Preventing Childhood Tuberculosis in Lesotho (PREVENT Study)

描述（由申请人提供）：在提交这个NIH指导研究科学家发展奖，我的首要目标是成为一个独立的研究者，专注于开发和测试可行的，有效的干预措施，以预防儿童结核病（TB）在资源有限的环境。鉴于艾滋病毒高流行率国家的儿童结核病发病率空前之高，以及减少儿童结核病负担的干预措施有限，这一调查领域至关重要。虽然结核病是可以治愈和预防的，但研究表明，幼儿，特别是感染艾滋病毒的儿童的死亡率和发病率较高，这突出表明了在这一人群中预防结核病的重要性。迫切需要采取有效的干预措施，为政策和方案设计提供信息，以便在艾滋病毒/结核病高负担、资源有限的环境中预防这一人群的结核病。我的长期职业目标是将从儿科结核病研究中获得的知识和经验应用于其他传染病，并最终应用于影响儿童并威胁其健康的其他疾病。此K 01应用程序的目的是提出一个研究和培训计划，这将有助于实现这些目标。我的近期目标是开发和测试一种干预措施 莱索托是南部非洲的一个小国，结核病/艾滋病负担很重。与许多资源有限的国家一样，特别是在撒哈拉以南非洲，莱索托对成人结核病儿童接触者实施的经证实的追踪、筛查和治疗战略有限。拟议的研究将位于ICAP已建立的莱索托计划内，该计划旨在加强国家、地区、设施和社区层面的结核病/艾滋病毒整合，并由共同导师Andrea霍华德博士领导。利用ICAP在莱索托广泛的基础设施，将使我能够以及时、具有成本效益的方式，最重要的是，与国内的结核病控制实体合作，领导和开展这项重要的研究。本研究将采用两组分组随机试验设计，在卫生机构水平进行随机化，以评价基于社区的干预（CBI）与标准治疗（SOC）的有效性和可接受性，以确定莱索托马费滕成人结核病病例的儿童接触者，并根据指示为他们提供异烟肼预防性治疗（IPT）。10个健康中心将被纳入研究，并随机分配以提供CBI或SOC，并按机构规模分层（即，登记的结核病患者人数）。CBI包括结构，临床和心理社会组成部分，以解决卫生保健工作者（HCW），儿童和监护人在为儿童接触者提供IPT时面临的挑战。在CBI研究中心，HCW和村卫生工作者（VHW）将接受培训，向成人结核病例及其儿童接触者提供研究内容。SOC研究中心将遵循国家指南进行接触者追踪、筛查和IPT提供。社区倡议包括三个组成部分，以最大限度地发挥作用：1）提供关于积极追踪社区接触者、评估儿童接触者是否符合IPT资格和提供IPT的培训; 2）对儿童和监护人进行具体干预，使其了解儿童筛查、启动和完成IPT、艾滋病毒检测以及与护理艾滋病毒感染儿童的联系的重要性;及3）VHW的社区外展团队与设施团队合作。这项研究将有一个强有力的定性研究组成部分，其中包括干预前后的焦点小组讨论和干预后监护人的主要知情人访谈。使用顺序的解释阶段，定量数据收集和分析，然后收集和分析定性数据，可能有助于解释前一阶段的结果，将允许评估供应商和监护人的可接受性和利用的干预组件。我的研究和补充培训计划将使我获得技能和知识，成为一名富有成效的独立调查员，能够设计和评估干预措施，以预防结核病/艾滋病毒高负担，资源有限的环境中的儿童结核病。迫切需要有效的循证干预措施来预防此类环境中的儿童结核病。在拟议的研究中，创新的方法将评估CBI的有效性和可接受性，全面解决复杂的提供者，患者和儿童结核病预防相关的障碍。预计采用可行的社区护理模式将改善对年幼、脆弱儿童的结核病预防。该研究将为在儿童中实施和扩大IPT提供的可行性提供证据，同时将急需的结核病和艾滋病毒服务纳入儿童。

DESCRIPTION (provided by applicant): In submitting this NIH Mentored Research Scientist Development Award, my overarching goal is to become an independent investigator focused on developing and testing feasible, effective interventions to prevent tuberculosis (TB) in children i resource-limited settings. This field of inquiry is critically important given the unprecedented hih pediatric TB rates in countries with high HIV prevalence and the limited availability of interventions to reduce the TB burden among children. Although TB is curable and preventable, studies have demonstrated higher mortality and morbidity in young children, particularly in HIV-infected children, highlighting the importance of preventing TB in this population. Effective interventions to inform policy and program design are urgently needed so that TB can be prevented in this population in high HIV/TB-burden, resource-limited settings. My long-term career goal is to apply acquired knowledge and experience from pediatric TB research to other infectious diseases and ultimately other conditions that affect children and threaten their well-being. The purpose of this K01 application is to propose a research and training program that will facilitate attainment of these goals. My immediate goal is to develop and test an intervention to reduce childhood TB in Lesotho, a small country in southern Africa with a substantial TB/HIV disease burden. As with many resource-limited countries, particularly in sub-Saharan Africa, there is limited implementation of proven tracing, screening, and treatment strategies for child contacts of adult TB in Lesotho. The proposed study will be situated within ICAP's established Lesotho programs, which aim to strengthen TB/HIV integration at national, district, facility, and community levels and which are led by co-mentor Dr. Andrea Howard. Using ICAP's extensive Lesotho infrastructure will enable me to lead and conduct this vital study in a timely, cost-effective manner and, most importantly, in partnership with TB control entities in-country. The study will utilize a two-arm cluster randomized trial design, randomized at health facility level, o evaluate the effectiveness and acceptability of a community-based intervention (CBI) versus standard of care (SOC) to identify child contacts of adult TB cases in Mafeteng, Lesotho, and provide them with isoniazid preventive therapy (IPT), as indicated. Ten health centers will be included in the study and randomized to deliver the CBI or SOC, with stratification by facility siz (i.e., number of registered TB patients). CBI includes structural, clinical, and psychosocial components to address the challenges faced by healthcare workers (HCW), children, and guardians in provision of IPT for child contacts. At CBI sites, HCW and village health workers (VHW) will be trained to deliver study components to adult TB cases and their child contacts. SOC sites will follow country guidelines for contact tracing, screening, and IPT provision. CBI includes 3 components to maximize effect: 1) provider training on active community contact tracing, evaluating child contacts for IPT eligibility, and IPT provision; 2) specific intervention for children and guardians on the importance of child screening, initiating and completing IPT, and HIV testing and linkage to care for HIV-infected children; and 3) community outreach teams of VHW working in concert with facility-based teams. The study will have a strong qualitative research component, which includes pre- and post-intervention focus group discussions and post-intervention guardian key informant interviews. Using a sequential explanatory phase, where quantitative data collection and analysis is followed by collection and analysis of qualitative data that may help explain previous-phase results, will permit evaluation of provider and guardian acceptability and utilization of intervention components. My research and complementary training plan will allow me to acquire the skills and knowledge to become a productive, independent investigator able to design and evaluate interventions to prevent TB in children in high TB/HIV-burden, resource-limited settings. Effective, evidence-based interventions to prevent childhood TB in such settings are urgently needed. In the proposed study, innovative methodology will assess effectiveness and acceptability of a CBI that holistically addresses the complex provider-, patient-, and guardian-related barriers to prevention of childhood TB. It is anticipated that using a feasible community-based model of care will improve TB prevention in young, vulnerable children. The study will provide evidence for the feasible implementation and scale-up of IPT provision in children while integrating much-needed TB and HIV services in children.