支持性治疗
对疑似马尔堡病毒病的患者与其他感染性、出血性疾病或其他疾病患者进行正确分诊存在较大难度,但在疾病暴发和病例隔离的情况下,是关键的第一步。一旦诊断疑似马尔堡病毒病或其他病毒性出血热,则患者隔离是预防院内传播关键的第一步。[23]Centers for Disease Control and Prevention. Marburg (Marburg virus disease). Jun 2023 [internet publication].
https://www.cdc.gov/vhf/marburg
目前尚无针对马尔堡病毒感染的特异性治疗。早期积极的支持性治疗是管理的主要手段。[4]Bebell LM, Riley LE. Ebola virus disease and Marburg disease in pregnancy: a review and management considerations for filovirus infection. Obstet Gynecol. 2015 Jun;125(6):1293-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443859
http://www.ncbi.nlm.nih.gov/pubmed/26000499?tool=bestpractice.com
[23]Centers for Disease Control and Prevention. Marburg (Marburg virus disease). Jun 2023 [internet publication].
https://www.cdc.gov/vhf/marburg
在资源允许的情况下,应将疑似马尔堡病毒病的患者收入重症监护病房或其他密切监测的隔离病床。[32]Leligdowicz A, Fischer WA 2nd, Uyeki TM, et al. Ebola virus disease and critical illness. Crit Care. 2016 Jul 29;20(1):217.
http://ccforum.biomedcentral.com/articles/10.1186/s13054-016-1325-2
http://www.ncbi.nlm.nih.gov/pubmed/27468829?tool=bestpractice.com
总体而言,尽管纤丝病毒感染患者与其他类型的脓毒症患者在疾病发病机制和临床病程方面存在明显差异,但可根据重症脓毒症或登革热管理指南进行治疗。[41]Deen J, Dondorp AM, White NJ. Treatment of Ebola. N Engl J Med. 2015 Apr 23;372(17):1673-4.
http://www.ncbi.nlm.nih.gov/pubmed/25901440?tool=bestpractice.com
[42]Clark DV, Jahrling PB, Lawler JV. Clinical management of filovirus-infected patients. Viruses. 2012 Sep;4(9):1668-86.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499825
http://www.ncbi.nlm.nih.gov/pubmed/23170178?tool=bestpractice.com
一旦诊断为疑似马尔堡病毒病,并开始隔离,医务人员就应立即穿戴全套个人防护用品 (PPE),使用具有防腐剂涂层的非肝素抗凝采血管采集 4 mL 全血,并立即将其冷藏或冷冻,以便运往参考实验室。在北美和欧洲以外地区,使用逆转录酶聚合酶链反应 (reverse transcriptase polymerase chain reaction, RT-PCR) 血液检测或口腔拭子来发现马尔堡病毒 RNA。[43]Kurosaki Y, Magassouba N, Oloniniyi OK, et al. Development and evaluation of reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay coupled with a portable device for rapid diagnosis of Ebola virus disease in Guinea. PLoS Negl Trop Dis. 2016 Feb 22;10(2):e0004472.
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004472
http://www.ncbi.nlm.nih.gov/pubmed/26900929?tool=bestpractice.com
这些检查可能在几小时内或几天内返回结果,具体取决于使用当地实验室,还是参考实验室。此时,医务人员应考虑小心置入中心静脉导管(如可能)或放置多个外周静脉导管,以获得良好的静脉通路。[33]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.
http://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
获得静脉通路后,如果可能,应尽快送检血液,以进行针对可能的鉴别诊断的实验室检查、疟疾检查、全血细胞计数、肾功能和电解质检查以及血乳酸水平检测。[33]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.
http://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
[44]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
初始生命体征应指导初始治疗。液体复苏是主要的支持性治疗,对于胃肠道容量显著丢失的患者,可能需要大量补液,并严格关注对持续体液丢失的补充。[4]Bebell LM, Riley LE. Ebola virus disease and Marburg disease in pregnancy: a review and management considerations for filovirus infection. Obstet Gynecol. 2015 Jun;125(6):1293-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443859
http://www.ncbi.nlm.nih.gov/pubmed/26000499?tool=bestpractice.com
[32]Leligdowicz A, Fischer WA 2nd, Uyeki TM, et al. Ebola virus disease and critical illness. Crit Care. 2016 Jul 29;20(1):217.
http://ccforum.biomedcentral.com/articles/10.1186/s13054-016-1325-2
http://www.ncbi.nlm.nih.gov/pubmed/27468829?tool=bestpractice.com
[42]Clark DV, Jahrling PB, Lawler JV. Clinical management of filovirus-infected patients. Viruses. 2012 Sep;4(9):1668-86.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499825
http://www.ncbi.nlm.nih.gov/pubmed/23170178?tool=bestpractice.com
成人患者通常需要≥5-10 L/日的静脉补液或口服补液,以在持续胃肠道体液丢失的情况下维持循环血容量。[33]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.
http://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
监测并积极纠正钾水平、酸碱平衡紊乱和其他电解质紊乱,有助于预防危及生命的心律失常和代谢并发症。[33]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.
http://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
应开始使用经验性广谱抗生素(如头孢曲松、环丙沙星或氨苄西林/舒巴坦),以治疗可能发生的肠道细菌移位。[33]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.
http://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
[44]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
对于所有疑似纤丝病毒病患者,推荐基于青蒿琥酯的经验性抗疟治疗,这是因为,接受这些药物治疗的埃博拉病毒感染者的死亡风险比接受其他抗疟治疗患者的死亡风险低 31%。生存期的增加可能是由于对疟疾混合感染的治疗、预防混合感染的措施(特别是在疟疾高发地区),或者甚至可能是其中一些药物对纤丝病毒活性有直接影响。[25]Gignoux E, Azman AS, de Smet M, et al. Effect of artesunate-amodiaquine on mortality related to Ebola virus disease. N Engl J Med. 2016 Jan 7;374(1):23-32.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504605
http://www.ncbi.nlm.nih.gov/pubmed/26735991?tool=bestpractice.com
发热和疼痛的一线治疗为对乙酰氨基酚。治疗更严重的疼痛首选阿片类止痛剂(例如吗啡)。由于相关的出血风险增加和潜在的肾毒性,应避免使用非甾体抗炎药(包括阿司匹林)。[45]World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Feb 2016 [internet publication].
http://apps.who.int/iris/bitstream/10665/205570/1/9789241549608_eng.pdf?ua=1
只要腹泻为非血性,并且未怀疑其他肠道病原体感染,推荐早期使用止吐剂和止泻药进行治疗。[28]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.
http://www.nejm.org/doi/full/10.1056/NEJMp1413084
http://www.ncbi.nlm.nih.gov/pubmed/25372854?tool=bestpractice.com
[33]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.
http://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
[44]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
输注血制品(包括输注血小板、浓缩红细胞,甚至是恢复期捐献者的血浆)可能对患者有获益。[44]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
多器官功能障碍是晚期感染的一种常见特征,可能包括急性肾损伤、胰腺炎、肾上腺功能衰竭和肝损伤。肝损伤(如转氨酶升高)常见;然而,黄疸并非一种常见特征。[13]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
[27]van Paassen J, Bauer MP, Arbous MS, et al. Acute liver failure, multiorgan failure, cerebral oedema, and activation of proangiogenic and antiangiogenic factors in a case of Marburg haemorrhagic fever. Lancet Infect Dis. 2012 Aug;12(8):635-42.
http://www.sciencedirect.com/science/article/pii/S147330991270018X
http://www.ncbi.nlm.nih.gov/pubmed/22394985?tool=bestpractice.com
[46]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
肾功能障碍常见于晚期,但在早期可能通过积极液体复苏逆转。[13]Mehedi M, Groseth A, Feldmann H, et al. Clinical aspects of Marburg hemorrhagic fever. Future Virol. 2011 Sep;6(9):1091-1106.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201746
http://www.ncbi.nlm.nih.gov/pubmed/22046196?tool=bestpractice.com
[46]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
一例对液体复苏无反应的无尿马尔堡病毒病患者接受了肾脏替代治疗,这种干预措施也曾用于治疗重症埃博拉病毒病患者。然而,尚无临床试验数据支持该干预措施的疗效。在欧洲和北美,采用有创机械通气和肾脏替代治疗对 5 例有多器官衰竭的重症埃博拉病毒病的患者进行治疗,其中 3 例死亡。[44]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
[47]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1411677
http://www.ncbi.nlm.nih.gov/pubmed/25337633?tool=bestpractice.com
[48]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1409838
http://www.ncbi.nlm.nih.gov/pubmed/25390460?tool=bestpractice.com
[49]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.
http://www.ncbi.nlm.nih.gov/pubmed/25534190?tool=bestpractice.com
[50]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://jasn.asnjournals.org/content/26/1/31.long
http://www.ncbi.nlm.nih.gov/pubmed/25398785?tool=bestpractice.com
在资源允许的情况下,呼吸支持性治疗可能有用,包括辅助供氧、无创通气或有创机械通气(如果无创通气失败)。[44]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
应尽可能提供全面的支持性治疗,这能够降低纤丝病毒病患者的死亡率:在西非以外地区接受治疗的埃博拉病毒病患者中,报告的存活率为 82%。[44]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
就既往而言,马尔堡病毒病经常致死,以往约有 70%(范围为 23%-100%)的病例死亡。[5]Centers for Disease Control and Prevention. History of Marburg virus disease (MVD) outbreaks. Jun 2023 [internet publication].
https://www.cdc.gov/vhf/marburg/outbreaks/chronology.html
在撒哈拉以南的非洲,马尔堡和埃博拉病毒病患者的高病死率可能与疾病暴发的农村地区资源匮乏、缺乏全面的支持性治疗有关。[51]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1411100
http://www.ncbi.nlm.nih.gov/pubmed/25244186?tool=bestpractice.com
生命体征和临床监测应指导积极的支持性治疗和其他治疗。[28]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.
http://www.nejm.org/doi/full/10.1056/NEJMp1413084
http://www.ncbi.nlm.nih.gov/pubmed/25372854?tool=bestpractice.com
[33]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.
http://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
[44]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
对于发生低血压的患者,应根据需要给予升压药支持性治疗。[28]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.
http://www.nejm.org/doi/full/10.1056/NEJMp1413084
http://www.ncbi.nlm.nih.gov/pubmed/25372854?tool=bestpractice.com
[33]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.
http://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
[44]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
应考虑使用维生素 K 改善凝血障碍,对发生出血的患者,也可给予该药。[28]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.
http://www.nejm.org/doi/full/10.1056/NEJMp1413084
http://www.ncbi.nlm.nih.gov/pubmed/25372854?tool=bestpractice.com
[33]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.
http://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
[44]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
当血小板或纤维蛋白原水平较低时,输注血小板和冷沉淀也可能有帮助。[28]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.
http://www.nejm.org/doi/full/10.1056/NEJMp1413084
http://www.ncbi.nlm.nih.gov/pubmed/25372854?tool=bestpractice.com
[33]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.
http://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
[44]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
应当注意的是,针对纤丝病毒病的治疗推荐基于治疗暴发期间患者的临床经验,并且循证指南有限。