仅当满足恰当的临床病例定义,且诊断通过实验室检测证实时,才能确诊。
在评估有特征性皮疹者时,特别是当患者符合流行病学标准之一时,建议高度怀疑。由于临床表现可能不典型,当患者出现与性传播感染(sexually transmitted infection, STI)相关或类似 STI 的皮疹时,即使皮疹呈局限性而非(尚未呈)弥漫性,也应将 mpox 纳入鉴别诊断。
mpox 是应予通报的疾病,出现一例即被认为是暴发。应立即向国家或当地公共卫生机构报告疑似病例,无论是否正在探究其他可能诊断。
筛查和分诊
在进入卫生系统的第一个地点,对所有出现皮疹、发热或淋巴结肿大的人员进行筛查和分诊,以识别疑似或确诊感染者。[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
在进入医疗机构时,可使用一份基于世界卫生组织(World Health Organization, WHO)病例定义(根据当地流行病学进行调整)的简化问卷和筛查方案。
进行筛查活动时,与患者保持至少 1 米的距离,并采用 "不接触 "的方式。在某些情况下,根据当地的路径,可使用远程医疗进行筛查。
将症状符合疑似感染病例定义的患者立即转至 mpox 临床诊疗路径。向患者提供适配良好的面罩,将其隔离在通气良好的单人房间。
采用标准化分诊工具来分诊患者。
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)。
病史
采集患者的全面病史,评估潜在暴露情况或流行病学风险因素,包括详细的性行为史。[192]Centers for Disease Control and Prevention. Clinical overview of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-overview/index.html
对于表现出不明原因急性皮疹的患者,尤其当患者在症状出现之前 21 日满足某一项流行病学标准时,应考虑该诊断。
流行病学诊断标准包括:[116]World Health Organization. Surveillance, case investigation and contact tracing for mpox (monkeypox): interim guidance, 20 March 2024. Mar 2024 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Surveillance-2022.4
[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
[194]Centers for Disease Control and Prevention. Mpox case definitions. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/case-definitions
近期到访流行国家(或当前疫情暴发的国家)
与疑似、拟诊、可能或确诊病例(或受污染物料)接触
与正在经历 mpox 活动的社交网络的人员(例如男男性行为人群 [men who have sex with men, MSM])、有多个性伴侣和/或随意性伴侣者)产生亲密的躯体接触(包括性接触)
接触非洲特有的野生动物物种或奇异宠物(死的或活的)或这些动物制品
流行病学标准和病例定义因地区而异。请咨询当地公共卫生部门,获取更多信息。请参阅“诊断标准”,了解病例定义。
然而,对于出现与猴痘相符皮疹的任何人,无论其是否存在流行病学风险,均应警惕猴痘。美国一项调查研究,在 13 家急诊科进行猴痘相符皮疹评估的 196 例患者中,不管其流行病学风险如何,检测到 3 例猴痘病例(1.5%)。所有病例均为未接种疫苗的 MSM,他们均有通过约会应用软件与一个或多个伴侣发生亲密关系。[195]Berdahl CT, Krishnadasan A, Pathmarajah K, et al. Mpox surveillance based on rash characteristics - 13 emergency departments, United States, June-December 2023. MMWR Morb Mortal Wkly Rep. 2024 Jun 6;73(22):507-13.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166258
http://www.ncbi.nlm.nih.gov/pubmed/38843078?tool=bestpractice.com
值得注意的是,并非所有有风险的 MSM 都会认定自己面临风险,也并不都会披露这一信息。[196]Mulka L, Cassell J. The changing face of monkeypox. BMJ. 2022 Aug 10;378:o1990.
https://www.bmj.com/content/378/bmj.o1990
http://www.ncbi.nlm.nih.gov/pubmed/35948354?tool=bestpractice.com
确定所有有性行为成人和青少年的 HIV 感染状况,因为 HIV 相关免疫功能低下的患者具有更高的风险出现严重表现。[197]Centers for Disease Control and Prevention. Health alert network (HAN) health advisory: severe manifestations of monkeypox among people who are immunocompromised due to HIV or other conditions. September 2022 [internet publication].
https://emergency.cdc.gov/han/2022/han00475.asp
临床表现
mpox 分支 Ⅰ 和 mpox 分支 Ⅱ 所致感染的临床表现通常相同。
在潜伏期(范围 1-21 日),患者通常没有任何症状,并可能诉其感觉良好。而在潜伏期不具有传染性。患者通常在皮疹/病损出现之前出现前驱症状,可能持续 1-5 日。但是,皮疹出现后可能会出现全身症状,而有些患者可能完全无症状。[198]Centers for Disease Control and Prevention. Clinical features of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-signs
[199]Philpott D, Hughes CM, Alroy KA, et al. Epidemiologic and clinical characteristics of monkeypox cases: United States, May 17 – July 22, 2022. MMWR Morb Mortal Wkly Rep. 2022 Aug 12;71(32):1018-22.
https://www.cdc.gov/mmwr/volumes/71/wr/mm7132e3.htm
http://www.ncbi.nlm.nih.gov/pubmed/35951487?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
常见症状包括:[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
[96]Fenner F, Henderson DA, Arita I, et al. Chapter 29: Human monkeypox and other poxvirus infections of man. In: Smallpox and its eradication. Geneva: World Health Organization; 1988.
http://apps.who.int/iris/handle/10665/39485
[198]Centers for Disease Control and Prevention. Clinical features of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-signs
皮疹/病损
肛门直肠症状
发热
畏寒
淋巴结肿大
疲劳/虚弱/周身不适
肌痛
头痛
咽痛
背痛
咳嗽
恶心/呕吐
较不常见的症状包括:[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
[96]Fenner F, Henderson DA, Arita I, et al. Chapter 29: Human monkeypox and other poxvirus infections of man. In: Smallpox and its eradication. Geneva: World Health Organization; 1988.
http://apps.who.int/iris/handle/10665/39485
虽然皮损仍是典型的症状,但是在近来的暴发中皮损的解剖部位分布已有不同。与既往暴发相比,生殖器受累更为常见。肛门直肠症状是此次暴发的特有表现,之前并无相关描述。[34]Li P, Li J, Ayada I, et al. Clinical features, antiviral treatment and patient outcomes: a systematic review and comparative analysis of the previous and the 2022 mpox outbreaks. J Infect Dis. 2023 Feb 3 [Epub ahead of print].
https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiad034/7025706?login=false
http://www.ncbi.nlm.nih.gov/pubmed/36735342?tool=bestpractice.com
[59]Hatami H, Jamshidi P, Arbabi M, et al. Demographic, epidemiologic, and clinical characteristics of human Monkeypox disease pre- and post-2022 Outbreaks: a systematic review and meta-analysis. Biomedicines. 2023 Mar 20;11(3):957.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045775
http://www.ncbi.nlm.nih.gov/pubmed/36979936?tool=bestpractice.com
皮疹/病损(95%)、发热(58%)和淋巴结肿大(53%)是最常报告的症状,而 18.5% 的患者报告肛门直肠疼痛/直肠炎。[16]Liu Q, Fu L, Wang B, et al. Clinical characteristics of human mpox (monkeypox) in 2022: a systematic review and meta-analysis. Pathogens. 2023 Jan 15;12(1):146.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861547
http://www.ncbi.nlm.nih.gov/pubmed/36678494?tool=bestpractice.com
与肛周/直肠病变和直肠炎有关的剧烈肛门直肠疼痛(包括排便时的严重疼痛)、里急后重、直肠出血或脓/血便一直是非典型表现。出现直肠炎的患者可能没有皮疹的征象。[198]Centers for Disease Control and Prevention. Clinical features of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-signs
[199]Philpott D, Hughes CM, Alroy KA, et al. Epidemiologic and clinical characteristics of monkeypox cases: United States, May 17 – July 22, 2022. MMWR Morb Mortal Wkly Rep. 2022 Aug 12;71(32):1018-22.
https://www.cdc.gov/mmwr/volumes/71/wr/mm7132e3.htm
http://www.ncbi.nlm.nih.gov/pubmed/35951487?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
[202]Pfäfflin F, Wendisch D, Scherer R, et al. Monkeypox in-patients with severe anal pain. Infection. 2022 Aug 12 [Epub ahead of print].
https://link.springer.com/article/10.1007/s15010-022-01896-7
http://www.ncbi.nlm.nih.gov/pubmed/35960457?tool=bestpractice.com
[203]Yakubovsky M, Shasha D, Reich S, et al. Monkeypox presenting as proctitis in men who have sex with men. Clin Infect Dis. 2022 Sep 6 [Epub ahead of print].
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac737/6692817
http://www.ncbi.nlm.nih.gov/pubmed/36066470?tool=bestpractice.com
其他肛门症状可能包括瘙痒、大便困难、烧灼感、肿胀和黏液分泌物。[204]Rekik S, Pluart DL, Ferré V, et al. Anogenital symptoms and lesions in a series of 20 patients infected with monkeypox virus. Colorectal Dis. 2023 Feb 8 [Epub ahead of print].
https://onlinelibrary.wiley.com/doi/10.1111/codi.16513
http://www.ncbi.nlm.nih.gov/pubmed/36756717?tool=bestpractice.com
进行被动肛交性行为的男性比未进行被动肛交性行为的男性更常出现直肠炎。[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
耳鼻喉科表现(例如,头痛、咽痛、咳嗽、颈部淋巴结肿大)在既往暴发中更为常见。[206]Shah J, Saak TM, Desai AN, et al. Otolaryngologic manifestations among MPOX patients: a systematic review and meta-analysis. Am J Otolaryngol. 2023 Nov-Dec;44(6):103991.
http://www.ncbi.nlm.nih.gov/pubmed/37487464?tool=bestpractice.com
特殊患者群体
儿童和青少年:临床表现与成人类似。[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
婴幼儿严重并发症已见诸报道。[127]Huang YA, Howard-Jones AR, Durrani S, et al. Monkeypox: a clinical update for paediatricians. J Paediatr Child Health. 2022 Sep;58(9):1532-8.
https://onlinelibrary.wiley.com/doi/10.1111/jpc.16171
http://www.ncbi.nlm.nih.gov/pubmed/35979896?tool=bestpractice.com
孕妇:临床表现与非妊娠者相似。[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
免疫功能低下者(包括晚期或未控制 HIV 感染者):可能出现非典型表现或更严重的疾病(例如,脓毒症、播散性皮疹、出血性疾病、大量融合性病损、坏死病损、可能导致梗阻的重度淋巴结肿大、眼部或眶周感染、肺部受累、脑炎、心肌炎或其他需要住院治疗的并发症)。[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
[207]Boesecke C, Monin MB, van Bremen K, et al. Severe monkeypox-virus infection in undiagnosed advanced HIV infection. Infection. 2022 Dec;50(6):1633-4.
https://link.springer.com/article/10.1007/s15010-022-01901-z
http://www.ncbi.nlm.nih.gov/pubmed/35969365?tool=bestpractice.com
然而,合并 HIV 感染的患者更可能出现腹泻、肛周区皮疹/病损、直肠疼痛、肛门直肠脓肿、包茎、肺炎,以及更高的皮疹负担。[141]Chastain DB, Motoa G, Ortiz-Martínez Y, et al. Characteristics and clinical manifestations of monkeypox among people with and without HIV in the United States: a retrospective cohort. AIDS. 2023 Mar 15;37(4):611-6.
http://www.ncbi.nlm.nih.gov/pubmed/36729995?tool=bestpractice.com
[208]Angelo KM, Smith T, Camprubí-Ferrer D, et al. Epidemiological and clinical characteristics of patients with monkeypox in the GeoSentinel Network: a cross-sectional study. Lancet Infect Dis. 2022 Oct 7 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546520
http://www.ncbi.nlm.nih.gov/pubmed/36216018?tool=bestpractice.com
各地区病例定义有所不同。请咨询当地公共卫生部门,获取更多信息。请参阅诊断标准,了解病例定义。
体格检查
皮疹或皮肤病损通常是感染的第一迹象。体格检查可能会发现皮疹或病损,并且可能有淋巴结肿大。进行彻底的皮肤和黏膜(例如肛门、阴道、口腔、鼻腔、眼科)检查。[192]Centers for Disease Control and Prevention. Clinical overview of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-overview/index.html
检查可能发现患者可能未注意到的病变,或者可能根本没有发现任何病变。
通常,患者在急性发热性疾病发作后大约 1-3 天出现特征性皮疹。皮疹通常始于面部和身体,并通过离心方式扩散到手掌和脚底(此前 24 h 中可能会出现累及口咽和舌的皮疹,但常常会被忽略)。病损同时进展,经过四个阶段——斑疹、丘疹、水疱和脓疱期,每个阶段持续 1-2 天,然后结痂、消退。病损直径通常为 5-10 mm,可能呈离散或融合性,数量可能很少或达数千个。水疱边界清晰,位于真皮深处。皮疹通常在 2-4 周内消退。[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
[11]World Health Organization. Mpox (monkeypox): fact sheet. Aug 2024 [internet publication].
https://www.who.int/en/news-room/fact-sheets/detail/monkeypox
[96]Fenner F, Henderson DA, Arita I, et al. Chapter 29: Human monkeypox and other poxvirus infections of man. In: Smallpox and its eradication. Geneva: World Health Organization; 1988.
http://apps.who.int/iris/handle/10665/39485
[178]McCollum AM, Damon IK. Human monkeypox. Clin Infect Dis. 2014 Jan;58(2):260-7.
https://academic.oup.com/cid/article/58/2/260/335791
http://www.ncbi.nlm.nih.gov/pubmed/24158414?tool=bestpractice.com
[198]Centers for Disease Control and Prevention. Clinical features of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-signs
在近来的暴发中,临床表现呈不典型,皮疹主要出现在肛门生殖器区域。[58]Sukhdeo S, Mishra S, Walmsley S. Human monkeypox: a comparison of the characteristics of the new epidemic to the endemic disease. BMC Infect Dis. 2022 Dec 12;22(1):928.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9742013
http://www.ncbi.nlm.nih.gov/pubmed/36503476?tool=bestpractice.com
病损往往局限于生殖器、会阴/肛周或口周区域,通常不会进一步扩散。这表明传播由于性交过程中的接触而发生,病损可能从病原体植入部位开始发作。[74]World Health Organization. Multi-country monkeypox outbreak: situation update. 27 June 2022 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON396
[198]Centers for Disease Control and Prevention. Clinical features of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-signs
[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
[210]European Centre for Disease Prevention and Control. Monkeypox cases reported in UK and Portugal. May 2022 [internet publication].
https://www.ecdc.europa.eu/en/news-events/monkeypox-cases-reported-uk-and-portugal
[211]Patrocinio-Jesus R, Peruzzu F. Monkeypox genital lesions. N Engl J Med. 2022 Jul 7;387(1):66.
https://www.nejm.org/doi/10.1056/NEJMicm2206893
http://www.ncbi.nlm.nih.gov/pubmed/35704421?tool=bestpractice.com
[212]Orviz E, Negredo A, Ayerdi O, et al. Monkeypox outbreak in Madrid (Spain): clinical and virological aspects. J Infect. 2022 Oct;85(4):412-7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534097
http://www.ncbi.nlm.nih.gov/pubmed/35830908?tool=bestpractice.com
[213]Català A, Clavo Escribano P, Riera J, et al. Monkeypox outbreak in Spain: clinical and epidemiological findings in a prospective cross-sectional study of 185 cases. Br J Dermatol. 2022 Nov;187(5):765-72.
https://onlinelibrary.wiley.com/doi/10.1111/bjd.21790
http://www.ncbi.nlm.nih.gov/pubmed/35917191?tool=bestpractice.com
大量的口咽部病变与口交相关,而大量的肛周区域病变与被动肛交有关。[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
其他不典型特征包括:[74]World Health Organization. Multi-country monkeypox outbreak: situation update. 27 June 2022 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON396
[198]Centers for Disease Control and Prevention. Clinical features of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-signs
[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
[214]Quattri E, Avallone G, Maronese CA, et al. Unilesional monkeypox: a report of two cases from Italy. Travel Med Infect Dis. 2022 Aug 10;49:102424.
https://www.sciencedirect.com/science/article/pii/S1477893922001703
http://www.ncbi.nlm.nih.gov/pubmed/35961491?tool=bestpractice.com
[Figure caption and citation for the preceding image starts]: 个体病损的图像(2022 年全球暴发)UKHSA [Citation ends].
大多数患者(64%)有 <10 个皮损,2022 年分支 Ⅱ 所致全球 mpox 暴发中大约 10% 的患者仅有单个生殖器皮损。[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
部分患者可能无皮肤/黏膜病变,在诊断时仅有全身性体征/症状。[215]Ciccarese G, Brucci G, Di Biagio A, et al. Two cases of monkeypox virus infection without detectable cutaneous/mucosal lesions. Travel Med Infect Dis. 2023 Jul-Aug;54:102605.
https://www.sciencedirect.com/science/article/pii/S1477893923000650?via%3Dihub
非典型的单一病损可与脓肿和其他深层组织病变表现相似。[196]Mulka L, Cassell J. The changing face of monkeypox. BMJ. 2022 Aug 10;378:o1990.
https://www.bmj.com/content/378/bmj.o1990
http://www.ncbi.nlm.nih.gov/pubmed/35948354?tool=bestpractice.com
在一项研究中,约有三分之一患者在一个时间点出现了不同阶段的病损。[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
2022 年全球分支 Ⅱ 型 mpox 暴发中最常见的皮损类型为生殖器皮损(66%)。21% 的患者出现口咽/口腔病变。[16]Liu Q, Fu L, Wang B, et al. Clinical characteristics of human mpox (monkeypox) in 2022: a systematic review and meta-analysis. Pathogens. 2023 Jan 15;12(1):146.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861547
http://www.ncbi.nlm.nih.gov/pubmed/36678494?tool=bestpractice.com
口腔病损可能见于口腔黏膜的不同部位,包括唇、舌以及最常见的扁桃体。食管病损也已有报道。[216]Ardila CM, Arrubla-Escobar DE, Vivares-Builes AM. Oral lesions in patients with human monkeypox: a systematic scoping review. J Oral Pathol Med. 2022 Oct 20 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/36263594?tool=bestpractice.com
[217]Mishra S, Khan R, Krizova A, et al. Esophageal monkeypox lesion. Clin Gastroenterol Hepatol. 2022 Sep 26 [Epub ahead of print].
https://www.cghjournal.org/article/S1542-3565(22)00922-3/pdf
http://www.ncbi.nlm.nih.gov/pubmed/36174941?tool=bestpractice.com
在极少数情况下,可能会出现耳部皮损。[218]Williams G, Watters C, Watson N. Auricular manifestation of mpox (monkeypox). BMJ Case Rep. 2023 Jan 19;16(1):e252931.
https://casereports.bmj.com/content/16/1/e252931.long
http://www.ncbi.nlm.nih.gov/pubmed/36657823?tool=bestpractice.com
尽管 2022 年全球分支 Ⅱ 型 mpox 暴发中的大多数患者为男性,但据报道,女性患者有出现局部生殖器皮损(外阴和阴道内)和宫颈病变。[219]Portela-Dias J, Sereno S, Falcão-Reis I, et al. Female monkeypox infection with localized genital lesions. Am J Obstet Gynecol. 2022 Aug 25 [Epub ahead of print].
https://www.ajog.org/article/S0002-9378(22)00689-5/pdf
http://www.ncbi.nlm.nih.gov/pubmed/36030847?tool=bestpractice.com
[220]Vallée A, Chatelain A, Carbonnel M, et al. Monkeypox virus infection in 18-year-old woman after sexual intercourse, France, September 2022. Emerg Infect Dis. 2022 Nov 10;29(1).
https://wwwnc.cdc.gov/eid/article/29/1/22-1643_article
http://www.ncbi.nlm.nih.gov/pubmed/36355630?tool=bestpractice.com
[221]Zayat N, Huang S, Wafai J, et al. Monkeypox virus infection in 22-year-old woman after sexual intercourse, New York, USA. Emerg Infect Dis. 2022 Nov 10;29(1).
https://wwwnc.cdc.gov/eid/article/29/1/22-1662_article
http://www.ncbi.nlm.nih.gov/pubmed/36355634?tool=bestpractice.com
[222]Ramírez M, Delso V, Sánchez MJ, et al. Mpox (monkeypox) presenting as cervical and vulvar disease. Obstet Gynecol. 2023 Jan 10 [Epub ahead of print].
https://journals.lww.com/greenjournal/Fulltext/9900/Mpox__Monkeypox__Presenting_as_Cervical_and_Vulvar.671.aspx
http://www.ncbi.nlm.nih.gov/pubmed/36626748?tool=bestpractice.com
顺性别女性患者以外阴皮损为主,跨性别女性患者则以肛门直肠症状为主,这从解剖学角度反映了性行为形式。[39]Thornhill JP, Palich R, Ghosn J, et al. Human monkeypox virus infection in women and non-binary individuals during the 2022 outbreaks: a global case series. Lancet. 2022 Dec 3;400(10367):1953-65.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02187-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36403584?tool=bestpractice.com
病损可分为丘疹、小水疱、水疱、脓疱、糜烂、溃疡或结痂。[223]Prasad S, Casas CG, Strahan AG, et al. A dermatologic assessment of 101 mpox (monkeypox) cases from 13 countries during the 2022 outbreak: skin lesion morphology, clinical course, and scarring. J Am Acad Dermatol. 2023 Jan 11 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9833815
http://www.ncbi.nlm.nih.gov/pubmed/36641010?tool=bestpractice.com
病损最初可能很疼痛,在愈合阶段会瘙痒。
外生殖器病损可引发严重肿胀和疼痛。口腔病损可能引起进食和饮水困难,从而可能导致脱水和营养不良。根据皮疹/病损的位置,患者可能会出现以下并发症(请查阅 “并发症”):[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
[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
据报道,部分患者出现红色斑丘疹、全身紫癜性和麻疹样皮疹。[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
[223]Prasad S, Casas CG, Strahan AG, et al. A dermatologic assessment of 101 mpox (monkeypox) cases from 13 countries during the 2022 outbreak: skin lesion morphology, clinical course, and scarring. J Am Acad Dermatol. 2023 Jan 11 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9833815
http://www.ncbi.nlm.nih.gov/pubmed/36641010?tool=bestpractice.com
[225]Simon-Gozalbo A, Gamo-Guerrero M, Alonso-Garcia S, et al. Haemorrhagic monkeypox infection in an immunosuppressed patient with human immunodeficiency virus: beyond the pustules. Clin Microbiol Infect. 2023 Jan;29(1):122-4.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534161
http://www.ncbi.nlm.nih.gov/pubmed/36206864?tool=bestpractice.com
淋巴结肿大
淋巴结肿大可呈全身性,或者局限于若干区域。其通常伴随发热出现,在皮疹之前出现,或者罕见情况下,与皮疹同时出现。可出现于颌下、颈部、腋下或腹股沟,还可出现于躯体两侧或仅一侧。
肿大的淋巴结直径约为 1 至 4 cm,质地坚硬,伴触痛,有时可呈现疼痛。[178]McCollum AM, Damon IK. Human monkeypox. Clin Infect Dis. 2014 Jan;58(2):260-7.
https://academic.oup.com/cid/article/58/2/260/335791
http://www.ncbi.nlm.nih.gov/pubmed/24158414?tool=bestpractice.com
淋巴结肿大是一种常见的鉴别特征,在患天花和鉴别诊断中的其他疾病时罕见。[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
[49]Huhn GD, Bauer AM, Yorita K, et al. Clinical characteristics of human monkeypox, and risk factors for severe disease. Clin Infect Dis. 2005 Dec 15;41(12):1742-51.
https://academic.oup.com/cid/article/41/12/1742/344953
http://www.ncbi.nlm.nih.gov/pubmed/16288398?tool=bestpractice.com
[96]Fenner F, Henderson DA, Arita I, et al. Chapter 29: Human monkeypox and other poxvirus infections of man. In: Smallpox and its eradication. Geneva: World Health Organization; 1988.
http://apps.who.int/iris/handle/10665/39485
[178]McCollum AM, Damon IK. Human monkeypox. Clin Infect Dis. 2014 Jan;58(2):260-7.
https://academic.oup.com/cid/article/58/2/260/335791
http://www.ncbi.nlm.nih.gov/pubmed/24158414?tool=bestpractice.com
疾病严重程度和重症的危险因素
多数病例较轻,然而疾病程度可呈轻重各异,甚至可致死。
患者的疾病严重程度取决于其初始健康状况、免疫应答、既往疫苗接种情况、是否有合并症、暴露途径和病毒株。[198]Centers for Disease Control and Prevention. Clinical features of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-signs
与分支 Ⅰ 病毒相比,分支 Ⅱ 病毒所致病例的病情更轻。[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
无症状感染已得到描述,但无症状感染可能呈现的疾病严重程度尚不明确。[96]Fenner F, Henderson DA, Arita I, et al. Chapter 29: Human monkeypox and other poxvirus infections of man. In: Smallpox and its eradication. Geneva: World Health Organization; 1988.
http://apps.who.int/iris/handle/10665/39485
[97]Reda A, El-Qushayri AE, Shah J. Asymptomatic monkeypox infection: a call for greater control of infection and transmission. Lancet Microbe. 2023 Jan;4(1):e15-6.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536807
http://www.ncbi.nlm.nih.gov/pubmed/36209756?tool=bestpractice.com
过去进行疫苗接种所获免疫力极大降低了临床征象和症状的发作频率及强度。[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
评估患者,确定其是否存在重度疾病或有并发症疾病的症状和体征。[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
并发症的临床症状和体征:
恶心和呕吐
有疼痛的颈部淋巴结肿大引起吞咽困难
经口摄入不足或脱水
眼睛疼痛或视力异常
肝肿大
脓毒症
呼吸窘迫/肺炎
意识错乱
实验室检查结果异常:
肝脏转氨酶升高
尿素较低
低白蛋白血症
白细胞增多
血小板减少症
皮损严重程度评分:
轻度(<25 个皮损)
中度(25-99 个皮损)
重度(100-250 个皮损)
极重度(>250 个皮损)
在美国,疾病预防控制中心将重症定义为以下患者:[226]Centers for Disease Control and Prevention. Clinical treatment of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care
评估患者,确定其是否存在任何危险因素。有较高的重症或并发症风险的患者组包括:[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
[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
在评估合并 HIV 感染的患者时,在确定患者的严重结局风险时要考虑病毒抑制和 CD4 计数。[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
初始检查
确定性诊断需要实验室确诊。地区公共卫生实验室可进行检测。
对于疑似感染的患者,应尽快实施检测。[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
对所有符合疑似或拟诊病例定义者予以检测。[228]World Health Organization. Diagnostic testing for the monkeypox virus (MPXV): interim guidance. May 2024 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Laboratory-2024.1
应根据临床和流行病学因素,并结合对感染可能性的评估来决定是否进行检测。
在鉴别诊断中,与 mpox 检查同时进行针对其他疾病的诊断性检查。
在患者检测结果出来之前,仍应隔离患者。
鉴于采用实时聚合酶链反应(real-time reverse transcription polymerase chain reaction, RT-PCR)或传统 PCR 的核酸扩增检测(nucleic acid amplification testing, NAAT)具有较高的准确度和灵敏度,是首选的实验室检查。它可单用或联合测序用于确定病毒分支。[228]World Health Organization. Diagnostic testing for the monkeypox virus (MPXV): interim guidance. May 2024 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Laboratory-2024.1
[229]UK Health Security Agency. Mpox: diagnostic testing. Sep 2024 [internet publication].
https://www.gov.uk/guidance/monkeypox-diagnostic-testing
[230]Altindis M, Puca E, Shapo L. Diagnosis of monkeypox virus: an overview. Travel Med Infect Dis. 2022 Sep 13;50:102459.
https://www.sciencedirect.com/science/article/pii/S1477893922002058
http://www.ncbi.nlm.nih.gov/pubmed/36109000?tool=bestpractice.com
[231]Gul I, Liu C, Yuan X, et al. Current and perspective sensing methods for monkeypox virus. Bioengineering (Basel). 2022 Oct 18;9(10):571.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598380
http://www.ncbi.nlm.nih.gov/pubmed/36290539?tool=bestpractice.com
[232]Centers for Disease Control and Prevention. Guidelines for collecting and handling specimens for mpox testing. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/diagnosis-testing/collecting-specimens.html
NAAT 可通用于正痘病毒检测,或专门用于猴痘病毒检测(首选)。正痘病毒 PCR 检测结果呈阳性时,随后应进行猴痘病毒 PCR 检测和/或测序以确诊。分支特定 NAAT 未能检测到猴痘时,随后可能使用测序法来确定病毒分支及基因特征。[228]World Health Organization. Diagnostic testing for the monkeypox virus (MPXV): interim guidance. May 2024 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Laboratory-2024.1
由于存在假阳性结果风险,对感染验前概率较低患者(例如缺乏流行病学关联、非 MSM 人群、不符合 mpox 的体征/症状)的单次检测结果进行解读时,需要保持谨慎。[233]Minhaj FS, Petras JK, Brown JA, et al. Orthopoxvirus testing challenges for persons in populations at low risk or without known epidemiologic link to monkeypox: United States, 2022. MMWR Morb Mortal Wkly Rep. 2022 Sep 9;71(36):1155-8.
https://www.cdc.gov/mmwr/volumes/71/wr/mm7136e1.htm
http://www.ncbi.nlm.nih.gov/pubmed/36074752?tool=bestpractice.com
建议 RT-PCR 循环阈值较高(即 ≥34)的患者进行重复检测(重新提取和检测标本),因为这表明病毒 DNA 水平较低,标本感染性较差,或不具感染性。[233]Minhaj FS, Petras JK, Brown JA, et al. Orthopoxvirus testing challenges for persons in populations at low risk or without known epidemiologic link to monkeypox: United States, 2022. MMWR Morb Mortal Wkly Rep. 2022 Sep 9;71(36):1155-8.
https://www.cdc.gov/mmwr/volumes/71/wr/mm7136e1.htm
http://www.ncbi.nlm.nih.gov/pubmed/36074752?tool=bestpractice.com
[234]Paran N, Yahalom-Ronen Y, Shifman O, et al. Monkeypox DNA levels correlate with virus infectivity in clinical samples, Israel, 2022. Euro Surveill. 2022 Sep;27(35).
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2022.27.35.2200636
http://www.ncbi.nlm.nih.gov/pubmed/36052723?tool=bestpractice.com
测序有助于确定病毒分支和理解流行病学。在 2023 年首次发现经性传播感染分支 Ⅰ 的聚集性病例(由新发现的分支 Ⅰb 所致)后,建议对所有 mpox 检测阳性个体进行分支确认。[229]UK Health Security Agency. Mpox: diagnostic testing. Sep 2024 [internet publication].
https://www.gov.uk/guidance/monkeypox-diagnostic-testing
[235]McQuiston JH, Luce R, Kazadi DM, et al. U.S. preparedness and response to increasing clade I mpox cases in the Democratic Republic of the Congo - United States, 2024. MMWR Morb Mortal Wkly Rep. 2024 May 16;73(19):435-40.
https://www.cdc.gov/mmwr/volumes/73/wr/mm7319a3.htm
http://www.ncbi.nlm.nih.gov/pubmed/38753567?tool=bestpractice.com
推荐样本类型为皮损组织,包括皮损渗出物拭子、一个以上皮损的病灶组织,或皮损结痂。[228]World Health Organization. Diagnostic testing for the monkeypox virus (MPXV): interim guidance. May 2024 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Laboratory-2024.1
[229]UK Health Security Agency. Mpox: diagnostic testing. Sep 2024 [internet publication].
https://www.gov.uk/guidance/monkeypox-diagnostic-testing
[232]Centers for Disease Control and Prevention. Guidelines for collecting and handling specimens for mpox testing. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/diagnosis-testing/collecting-specimens.html
建议采集两份样本,以确保有足够的样本量进行确认性检测。[229]UK Health Security Agency. Mpox: diagnostic testing. Sep 2024 [internet publication].
https://www.gov.uk/guidance/monkeypox-diagnostic-testing
皮损拭子是利用 PCR 检测猴痘病毒 DNA 最有效的手段。[236]Martins-Filho PR, Tanajura DM, Alves Dos Santos C. Polymerase chain reaction positivity and cycle threshold values in biological samples from patients with monkeypox: a meta-analysis. Travel Med Infect Dis. 2022 Sep 7;50:102448.
https://www.sciencedirect.com/science/article/pii/S1477893922001946
http://www.ncbi.nlm.nih.gov/pubmed/36087645?tool=bestpractice.com
[237]Hasso M, Perusini S, Eshaghi A, et al. Monkeypox virus detection in different clinical specimen types. Emerg Infect Dis. 2022 Oct 12;28(12).
https://wwwnc.cdc.gov/eid/article/28/12/22-1160_article
http://www.ncbi.nlm.nih.gov/pubmed/36223653?tool=bestpractice.com
选取的样本类型可能因皮疹所处分期而异。对于疑似或确诊病例的接触者,无肉眼可见皮损或黏膜病变时,可采集其他类型的样本(例如,口咽拭子)。但这可能对症状出现前病例缺乏敏感性,因此应该在出现皮疹或黏膜病变后再次取样进行检测。[228]World Health Organization. Diagnostic testing for the monkeypox virus (MPXV): interim guidance. May 2024 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Laboratory-2024.1
由于存在锐器损伤风险,在拭子采样前,没有必要(或不建议)对病灶进行抽吸或去顶。
根据参考实验室工作流程,采集其他诊断性样本,例如口咽拭子、肛门直肠拭子、加入乙二胺四乙酸(ethylenediamine tetra-acetic acid, EDTA)的血液样本,精液或尿液样本。
建议对确诊或高度拟诊病例的高危接触者进行口咽拭子采样,这些接触者已出现全身症状,但没有皮疹或病损可供采样。如果有咽部病损,还应采集咽拭子。[229]UK Health Security Agency. Mpox: diagnostic testing. Sep 2024 [internet publication].
https://www.gov.uk/guidance/monkeypox-diagnostic-testing
然而,病变拭子的病毒载量高于咽样本,并且已知口咽拭子是初步诊断不可靠的独立样本类型。[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
[238]Nörz D, Brehm TT, Tang HT, et al. Clinical characteristics and comparison of longitudinal qPCR results from different specimen types in a cohort of ambulatory and hospitalized patients infected with monkeypox virus. J Clin Virol. 2022 Aug 11;155:105254.
https://www.sciencedirect.com/science/article/pii/S138665322200186X
http://www.ncbi.nlm.nih.gov/pubmed/36057206?tool=bestpractice.com
支持使用除直接从皮损处所采集拭子样本外的其他样本类型(例如血液、唾液)进行检测的数据有限。检测非取自皮损的样本可能导致假阳性结果。[239]US Food and Drug Administration. For monkeypox testing, use lesion swab samples to avoid false results: FDA safety communication. July 2022 [internet publication].
https://www.fda.gov/medical-devices/safety-communications/monkeypox-testing-use-lesion-swab-samples-avoid-false-results-fda-safety-communication
[240]Veintimilla C, Catalán P, Alonso R, et al. The relevance of multiple clinical specimens in the diagnosis of monkeypox virus, Spain, June 2022. Euro Surveill. 2022 Aug;27(33).
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2022.27.33.2200598
http://www.ncbi.nlm.nih.gov/pubmed/35983771?tool=bestpractice.com
[241]Allan-Blitz LT, Carragher K, Sukhija-Cohen A, et al. Laboratory validation and clinical performance of a saliva-based test for monkeypox virus. J Med Virol. 2023 Jan;95(1):e28191.
https://onlinelibrary.wiley.com/doi/10.1002/jmv.28191
http://www.ncbi.nlm.nih.gov/pubmed/36183189?tool=bestpractice.com
推荐的样本可能因检测的实验室而异,因而请务必查阅当地指南。
根据当地或国家规程,进行样本采集、标记、包装和送检。样本送检之前,通知实验室可能为 mpox。关于在实验室安全处理此类样本,以及将此类病毒学样本进一步转送至参考实验室,已有当地规程可供参考。对于疑似分支 Ⅰb 感染,可加快检测;因此,如果出现这种情况,请提醒当地的实验室。单独包装用于其他感染检测的样本。
还需对患者进行常规血液检验,包括:
对所有有性行为的成人和青少年进行 HIV 感染和其他 STI 检测,尤其是出现肛门、生殖器或肛周溃疡、直肠炎或弥漫性皮疹的患者。[192]Centers for Disease Control and Prevention. Clinical overview of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-overview/index.html
[197]Centers for Disease Control and Prevention. Health alert network (HAN) health advisory: severe manifestations of monkeypox among people who are immunocompromised due to HIV or other conditions. September 2022 [internet publication].
https://emergency.cdc.gov/han/2022/han00475.asp
其他检查
对于重度肛门直肠直肠炎患者,考虑腹部/盆腔计算机体层成像(computed tomography, CT)扫描。造影剂增强 CT 可发现周向肛门直肠壁增厚,伴壁内溃疡所致的广泛离散的非增强低衰减区。其他发现可能包括直肠周围脂肪浸润、骶前水肿、腹水和腹股沟小淋巴结数量增加。[242]Messina MD, Wolf EL, Kanmaniraja D, et al. Imaging features of anorectal proctitis in monkeypox infection. Clin Imaging. 2022 Dec;92:109-11.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9583688
http://www.ncbi.nlm.nih.gov/pubmed/36302321?tool=bestpractice.com
如果怀疑皮肤病灶存在细菌超级感染,或怀疑体弱患者存在细菌感染,则应在患者处于隔离状态时,且在给予抗生素治疗前,进行血培养。
血清学、细胞培养和抗原检测目前不建议用于诊断。
如果检测样本的结果与分子学检测结果不一致,血清学检查(双份血清样本,首次在发病一周内采样,第二次采样间隔至少 14-21 天)可帮助诊断。近期疫苗接种可能干扰血清学检测结果。[228]World Health Organization. Diagnostic testing for the monkeypox virus (MPXV): interim guidance. May 2024 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Laboratory-2024.1
血清学可有助于流行病学调查、既往感染的回顾性诊断,以及对后期临床表现的诊断。[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
正痘病毒在血清学上具有交叉反应性;所以,血清学检测对 mpox 不具有特异性。[244]El Eid R, Allaw F, Haddad SF, et al. Human monkeypox: a review of the literature. PLoS Pathog. 2022 Sep;18(9):e1010768.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9498972
http://www.ncbi.nlm.nih.gov/pubmed/36136979?tool=bestpractice.com
细胞培养只限于在经认证的生物安全 3 级参考实验室进行。基于培养诊断的主要缺点是测定时间长,这不适合大规模检测场景。[231]Gul I, Liu C, Yuan X, et al. Current and perspective sensing methods for monkeypox virus. Bioengineering (Basel). 2022 Oct 18;9(10):571.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598380
http://www.ncbi.nlm.nih.gov/pubmed/36290539?tool=bestpractice.com
[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
对于任何到过疟疾流行地区的发热患者,尤其是在发热之前 3 周内去过疟疾流行地区的患者,始终应排除疟疾混合感染的可能性。抗原检测给实验室工作人员带来的感染隐患小于制备厚血膜涂片和薄血膜涂片带来的隐患。
现有几种新兴的诊断方法。对于严重的免疫功能受损患者,可考虑进行受累组织活检,有助于更好地了解特定症状的原因,但可能仅建议用于某些可进行检测的部位。[245]Centers for Disease Control and Prevention. Additional testing of biopsy tissues in severe mpox infections. Sep 2024 [internet publication].
https//www.cdc.gov/mpox/hcp/diagnosis-testing/biopsy.html
基于 CRISPR 的检测方法正在开发中,以作为 PCR 的更快速替代选择,但目前尚不可用。[246]Sui Y, Xu Q, Liu M, et al. CRISPR-Cas12a-based detection of monkeypox virus. J Infect. 2022 Dec;85(6):702-69.
https://www.journalofinfection.com/article/S0163-4453(22)00527-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36084670?tool=bestpractice.com
用于特异性检测猴痘病毒的环介导等温扩增(loop-mediated isothermal amplification, LAMP)检测法也正在研发中。[231]Gul I, Liu C, Yuan X, et al. Current and perspective sensing methods for monkeypox virus. Bioengineering (Basel). 2022 Oct 18;9(10):571.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598380
http://www.ncbi.nlm.nih.gov/pubmed/36290539?tool=bestpractice.com
[247]Feng J, Xue G, Cui X, et al. Development of a loop-mediated isothermal amplification method for rapid and visual detection of monkeypox virus. Microbiol Spectr. 2022 Sep 26:e0271422.
https://journals.asm.org/doi/10.1128/spectrum.02714-22
http://www.ncbi.nlm.nih.gov/pubmed/36154444?tool=bestpractice.com
当前还在开发基于图像分析的工具。[231]Gul I, Liu C, Yuan X, et al. Current and perspective sensing methods for monkeypox virus. Bioengineering (Basel). 2022 Oct 18;9(10):571.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598380
http://www.ncbi.nlm.nih.gov/pubmed/36290539?tool=bestpractice.com
[248]Thieme AH, Zheng Y, Machiraju G, et al. A deep-learning algorithm to classify skin lesions from mpox virus infection. Nat Med. 2023 Mar;29(3):738-47.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10033450
http://www.ncbi.nlm.nih.gov/pubmed/36864252?tool=bestpractice.com
鉴别诊断
这种皮疹可能与临床实践中更常遇到的其他疾病的皮疹相混淆。[192]Centers for Disease Control and Prevention. Clinical overview of mpox. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-overview/index.html
[249]Hussain A, Kaler J, Lau G, et al. Clinical conundrums: differentiating monkeypox from similarly presenting infections. Cureus. 2022 Oct;14(10):e29929.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9634140
http://www.ncbi.nlm.nih.gov/pubmed/36348880?tool=bestpractice.com
应谨记可能的鉴别诊断,因为这些诊断更有可能是病因(mpox 通常罕见,但在暴发时可能更常见于某些人群)
临床特征可能易与一些 STI 或直肠炎的其他病因相混淆。因此,对于出现生殖器/肛周溃疡或直肠炎的患者,全面评估有无 STI 和在鉴别诊断中考虑 mpox 很重要。但可能存在 STI 混合感染,存在 STI 并不能排除 mpox。
也可能存在引起类似症状的其他感染病原体混合感染,例如严重急性呼吸综合征冠状病毒 2(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)、A 族链球菌。[250]El-Qushayri AE, Reda A, Shah J. COVID-19 and monkeypox co-infection: a rapid systematic review. Front Immunol. 2022 Dec 14;13:1094346.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794570
http://www.ncbi.nlm.nih.gov/pubmed/36591217?tool=bestpractice.com
[251]Kaiser RM, Cash-Goldwasser S, Lehnertz N, et al. Pharyngeal co-infections with monkeypox virus and group A streptococcus, United States, 2022. Emerg Infect Dis. 2023 Sep;29(9):1855-8.
https://wwwnc.cdc.gov/eid/article/29/9/23-0469_article
http://www.ncbi.nlm.nih.gov/pubmed/37437558?tool=bestpractice.com
对于高危人群,不应在出现 SARS-CoV-2 阳性和流感样症状时就不进行 mpox 检测。[250]El-Qushayri AE, Reda A, Shah J. COVID-19 and monkeypox co-infection: a rapid systematic review. Front Immunol. 2022 Dec 14;13:1094346.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794570
http://www.ncbi.nlm.nih.gov/pubmed/36591217?tool=bestpractice.com
参阅 鉴别诊断。
儿童和青少年
妊娠
出现皮疹之前,发热的原因可能难以与其他感染(如绒毛膜羊膜炎)鉴别。具有 mpox 危险因素的孕妇出现皮疹时,需要与妊娠皮肤病相鉴别。[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
通过 PCR 检测,可以排除孕妇水泡性皮疹常见原因(例如水痘带状疱疹、梅毒、单纯疱疹)。[130]Dashraath P, Nielsen-Saines K, Rimoin A, et al. Monkeypox and pregnancy: virology, clinical presentation, and obstetric management. Am J Obstet Gynecol. 2022 Dec;227(6):849-61.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534101
http://www.ncbi.nlm.nih.gov/pubmed/35985514?tool=bestpractice.com