Impact of Pregnancy on Tuberculosis

 描述（由申请人提供）：印度占全球结核病（TB）负担的四分之一，包括估计20，000 - 40，000例孕妇病例。流行病学研究表明，产后结核病风险增加，可能是由于怀孕期间发现的疾病增加。尚未进行连续的前瞻性研究来解决这个问题。结核病是育龄妇女死亡的主要原因，并使新生儿处于危险之中。然而，这些关于妊娠期结核病的声明是基于小型回顾性研究。因此，目前关于妊娠期结核病的诊断和管理的建议不是以证据为基础的。艾滋病毒感染进一步推动了加强指南所依据证据的质量，并更好地描述妊娠期结核病，因为更多的孕妇将接受治疗，更多的新生儿将接触抗结核药物。波士顿大学医学院、罗格斯大学和Jawaharlal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一项队列研究的基础上，通过印度-美国疫苗行动计划（结核病区域前瞻性观察研究，印度报告）资助，重点关注妊娠期结核病。通过报告印度，我们计划在5年内招募2500例结核病例和3300例暴露的家庭接触者。这些队列将提供足够数量的孕妇、在随访期间将怀孕的具有潜伏性TB感染（LTBI）的家庭接触者中的TB病例，以及适当的对照，以解决以下假设：i）妊娠的免疫抑制调节LTBI的诊断生物标志物，混淆其诊断，并且与指示疾病风险的宿主生物标志物相关; ii）怀孕增加了结核病的风险和严重程度; iii）不良的出生结果在结核病孕妇中更常见，以及iv）对抗结核病药物的反应是次优的。本提案的具体目标是：1.确定怀孕对LTBI诊断生物标志物和可能预测进展为TB风险的宿主生物标志物的影响。2.确定妊娠期结核病的风险，描述疾病的严重程度、治疗反应和妊娠结局。3.评价妊娠期结核药物的药代动力学及胎儿暴露情况。这项研究将提供关于孕妇结核病的关键数据，这是一个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，并注意最大限度地减少对胎儿的潜在有害影响。

 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.