Latent rheumatic heart disease in West Africa: a pilot multi-country study

西非的潜在风湿性心脏病：一项多国试点研究

• 批准号: MR/T003952/1
• 负责人: Annette Erhart
• 金额: $ 19.29万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT003952%2F1
• 关键词: Latent; rheumatic; heart; disease; West

Rheumatic heart disease (RHD) is a disease of poverty affecting the poorest countries in the world, with Sub-Saharan Africa bearing a heavy toll. In 2015, over 33 millions clinical cases and >300,000 deaths worldwide were estimated to be due to RHD. RHD is caused by an excessive immune reaction ("rheumatic fever" (ARF)) to throat or skin infections by Group A Streptococcus (GAS) which further damages the heart valves. Complications include heart failure and stroke that result in premature death, usually before 25 years old, and women with RHD are at higher risk of complication during delivery. RHD patients with early symptoms can be treated with monthly injections of benzathin penicillin G which stops the evolution of the heart lesions. However, in many countries, including The Gambia, RHD is usually diagnosed in patients attending health facilities at a late stage, with heart failure or other complications, when the efficacy of penicilllin treatment to prevent RHD adverse outcomes is limited. Ideally, penicillin treatment should be started as early as possible although its benefits in individuals with latent RHD, i.e. with cardiac lesions diagnosed by echocardiography but without symptoms, is unknown. Latent RHD represents a potential window of opportunity for early treatment with penicillin to prevent its progression towards overt clinical disease. This intervention needs to be evaluated with a large randomized clinical trial that will recruit hundreds of individuals with latent RHD. Therefore, considering the prevalence of latent RHD is probably 0.5-1% in children (up to 3% in young adults), the study team would need to rapidly screen thousands of individuals to attain the required sample size within a reasonable time period. Handheld echocardiography (HHEC) by non expert users has been proved as a reliable tool to detect RHD and is considered the best option for mass screening. This Trial Development Grant (TDG) will determine i) the prevalence of RHD (latent- and symptomatic) among school-aged children and young adults in peri-urban areas of The Gambia, Senegal and Nigeria; ii) whether non-experts users in the three study sites can be adequately trained for RHD screening using HHEC, and iii) the feasibility and acceptability of community-based screening by HHEC in the three study sites. After HHEC training (3 months), 3,000 children and 3,000 adults per country will be screened and all suspected RHD cases will be confirmed by standard EC before referral to the nearest teaching hospital for adequate management. The feasibility and acceptability of HHEC screenings will be evaluated as an ongoing process through early and regular engagement with participants and all stakeholders involved. Therefore, this TGD will provide useful information on RHD prevalence (both latent and symptomaticin different age groups) and the feasibility and acceptability of mass screening with HHEC, allowing to adapt accordingly the future trial design in the three West African countries. Results of such trial are crucially needed to issue new consensus guidelines on the management of latent RHD and further improve the control of RHD.

风湿性心脏病（RHD）是一种影响世界上最贫穷国家的贫困疾病，撒哈拉以南非洲地区的死亡人数很高。2015年，全球估计有超过3300万例临床病例和> 30万例死亡是由于RHD。风湿性心脏病是由A组链球菌（GAS）对咽喉或皮肤感染的过度免疫反应（“风湿热”（ARF））引起的，这进一步损害了心脏瓣膜。并发症包括心力衰竭和中风，导致过早死亡，通常在25岁之前，患有RHD的女性在分娩期间并发症的风险更高。有早期症状的风湿性心脏病患者可以每月注射苄星青霉素G，阻止心脏病变的发展。然而，在许多国家，包括冈比亚，风湿性心脏病通常是在晚期诊断的患者前往卫生设施，心脏衰竭或其他并发症，当青霉素治疗，以防止风湿性心脏病不良后果的疗效是有限的。理想情况下，青霉素治疗应尽早开始，尽管其对潜伏性RHD患者（即超声心动图诊断为心脏病变但无症状的患者）的益处尚不清楚。潜伏性RHD代表了早期青霉素治疗的潜在机会窗口，以防止其向明显的临床疾病进展。这种干预措施需要通过一项大型随机临床试验进行评估，该试验将招募数百名潜伏性RHD患者。因此，考虑到潜伏性RHD的患病率在儿童中可能为0.5-1%（在年轻人中高达3%），研究小组需要快速筛查数千人，以在合理的时间内达到所需的样本量。由非专业用户进行的手持超声心动图（HHEC）已被证明是检测RHD的可靠工具，并被认为是大规模筛查的最佳选择。本试验开发补助金（TDG）将确定i）冈比亚、塞内加尔和尼日利亚城市周边地区学龄儿童和年轻人中RHD（潜伏性和症状性）的患病率; ii）三个研究中心的非专家用户是否可以接受使用HHEC进行RHD筛查的充分培训，以及iii）三个研究中心HHEC进行基于社区的筛查的可行性和可接受性。在HHEC培训（3个月）后，每个国家的3，000名儿童和3，000名成人将接受筛查，所有疑似RHD病例将在转诊到最近的教学医院进行适当管理之前由标准EC确认。HHEC筛查的可行性和可接受性将作为一个持续的过程，通过早期和定期与参与者和所有利益相关者的接触进行评估。因此，本TGD将提供有关RHD患病率（不同年龄组的潜伏性和潜伏性）以及HHEC大规模筛查的可行性和可接受性的有用信息，从而允许在三个西非国家相应调整未来的试验设计。这些试验的结果是至关重要的，以发布新的共识指南的管理潜在的RHD和进一步提高控制RHD。