Investigating parasitism-induced immune dysregulation and susceptibility to acute rheumatic fever in children

研究寄生引起的免疫失调和儿童对急性风湿热的易感性

基本信息

  • 批准号:
    10303850
  • 负责人:
  • 金额:
    $ 22.18万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-06-22 至 2023-05-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Rheumatic heart disease (RHD) is the leading cause of acquired cardiac morbidity and mortality in young people worldwide. RHD, a complication of acute rheumatic fever (ARF), develops as a result of strep throat (causative agent Streptococcus pyogenes). While strep throat is common in pediatric populations, only a small percentage of infected patients will progress to the severe clinical complications of ARF and RHD. Currently, we cannot predict which children will progress to the more severe form of disease. The epidemiology and clinical pathology of RHD is complex and ill-defined. The incidence of RHD in the United States has sharply declined since the early 1900s, though the incidence of strep throat has remained constant. In high-income countries, even when strep throat is not appropriately treated, ARF and RHD are extremely rare. Conversely, RHD and strep throat both remain significant problems in low and middle-income countries (LMIC). Interestingly, the initial decline in clinicial cases was noted prior to the implementation of regular penicilin use. This decline does, however, correspond with implementation of more rigorous hygiene practices and the reduced burden of childhood parasitic infections. Many LMICs, such as Malawi, continue to struggle with a high burden of parasitic infections and RHD within their population. Parasitic infections cause several systemic health problems such as nutritional deficiencies, cognitive impairment, and increased susceptibility to secondary infections. Most importantly, certain parasitic infections skew the immune profile towards Th2 innate and adaptive responses. We believe that this skewed immune response due to parasitic infection is a driving factor in the development of ARF and RHD in people with strep throat. This study aims to investigate the role of immune modulation due to co-infection with gastrointestinal parasites in the progression of strep throat to ARF. We hypothesize that children presenting with ARF in a highly endemic region of Malawi will more commonly have a co-infection with one or more parasite when compared to age-matched controls, thereby providing evidence that a parasite-induced altered immune response leads to increased susceptibility to ARF and severe disease. The overall goal of this study is to determine if parasite co-infection is significantly higher in ARF and RHD patients and to determine alterations to the immune profile. Our aims are as follows: (1) Identify the prevalence of parasite infections in children with acute rheumatic fever who present to health care centers in Malawi compared to age-matched controls, (2) Examine the extent of immune dysregulation in children with ARF compared to age-matched controls. Our overall expected outcome from this study is that we will identify a correlation between parasite burden and ARF and explain the skewed immune profiles that increase risk of severe disease. This study will generate important data to inform larger prospective studies to identify targets for public health intervention and treatment strategies. We believe this is an important first step in identifying underlying causes of ARF and RHD.
项目总结 风湿性心脏病(RHD)是年轻人后天心脏病发病率和死亡率的主要原因 全世界。风湿性心脏病是急性风湿热(ARF)的一种并发症,由链球菌咽喉(致病)引起 化脓性链球菌)。虽然链球菌咽喉炎在儿科人群中很常见,但只有一小部分人 的患者将进展为ARF和RHD的严重临床并发症。目前,我们不能 预测哪些儿童会发展为更严重的疾病形式。流行病学与临床病理学 风湿性心脏病的定义是复杂和模糊的。风湿性心脏病在美国的发病率自 20世纪初,尽管链球菌性咽喉炎的发病率一直保持不变。在高收入国家,即使在 链球菌性咽喉没有得到适当的治疗,ARF和RHD是极其罕见的。相反,风湿性心脏病和链球菌性咽喉炎 这两个问题在低收入和中等收入国家仍然是严重的问题。有趣的是,最初的下降 临床病例在实施常规青霉素使用之前被记录下来。然而,这种下降确实是, 与实施更严格的卫生做法和减轻儿童负担相对应 寄生虫感染。许多小岛屿发展中国家,如马拉维,继续与寄生虫感染的沉重负担作斗争。 以及他们人口中的风湿性心脏病。寄生虫感染会导致几个系统性的健康问题,如营养 缺陷、认知障碍和对继发感染的易感性增加。最重要的是,确定 寄生虫感染使免疫图谱向Th2先天和适应性反应倾斜。我们相信这一点 寄生虫感染引起的免疫应答失衡是ARF和RHD发生的驱动因素 患有链球菌性咽喉炎的人。本研究旨在探讨混合感染在免疫调节中的作用。 胃肠道寄生虫在链球菌性咽喉炎向急性肾功能衰竭的进展。我们假设呈现给我们的孩子 马拉维高度流行地区的ARF通常会与一种或多种寄生虫合并感染。 与年龄匹配的对照组相比,从而提供了寄生虫诱导的免疫改变的证据 反应导致对ARF和严重疾病的易感性增加。这项研究的总体目标是 确定ARF和RHD患者的寄生虫合并感染是否显著更高,并确定 免疫特征。我们的目标如下:(1)确定儿童寄生虫感染的流行率 马拉维卫生保健中心的急性风湿热患者与年龄匹配的对照组比较(2) 与年龄匹配的对照组相比,检查ARF儿童免疫失调的程度。我们的整体 这项研究的预期结果是,我们将确定寄生虫负担与ARF和 解释会增加严重疾病风险的扭曲的免疫模式。这项研究将产生重要的数据 为更大规模的前瞻性研究提供信息,以确定公共卫生干预和治疗战略的目标。我们 相信这是确定ARF和RHD根本原因的重要的第一步。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Sarah Murphy Gunter其他文献

Sarah Murphy Gunter的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Sarah Murphy Gunter', 18)}}的其他基金

Determining the vector ecology and epidemiology of tick-borne spotted fever group Rickettsia in a large urban setting of Houston, TX.
确定德克萨斯州休斯顿大城市环境中蜱传斑热病立克次体的媒介生态学和流行病学。
  • 批准号:
    10359130
  • 财政年份:
    2021
  • 资助金额:
    $ 22.18万
  • 项目类别:
Investigating parasitism-induced immune dysregulation and susceptibility to acute rheumatic fever in children
研究寄生引起的免疫失调和儿童对急性风湿热的易感性
  • 批准号:
    10436354
  • 财政年份:
    2021
  • 资助金额:
    $ 22.18万
  • 项目类别:
Next generation mosquito control through technology-driven trap development and artificial intelligence guided detection of mosquito breeding habitats
通过技术驱动的诱捕器开发和人工智能引导的蚊子繁殖栖息地检测来控制下一代蚊子
  • 批准号:
    10490916
  • 财政年份:
    2021
  • 资助金额:
    $ 22.18万
  • 项目类别:
Determining the vector ecology and epidemiology of tick-borne spotted fever group Rickettsia in a large urban setting of Houston, TX.
确定德克萨斯州休斯顿大城市环境中蜱传斑热病立克次体的媒介生态学和流行病学。
  • 批准号:
    10218814
  • 财政年份:
    2021
  • 资助金额:
    $ 22.18万
  • 项目类别:
Next generation mosquito control through technology-driven trap development and artificial intelligence guided detection of mosquito breeding habitats
通过技术驱动的诱捕器开发和人工智能引导的蚊子繁殖栖息地检测来控制下一代蚊子
  • 批准号:
    10339610
  • 财政年份:
    2021
  • 资助金额:
    $ 22.18万
  • 项目类别:
Next generation mosquito control through technology-driven trap development and artificial intelligence guided detection of mosquito breeding habitats
通过技术驱动的诱捕器开发和人工智能引导的蚊子繁殖栖息地检测来控制下一代蚊子
  • 批准号:
    10687199
  • 财政年份:
    2021
  • 资助金额:
    $ 22.18万
  • 项目类别:

相似国自然基金

靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
  • 批准号:
    JCZRQN202500010
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
  • 批准号:
    2025JJ70209
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
  • 批准号:
  • 批准年份:
    2024
  • 资助金额:
    0 万元
  • 项目类别:
    面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
  • 批准号:
    2023JJ50274
  • 批准年份:
    2023
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
  • 批准号:
  • 批准年份:
    2022
  • 资助金额:
    33 万元
  • 项目类别:
    地区科学基金项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
  • 批准号:
  • 批准年份:
    2022
  • 资助金额:
    10.0 万元
  • 项目类别:
    省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
  • 批准号:
    81973577
  • 批准年份:
    2019
  • 资助金额:
    55.0 万元
  • 项目类别:
    面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
  • 批准号:
    81602908
  • 批准年份:
    2016
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
  • 批准号:
    81501928
  • 批准年份:
    2015
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

PROTEMO: Emotional Dynamics Of Protective Policies In An Age Of Insecurity
PROTEMO:不安全时代保护政​​策的情绪动态
  • 批准号:
    10108433
  • 财政年份:
    2024
  • 资助金额:
    $ 22.18万
  • 项目类别:
    EU-Funded
The role of dietary and blood proteins in the prevention and development of major age-related diseases
膳食和血液蛋白在预防和发展主要与年龄相关的疾病中的作用
  • 批准号:
    MR/X032809/1
  • 财政年份:
    2024
  • 资助金额:
    $ 22.18万
  • 项目类别:
    Fellowship
Atomic Anxiety in the New Nuclear Age: How Can Arms Control and Disarmament Reduce the Risk of Nuclear War?
新核时代的原子焦虑:军控与裁军如何降低核战争风险?
  • 批准号:
    MR/X034690/1
  • 财政年份:
    2024
  • 资助金额:
    $ 22.18万
  • 项目类别:
    Fellowship
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
  • 批准号:
    2341426
  • 财政年份:
    2024
  • 资助金额:
    $ 22.18万
  • 项目类别:
    Continuing Grant
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
  • 批准号:
    2341424
  • 财政年份:
    2024
  • 资助金额:
    $ 22.18万
  • 项目类别:
    Continuing Grant
Doctoral Dissertation Research: Effects of age of acquisition in emerging sign languages
博士论文研究:新兴手语习得年龄的影响
  • 批准号:
    2335955
  • 财政年份:
    2024
  • 资助金额:
    $ 22.18万
  • 项目类别:
    Standard Grant
The economics of (mis)information in the age of social media
社交媒体时代(错误)信息的经济学
  • 批准号:
    DP240103257
  • 财政年份:
    2024
  • 资助金额:
    $ 22.18万
  • 项目类别:
    Discovery Projects
How age & sex impact the transcriptional control of mammalian muscle growth
你多大
  • 批准号:
    DP240100408
  • 财政年份:
    2024
  • 资助金额:
    $ 22.18万
  • 项目类别:
    Discovery Projects
Supporting teachers and teaching in the age of Artificial Intelligence
支持人工智能时代的教师和教学
  • 批准号:
    DP240100111
  • 财政年份:
    2024
  • 资助金额:
    $ 22.18万
  • 项目类别:
    Discovery Projects
Enhancing Wahkohtowin (Kinship beyond the immediate family) Community-based models of care to reach and support Indigenous and racialized women of reproductive age and pregnant women in Canada for the prevention of congenital syphilis
加强 Wahkohtowin(直系亲属以外的亲属关系)以社区为基础的护理模式,以接触和支持加拿大的土著和种族育龄妇女以及孕妇,预防先天梅毒
  • 批准号:
    502786
  • 财政年份:
    2024
  • 资助金额:
    $ 22.18万
  • 项目类别:
    Directed Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了