Article(id=1203002063585243431, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203002056400396334, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2023.06.0648, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1665158400000, receivedDateStr=2022-10-08, revisedDate=null, revisedDateStr=null, acceptedDate=1669478400000, acceptedDateStr=2022-11-27, onlineDate=1764747642655, onlineDateStr=2025-12-03, pubDate=1687881600000, pubDateStr=2023-06-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1764747642655, onlineIssueDateStr=2025-12-03, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1764747642655, creator=13701087609, updateTime=1764747642655, updator=13701087609, issue=Issue{id=1203002056400396334, tenantId=1146029695717560320, journalId=1189873630562394117, year='2023', volume='48', issue='6', pageStart='627', pageEnd='748', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1764747640943, creator=13701087609, updateTime=1764747714497, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1203002364979540735, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203002056400396334, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1203002364979540736, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203002056400396334, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=648, endPage=652, ext={EN=ArticleExt(id=1203002063933370683, articleId=1203002063585243431, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Treatment and management of tuberculosis in newborns, columnId=1203002057176342576, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Prevention, Diagnosis and Treatment of Tuberculosis, runingTitle=null, highlight=null, articleAbstract=

Tuberculosis (TB) is still a big threat to public health. TB in newborns includes congenital TB and neonatal TB. Although not common, rapid progress and high mortality rates must attract the attention of clinicians. Congenital TB is transmitted vertically from mother, mainly acquired in utero through haematogenous spread via the umbilical cord or at the time of delivery through aspiration or ingestion of infected amniotic fluid or cervicovaginal secretions. Neonatal TB is acquired after birth through exposure to a person with infectious TB. It is often difficult to distinguish congenital TB and neonatal TB. But treatment and management is the same. This paper discusses the prenatal (epidemiology, early detection and reasonable treatment of TB in pregnancy) and postpartum (evaluation and treatment of newborns with high risk factors for TB) management of tuberculosis in newborns in order to provide useful information for clinicians to identify congenital tuberculosis and neonatal tuberculosis in the early stage and take reasonable and effective treatment measures as soon as possible.

, correspAuthors=A-Dong Shen, authorNote=null, correspAuthorsNote=
* E-mail:
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结核病仍然是严重危害公众健康的重要疾病。新生儿期结核病包括先天性结核病和新生儿结核病,尽管并不常见,但由于进展迅速、病死率高,临床医师应予以重视。先天性结核病从母亲垂直传播而来,新生儿结核病则是在出生后通过接触传染性结核病患者而获得,两者在临床上通常难以区分,但治疗和管理是相同的。本文从新生儿期结核病的产前管理(即妊娠结核病的流行现状、早期识别和合理治疗)及产后管理(即高危患儿的评估和治疗)两个方面进行论述,以期为临床医师早期识别新生儿期结核病、采取合理有效的治疗措施提供参考。

, correspAuthors=申阿东, authorNote=null, correspAuthorsNote=
申阿东,E-mail:
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焦伟伟,医学博士,研究员,主要从事儿童结核病诊断、治疗及耐药机制方面的研究

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焦伟伟,医学博士,研究员,主要从事儿童结核病诊断、治疗及耐药机制方面的研究

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新生儿期结核病的诊治与管理
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焦伟伟 1, 2 , 蒋婷婷 2 , 申阿东 1, 2, *
解放军医学杂志 | 结核病的预防、诊断与治疗专题 2023,48(6): 648-652
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解放军医学杂志 | 结核病的预防、诊断与治疗专题 2023, 48(6): 648-652
新生儿期结核病的诊治与管理
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焦伟伟1, 2, 蒋婷婷2, 申阿东1, 2, *
作者信息
  • 1国家儿童医学中心/首都医科大学附属北京儿童医院/北京市儿科研究所/儿科学国家重点学科/儿科重大疾病研究教育部重点实验室/国家呼吸系统疾病临床医学研究中心/儿童呼吸道感染性疾病研究北京市重点实验室,北京 100045
  • 2首都医科大学附属北京儿童医院保定医院/保定市儿童感染性疾病精准诊治重点实验室,河北保定 071000
  • 焦伟伟,医学博士,研究员,主要从事儿童结核病诊断、治疗及耐药机制方面的研究

通讯作者:

申阿东,E-mail:
Treatment and management of tuberculosis in newborns
Wei-Wei Jiao1, 2, Ting-Ting Jiang2, A-Dong Shen1, 2, *
Affiliations
  • 1Beijing Key Laboratory of Pediatric Respiratory Infection Disease/National Clinical Research Center for Respiratory Diseases/Key Laboratory of Major Diseases in Children, Ministry of Education/National Key Discipline of Pediatrics (Capital Medical University) /Beijing Pediatric Research Institute/Beijing Children’s Hospital, Capital Medical University/National Center for Children’s Health, Beijing 100045, China
  • 2Baoding Key Laboratory for Precision Diagnosis and Treatment of Infectious Diseases in Children/Baoding Hospital of Beijing Children’s Hospital, Capital Medical University, Baoding, Hebei 071051, China
出版时间: 2023-06-28 doi: 10.11855/j.issn.0577-7402.2023.06.0648
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结核病仍然是严重危害公众健康的重要疾病。新生儿期结核病包括先天性结核病和新生儿结核病,尽管并不常见,但由于进展迅速、病死率高,临床医师应予以重视。先天性结核病从母亲垂直传播而来,新生儿结核病则是在出生后通过接触传染性结核病患者而获得,两者在临床上通常难以区分,但治疗和管理是相同的。本文从新生儿期结核病的产前管理(即妊娠结核病的流行现状、早期识别和合理治疗)及产后管理(即高危患儿的评估和治疗)两个方面进行论述,以期为临床医师早期识别新生儿期结核病、采取合理有效的治疗措施提供参考。

结核病  /  新生儿感染  /  管理

Tuberculosis (TB) is still a big threat to public health. TB in newborns includes congenital TB and neonatal TB. Although not common, rapid progress and high mortality rates must attract the attention of clinicians. Congenital TB is transmitted vertically from mother, mainly acquired in utero through haematogenous spread via the umbilical cord or at the time of delivery through aspiration or ingestion of infected amniotic fluid or cervicovaginal secretions. Neonatal TB is acquired after birth through exposure to a person with infectious TB. It is often difficult to distinguish congenital TB and neonatal TB. But treatment and management is the same. This paper discusses the prenatal (epidemiology, early detection and reasonable treatment of TB in pregnancy) and postpartum (evaluation and treatment of newborns with high risk factors for TB) management of tuberculosis in newborns in order to provide useful information for clinicians to identify congenital tuberculosis and neonatal tuberculosis in the early stage and take reasonable and effective treatment measures as soon as possible.

tuberculosis  /  neonatal infection  /  management
焦伟伟, 蒋婷婷, 申阿东. 新生儿期结核病的诊治与管理. 解放军医学杂志, 2023 , 48 (6) : 648 -652 . DOI: 10.11855/j.issn.0577-7402.2023.06.0648
Wei-Wei Jiao, Ting-Ting Jiang, A-Dong Shen. Treatment and management of tuberculosis in newborns[J]. Medical Journal of Chinese People’s Liberation Army, 2023 , 48 (6) : 648 -652 . DOI: 10.11855/j.issn.0577-7402.2023.06.0648
新生儿期结核病包括先天性结核病及出生后获得的结核病(通常称为新生儿结核病)[1]。新生儿期结核病较罕见,既往文献多为个案报道[2-4]。然而,近年来由于全球结核病疫情的加剧(尤其是在育龄妇女中)和人类免疫缺陷病毒(human immunodeficiency virus,HIV)的流行,新生儿期结核病有所增多。1985-1992年美国新生儿结核病的发病率增高了40%,1998年伦敦的新生儿结核病发病率达143.3/10万[5-6]。此外,新生儿期结核病进展快,病死率高达40%~60%,如未及时诊断和治疗,病死率更高[5]。因此,必须重视新生儿期结核病的管理。本文从产前管理(即妊娠结核病的危害与流行现状、早期识别和合理治疗)及产后管理(即高危患儿的评估和治疗)两个方面进行论述,旨在提高临床医师早期识别新生儿期结核病的能力,进而采取合理有效的治疗措施。
据统计,在所有孕产妇死亡病例中,结核病导致的死亡占6%~15%;此外,结核病还可导致不良妊娠结局[7-8]。瑞典一项基于全国登记数据的大型回顾性队列研究发现,孕妇和产妇的结核病发病率分别为非孕妇的1.4倍和1.9倍[9],而产后结核病发病率增高可能是由于怀孕期间相关的生理和免疫变化导致结核病早期发现延迟所致[10]。妊娠结核病与孕产妇临床不良结局及分娩并发症相关,如先兆子痫、子痫、阴道出血、住院和流产等;同时,妊娠结核病可使围产儿出现早产、低出生体重和宫内发育迟缓的风险增加2倍,死亡风险增加6倍[11-13]。孕产妇结核病不仅使HIV垂直传播的风险增加了1倍以上[14],而且还增加了新生儿及家庭中其他幼儿的死亡风险[15]
目前尚无妊娠结核病发病情况的确切数据,根据模型估算,每年有超过21.5万孕产妇罹患结核病,其中绝大多数病例发生在非洲和东南亚地区[16]。但是,该模型在估算时假定孕产妇与未怀孕妇女的结核病筛查和诊断方法敏感性相同,因此可能低估了实际的发病情况。
妊娠结核病的临床表现与非妊娠期女性相似。有研究发现,在27例患有活动性结核病的孕妇中,常见的症状有咳嗽(71%)、体重减轻(41%)、发热(30%)、疲劳(30%),但该队列中仍有高达20%的女性无临床症状[17]。怀孕本身会掩盖结核病的早期症状如呼吸急促、疲劳、体重减轻等,由此可能延误诊断及治疗。在进行结核病筛查和诊断的孕妇中,大多数无临床症状,且不知道自己患有结核病[18]。未能及时得到识别和治疗的妊娠结核病可导致婴儿的先天性感染,部分母亲甚至是在其婴儿诊断后才被诊断为结核病。
在妊娠结核病患者中,体重不增是一个需要重点考虑的症状。肺结核是妊娠结核病最常见的类型。播散性结核病占妊娠结核病的5%~10%,是新生儿先天性结核病的特殊危险因素[19]。HIV感染可进一步加剧结核病的严重程度。因此,应对结核病和HIV流行地区的所有孕妇进行结核病相关筛查,同样,对疑似结核病的孕妇也要进行HIV检测[20]
患有活动性肺结核的孕妇应在确诊后立即开始治疗,因为结核病传播给婴儿带来的风险超过了药物不良反应给母亲带来的风险。妊娠结核病的治疗方案与非妊娠期妇女相同,首选治疗方案是联合使用异烟肼、利福平和乙胺丁醇,其中利福平和异烟肼可自由通过胎盘;如加用吡嗪酰胺,建议治疗6个月,如不使用吡嗪酰胺,则建议治疗9个月。链霉素存在导致婴儿神经性听力丧失的风险,因此不建议使用[21]。所有采用一线抗结核药物治疗的产妇均可进行母乳喂养。
如孕妇对一线抗结核药物耐药,则应权衡二线药物的风险与收益后再考虑使用。大多数二线药物均可能对胎儿产生不良影响。在动物实验中,乙硫异烟胺和环丝氨酸具有致畸作用[22]。氨基糖苷类药物(包括卡那霉素、卷曲霉素和阿米卡星)可能与链霉素同样具有耳毒性[22]。氟喹诺酮类药物已被证实会损害生长中的软骨,因此在怀孕期间应尽可能避免使用[21]。目前在妊娠期使用德拉马尼和贝达喹啉治疗耐药结核病的安全性数据有限[23-24]。耐药结核病的治疗时间一般应延长至18~24个月。
先天性结核病是由母亲的结核病垂直传播而来的,指母亲在妊娠期间患结核病时,胎儿在子宫内通过脐带血源性传播或在分娩时通过吸入或摄入被结核分枝杆菌感染的羊水或阴道分泌物而获得的结核病。先天性结核病通常在患儿出生后3周内发病,最常受累部位为肝脏和肺,病死率很高[25-26]。新生儿结核病是指在出生后通过接触传染性结核病患者(通常是母亲,也可以是其他密切接触者)而获得的结核病。先天性结核病与新生儿结核病的区分标准是由Cantwell等[27]于1994年修订的,其中先天性结核病需至少满足以下标准之一:(1)病变发生在出生后第1周;(2)存在肝脏原发性复合体或干酪样肝肉芽肿;(3)胎盘或产妇生殖道存在结核感染;(4)对患儿接触者(包括医院工作人员)进行仔细和全面评估后,排除产后传播的可能性。临床上,虽然先天性结核病与新生儿结核病难以区分,但二者的治疗和管理是相同的[1]
新生儿期结核病的症状通常是非特异性的,包括嗜睡、发热、喂养困难、低出生体重和体重不增;其体征也是非特异性的,包括呼吸窘迫、反复肺炎、肝脾肿大、淋巴结炎、腹胀伴腹水,以及播散性结核病时出现的“新生儿败血症”样临床表现[12628]。对常规抗菌药物治疗反应差的慢性新生儿感染需考虑结核病。新生儿结核病诊断最重要的指标是母亲有结核病病史或HIV感染史。孕产妇病史的关键点为反复肺炎、既往抗结核治疗史、传染性结核病例暴露史,以及正在进行抗结核治疗[20]
有研究系统分析了国内外92例先天性结核病患儿的临床资料发现,大多数患儿发病时年龄<3周;肺结核89例,肝结核20例;71例患儿母亲存在活动性肺结核;发热、发绀、黄疸、气短、咳嗽、肺湿啰音、肝大、脾大、腹胀是发病时的主要临床症状/体征;胸部、腹部和头部影像学异常率分别为97.5%、75.0%和81.3%;痰涂片抗酸染色阳性率为62.5%(15/24),结核分枝杆菌核酸阳性率为66.7%(12/18);误诊率为59.8%,病死率高达43.5%,接受抗结核治疗的先天性结核病患儿的病死率为15.4%[29]
先天性结核病和新生儿结核病的治疗方案相同。临床医师应对产妇和新生儿进行全面检查以协助确诊,包括结核菌素皮肤试验(tuberculin skin test,TST)、X线胸片、培养及分子生物学检测(如Xpert MTB/RIF或Ultra)。新生儿期结核病进展迅速,在细菌学确认前如高度怀疑结核病,应立即开始抗结核治疗。3个月以下或体重<3 kg(包括37周前早产)的婴儿,若怀疑或确诊患有肺结核或淋巴结结核,应立即采用6个月方案[2HRZ(E)/4HR]进行治疗。药物剂量应根据新生儿的年龄和可能存在的毒性进行调整。由于新生儿体重增长快,还需及时依据体重进行剂量调整。世界卫生组织关于耐药结核病的治疗建议也适用于新生儿[1]。此外,若新生儿母亲也诊断为结核病,应进行有效的抗结核治疗,以降低其传染性。
患儿对治疗的反应良好时,临床可表现为食欲增加、体重增加及影像学表现改善。无论母亲是否患有结核病,均建议进行母乳喂养。结核病通过母乳传播的风险极低,尽管常用的抗结核药物会少量通过母乳排出,但目前尚无证据表明会导致耐药。此外,不建议新生儿与母亲分离,尤其是在资源有限的环境中,母乳喂养可能对患儿的生存至关重要。如患有急性感染性疾病的新生儿母亲疑似或确诊为结核病,应立即将新生儿与其母亲转移至隔离病房,以防止出现病房内交叉感染[20]
疑似或确诊为结核病孕妇的新生儿应进行结核病排查,需确定母亲的传染性和药物的敏感性。新生儿无须与母亲隔离,应继续母乳喂养,建议母亲在接近新生儿时佩戴外科口罩[12]。有结核病接触史的新生儿若正在进行结核病或结核潜伏感染的筛查,应暂缓接种卡介苗,因接种卡介苗会影响TST的结果,降低诊断的有效性。
经病原学确诊肺结核的产妇所生的新生儿,在排除结核病后,应接受结核预防性治疗(tuberculosis preventive treatment,TPT),并暂缓接种卡介苗[30-31]。对于无HIV暴露的新生儿,其TPT方案可以采用3HR;若新生儿有HIV暴露(如母亲感染HIV)并正在接受奈韦拉平治疗,应进行异烟肼预防治疗(因利福霉素会降低奈韦拉平的血药浓度,故奈韦拉平不宜与利福霉素合用)。接受TPT的婴儿应同时补充维生素B6 5~10 mg/d,并定期进行监测和随访,以确定是否出现结核病相关的症状和体征。如婴儿在完成TPT后仍无结核病相关症状,在条件允许的情况下,可进行结核感染检测(TST或γ干扰素释放试验)。若检测结果为阴性或无法获得,且婴儿无HIV感染,则应在TPT结束2周后接种卡介苗[32-33];若检测结果为阳性,则无须接种卡介苗。
如母亲的结核病不具有传染性,当新生儿结核病筛查后无结核病证据时,应定期对婴儿进行随访,以确保不会进展为结核病,并可考虑进行TPT。若母亲正在进行抗结核治疗或TPT,则母乳喂养的新生儿应在母亲治疗期间补充维生素B6。耐多药结核病产妇的新生儿应转诊至对儿童耐多药结核病治疗管理有丰富经验的医疗卫生机构,同时母亲应采取佩戴口罩等感染防控措施,以降低传染给新生儿的风险[20]
结核病仍然是严重危害公众健康的传染性疾病,虽然新生儿期结核病罕见,但因其进展快,病死率高,临床医师仍需考虑到该疾病的可能性。早期发现、合理治疗妊娠结核病是获得良好妊娠结局以及有效避免新生儿期结核病的关键。母亲存在结核病高危因素的重症婴儿应接受全面评估。如高度怀疑新生儿期结核病,应及时给予抗结核治疗。尽管感染的婴儿传染性很低,但仍需做好相应的隔离措施,以避免不必要的传播。未出现结核病症状但其母亲病原学已确诊的婴儿应给予TPT。大多数先天性结核病发生在母亲不知道感染的情况下,若母亲存在结核病相关危险因素,临床医师须考虑到先天性结核病的可能性。
  • 北京市卫生健康委员会高层次公共卫生技术人才培养计划(2022-3-041)
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doi: 10.11855/j.issn.0577-7402.2023.06.0648
  • 接收时间:2022-10-08
  • 首发时间:2025-12-03
  • 出版时间:2023-06-28
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  • 收稿日期:2022-10-08
  • 录用日期:2022-11-27
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Training Plan for High-Level Public Health Technical Talents of Beijing Municipal Health Commission(2022-3-041)
北京市卫生健康委员会高层次公共卫生技术人才培养计划(2022-3-041)
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    1国家儿童医学中心/首都医科大学附属北京儿童医院/北京市儿科研究所/儿科学国家重点学科/儿科重大疾病研究教育部重点实验室/国家呼吸系统疾病临床医学研究中心/儿童呼吸道感染性疾病研究北京市重点实验室,北京 100045
    2首都医科大学附属北京儿童医院保定医院/保定市儿童感染性疾病精准诊治重点实验室,河北保定 071000

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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