Impact of Pregnancy on Tuberculosis

 描述(由申请人提供)：印度占全球结核病负担的四分之一，其中估计有20,000-40,000例孕妇。流行病学研究表明，产后结核病风险增加，这可能是由于怀孕期间疾病的检测增加所致。还没有进行明确的前瞻性研究来解决这个问题。结核病是妇女在生育期死亡的主要原因，并将新生儿置于危险之中。然而，这些关于怀孕期间结核病的声明是基于小规模的回顾研究。因此，目前关于妊娠期结核病诊断和管理的建议没有证据。艾滋病毒感染提供了进一步的动力，以加强作为指南依据的证据的质量，并更好地描述怀孕期间的结核病，因为将有更多的孕妇得到治疗，更多的新生儿接触到抗结核病药物。波士顿大学医学院、罗格斯大学和贾瓦哈拉尔研究生医学教育与研究所的美国和印度研究人员建议在现有的由印美疫苗行动计划(区域前瞻性结核病观察研究，报告印度)资助的队列研究的基础上，重点关注怀孕期间的结核病。通过《印度报告》，我们预计在5年内登记2500例结核病病例和3300名暴露的家庭接触者。这些队列将提供足够数量的孕妇结核病病例、将在随访期内怀孕的潜在结核病感染(LTBI)的家庭接触者和适当的对照，以解决下列假设：i)怀孕的免疫抑制调节LTBI的诊断生物标记物，混淆其诊断，并与指示疾病风险的宿主生物标记物相关；ii)怀孕增加结核病的风险和严重程度；iii)在患有结核病的孕妇中更常见的是不良的出生结局，以及iv)抗结核药物的反应不佳。这项建议的具体目的是：1.确定怀孕对LTBI的诊断生物标记物和可能预测进展为结核病风险的宿主生物标记物的影响。2.确定怀孕期间患结核病的风险，描述疾病的严重程度、对治疗的反应和妊娠结局。3.评估结核病药物在孕期的药代动力学，并评估胎儿对其的暴露。这项研究将提供孕妇结核病的关键数据，孕妇是长期被忽视的高危人群，并为循证建议提供基础，以改善LTBI的诊断和结核病的治疗，并注意将对胎儿的潜在有害影响降至最低。

 DESCRIPTION (provided by applicant): India accounts for one fourth of the global burden of tuberculosis (TB) including an estimated 20,000-40,000 cases in pregnant women. Epidemiologic studies have shown that TB risk is increased post-partum, probably due to increased detection of disease that developed during pregnancy. Definitive prospective studies have not been done to address this issue. TB is a leading cause of death in women during their reproductive years and places the neonate at risk. Yet, these statements about TB in pregnancy are based on small retrospective studies. As a result, current recommendations concerning diagnosis and management of TB in pregnancy are not evidence-based. HIV infection provides further impetus to strengthen the quality of evidence underlying the guidelines and better characterize TB in pregnancy because more pregnant women will be treated and more neonates exposed to anti-TB drugs. US and Indian investigators at Boston University School of Medicine, Rutgers University, and Jawaharlal Institute of Postgraduate Medical Education & Research propose to build on an existing cohort study funded through the Indo-US Vaccine Action Plan (Regional Prospective Observational Research on TB, RePORT India) to focus on TB in pregnancy. Through RePORT India we project enrollment of 2500 TB cases and 3300 exposed household contacts over 5 years. The cohorts will provide access to sufficient numbers of TB cases in pregnant women, household contacts with latent TB infection (LTBI) that will become pregnant during the follow-up period, and appropriate controls to address the following hypotheses: i) the immunosuppression of pregnancy modulates the diagnostic biomarkers of LTBI, confounding its diagnosis and is associated with host biomarkers indicative of risk of disease; ii) pregnancy increases the risk and severity of TB; iii) poor birth outcomes are more common in pregnant women with TB, and iv) The response to anti-tuberculous drugs is sub-optimal. Specific Aims of this proposal are: 1. To determine the impact of becoming pregnant on diagnostic biomarkers of LTBI and on host biomarkers that may predict risk of progression to TB. 2. To determine the risk of TB in pregnancy and describe the severity of disease, the response to treatment, and pregnancy outcomes. 3.To evaluate the pharmacokinetics of TB drugs during pregnancy and assess exposure of the fetus to them. This research will provide critical data on TB in pregnant women, a long-neglected at-risk population, and provide the foundation for evidence-based recommendations to improve diagnosis of LTBI and treatment of TB disease with attention to minimizing potentially deleterious effects on the fetus.