Evaluating novel diagnostics and enabling preventive measures for childhood tuberculosis between the UK and partners in Sub-Saharan Africa

该项目旨在为儿童结核病患者开发和验证更好的诊断工具（发现和治疗），以及为那些已经感染但尚未患病，但如果不接受建议的干预措施（筛查和预防）可能会发展为疾病的人实施预防性治疗。结核病在LMIC的重要性：每年约有100万儿童因结核病患病，14万人死亡。许多国家努力向世卫组织提供儿童结核病的年龄分层通知，并且在许多情况下不愿意参与儿童结核病的诊断和治疗，因为工作人员感到没有能力根据微生物学证据确认“金标准”诊断。这种情况与非洲有关，并继续导致不必要的发病率和死亡率，并为今后积累病例。消除结核病的路线图为实现全球结核病控制设定了优先事项，在这一努力中，儿童结核病已被确定为一个被忽视的问题，但对总体结核病控制非常重要（世卫组织全球结核病计划）。适当地诊断病例并进行治疗-发现和治疗-以及2.预防结核病暴露儿童的继发性病例，这可以通过提供预防性药物--筛查和预防--成功地做到。为什么儿童结核病的诊断更困难？由于分枝杆菌中所含的分枝杆菌数量有限，传统的微生物诊断在儿童中表现不佳。除非能够开发出更敏感的少杆菌病诊断方法，否则目前三分之二的儿童在未经确诊的情况下接受结核病治疗的状况不太可能改变。因此，血液或尿液中宿主衍生的生物特征有望发展为儿童结核病的即时检测。我们想做什么？我们在英国和冈比亚的儿童结核病管理方面拥有丰富的经验，该项目旨在让非洲的新合作伙伴参与进来，使用现有和新的诊断方法发现和治疗结核病儿童。我们已经开发了这种新的检测方法，但还需要在感染艾滋病毒或营养不良的儿童中进一步验证。因此，我们将招募一大批可能患有结核病的儿童，以验证新的诊断方法。此外，我们希望与伙伴国家的国家结核病规划（NTP）合作，实施一项预防战略，该战略得到世卫组织的支持，但尚未在实地实施。我们希望了解护理路径中的瓶颈，并培训NTP成员识别儿童结核病，并采取必要的预防措施，以避免家庭中的继发病例。根据英国的模式，我们已经在冈比亚建立了一个筛查和预防方案，对家庭中接触结核病的儿童进行接触筛查，该方案得到了国家结核控制规划的支持。我们的发现和治疗以及筛查和预防活动在过去3年中使病例通知增加了50%。这种方法现在需要完全纳入其他国家的国家结核控制规划，并进行系统的评估，以确定其对我们伙伴国家的国家结核病数字的长期影响。它可以作为世卫组织改善全球结核病预防战略的一个重要模式，但每个国家可能有具体的要求，我们的项目将提供来自4个不同非洲环境的数据，为建议提供信息。我们希望我们的工作可以改善结核病控制，我们可以在非洲建立一个拥有儿童结核病专业知识的卓越网络，就像我们在欧洲所做的那样。

This project aims to develop and validate better diagnostic tools for children with TB (Find and Treat), as well as looking at implementation of preventive therapy for those already infected but not yet ill, but who might progress to disease if not receiving the recommended intervention- (Screen and Prevent).Importance of TB in LMIC:Around 1 million children fall ill from TB each year and 140 000 die. Many countries struggle to deliver the age-stratified notifications for TB in children to the WHO, and there is reluctance to engage in diagnosing and treating TB in children in many settings, as staff feel ill equipped to confirm a "gold standard" diagnosis, based on microbiological evidence. This situation is pertinent in Africa and continues to lead to unnecessary morbidity and mortality and a reservoir of cases for the future. The roadmap for the elimination of TB sets priorities for achieving global TB control and within this effort, childhood TB has been identified as a neglected problem, but of great importance for overall TB control (WHO Global Plan for TB).This requires two interventions: 1. to appropriately diagnose the cases and place on treatment -find and treat- and 2. to prevent secondary cases in TB-exposed children, which can be done successfully by delivering preventive medication- screen and prevent.Why is it more difficult to diagnose TB in children?Due to the limited number of mycobacteria contained in their sputa, conventional microbiological diagnostics perform poorly in children. Unless more sensitive diagnostics for paucibacillary disease can be developed, it is unlikely that the current situation of two thirds of children receiving treatment for TB without a confirmed diagnosis will change. Host-derived biosignatures in blood or urine therefore hold promise for development into point-of care tests for childhood TB.What do we want to do?We have considerable experience in the management of childhood TB in both the UK and The Gambia, and this project aims to involve new partners in Africa to find and treat children with TB using existing and new diagnostics. We have already developed such new tests but they need to be further validate also in children who have HIV or malnutrition. We will therefor recruit a large prospective court of children likely o have TB to validate the new diagnostics.In addition, we want to work the National TB programs (NTP) in the partner countries to implement a preventive strategy, as supported by the WHO but not implemented on the ground. We want to understand the bottlenecks within the care path and train members of the NTP to recognise TB in children and take the necessary preventive steps to avoid secondary cases in families. Based on the UK model, we have already established a screen-and-prevent- program of contact screening for children exposed to TB in their households in The Gambia, which has the support of the NTP. Our find and treat and screen and prevent activities have increased the case notifications by 50% over the last 3 years. This approach now requires full integration into the NTP programs in other countries and systematic evaluation to determine its long term impact on national TB figures also in our partner countries. It could serve as an important model for the WHO strategy o improve prevention of TB worldwide but each country might have specific requirements and our project will deliver data from 4 different African settings to inform the recommendations.We expect that our work can improve TB control and that we can create a network of excellence with specialist knowledge for childhood TB in Africa, as we have already done in Europe.