Technical specification for clinical diagnosis and treatment of human parvovirus B19 infection in kidney transplant recipients (2022 edition)
-
摘要: 肾移植受者长期使用免疫抑制剂,导致其免疫功能低下,容易伴发各种病原体感染。近年来随着人类微小病毒B19(HPV-B19)感染的检测技术发展和肾移植手术的增多,肾移植术后HPV-B19的感染率呈逐年上升的趋势,是导致术后纯红细胞再生障碍性贫血(PRCA)的重要原因之一,影响移植肾功能恢复,甚至导致移植肾损伤或预后不良。为了进一步规范肾移植受者HPV-B19感染的诊断和治疗,中华医学会器官移植学分会和国家肾脏移植质控中心组织专家,从HPV-B19病原学、流行病学特点、临床表现、诊断、预防、治疗、存在的问题及展望等方面,制订肾移植术后HPV-B19感染的临床诊疗规范,以期为我国肾移植术后HPV-B19感染的规范化防治提供指导。
-
关键词:
- 人类微小病毒B19(HPV-B19) /
- 纯红细胞再生障碍性贫血(PRCA) /
- 促红细胞生成素(EPO) /
- 信号转导和转录激活因子(STAT) /
- 抗人T细胞免疫球蛋白(ALG) /
- 静脉注射用人免疫球蛋白(IVIG) /
- 二代测序(NGS) /
- 西多福韦 /
- 羟基脲 /
- 膦甲酸钠
Abstract: Long-term use of immunosuppressant in kidney transplant recipients leads to poor immune function and infection with various pathogens. In recent years, along with the advancement of detection technique of human parvovirus B19 (HPV-B19) infection and the increasing quantity of kidney transplantation, the infection rate of HPV-B19 after kidney transplantation has been elevated year by year, becoming one of the major causes of pure red cell aplasia (PRCA), affecting the recovery of renal allograft function, and even leading to the injury or poor prognosis of renal allograft. To further standardize the diagnosis and treatment of HPV-B19 infection in kidney transplant recipients, Branch of Organ Transplantation of Chinese Medical Association and National Kidney Transplantation Quality Control Center jointly organized experts to formulate the clinical diagnosis and treatment specification for HPV-B19 infection after kidney transplantation from the perspectives of etiology, epidemiological characteristics, clinical manifestations, diagnosis, prevention, treatment, existing problems and prospects of HPV-B19, aiming to provide guidance for standardized prevention and treatment of HPV-B19 infection post-kidney transplantation in China.-
Key words:
- Human parvovirus B19 (HPV-B19) /
- Pure red cell aplasia (PRCA) /
- Erythropoietin (EPO) /
- Signal transducer and activator of transcription (STAT) /
- Anti-human T lymphocyte immunoglobulin (ALG) /
- Intravenous immunoglobulin (IVIG) /
- Next generation sequencing (NGS) /
- Cidofovir /
- Hydroxyurea /
- Foscarnet sodium
-
表 1 肾移植受者HPV-B19感染的主要危险因素
Table 1. Main risk factors of HPV-B19 infection in kidney transplant recipients
分类 危险因素 供者
因素HPV-B19血清学或HPV-B19 DNA阳性 尸体供肾移植或心脏死亡器官捐献供肾移植 术前隐性HPV-B19感染 HLA ①高度不匹配(≥ 4个不匹配) 儿童 受者
因素他克莫司血药浓度较高(> 8 ng/mL) ALG多克隆抗体诱导治疗 输血或血液制品(凝血因子Ⅷ、凝血酶原复合物、纤维蛋白原、冷沉淀等) 贫血或发病前3个月内血红蛋白下降水平 全血细胞减少 注:① HLA为人类白细胞抗原。 表 2 HPV-B19感染相关的几种疾病
Table 2. Several diseases related to HPV-B19 infection
疾病类别 常见发病人群 慢性PRCA 免疫抑制患者 器官侵袭性疾病 免疫抑制患者 关节病 免疫力正常成人 感染性红斑 免疫力正常儿童 心肌炎 免疫力正常儿童 胎儿水肿或胎儿死亡 胎儿或妊娠期女性 短暂再生障碍性贫血危象 溶血性贫血患者 特发性血小板减少性紫癜 免疫力正常儿童 血管性紫癜 儿童或成人 血管炎 儿童或成人 表 3 肾移植受者HPV-B19感染的临床诊断
Table 3. Clinical diagnosis of HPV-B19 infection in kidney transplant recipients
分类 诊断依据 怀疑HPV-B19感染的临床表现:符合表中(1)+(2)+(3),和(或)(4) (1)贫血:持续性或严重贫血(Hb < 60 g/L),且伴RET减少症和对EPO缺乏反应;可伴或不伴发热、关节痛、皮疹、白细胞减少及血小板减少等 (2)排除药物因素或其他原因导致的贫血,如骨髓抑制、失血、肿瘤或营养缺乏等因素 (3)实验室检查:Hb呈进行性下降,红细胞明显减少,RET显著减少(RET% < 0.5%),部分患者可伴有全血细胞减少 (4)器官侵袭性疾病:如肾小球疾病、肝炎、心肌炎、肺炎、血管炎及神经系统疾病等,且排除其他导致这些疾病的因素 疑似HPV-B19感染的初步检查 (1)HPV-B19的血清学(IgG和IgM):HPV-B19 IgM阳性 (2)血清或全血qRT-PCR:HPV-B19 DNA阳性 (3)NGS技术:检出高序列数的HPV-B19 当强烈怀疑HPV-B19感染,血清学和PCR呈阴性时 (1)进行骨髓穿刺活检及原位杂交或免疫组织化学染色 (2)骨髓表现:符合HPV-B19相关PRCA的特点 -
[1] LOBBES H, MAHÉVAS M, ALVISET S, et al. Pure red cell aplasia in systemic lupus erythematosus, a nationwide retrospective cohort and review of the literature[J]. Rheumatology (Oxford), 2021, 61(1): 355-366. DOI: 10.1093/rheumatology/keab363. [2] REZAHOSSEINI O, EKENBERG C, MØLLER DL, et al. Incidence and impact of parvovirus B19 infection in seronegative solid organ transplant recipients[J]. J Infect Dis, 2021, 224(5): 865-869. DOI: 10.1093/infdis/jiab024. [3] EID AJ, ARDURA MI, AST Infectious Diseases Community of Practice. Human parvovirus B19 in solid organ transplantation: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice[J]. Clin Transplant, 2019, 33(9): e13535. DOI: 10.1111/ctr.13535. [4] 涂金鹏. 实体器官移植术后人微小病毒B19感染研究进展[J/CD]. 泌尿外科杂志(电子版), 2021, 13(2): 15-18. DOI: 10.3969/j.issn.1674-7410.2021.02.004.TU JP. Research progress on human parvovirus B19 infection after solid organ transplantation[J/CD]. J Urol Clin(Electr Vers), 2021, 13(2): 15-18. DOI: 10.3969/j.issn.1674-7410.2021.02.004.j.issn.1674-7410.2021.02.004. [5] GARCIA RCNC, LEON LA. Human parvovirus B19: a review of clinical and epidemiological aspects in Brazil[J]. Future Microbiol, 2021, 16(1): 37-50. DOI: 10.2217/fmb-2020-0123. [6] GANAIE SS, QIU J. Recent advances in replication and infection of human parvovirus B19[J]. Front Cell Infect Microbiol, 2018, 8: 166. DOI: 10.3389/fcimb.2018.00166. [7] BROWN KE, HIBBS JR, GALLINELLA G, et al. Resistance to parvovirus B19 infection due to lack of virus receptor (erythrocyte P antigen)[J]. N Engl J Med, 1994, 330(17): 1192-1196. DOI: 10.1056/NEJM199404283301704. [8] NOURI M, KAMAKIFAR P, KHODABANDEHLOU N, et al. Association between parvovirus B19 and anemia in HIV-infected patients[J]. Med J Islam Repub Iran, 2019, 33: 137. DOI: 10.34171/mjiri.33.137. [9] 段继惠, 穆红, 唐志琴, 等. 肾移植受者感染人类细小病毒B19后对T淋巴细胞的影响[J]. 中华实验外科杂志, 2014, 31(4): 902. DOI: 10.3760/cma.j.issn.1001-9030.2014.04.083.DUAN JH, MU H, TANG ZQ, et al. Effect of renal transplant recipients infected with human parvovirus B19 on T lymphocytes[J]. Chin J Exp Surg, 2014, 31(4): 902. DOI: 10.3760/cma.j.issn.1001-9030.2014.04.083. [10] SIM JY, CHANG LY, CHEN JM, et al. Human parvovirus B19 infection in patients with or without underlying diseases[J]. J Microbiol Immunol Infect, 2019, 52(4): 534-541. DOI: 10.1016/j.jmii.2019.05.009. [11] KI CS, KIM IS, KIM JW, et al. Incidence and clinical significance of human parvovirus B19 infection in kidney transplant recipients[J]. Clin Transplant, 2005, 19(6): 751-755. DOI: 10.1111/j.1399-0012.2005.00415.x. [12] GOSSET C, VIGLIETTI D, HUE K, et al. How many times can parvovirus B19-related anemia recur in solid organ transplant recipients?[J]. Transpl Infect Dis, 2012, 14(5): E64-E70. DOI: 10.1111/j.1399-3062.2012.00773.x. [13] 张欢, 肖霞, 李玉明, 等. 实体器官移植后细小病毒B19感染导致单纯红细胞再生障碍性贫血3例并文献复习[J]. 中华实验和临床病毒学杂志, 2020, 34(5): 543-546. DOI: 10.3760/cma.j.cn112866-20191230-00210.ZHANG H, XIAO X, LI YM, et al. Three cases of pure red cell aplasia caused by parvovirus B19 infection after solid organ transplantation and literature review[J]. Chin J Exp Clin Virol, 2020, 34(5): 543-546. DOI: 10.3760/cma.j.cn112866-20191230-00210. [14] ALTHEABY A, ALOTAIBI M, ALAJLAN N, et al. Parvovirus B19 infection due to over immunosuppression in kidney transplant recipients: case reports and literature review[J]. Case Rep Transplant, 2021: 7651488. DOI: 10.1155/2021/7651488. [15] PORIGNAUX R, VUIBLET V, BARBE C, et al. Frequent occurrence of parvovirus B19 DNAemia in the first year after kidney transplantation[J]. J Med Virol, 2013, 85(6): 1115-1121. DOI: 10.1002/jmv.23557. [16] THONGPRAYOON C, KHOURY NJ, BATHINI T, et al. Epidemiology of parvovirus B19 and anemia among kidney transplant recipients: a Meta-analysis[J]. Urol Ann, 2020, 12(3): 241-247. DOI: 10.4103/UA.UA_89_19. [17] MENDE M, SOCKEL K. Parvovirus B19 infection[J]. N Engl J Med, 2018, 379(24): 2361. DOI: 10.1056/NEJMicm1807156. [18] YU Y, WEI C, LYU J, et al. Donor-derived human parvovirus B19 infection in kidney transplantation[J]. Front Cell Infect Microbiol, 2021, 11: 753970. DOI: 10.3389/fcimb.2021.753970. [19] BAEK CH, KIM H, YANG WS, et al. Risk factors and long-term outcomes of parvovirus B19 infection in kidney transplant patients[J]. Transpl Infect Dis, 2017, 19(5). DOI: 10.1111/tid.12754. [20] KOOISTRA K, MESMAN HJ, DE WAAL M, et al. Epidemiology of high-level parvovirus B19 viraemia among Dutch blood donors, 2003-2009[J]. Vox Sang, 2011, 100(3): 261-266. DOI: 10.1111/j.1423-0410.2010.01423.x. [21] 耿彦生, 张印法. 血液、血制品与人类微小病毒B19的传播[J]. 疾病控制杂志, 2007, 11(5): 516-519. DOI: 10.3969/j.issn.1674-3679.2007.05.022.GEN YS, ZHANG YF. Human parvovirus B19 and the safety of blood and blood-derived products[J]. Chin J Dis Control Prev, 2007, 11(5): 516-519. DOI: 10.3969/j.issn.1674-3679.2007.05.022. [22] ZHANG W, KE L, CHANGQING L, et al. Parvovirus B19V DNA contamination in Chinese plasma and plasma derivatives[J]. J Transl Med, 2012, 10: 194. DOI: 10.1186/1479-5876-10-194. [23] BARZON L, MURER L, PACENTI M, et al. Detection of viral DNA in kidney graft preservation and washing solutions is predictive of posttransplant infections in pediatric recipients[J]. J Infect Dis, 2009, 200(9): 1425-1433. DOI: 10.1086/644504. [24] 熊睿, 丁利民, 柳祝菁, 等. 肾移植后细小病毒B19感染所致贫血的诊疗策略[J/CD]. 实用器官移植电子杂志, 2021, 9(3): 249-252. DOI: 10.3969/j.issn.2095-5332.2021.03.019.XIONG R, DING LM, LIU ZJ, et al. Diagnosis and treatment strategies for anemia caused by parvovirus B19 infection after kidney transplantation[J/CD]. Pract J Organ Transplant(Electr Vers), 2021, 9(3): 249-252. DOI: 10.3969/j.issn.2095-5332.2021.03.019. [25] KAUFFMANN M, BOBOT M, DANIEL L, et al. Parvovirus B19 infection and kidney injury: report of 4 cases and analysis of immunization and viremia in an adult cohort of 100 patients undergoing a kidney biopsy[J]. BMC Nephrol, 2020, 21(1): 260. DOI: 10.1186/s12882-020-01911-9. [26] BARZON L, MURER L, PACENTI M, et al. Investigation of intrarenal viral infections in kidney transplant recipients unveils an association between parvovirus B19 and chronic allograft injury[J]. J Infect Dis, 2009, 199(3): 372-380. DOI: 10.1086/596053. [27] ABDELRAHMAN D, AL-SADEQ DW, SMATTI MK, et al. Prevalence and phylogenetic analysis of parvovirus (B19V) among blood donors with different nationalities residing in Qatar[J]. Viruses, 2021, 13(4): 540. DOI: 10.3390/v13040540. [28] 胡娜娜, 许书添, 董建华, 等. 肾移植术后人细小病毒B19感染[J]. 肾脏病与透析肾移植杂志, 2018, 27(6): 589-593. DOI: 10.3969/j.issn.1006-298X.2018.06.020.HU NN, XU ST, DONG JH, et al. Human parvovirus B19 infection after renal transplantation[J]. Chin J Nephrol Dial Transplant, 2018, 27(6): 589-593. DOI: 10.3969/j.issn.1006-298X.2018.06.020. [29] DAS P, CHATTERJEE K, CHATTOPADHYAY NR, et al. Evolutionary aspects of parvovirus B-19V associated diseases and their pathogenesis patterns with an emphasis on vaccine development[J]. Virusdisease, 2019, 30(1): 32-42. DOI: 10.1007/s13337-019-00525-6. [30] ROSADO-CANTO R, CARRILLO-PÉREZ DL, JIMÉNEZ JV, et al. Treatment strategies and outcome of parvovirus B19 infection in kidney transplant recipients: a case series and literature review of 128 patients[J]. Rev Invest Clin, 2019, 71(4): 265-274. DOI: 10.24875/RIC.19002921. [31] HAZEBROEK MR, HENKENS MTHM, RAAFS AG, et al. Intravenous immunoglobulin therapy in adult patients with idiopathic chronic cardiomyopathy and cardiac parvovirus B19 persistence: a prospective, double-blind, randomized, placebo-controlled clinical trial[J]. Eur J Heart Fail, 2021, 23(2): 302-309. DOI: 10.1002/ejhf.2082. [32] WASSERMAN RL. Immunoglobulin replacement for primary immunodeficiency: indications for initiating and continuing treatment[J]. Allergy Asthma Proc, 2021, 42(6): 489-494. DOI: 10.2500/aap.2021.42.210082. [33] CRABOL Y, TERRIER B, ROZENBERG F, et al. Intravenous immunoglobulin therapy for pure red cell aplasia related to human parvovirus B19 infection: a retrospective study of 10 patients and review of the literature[J]. Clin Infect Dis, 2013, 56(7): 968-977. DOI: 10.1093/cid/cis1046. [34] 张晓伟, 张雷, 赵闻雨, 等. 肾移植术后微小病毒B19感染22例临床治疗经验[J]. 中华器官移植杂志, 2019, 40(6): 323-327. DOI: 10.3760/cma.j.issn.0254-1785.2019.06.002.ZHANG XW, ZHANG L, ZHAO WY, et al. Parvovirus B19 infection in patients after renal transplantation: a report of 22 cases[J]. Chin J Organ Transplant, 2019, 40(6): 323-327. DOI: 10.3760/cma.j.issn.0254-1785.2019.06.002. [35] BUA G, CONTI I, MANARESI E, et al. Antiviral activity of brincidofovir on parvovirus B19[J]. Antiviral Res, 2019, 162: 22-29. DOI: 10.1016/j.antiviral.2018.12.003. [36] MANARESI E, GALLINELLA G. Advances in the development of antiviral strategies against parvovirus B19[J]. Viruses, 2019, 11(7): 659. DOI: 10.3390/v11070659. [37] BARAL A, POUDEL B, AGRAWAL RK, et al. Pure red cell aplasia caused by parvo B19 virus in a kidney transplant recipient[J]. JNMA J Nepal Med Assoc, 2012, 52(186): 75-78. http://jnma.com.np/jnma/index.php/jnma/article/download/73/345 -