对确诊患者治疗方案包括观察和监测、口服或输注抗微生物剂和/或进行换血疗法。只有巴贝虫涂片或巴贝虫 DNA 的 PCR 检查等实验室检查结果呈阳性,才能明确诊断。应对未经实验室诊断确诊但有症状的患者进行观察和监测,但无需治疗。[6]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134. [Erratum in: Clin Infect Dis. 2007;45:941.]http://cid.oxfordjournals.org/content/43/9/1089.longhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com
治疗目的是减轻疾病症状,消除寄生虫血症同时预防疾病并发症。确定性治疗取决于患者疾病的严重程度(轻度、中度或重度),但是目前并无病情为轻度或中重度的严格定义。目前的治疗建议主要针对田鼠巴贝虫。
分歧巴贝虫和分歧巴贝虫样种属(如 MO-1)感染属于医疗急症,应按医疗急症进行治疗。如果有条件,应请危重症专家和传染病专家会诊,也可能需要积极的支持性治疗。这些患者通常表现出中重度病情。
通过检测外周血样涂片中寄生虫血症水平,评估治疗的微生物学反应。若患者外周血涂片显示持续性寄生虫血症(> 5% 的红细胞中有寄生虫)或症状持久,则应重复进行 PCR 检查,测定巴贝虫 DNA。
无症状患者
不需要治疗。[6]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134. [Erratum in: Clin Infect Dis. 2007;45:941.]http://cid.oxfordjournals.org/content/43/9/1089.longhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com若寄生虫血症持续时间超过 3 个月,应重复进行巴贝虫涂片检查和/或 PCR 检查,并考虑进行治疗。[6]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134. [Erratum in: Clin Infect Dis. 2007;45:941.]http://cid.oxfordjournals.org/content/43/9/1089.longhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com在证实寄生虫血症清除前,患者应避免献血。
病情轻微的症状性患者
确诊患有巴贝虫病但无需住院的患者,应联合使用阿奇霉素加阿托伐醌或奎宁加克林霉素进行为期 7-10 天的治疗。[6]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134. [Erratum in: Clin Infect Dis. 2007;45:941.]http://cid.oxfordjournals.org/content/43/9/1089.longhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com[27]Sanchez E, Vannier E, Wormser GP, et al. Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: a review. JAMA. 2016;315:1767-1777.http://www.ncbi.nlm.nih.gov/pubmed/27115378?tool=bestpractice.com抗田鼠巴贝虫效果:有高质量证据证明,克林霉素加奎宁或阿奇霉素加阿托伐醌可有效治疗巴贝虫病。[6]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134. [Erratum in: Clin Infect Dis. 2007;45:941.]http://cid.oxfordjournals.org/content/43/9/1089.longhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。
克林霉素和奎宁联合用药,是第一种广泛用于治疗巴贝虫病的疗法,其常见治疗副作用有:耳鸣、眩晕和胃肠不适。因此,阿奇霉素和阿托伐醌联合用药更常用于无致命威胁病情的患者。
预期临床症状在开始治疗后 48 小时内发生改善,在开始治疗后 3 个月内症状应完全消退。若初始治疗超过 3 个月以后症状仍持续,或血样涂片显示寄生虫,或 PCR 检测到巴贝虫 DNA,则不论是否有症状,都可能需要再次治疗。
在证实寄生虫血症清除前,患者应避免献血。
病情为中重度的症状性患者
确诊为巴贝虫病且病情为中重度的患者需接受静脉注射克林霉素和口服奎宁联合用药至少 7-10 天。[6]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134. [Erratum in: Clin Infect Dis. 2007;45:941.]http://cid.oxfordjournals.org/content/43/9/1089.longhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com[27]Sanchez E, Vannier E, Wormser GP, et al. Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: a review. JAMA. 2016;315:1767-1777.http://www.ncbi.nlm.nih.gov/pubmed/27115378?tool=bestpractice.com抗田鼠巴贝虫的疗效:有中等质量证据证明,静脉注射克林霉素加奎宁可有效治疗中重度巴贝虫病。[6]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134. [Erratum in: Clin Infect Dis. 2007;45:941.]http://cid.oxfordjournals.org/content/43/9/1089.longhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。虽然还未有对照研究对延长治疗进行评估,但是对于寄生虫血症水平非常高或症状持久或严重的患者,可能需要延长治疗时间。一项研究支持对免疫功能受损患者进行最短 6 周的治疗。[27]Sanchez E, Vannier E, Wormser GP, et al. Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: a review. JAMA. 2016;315:1767-1777.http://www.ncbi.nlm.nih.gov/pubmed/27115378?tool=bestpractice.com
部分或全部红细胞换血适用于寄生虫血症水平超过 10% 以及严重溶血或肾脏、肝脏和肺功能不全患者。建议请传染病专家和血液学专家会诊。[6]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134. [Erratum in: Clin Infect Dis. 2007;45:941.]http://cid.oxfordjournals.org/content/43/9/1089.longhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com抗田鼠巴贝虫的疗效:有中等质量证据证明,换血疗法可减轻重度巴贝虫感染病例的寄生虫血症。[6]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134. [Erratum in: Clin Infect Dis. 2007;45:941.]http://cid.oxfordjournals.org/content/43/9/1089.longhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。目前尚未发表对单独使用抗微生物治疗和抗微生物治疗加换血联合治疗进行系统性比较的研究。
治疗期间密切监测患者,以确保改善临床症状,减轻寄生虫血症以及改善其他实验室异常(如贫血或肾功能障碍)。每天或隔天监测病情严重患者的红细胞压积和寄生虫血症百分比,直至寄生虫血症水平降至 5% 以下,且患者临床症状得到改善。[6]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134. [Erratum in: Clin Infect Dis. 2007;45:941.]http://cid.oxfordjournals.org/content/43/9/1089.longhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com患者完成治疗后的几个月内可能会出现持续性低水平寄生虫血症。
在证实寄生虫血症清除前,患者应避免献血。
适当治疗后,若患者持续存在症状或病情特别严重,则患者可能合并感染了伯氏疏螺旋体或嗜吞噬细胞无形体或两者同时感染。合并感染患者需接受 14-21 天的多西环素治疗。[16]Weiss LM. Babesiosis in humans: a treatment review. Expert Opin Pharmacother. 2002;3:1109-1115.http://www.ncbi.nlm.nih.gov/pubmed/12150690?tool=bestpractice.com对适当治疗后仍病情严重或长期不愈的患者,应排除潜在免疫缺陷的可能。
复发性或难治性疾病
在免疫功能受损的患者(尤其是携带 HIV 的患者)中,常见复发性或长期性寄生虫血症。[1]Vannier E, Krause PJ. Human babesiosis. N Engl J Med. 2012;366:2397-2407.http://www.ncbi.nlm.nih.gov/pubmed/22716978?tool=bestpractice.com
若初始治疗超过 3 个月以后,血样涂片显示寄生虫或 PCR 检测到巴贝虫 DNA,则无论是否具有症状,都可能需要按复发病情的严重程度,再次接受抗巴贝虫治疗。[6]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134. [Erratum in: Clin Infect Dis. 2007;45:941.]http://cid.oxfordjournals.org/content/43/9/1089.longhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com抗田鼠巴贝虫的疗效:有中等质量证据证明,症状性患者接受针对复发性寄生虫血症的治疗有益处,且增加感染清除概率。[6]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134. [Erratum in: Clin Infect Dis. 2007;45:941.]http://cid.oxfordjournals.org/content/43/9/1089.longhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。因此,持续性病情轻微的患者可能获益于奎宁加克林霉素或阿奇霉素加阿托伐醌再次治疗;更严重患者可能需要静脉注射克林霉素和口服奎宁。
有研究表明,某些免疫功能重度受损的患者对治疗有一定的抗性,可能需要多疗程治疗。[28]Wormser GP, Prasad A, Neuhaus E, et al. Emergence of resistance to azithromycin-atovaquone in immunocompromised patients with Babesia microti infection. Clin Infect Dis. 2010;50:381-386.http://cid.oxfordjournals.org/content/50/3/381.longhttp://www.ncbi.nlm.nih.gov/pubmed/20047477?tool=bestpractice.com在这些病例中,需要使用阿奇霉素加阿托伐醌进行长期治疗。对于免疫功能受损的患者,可能需要增加阿奇霉素剂量。[6]Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134. [Erratum in: Clin Infect Dis. 2007;45:941.]http://cid.oxfordjournals.org/content/43/9/1089.longhttp://www.ncbi.nlm.nih.gov/pubmed/17029130?tool=bestpractice.com