A5043592582- Tuberculosis Research and Epidemiology
- Pneumocystis jirovecii pneumonia detection and treatment
- Mycobacterium research and diagnosis
- Pneumonia and Respiratory Infections
- Diagnosis and treatment of tuberculosis
- Infectious Diseases and Tuberculosis
- HIV/AIDS drug development and treatment
- Animal Virus Infections Studies
- HIV/AIDS oral health manifestations
- Viral gastroenteritis research and epidemiology
- Pharmacovigilance and Adverse Drug Reactions
- Respiratory viral infections research
- Acute Lymphoblastic Leukemia research
- Bioinformatics and Genomic Networks
- Machine Learning in Healthcare
- Pharmacological Effects and Toxicity Studies
- SARS-CoV-2 and COVID-19 Research
- Biosimilars and Bioanalytical Methods
- Clostridium difficile and Clostridium perfringens research
- Immune responses and vaccinations
- Genomics and Rare Diseases
- Biliary and Gastrointestinal Fistulas
- Long-Term Effects of COVID-19
- Cytokine Signaling Pathways and Interactions
- HIV/AIDS Impact and Responses
Vanderbilt University Medical Center
2019-2025
Vanderbilt University
2018-2024
TuBerculosis Vaccine Initiative
2024
South African Tuberculosis Vaccine Initiative
2024
University of Cape Town
2024
Office of Infectious Diseases
2021
University of Minnesota
2013
Abstract There are insufficient predictors of progression to tuberculosis among contacts. A case-control study within RePORT-Brazil matched 20 QuantiFERON-positive progressors and 40 non-progressors by sex, age, exposure duration. Twenty-nine cytokines were measured Luminex in QuantiFERON-TB Gold Plus supernatants collected at baseline evaluated using machine learning for prediction. The same markers 8 QuantiFERON positive 12 from India. IL-8, IL-10, CCL3 levels predicted incident (AUC:...
Although genetic factors contribute to tuberculosis (TB) risk, no cross-population causal variants have been identified by genome-wide association studies (GWAS). Here, we utilized low-pass whole genome sequencing (lpWGS) with imputation plus detailed epidemiologic risk and single-cell expression quantitative loci (sceQTL) address prior GWAS limitations. Using 947 pulmonary (PTB) cases 1807 close contact controls in the Regional Prospective Observational Research TB (RePORT) study Brazil,...
Abstract Background Diagnosis of active tuberculosis (ATB) currently relies on detection Mycobacterium (Mtb). Identifying patients with extrapulmonary TB (EPTB) remains challenging because microbiological confirmation is often not possible. Highly accurate blood-based tests could improve diagnosis both EPTB and pulmonary (PTB) timely initiation anti-TB therapy. Methods A case-control study was performed using discriminant analyses to validate an approach Mtb-specific CD4+T-cell activation...
BackgroundA major goal of tuberculosis (TB) epidemiological studies is to obtain results that can be generalized the larger population with TB. The ability extrapolate findings on determinants TB treatment outcomes also important.MethodsWe compared baseline clinical and demographic characteristics anti-TB between persons enrolled in Regional Prospective Observational Research Tuberculosis (RePORT)-Brazil cohort June 2015 2019, registry cases reported Brazilian National Program (Information...
Tuberculosis (TB) remains a major plague of humanity. People with TB (PWTB) are commonly anemic. Here, we assessed whether the severity anemia in PWTB prior to anti-TB treatment (ATT) was risk factor for an unfavorable outcome.
The high burden of drug-resistant tuberculosis (TB) is a problem to achieve the goals End TB Strategy by 2035. Whether isoniazid monoresistance (Hr) affects anti-TB treatment (ATT) outcomes remains unknown in high-burden countries.
Tuberculosis-diabetes mellitus (TB-DM) is linked to a distinct inflammatory profile, which can be assessed using multi-omics analyses. Here, machine learning algorithm was applied multi-platform data, including cytokines and gene expression in peripheral blood eicosanoids urine, Brazilian multi-center TB cohort. There were four clinical groups: TB-DM(n = 24), only(n 28), DM(HbA1c ≥ 6.5%) 11), control group of close contacts who did not have or DM(n 13). After cross-validation, baseline...
Abstract Background Approximately 5% of people infected with Mycobacterium tuberculosis progress to (TB) disease without preventive therapy. There is a need for prognostic test identify those at highest risk incident TB so that therapy can be targeted. We evaluated host blood transcriptomic signatures progression disease. Methods Close contacts (≥4 hours exposure per week) adult patients culture-confirmed pulmonary were enrolled in Brazil. Investigation incident, microbiologically confirmed,...
It is unclear whether diabetes or prediabetes affects unfavorable treatment outcomes and death in people with tuberculosis (PWTB).
Abstract Background The Xpert MTB/RIF rapid molecular test provides a quantitative measure of Mycobacterium tuberculosis (Mtb) DNA in the form cycle threshold (Ct) values. This information can be translated into mycobacterial load and used as potential risk bacterial spread for (TB) cases, which impact infection control. However, role Ct values assessing Mtb transmission to close contacts has not yet been demonstrated. Methods A prospective study was performed investigate association between...
Tuberculosis (TB) is a leading infectious cause of death globally. It the most common opportunistic infection in people living with HIV, and their morbidity mortality. Following TB treatment, surviving individuals may be at risk for post-TB lung disease. The Sentinel Research Network (TB-SRN) provides platform coordinated observational research within International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. This prospective, cohort study will assess treatment post-treatment...
Abstract Background Approximately 95% of persons infected with M. tuberculosis do not progress to (TB) disease. Identifying key determinants TB progression could focus prevention efforts. Methods Contacts pulmonary cases were enrolled in a prospective multi-center cohort study (RePORT-Brazil) from 2015-2019 and followed for 24 months. Dimension reduction techniques included empirical review LASSO regression, using clinical laboratory information at baseline, determine factors inclusion...
Abstract Early delineation of host immune responses at the moment Mycobacterium tuberculosis (Mtb) exposure and infection is critical to identify individuals risk progressing active (TB). We performed single-cell transcriptional profiling over 500,000 peripheral blood mononuclear cells from 57 HIV-negative close contacts TB cases in Brazil, including 25 who developed disease within two years (progressors) 32 matched controls remained disease-free (non-progressors). Cells were stimulated...
Abstract Background Despite widespread availability of curative therapy, tuberculosis (TB) treatment outcomes remain suboptimal. Clinical prediction models can inform strategies to improve outcomes. Using baseline clinical data, we developed a model for unsuccessful TB outcome and evaluated the incremental value human immunodeficiency virus (HIV)–related severity isoniazid acetylator status. Methods Data originated from Regional Prospective Observational Research Tuberculosis Brazil cohort,...
Abstract Background Successful tuberculosis (TB) treatment is necessary for disease control. The World Health Organization (WHO) has a target TB success rate of ≥90%. We assessed whether the different types unfavorable outcome had predictors. Methods Using data from Regional Prospective Observational Research Tuberculosis-Brazil, we evaluated biological and behavioral factors associated with each component unsuccessful outcomes, recently updated by WHO (death, loss to follow-up [LTFU],...
It is unknown whether dysglycemia associated with Mycobacterium tuberculosis transmission.We assessed epidemiological and clinical characteristics of patients culture-confirmed pulmonary their close contacts, enrolled in a multicenter prospective cohort Brazil. Contacts were investigated at baseline 6 months after enrollment. QuantiFERON positivity conversion (from negative to positive month 6) compared between subgroups contacts according glycemic status persons (PWTB) as diabetes mellitus...
Abstract Diabetes mellitus (DM) increases tuberculosis (TB) severity. We compared blood gene expression in adults with pulmonary TB, or without diabetes from sites Brazil and India. RNA sequencing (RNAseq) performed at baseline during TB treatment. Publicly available RNAseq data South Africa Romania reported by the TANDEM Consortium were also analyzed. Across sites, differentially expressed genes varied for each condition (DM, TBDM) no pattern classified any one group across all sites. A...
Introduction Factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care contacts patients (TB) were investigated a multicentre prospective cohort from highly endemic regions Brazil. Methods Close 1187 culture-confirmed pulmonary TB prospectively studied between 2015 and 2019, follow-up 6–24 months. Data on screening by clinical investigation, radiographic examination interferon-gamma release assay (IGRA) collected. Multivariable regressions used to identify...
Abstract Background Tuberculosis (TB) treatment–related adverse drug reactions (TB-ADRs) can negatively affect adherence and treatment success rates. Methods We developed prediction models for TB-ADRs, considering participants with drug-susceptible pulmonary TB who initiated standard therapy. TB-ADRs were determined by the physician attending participant, assessing causality to drugs, affected organ system, grade. Potential baseline predictors of TB-ADR included concomitant medication (CM)...
Abstract Background Tuberculosis (TB) elimination requires treatment of millions persons with latent M. tuberculosis infection (LTBI). LTBI acceptance depends on population-wide TB knowledge and low stigma, but limited data are available the relationship between stigma knowledge. We assessed disease throughout Brazil examined their association incidence. Methods performed a nationwide survey multi-stage probability design through AmericasBarometer from April–May 2017; sample was...
Background Neutrophils have been associated with lung tissue damage in many diseases, including tuberculosis (TB). Whether neutrophil count can serve as a predictor of adverse treatment outcomes is unknown. Methods We prospectively assessed 936 patients (172 HIV-seropositive) culture-confirmed pulmonary TB, enrolled multicenter prospective cohort study from different regions Brazil, June 2015 to 2019, and were followed up two years. TB had baseline visit before (month 0) visits at month 2 6...
Weight change may inform tuberculosis treatment response, but its predictive power be confounded by human immunodeficiency virus (HIV).We prospectively followed up adults with culture-confirmed, drug-susceptible, pulmonary receiving standard 4-drug therapy (isoniazid, rifampin, pyrazinamide, and ethambutol) in Brazil. We examined median weight 2 months after initiation HIV status, using quantile regression, unsuccessful outcome (treatment failure, recurrence, or death) Cox regression.Among...
Background The impact of previous SARS-CoV-2 infection on the systemic immune response during tuberculosis (TB) disease has not been explored. Methods An observational, cross-sectional cohort was established to evaluate in persons with pulmonary or without infection. Those participants were recruited an outpatient referral clinic Rio de Janeiro, Brazil. TB defined as a positive Xpert-MTB/RIF Ultra and/or culture Mycobacterium from sputum. Stored plasma used perform specific serology identify...
Therapeutic drug ranges (TDR) for standard anti-tuberculosis (TB) treatment have been determined based on expected levels at least 2 hours after taking the dose. In this study we constructed TDR TB minimizing toxicity and maximizing effectiveness.