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困疾病，撒哈拉以南非洲地区损失惨重。2015年，全球估计有超过3300万临床病例和30万人死于风湿性心脏病。风湿性心脏病是由A组链球菌(GAS)对喉咙或皮肤感染的过度免疫反应(风湿热(ARF))引起的，这会进一步损害心脏瓣膜。并发症包括导致过早死亡的心力衰竭和中风，通常在25岁之前，患有风湿性心脏病的妇女在分娩期间发生并发症的风险更高。有早期症状的风湿性心脏病患者可以每月注射青霉素G来治疗，这种药物可以阻止心脏病变的演变。然而，在包括冈比亚在内的许多国家，风湿性心脏病通常在到卫生机构就诊的晚期患者中被诊断出患有心力衰竭或其他并发症，此时青霉素治疗预防风湿性心脏病不良后果的效果有限。理想情况下，青霉素治疗应该尽早开始，尽管它对潜伏性风湿性心脏病患者的益处尚不清楚，即超声心动图诊断为心脏损害，但没有症状。潜伏性风湿性心脏病是早期使用青霉素治疗以防止其发展为临床显性疾病的潜在机会之窗。这一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在的风湿性心脏病患者。因此，考虑到潜伏性风湿性心脏病在儿童中的患病率可能为0.5%-1%(在年轻人中高达3%)，研究小组将需要快速筛查数千人，以在合理的时间段内达到所需的样本量。由非专家用户使用的手持式超声心动图(HHEC)已被证明是检测风湿性心脏病的可靠工具，被认为是大规模筛查的最佳选择。这项试验发展赠款(TDG)将决定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风湿性心脏病(潜伏期和症状性)的患病率；ii)三个研究地点的非专家用户是否能够接受使用HHEC进行风湿性心脏病筛查的充分培训；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)后，将对每个国家的3,000名儿童和3,000名成年人进行筛查，所有疑似风湿性心脏病病例将由标准EC确认，然后转介到最近的教学医院进行适当处理。HHEC筛查的可行性和可接受性将作为一个持续的过程进行评估，方法是及早和定期与参与者和所有相关利益攸关方接触。因此，这项TGD将提供关于风湿性心脏病患病率(不同年龄组中的潜伏性和症状性)以及使用HHEC进行大规模筛查的可行性和可接受性的有用信息，从而使其能够相应地调整三个西非国家的未来试验设计。迫切需要这种试验的结果，以发布关于管理潜伏性风湿性心脏病的新的共识指南，并进一步改善风湿性心脏病的控制。

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.