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

风湿性心脏病（RHD）是一种影响世界上最贫穷国家的贫穷疾病，撒哈拉以南非洲地区的死亡率很高。2015年，估计全世界有3300多万临床病例和100多万例死亡是由RHD引起的。RHD是由喉咙或皮肤感染A群链球菌（GAS）引起的过度免疫反应（“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，而患有RHD的女性在分娩时并发症的风险更高。有早期症状的RHD患者可以通过每月注射苄星青霉素G来治疗，这可以阻止心脏病变的发展。然而，在包括冈比亚在内的许多国家，RHD通常是在患有心力衰竭或其他并发症的晚期患者就诊时诊断出来的，这时青霉素治疗对预防RHD不良后果的效果有限。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（即超声心动图诊断出心脏病变但无症状的患者）的益处尚不清楚。潜伏性RHD代表了一个潜在的机会窗口，可以用青霉素进行早期治疗，以防止其发展为明显的临床疾病。这种干预需要通过一项大型随机临床试验来评估，该试验将招募数百名潜伏性RHD患者。因此，考虑到潜伏性RHD在儿童中的患病率可能为0.5-1%（在年轻人中高达3%），研究小组需要在合理的时间内快速筛选数千人以达到所需的样本量。非专业用户的手持式超声心动图（HHEC）已被证明是检测RHD的可靠工具，被认为是大规模筛查的最佳选择。这项试验发展赠款将确定：(1)冈比亚、塞内加尔和尼日利亚城郊地区学龄儿童和青年中RHD（潜伏和症状性）的患病率；ii)三个研究地点的非专家用户是否能够接受充分的培训，以便使用HHEC进行RHD筛查，以及iii) HHEC在三个研究地点进行社区筛查的可行性和可接受性。在HHEC培训（3个月）之后，每个国家将筛查3,000名儿童和3,000名成人，所有疑似RHD病例将通过标准EC确认，然后转诊到最近的教学医院进行适当管理。hec筛查的可行性和可接受性将作为一个持续的过程，通过与参与者和所有相关利益攸关方的早期和定期接触进行评估。因此，该TGD将提供有关RHD患病率（不同年龄组的潜伏性和症状性）以及hec大规模筛查的可行性和可接受性的有用信息，从而允许相应地调整三个西非国家未来的试验设计。这项试验的结果对于发布新的共识性指导方针来管理潜伏性RHD和进一步改善RHD的控制至关重要。

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.