Novel nanoparticular diagnostics for cerebral toxoplasmosis and Chagas in HIV patients living in Latin America
针对生活在拉丁美洲的艾滋病毒患者的脑弓形体病和恰加斯病的新型纳米诊断
基本信息
- 批准号:10405524
- 负责人:
- 金额:$ 64.52万
- 依托单位:
- 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:2018-06-18 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS/HIV problemAcuteAffectAffinityAlgorithmsAnti-Retroviral AgentsAntigen TargetingAntigensApplications GrantsAreaBindingBiological AssayBloodBody FluidsBoliviaBolivianCentral Nervous System InfectionsCerebral ToxoplasmosisCerebrospinal FluidChagas DiseaseClinicalCountryCryptococcal MeningitisDataDevelopmentDiagnosisDiagnosticDiagnostic ProcedureDiagnostic SensitivityDiagnostic testsDiseaseDot ImmunoblottingDyesHIVHIV InfectionsHIV SeropositivityImmobilizationImmunoassayImmunosuppressionIndividualInfectionLatin AmericaLifeLungMeningeal TuberculosisMycobacterium tuberculosisNeuraxisNeurologicOpportunistic InfectionsPathologicPathologyPatientsPersonsPeruPeruvianPhysiciansPilot ProjectsPopulationProceduresResource-limited settingResourcesRiskSavingsSensitivity and SpecificitySeroprevalencesSiteSouth AmericaSouth AmericanSpecificitySpinal PunctureSymptomsSyndromeTechniquesTechnologyTestingTimeToxoplasma gondiiToxoplasmosisTrypanosoma cruziUrineWorkantigen detectionantiretroviral therapybaseclinical diagnosisco-infectioncohortdiagnostic assayeffective therapyinfection rateinnovationlateral flow assaylipoarabinomannanlow and middle-income countriesnanoparticlenervous system disorderneuroAIDSnovelnovel diagnosticsopportunistic pathogenpathogenpilot testpreservationreactivation from latencytoxoplasmic encephalitisurinary
项目摘要
PROJECT SUMMARY
Among the most devastating opportunistic diseases associated with human immunodeficiency virus (HIV) are
those that affect the central nervous system (CNS). Their nonspecific presentation makes diagnosis difficult even
in the best-resourced settings, and in Low and Middle Income Countries (LMICs), a definitive diagnosis can be
all but impossible. In this context, CNS infections such as toxoplasmic encephalitis (TE) and CNS Chagas
disease are often treated empirically, which can be fatal when physicians' best guesses are incorrect.
Toxoplasma gondii seroprevalence is estimated to be highest in Latin America, but diagnosis in HIV-positive
patients is difficult without expensive technologies that are unavailable in resource-poor countries. Similarly,
Chagas disease, caused by Trypanosoma cruzi, is a serious opportunistic infection in people living with
HIV/AIDS, and is also difficult to diagnose. Finally, tuberculosis meningitis (TBM) is difficult to diagnose and
frequently fatal because of the delay in diagnosis. 33% of Peruvians and Bolivians are at risk for the development
of TB, when patients are HIV positive they are at risk of TBM. Much of South America, including our study site
in Bolivia, is highly endemic for both T. cruzi and T. gondii as well as other common CNS opportunistic
pathogens. We propose the development and pilot testing of a novel diagnostic assays and their use in clinical
diagnosis of TE and CNS Chagas disease through the following aims:
Specific Aim 1: Development of parallel lateral flow assays for TE, TBM, and CNS Chagas. In addition to
our already developed dot blot assays for Chagas and TB, we have preliminary data that demonstrates
nanoparticles' ability to capture and detect multiple T. gondii antigens. (3-5) With further development, we will
be able to transition these individual immunoassays into a simultaneous lateral flow test.
Specific Aim 2. To determine the sensitivity and specificity of the nanoparticle diagnostic assays for TE,
TBM and CNS Chagas disease in a well-characterized cohort of HIV-infected patients with acute
neurological syndromes. We expect that the proportion of neurological syndromes due to toxoplasmosis, TBM,
and cryptococcal meningitis will be similar to those in other South American HIV populations. We anticipate,
however, that CNS Chagas disease will also cause a substantial proportion of neurological disease in the
Bolivian population, which may have been underdiagnosed.
This project will help define the clinical spectrum of HIV-associated neurological disease in Latin America and
use innovative diagnostic techniques to distinguish between CNS Chagas disease, TBM, TE, and other CNS
infections. Where multiple pathogens are endemic and are rapidly fatal, more rapid, sensitive, and specific tests
could accelerate the initiation of specific and potentially life-saving therapy.
项目总结
与人类免疫缺陷病毒(HIV)相关的最具破坏性的机会性疾病包括
那些影响中枢神经系统(CNS)的疾病。它们的非特异性表现甚至使诊断变得困难
在资源最充足的情况下,在低收入和中等收入国家(LMIC),一个明确的诊断可能是
几乎是不可能的。在这方面,弓形体脑炎和查加斯等中枢神经系统感染
疾病通常是凭经验治疗的,当医生的最佳猜测不正确时,这可能是致命的。
据估计,弓形虫血清阳性率在拉丁美洲最高,但在艾滋病毒阳性的患者中被诊断为弓形虫
如果没有昂贵的技术,患者是很困难的,而这些技术在资源匮乏的国家是无法获得的。同样,
由克氏锥虫引起的恰加斯病是一种严重的机会性感染。
艾滋病毒/艾滋病,也很难诊断。最后,结核病脑膜炎(TBM)很难诊断和
由于诊断的延迟,常常是致命的。33%的秘鲁人和玻利维亚人面临着发展的风险
在结核病方面,当患者艾滋病毒呈阳性时,他们有患结核病的风险。南美洲大部分地区,包括我们的研究站点
在玻利维亚,克鲁兹弓形虫和弓形虫以及其他常见的中枢神经系统机会性疾病高度流行
病原体。我们建议开发和中试一种新的诊断分析方法,并将其用于临床。
通过以下目的诊断TE和CNS恰加斯病:
具体目标1:开发TE、TBM和CNS Chagas的平行侧向流动分析方法。除了……之外
我们已经开发了查加斯和结核病的斑点印迹分析,我们有初步数据表明
纳米颗粒捕获和检测多种弓形虫抗原的能力。(3-5)随着进一步的发展,我们将
能够将这些单独的免疫分析转换为同步的侧向流动测试。
具体目的2.为了确定用于TE的纳米颗粒诊断分析的敏感性和特异性,
急性HIV感染者队列中的特发性结缔组织病和中枢神经系统恰加斯病
神经综合征。我们预计,由于弓形虫病、TBM、
隐球菌性脑膜炎将与南美其他艾滋病毒人群的脑膜炎相似。我们预计,
然而,中枢神经系统恰加斯病也会导致相当大比例的神经系统疾病
玻利维亚人口,这可能被低估了。
该项目将有助于确定拉丁美洲和拉丁美洲艾滋病毒相关神经疾病的临床谱系
使用创新的诊断技术来区分CNS Chagas病、TBM、TE和其他CNS
感染。如果多种病原体是地方性的,并且是迅速致命的,则进行更快速、更敏感和更特异的检测
可以加速启动特定的和潜在的挽救生命的疗法。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Evaluation of pathogen specific urinary peptides in tick-borne illnesses.
- DOI:10.1038/s41598-020-75051-3
- 发表时间:2020-11-09
- 期刊:
- 影响因子:4.6
- 作者:Magni R;Almofee R;Yusuf S;Mueller C;Vuong N;Almosuli M;Hoang MT;Meade K;Sethi I;Mohammed N;Araujo R;McDonald TK;Marcelli P;Espina V;Kim B;Garritsen A;Green C;Russo P;Zhou W;Vaisman I;Petricoin EF 3rd;Hoadley D;Molestina RE;McIntyre H;Liotta LA;Luchini A
- 通讯作者:Luchini A
{{
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 }}
ROBERT H GILMAN其他文献
UNDERSTANDING ALL-CAUSE MORTALITY AND COPD IN PERU: WHY SPIROMETRY SCREENING MATTERS FOR DIVERSE POPULATIONS
- DOI:
10.1016/j.chest.2022.08.1579 - 发表时间:
2022-10-01 - 期刊:
- 影响因子:
- 作者:
ERICA L CROSLEY;SHAKIR HOSSEN;ROBERT H GILMAN;J. JAIME MIRANDA;ANTONIO BERNABÉ-ORTIZ;ROBERT A WISE;WILLIAM CHECKLEY - 通讯作者:
WILLIAM CHECKLEY
ROBERT H GILMAN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('ROBERT H GILMAN', 18)}}的其他基金
Infectious Diseases Training program in Bolivia: South-South Training with Peru
玻利维亚传染病培训项目:与秘鲁的南南培训
- 批准号:
10838920 - 财政年份:2024
- 资助金额:
$ 64.52万 - 项目类别:
Diagnostic Innovations for Pediatric Tuberculosis in Bolivia
玻利维亚儿童结核病的诊断创新
- 批准号:
10731855 - 财政年份:2023
- 资助金额:
$ 64.52万 - 项目类别:
Using the Mycobacterium tuberculosis Genome to Predict Tuberculosis Pathology, Drug Resistance Acquisition and Identify Community Transmission Sites
使用结核分枝杆菌基因组预测结核病病理、耐药性获得和识别社区传播位点
- 批准号:
10392356 - 财政年份:2020
- 资助金额:
$ 64.52万 - 项目类别:
Using the Mycobacterium tuberculosis Genome to Predict Tuberculosis Pathology, Drug Resistance Acquisition and Identify Community Transmission Sites
使用结核分枝杆菌基因组预测结核病病理、耐药性获得和识别社区传播位点
- 批准号:
10598532 - 财政年份:2020
- 资助金额:
$ 64.52万 - 项目类别:
Novel nanoparticular diagnostics for cerebral toxoplasmosis and Chagas in HIV patients living in Latin America
针对生活在拉丁美洲的艾滋病毒患者的脑弓形体病和恰加斯病的新型纳米诊断
- 批准号:
10207356 - 财政年份:2018
- 资助金额:
$ 64.52万 - 项目类别:
Oxfendazole as a Broad Spectrum Deworming Medicine in Humans: Phase II Efficacy Study in Geohelminths
奥芬达唑作为人类广谱驱虫药:对土蠕虫的 II 期疗效研究
- 批准号:
9143283 - 财政年份:2016
- 资助金额:
$ 64.52万 - 项目类别:
Infectious Diseases Training program in Bolivia: South-South Training with Peru
玻利维亚传染病培训项目:与秘鲁的南南培训
- 批准号:
10580728 - 财政年份:2015
- 资助金额:
$ 64.52万 - 项目类别:
Infectious Diseases Training program in Bolivia: South-South Training with Peru
玻利维亚传染病培训项目:与秘鲁的南南培训
- 批准号:
10328561 - 财政年份:2015
- 资助金额:
$ 64.52万 - 项目类别:
Natural infection of norovirus and sapovirus in a birth cohort in a Peruvian periurban community
秘鲁城郊社区出生队列中诺如病毒和沙波病毒的自然感染
- 批准号:
8961698 - 财政年份:2015
- 资助金额:
$ 64.52万 - 项目类别:
Infectious Diseases Training program in Bolivia: South-South Training with Peru
玻利维亚传染病培训项目:与秘鲁的南南培训
- 批准号:
9065693 - 财政年份:2015
- 资助金额:
$ 64.52万 - 项目类别:
相似海外基金
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
$ 64.52万 - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
$ 64.52万 - 项目类别:
Collaborative R&D
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
$ 64.52万 - 项目类别:
Fellowship
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
$ 64.52万 - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
$ 64.52万 - 项目类别:
Research Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
$ 64.52万 - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
$ 64.52万 - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
$ 64.52万 - 项目类别:
Standard Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
$ 64.52万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Acute human gingivitis systems biology
人类急性牙龈炎系统生物学
- 批准号:
484000 - 财政年份:2023
- 资助金额:
$ 64.52万 - 项目类别:
Operating Grants