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妊娠期潜伏性结核:一项系统评价

Latent Tuberculosis in Pregnancy: A Systematic Review.

作者信息

Malhamé Isabelle, Cormier Maxime, Sugarman Jordan, Schwartzman Kevin

机构信息

Department of Medicine, McGill University, Montreal, Quebec, Canada.

Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, Montreal, Quebec, Canada.

出版信息

PLoS One. 2016 May 5;11(5):e0154825. doi: 10.1371/journal.pone.0154825. eCollection 2016.

Abstract

BACKGROUND

In countries with low tuberculosis (TB) incidence, immigrants from higher incidence countries represent the major pool of individuals with latent TB infection (LTBI). The antenatal period represents an opportunity for immigrant women to access the medical system, and hence for potential screening and treatment of LTBI. However, such screening and treatment during pregnancy remains controversial.

OBJECTIVES

In order to further understand the prevalence, natural history, screening and management of LTBI in pregnancy, we conducted a systematic literature review addressing the screening and treatment of LTBI, in pregnant women without known HIV infection.

METHODS

A systematic review of 4 databases (Embase, Embase Classic, Medline, Cochrane Library) covering articles published from January 1st 1980 to April 30th 2014. Articles in English, French or Spanish with relevant information on prevalence, natural history, screening tools, screening strategies and treatment of LTBI during pregnancy were eligible for inclusion. Articles were excluded if (1) Full text was not available (2) they were case series or case studies (3) they focused exclusively on prevalence, diagnosis and treatment of active TB (4) the study population was exclusively HIV-infected.

RESULTS

Of 4,193 titles initially identified, 208 abstracts were eligible for review. Of these, 30 articles qualified for full text review and 22 were retained: 3 cohort studies, 2 case-control studies, and 17 cross-sectional studies. In the USA, the estimated prevalence of LTBI ranged from 14 to 48% in women tested, and tuberculin skin test (TST) positivity was associated with ethnicity. One study suggested that incidence of active TB was significantly increased during the 180 days postpartum (Incidence rate ratio, 1.95 (95% CI 1.24-3.07). There was a high level of adherence with both skin testing (between 90-100%) and chest radiography (93-100%.). In three studies from low incidence settings, concordance between TST and an interferon-gamma release assay was 77, 88 and 91% with kappa values ranging from 0.26 to 0.45. In low incidence settings, an IGRA may be more specific and less sensitive than TST, and results do not appear to be altered by pregnancy. The proportion of women who attended follow-up visits after positive tuberculin tests varied from 14 to 69%, while 5 to 42% of those who attended follow-up visits completed a minimum of 6 months of isoniazid treatment. One study raised the possibility of an association of pregnancy/post-partum state with INH hepatitis (risk ratio 2,5, 95% CI 0.8-8.2) and fatal hepatotoxicity (rate ratio 4.0, 95% CI 0.2-258). One study deemed INH safe during breastfeeding based on peak concentrations in plasma and breast milk after INH administration.

CONCLUSION

Pregnancy is an opportunity to screen for LTBI. Interferon-gamma release assays are likely comparable to tuberculin skin tests and may be used during pregnancy. Efforts should be made to improve adherence with follow-up and treatment post-partum. Further data are needed with respect to safety and feasibility of antepartum INH therapy, and with respect to alternative treatment regimens.

摘要

背景

在结核病(TB)发病率较低的国家,来自高发病率国家的移民是潜伏性结核感染(LTBI)个体的主要群体。孕期为移民妇女提供了接触医疗系统的机会,从而有可能对LTBI进行筛查和治疗。然而,孕期进行此类筛查和治疗仍存在争议。

目的

为了进一步了解孕期LTBI的患病率、自然史、筛查和管理情况,我们针对未感染已知HIV的孕妇中LTBI的筛查和治疗进行了一项系统文献综述。

方法

对4个数据库(Embase、Embase Classic、Medline、Cochrane图书馆)进行系统检索,涵盖1980年1月1日至2014年4月30日发表的文章。纳入英文、法文或西班牙文撰写的、包含孕期LTBI患病率、自然史、筛查工具、筛查策略及治疗相关信息的文章。若文章存在以下情况则排除:(1)无全文;(2)为病例系列或病例研究;(3)仅关注活动性结核的患病率、诊断和治疗;(4)研究人群仅为HIV感染者。

结果

最初检索到4193篇文献标题,其中208篇摘要符合综述要求。其中,30篇文章符合全文审查标准,最终保留22篇:3项队列研究、2项病例对照研究和17项横断面研究。在美国,接受检测的女性中LTBI估计患病率为14%至48%,结核菌素皮肤试验(TST)阳性与种族有关。一项研究表明,产后180天内活动性结核发病率显著增加(发病率比值比,1.95(95%CI 1.24 - 3.07))。皮肤试验(90 - 100%)和胸部X线检查(93 - 100%)的依从性都很高。在三项来自低发病率地区的研究中,TST与干扰素 - γ释放试验的一致性分别为77%、88%和91%,kappa值范围为0.26至0.45。在低发病率地区,干扰素 - γ释放试验可能比TST更具特异性但敏感性较低,且结果似乎不受妊娠影响。结核菌素试验阳性后接受随访的女性比例为14%至69%,而接受随访的女性中5%至42%至少完成了6个月的异烟肼治疗。一项研究提出妊娠/产后状态与异烟肼肝炎(风险比2.5,95%CI 0.8 - 8.2)和致命肝毒性(发病率比值比4.0,95%CI 0.2 - 258)之间可能存在关联。一项研究基于异烟肼给药后血浆和母乳中的峰值浓度,认为母乳喂养期间异烟肼是安全的。

结论

孕期是筛查LTBI的时机。干扰素 - γ释放试验可能与结核菌素皮肤试验相当,可在孕期使用。应努力提高产后随访和治疗的依从性。关于产前异烟肼治疗的安全性和可行性以及替代治疗方案还需要更多数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2928/4858222/56b6e9c51085/pone.0154825.g001.jpg

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