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
皮肤病损的管理和伤口护理
并发症管理
抗病毒治疗。
大部分患者可以仅接受支持性治疗,并在病程早期进行疼痛控制。然而,这对某些患者(例如病情严重的患者)来说可能存在治疗不足,而他们可能需要进行抗病毒治疗。[226]Centers for Disease Control and Prevention. Clinical treatment of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care
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。[259]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
本章节的建议主要基于世界卫生组织(World Health Organization, WHO)和疾病预防控制中心(Centers for Disease Control and Prevention, CDC)指南,适用于疑诊或确诊感染患者。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. Jun 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[226]Centers for Disease Control and Prevention. Clinical treatment of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care
考虑酌情咨询传染病、皮肤科、伤口护理、胃肠病学、神经病学、眼科、泌尿科、危重症诊疗和外科领域的专科医师。
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. Jun 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 mpox 病例时,如果同时怀疑水痘,则建议在排除水痘前采取空气传播预防措施。当照护 mpox 确诊病例时,推荐佩戴口罩。在进行产生气溶胶的操作时,或者怀疑或确认感染 mpox 病毒分支 Ⅰ,也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疫苗接种。
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。[191]UK Health Security Agency; Public Health Wales; Public Health Agency (Northern Ireland). Principles for control of non-HCID mpox in the UK: 4 nations consensus statement. Oct 2024 [internet publication].
https://www.gov.uk/government/publications/principles-for-monkeypox-control-in-the-uk-4-nations-consensus-statement
请参阅当地指南,获取有关感染预防和控制措施的指导信息。推荐意见可能根据不同的猴痘病毒分支而异,通常推荐对猴痘病毒分支 Ⅰ 采取强化措施(例如,空气传播预防措施)。
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。[11]World Health Organization. Mpox (monkeypox): fact sheet. Aug 2024 [internet publication].
https://www.who.int/en/news-room/fact-sheets/detail/monkeypox
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. Jun 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、重症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。
考虑将重症风险较高的患者(例如儿童、孕妇、免疫功能受损者、皮肤疾病者)收治住院,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,基于临床医师评估并遵循 UKHSA 指导,疑似病例可采取居家自我隔离。但应与当地感染防控小组和输入性发热性疾病管理机构讨论符合分支 Ⅰ 型 mpox 具有严重后果的传染病 (HCID) 病例定义的疑似病例,因为他们将审查风险评估并就下一步调查和管理提出建议。[193]UK Health Security Agency. Mpox: guidance on when to suspect a case of mpox. Oct 2024 [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。
收治因临床状况需要住院的患者,或在临床评估后因社会或医疗原因而无法自我隔离的患者。
英格兰 NHS 建议采用风险分层的临床方法来辅助决策制定。[227]NHS England. Management of laboratory confirmed mpox infections. February 2023 [internet publication].
https://www.england.nhs.uk/publication/management-of-laboratory-confirmed-mpox-infections
在英国,所有分支 Ⅱ(分支 Ⅱa 和分支 Ⅱb)病毒感染均不被归类为 HCID。但分支 Ⅰ 病毒引起的感染则被视为 HCID。[260]UK Health Security Agency. HCID status of mpox (monkeypox). Oct 2024 [internet publication].
https://www.gov.uk/guidance/hcid-status-of-monkeypox
2023 年首次发现经性传播感染的分支 Ⅰ (由新发现的分支 Ⅰb 变异株引起 )所致聚集性病例后,在存在分支 Ⅱ 感染的情况下,未被发现的 HCID 感染风险增加。[229]UK Health Security Agency. Mpox: diagnostic testing. Sep 2024 [internet publication].
https://www.gov.uk/guidance/monkeypox-diagnostic-testing
建议给予适当的对症治疗(关注疼痛控制)和支持性治疗,这些对大部分患者来说就已足够。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. Jun 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。[261]Centers for Disease Control and Prevention. Clinical considerations for pain management. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/pain-management.html
[262]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. Jun 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[261]Centers for Disease Control and Prevention. Clinical considerations for pain management. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/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. Jun 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[261]Centers for Disease Control and Prevention. Clinical considerations for pain management. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/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。[261]Centers for Disease Control and Prevention. Clinical considerations for pain management. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/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. Jun 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[261]Centers for Disease Control and Prevention. Clinical considerations for pain management. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/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. Jun 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[261]Centers for Disease Control and Prevention. Clinical considerations for pain management. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/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。[263]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。
尽管疼痛管理是管理的关键考量因素(超过一半的患者报告有一定程度的疼痛),但目前没有高质量的证据可以指导临床决策。该领域缺乏随机对照试验,也缺乏有助于标准化疼痛控制计划的研究。[264]Hallo-Carrasco A, Hunt CL, Prusinski CC, et al. Pain associated with monkeypox virus: a rapid review. Cureus. 2023 Feb;15(2):e34697.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9995223
http://www.ncbi.nlm.nih.gov/pubmed/36909034?tool=bestpractice.com
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。[261]Centers for Disease Control and Prevention. Clinical considerations for pain management. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/pain-management.html
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)。[261]Centers for Disease Control and Prevention. Clinical considerations for pain management. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/pain-management.html
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。
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. Jun 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[261]Centers for Disease Control and Prevention. Clinical considerations for pain management. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/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. Jun 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
建议患者吃软食,确保经口补液充分。在严重吞咽痛的情况下,可能需要静脉补液。[265]Maredia H, Sartori-Valinotti JC, Ranganath N, et al. Supportive care management recommendations for mucocutaneous manifestations of monkeypox infection. Mayo Clin Proc. 2023 Apr 29 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148669
http://www.ncbi.nlm.nih.gov/pubmed/37125977?tool=bestpractice.com
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)。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. Jun 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
根据标准推荐,提供维生素 A 补剂,因其有助于伤口愈合和促进眼健康。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. Jun 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
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. Jun 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. Jun 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。[5]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)。[266]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。[209]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。
建议进行适当的伤口护理,并应包括以下一般原则:[267]American Academy of Dermatology Association. Mpox: treating severe lesions [internet publication].
https://www.aad.org/member/clinical-quality/clinical-care/mpox/severe-lesions
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. Jun 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
重症或有并发症的疾病或者有重症高风险的患者
对于重症患者或有重症高风险的患者,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)。[106]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
[200]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
[201]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
[205]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
[224]Gomez-Garberi M, Sarrio-Sanz P, Martinez-Cayuelas L, et al. Genitourinary lesions due to monkeypox. Eur Urol. 2022 Dec;82(6):625-30.
https://www.sciencedirect.com/science/article/pii/S0302283822026252
http://www.ncbi.nlm.nih.gov/pubmed/36096858?tool=bestpractice.com
[227]NHS England. Management of laboratory confirmed mpox infections. February 2023 [internet publication].
https://www.england.nhs.uk/publication/management-of-laboratory-confirmed-mpox-infections
[268]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
[269]Fink DL, Callaby H, Luintel A, et al. Clinical features and management of individuals admitted to hospital with monkeypox and associated complications across the UK: a retrospective cohort study. Lancet Infect Dis. 2022 Dec 22 [Epub ahead of print].
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00806-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36566771?tool=bestpractice.com
2022 年全球分支 Ⅱ 型 mpox 暴发数据表明,大约 7%-13% 的病例需要接受入院治疗。一项纳入 7000 多例病例的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% 下降至 2022 年暴发期间的 5.8%。[270]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。
最常见的住院原因是:[271]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”。
对于重症或有并发症的疾病患者,或者有发生重症或并发症高风险的患者,需收治住院,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. Jun 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. Jun 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。
对于具有严重疾病或迁延不愈或危及生命疾病(或发生此类疾病风险较高)的患者,考虑抗病毒治疗。[1]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. Jun 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[226]Centers for Disease Control and Prevention. Clinical treatment of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care
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 mpox 活性,可能带来获益。[243]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
[272]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
[273]Shamim MA, Padhi BK, Satapathy P, et al. The use of antivirals in the treatment of human monkeypox outbreaks: a systematic review. Int J Infect Dis. 2023 Feb;127:150-61.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719850
http://www.ncbi.nlm.nih.gov/pubmed/36470502?tool=bestpractice.com
对于具有严重疾病或迁延不愈或危及生命疾病(或发生此类疾病风险较高)的患者,考虑抗病毒治疗,此类患者包括严重免疫功能受损患者、特应性皮炎患者及其他影响皮肤完整性疾病患者、儿童,以及妊娠/哺乳女性。应在病程早期开始治疗。然而,目前还没有人类相关安全性和有效性数据来支持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. Jun 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
[226]Centers for Disease Control and Prevention. Clinical treatment of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care
CDC 已经制定了处理疑诊、拟诊或确诊猴痘患者的管理流程,尤其是具有迁延不愈或危及生命表现的患者,以帮助治疗应用相关决策制定。[274]Centers for Disease Control and Prevention. Interim clinical treatment considerations for severe manifestations of Mpox — United States, February 2023. Mar 2023 [internet publication].
https://www.cdc.gov/mmwr/volumes/72/wr/mm7209a4.htm?s_cid=mm7209a4_x
对于需要抗病毒治疗的患者,通常建议特考韦瑞(正痘病毒 VP37 包膜蛋白抑制剂)作为一线治疗。[226]Centers for Disease Control and Prevention. Clinical treatment of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care
它在英国和欧洲被批准用于治疗 mpox。在英国,可提供给因重度或复杂性感染入院的有症状患者。
美国已批准该药用于天花,但可能在研究型新药试验方案扩展使用情况下用于治疗符合入选标准患者的猴痘。也可通过参加美国国立过敏与传染病研究所资助的特考韦瑞猴痘病毒研究(Study of Tecovirimat for Mpox, STOMP)试验来获取该药。
可能获批或推荐用于天花的替代抗病毒药物包括 brincidofovir(一种正痘病毒核苷酸类似物 DNA 聚合酶抑制剂和 cidofovir 前体药物)、cidofovir(一种具有抗痘病毒活性的核苷酸类似物抗病毒药物)或牛痘免疫球蛋白(请参阅新兴治疗)。
brincidofovir 在欧洲获得天花治疗孤儿药资格认定。它在美国获批用于治疗天花,但根据美国食品药品监督管理局授权的单名患者紧急使用试验用新药扩展供药方案,也可用于治疗选定患者的 mpox。[226]Centers for Disease Control and Prevention. Clinical treatment of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care
cidofovir 在美国获批用于治疗 AIDS 患者的巨细胞病毒性视网膜炎,但可考虑超说明书用于重度 mpox 患者。[226]Centers for Disease Control and Prevention. Clinical treatment of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care
在部分国家,根据当地公共卫生部门指导,这些替代药物可超说明书用药,用于 mpox 治疗。
美国 CDC 建议这些治疗可用于以下情况的辅助治疗或替代治疗:[226]Centers for Disease Control and Prevention. Clinical treatment of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care
眼部感染
例如,因为严重免疫功能受损而存在猴痘迁延不愈或危及生命表现的患者
tecovirimat 治疗后出现临床显著疾病进展,或经 tecovirimat 治疗获得初期改善后复发的患者
存在 tecovirimat 耐药性忧虑的患者
对 tecovirimat 过敏,或因其他原因无法接受 tecovirimat 的患者。
应根据个体病例及临床和其他参数来作出决定。几乎所有采用 brincidofovir 或 cidofovir 治疗的患者都是严重免疫功能受损,需要联合特考韦瑞治疗。
据报道,在免疫功能受损的患者中出现了经实验室证实的特考韦瑞耐药性个案和聚集性病例,尤其是接受特考韦瑞多个疗程或延长疗程治疗者,以及无既往特考韦瑞治疗记录者(由特考韦瑞耐药性猴痘病毒变异株的播散所致)。[275]Smith TG, Gigante CM, Wynn NT, et al. Tecovirimat resistance in mpox patients, United States, 2022-2023. Emerg Infect Dis. 2023 Oct 19;29(12).
https://wwwnc.cdc.gov/eid/article/29/12/23-1146_article
http://www.ncbi.nlm.nih.gov/pubmed/37856204?tool=bestpractice.com
[276]Mertes H, Rezende AM, Brosius I, et al. Tecovirimat resistance in an immunocompromised patient with mpox and prolonged viral shedding. Ann Intern Med. 2023 Aug;176(8):1141-3.
https://www.acpjournals.org/doi/10.7326/L23-0131
[277]Gigante CM, Takakuwa J, McGrath D, et al. Notes from the field: mpox cluster caused by tecovirimat-resistant monkeypox virus - five states, October 2023-February 2024. MMWR Morb Mortal Wkly Rep. 2024 Oct 10;73(40):903-5.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11466377
http://www.ncbi.nlm.nih.gov/pubmed/39388389?tool=bestpractice.com
对于完成 14 日治疗后出现持续性或新发皮损的任何患者,考虑采集皮损拭子样本进行特考韦瑞耐药性检测,并采集血浆样本行药代动力学分析(观察药物水平是否低于目标浓度)。[278]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
据报道,在 tecovirimat 用药后出现治疗后病变(即,在完成推荐的 14 日疗程后以及初始病变改善或消退后≤30 日,很可能或确诊的 mpox 的患者出现新的皮肤或黏膜病变)。需要开展进一步研究以了解这些新病变的病因。[279]Seifu L, Garcia E, McPherson TD, et al. Notes from the field: posttreatment lesions after tecovirimat treatment for Mpox - New York City, August-September 2022. MMWR Morb Mortal Wkly Rep. 2023 Apr 28;72(17):471-2.
https://www.cdc.gov/mmwr/volumes/72/wr/mm7217a5.htm?s_cid=mm7217a5_w
http://www.ncbi.nlm.nih.gov/pubmed/37104293?tool=bestpractice.com
支持使用抗病毒疗法的证据有限。没有支持使用抗病毒药物的随机对照试验数据。一项 Cochrane 评价没有发现来自随机对照试验的证据,表明这些药物的安全性和有效性,但 tecovirimat 在成人和儿童中的试验正在进行中。[280]Fox T, Gould S, Princy N, et al. Therapeutics for treating mpox in humans. Cochrane Database Syst Rev. 2023 Mar 14;(3):CD015769.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015769/full
http://www.ncbi.nlm.nih.gov/pubmed/36916727?tool=bestpractice.com
Tecovirimat
其有效性已在两项使用正痘病毒的动物模型研究中得到证实,而安全性则已在一项 3 期临床试验中得到证实,该试验纳入了 359 名健康人类志愿者。[281]ClinicalTrials.gov. A trial to assess the safety, tolerability, and pharmacokinetics of the anti-orthopoxvirus compound tecovirimat (SIGA246-008). November 2017 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT02474589
[282]Grosenbach DW, Honeychurch K, Rose EA, et al. Oral tecovirimat for the treatment of smallpox. N Engl J Med. 2018 Jul 5;379(1):44-53.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086581
http://www.ncbi.nlm.nih.gov/pubmed/29972742?tool=bestpractice.com
对于人类 mpox 的有效性仅限于病例报告和病例研究。[283]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
[284]Matias WR, Koshy JM, Nagami EH, et al. Tecovirimat for the treatment of human monkeypox: an initial series from Massachusetts, United States. Open Forum Infect Dis. 2022 Aug;9(8):ofac377.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356679
http://www.ncbi.nlm.nih.gov/pubmed/35949403?tool=bestpractice.com
[285]Desai AN, Thompson GR 3rd, Neumeister SM, et al. Compassionate use of tecovirimat for the treatment of monkeypox infection. JAMA. 2022 Oct 4;328(13):1348-50.
https://jamanetwork.com/journals/jama/fullarticle/2795743
http://www.ncbi.nlm.nih.gov/pubmed/35994281?tool=bestpractice.com
[286]O'Laughlin K, Tobolowsky FA, Elmor R, et al. Clinical use of tecovirimat (Tpoxx) for treatment of monkeypox under an investigational new drug protocol: United States, May - August 2022. MMWR Morb Mortal Wkly Rep. 2022 Sep 16;71(37):1190-5.
https://www.cdc.gov/mmwr/volumes/71/wr/mm7137e1.htm
http://www.ncbi.nlm.nih.gov/pubmed/36107794?tool=bestpractice.com
[287]Viguier C, de Kermel T, Boumaza X, et al. A severe monkeypox infection in a patient with an advanced HIV infection treated with tecovirimat: clinical and virological outcome. Int J Infect Dis. 2022 Oct 29;125:135-7.
https://www.ijidonline.com/article/S1201-9712(22)00568-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36397606?tool=bestpractice.com
[288]Mbrenga F, Nakouné E, Malaka C, et al. Tecovirimat for monkeypox in Central African Republic under expanded access. N Engl J Med. 2022 Dec 15;387(24):2294-5.
https://www.nejm.org/doi/10.1056/NEJMc2210015
http://www.ncbi.nlm.nih.gov/pubmed/36449745?tool=bestpractice.com
[289]Wu EL, Osborn RL, Bertram CM, et al. Tecovirimat use in ambulatory and hospitalized patients with monkeypox virus infection. Sex Transm Dis. 2022 Dec 2 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/36455293?tool=bestpractice.com
[290]Hermanussen L, Brehm TT, Wolf T, et al. Tecovirimat for the treatment of severe mpox in Germany. Infection. 2023 Oct;51(5):1563-8.
https://link.springer.com/article/10.1007/s15010-023-02049-0
http://www.ncbi.nlm.nih.gov/pubmed/37273167?tool=bestpractice.com
缺乏针对孕妇或哺乳期妇女和儿童的安全性和有效性数据。对孕妇使用 tecovirimat 的建议基于未观察到胚胎-胎儿发育毒性的动物研究。[36]Centers for Disease Control and Prevention. Clinical considerations for mpox in children and adolescents in the U.S. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/pediatric.html
[129]Centers for Disease Control and Prevention. Mpox considerations for people who are pregnant or breastfeeding. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/pregnancy.html
根据病例报告,早期使用 tecovirimat 进行治疗可有助于重度直肠炎患者的疼痛控制。[263]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。
随机对照试验目前仍在研发或进行中(例如,STOMP 试验),应鼓励患者尽可能加入试验。[291]Rojek A, Dunning J, Olliaro P. Monkeypox: how will we know if the treatments work? Lancet Infect Dis. 2022 Sep;22(9):1269-70.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00514-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/35931096?tool=bestpractice.com
[292]National Institute for Health and Care Research. Efficacy of tecovirimat for the treatment of non-hospitalised patients with confirmed monkeypox: research brief. May 2022 [internet publication].
https://www.nihr.ac.uk/documents/efficacy-of-tecovirimat-for-the-treatment-of-non-hospitalised-patients-with-confirmed-monkeypox-research-brief/30705
[293]University of Oxford. PLATINUM: placebo-controlled randomised trial of tecovirimat in non-hospitalised monkeypox patients. 2022 [internet publication].
https://www.platinumtrial.ox.ac.uk
[294]National Institutes of Health. STOMP: study of tecovirimat for human monkeypox virus. 2022 [internet publication].
https://www.stomptpoxx.org/main
PALM007 试验(一项在刚果民主共和国进行的随机安慰剂对照试验)的初步分析表明,与安慰剂相比,特考韦瑞并未缩短分支 Ⅰ 型 mpox 儿童和成人的皮损持续时间。然而,该研究中的总体死亡率低于刚果民主共和国报告的所有病例的总体死亡率(即 1.7% vs. 3.6%),这可能是由于该研究的参与者都在医院接受了支持性治疗。[295]ClinicalTrials.gov. Tecovirimat for treatment of monkeypox virus. Jul 2024 [internet publication].
https://clinicaltrials.gov/study/NCT05559099
[296]National Institutes of Health. The antiviral tecovirimat is safe but did not improve clade I mpox resolution in Democratic Republic of the Congo. Aug 2024 [internet publication].
https://www.nih.gov/news-events/news-releases/antiviral-tecovirimat-safe-did-not-improve-clade-i-mpox-resolution-democratic-republic-congo
该研究尚未发表。
HIV 状态似乎不会影响 tecovirimat 的治疗结局。[297]McLean J, Stoeckle K, Huang S, et al. Tecovirimat treatment of people with HIV during the 2022 Mpox outbreak : a retrospective cohort study. Ann Intern Med. 2023 May 2 [Epub ahead of print].
https://www.acpjournals.org/doi/10.7326/M22-3132
http://www.ncbi.nlm.nih.gov/pubmed/37126820?tool=bestpractice.com
[298]Aldred B, Lyles RH, Scott JY, et al. Early tecovirimat treatment for mpox disease among people with HIV. JAMA Intern Med. 2024 Mar 1;184(3):275-9.
http://www.ncbi.nlm.nih.gov/pubmed/38190312?tool=bestpractice.com
一项 Cochrane 评价发现了来自非随机研究的极低确定性证据,表明 tecovirimat 没有严重的安全性信号。[280]Fox T, Gould S, Princy N, et al. Therapeutics for treating mpox in humans. Cochrane Database Syst Rev. 2023 Mar 14;(3):CD015769.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015769/full
http://www.ncbi.nlm.nih.gov/pubmed/36916727?tool=bestpractice.com
布林西多福韦
目前尚无 brincidofovir 治疗人类 mpox 病例的有效性相关数据。
一项 Cochrane 评价发现了极低确定性证据,表明 brincidofovir 有肝损伤的安全性信号。[280]Fox T, Gould S, Princy N, et al. Therapeutics for treating mpox in humans. Cochrane Database Syst Rev. 2023 Mar 14;(3):CD015769.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015769/full
http://www.ncbi.nlm.nih.gov/pubmed/36916727?tool=bestpractice.com
西多福韦
体外和猕猴激发研究表明 cidofovir 可能对 mpox 有所益处。[299]Stittelaar KJ, Neyts J, Naesens L, et al. Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection. Nature. 2006 Feb 9;439(7077):745-8.
https://www.nature.com/articles/nature04295
http://www.ncbi.nlm.nih.gov/pubmed/16341204?tool=bestpractice.com
[300]Huggins J, Goff A, Hensley L, et al. Nonhuman primates are protected from smallpox virus or monkeypox virus challenges by the antiviral drug ST-246. Antimicrob Agents Chemother. 2009 Jun;53(6):2620-5.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687232
http://www.ncbi.nlm.nih.gov/pubmed/19349521?tool=bestpractice.com
然而,关于 cidofovir 治疗人类 mpox 病例的有效性数据非常有限。[301]Fabrizio C, Bruno G, Cristiano L, et al. Cidofovir for treating complicated monkeypox in a man with acquired immune deficiency syndrome. Infection. 2022 Nov 10 [Epub ahead of print].
https://link.springer.com/article/10.1007/s15010-022-01949-x
http://www.ncbi.nlm.nih.gov/pubmed/36355271?tool=bestpractice.com
[302]Raccagni AR, Candela C, Bruzzesi E, et al. Real-life use of cidofovir for the treatment of severe monkeypox cases. J Med Virol. 2022 Oct 13 [Epub ahead of print].
https://onlinelibrary.wiley.com/doi/10.1002/jmv.28218
http://www.ncbi.nlm.nih.gov/pubmed/36229902?tool=bestpractice.com
[303]Mondi A, Gagliardini R, Mazzotta V, et al. Clinical experience with use of oral tecovirimat or intravenous cidofovir for the treatment of monkeypox in an Italian reference hospital. J Infect. 2022 Nov 5 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637020
http://www.ncbi.nlm.nih.gov/pubmed/36347428?tool=bestpractice.com
[304]Labate L, Brucci G, Ciccarese G, et al. Nasal monkeypox virus infection successfully treated with cidofovir in a patient newly diagnosed with HIV. Int J STD AIDS. 2022 Dec 15 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/36520997?tool=bestpractice.com
[305]Stafford A, Rimmer S, Gilchrist M, et al. Use of cidofovir in a patient with severe mpox and uncontrolled HIV infection. Lancet Infect Dis. 2023 Feb 8 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9908088
http://www.ncbi.nlm.nih.gov/pubmed/36773621?tool=bestpractice.com
此类药物在部分国家可能有库存,但暂未广泛普及。
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. Jun 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。[258]Centers for Disease Control and Prevention. Mpox infection prevention and control in healthcare settings. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/infection-control/healthcare-settings.html
一般而言,在所有皮损消退并长出新的皮肤前,应继续采取预防措施。
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。[283]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:[306]UK Health Security Agency. De-isolation and discharge of mpox-infected patients. Sep 2024 [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)。
UKHSA 建议,在家庭环境中,一旦符合以下皮损标准,患者即可结束居家自我隔离。[306]UK Health Security Agency. De-isolation and discharge of mpox-infected patients. Sep 2024 [internet publication].
https://www.gov.uk/guidance/de-isolation-and-discharge-of-monkeypox-infected-patients-interim-guidance
当患者符合以下皮损标准时,即可完全恢复正常活动,不受任何限制(完全解除隔离):[306]UK Health Security Agency. De-isolation and discharge of mpox-infected patients. Sep 2024 [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
对于疑诊、拟诊或确诊的 mpox 儿童和青少年,如果他们发生重症或有重症的风险(例如,1 岁以下儿童、严重的免疫功能受损、存在破坏皮肤完整性的疾病),或累及可能导致严重后遗症的解剖区域,则应根据具体情况考虑治疗方案。对于<6 月龄儿童,可考虑采取抗病毒治疗(咨询当地公共卫生机构),因为尚不清楚幼儿是否会发生更严重的病情。而疾病管理大体与成人患者相同,除少数例外。[36]Centers for Disease Control and Prevention. Clinical considerations for mpox in children and adolescents in the U.S. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/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。[129]Centers for Disease Control and Prevention. Mpox considerations for people who are pregnant or breastfeeding. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/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. Jun 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,在妊娠或母乳喂养期间的人类使用数据有限,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)。[129]Centers for Disease Control and Prevention. Mpox considerations for people who are pregnant or breastfeeding. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/pregnancy.html
在一项纳入 23 名孕妇的研究中,11 名孕妇接受了特考韦瑞治疗(包括在早期妊娠使用),无任何不良反应报告。[20]Oakley LP, Hufstetler K, O'Shea J, et al. Mpox cases among cisgender women and pregnant persons: United States, May 11 - November 7, 2022. MMWR Morb Mortal Wkly Rep. 2023 Jan 6;72(1):9-14.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815154
http://www.ncbi.nlm.nih.gov/pubmed/36602932?tool=bestpractice.com
已经报告了一例孕妇在妊娠晚期接受 tecovirimat 的案例。未报告孕产妇或新生儿并发症,也没有新生儿感染的证据。[307]Sampson MM, Magee G, Schrader EA, et al. Mpox (Monkeypox) infection during pregnancy. Obstet Gynecol. 2023 May 1;141(5):1007-10.
http://www.ncbi.nlm.nih.gov/pubmed/36928418?tool=bestpractice.com
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。[129]Centers for Disease Control and Prevention. Mpox considerations for people who are pregnant or breastfeeding. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/pregnancy.html
已经提出管理孕妇的进一步指南。[308]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
[309]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
免疫受损
对于 HIV 相关免疫抑制患者(即 CD4 细胞计数<200 个细胞/μL,尤其是<50 个细胞/μL),以及因其他疾病或使用免疫抑制剂而导致免疫功能受损的患者,出现重症或病程迁延、住院治疗和播散性病变的风险增加(尤其是那些严重的免疫功能受损者)。应优先对这些患者进行治疗和密切监测。[37]Centers for Disease Control and Prevention. Clinical considerations for mpox in immunocompromised people. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/immunocompromised-people.html
[38]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
与 CD4 计数<300 个细胞/μL 的患者相比,CD4 计数<100 个细胞/μL 的患者更常见严重并发症,包括坏死性皮肤病损、肺功能障碍、继发感染和脓毒症。所有死亡都发生在 CD4 计数<200 个细胞/μL 的患者中,大多数发生在 HIV 病毒载量高的患者中。[144]Mitjà O, Alemany A, Marks M, et al. Mpox in people with advanced HIV infection: a global case series. Lancet. 2023 Mar 18;401(10380):939-49.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00273-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36828001?tool=bestpractice.com
对于免疫功能受损的患者,早期改善其免疫功能很重要。在治疗期间应尽可能延迟化疗或免疫调节疗法(或降低剂量)。尚无高质量的证据支持或发对将免疫调节剂用于治疗猴痘患者。然而,有模型表明皮质类固醇与感染正痘病毒动物出现重症(甚至死亡)有关。谨慎使用全身性免疫调节剂(包括皮质类固醇),或在可行的情况下减少使用,权衡其风险和获益。[274]Centers for Disease Control and Prevention. Interim clinical treatment considerations for severe manifestations of Mpox — United States, February 2023. Mar 2023 [internet publication].
https://www.cdc.gov/mmwr/volumes/72/wr/mm7209a4.htm?s_cid=mm7209a4_x
对于 HIV 感染者:[37]Centers for Disease Control and Prevention. Clinical considerations for mpox in immunocompromised people. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/immunocompromised-people.html
[38]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
在管理猴痘期间继续(或开始/重新开始)抗逆转录病毒治疗(antiretroviral therapy, ART)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。在接受 ART 治疗以进行暴露前或暴露后预防的患者应继续接受治疗。未接受 ART 治疗的患者应尽快开始使用 ART 药物(咨询 HIV 治疗专家)以改善免疫功能,最好与 mpox 疗法同时进行。
每次都要检查猴痘治疗用抗病毒药物与 HIV 感染 ART 药物(或其他治疗)间是否存在药物相互作用。
在治疗和随访期间监测病毒载量和 CD4 计数。病例系列研究表明,在感染期间,这些参数可能会发生变化。[310]Raccagni AR, Mileto D, Galli L, et al. HIV viral load monitoring during monkeypox virus infection among PLWH. AIDS. 2023 Jan 9 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/36689645?tool=bestpractice.com
如果免疫功能受损患者有治疗指征,则建议一线治疗使用特考韦瑞(可能是静脉制剂)。尽快开始治疗,并根据每日情况考虑将疗程延长至标准的 14 日以上。对于使用特考韦瑞期间病情无改善或出现进展的患者,或者根据免疫功能受损和不受控制的病毒复制的程度,可考虑加用其他治疗(如西多福韦、布林西多福韦、牛痘免疫球蛋白)。[37]Centers for Disease Control and Prevention. Clinical considerations for mpox in immunocompromised people. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/immunocompromised-people.html
[38]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
[311]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: mpox. Jul 2023 [internet publication].
https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/mpox?view=full
对于重症者,可在首次就诊时考虑联合治疗(咨询当地公共卫生机构或 mpox 管理专家)。[311]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: mpox. Jul 2023 [internet publication].
https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/mpox?view=full
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。[167]British HIV Association. BHIVA rapid guidance on monkeypox virus. October 2022 [internet publication].
https://www.bhiva.org/rapid-guidance-on-monkeypox-virus