预后
埃博拉病毒感染的自然临床病程因病毒种属和支持性医疗保健水平的不同而存在显著差异。最致命的种属是扎伊尔型埃博拉病毒,据报道病死率高达 90%。在 2014 年西非的大暴发中,大多数治疗中心的平均病死率约为 50%,但在过去其他的暴发事件中,病死率的范围为 25%-90%,[2]World Health Organization. Ebola virus disease fact sheet. Feb 2020 [internet publication]. https://www.who.int/mediacentre/factsheets/fs103/en 大多数疾病流行发生在资源匮乏的地区,这些地区所能获得的支持性治疗极少;因此,其他机构的病死率可能<40%。[112]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
更年幼的儿童(<5 岁)和 40 岁以上成人的病死率高于青少年和较年轻的成人。与男性相比,女性的生存率略高。[173]WHO Ebola Response Team. Ebola virus disease among male and female persons in West Africa. N Engl J Med. 2016 Jan 7;374(1):96-8. https://www.nejm.org/doi/full/10.1056/NEJMc1510305 http://www.ncbi.nlm.nih.gov/pubmed/26736011?tool=bestpractice.com 高病毒载量、急性肾损伤和神经系统受累也是结局不良的预测因素。[4]Leroy EM, Gonzalez JP, Baize S. Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa. Clin Microbiol Infect. 2011 Jul;17(7):964-76. https://onlinelibrary.wiley.com/doi/10.1111/j.1469-0691.2011.03535.x/full http://www.ncbi.nlm.nih.gov/pubmed/21722250?tool=bestpractice.com [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 [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 [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 [97]Mupere E, Kaducu OF, Yoti Z. Ebola haemorrhagic fever among hospitalised children and adolescents in northern Uganda: epidemiologic and clinical observations. Afr Health Sci. 2001 Dec;1(2):60-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2141551 http://www.ncbi.nlm.nih.gov/pubmed/12789118?tool=bestpractice.com [98]Peacock G, Uyeki TM, Rasmussen SA. Ebola virus disease and children: what pediatric health care professionals need to know. JAMA Pediatr. 2014 Dec;168(12):1087-8. https://jamanetwork.com/journals/jamapediatrics/fullarticle/1918461 http://www.ncbi.nlm.nih.gov/pubmed/25325785?tool=bestpractice.com [111]McElroy AK, Erickson BR, Flietstra TD, et al. Biomarker correlates of survival in pediatric patients with ebola virus disease. Emerg Infect Dis. 2014 Oct;20(10):1683-90. https://wwwnc.cdc.gov/eid/article/20/10/14-0430_article http://www.ncbi.nlm.nih.gov/pubmed/25279581?tool=bestpractice.com [164]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 [165]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 [166]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
1995 年埃博拉病毒感染疫情暴发期间进行的一项观察研究显示,疫情暴发初期到末期的病死率从 93% 显著下降至 69%。[174]Sadek RF, Khan AS, Stevens G, et al. Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995: determinants of survival. J Infect Dis. 1999 Feb;179 Suppl 1:S24-7. https://jid.oxfordjournals.org/content/179/Supplement_1/S24.long http://www.ncbi.nlm.nih.gov/pubmed/9988161?tool=bestpractice.com 这表明后期病例早在疾病初期就被鉴别出来,并可能获得更优质的护理。
孕妇的流产率高,而且埃博拉病毒感染对这些孕妇而言通常是致命的。[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 [159]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 [161]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 [162]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
HIV 感染对预后影响的数据目前尚不可得。一项研究表明,GB 病毒 C 型感染(一种免疫调节 Pegivirus,西非人的感染率高达 28%)与急性埃博拉病毒病的存活率更高相关。[175]Lauck M, Bailey AL, Andersen KG, et al. GB virus C co-infections in West African Ebola patients. J Virol. 2015 Feb;89(4):2425-9. https://jvi.asm.org/content/89/4/2425.long http://www.ncbi.nlm.nih.gov/pubmed/25473056?tool=bestpractice.com
感染病程
死于埃博拉病毒感染的患者往往会在感染早期出现临床症状,且通常会在感染后的 6-16 天内死亡(通常是由于休克和多器官衰竭)。[4]Leroy EM, Gonzalez JP, Baize S. Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa. Clin Microbiol Infect. 2011 Jul;17(7):964-76. https://onlinelibrary.wiley.com/doi/10.1111/j.1469-0691.2011.03535.x/full http://www.ncbi.nlm.nih.gov/pubmed/21722250?tool=bestpractice.com [13]McElroy AK, Erickson BR, Flietstra TD, et al. Ebola hemorrhagic fever: novel biomarker correlates of clinical outcome. J Infect Dis. 2014 Aug 15;210(4):558-66. https://jid.oxfordjournals.org/content/210/4/558.long http://www.ncbi.nlm.nih.gov/pubmed/24526742?tool=bestpractice.com [14]Mahanty S, Bray M. Pathogenesis of filoviral haemorrhagic fevers. Lancet Infect Dis. 2004 Aug;4(8):487-98. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(04)01103-X/fulltext http://www.ncbi.nlm.nih.gov/pubmed/15288821?tool=bestpractice.com [15]Yan T, Mu J, Qin E, et al. Clinical characteristics of 154 patients suspected of having Ebola disease in the Ebola holding centre of Jui government hospital in Sierra Leone during the 2014 Ebola outbreak. Eur J Microbiol Infect Dis. 2015 Oct;34(10):2089-95. http://www.ncbi.nlm.nih.gov/pubmed/26223324?tool=bestpractice.com 最终康复的患者通常会在 6-11 天病情缓解时出现几天仅有发热的情况。[111]McElroy AK, Erickson BR, Flietstra TD, et al. Biomarker correlates of survival in pediatric patients with ebola virus disease. Emerg Infect Dis. 2014 Oct;20(10):1683-90. https://wwwnc.cdc.gov/eid/article/20/10/14-0430_article http://www.ncbi.nlm.nih.gov/pubmed/25279581?tool=bestpractice.com
预后指标
多项观察性研究表明,与存活患者相比,致死性疾病患者会在感染病程早期出现感染晚期特征(例如虚脱、反应迟钝、低血压、神经系统受累),从症状发作之日起观察到的中位生存期为 9 天。[4]Leroy EM, Gonzalez JP, Baize S. Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa. Clin Microbiol Infect. 2011 Jul;17(7):964-76. https://onlinelibrary.wiley.com/doi/10.1111/j.1469-0691.2011.03535.x/full http://www.ncbi.nlm.nih.gov/pubmed/21722250?tool=bestpractice.com [13]McElroy AK, Erickson BR, Flietstra TD, et al. Ebola hemorrhagic fever: novel biomarker correlates of clinical outcome. J Infect Dis. 2014 Aug 15;210(4):558-66. https://jid.oxfordjournals.org/content/210/4/558.long http://www.ncbi.nlm.nih.gov/pubmed/24526742?tool=bestpractice.com 急性肾损伤和较高的病毒载量均与不良结局和死亡率升高有关。[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 [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 [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 [69]Sanchez A, Lukwiya M, Bausch D, et al. Analysis of human peripheral blood samples from fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels. J Virol. 2004 Oct;78(19):10370-7. https://jvi.asm.org/content/78/19/10370.full http://www.ncbi.nlm.nih.gov/pubmed/15367603?tool=bestpractice.com [107]World Health Organization. Laboratory diagnosis of Ebola virus disease: interim guidance. September 2014 [internet publication]. https://apps.who.int/iris/bitstream/handle/10665/134009/WHO_EVD_GUIDANCE_LAB_14.1_eng.pdf [109]Towner JS, Rollin PE, Bausch DG, et al. Rapid diagnosis of Ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome. J Virol. 2004 Apr;78(8):4330-41. https://jvi.asm.org/content/78/8/4330.full http://www.ncbi.nlm.nih.gov/pubmed/15047846?tool=bestpractice.com 生物标志物用作预后指标需要进一步研究。[13]McElroy AK, Erickson BR, Flietstra TD, et al. Ebola hemorrhagic fever: novel biomarker correlates of clinical outcome. J Infect Dis. 2014 Aug 15;210(4):558-66. https://jid.oxfordjournals.org/content/210/4/558.long http://www.ncbi.nlm.nih.gov/pubmed/24526742?tool=bestpractice.com [92]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 [111]McElroy AK, Erickson BR, Flietstra TD, et al. Biomarker correlates of survival in pediatric patients with ebola virus disease. Emerg Infect Dis. 2014 Oct;20(10):1683-90. https://wwwnc.cdc.gov/eid/article/20/10/14-0430_article http://www.ncbi.nlm.nih.gov/pubmed/25279581?tool=bestpractice.com
恢复和逐渐康复
度过感染第 2 周的患者的存活率> 75%。[16]Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6. https://jid.oxfordjournals.org/content/204/suppl_3/S810.long http://www.ncbi.nlm.nih.gov/pubmed/21987756?tool=bestpractice.com 但凡能走动、自我照顾、显著症状消失(例如腹泻、呕吐、出血)且间隔 48 小时的两次埃博拉病毒逆转录聚合酶链反应 (RT-PCR) 检测结果呈阴性,患者通常可以从隔离病房转到普通病房。[107]World Health Organization. Laboratory diagnosis of Ebola virus disease: interim guidance. September 2014 [internet publication]. https://apps.who.int/iris/bitstream/handle/10665/134009/WHO_EVD_GUIDANCE_LAB_14.1_eng.pdf 精液的病毒排出期可能会延续至恢复后的一年半以上。[43]Bausch DG, Towner JS, Dowell SF, et al. Assessment of the risk of Ebola virus transmission from bodily fluids and fomites. J Infect Dis. 2007 Nov 15;196 Suppl 2:S142-7. https://jid.oxfordjournals.org/content/196/Supplement_2/S142.long http://www.ncbi.nlm.nih.gov/pubmed/17940942?tool=bestpractice.com [48]Emond RT, Evans B, Bowen ET, et al. A case of Ebola virus infection. Br Med J. 11977 Aug 27;2(6086):541-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1631428/pdf/brmedj00478-0011.pdf http://www.ncbi.nlm.nih.gov/pubmed/890413?tool=bestpractice.com [49]Rowe AK, Bertolli J, Khan AS, et al. Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidémies à Kikwit. J Infect Dis. 1999 Feb;179 Suppl 1:S28-35. http://www.ncbi.nlm.nih.gov/pubmed/9988162?tool=bestpractice.com [51]Rogstad KE, Tunbridge A. Ebola virus as sexually transmitted infection. Curr Opin Infect Dis. 2015 Feb;28(1):83-5. http://www.ncbi.nlm.nih.gov/pubmed/25501666?tool=bestpractice.com [52]Sonnenberg P, Field P. Sexual and mother-to-child transmission of Ebola virus in the post-convalescent period. Clin Infect Dis. 2015 Mar 15;60(6):974-5. http://www.ncbi.nlm.nih.gov/pubmed/25501984?tool=bestpractice.com [54]Crozier I. Ebola virus RNA in the semen of male survivors of Ebola virus disease: the uncertain gravitas of a privileged persistence. J Infect Dis. 2016 Nov 15;214(10):1467-9. https://jid.oxfordjournals.org/content/early/2016/05/03/infdis.jiw079.long http://www.ncbi.nlm.nih.gov/pubmed/27142203?tool=bestpractice.com [55]Thorson A, Formenty P, Lofthouse C, et al. Systematic review of the literature on viral persistence and sexual transmission from recovered Ebola survivors: evidence and recommendations. BMJ Open. 2016 Jan 7;6(1):e008859. https://bmjopen.bmj.com/content/6/1/e008859 http://www.ncbi.nlm.nih.gov/pubmed/26743699?tool=bestpractice.com [176]Deen GF, Broutet N, Xu W, et al. Ebola RNA persistence in semen of Ebola virus disease survivors - final report. N Engl J Med. 2017 Oct 12;377(15):1428-37. https://www.nejm.org/doi/full/10.1056/NEJMoa1511410 http://www.ncbi.nlm.nih.gov/pubmed/26465681?tool=bestpractice.com [177]Soka MJ, Choi MJ, Baller A, et al. Prevention of sexual transmission of Ebola in Liberia through a national semen testing and counselling programme for survivors: an analysis of Ebola virus RNA results and behavioural data. Lancet Glob Health. 2016 Oct;4(10):e736-43. https://thelancet.com/journals/langlo/article/PIIS2214-109X(16)30175-9/fulltext http://www.ncbi.nlm.nih.gov/pubmed/27596037?tool=bestpractice.com [178]Etard JF, Sow MS, Leroy S, et al; Postebogui Study Group. Multidisciplinary assessment of post-Ebola sequelae in Guinea (Postebogui): an observational cohort study. Lancet Infect Dis. 2017 May;17(5):545-52. https://thelancet.com/journals/laninf/article/PIIS1473-3099(16)30516-3/fulltext http://www.ncbi.nlm.nih.gov/pubmed/28094208?tool=bestpractice.com 急性感染恢复后 4 至 6 个月时,62% 男性的精液中可检测到病毒。[176]Deen GF, Broutet N, Xu W, et al. Ebola RNA persistence in semen of Ebola virus disease survivors - final report. N Engl J Med. 2017 Oct 12;377(15):1428-37. https://www.nejm.org/doi/full/10.1056/NEJMoa1511410 http://www.ncbi.nlm.nih.gov/pubmed/26465681?tool=bestpractice.com 另一项研究发现,63% 的男性在恢复后 12 个月或更长时间检测出精液中病毒阳性,从样本收集到治疗病房出院之间的间隔最长为 565 天。[177]Soka MJ, Choi MJ, Baller A, et al. Prevention of sexual transmission of Ebola in Liberia through a national semen testing and counselling programme for survivors: an analysis of Ebola virus RNA results and behavioural data. Lancet Glob Health. 2016 Oct;4(10):e736-43. https://thelancet.com/journals/langlo/article/PIIS2214-109X(16)30175-9/fulltext http://www.ncbi.nlm.nih.gov/pubmed/27596037?tool=bestpractice.com 5% 的男性在发病后长达 548 天时还能在精液中检测到病毒。[178]Etard JF, Sow MS, Leroy S, et al; Postebogui Study Group. Multidisciplinary assessment of post-Ebola sequelae in Guinea (Postebogui): an observational cohort study. Lancet Infect Dis. 2017 May;17(5):545-52. https://thelancet.com/journals/laninf/article/PIIS1473-3099(16)30516-3/fulltext http://www.ncbi.nlm.nih.gov/pubmed/28094208?tool=bestpractice.com 精液中埃博拉病毒的脱落可能是间歇性的;一项研究报道了30名男性患者在连续两次检测结果呈阴性后,精液中埃博拉病毒RNA再次出现。[179]PREVAIL III Study Group, Sneller MC, Reilly C, et al. A longitudinal study of Ebola sequelae in Liberia. N Engl J Med. 2019 Mar 7;380(10):924-34. https://www.nejm.org/doi/full/10.1056/NEJMoa1805435 http://www.ncbi.nlm.nih.gov/pubmed/30855742?tool=bestpractice.com 利比里亚的基因组研究已经证实,男性可通过性传播将病毒传给性伴侣。[53]Mate SE, Kugelman JR, Nyenswah TG, et al. Molecular evidence of sexual transmission of Ebola virus. N Engl J Med. 2015 Dec 17;373(25):2448-54. https://www.nejm.org/doi/full/10.1056/NEJMoa1509773#t=article http://www.ncbi.nlm.nih.gov/pubmed/26465384?tool=bestpractice.com 在阴道分泌物中同样检测到了埃博拉病毒。[56]Rodriguez LL, De Roo A, Guimard Y, et al. Persistence and genetic stability of Ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis. 1999 Feb;179 Suppl 1:S170-6. https://jid.oxfordjournals.org/content/179/Supplement_1/S170.long http://www.ncbi.nlm.nih.gov/pubmed/9988181?tool=bestpractice.com 世界卫生组织 (WHO) 建议,男性应从症状发作 3 个月后每月接受精液检测,并最好禁欲或使用安全套,直到两次精液检测(之间相距一个月)均呈阴性(或直到症状消退后至少 12 个月)。[50]World Health Organization. Clinical care for survivors of Ebola virus disease: interim guidance. April 2016 [internet publication]. https://apps.who.int/iris/handle/10665/204235 即使没有病毒血症,在汗液(长至第 40 天)、尿液(长至第 30 天)、结膜液(长至第 22 天)、粪便(长至第 19 天)和母乳(长至第 17 天)中也可检测到病毒。[180]Chughtai AA, Barnes M, Macintyre CR. Persistence of Ebola virus in various body fluids during convalescence: evidence and implications for disease transmission and control. Epidemiol Infect. 2016 Jun;144(8):1652-60. https://www.cambridge.org/core/journals/epidemiology-and-infection/article/persistence-of-ebola-virus-in-various-body-fluids-during-convalescence-evidence-and-implications-for-disease-transmission-and-control/5D3D2C2A4C9652C2DF813DA59185EEC2/core-reader http://www.ncbi.nlm.nih.gov/pubmed/26808232?tool=bestpractice.com
存活患者通常表现为恢复迁延,特征性表现为关节痛 (76%-77%)、疲劳 (69%)、眼部症状 (14%-60%)、头痛 (48%-54%)、腹痛 (54%)、贫血 (50%)、皮肤疾病 (49%) 和听觉症状 (24%)。[181]Mattia JG, Vandy MJ, Chang JC, et al. Early clinical sequelae of Ebola virus disease in Sierra Leone: a cross-sectional study. Lancet Infect Dis. 2016 Mar;16(3):331-8. http://www.ncbi.nlm.nih.gov/pubmed/26725449?tool=bestpractice.com [182]Scott JT, Sesay FR, Massaquoi TA, et al. Post-Ebola syndrome, Sierra Leone. Emerg Infect Dis. 2016 Apr;22(4):641-6. https://wwwnc.cdc.gov/eid/article/22/4/15-1302_article http://www.ncbi.nlm.nih.gov/pubmed/26983037?tool=bestpractice.com [183]Tiffany A, Vetter P, Mattia J, et al. Ebola virus disease complications as experienced by survivors in Sierra Leone. Clin Infect Dis. 2016 Jun 1;62(11):1360-6. https://academic.oup.com/cid/article/62/11/1360/1745263/Ebola-Virus-Disease-Complications-as-Experienced http://www.ncbi.nlm.nih.gov/pubmed/27001797?tool=bestpractice.com 一项纵向研究将埃博拉病毒抗体阳性存活者与抗体阴性密切接触者(对照组)进行了为期12个月的比较,结果发现,与对照组相比,存活者中6种症状的报告频率更为高发:尿频(14.7% 对 3.4%);头痛(47.6% 对 35.6%);乏力(18.4% 对 6.3%);肌肉疼痛(23.1% 对 10.1%);失忆(29.2%对4.8%);以及关节疼痛(47.5%对17.5%)。与对照组相比,更多的存活者同时也有异常的胸部、腹部、神经,和肌肉骨骼发现。[184]PREVAIL III Study Group, Sneller MC, Reilly C, et al. A longitudinal study of Ebola sequelae in Liberia. N Engl J Med. 2019 Mar 7;380(10):924-34. https://www.nejm.org/doi/full/10.1056/NEJMoa1805435 http://www.ncbi.nlm.nih.gov/pubmed/30855742?tool=bestpractice.com
恢复期的晚期表现可能包括睾丸炎、脊髓炎、腮腺炎、胰腺炎、肝炎和精神病。[17]Bwaka MA, Bonnet MJ, Calain P, et al. Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. J Infect Dis. 1999 Feb;179 Suppl 1:S1-7. https://jid.oxfordjournals.org/content/179/Supplement_1/S1.long http://www.ncbi.nlm.nih.gov/pubmed/9988155?tool=bestpractice.com 幸存者也有患葡萄膜炎(前、后或全葡萄膜炎)的风险,这可能导致继发结构性并发症、视力障碍或失明。[185]Shantha JG, Yeh S, Nguyen QD. Ebola virus disease and the eye. Curr Opin Ophthalmol. 2016 Nov;27(6):538-44. http://www.ncbi.nlm.nih.gov/pubmed/27585217?tool=bestpractice.com 一项无对照的回顾性横断面研究发现,约 28% 的幸存者发生埃博拉病毒相关的葡萄膜炎,3% 的患者发生埃博拉病毒相关的视神经病。据发现,在葡萄膜炎患者中,发现 38.5% 的患者失明(视力>20/400)。[186]Shantha JG, Crozier I, Hayek BR, et al. Ophthalmic manifestations and causes of vision impairment in Ebola virus disease survivors in Monrovia, Liberia. Ophthalmology. 2017 Feb;124(2):170-7. http://www.ncbi.nlm.nih.gov/pubmed/27914832?tool=bestpractice.com 一名幸存者在感染发病后 14 周、病毒从血液中清除后 9 周时发生急性葡萄膜炎,并被检测到活的埃博拉病毒。[187]Varkey JB, Shanth JG, Crozier I, et al. Persistence of Ebola virus in ocular fluid during convalescence. N Engl J Med. 2015 Jun 18;372(25):2423-7. http://www.ncbi.nlm.nih.gov/pubmed/25950269?tool=bestpractice.com [188]Chancellor JR, Padmanabhan SP, Greenough TC, et al. Uveitis and systemic inflammatory markers in convalescent phase of Ebola virus disease. Emerg Infect Dis. 2016 Feb;22(2):295-7. https://wwwnc.cdc.gov/eid/article/22/2/15-1416_article http://www.ncbi.nlm.nih.gov/pubmed/26812218?tool=bestpractice.com 还报告了单眼白内障和解剖上沿视神经轴突分布的新型视网膜病变。[189]Steptoe PJ, Scott JT, Baxter JM, et al. Novel retinal lesion in Ebola survivors, Sierra Leone, 2016. Emerg Infect Dis. 2017 Jul;23(7):1102-9. https://wwwnc.cdc.gov/eid/article/23/7/16-1608_article http://www.ncbi.nlm.nih.gov/pubmed/28628441?tool=bestpractice.com 这些表现的病因尚不明确,但可能与免疫复合物现象或埃博拉病毒在免疫豁免部位的持续存在有关。建议在恢复后对幸存者进行定期检查至少 18 个月。[178]Etard JF, Sow MS, Leroy S, et al; Postebogui Study Group. Multidisciplinary assessment of post-Ebola sequelae in Guinea (Postebogui): an observational cohort study. Lancet Infect Dis. 2017 May;17(5):545-52. https://thelancet.com/journals/laninf/article/PIIS1473-3099(16)30516-3/fulltext http://www.ncbi.nlm.nih.gov/pubmed/28094208?tool=bestpractice.com
感染存活者可能会获得对埃博拉病毒的终身免疫力。研究显示,存活者有长期持续存在的 T 细胞应答以及持续高滴度的中和抗体。[190]Thom R, Tipton T, Strecker T, et al. Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study. Lancet Infect Dis. 2020 Oct 13;S1473-3099(20)30736-2. https://www.doi.org/10.1016/S1473-3099(20)30736-2 http://www.ncbi.nlm.nih.gov/pubmed/33065039?tool=bestpractice.com 因此,感染康复的患者对活动性感染患者的治疗拥有无法估量的价值。然而,目前对免疫豁免部位病毒持久存在的了解仍不全面。2015 年,一名外籍医务工作者在原发性重度埃博拉病毒病恢复后 9 个月时,出现埃博拉病毒性脑膜脑炎(CSF 和血浆 RT-PCR 检测呈埃博拉病毒阳性)。[191]Jacobs M, Rodger A, Bell DJ, et al. Late Ebola virus relapse causing meningoencephalitis: a case report. Lancet. 2016 Jul 30;388(10043):498-503. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967715 http://www.ncbi.nlm.nih.gov/pubmed/27209148?tool=bestpractice.com 还报道了一例迟发性脑炎和多发性关节炎[192]Howlett P, Brown C, Helderman T, et al. Ebola virus disease complicated by late-onset encephalitis and polyarthritis, Sierra Leone. Emerg Infect Dis. 2016 Jan;22(1):150-2. https://wwwnc.cdc.gov/eid/article/22/1/15-1212_article http://www.ncbi.nlm.nih.gov/pubmed/26690042?tool=bestpractice.com 以及疑似由一例康复后一年持续性感染患者再次传播的病例。[193]Dokubo EK, Wendland A, Mate SE, et al. Persistence of Ebola virus after the end of widespread transmission in Liberia: an outbreak report. Lancet Infect Dis. 2018 Sep;18(9):1015-24. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30417-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/30049622?tool=bestpractice.com 疾病长期存在和晚期复发的可能性,很可能会改变对于出现继发疾病幸存者的流行病学管理和临床治疗方法。此外,对于急性埃博拉感染恢复后很快就妊娠的患者管理,也存在理论上的考量。
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