疾病在免疫功能正常的患者中具有自限性。通常无需进行治疗,但要采取措施,以防出现脱水,如口服补液溶液。治疗方法有限。可以给予 1 岁以上的免疫功能正常的患者硝唑尼特治疗,但通常无需进行特异性治疗,因为该病在此类患者群中具有自限性。对患有重度或难治性疾病的免疫功能受损的患者,尽管可给予硝唑尼特治疗,但该药物的疗效仍待证实。
免疫功能正常和免疫功能受损患者均可出现无症状携带;此类患者无需治疗。
免疫功能正常患者
疾病在免疫功能正常的患者中具有自限性。尽管症状可能会持续长达 3~4 周,但通常会在 7~14 天内消退(在需就医的患者中,平均值是 13 天,中位数是 11 天)。[24]Hunter PR, Hughes S, Woodhouse S, et al. Sporadic cryptosporidiosis case-control study with genotyping. Emerg Infect Dis. 2004;10:1241-1249.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323324/http://www.ncbi.nlm.nih.gov/pubmed/15324544?tool=bestpractice.com大约三分之一患者的症状会在短暂复发后缓解。[24]Hunter PR, Hughes S, Woodhouse S, et al. Sporadic cryptosporidiosis case-control study with genotyping. Emerg Infect Dis. 2004;10:1241-1249.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323324/http://www.ncbi.nlm.nih.gov/pubmed/15324544?tool=bestpractice.com[57]MacKenzie WR, Schell WL, Blair KA, et al. Massive outbreak of waterborne Cryptosporidium infection in Milwaukee, Wisconsin: recurrence of illness and risk of secondary transmission. Clin Infect Dis. 1995;21:57-62.http://www.ncbi.nlm.nih.gov/pubmed/7578760?tool=bestpractice.com通常无需进行治疗,但要采取措施,以防出现脱水,如口服补液溶液。
若须进行治疗(例如症状持续存在),则可以给予 1 岁以上、耐受性好、免疫功能正常的患者硝唑尼特治疗。然而 80% 的患者即使接受治疗,腹泻症状仍会持续 5 天,才会消退。[66]Rossignol JF, Ayoub A, Ayers MS. Treatment of diarrhea caused by Cryptosporidium parvum: a prospective randomized, double-blind, placebo-controlled study of nitazoxanide. J Infect Dis. 2001;184:103-106.http://www.ncbi.nlm.nih.gov/pubmed/11398117?tool=bestpractice.com若症状几乎无改善,患者需接受以 3 天为一疗程的多疗程硝唑尼特治疗,[67]Diaz E, Mondragon J, Ramirez E, et al. Epidemiology and control of intestinal parasites with nitazoxanide in children in Mexico. Am J Trop Med Hyg. 2003;68:384-385.http://www.ajtmh.org/cgi/content/full/68/4/384http://www.ncbi.nlm.nih.gov/pubmed/12875284?tool=bestpractice.com此外,7 天为一疗程的方案也已用于临床。[68]Favennec L, Jave Ortiz J, Gargala G, et al. Double-blind, randomized, placebo-controlled study of nitazoxanide in the treatment of fascioliasis in adults and children from northern Peru. Aliment Pharmacol Ther. 2003;17:265-270.http://www3.interscience.wiley.com/cgi-bin/fulltext/118880232/HTMLSTARThttp://www.ncbi.nlm.nih.gov/pubmed/12534412?tool=bestpractice.com[69]Doumbo O, Rossignol JF, Pichard E, et al. Nitazoxanide in the treatment of cryptosporidial diarrhea and other intestinal parasitic infections associated with acquired immunodeficiency syndrome in tropical Africa. Am J Trop Med Hyg. 1997;56:637-639.http://www.ncbi.nlm.nih.gov/pubmed/9230795?tool=bestpractice.com
对于何时开始治疗尚无明确标准,且治疗并非强制性,即便腹泻持续超过 7 天;然而,一些医生仍可选择在诊断后立即开始治疗。
免疫功能受损患者
对于免疫功能受损的患者而言,疾病可能会比较持久,并且难以治疗。抗菌疗法可能会缓解症状,但几乎无效,往往会在停止治疗后复发。其他并发的机会性感染应被排除。一般情况下,对于免疫功能受损的患者而言,其治疗原则是治疗潜在的免疫功能缺陷,继而缓解隐孢子虫病病情。
对 HIV 感染患者而言,高效抗逆转录病毒疗法 (HAART) 是一种治疗选择。蛋白酶抑制剂可改善 CD4 细胞水平,恢复免疫力,减少隐孢子虫孢子体和在体外发育的成虫对宿主细胞的侵袭。[70]Hommer V, Eichholz J, Petry F. Effect of antiretroviral protease inhibitors alone, and in combination with paromomycin, on the excystation, invasion and in vitro development of Cryptosporidium parvum. J Antimicrob Chemother. 2003;52:359-364.http://jac.oxfordjournals.org/cgi/content/full/52/3/359http://www.ncbi.nlm.nih.gov/pubmed/12888587?tool=bestpractice.com对于其他类型的免疫功能缺陷患者,通过治疗原发性疾病提高免疫力(如果可能),也可缓解病情。[71]Abdo A, Klassen J, Urbanski S, et al. Reversible sclerosing cholangitis secondary to cryptosporidiosis in a renal transplant patient. J Hepatol. 2003;38:688-691.http://www.ncbi.nlm.nih.gov/pubmed/12713884?tool=bestpractice.com重度隐孢子虫病高风险患者包括白血病和淋巴瘤患者(特别是儿童),或原发性 T 细胞免疫功能缺陷患者。对重度隐孢子虫病患者可能需进行支持性治疗;包括静脉补液和纠正电解质水平(如果体液大量流失)。
对免疫功能受损患者给予硝唑尼特治疗尚未批准,因为尚无研究证实硝唑尼特在此类患者中的疗效优于安慰剂。当免疫功能受损的患者患有隐孢子虫病时(若患有难治性和/或重度隐孢子虫病,则可能会致命),医生仍可选择硝唑尼特。对于 HIV 感染患者,可以联合硝唑尼特(14 天为一疗程)和抗逆转录病毒进行治疗。[72]Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children. December 2016. https://aidsinfo.nih.gov (last accessed 11 August 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/oi_guidelines_pediatrics.pdf[73]Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. August 2017. http://aidsinfo.nih.gov/ (last accessed 11 August 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf艾滋病成年患者的寄生虫学治疗:有中等质量的证据表明,在临床试验条件下,给予 22 名患有隐孢子虫病的爱滋病成年患者硝唑尼特治疗 28 天(剂量高达 1000 mg,每天 2 次)后,19 名患者的寄生虫病得以治愈。[74]Rossignol JF, Hidalgo H, Feregrino M, et al. A double-'blind' placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico. Trans R Soc Trop Med Hyg. 1998;92:663-666.http://www.ncbi.nlm.nih.gov/pubmed/10326116?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。
其他药物
一些其他药物也已被用来治疗隐孢子虫病,但这些药物的疗效证据仍较弱,且尚未获得用于治疗该适应症的临床应用许可证。[72]Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children. December 2016. https://aidsinfo.nih.gov (last accessed 11 August 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/oi_guidelines_pediatrics.pdf
巴龙霉素
氨基糖苷类巴龙霉素在胃肠道内的吸收效果不佳,但已被用作治疗隐孢子虫病的口服药物,有研究显示该药对 HIV/艾滋病患者具有一定的疗效。[75]White AC Jr, Chappell CL, Hayat CS, et al. Paromomycin for cryptosporidiosis in AIDS: a prospective, double-blind trial. J Infect Dis. 1994;170:419-424.http://www.ncbi.nlm.nih.gov/pubmed/8035029?tool=bestpractice.com[76]Bissuel F, Cotte L, Rabodonirina M, et al. Paromomycin: an effective treatment for cryptosporidial diarrhea in patients with AIDS. Clin Infect Dis. 1994;18:447-449.http://www.ncbi.nlm.nih.gov/pubmed/8011833?tool=bestpractice.com[77]Hewitt RG, Yiannoutsos CT, Higgs ES, et al. Paromomycin: no more effective than placebo for treatment of cryptosporidiosis in patients with advanced human immunodeficiency virus infection. Clin Infect Dis. 2000;31:1084-1092.http://cid.oxfordjournals.org/content/31/4/1084.longhttp://www.ncbi.nlm.nih.gov/pubmed/11049793?tool=bestpractice.comHIV 感染患者的临床和寄生虫学反应:有低等质量的证据表明,巴龙霉素可用来治疗隐孢子虫病。在 24 名患有隐孢子虫病的 HIV 感染患者中进行的一项开放、无对照、前瞻性巴龙霉素研究显示,22 名患者出现临床疗效(18 名患者的病情完全缓解);然而,必须给予持续性维持治疗,以防病情复发。[76]Bissuel F, Cotte L, Rabodonirina M, et al. Paromomycin: an effective treatment for cryptosporidial diarrhea in patients with AIDS. Clin Infect Dis. 1994;18:447-449.http://www.ncbi.nlm.nih.gov/pubmed/8011833?tool=bestpractice.com在 CD4 细胞计数小于 150/mm^3 且感染隐孢子虫的 35 名 HIV 感染患者中进行的另一项前瞻性、双盲、安慰剂对照试验表明,巴龙霉素的疗效并不优于安慰剂,但该研究不足以明确反驳巴龙霉素的有效性。[77]Hewitt RG, Yiannoutsos CT, Higgs ES, et al. Paromomycin: no more effective than placebo for treatment of cryptosporidiosis in patients with advanced human immunodeficiency virus infection. Clin Infect Dis. 2000;31:1084-1092.http://cid.oxfordjournals.org/content/31/4/1084.longhttp://www.ncbi.nlm.nih.gov/pubmed/11049793?tool=bestpractice.com在 10 名患有隐孢子虫病的艾滋病患者中进行的一项样本数极少的巴龙霉素随机双盲临床试验表明,临床和寄生虫学疗效具有统计学意义。[75]White AC Jr, Chappell CL, Hayat CS, et al. Paromomycin for cryptosporidiosis in AIDS: a prospective, double-blind trial. J Infect Dis. 1994;170:419-424.http://www.ncbi.nlm.nih.gov/pubmed/8035029?tool=bestpractice.com低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。
阿奇霉素
尽管有一些阿奇霉素疗效的单例报告,[78]Kadappu KK, Nagaraja MV, Rao PV, et al. Azithromycin as treatment for cryptosporidiosis in human immunodeficiency virus disease. J Postgrad Med. 2002;48:179-181.http://www.jpgmonline.com/article.asp?issn=0022-3859;year=2002;volume=48;issue=3;spage=179;epage=81;aulast=Kadappuhttp://www.ncbi.nlm.nih.gov/pubmed/12432190?tool=bestpractice.com[79]Allam AF, Shehab AY. Efficacy of azithromycin, praziquantel and mirazid in treatment of cryptosporidiosis in school children. J Egypt Soc Parasitol. 2002;32:969-978.http://www.ncbi.nlm.nih.gov/pubmed/12512828?tool=bestpractice.com[80]Russell TS, Lynch J, Ottolini MG. Eradication of Cryptosporidium in a child undergoing maintenance chemotherapy for leukemia using high dose azithromycin therapy. J Pediatr Hematol Oncol. 1998;20:83-85.http://www.ncbi.nlm.nih.gov/pubmed/9482419?tool=bestpractice.com但其他报告尚未发现任何疗效。[81]Blanshard C, Shanson DC, Gazzard BG. Pilot studies of azithromycin, letrazuril and paromomycin in the treatment of cryptosporidiosis. Int J STD AIDS. 1997;8:124-129.http://www.ncbi.nlm.nih.gov/pubmed/9061412?tool=bestpractice.com
一些病例报告和一系列针对艾滋病患者的无对照研究表明,阿奇霉素联用巴龙霉素治疗是有效的。[82]Palmieri F, Cicalini S, Froio N, et al. Pulmonary cryptosporidiosis in an AIDS patient: successful treatment with paromomycin plus azithromycin. Int J STD AIDS. 2005;16:515-517.http://www.ncbi.nlm.nih.gov/pubmed/16004637?tool=bestpractice.com[83]Smith NH, Cron NS, Valdez LM, et al. Combination drug therapy for cryptosporidiosis in AIDS. J Infect Dis. 1998;178:900-903.http://www.ncbi.nlm.nih.gov/pubmed/9728569?tool=bestpractice.com艾滋病患者的临床疗效:有低等质量的证据表明,阿奇霉素联用巴龙霉素可用来治疗隐孢子虫病。一些病例报告和一系列针对艾滋病患者的无对照研究表明,阿奇霉素联用巴龙霉素治疗是有效的。[82]Palmieri F, Cicalini S, Froio N, et al. Pulmonary cryptosporidiosis in an AIDS patient: successful treatment with paromomycin plus azithromycin. Int J STD AIDS. 2005;16:515-517.http://www.ncbi.nlm.nih.gov/pubmed/16004637?tool=bestpractice.com[83]Smith NH, Cron NS, Valdez LM, et al. Combination drug therapy for cryptosporidiosis in AIDS. J Infect Dis. 1998;178:900-903.http://www.ncbi.nlm.nih.gov/pubmed/9728569?tool=bestpractice.com低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。因此,一些对治疗免疫功能受损患者的重度或致命性隐孢子虫病有丰富经验的临床医生主张联合硝唑尼特、巴龙霉素和阿奇霉素进行治疗。