Diagnostic Innovations for Pediatric Tuberculosis in Bolivia
Diagnostic Innovations for Pediatric Tuberculosis in Bolivia
批准号:
10731855
负责人:
ROBERT H GILMAN
金额:
$75.1万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-06-07 至 2028-05-31
关键词:
AddressAdultAgeAntibiotic TherapyAreaAutomobile DrivingBacteriaBiological AssayBiological MarkersBlood specimenBoliviaCellsChestChildChildhoodClinicClinicalClustered Regularly Interspaced Short Palindromic RepeatsCollaborationsComputational algorithmComputer AssistedConsensusControl GroupsCountryCryopreservationDNADetectionDevelopmentDevicesDiagnosisDiagnosticDiagnostic ProcedureDiagnostic testsDiseaseEnrollmentGenesGoalsGuidelinesHIVHealth ProfessionalHigh PrevalenceHouseholdImageLaboratoriesLungLung diseasesMeasuresMediatingMethodsMolecularMycobacterium tuberculosisNatureOrganPediatric HospitalsPeruPilot ProjectsPolymerase Chain ReactionPopulationPredictive ValueProcessProteomicsPulmonary PathologyRadiology SpecialtyRapid diagnosticsReactionResearchResource-limited settingRespiratory DiseaseRiskSerumSpecificitySpecimenSputumSubgroupSystemTechniquesTestingThoracic RadiographyTimeTuberculosisUltrasonographyUnited States National Institutes of HealthUniversitiesValidationautomated algorithmcell free DNAcofactorcohortcostcost effectivedetection methoddiagnostic criteriadiagnostic platformdiagnostic strategydiagnostic toolgenomic toolshigh riskimaging biomarkerimprovedinnovationlow and middle-income countriesmachine learning algorithmnovelnovel diagnosticspathology imagingperipheral bloodpoint of careportabilityprismaquantitative imagingresponseresponse biomarkerstudy populationtooltreatment responsetuberculosis treatmentultrasound
中文摘要
在低收入和中等收入国家,儿童结核病(TB)继续构成诊断挑战
英文摘要
Pediatric tuberculosis (TB) continues to pose diagnostic challenges in low- and middle-income countries with
high rates of TB disease, due to the well-described impact of paucibacillary disease in children, and current TB
culture and polymerase-chain reaction tests are of limited usefulness due to cost, restricted availability, and
poor sensitivity in specimens available from younger children. Our team of experts from Tulane, Johns
Hopkins University, Universidad Peruana Cayetano Heredia, and Asociación Benéfica Prisma have confronted
all of these challenges through more than 25 years of collaboration in Peru and Bolivia. Our goal is to directly
address the challenges of TB in children by evaluating a new diagnostic approach developed by MPI Tony Hu
at Tulane University using a CRISPR-mediated TB assay (CRISPR-TB) optimized to detect circulating
Mycobacterium tuberculosis cell-free DNA (Mtb-cfDNA), and used to analyze cryopreserved serum in pilot
studies from adults and children with presumptive TB, their asymptomatic household contacts, and a cohort of
symptomatic children living with HIV (CLHIV) at high risk for TB. Results from symptomatic adult cohorts
yielded a pooled sensitivity of 93%; specificity of 93%; positive predictive value of 95%; and negative predictive
value of 92%. In limited pilot studies in CLHIV CRISPR-TBD results accurately identified all confirmed TB
(13/13) and most children with unconfirmed TB (80%; 52/65). We propose to enroll 200 presumptive TB
cases and an equal number of well control subjects in each of 2 study populations (test population and
validation population) identified through clinics associated with the “Dr. Mario Ortiz Suarez” Children's Hospital
in Santa Cruz, Bolivia. We will determine the distribution of cfDNA concentrations in peripheral blood in a “test
population” composed of two age-based groups of children (2 months-6 years, 7-14 years) with respiratory
disease grouped by likelihood of TB based on the NIH consensus case definitions (confirmed TB, unconfirmed
TB, and unlikely TB) and in age-matched controls grouped by presence of latent TB infection (LTBI), with
cfDNA measured serially in time among TB cases receiving antibiotic therapy. We will also validate standard
ranges of quantitative cfDNA established for clinical subgroups of children with TB disease or LTBI in an
independent validation cohort. An additional aim will determine the correlation between quantitative cfDNA and
quantitative imaging-based TB scores based on evidence of disease in the lung, the primary target organ in TB
disease, by (1) chest radiograph, measured by computer-aided analysis using the CAD4TB v7 system, and by
(2) lung ultrasound, performed with a portable/low-cost probe assisted by machine learning algorithms for
automatic interpretation. These biomarkers will be tested as potential cofactors that may be combined with
cfDNA levels in peripheral blood, to improve the detection of TB disease in children. The results of this study
will be the first step in a process to find a path to allow detection of the many “unconfirmed” TB cases and
ideally make the diagnosis of pediatric TB in reach for low resource settings where it is so critically needed.
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Infectious Diseases Training program in Bolivia: South-South Training with Peru
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批准号:10838920
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项目类别:
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资助金额:$30.03万
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财政年份:2024
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负责人:ROBERT H GILMAN
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依托单位:
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批准号:10392356
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项目类别:
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资助金额:$65.05万
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财政年份:2020
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依托单位:
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批准号:10598532
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资助金额:$65.2万
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财政年份:2020
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Novel nanoparticular diagnostics for cerebral toxoplasmosis and Chagas in HIV patients living in Latin America
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批准号:10405524
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项目类别:
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资助金额:$64.52万
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财政年份:2018
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负责人:ROBERT H GILMAN
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Novel nanoparticular diagnostics for cerebral toxoplasmosis and Chagas in HIV patients living in Latin America
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批准号:10207356
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项目类别:
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资助金额:$64.83万
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财政年份:2018
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负责人:ROBERT H GILMAN
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批准号:9143283
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项目类别:
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资助金额:$23.32万
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财政年份:2016
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负责人:ROBERT H GILMAN
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依托单位:
Infectious Diseases Training program in Bolivia: South-South Training with Peru
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批准号:10580728
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项目类别:
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资助金额:$29.39万
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财政年份:2015
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负责人:ROBERT H GILMAN
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依托单位:
Infectious Diseases Training program in Bolivia: South-South Training with Peru
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批准号:10328561
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项目类别:
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资助金额:$29.38万
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财政年份:2015
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负责人:ROBERT H GILMAN
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依托单位:
Natural infection of norovirus and sapovirus in a birth cohort in a Peruvian periurban community
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批准号:8961698
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项目类别:
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资助金额:$73.16万
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财政年份:2015
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负责人:ROBERT H GILMAN
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依托单位:
Infectious Diseases Training program in Bolivia: South-South Training with Peru
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批准号:9065693
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项目类别:
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资助金额:$26.99万
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财政年份:2015
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负责人:ROBERT H GILMAN
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依托单位:
Predictors of cardiomyopathy progression in a Chagas disease cohort in Bolivia
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批准号:10471779
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项目类别:
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资助金额:$70.83万
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财政年份:2014
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负责人:ROBERT H GILMAN
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依托单位:
Predictors of cardiomyopathy progression in a Chagas disease cohort in Bolivia
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批准号:10656420
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项目类别:
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资助金额:$71.79万
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财政年份:2014
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负责人:ROBERT H GILMAN
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依托单位:
Predictors of cardiomyopathy progression in a Chagas disease cohort in Bolivia
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批准号:8994261
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项目类别:
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资助金额:$59.97万
-
财政年份:2014
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负责人:ROBERT H GILMAN
-
依托单位:
Predictors of cardiomyopathy progression in a Chagas disease cohort in Bolivia
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批准号:10183142
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项目类别:
-
资助金额:$71.02万
-
财政年份:2014
-
负责人:ROBERT H GILMAN
-
依托单位:
Predictors of cardiomyopathy progression in a Chagas disease cohort in Bolivia
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批准号:9208732
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项目类别:
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资助金额:$58.74万
-
财政年份:2014
-
负责人:ROBERT H GILMAN
-
依托单位:
Predictors of cardiomyopathy progression in a Chagas disease cohort in Bolivia
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批准号:8696019
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项目类别:
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资助金额:$67.26万
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财政年份:2014
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负责人:ROBERT H GILMAN
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依托单位:
Family Cluster Analysis of Norovirus Variants by Multiple-region Sequence Typing
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批准号:8283947
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项目类别:
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资助金额:$22.09万
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财政年份:2012
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负责人:ROBERT H GILMAN
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依托单位:
Launching a salt substitute to reduce blood pressure at the population level-Peru
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批准号:8466372
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项目类别:
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资助金额:$46.81万
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财政年份:2012
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负责人:ROBERT H GILMAN
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依托单位:
Macrophage polarization and glutathione levels in the TB-helminth co-infection
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批准号:8510569
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项目类别:
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资助金额:$15.4万
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财政年份:2012
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负责人:ROBERT H GILMAN
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依托单位:
Family Cluster Analysis of Norovirus Variants by Multiple-region Sequence Typing
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批准号:8432436
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项目类别:
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资助金额:$16.61万
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财政年份:2012
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负责人:ROBERT H GILMAN
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依托单位:
海外基金