权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Optimizing Benefits While Reducing Risks of Iron in Malaria-Endemic Areas

在疟疾流行地区优化铁的效益同时降低风险

基本信息

批准号：
10428352
负责人：
Sarah Cusick
金额：
$ 53.51万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-05 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10428352
关键词：
Africa South of the Sahara Aftercare Anemia Antimalarials Area Behavioral Brain Cells Cessation of life Child Cognitive Data Development Ensure Erythrocytes Funding Future Goals Growth Health Hemoglobin Hepatic Hospitalization Impaired cognition Incidence Infection Inflammatory Response Intervention Intestines Iron Island Lead Link Malaria Methods Morbidity - disease rate Oral Outcome Pathogenicity Pemba Pharmaceutical Preparations Physiology Pilot Projects Placebo Control Proteins Public Health Randomized Clinical Trials Randomized Controlled Trials Regimen Reporting Risk Standardization Testing Translating Translational Research World Health Organization behavior test behavioral outcome cognitive testing follow-up functional outcomes gut microbiome health goals hepcidin improved infection risk insight intervention program iron absorption iron deficiency iron supplementation mortality neurobehavioral pathogenic bacteria prophylactic public health relevance stable isotope standard of care

项目摘要

ABSTRACT Ensuring sufficient iron for the brain development of tens of millions of children living in malaria-endemic areas while also protecting them from infection has been an unachieved public health goal for more than a decade. Iron supplementation in these global areas is linked with increased risks of malaria and other infections. One solution to safely and effectively treat coexisting malaria and iron deficiency is to stagger the interventions, treating malaria first and delaying the start of iron until 28 days later. Preliminary data from our recent R03 pilot study demonstrate that this strategy causes the hepatic protein hepcidin to decline, allowing oral iron to be better absorbed and incorporated into hemoglobin, and also reduces the risk of infections in the short-term.11 The objective of this application is to conduct a placebo-controlled, randomized clinical trial to determine whether iron treatment begun concurrently with vs. 28 days after antimalarial treatment in Ugandan children 6- 48 months with malaria and iron deficiency results in better long-term iron status, fewer infections, and better neurobehavioral development after 12 months. The central hypothesis is that better iron incorporation and lower incidence of infectious illness observed with 28-day delayed iron in the R03 study with only 8 weeks follow-up will translate into sustained improvements iron status, lowered risk of infection, and improved cognitive and behavioral outcomes. The rationale of this study is that staggering antimalarial treatment and iron therapy protects against immediate morbidity while also optimizing long-term neurobehavioral development. Guided by strong preliminary data, the specific aims are: 1) Establish the effect of immediate vs. delayed iron treatment on long-term iron status; 2) Determine the effect of delayed iron treatment on the incidence of infectious illness; and 3) Establish the effect of delayed iron treatment on neurobehavioral development. Analysis of the gut microbiome in the delayed and immediate iron group will provide insight into potential mechanisms of any observed differences in morbidity between the groups. The translational research team is uniquely suited to assess neurobehavioral outcomes, a critical, but typically unmeasured functional outcome of a successful management approach for iron deficiency and infection. Establishment of methods to safely and effectively ensure brain iron while also protecting from infection will permit attainment of full cognitive and behavioral development for tens of millions of children worldwide suffering from iron deficiency and malaria.

摘要确保为生活在疟疾流行区的数千万儿童的大脑发育提供足够的铁同时保护他们免受感染也是十多年来一直没有实现的公共卫生目标。在这些全球地区补充铁与增加疟疾和其他感染的风险有关。一安全有效地治疗疟疾和缺铁共存的解决方案是错开干预措施，首先治疗疟疾，并将铁的开始时间推迟到28天后。我们最近的R03试飞的初步数据研究表明，这一策略会导致肝脏蛋白质海普西丁下降，从而使口服铁更好地吸收和结合到血红蛋白中，并在短期内降低感染风险。该应用的目的是进行一项安慰剂对照的随机临床试验，以确定在乌干达儿童中，铁治疗是否与抗疟疾治疗后28天同时开始6- 患有疟疾和缺铁的48个月会导致更好的长期铁状况，更少的感染，以及更好的 12个月后神经行为发育。中心假设是更好的铁结合和在只有8周的R03研究中，观察到28天延迟铁剂的感染性疾病发生率较低后续将转化为持续改善铁的状况，降低感染风险，并改善认知和行为结果。这项研究的基本原理是惊人的抗疟疾治疗和铁剂疗法预防即刻发病，同时优化长期神经行为发展。在强劲的初步数据指导下，具体目标是：1)建立即时与非即时的效果。延迟铁处理对长期铁状态的影响；2)确定延迟铁处理对感染性疾病的发生率；以及3)确定延迟铁剂治疗对神经行为的影响发展。对延迟组和即刻铁组的肠道微生物组的分析将提供对两组之间观察到的发病率差异的潜在机制。翻译研究团队是唯一适合评估神经行为结果的团队，这是一个关键但通常无法测量的功能铁缺乏和感染的成功管理方法的结果。建立方法，以安全有效地确保脑铁，同时防止感染，将允许充分全球数千万缺铁儿童的认知和行为发育还有疟疾。