Determinants of TB control, relapse and reinfection
结核病控制、复发和再感染的决定因素
基本信息
- 批准号:10621299
- 负责人:
- 金额:$ 256.5万
- 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:2021-07-01 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AftercareAntibiotic TherapyAntibioticsAntimycobacterial AgentsAntitubercular AntibioticsBacillusBacteriaBiologicalBiological MarkersBlood specimenBody FluidsCellsChemotherapy-Oncologic ProcedureClinicalClinical DataCountryDiseaseDrug KineticsEnrollmentFailureFamilyGenesGeneticGoalsGrowthHaitiHumanHuman GeneticsImmuneImmune systemImmunologicsImmunophenotypingIndividual DifferencesInfectionInfection ControlIntegration Host FactorsKnowledgeLengthMachine LearningMaintenanceMeasuresMediatingModelingMouse StrainsMusMycobacterium tuberculosisOrganPatientsPersonsPharmaceutical PreparationsPharmacologyPharmacotherapyPlasmaPopulationPredispositionProcessRecurrenceRelapseResearch PersonnelResolutionResourcesRoleSamplingSampling StudiesSiblingsSterilizationTYK2TestingTissuesTreatment outcomeTuberculosisWorkchemotherapeutic agentchemotherapychronic infectionclinical research sitecohortdata managementdesignempowermentexperiencegenetic variantglobal healthgut microbiomehigh dimensionalityhigh riskimmunopathologyinsightmicrobiomemicrobiome compositionmicrobiome researchmouse modelnext generation sequencingpathogenpressurerecruitrelapse preventionrelapse riskresponsesuccesssynergismtranscriptomicstreatment responsetuberculosis chemotherapytuberculosis drugstuberculosis treatment
项目摘要
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), continues to be a severe global
health problem. TB is multifaceted, but a central clinical and microbiologic feature of the disease is the ability of
Mtb to resist complete elimination, both by the host immune system and by chemotherapeutic agents with potent
growth inhibitory activity. This persistence in the face of immunologic and antibiotic pressure underlies several
important facets of TB disease, including 1) the existence of latent tuberculosis infection (LTBI) and, in the setting
of immunologic failure of LTBI control, its role in the genesis of active TB and 2) the prolonged course of TB
antibiotic therapy, which requires 6 months of multidrug therapy to achieve reliable clinical cure. Rather than
producing complete bacterial eradication in all treated subjects, cure following TB chemotherapy is now
understood to be an antibiotic induced paucibacillary state in which prevention of relapse depends in part on
poorly understood host factors. The host and bacterial determinants that mediate these two interrelated types of
persistence are only partially understood, a knowledge gap the Tri-I-TBRU aims to fill. We propose a set of 3
intersecting projects and 3 cores all focused on different facets of the problem of paucibacillary TB, both post
treatment and LTBI. The projects will use samples and clinical data from TB cohorts at our clinical site at
GHESKIO in Port Au Prince Haiti, to examine the immunologic, microbiomic, transcriptomic, pharmacokinetic,
and genetic factors that influence or predict the transition points between paucibacillary states of TB disease and
active transmissible infection. These human studies will be compared and contrasted with a new mouse model
of paucibacillary infection that will allow us to test mechanistic hypotheses about the host and bacterial
determinants of paucibacillary disease. This work with be conducted by a team of highly collaborative
investigators who have who have worked well together for several years.
结核分枝杆菌(Mtb),结核病(TB)的病原体,继续是一个严重的全球
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Inborn errors of human transcription factors governing IFN-γ antimycobacterial immunity.
控制 IFN-γ 抗分枝杆菌免疫的人类转录因子的先天性错误。
- DOI:10.1016/j.coi.2023.102296
- 发表时间:2023
- 期刊:
- 影响因子:7
- 作者:Ogishi,Masato;Yang,Rui;Rosain,Jérémie;Bustamante,Jacinta;Casanova,Jean-Laurent;Boisson-Dupuis,Stéphanie
- 通讯作者:Boisson-Dupuis,Stéphanie
Genome-wide detection of human intronic AG-gain variants located between splicing branchpoints and canonical splice acceptor sites.
- DOI:10.1073/pnas.2314225120
- 发表时间:2023-11-14
- 期刊:
- 影响因子:11.1
- 作者:Zhang, Peng;Chaldebas, Matthieu;Ogishi, Masato;Al Qureshah, Fahd;Ponsin, Khoren;Feng, Yi;Rinchai, Darawan;Milisavljevic, Baptiste;Han, Ji Eun;Moncada-Velez, Marcela;Keles, Sevgi;Schroeder, Bernd;Stenson, Peter D.;Cooper, David N.;Cobat, Aurelie;Boisson, Bertrand;Zhang, Qian;Boisson-Dupuis, Stephanie;Abel, Laurent;Casanova, Jean- Laurent
- 通讯作者:Casanova, Jean- Laurent
Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis.
- DOI:10.1084/jem.20220484
- 发表时间:2023-01-02
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli.
尽管存在艾滋病毒,但结核分枝杆菌仍具有抵抗力,其肺泡中的 T 细胞和巨噬细胞被激活。
- DOI:10.21203/rs.3.rs-3889020/v1
- 发表时间:2024
- 期刊:
- 影响因子:0
- 作者:Schurr,Erwin;Dallmann-Sauer,Monica;Fava,Vinicius;Malherbe,Stephanus;McDonald,Candice;Orlova,Marianna;Kroon,Elouise;Cobat,Aurélie;Boisson-Dupuis,Stéphanie;Hoal,Eileen;Abel,Laurent;Möller,Marlo;Casanova,Jean-Laurent;Walzl,Gerhard;
- 通讯作者:
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{{ truncateString('SABINE EHRT', 18)}}的其他基金
M. tuberculosis carbon metabolism during infection
结核分枝杆菌感染期间的碳代谢
- 批准号:
10716619 - 财政年份:2023
- 资助金额:
$ 256.5万 - 项目类别:
Turning Mycobacterium tuberculosis appetite for fatty acids against itself
结核分枝杆菌对脂肪酸的需求与自身相悖
- 批准号:
10592602 - 财政年份:2022
- 资助金额:
$ 256.5万 - 项目类别:
Determinants of TB control, relapse and reinfection
结核病控制、复发和再感染的决定因素
- 批准号:
10268801 - 财政年份:2021
- 资助金额:
$ 256.5万 - 项目类别:
Determinants of Paucibacillary Mtb Infection in Mice
小鼠少杆菌 Mtb 感染的决定因素
- 批准号:
10430228 - 财政年份:2021
- 资助金额:
$ 256.5万 - 项目类别:
Determinants of TB control, relapse and reinfection
结核病控制、复发和再感染的决定因素
- 批准号:
10430221 - 财政年份:2021
- 资助金额:
$ 256.5万 - 项目类别:
Determinants of Paucibacillary Mtb Infection in Mice
小鼠少杆菌 Mtb 感染的决定因素
- 批准号:
10268807 - 财政年份:2021
- 资助金额:
$ 256.5万 - 项目类别:
Determinants of Paucibacillary Mtb Infection in Mice
小鼠少杆菌 Mtb 感染的决定因素
- 批准号:
10621309 - 财政年份:2021
- 资助金额:
$ 256.5万 - 项目类别:
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