549608_eng.pdf?ua=1
隔离设施内现场备有床旁诊断化验,有助于更有效地监测患者的生化状态,并减少与标本运送相关的风险。[115]Fowler RA, Fletcher T, Fischer WA 2nd, et al. Caring for critically ill patients with Ebola virus disease. Perspectives from West Africa. Am J Respir Crit Care Med. 2014 Oct 1;190(7):733-7.
https://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
应每天进行电解质监测,必要时充分给予。[20]Bah EI, Lamah MC, Fletcher T, et al. Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N Engl J Med. 2015 Jan 1;372(1):40-7.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411249#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25372658?tool=bestpractice.com
如果正在进行大量静脉输液,或者出现严重的生化异常,可以考虑提高监测频率。血乳酸水平高是低灌注的可靠指标,有助于指导进行液体复苏。[115]Fowler RA, Fletcher T, Fischer WA 2nd, et al. Caring for critically ill patients with Ebola virus disease. Perspectives from West Africa. Am J Respir Crit Care Med. 2014 Oct 1;190(7):733-7.
https://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
应参阅世界卫生组织的相关指南,以了解有关液体和电解质管理,以及急性期和康复期维持营养充足的具体建议。
WHO: optimized supportive care for Ebola virus disease
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WHO: manual for the care and management of patients in Ebola care units/community care centres - interim emergency guidance
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WHO: clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker
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症状管理
发热和疼痛:
胃肠道症状:
2014 年西非疫情暴发时,粪便管理系统在严重腹泻患者中的应用非常成功。其耐受性良好,且可预防医务工作者的感染以及有益于感染控制。[117]Dickson SJ, Clay KA, Adam M, et al. Enhanced case management can be delivered for patients with EVD in Africa: experience from a UK military Ebola treatment centre in Sierra Leone. J Infect. 2018 Apr;76(4):383-92.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903873
http://www.ncbi.nlm.nih.gov/pubmed/29248587?tool=bestpractice.com
烧心症状/吞咽困难/腹痛:
癫痫发作:
激越:
呼吸窘迫:
某些患者可能需要建立骨内通路。[Figure caption and citation for the preceding image starts]: 为一名危重的成年埃博拉病毒病患者插入骨内管路(西非)来自 Tom E. Fletcher (MBE, MBChB, MRCP, DTM&H) 收集的资料;经许可后使用 [Citation ends].
显著出血
大出血不常发生,但却是严重感染的表现,严重感染通常为致死性,但并非每次都是致命的。
若条件允许,应根据当地政策给予新鲜全血或血小板和血浆,并由临床指标和实验室(若有条件的话)指标(如血红蛋白、红细胞比容、国际标准化比值)指导后续治疗。[152]World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Feb 2016 [internet publication].
https://apps.who.int/iris/bitstream/10665/205570/1/9789241549608_eng.pdf?ua=1
[154]Wada H, Thachil J, Di Nisio M, et al. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemost. 2013 Feb 4;11(4):761-7.
https://onlinelibrary.wiley.com/doi/10.1111/jth.12155/full
http://www.ncbi.nlm.nih.gov/pubmed/23379279?tool=bestpractice.com
[155]Warren T, Jordan R, Lo M, et al. Nucleotide prodrug GS-5734 is a broad-spectrum Filovirus inhibitor that provides complete therapeutic protection against the development of Ebola Virus Disease (EVD) in infected non-human primates. Late breaker abstract 2. Presented at IDWeek. San Diego, 2015.
https://idsa.confex.com/idsa/2015/webprogram/Paper54208.html
对于正在出血的患者,使用维生素 K、氨甲环酸或质子泵抑制剂(用于消化道出血)是合理的治疗选择。[143]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
[152]World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Feb 2016 [internet publication].
https://apps.who.int/iris/bitstream/10665/205570/1/9789241549608_eng.pdf?ua=1
器官功能障碍
多器官功能障碍是晚期感染的常见症状,包括急性肾损伤、胰腺炎、肾上腺衰竭和肝损伤。肝损伤(例如肝炎)常见;然而,黄疸并不常见。[69]Fletcher T, Fowler RA, Beeching NJ. Understanding organ dysfunction in Ebola virus disease. Intensive Care Med. 2014 Dec;40(12):1936-9.
http://www.ncbi.nlm.nih.gov/pubmed/25366120?tool=bestpractice.com
肾功能障碍常见,但是在初期阶段通过使用足量液体复苏可逆转肾功能障碍。[69]Fletcher T, Fowler RA, Beeching NJ. Understanding organ dysfunction in Ebola virus disease. Intensive Care Med. 2014 Dec;40(12):1936-9.
http://www.ncbi.nlm.nih.gov/pubmed/25366120?tool=bestpractice.com
在对液体复苏无反应的无尿患者中,已经在应用肾替代疗法,但没有任何试验数据支持这种干预的有效性。在欧洲和北美 5 名多器官衰竭的重症患者接受了有创机械通气和肾脏替代治疗,其中有 3 例患者死亡。[45]Kreuels B, Wichmann D, Emmerich P, et al. A case of severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med. 2014 Dec 18;371(25):2394-401.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411677#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25337633?tool=bestpractice.com
[107]Lyon GM, Mehta AK, Varkey JB, et al; Emory Serious Communicable Diseases Unit. Clinical care of two patients with Ebola virus disease in the United States. N Engl J Med. 2014 Dec 18;371(25):2402-9.
https://www.nejm.org/doi/full/10.1056/NEJMoa1409838#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25390460?tool=bestpractice.com
[134]Wolf T, Kann G, Becker S, et al. Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. Lancet. 2015 Apr 11;385(9976):1428-35.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962384-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25534190?tool=bestpractice.com
[136]Uyeki TM, Mehta AK, Davey RT Jr, et al. Clinical management of Ebola virus disease in the United States and Europe. N Engl J Med. 2016 Feb 18;374(7):636-46.
https://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
[156]Connor MJ Jr, Kraft C, Mehta AK, et al. Successful delivery of RRT in Ebola virus disease. J Am Soc Nephrol. 2015 Jan;26(1):31-7.
http://www.ncbi.nlm.nih.gov/pubmed/25398785?tool=bestpractice.com
输注源自康复期患者的全血或血浆
来自以往埃博拉病毒感染疫情暴发期间的有限证据表明,在急性感染期,输注康复患者的血液可能使患者受益,并可能降低病死率。[6]Roddy P, Howard N, Van Kerkhove MD, et al. Clinical manifestations and case management of Ebola haemorrhagic fever caused by a newly identified virus strain, Bundibugyo, Uganda, 2007-2008. PLoS One. 2012 Dec 28;7(12):e52986.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0052986
http://www.ncbi.nlm.nih.gov/pubmed/23285243?tool=bestpractice.com
[157]World Health Organization. Interim guidance: potential Ebola therapies and vaccines. Nov 2014 [internet publication].
https://apps.who.int/iris/bitstream/10665/137590/1/WHO_EVD_HIS_EMP_14.1_eng.pdf?ua=1
与使用全血相比,使用康复期患者血浆很可能更切实可行且更有效。[158]Kreil TR. Treatment of Ebola virus infection with antibodies from reconvalescent donors. Emerg Infect Dis. 2015 Mar;21(3):521-3.
https://wwwnc.cdc.gov/eid/article/21/3/14-1838_article
http://www.ncbi.nlm.nih.gov/pubmed/25695274?tool=bestpractice.com
[159]Gutfraind A, Myers LA. Evaluating large-scale blood transfusion therapy for the current Ebola epidemic in Liberia. J Infect Dis. 22015 Apr 15;211(8):1262-7.
https://jid.oxfordjournals.org/content/211/8/1262
http://www.ncbi.nlm.nih.gov/pubmed/25635118?tool=bestpractice.com
世界卫生组织制定了有关使用康复患者血液/血浆的临时指南。在几内亚进行的临床试验中,未能证实接受康复者血浆治疗的患者可以获得生存获益,尽管该治疗似乎是安全的,且无严重并发症的记录。[160]van Griensven J, Edwards T, de Lamballerie X, et al. Evaluation of convalescent plasma for Ebola virus disease in Guinea. N Engl J Med. 2016 Jan 7;374(1):33-42.
https://www.nejm.org/doi/full/10.1056/NEJMoa1511812#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26735992?tool=bestpractice.com
[161]van Griensven J, De Weiggheleire A, Delamou A, et al. The use of Ebola convalescent plasma to treat Ebola virus disease in resource-constrained settings: a perspective from the field. Clin Infect Dis. 2016 Jan 1;62(1):69-74.
https://academic.oup.com/cid/article/62/1/69/2462604/The-Use-of-Ebola-Convalescent-Plasma-to-Treat
http://www.ncbi.nlm.nih.gov/pubmed/26261205?tool=bestpractice.com
WHO: use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an empirical treatment during outbreaks
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WHO: ethics of using convalescent whole blood and convalescent plasma during the Ebola epidemic
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抗病毒治疗
现已有治疗性抗病毒单克隆抗体可用。WHO 强烈建议将 atoltivimab/maftivimab/odesivimab(也称为 REGN-EB3)或 ansuvimab(也称为 mAb114)用于确诊的埃博拉病毒(扎伊尔型正埃博拉病毒)感染患者,以及确诊埃博拉病毒(扎伊尔型正埃博拉病毒)感染母亲所生的未确诊感染的≤7 日龄新生儿。[162]World Health Organization. Therapeutics for Ebola virus disease - Democratic Republic of the Congo. Aug 2022 [internet publication].
https://www.who.int/publications/i/item/9789240055742
atoltivimab/maftivimab/odesivimab
在 PALM 试验中得到评价,该试验是一项多中心、开放标签、随机对照试验,2018 年暴发期间,是在刚果民主共和国(Democratic Republic of the Congo, DRC)开展的一项扩展供药计划的一部分。此试验的主要疗效终点为 28 天死亡率。在接受 atoltivimab/maftivimab/odesivimab 治疗的患者中,28 天死亡率为 33.5%,对照组(ZMapp)为 51%。[163]Mulangu S, Dodd LE, Davey RT Jr, et al. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med. 2019 Dec 12;381(24):2293-303.
https://www.doi.org/10.1056/NEJMoa1910993
http://www.ncbi.nlm.nih.gov/pubmed/31774950?tool=bestpractice.com
ansuvimab
一种靶向埃博拉病毒(扎伊尔型正埃博拉病毒)糖蛋白的人 IgG1 单克隆抗体。它是由 1995 年基奎特(刚果民主共和国)疫情暴发中人类存活者分离得来,由美国国立卫生研究院研制。
FDA 批准其用于治疗埃博拉病毒(扎伊尔型正埃博拉病毒)感染的成人和儿童患者。[144]Centers for Disease Control and Prevention. Clinical guidance for Ebola disease. May 2024 [internet publication].
https://www.cdc.gov/ebola/hcp/clinical-guidance
PALM 试验发现,在降低死亡率方面,ansuvimab 优于ZMapp(请参阅新兴治疗章节)。接受 ansuvimab 治疗的患者中,28 天死亡率为 35.1%,对照组(ZMapp)则为 49.7%。[163]Mulangu S, Dodd LE, Davey RT Jr, et al. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med. 2019 Dec 12;381(24):2293-303.
https://www.doi.org/10.1056/NEJMoa1910993
http://www.ncbi.nlm.nih.gov/pubmed/31774950?tool=bestpractice.com
与标准治疗、ZMapp 和 remdesivir 相比,atoltivimab/maftivimab/odesivimab 和 ansuvimab 可能降低死亡率(中等确定性证据)。然而,它们可能对病毒清除所需时间影响很小或没有影响。尚不确定它们是否会增加严重不良事件的风险。[162]World Health Organization. Therapeutics for Ebola virus disease - Democratic Republic of the Congo. Aug 2022 [internet publication].
https://www.who.int/publications/i/item/9789240055742
[164]Gao Y, Zhao Y, Guyatt G, et al. Effects of therapies for Ebola virus disease: a systematic review and network meta-analysis. Lancet Microbe. 2022 Sep;3(9):e683-92.
https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(22)00123-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/35803293?tool=bestpractice.com
尚未确定其用于其他正埃博拉病毒种的效果。
这些治疗不得同时使用,应视为彼此的替代选择。两种治疗均为单次静脉输注给药,应在确诊后尽快给药。它们可用于老年人、孕妇和哺乳期女性以及儿童和新生儿。在世界许多地区,获得这些治疗药物具有挑战,选择取决于可得性。在疾病暴发期间,可能需要在同情用药框架下使用。
合并疟疾感染
应检查是否发生疟疾,发生疟疾时应给予适当的抗疟治疗,同时应谨记患者存在埃博拉病毒病风险和双重感染的可能性。在流行区,常规治疗方案通常包括抗疟治疗(不论是否确诊此类感染)。给予经验性抗生素治疗,直至疟疾检测呈阴性或完成疗程。[143]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
孕妇
2014-2020 年疫情暴发中,几乎所有孕妇都有不良妊娠结局,但妊娠患者的死亡率并未高于非妊娠患者。[165]Foeller ME, Carvalho Ribeiro do Valle C, Foeller TM, et al. Pregnancy and breastfeeding in the context of Ebola: a systematic review. Lancet Infect Dis. 2020 Jul;20(7):e149-58.
https://www.doi.org/10.1016/S1473-3099(20)30194-8
http://www.ncbi.nlm.nih.gov/pubmed/32595045?tool=bestpractice.com
然而,在既往暴发中,报道的孕妇患者病死率高于非妊娠女性。[166]Mupapa K, Mukundu W, Bwaka MA, et al. Ebola hemorrhagic fever and pregnancy. J Infect Dis. 1999 Feb;179 Suppl 1:S11-2.
https://jid.oxfordjournals.org/content/179/Supplement_1/S11.long
http://www.ncbi.nlm.nih.gov/pubmed/9988157?tool=bestpractice.com
2014 年埃博拉疫情暴发期间的经验表明,偶尔可以获得良好的结局。[167]Baggi FM, Taybi A, Kurth A, et al. Management of pregnant women infected with Ebola virus in a treatment centre in Guinea, June 2014. Euro Surveill. 2014 Dec 11;19(49):20983.
https://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20983
http://www.ncbi.nlm.nih.gov/pubmed/25523968?tool=bestpractice.com
未接受实验性用药或同情性用药的孕妇,有非常高的自然流产、死胎或新生儿死亡风险。产时出血和自然流产较为常见;因此,产科管理应注重监测,并及早治疗出血性并发症。[21]Chertow DS, Kleine C, Edwards JK, et al. Ebola virus disease in West Africa - clinical manifestations and management. N Engl J Med. 2014 Nov 27;371(22):2054-7.
https://www.nejm.org/doi/full/10.1056/NEJMp1413084
http://www.ncbi.nlm.nih.gov/pubmed/25372854?tool=bestpractice.com
[166]Mupapa K, Mukundu W, Bwaka MA, et al. Ebola hemorrhagic fever and pregnancy. J Infect Dis. 1999 Feb;179 Suppl 1:S11-2.
https://jid.oxfordjournals.org/content/179/Supplement_1/S11.long
http://www.ncbi.nlm.nih.gov/pubmed/9988157?tool=bestpractice.com
[168]Jamieson DJ, Uyeki TM, Callaghan WM, et al. What obstetrician-gynecologists should know about Ebola: a perspective from the Centers for Disease Control and Prevention. Obstet Gynecol. 2014 Nov;124(5):1005-10.
http://www.ncbi.nlm.nih.gov/pubmed/25203368?tool=bestpractice.com
[169]Association of Women's Health, Obstetric and Neonatal Nurses. Ebola: caring for pregnant and postpartum women and newborns in the United States: AWHONN practice brief number 3. J Obstet Gynecol Neonat Nurs. 2015 Jan-Feb;44(1):164-5
https://onlinelibrary.wiley.com/doi/10.1111/1552-6909.12518/full
http://www.ncbi.nlm.nih.gov/pubmed/25421426?tool=bestpractice.com
[170]Kitching A, Walsh A, Morgan D. Ebola in pregnancy: risk and clinical outcomes. BJOG. 2015 Feb;122(3):287.
http://www.ncbi.nlm.nih.gov/pubmed/25585496?tool=bestpractice.com
WHO 推荐以下主要管理原则:
同时使用标准预防措施和针对埃博拉病毒感染的防控措施。
所有孕妇的临床治疗包括优化支持性治疗。
在严谨研究背景下或者依照当地规程,可给予孕妇 atoltivimab/maftivimab/odesivimab 和 ansuvimab;然而,此推荐的证据基础较弱。
对于急性感染孕妇,不应由于胎儿指征而进行引产或实施有创操作。
疑似或确诊急性感染的女性,建议不哺乳,直至相隔 24 小时的两次母乳检测(逆转录聚合酶链反应 [reverse-transcription polymerase chain reaction, RT-PCR] 检测)结果呈阴性。同时,婴儿应与母体分离,并给予合适的母乳替代物。
CDC 已发布孕妇和新生儿诊疗特定指南。
儿童
儿童应交由具有儿科专业知识的医护人员进行治疗。非流行区的儿童治疗规划非常复杂,提倡重症监护医生在切实可行的情况下尽早参与治疗。[171]Olupot-Olupot P. Ebola in children: epidemiology, clinical features, diagnosis and outcomes. Pediatr Infect Dis J. 2015 Mar;34(3):314-6.
http://www.ncbi.nlm.nih.gov/pubmed/25522340?tool=bestpractice.com
[172]Herberg JA, Emonts M, Jacobs M, et al. UK preparedness for children with Ebola infection. Arch Dis Child. 2015 May;100(5):421-3.
http://www.ncbi.nlm.nih.gov/pubmed/25694613?tool=bestpractice.com
[173]Eriksson CO, Uyeki TM, Christian MD, et al. Care of the child with Ebola virus disease. Pediatr Crit Care Med. 2015 Feb;16(2):97-103.
http://www.ncbi.nlm.nih.gov/pubmed/25647119?tool=bestpractice.com
与家人的联络
患者在医院被隔离可对其心理健康产生影响,包括抑郁、焦虑、愤怒、恐惧和孤独感的增加。医务工作者应协助患者与家人和朋友的联络(例如,利用移动电话或网络),以期在不增加感染风险的前提下降低患者的心理困扰。[145]Lamontagne F, Fowler RA, Adhikari NK, et al. Evidence-based guidelines for supportive care of patients with Ebola virus disease. Lancet. 2018 Feb 17;391(10121):700-8.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31795-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29054555?tool=bestpractice.com