治疗方法因寄生虫位置和数量,以及宿主反应而异。抗寄生虫治疗是大多数患者的主要治疗方法;然而,在肠外疾病中可能需要额外的干预措施,包括皮质类固醇、抗惊厥药物和手术干预。脑囊虫病患者可能出现颅内压增高,这是一种医学急症。[34]White AC Jr, Garcia HH. Updates on the management of neurocysticercosis. Curr Opin Infect Dis. 2018 Oct;31(5):377-82.http://www.ncbi.nlm.nih.gov/pubmed/30095486?tool=bestpractice.com
肠道感染
若粪便中查找到绦虫感染的证据(例如微小膜壳绦虫、阔节裂头绦虫、牛肉绦虫和猪肉绦虫),则首选广谱抗寄生虫药物吡喹酮。吡喹酮具有很好的广谱抗绦虫活性。成人和儿童均为单次给药。[35]Centers for Disease Control and Prevention. Parasites - taeniasis: resources for health professionals. Jan 2013 [internet publication].https://www.cdc.gov/parasites/taeniasis/health_professionals/index.html 微小膜壳绦虫感染需给予较大剂量的吡喹酮。同时也存在其他有效的抗寄生虫药物,例如氯硝柳胺。
中枢神经系统 (CNS) 表现
中枢神经系统感染表现包括猪肉绦虫(脑囊虫病)或棘球蚴病的表现。脑囊虫病患者的具体治疗取决于囊肿的位置。
颅内压增高可能危及生命,应立即进行治疗。在颅内压稳定之前,不建议进行抗寄生虫治疗。在颅内压增高患者中使用抗寄生虫治疗可导致致命的不良事件(例如,疝出)。[25]White AC Jr, Coyle CM, Rajshekhar V, et al. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2018 Apr 3;66(8):e49-75.https://academic.oup.com/cid/article/66/8/e49/4885412http://www.ncbi.nlm.nih.gov/pubmed/29481580?tool=bestpractice.com 患者稳定后,可以视脑囊虫病的类型决定治疗方案。
脑实质型疾病活动期:
未经治疗的脑积水或弥漫性脑水肿(囊虫性脑炎)患者需要使用皮质类固醇紧急处理颅内压增高,以治疗弥漫性脑水肿,或采用手术治疗脑积水。[25]White AC Jr, Coyle CM, Rajshekhar V, et al. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2018 Apr 3;66(8):e49-75.https://academic.oup.com/cid/article/66/8/e49/4885412http://www.ncbi.nlm.nih.gov/pubmed/29481580?tool=bestpractice.com 随后即开始抗寄生虫治疗(即阿苯达唑或吡喹酮)。此外,添加皮质类固醇可有效减轻活动性脑实质包囊患者发生癫痫全身性发作的风险。[25]White AC Jr, Coyle CM, Rajshekhar V, et al. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2018 Apr 3;66(8):e49-75.https://academic.oup.com/cid/article/66/8/e49/4885412http://www.ncbi.nlm.nih.gov/pubmed/29481580?tool=bestpractice.com[30]Webb CM, White AC Jr. Update on the diagnosis and management of neurocysticercosis. Curr Infect Dis Rep. 2016 Dec;18(12):44.http://www.ncbi.nlm.nih.gov/pubmed/27787774?tool=bestpractice.com[36]Baird RA, Wiebe S, Zunt JR, et al. Evidence-based guideline: treatment of parenchymal neurocysticercosis: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013 Apr 9;80(15):1424-9.http://www.neurology.org/content/80/15/1424.longhttp://www.ncbi.nlm.nih.gov/pubmed/23568997?tool=bestpractice.com[37]Otte WM, Singla M, Sander JW, et al. Drug therapy for solitary cysticercus granuloma: a systematic review and meta-analysis. Neurology. 2013 Jan 8;80(2):152-62.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589189/http://www.ncbi.nlm.nih.gov/pubmed/23269591?tool=bestpractice.com
非活动性脑实质型疾病:
非活动性实质疾病(伴有钙化灶)因无活性囊肿,无需抗寄生虫治疗。然而,钙化病灶可能会导致患者出现有症状的病灶周围水肿,有些专家建议使用皮质类固醇治疗,[38]García HH, Evans CA, Nash TE, et al. Current consensus guidelines for treatment of neurocysticercosis. Clin Microbiol Rev. 2002 Oct;15(4):747-56.http://cmr.asm.org/content/15/4/747.longhttp://www.ncbi.nlm.nih.gov/pubmed/12364377?tool=bestpractice.com 但其不作为常规治疗。在选定的患者中可以考虑手术切除癫痫灶。[25]White AC Jr, Coyle CM, Rajshekhar V, et al. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2018 Apr 3;66(8):e49-75.https://academic.oup.com/cid/article/66/8/e49/4885412http://www.ncbi.nlm.nih.gov/pubmed/29481580?tool=bestpractice.com
脑室疾病:
脑室型脑囊尾蚴病活动期患者可出现梗阻性脑积水。 这些患者可通过脑室腹腔分流减轻颅内高压。
待颅内压稳定后,通过神经内镜切除侧脑室和第三脑室中的囊尾蚴,同时建议手术切除第四脑室中的囊尾蚴。[25]White AC Jr, Coyle CM, Rajshekhar V, et al. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2018 Apr 3;66(8):e49-75.https://academic.oup.com/cid/article/66/8/e49/4885412http://www.ncbi.nlm.nih.gov/pubmed/29481580?tool=bestpractice.com 若患者磁共振成像 (MRI) 表现出室管膜显著增强(继发于病变粘连室管膜后),则可能不适合进行此类手术。[24]Cuetter AC, Garcia-Bobadilla J, Guerra LG, et al. Neurocysticercosis: focus on intraventricular disease. Clin Infect Dis. 1997 Feb;24(2):157-64.http://www.ncbi.nlm.nih.gov/pubmed/9114141?tool=bestpractice.com
一些专家不建议在手术切除前进行抗寄生虫治疗,因为它可能破坏寄生虫的完整性并引起炎症反应,从而妨碍囊肿切除。
皮质类固醇推荐用于围手术期,或在分流术后与抗寄生虫治疗联合使用。[25]White AC Jr, Coyle CM, Rajshekhar V, et al. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2018 Apr 3;66(8):e49-75.https://academic.oup.com/cid/article/66/8/e49/4885412http://www.ncbi.nlm.nih.gov/pubmed/29481580?tool=bestpractice.com
蛛网膜下腔疾病:
蛛网膜下腔型脑囊尾蚴病疾病相对罕见,预后很差,因此治疗方案推荐的证据也很有限。 目前无关于蛛网膜下腔型脑囊尾蚴病对照试验,但是关于抗寄生虫药、皮质类固醇联合脑室分流治疗该疾病的病例研究证实该治疗方案可改善疾病的预后。[39]Proaňo JV, Madrazo I, Avelar F, et al. Medical treatment for neurocysticercosis characterized by giant subarachnoid cysts. N Engl J Med. 2001 Sep 20;345(12):879-85.http://www.nejm.org/doi/full/10.1056/NEJMoa010212#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/11565520?tool=bestpractice.com
建议最初采用分流治疗颅内压升高,并延长抗寄生虫治疗时间(即数月至 1 年以上),同时给予皮质类固醇治疗,缓慢减量。[39]Proaňo JV, Madrazo I, Avelar F, et al. Medical treatment for neurocysticercosis characterized by giant subarachnoid cysts. N Engl J Med. 2001 Sep 20;345(12):879-85.http://www.nejm.org/doi/full/10.1056/NEJMoa010212#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/11565520?tool=bestpractice.com 甲氨蝶呤也可用作激素节省制剂,以减少与长期皮质类固醇使用相关的不良反应。[39]Proaňo JV, Madrazo I, Avelar F, et al. Medical treatment for neurocysticercosis characterized by giant subarachnoid cysts. N Engl J Med. 2001 Sep 20;345(12):879-85.http://www.nejm.org/doi/full/10.1056/NEJMoa010212#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/11565520?tool=bestpractice.com[40]Mitre E, Talaat KR, Sperling MR, et al. Methotrexate as a corticosteroid-sparing agent in complicated neurocysticercosis. Clin Infect Dis. 2007 Feb 15;44(4):549-53.http://www.ncbi.nlm.nih.gov/pubmed/17243058?tool=bestpractice.com 一些患者也可能受益于减瘤手术。[25]White AC Jr, Coyle CM, Rajshekhar V, et al. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2018 Apr 3;66(8):e49-75.https://academic.oup.com/cid/article/66/8/e49/4885412http://www.ncbi.nlm.nih.gov/pubmed/29481580?tool=bestpractice.com
脊柱/眼科疾病:
针对具体病例的个体化手术,是治疗脊髓疾病的主要手段。同时推荐使用皮质类固醇抗寄生虫治疗(特别是在脊髓功能障碍病例中)。应通过手术切除,治疗眼内囊尾蚴。[25]White AC Jr, Coyle CM, Rajshekhar V, et al. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2018 Apr 3;66(8):e49-75.https://academic.oup.com/cid/article/66/8/e49/4885412http://www.ncbi.nlm.nih.gov/pubmed/29481580?tool=bestpractice.com
治疗的一般原则:
抗寄生虫治疗:通常建议使用阿苯达唑进行单药治疗。然而,疾病负担较重的患者(即,>2 个活性囊肿)可以从抗寄生虫联合疗法(即阿苯达唑加吡喹酮)中受益。该建议源于对实质型疾病患者的研究。[25]White AC Jr, Coyle CM, Rajshekhar V, et al. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2018 Apr 3;66(8):e49-75.https://academic.oup.com/cid/article/66/8/e49/4885412http://www.ncbi.nlm.nih.gov/pubmed/29481580?tool=bestpractice.com 一项随机、双盲、安慰剂对照、II 期试验发现,阿苯达唑与吡喹酮联合治疗与单用阿苯达唑相比,前者可产生更大的杀囊虫活性(囊肿缓解率分别是 95% 与 30%;完全囊肿清除率分别是 75% 与 25%)。[41]Garcia HH, Lescano AG, Gonzales I, et al. Cysticidal efficacy of combined treatment with praziquantel and albendazole for parenchymal brain cysticercosis. Clin Infect Dis. 2016 Jun 1;62(11):1375-9.http://www.ncbi.nlm.nih.gov/pubmed/26984901?tool=bestpractice.com 在一项 III 期研究(双盲、安慰剂对照)中证实了上述发现,后者也发现,在活动性脑实质型脑囊尾蚴病患者中,阿苯达唑与吡喹酮联合治疗与单独阿苯达唑治疗相比具有更好的驱虫效果。 在含有3个或3个以上包囊的患者中,联合治疗的优势更明显。 在联合抗寄生虫治疗组中未见副作用增多。[42]Garcia HH, Gonzales I, Lescano AG, et al. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis. 2014 Aug;14(8):687-95.http://www.ncbi.nlm.nih.gov/pubmed/24999157?tool=bestpractice.com
抗惊厥药:无论脑囊虫病是何类型,都可以使用抗惊厥药对癫痫发作进行控制。如果患者一段时间无癫痫发作(取决于囊肿的位置),若他们没有癫痫复发的危险因素,则可以在 MRI 观察到囊肿消退后逐渐减量,并停止使用抗惊厥药。抗惊厥药的选择取决于可用性、药物相互作用、不良反应和成本。由于许多抗惊厥药有致畸作用,因此不应用于孕妇。[25]White AC Jr, Coyle CM, Rajshekhar V, et al. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2018 Apr 3;66(8):e49-75.https://academic.oup.com/cid/article/66/8/e49/4885412http://www.ncbi.nlm.nih.gov/pubmed/29481580?tool=bestpractice.com
皮质类固醇:抗寄生虫治疗时给予辅助皮质类固醇的最佳剂量、持续时间和剂型尚未确立。一项开放标签的随机临床试验在最近(6 个月内)有癫痫发作的活动性实质型脑囊虫病患者中,对传统地塞米松给药与强化地塞米松给药进行了比较。虽然研究并未达到其减少癫痫发作天数,或减少癫痫发作个体数量的主要终点,但研究有两个重要发现。首先,该研究发现,癫痫活动性在第 1-21 天间升高,第 21 天后减弱;其次,强化地塞米松给药可减少第 1-21 天间的癫痫活动。两组间不良反应无差异。上述数据表明,在治疗初始的 21 天中,有癫痫发作风险的实质内活动性脑囊虫病患者可能会从强化皮质类固醇治疗方案中获益。[43]Garcia HH, Gonzales I, Lescano AG, et al. Enhanced steroid dosing reduces seizures during antiparasitic treatment for cysticercosis and early after. Epilepsia. 2014 Sep;55(9):1452-9.http://onlinelibrary.wiley.com/doi/10.1111/epi.12739/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25092547?tool=bestpractice.com 皮质类固醇通常在抗寄生虫治疗之前开始给药。
肝脏或胸部受累疾病的临床特点
肝脏或胸部受累的表现可来自包虫病(棘球绦虫疾病)和囊尾蚴病(猪肉绦虫感染)。手术切除是治疗肝棘球蚴病的主要方法。大范围的手术切除(例如肝叶切除或肝移植)可保证包囊全部清除。同时进行抗寄生虫治疗,需手术前至少 2 周开始,直至手术后至少 1 个月。对于肺包虫病,在术前 2- 4 周或 8 周开始阿苯达唑和吡喹酮联合治疗可提高杀灭绦虫头节的疗效。如果患者术中囊肿破裂的风险很高,可以考虑延长抗寄生虫预治疗的时间。[44]Koul PA, Singh AA, Ahanger AG, et al. Optimal duration of preoperative anti-helminthic therapy for pulmonary hydatid surgery. ANZ J Surg. 2010 May;80(5):354-7.http://www.ncbi.nlm.nih.gov/pubmed/20557511?tool=bestpractice.com
单独进行药物治疗可能治愈一小部分患者,但如果无手术干预治疗,疾病常复发。根据报告, PAIR(穿刺、抽吸、注射、再抽吸)方案在一些适合的患者人群中取得了良好的治疗效果。在采用 PAIR 方案的同时应联合阿苯达唑治疗,以减少囊肿播散风险。在计算机断层扫描引导下先抽吸出包虫囊肿中的液体,再向囊腔注入杀绦虫头节剂,随后再次抽吸出液体。[45]Khuroo MS, Wani NA, Javid G, et al. Percutaneous drainage compared with surgery for hepatic hydatid cysts. N Engl J Med. 1997 Sep 25;337(13):881-7.http://www.nejm.org/doi/full/10.1056/NEJM199709253371303#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/9302302?tool=bestpractice.com[46]Smego RA Jr, Bhatti S, Khaliq AA, et al. Percutaneous aspiration-injection-reaspiration drainage plus albendazole or mebendazole for hepatic cystic echinococcosis: a meta-analysis. Clin Infect Dis. 2003 Oct 15;37(8):1073-83.http://www.ncbi.nlm.nih.gov/pubmed/14523772?tool=bestpractice.com
特殊患者群体
孕妇的治疗方法与非妊娠人群相同,治疗时需要考虑以下因素:抗寄生虫治疗应延迟到分娩后;必要时可安全使用皮质类固醇;决定适用的抗惊厥药时应考虑致畸作用。儿童通常采用与成人相同的治疗。[25]White AC Jr, Coyle CM, Rajshekhar V, et al. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2018 Apr 3;66(8):e49-75.https://academic.oup.com/cid/article/66/8/e49/4885412http://www.ncbi.nlm.nih.gov/pubmed/29481580?tool=bestpractice.com