Impact of Pregnancy on Tuberculosis

怀孕对结核病的影响

• 批准号: 9007530
• 负责人: Jerrold J. Ellner
• 金额: $ 64.22万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-25 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9007530
• 关键词: Accounting; Address; Adverse effects; Antitubercular Agents; Attention; Biological Markers; Birth; Boston; Cause of Death; Cohort Studies; Comorbidity; Data; Detection; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Dose; Drug Kinetics; Enrollment; Epidemiologic Studies; Fetus; Foundations; Funding; Guidelines; HIV Infections; Household; Immunologics; Immunosuppression; India; Infection; Institutes; Low Birth Weight Infant; Medical Education; Medical Research; Mothers; Nature; Observational Study; Outcome; Perinatal; Pharmaceutical Preparations; Populations at Risk; Predisposition; Pregnancy; Pregnancy Outcome; Pregnant Women; Prospective Studies; Recommendation; Research; Research Design; Research Personnel; Retrospective Studies; Rifamycins; Risk; Severities; Severity of illness; Treatment Failure; Tuberculosis; Universities; Vaccines; Woman; base; cohort; disorder risk; evidence base; evidence based guidelines; follow-up; improved; medical schools; neglect; neonate; pregnant; premature; prospective; public health relevance; reproductive; response; stillbirth; tuberculosis drugs; tuberculosis treatment

 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.

 描述（由申请人提供）：印度结核病 (TB) 负担占全球的四分之一，其中估计有 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，可能是由于检出率增加。尚未进行明确的前瞻性研究来解决这一问题，结核病是育龄期妇女死亡的主要原因，并将新生儿置于危险之中。然而，这些关于妊娠期结核病的陈述是基于小型回顾性研究，因此，目前有关妊娠期结核病诊断和治疗的建议并没有以证据为基础，这进一步推动了指南和证据的质量。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学院的美国和印度研究人员将在现有的基础上更好地描述妊娠期结核病的特征，因为更多的孕妇将接受治疗，更多的新生儿将接触到抗结核药物。队列研究资助通过印度-美国疫苗行动计划（结核病区域前瞻性观察研究，RePORT India），重点关注妊娠期结核病。通过RePORT India，我们预计将在 5 年内招募 2500 名结核病病例和 3300 名暴露的家庭接触者。足够数量的孕妇结核病病例、在随访期间将怀孕的潜伏性结核感染 (LTBI) 家庭接触者，以及适当的控制措施来解决以下假设： i) 妊娠的免疫抑制会调节 LTBI 的诊断生物标志物，从而混淆其诊断，并与疾病风险的宿主生物标志物指标相关；ii) 妊娠会增加结核病的风险和严重程度；iii) 孕妇的不良出生结果更为常见。结核病，以及 iv) 对抗结核药物的反应不是最佳的 该提案的具体目标是： 1. 确定怀孕对 LTBI 和 LTBI 诊断生物标志物的影响。 2. 确定妊娠期结核病风险并描述疾病的严重程度、治疗反应和妊娠结局 3. 评估妊娠期和妊娠期结核病药物的药代动力学。评估胎儿接触这些物质的情况，这项研究将为长期被忽视的高危人群孕妇结核病提供重要数据，并为基于证据的建议奠定基础，以改善 LTBI 的诊断和重视结核病的治疗。到可能最大限度地减少对胎儿的有害影响。