Pilot study of Newborn screening for hemoglobinopathies in South Gujarat India

说明(申请人提供)：血红蛋白病是世界范围内发病率和过早死亡的主要病例。据估计，每年有1万多名地中海贫血婴儿和5200名镰状细胞病婴儿出生，在印度，血红蛋白疾病已成为一个主要的公共卫生问题。新生儿筛查(NBS)可以通过促进早期青霉素预防和参加综合护理来显著降低镰状细胞病(SCD)的发病率和死亡率。然而，发达国家主要在高度结构化的卫生系统中实施了针对血红蛋白疾病或其他遗传和代谢性疾病的NBS。在印度，SCD在被归类为预定部落的土著人口中最为普遍，这些人社会经济劣势的发生率很高，生活在农村或森林地区。拥有大量预定部落人口的古吉拉特邦是第一个启动全面血红蛋白疾病计划的邦。该项目是匹兹堡儿童医院和奥克兰儿童医院的研究人员与孟买免疫血液学研究所和瓦尔萨德·罗克塔丹·肯德拉和古吉拉特邦镰状细胞疾病治疗和控制计划的研究人员之间的印美合作，瓦尔萨德将在南古吉拉特邦试点新生儿血红蛋白疾病筛查。具体目标是：1.检验在古吉拉特邦南部部落地区建立新生儿镰状细胞病筛查和随访计划的可行性。2.确定将确诊为镰状细胞病的无症状婴儿纳入综合护理的可行性；3.检查新生儿筛查、随访以及对国家统计局发现的血红蛋白疾病进行遗传检测和咨询的可接受性。我们将结合高通量实验室筛查方法、系统随访、标准化临床护理、用于跟踪患者护理的综合实验室和儿童健康信息系统、绕过基础设施空白的电信和社会行为研究，以确定NBS和对血红蛋白疾病的随访的可行性、有效性和可接受性。国家统计局将把目标对准该区域预定部落的土著人民，这些人的血红蛋白疾病携带率很高，生活在半城市、农村或森林地区，经常流动，社会经济不利因素的发生率很高。这些研究的结果将为印度发展普遍的新生儿筛查和全面的血红蛋白疾病护理提供基础。这也将作为国家统计局在印度治疗其他遗传和代谢障碍的模式，并产生可能有助于向贫困部门提供初级卫生保健的见解，以及其他慢性病的疾病管理计划。 镰状细胞病是一种遗传性的血红蛋白疾病，由于一种名为肺炎球菌的细菌的感染，这种疾病在婴儿时期可能很快就会致命。对新生儿进行这种疾病的筛查可以导致早期诊断，并开始使用青霉素和全面护理进行预防，大大减少这种疾病的痛苦和早期死亡。在与来自印度和美国的研究人员的合作中，我们建议采用美国成功的新生儿筛查模式，在印度古吉拉特邦农村弱势土著人口中试行新生儿筛查和镰状细胞疾病综合护理。

DESCRIPTION (provided by applicant): Hemoglobinopathies are a major case of morbidity and premature mortality worldwide. With an estimated over 10,000 live birth each year of infants with Thalassemia major and 5,200 live births of infants with sickle cell disease each year, hemoglobinopathies have emerged as a major public health problem in India. Newborn screening (NBS) can dramatically reduce morbidity and mortality from sickle cell disease (SCD) by facilitating early initiation of penicillin prophylaxis and enrollment in comprehensive care. However, NBS for hemoglobinopathies or other genetic and metabolic diseases has primarily been implemented in highly structured health systems in developed countries. In India, SCD is most prevalent in indigenous populations classified as scheduled tribes who have a high prevalence of socioeconomic disadvantage and who live in rural or forested regions. Gujarat state with large population of scheduled tribes is the first state to initiate a comprehensive hemoglobinopathies program. This project is a Indo-US collaboration between investigators at Children's Hospital of Pittsburgh and Children's hospital of Oakland and the Institute of Immunohematology, Mumbai and Valsad Raktadan Kendra and Gujarat State sickle cell disease treatment and control program, Valsad to pilot newborn screening for hemoglobinopathies in South Gujarat. Specific aims are 1. Test the feasibility of establishing a newborn screening and follow-up program for sickle cell disease in the tribal regions of south Gujarat. 2. Determine the feasibility of enrolling asymptomatic infants diagnosed with sickle cell disease in comprehensive care and 3. Examine the acceptability of newborn screening follow-up and genetic testing and counseling for hemoglobinopathies detected on NBS. We will combine high throughput laboratory screening methods, systematic follow-up, standardized clinical care, integrated laboratory and child health informatics system for tracking patient care, telecommunication to bypass gaps in infrastructure and socio- behavioral studies to determine the feasibility, efficacy and acceptability of NBS and follow-up for hemoglobinopathies. NBS will be targeted to the indigenous peoples of the scheduled tribes, in this region who have a very high carrier frequency of hemoglobinopathies, live in semi-urban, rural or forested regions, are frequently mobile and have high prevalence of socioeconomic disadvantage. Results of these studies will provide the basis for developing universal newborn screening, and comprehensive care for hemoglobinopathies, India. This will also serve as a model for NBS for other genetic and metabolic disorders in India, as well as generate insights that may be useful in the delivery of primary health care to disadvantaged sections and disease management programs for other chronic disorders. Sickle cell disease is an inherited disorder of hemoglobin which can be rapidly fatal in infancy be cause of infection by a bacterium called pneumococcus. Screening of newborns for this disease leads to early diagnosis and initiation of prophylaxis with penicillin and comprehensive care and a dramatic reduction in suffering and early death from this disease. In this collaboration with investigators from India and the USA we propose to adapt a successful model of newborn screening in the USA to pilot newborn screening and comprehensive care for sickle cell disease among a rural disadvantaged indigenous population in Gujarat State of India.