非洲锥虫病

推荐作为一线治疗药物。[2]World Health Organization. Control and surveillance of human African trypanosomiasis. Technical Report Series 984. Geneva, Switzerland: WHO; 2013.http://apps.who.int/iris/bitstream/10665/95732/1/9789241209847_eng.pdf?ua=1[140]Centers for Disease Control and Prevention. Parasites - African trypanosomiasis (also known as sleeping sickness): resources for health professionals. August 2016 [internet publication].https://www.cdc.gov/parasites/sleepingsickness/health_professionals/index.html

注射喷他脒时较痛。患者应在注射前摄入适量糖分，以预防低血糖风险；接受喷他脒治疗之后，患者应仰卧 1-2 个小时，同时监测患者血压和心律。推荐在治疗期间监测患者血糖、血钙、肾功能和胰腺功能、钾和血清肌酐水平。应定期对患者进行心电图 (ECG) 监测。[68]Blum JA, Schmid C, Burri C, et al. Cardiac alterations in human African trypanosomiasis (T b gambiense) with respect to the disease stage and antiparasitic treatment. PLoS Negl Trop Dis. 2009;3(2):e383.http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0000383http://www.ncbi.nlm.nih.gov/pubmed/19221604?tool=bestpractice.com

目前的有效率为 95%-98%。[2]World Health Organization. Control and surveillance of human African trypanosomiasis. Technical Report Series 984. Geneva, Switzerland: WHO; 2013.http://apps.who.int/iris/bitstream/10665/95732/1/9789241209847_eng.pdf?ua=1[141]Balasegaram M, Harris S, Checchi F, et al. Treatment outcomes and risk factors for relapse in patients with early-stage human African trypanosomiasis (HAT) in the Republic of the Congo. Bull World Health Organ. 2006 Oct;84(10):777-82.http://www.ncbi.nlm.nih.gov/pubmed/17128357?tool=bestpractice.com

喷他脒已被认为无致突变性且无遗传毒性，推荐用于治疗孕妇的早期疾病。[154]Stauffert I, Paulini H, Steinmann U, et al. Investigations on mutagenicity and genotoxicity of pentamidine and some related trypanocidal diamidines. Mutation Research. 1990 Oct;245(2):93-8.http://www.ncbi.nlm.nih.gov/pubmed/2215556?tool=bestpractice.com

可以从世界卫生组织的疾病创新和强化管理 (World Health Organization's Innovative and Intensified Disease Management) 项目中免费获取所有推荐药物。[139]Simarro PP, Franco J, Diarra A, et al. Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis. Parasitology. 2012 Jun;139(7):842-6.http://www.ncbi.nlm.nih.gov/pubmed/22309684?tool=bestpractice.com

可以将静脉输注依氟鸟氨酸用作一线治疗药物，单药治疗或联合硝呋莫司使用皆可。[2]World Health Organization. Control and surveillance of human African trypanosomiasis. Technical Report Series 984. Geneva, Switzerland: WHO; 2013.http://apps.who.int/iris/bitstream/10665/95732/1/9789241209847_eng.pdf?ua=1[140]Centers for Disease Control and Prevention. Parasites - African trypanosomiasis (also known as sleeping sickness): resources for health professionals. August 2016 [internet publication].https://www.cdc.gov/parasites/sleepingsickness/health_professionals/index.html

依氟鸟氨酸作为单药治疗时需要以静脉输注方式连续治疗 14 天。[124]Priotto G, Pinoges L, Fursa IB, et al. Safety and effectiveness of first line eflornithine for Trypanosoma brucei gambiense sleeping sickness in Sudan: cohort study. BMJ. 2008 Mar 29;336(7646):705-8.http://www.bmj.com/content/336/7646/705.fullhttp://www.ncbi.nlm.nih.gov/pubmed/18321960?tool=bestpractice.com[142]Balasegaram M, Harris S, Checchi F, et al. Melarsoprol versus eflornithine for treating late-stage Gambian trypanosomiasis in the Republic of the Congo. Bull World Health Organ. 2006 Oct;84(10):783-91.http://www.ncbi.nlm.nih.gov/pubmed/17128358?tool=bestpractice.com[143]Chappuis F. Melarsoprol-free drug combinations for second-stage Gambian sleeping sickness: the way to go. Clin Infect Dis. 2007 Dec 1;45(11):1443-5.http://www.ncbi.nlm.nih.gov/pubmed/17990226?tool=bestpractice.com[144]Balasegaram M, Young H, Chappuis F, et al. Effectiveness of melarsoprol and eflornithine as first-line regimens for gambiense sleeping sickness in nine Medecins Sans Frontieres programmes. Trans R Soc Trop Med Hyg. 2009 Mar;103(3):280-90.http://www.ncbi.nlm.nih.gov/pubmed/18947846?tool=bestpractice.com[145]Lutje V, Seixas J, Kennedy A. Chemotherapy for second-stage human African trypanosomiasis. Cochrane Database Syst Rev. 2013 Jun 28;(6):CD006201.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006201.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23807762?tool=bestpractice.com[146]Priotto G, Kasparian S, Mutombo W, et al. Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial. Lancet. 2009 Jul 4;374(9683):56-64.http://www.ncbi.nlm.nih.gov/pubmed/19559476?tool=bestpractice.com 依氟鸟氨酸联合使用硝呋莫司治疗已被用于临床实践，以减少依氟鸟氨酸单药治疗的持续时间和负荷，延缓耐药性的出现。[145]Lutje V, Seixas J, Kennedy A. Chemotherapy for second-stage human African trypanosomiasis. Cochrane Database Syst Rev. 2013 Jun 28;(6):CD006201.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006201.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23807762?tool=bestpractice.com[146]Priotto G, Kasparian S, Mutombo W, et al. Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial. Lancet. 2009 Jul 4;374(9683):56-64.http://www.ncbi.nlm.nih.gov/pubmed/19559476?tool=bestpractice.com[148]Alirol E, Schrumpf D, Amici Heradi J, et al. Nifurtimox-eflornithine combination therapy for second-stage Gambiense human African trypanosomiasis: Médecins sans Frontières experience in the Democratic Republic of the Congo. Clin Infect Dis. 2013 Jan;56(2):195-203.https://academic.oup.com/cid/article/56/2/195/318180/Nifurtimox-Eflornithine-Combination-Therapy-forhttp://www.ncbi.nlm.nih.gov/pubmed/23074318?tool=bestpractice.com 在无法获得硝呋莫司的地区，可以给予依氟鸟氨酸单药治疗。

可以将美拉胂醇与泼尼松龙联合用于（以预防美拉胂醇相关性脑病）疾病复发的患者。[2]World Health Organization. Control and surveillance of human African trypanosomiasis. Technical Report Series 984. Geneva, Switzerland: WHO; 2013.http://apps.who.int/iris/bitstream/10665/95732/1/9789241209847_eng.pdf?ua=1[142]Balasegaram M, Harris S, Checchi F, et al. Melarsoprol versus eflornithine for treating late-stage Gambian trypanosomiasis in the Republic of the Congo. Bull World Health Organ. 2006 Oct;84(10):783-91.http://www.ncbi.nlm.nih.gov/pubmed/17128358?tool=bestpractice.com[149]Schmid C, Richer M, Bilenge CM, et al. Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (Impamel II). J Infect Dis. 2005 Jun 1;191(11):1922-31.https://academic.oup.com/jid/article/191/11/1922/2191985/Effectiveness-of-a-10-Day-Melarsoprol-Schedule-forhttp://www.ncbi.nlm.nih.gov/pubmed/15871127?tool=bestpractice.com 推荐在使用过程中密切监测血液参数、肾功能和肝功能。治疗期间禁止饮酒。

目前针对人类非洲锥虫病（HAT）感染儿童患者的治疗数据有限，但是一般来说，对 儿童的治疗通常遵循与成人相同的治疗方案。[151]Eperon G, Schmid C, Loutan L, et al. Clinical presentation and treatment outcome of sleeping sickness in Sudanese pre-school children. Acta Trop. 2007 Jan;101(1):31-9.http://www.ncbi.nlm.nih.gov/pubmed/17207760?tool=bestpractice.com 曾有报告称对未满 12 岁儿童采用依氟鸟氨酸治疗，其生物利用度较低。 因此，给予儿童患者依氟鸟氨酸单药治疗时，须增加给药剂量。[152]Milord F, Pepin J, Loko L, et al. Efficacy and toxicity of eflornithine for treatment of Trypanosoma brucei gambiense sleeping sickness. Lancet. 1992 Sep 12;340(8820):652-5.http://www.ncbi.nlm.nih.gov/pubmed/1355219?tool=bestpractice.com

可以从世界卫生组织的疾病创新和强化管理 (WHO's Innovative and Intensified Disease Management, IDM) 项目免费获取所有推荐药物。[139]Simarro PP, Franco J, Diarra A, et al. Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis. Parasitology. 2012 Jun;139(7):842-6.http://www.ncbi.nlm.nih.gov/pubmed/22309684?tool=bestpractice.com

如果疾病并不严重，建议在妊娠和分娩期间给予喷他脒治疗，并对患者进行密切随访，但在产后需给予针对该病第二阶段的药物进行治疗。

妊娠期间使用抗锥虫药物治疗应考虑药物对孕妇和胎儿的潜在获益和危害，慎重作出决定。[153]World Health Organization. WHO model prescribing information: drugs used in parasitic diseases, 2nd edition. Geneva: World Health Organization, 1995.http://apps.who.int/medicinedocs/collect/medicinedocs/pdf/h2922e/h2922e.pdf 喷他脒已被认为无致突变性且无遗传毒性。[154]Stauffert I, Paulini H, Steinmann U, et al. Investigations on mutagenicity and genotoxicity of pentamidine and some related trypanocidal diamidines. Mutation Research. 1990 Oct;245(2):93-8.http://www.ncbi.nlm.nih.gov/pubmed/2215556?tool=bestpractice.com

注射喷他脒时较痛。 患者应在注射开始前摄入适量糖分，以降低低血糖风险；接受喷他脒治疗之后，患者应仰卧 1~2 个小时，同时密切监测患者血压和心律。 建议在治疗期间密切监测患者葡萄糖、血钙、肾功能和胰腺功能、钾和血清肌酐水平。 应对患者定期进行心电图检查。[68]Blum JA, Schmid C, Burri C, et al. Cardiac alterations in human African trypanosomiasis (T b gambiense) with respect to the disease stage and antiparasitic treatment. PLoS Negl Trop Dis. 2009;3(2):e383.http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0000383http://www.ncbi.nlm.nih.gov/pubmed/19221604?tool=bestpractice.com

可以从世界卫生组织的疾病创新和强化管理 (WHO's Innovative and Intensified Disease Management, IDM) 项目免费获取所有推荐药物。[139]Simarro PP, Franco J, Diarra A, et al. Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis. Parasitology. 2012 Jun;139(7):842-6.http://www.ncbi.nlm.nih.gov/pubmed/22309684?tool=bestpractice.com

如果患有重度冈比亚锥虫病，并且患者是高危孕产妇，推荐采用静脉注射依氟鸟氨酸和硝呋莫司进行治疗。在无法获得硝呋莫司的地区，可以给予依氟鸟氨酸单药治疗。可以将美拉胂醇与泼尼松龙联联合使用（以预防美拉胂醇相关性脑病），以治疗难治性疾病或复发性疾病患者。

妊娠期间使用抗锥虫药物治疗应考虑药物对孕妇和胎儿的潜在获益和危害，慎重作出决定。[153]World Health Organization. WHO model prescribing information: drugs used in parasitic diseases, 2nd edition. Geneva: World Health Organization, 1995.http://apps.who.int/medicinedocs/collect/medicinedocs/pdf/h2922e/h2922e.pdf 有报告称美拉胂醇是导致婴儿低出生体重、自然流产和畸形的原因。[156]Reinhardt MC, MacLeod CL. African trypanosomiasis (African sleeping sickness). In: MacLeod CL, ed. Parasitic infections in pregnancy and the newborn. Oxford: Oxford University Press; 1988:1-308. 依氟鸟氨酸已被认为可导致大鼠流产、胎儿较小和发育迟缓。[157]Kirchner DL, Mercieca MD, Crowell JA, et al. Developmental toxicity studies of 2-(difluoromethyl)-dl-ornithine (DFMO) in rats and rabbits. Toxicol Sci. 1999 Jul;50(1):127-35.http://toxsci.oxfordjournals.org/content/50/1/127.full.pdf+htmlhttp://www.ncbi.nlm.nih.gov/pubmed/10445761?tool=bestpractice.com

可以从世界卫生组织的疾病创新和强化管理 (WHO's Innovative and Intensified Disease Management, IDM) 项目免费获取所有推荐药物。[139]Simarro PP, Franco J, Diarra A, et al. Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis. Parasitology. 2012 Jun;139(7):842-6.http://www.ncbi.nlm.nih.gov/pubmed/22309684?tool=bestpractice.com

推荐作为一线治疗药物。[2]World Health Organization. Control and surveillance of human African trypanosomiasis. Technical Report Series 984. Geneva, Switzerland: WHO; 2013.http://apps.who.int/iris/bitstream/10665/95732/1/9789241209847_eng.pdf?ua=1[140]Centers for Disease Control and Prevention. Parasites - African trypanosomiasis (also known as sleeping sickness): resources for health professionals. August 2016 [internet publication].https://www.cdc.gov/parasites/sleepingsickness/health_professionals/index.html

建议密切监测患者血液参数和肾功能。

可以从世界卫生组织的疾病创新和强化管理 (WHO's Innovative and Intensified Disease Management, IDM) 项目免费获取所有推荐药物。[139]Simarro PP, Franco J, Diarra A, et al. Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis. Parasitology. 2012 Jun;139(7):842-6.http://www.ncbi.nlm.nih.gov/pubmed/22309684?tool=bestpractice.com

妊娠期间使用抗锥虫药物治疗应考虑药物对孕妇和胎儿的潜在获益和危害，慎重作出决定。[153]World Health Organization. WHO model prescribing information: drugs used in parasitic diseases, 2nd edition. Geneva: World Health Organization, 1995.http://apps.who.int/medicinedocs/collect/medicinedocs/pdf/h2922e/h2922e.pdf 喷他脒已被认为无致突变性且无遗传毒性。[154]Stauffert I, Paulini H, Steinmann U, et al. Investigations on mutagenicity and genotoxicity of pentamidine and some related trypanocidal diamidines. Mutation Research. 1990 Oct;245(2):93-8.http://www.ncbi.nlm.nih.gov/pubmed/2215556?tool=bestpractice.com

注射喷他脒时较痛。 患者应在注射开始前摄入适量糖分，以降低低血糖风险；接受喷他脒治疗之后，患者应仰卧1~2 个小时，同时密切监测其血压和心律。 建议在治疗期间密切监测患者葡萄糖、血钙、肾功能和胰腺功能、钾和血清肌酐水平。 应对患者定期进行心电图检查。[68]Blum JA, Schmid C, Burri C, et al. Cardiac alterations in human African trypanosomiasis (T b gambiense) with respect to the disease stage and antiparasitic treatment. PLoS Negl Trop Dis. 2009;3(2):e383.http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0000383http://www.ncbi.nlm.nih.gov/pubmed/19221604?tool=bestpractice.com

可以从世界卫生组织的疾病创新和强化管理 (WHO's Innovative and Intensified Disease Management, IDM) 项目免费获取所有推荐药物。[139]Simarro PP, Franco J, Diarra A, et al. Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis. Parasitology. 2012 Jun;139(7):842-6.http://www.ncbi.nlm.nih.gov/pubmed/22309684?tool=bestpractice.com

美拉胂醇是唯一可用来治疗晚期罗得西亚型人类非洲锥虫病的药物。[2]World Health Organization. Control and surveillance of human African trypanosomiasis. Technical Report Series 984. Geneva, Switzerland: WHO; 2013.http://apps.who.int/iris/bitstream/10665/95732/1/9789241209847_eng.pdf?ua=1[140]Centers for Disease Control and Prevention. Parasites - African trypanosomiasis (also known as sleeping sickness): resources for health professionals. August 2016 [internet publication].https://www.cdc.gov/parasites/sleepingsickness/health_professionals/index.html 使用此药物进行治疗时，应密切监测患者情况，一旦出现明显的副作用，应立即停止治疗。此药物通常与泼尼松龙联合使用，以预防美拉胂醇相关性脑病。

使用过程中建议密切监测血液参数、肾功能和肝功能。

可以从世界卫生组织的疾病创新和强化管理 (WHO's Innovative and Intensified Disease Management, IDM) 项目免费获取所有推荐药物。[139]Simarro PP, Franco J, Diarra A, et al. Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis. Parasitology. 2012 Jun;139(7):842-6.http://www.ncbi.nlm.nih.gov/pubmed/22309684?tool=bestpractice.com

如果疾病并不严重，建议在妊娠和分娩期间给予喷他脒治疗，并对患者进行密切随访，但在产后需给予针对该病第二阶段的药物进行治疗。

妊娠期间使用抗锥虫药物治疗应考虑药物对孕妇和胎儿的潜在获益和危害，慎重作出决定。[153]World Health Organization. WHO model prescribing information: drugs used in parasitic diseases, 2nd edition. Geneva: World Health Organization, 1995.http://apps.who.int/medicinedocs/collect/medicinedocs/pdf/h2922e/h2922e.pdf 喷他脒已被认为无致突变性且无遗传毒性。[154]Stauffert I, Paulini H, Steinmann U, et al. Investigations on mutagenicity and genotoxicity of pentamidine and some related trypanocidal diamidines. Mutation Research. 1990 Oct;245(2):93-8.http://www.ncbi.nlm.nih.gov/pubmed/2215556?tool=bestpractice.com

注射喷他脒时较痛。 患者应在注射开始前摄入适量糖分，以降低低血糖风险；接受喷他脒治疗之后，患者应仰卧1~2 个小时，同时密切监测其血压和心律。 建议在治疗期间密切监测患者葡萄糖、血钙、肾功能和胰腺功能、钾和血清肌酐水平。 应对患者定期进行心电图检查。[68]Blum JA, Schmid C, Burri C, et al. Cardiac alterations in human African trypanosomiasis (T b gambiense) with respect to the disease stage and antiparasitic treatment. PLoS Negl Trop Dis. 2009;3(2):e383.http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0000383http://www.ncbi.nlm.nih.gov/pubmed/19221604?tool=bestpractice.com

可以从世界卫生组织的疾病创新和强化管理 (WHO's Innovative and Intensified Disease Management, IDM) 项目免费获取所有推荐药物。[139]Simarro PP, Franco J, Diarra A, et al. Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis. Parasitology. 2012 Jun;139(7):842-6.http://www.ncbi.nlm.nih.gov/pubmed/22309684?tool=bestpractice.com

如果患有重度罗得西亚锥虫病，并且患者是高危孕产妇，推荐联用美拉胂醇和泼尼松龙（以预防美拉胂醇相关性脑病）。

妊娠期间使用抗锥虫药物治疗应考虑药物对孕妇和胎儿的潜在获益和危害，慎重作出决定。[153]World Health Organization. WHO model prescribing information: drugs used in parasitic diseases, 2nd edition. Geneva: World Health Organization, 1995.http://apps.who.int/medicinedocs/collect/medicinedocs/pdf/h2922e/h2922e.pdf 有报告称美拉胂醇是导致婴儿低出生体重、自然流产和畸形的原因。[156]Reinhardt MC, MacLeod CL. African trypanosomiasis (African sleeping sickness). In: MacLeod CL, ed. Parasitic infections in pregnancy and the newborn. Oxford: Oxford University Press; 1988:1-308.

使用过程中建议密切监测血液参数、肾功能和肝功能。

可以从世界卫生组织的疾病创新和强化管理 (WHO's Innovative and Intensified Disease Management, IDM) 项目免费获取所有推荐药物。[139]Simarro PP, Franco J, Diarra A, et al. Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis. Parasitology. 2012 Jun;139(7):842-6.http://www.ncbi.nlm.nih.gov/pubmed/22309684?tool=bestpractice.com