管理方案取决于疾病严重程度,重点关注以下原则:
感染预防和控制
对症治疗
优化支持性治疗
管理皮损
并发症管理
抗病毒治疗。
患者可获益于在病程早期实施的支持性治疗和疼痛控制。然而,这在一些患者(如免疫功能低下患者)中可能并不充分,可能需要抗病毒治疗。[105]Centers for Disease Control and Prevention. Interim clinical guidance for the treatment of monkeypox. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html
目前缺乏高质量的循证临床管理指南来指导临床决策。各指南的建议各不相同,针对不同风险组和并发症的建议有限。[192]Webb E, Rigby I, Michelen M, et al. Availability, scope and quality of monkeypox clinical management guidelines globally: a systematic review. BMJ Glob Health. 2022 Aug;7(8):e009838.
https://gh.bmj.com/content/7/8/e009838
http://www.ncbi.nlm.nih.gov/pubmed/35973747?tool=bestpractice.com
此章节中的建议主要基于世界卫生组织(World Health Organization, WHO)指南,适用于疑似或确诊感染的患者。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
感染预防和控制
如果临床怀疑感染,应立即与所在地区传染病部门联系。
这将触发启动相关程序,从而将患者安全转移至负压隔离区,并通知公共卫生团队。
重要之处在于,对于与有症状患者密切接触的每一个体(例如家庭密切接触者、助理医护人员和医护人员)以及是否存在任何潜在的动物病毒携带者,均应进行记录。
所有疑似或确诊病例都应由包括公共卫生官员在内的专家进行管理,以防止出现潜在的紧急情况。
遵循当地感染防控常规。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
建议采取标准预防措施、接触传播预防措施和飞沫传播预防措施。
在照护疑似猴痘病例时,如果怀疑水痘,则推荐采取空气传播预防措施,直至排除水痘。当照护猴痘确诊病例时,推荐穿戴呼吸器。如果要实施产生气溶胶的操作,推荐采取空气传播预防措施。
将所有污染材料(例如,亚麻织物、病号服)以及患者的体液/固体废物作为具有潜在传染性的物品进行处理。
理想情况下,所有可能接触患者、体液或污染物的人员均应已接受天花疫苗接种。[134]World Health Organization. Monkeypox: fact sheet. May 2022 [internet publication].
https://www.who.int/en/news-room/fact-sheets/detail/monkeypox
对于未接种疫苗的接触者,可建议采取暴露后疫苗接种(参阅 预防)。
如有可能,妊娠或严重的免疫功能低下医务工作者不应评估或护理疑似或确诊感染的患者。[135]UK Health Security Agency; Public Health Wales; Public Health Agency (Northern Ireland). Principles for monkeypox control in the UK: 4 nations consensus statement. November 2022 [internet publication].
https://www.gov.uk/government/publications/principles-for-monkeypox-control-in-the-uk-4-nations-consensus-statement
轻度或无并发症的疾病
多数病例为轻度,呈自限性,患者通常于 2 至 4 周内康复。
对于疑似或确诊感染且疾病轻微或不复杂的患者,如果无重度或有并发症疾病的高风险,并且家庭评估确定在家中能做到感染预防和疾病控制,则可在家隔离,持续整个感染期。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
作出个体化决策。应基于诸如疾病严重程度、存在的并发症、患者照护需求、营养和脱水情况、重度疾病危险因素以及疾病恶化时的医疗就诊途径等因素,作出决策。患者应能走动、水和食物摄入情况良好,并且能够管理自己的自我照护。
考虑将重度疾病风险较高的患者(例如儿童、孕妇、免疫功能低下者、有皮肤疾病者)收入医疗机构,以进行更密切的监测。还应考虑将与脆弱人群一起生活的患者收入院,在这种情况下,无法做到充分的感染预防和控制措施。
应尽可能使用远程医疗或电话进行随访。
患者遵循其地区家庭自我隔离指南很重要。参阅患者讨论。
在英国,英国卫生安全局(UK Health Security Agency, UKHSA)建议,基于临床医生评估并遵循 UKHSA 指导,疑似或拟诊病例可居家自我隔离。具有西非或中非旅行史的可能或疑似病例可能需要按照具有严重后果的传染病(high consequence infectious disease, HCID)进行管理;与输入性发热性疾病管理机构进行讨论。[136]UK Health Security Agency. Monkeypox: case definitions. August 2022 [internet publication].
https://www.gov.uk/guidance/monkeypox-case-definitions
根据临床或自我隔离的要求,评估所有确诊(或高度拟诊)病例是否需要入院治疗,并向当地卫生防护中心进行通报。
因临床原因需收住院治疗的患者,或经临床评估因社会原因或医学原因无法进行自我隔离的患者,应收入当地医院负压或中性压力单人病房,配备呼吸道防护装备和个人防护装备(进行恰当的感染防控)。
英格兰 NHS 建议采用风险分层的临床方法来辅助决策制定。[165]NHS England. Monkeypox. September 2022 [internet publication].
https://www.england.nhs.uk/publication/monkeypox
在英国,猴痘病毒分支(分支 Ⅱb 谱系 B.1)所致当前疫情暴发不再被归类为 HCID。然而,由分支 Ⅰ、分支 Ⅱa 和分支 Ⅱb(非谱系 B.1)所致感染仍被作为 HCID。[193]UK Health Security Agency. HCID status of monkeypox. September 2022 [internet publication].
https://www.gov.uk/guidance/hcid-status-of-monkeypox
建议予以适当的对症治疗(注意控制疼痛)和支持性治疗。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
应在病程早期开始治疗。
疼痛
疼痛管理是治疗的重要组成部分,因为疼痛常见并且可能剧烈(例如直肠疼痛/直肠炎、病变引起的疼痛、体格检查时不明显的黏膜病变引起的疼痛、淋巴结肿大引起的疼痛、头痛、肌肉疼痛)。
建议采用包括非药物和药物治疗的多模式方法。可能需要进行局部和/或全身治疗。疼痛管理策略应个体化、以患者为中心,并根据个体患者的需求和背景量身定制。最初评估疼痛,然后定期评估疼痛控制情况,并根据需要调整疼痛管理。对于难治性病例,可能需要咨询疼痛专科医生。建议延长随访以快速诊断长期伤害感受性综合征。[194]Centers for Disease Control and Prevention. Clinical considerations for pain management of monkeypox. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/pain-management.html
[195]Hans GH, Wildemeersch D, Meeus I. Integrated analgesic care in the current human monkeypox outbreak: perspectives on an integrated and holistic approach combining old allies with innovative technologies. Medicina (Kaunas). 2022 Oct 15;58(10):1454.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612138
http://www.ncbi.nlm.nih.gov/pubmed/36295614?tool=bestpractice.com
对于轻度疼痛,建议使用非处方药,如对乙酰氨基酚或布洛芬。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[194]Centers for Disease Control and Prevention. Clinical considerations for pain management of monkeypox. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/pain-management.html
在评估了与阿片类药物使用相关的获益和风险(例如,便秘、长期使用阿片类药物的使用障碍)后,建议将阿片类药物(如曲马多或吗啡)用于重度疼痛的短期管理(例如,由直肠炎引起的重度直肠疼痛)。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[194]Centers for Disease Control and Prevention. Clinical considerations for pain management of monkeypox. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/pain-management.html
根据个案报道,神经性止痛药(如加巴喷丁)已用于某些情况下(如重度直肠炎)疼痛的短期管理。[194]Centers for Disease Control and Prevention. Clinical considerations for pain management of monkeypox. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/pain-management.html
对于口腔病变,建议采用盐水漱口、使用抗菌漱口水(例如,氯己定)和给予局部麻醉(例如,利多卡因黏稠剂)。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[194]Centers for Disease Control and Prevention. Clinical considerations for pain management of monkeypox. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/pain-management.html
对于生殖器或肛门直肠病损,建议进行温水坐浴和/或局部使用利多卡因。外用皮质类固醇也可用于生殖器病损;但是,必须考虑在活动性病损上使用这些药物的风险和获益。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[194]Centers for Disease Control and Prevention. Clinical considerations for pain management of monkeypox. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/pain-management.html
根据病例报告,早期使用抗病毒药物 tecovirimat(参阅下文抗病毒治疗)进行治疗可有助于重度直肠炎患者的疼痛控制。[196]Lucar J, Roberts A, Saardi KM, et al. Monkeypox virus-associated severe proctitis treated with oral tecovirimat: a report of two cases. Ann Intern Med. 2022 Aug 18 [Epub ahead of print].
https://www.acpjournals.org/doi/10.7326/L22-0300
http://www.ncbi.nlm.nih.gov/pubmed/35981225?tool=bestpractice.com
但是并无证据对此加以支持。
直肠炎
疼痛可能为重度,需要适当的疼痛管理(见上文)。
可使用皮质类固醇/局部麻醉栓剂或局部用利多卡因凝胶以缓解疼痛、痉挛和炎症。[194]Centers for Disease Control and Prevention. Clinical considerations for pain management of monkeypox. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/pain-management.html
[197]British Association for Sexual Health and HIV. Monkeypox management recommendations (proctitis). June 2022 [internet publication].
https://www.bashh.org/news/monkeypox-resources
可考虑使用粪便软化剂以减轻排便相关疼痛(特别是当患者使用阿片类镇痛剂时)。[194]Centers for Disease Control and Prevention. Clinical considerations for pain management of monkeypox. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/pain-management.html
[197]British Association for Sexual Health and HIV. Monkeypox management recommendations (proctitis). June 2022 [internet publication].
https://www.bashh.org/news/monkeypox-resources
对于直肠炎并发症(例如,急性前列腺炎、前列腺脓肿),建议转诊至专科医生,因为可能需要使用抗生素。[197]British Association for Sexual Health and HIV. Monkeypox management recommendations (proctitis). June 2022 [internet publication].
https://www.bashh.org/news/monkeypox-resources
发热
瘙痒
为了治疗皮疹相关瘙痒,建议使用一种抗组胺药(例如,氯雷他定)。也可考虑外用制剂,如炉甘石洗剂、凡士林或胶态燕麦。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[194]Centers for Disease Control and Prevention. Clinical considerations for pain management of monkeypox. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/pain-management.html
恶心/呕吐
腹泻
消化不良
营养学
由于口咽病损或有疼痛的颈部淋巴结肿大,营养和水合状态可能受损。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
建议患者保持充足水化和营养。如果这不可能实现,应评估具体原因(例如,疼痛、呕吐、无力),并给予恰当处理(例如,镇痛、使用止吐药)。
根据标准推荐,提供维生素 A 补剂,因为此药能帮助伤口愈合和促进眼健康。
心理健康疗护
及时识别和评估焦虑和抑郁症状,以便启动基本的社会心理支持策略和一线干预措施,来管理新的焦虑和抑郁症状(例如,自我管理策略、心理或药物治疗)。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
建议使用心理社会支持策略管理睡眠问题(例如睡眠卫生建议)。
建议采用一种保守方案来处理皮损,目的是缓解不适、加快愈合及预防并发症。然而,尚不确定皮损的最佳管理。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
建议患者勿抓挠皮肤,并保持皮损处清洁(即,使用无菌盐水或抗菌溶液)和干燥。不应覆盖皮疹。避免使用粘性绷带。
监测皮损是否有继发性细菌感染(如发红、发热、硬结、疼痛加重、脓性或恶臭分泌物、反复发热),如果有,则应使用适当的口服抗生素治疗。
开始使用抗生素治疗的决策以及抗生素选择应基于个体临床评估和当地的抗微生物药物耐药模式。遵循当地常规。
不建议预防性使用抗生素。 使用抗生素预防继发性皮肤感染的证据为轶事证据,具有局限性。[7]Beer EM, Rao VB. A systematic review of the epidemiology of human monkeypox outbreaks and implications for outbreak strategy. PLoS Negl Trop Dis. 2019 Oct;13(10):e0007791.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816577
http://www.ncbi.nlm.nih.gov/pubmed/31618206?tool=bestpractice.com
尽管如此,部分医学中心可能仍对特定患者使用局部抗生素进行预防(例如病损位于肛门生殖器区域、免疫功能低下)。[198]de Sousa D, Frade J, Patrocínio J, et al. Monkeypox infection and bacterial cellulitis: a complication to look for. Int J Infect Dis. 2022 Oct;123:180-2.
https://www.ijidonline.com/article/S1201-9712(22)00494-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36055636?tool=bestpractice.com
少数有疼痛或感染的皮肤或黏膜病变患者可能需要入院治疗,以进行疼痛管理和/或抗生素治疗。[151]Girometti N, Byrne R, Bracchi M, et al. Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis. Lancet Infect Dis. 2022 Sep;22(9):1321-8.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00411-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/35785793?tool=bestpractice.com
请参阅以下章节。
如果怀疑有剥落或更深的软组织感染,应考虑转诊至专科。
监测患者的临床状况是否恶化。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
重度或有并发症疾病或者有重度疾病高风险的患者
对于重度疾病患者或有重度疾病高风险的患者,通常需收入院,给予支持性治疗和抗病毒治疗。
患者可能需要入院治疗疼痛和肿胀、吞咽困难(吞咽痛)、眼部病变或并发症(例如细菌重叠感染)。[40]Thornhill JP, Barkati S, Walmsley S, et al. Monkeypox virus infection in humans across 16 countries: April–June 2022. N Engl J Med. 2022 Aug 25;387(8):679-91.
https://www.nejm.org/doi/full/10.1056/NEJMoa2207323
http://www.ncbi.nlm.nih.gov/pubmed/35866746?tool=bestpractice.com
[141]Patel A, Bilinska J, Tam JCH, et al. Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series. BMJ. 2022 Jul 28;378:e072410.
https://www.bmj.com/content/378/bmj-2022-072410
http://www.ncbi.nlm.nih.gov/pubmed/35902115?tool=bestpractice.com
[142]World Health Organization. Update 79: Monkeypox outbreak update: situation - transmission - countermeasures. August 2022 [internet publication].
https://www.who.int/publications/m/item/update-79-monkeypox-outbreak-update
[146]Tarín-Vicente EJ, Alemany A, Agud-Dios M, et al. Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study. Lancet. 2022 Aug 27;400(10353):661-9.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01436-2/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/35952705?tool=bestpractice.com
[161]Gomez-Garberi M, Sarrio-Sanz P, Martinez-Cayuelas L, et al. Genitourinary lesions due to monkeypox. Eur Urol. 2022 Sep 9 [Epub ahead of print].
https://www.sciencedirect.com/science/article/pii/S0302283822026252
http://www.ncbi.nlm.nih.gov/pubmed/36096858?tool=bestpractice.com
[165]NHS England. Monkeypox. September 2022 [internet publication].
https://www.england.nhs.uk/publication/monkeypox
[199]Reda A, Hemmeda L, Brakat AM, et al. The clinical manifestations and severity of the 2022 monkeypox outbreak among 4080 patients. Travel Med Infect Dis. 2022 Sep 15 [Epub ahead of print].
https://www.sciencedirect.com/science/article/pii/S1477893922002022
http://www.ncbi.nlm.nih.gov/pubmed/36116767?tool=bestpractice.com
来自当前疫情暴发的数据表明,大约 7%-13% 的病例需要接受入院治疗。涉及 7000 多例病例的一项荟萃分析发现住院率为 14.1%;然而,该分析纳入了 2022 年暴发前的病例。住院率已从 2017 年前暴发的 49.8% 下降到 2022 年暴发期间的 5.8%。[200]DeWitt ME, Polk C, Williamson J, et al. Global monkeypox case hospitalisation rates: a rapid systematic review and meta-analysis. EClinicalMedicine. 2022 Dec;54:101710.
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00440-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36345526?tool=bestpractice.com
需要入院治疗的临床原因包括,肛门直肠疼痛和直肠炎、严重的阴茎水肿、便秘或尿潴留、软组织重叠感染、限制经口摄入的咽炎、合并性传播疾病的混合感染、需要外科干预的病变或眼部病损。
基于现有的数据,最常见的住院原因为:[201]de Oliveira-Júnior JM, Tenório MDL, Dos Santos Caduda S, et al. Reasons for hospitalization of patients with monkeypox: a quantitative evidence synthesis. Infection. 2022 Oct 18 [Epub ahead of print].
https://link.springer.com/article/10.1007/s15010-022-01937-1
http://www.ncbi.nlm.nih.gov/pubmed/36258119?tool=bestpractice.com
多数入院治疗者无严重并发症报告。然而,已观察到一些罕见的并发症,如会厌炎、扁桃体炎、扁桃体周围蜂窝织炎、扁桃体/扁桃体周围脓肿、包皮嵌顿/包茎、龟头炎、肛周/腹股沟脓肿、直肠穿孔、尿道炎、脑炎、肺炎和心肌炎。请参阅“并发症”。
对于重度或有并发症疾病患者,或者有发生重度疾病或并发症高风险的患者,需收住院,以给予更密切监测和临床诊疗。遵循当地常规。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
监测生命体征、神经系统状态、容量状态、呼吸系统和灌注体征。
监测实验室检测值,包括全血细胞计数、尿素和电解质,以及肝功能。
评估疼痛、一般状况、营养状况和皮疹特征(即阶段、位置、皮损数量、有无剥落或继发性细菌感染)。
根据需要,提供支持性治疗(见上述轻度或无并发症疾病)
采用最佳化支持性治疗措施管理患者。遵循当地常规。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
注意液体平衡、氧合、营养、症状缓解(见上述轻度或无并发症的疾病),及时治疗其他继发性细菌感染,治疗并发症以及预防长期后遗症。
为了处理由血管内容量损失引起的严重脱水,建议在密切监测液体反应性的情况下,以一次或多次大量快速输液的方式进行静脉或骨内补液。
如果患者无法耐受口服营养,可能需给予肠内营养。
如果病人情绪激动,对自己、其他患者或医护人员构成威胁,可能需要进行药物治疗。
参阅 并发症,获取并发症管理具体信息。
对于存在重症风险的患者,或者因重症就诊或已发生重症的患者,应考虑进行抗病毒治疗。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[105]Centers for Disease Control and Prevention. Interim clinical guidance for the treatment of monkeypox. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html
抗病毒治疗
为治疗天花而研发的抗病毒药物(例如 tecovirimat、brincidofovir、cidofovir)具有抗猴痘病毒活性,可能有所获益。[181]Titanji BK, Tegomoh B, Nematollahi S, et al. Monkeypox: a contemporary review for healthcare professionals. Open Forum Infect Dis. 2022 Jul;9(7):ofac310.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307103
http://www.ncbi.nlm.nih.gov/pubmed/35891689?tool=bestpractice.com
[202]Siegrist EA, Sassine J. Antivirals with activity against monkeypox: a clinically oriented review. Clin Infect Dis. 2022 Jul 29 [Epub ahead of print].
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac622/6651596
http://www.ncbi.nlm.nih.gov/pubmed/35904001?tool=bestpractice.com
对重症患者、有重症高风险的患者、累及可能导致严重后遗症(包括瘢痕形成或狭窄)的解剖区域(例如,咽部、阴茎包皮、外阴、阴道、尿道、直肠、肛门)的患者或严重感染患者(尤其是需要清创术等手术干预的患者),建议进行抗病毒治疗。应在病程早期开始治疗。然而,目前还没有人类中的安全性和有效性数据支持将抗病毒治疗用于这一适应证。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[105]Centers for Disease Control and Prevention. Interim clinical guidance for the treatment of monkeypox. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html
tecovirimat 通常推荐作为一线治疗。[105]Centers for Disease Control and Prevention. Interim clinical guidance for the treatment of monkeypox. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html
基于动物和人类研究结果,该药在英国和欧洲获批用于猴痘治疗。在英国,可提供给因重度或复杂性感染入院的有症状患者。目前正通过专门的区域成人传染病中心管理供应该药。[203]Medicines and Healthcare products Regulatory Agency. Tecovirimat as a treatment for patients hospitalised due to monkeypox viral infection. September 2022 [internet publication].
https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAlert.aspx?AlertID=103213
它在美国获批用于治疗天花,但在疫情暴发期间可按照试验用新药扩展使用方案用于治疗猴痘。
在部分国家,根据当地公共卫生部门指导,其他可能获批或推荐用于天花的抗病毒药物(例如 brincidofovir、cidofovir)或牛痘免疫球蛋白可超说明书用药,用于猴痘治疗。请参阅“新兴治疗”。
对于完成 14 天治疗后出现持续性或新发病变的任何患者,考虑检测病灶拭子样本检查 tecovirimat 耐药性和采集样本行血浆药代动力学分析(观察药物水平是否低于目标浓度)。已报道 2 例实验室证实的 tecovirimat 耐药。2 例患者均有免疫功能低下的情况,并有进行性猴痘严重表现。他们接受了延长疗程(>14 天)的 tecovirimat 治疗。到目前为止,尚无 tecovirimat 耐药性病毒传播的记录。[204]Centers for Disease Control and Prevention. Update on managing monkeypox in patients receiving therapeutics. November 2022 [internet publication].
https://emergency.cdc.gov/han/2022/han00481.asp
此类药物在部分国家可能尚有库存,但已无法广泛获取。
最好在随机临床试验中使用抗病毒药物,并收集标准化的临床和结局数据。如果不可行,可能根据拓展应用方案使用抗病毒药物。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
咨询当地公共卫生部门,获取抗病毒治疗应用指导。
隔离预防措施的终止和出院
关于停止隔离预防措施和出院的决定取决于患者是住院隔离还是居家隔离,应与当地公共卫生部门进行协商。[205]Centers for Disease Control and Prevention. Infection prevention and control of monkeypox in healthcare settings. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-healthcare.html
一般而言,应继续采取预防措施,直到所有病损消退,并形成新鲜皮层。
据报道,少数患者在皮损消退后出现长时间上呼吸道病毒脱落和病毒血症,导致其于院内接受长期隔离。[206]Adler H, Gould S, Hine P, et al. Clinical features and management of human monkeypox: a retrospective observational study in the UK. Lancet Infect Dis. 2022 Aug;22(8):1153-62.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00228-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/35623380?tool=bestpractice.com
对于住院患者,UKHSA 建议,若满足以下标准,隔离预防措施即可终止:[207]UK Health Security Agency. De-isolation and discharge of monkeypox-infected patients: interim guidance. September 2022 [internet publication].
https://www.gov.uk/guidance/de-isolation-and-discharge-of-monkeypox-infected-patients-interim-guidance
临床标准:根据管理患者的临床团队判断,患者临床状况足以安全解除隔离
实验室标准:患者以下三个样本的聚合酶链反应检测均呈阴性:
病损标准:48 小时无新发病损;无粘膜病损;所有病损均已结痂,痂皮脱落,下方皮肤完整。
只有满足上述所有临床标准、实验室标准和病损标准时,患者才能从隔离设施/病房出院,至另一医院病房、不同住院设施或居住设施(例如疗养院)。如果以上所有标准均可满足,患者可出院返家,而无需继续隔离。满足临床标准,但不满足实验室标准或病损标准的患者,经治临床医生若评估为安全之举,可予以出院后居家隔离(根据现行公共卫生法规)。
在家庭环境中,UKHSA 建议,一旦满足以下标准,患者即可终止居家自我隔离。[207]UK Health Security Agency. De-isolation and discharge of monkeypox-infected patients: interim guidance. September 2022 [internet publication].
https://www.gov.uk/guidance/de-isolation-and-discharge-of-monkeypox-infected-patients-interim-guidance
当满足以上临床标准和以下病损标准时,患者可不受限制恢复彻底正常活动(完全解除隔离)。[207]UK Health Security Agency. De-isolation and discharge of monkeypox-infected patients: interim guidance. September 2022 [internet publication].
https://www.gov.uk/guidance/de-isolation-and-discharge-of-monkeypox-infected-patients-interim-guidance
建议患者避免与免疫功能低下者、孕妇和 <12 岁儿童接触,直到其满足以上完全解除隔离标准(如果患者的工作需要与任何此类群体密切接触,则建议可能包括停止工作)。
儿童和青少年
对于有发生重症或并发症风险的疑似或确诊猴痘儿童和青少年患者,应根据具体情况考虑治疗。疾病管理通常与成人相同,除少数例外。[91]Centers for Disease Control and Prevention. Clinical considerations for monkeypox in children and adolescents. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/pediatric.html
在对需要住院的儿童进行隔离和感染控制时,需对儿童年龄、照护需求,以及家庭和照护者的偏好加以考虑。不论儿童是在医院还是居家,均应尽可能将照护者人数限制于单人。
特别注意保持皮损的遮盖,防止儿童抓挠皮损或触摸眼部,以防止自体接种和更严重的疾病。
如果具有治疗指征,tecovirimat 亦为推荐用于儿童和青少年的一线抗病毒药物。然而,目前缺乏安全性和有效性数据,亦尚未在儿童群体中进行过临床研究。其他抗病毒药物(例如 cidofovir、brincidofovir)因其具有潜在毒性,从而限定于不寻常情况下应用(例如极为严重的感染、尽管给予 tecovirimat 治疗后疾病仍出现进展、tecovirimat 具有用药禁忌或药物无法获取)。
孕妇或哺乳妇女
由于妊娠期间发生严重疾病的风险可能增加,以及存在传播给胎儿或新生儿的风险,优先考虑对妊娠(或近期妊娠)和母乳喂养女性进行治疗。[93]Centers for Disease Control and Prevention. Clinical considerations for monkeypox in people who are pregnant or breastfeeding. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/pregnancy.html
有轻度或无并发症疾病的孕妇(或近期受孕的女性)可能不需要住院;然而,可能首选在卫生机构进行密切监测。对于发生重度或有并发症疾病的孕妇,应收入院,进行最佳的支持性治疗和/或干预,以改善母亲或胎儿生存情况。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
应基于产科适应证和患者意愿,采取个体化分娩方式。仅当具备医学合理性且考虑到母体和胎儿情况时,才应实施引产或剖宫产。
密切监测新生儿是否有潜在的先天性或围产期暴露或感染的证据。
目前尚不清楚受感染母亲的母乳中是否存在病毒或抗体。因个体化评估婴儿的喂养实践,需考虑母亲的身体状况和疾病严重程度。
建议母亲在处理和喂养婴儿时采取一般感染预防和控制措施(例如,注意手部卫生,如果可行,应佩戴口罩,遮盖与婴儿直接接触的任何病损)。
妊娠(或近期妊娠)和母乳喂养女性应谨慎使用抗病毒疗法,由于有关该人群的数据有限,应仅在当地公共卫生部门的指导下使用。
如果有治疗指征,建议将 tecovirimat 用作妊娠(或近期妊娠)和母乳喂养女性的一线治疗。然而,尚无关于在妊娠或母乳喂养期间的人类使用数据,该建议是基于动物研究(未在动物研究中观察到对胚胎-胎儿发育的毒性)。[93]Centers for Disease Control and Prevention. Clinical considerations for monkeypox in people who are pregnant or breastfeeding. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/pregnancy.html
在动物研究中发现 cidofovir 和 brincidofovir 具有致畸性的证据,不应将其用于早期妊娠或母乳喂养的女性。[93]Centers for Disease Control and Prevention. Clinical considerations for monkeypox in people who are pregnant or breastfeeding. October 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/pregnancy.html
已经提出管理孕妇的进一步指南。[208]Dashraath P, Nielsen-Saines K, Mattar C, et al. Guidelines for pregnant individuals with monkeypox virus exposure. Lancet. 2022 Jul 2;400(10345):21-2.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01063-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/35750071?tool=bestpractice.com
[209]Khalil A, Samara A, O'Brien P, et al. Monkeypox and pregnancy: what do obstetricians need to know? Ultrasound Obstet Gynecol. 2022 Jul;60(1):22-7.
https://obgyn.onlinelibrary.wiley.com/doi/10.1002/uog.24968
http://www.ncbi.nlm.nih.gov/pubmed/35652380?tool=bestpractice.com
艾滋病病毒 (HIV) 感染
合并 HIV 感染的患者可能发生严重疾病的风险增加,对于这些患者,应优先考虑治疗和密切监测。[98]Centers for Disease Control and Prevention. Clinical considerations for treatment and prophylaxis of monkeypox virus infection in people with HIV. November 2022 [internet publication].
https://www.cdc.gov/poxvirus/monkeypox/clinicians/people-with-HIV.html
[99]O'Shea J, Filardo TD, Morris SB, et al. Interim guidance for prevention and treatment of monkeypox in persons with HIV infection: United States, August 2022. MMWR Morb Mortal Wkly Rep. 2022 Aug 12;71(32):1023-8.
https://www.cdc.gov/mmwr/volumes/71/wr/mm7132e4.htm
http://www.ncbi.nlm.nih.gov/pubmed/35951495?tool=bestpractice.com
正在接受抗逆转录病毒治疗进行暴露前或暴露后预防的患者应当继续这样做。
在进行猴痘治疗期间继续(或开始)抗逆转录病毒治疗和机会性感染预防治疗,因为治疗中断可导致病毒血症反弹,从而使病程变复杂。
始终检查用于治疗猴痘的抗病毒药物与治疗 HIV 感染的抗逆转录病毒疗法(或其他疗法)之间是否存在药物相互作用。
如果有治疗指征(例如,晚期或控制不佳的 HIV 感染),建议将 tecovirimat 作为合并 HIV 感染的患者的一线治疗。对于那些在使用 tecovirimat 而无改善或发生进展的患者,可以考虑增加其他治疗(例如,cidofovir、brincidofovir、牛痘免疫球蛋白)。
除对临床表现和暴露史保持警惕之外,英国 HIV 协会目前不建议对 HIV 感染者采取任何特定措施(考虑接种疫苗除外)。CD4 计数 <200 个细胞/μL、存在持续性病毒血症(>200 拷贝/mL)、近期出现 HIV 相关疾病或存在可能引起免疫抑制的合并疾病或治疗的患者,发生感染和并发症的风险可能更高,并且应该优先考虑专家检查。[124]British HIV Association. BHIVA rapid guidance on monkeypox virus. October 2022 [internet publication].
https://www.bhiva.org/rapid-guidance-on-monkeypox-virus