Digital Commons Network^™

Parallel Use Of Low-Complexity Automated Nucleic Acid Amplification Tests And Lateral Flow Urine Lipoarabinomannan Assays To Detect Tuberculosis Disease In Adults And Adolescents Living With Hiv, Stephanie Bjerrum, Bada Yang, Johanna Åhsberg, Ruvandhi R Nathavitharana, Laura Olbrich, Devan Jaganath, Alexander W Kay, Andreas Lundh, Maunank Shah

Faculty, Staff and Students Publications

This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To compare the diagnostic accuracy of parallel use of lateral flow urine lipoarabinomannan on urine and low-complexity automated nucleic acid amplification tests on respiratory samples versus each test alone for detection of tuberculosis disease in adults and adolescents living with HIV who present with presumptive tuberculosis. Secondary objectives To investigate the following sources of heterogeneity: clinical setting; signs and symptoms of tuberculosis; screening positivity for tuberculosis disease by chest x-ray, C-reactive protein elevation, and molecular World Health Organization-recommended rapid diagnostics; seriously ill; advanced HIV; and CD4 …

Performance Of A Stool-Based Quantitative Pcr Assay For The Diagnosis Of Tuberculosis In Adolescents And Adults: A Multinational, Prospective Diagnostic Accuracy Study, Alexander Kay, Anca Vasiliu, Lucia Carratala-Castro, Bariki Mtafya, Jose Euberto Mendez Reyes, Nontobeko Maphalala, Shilzia Munguambe, Durbbin Mulengwa, Tara Ness, Belen Saavedra, Jason Bacha, Gugu Maphalala, Rojelio Mejia, Godwin Mtetwa, Sozinho Acacio, Patricia Manjate, Edson Mambuque, Nosisa Shiba, Nokwanda Kota, Mangaliso Ziyane, Nyanda Elias Ntinginya, Christoph Lange, H Lester Kirchner, Andrew R Dinardo, Alberto L Garcia-Basteiro, Anna Maria Mandalakas, Stool4tb Global Partnership

Faculty, Staff and Students Publications

BACKGROUND: Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens.

METHODS: We undertook a prospective diagnostic accuracy study in Eswatini, Mozambique, and Tanzania from Sept 21, 2020, to Feb 2, 2023, to compare the diagnostic accuracy for tuberculosis of a novel stool qPCR …

Modeling The Transmission Dynamics Of Tuberculosis In Humans, Farida Kisinda, Joshua A. Mwasunda, Mbwiga S. Aloni

Tanzania Journal of Science

Tuberculosis (TB) is a major threat to human health particularly in most of developing countries. In this article, we formulate and analyze a deterministic model for the transmission dynamics of pulmonary and extra-pulmonary tuberculosis. The next generation method is employed to find the basic reproduction number which helps to determine whether TB clears or persists in the human population. Global stability of model equilibria is done through Lyapunov functions whereas the normalized forward sensitivity index method is adopted to determine parameters that drive tuberculosis. Analysis shows that both TB free and endemic equilibria exist. The TB free equilibrium is globally …

Chronic Pneumonia In A 1-Year-Old Male, Saritha Beauchamp, Irene Chern, Emily Souder

Tower Health Research Day

No abstract provided.

Lung Type 3 Innate Lymphoid Cells Respond Early Following Mycobacterium Tuberculosis Infection, Shibali Das, Kuldeep Singh Chauhan, Mushtaq Ahmed, Sadia Akter, Lan Lu, Marco Colonna, Shabaana A Khader

2020-Current year OA Pubs

UNLABELLED: Tuberculosis is the leading cause of death due to an infectious disease worldwide. Innate lymphoid type 3 cells (ILC3s) mediate early protection during

IMPORTANCE: Tuberculosis is a leading cause of death due to a single infectious agent accounting for 1.6 million deaths each year. In our study, we determined the role of type 3 innate lymphoid cells in early immune events necessary for achieving protection during

A Protective Role For Type I Interferon Signaling Following Infection With Mycobacterium Tuberculosis Carrying The Rifampicin Drug Resistance-Conferring Rpob Mutation H445y, Suhas Bobba, Kuldeep S. Chauhan, Sadia Akter, Shibali Das, Ekansh Mittal, Barun Mathema, Jennifer A. Philips, Shabaana A. Khader

2020-Current year OA Pubs

Interleukin-1 (IL-1) signaling is essential for controlling virulent Mycobacterium tuberculosis (Mtb) infection since antagonism of this pathway leads to exacerbated pathology and increased susceptibility. In contrast, the triggering of type I interferon (IFN) signaling is associated with the progression of tuberculosis (TB) disease and linked with negative regulation of IL-1 signaling. However, mice lacking IL-1 signaling can control Mtb infection if infected with an Mtb strain carrying the rifampin-resistance conferring mutation H445Y in its RNA polymerase β subunit (rpoB-H445Y Mtb). The mechanisms that govern protection in the absence of IL-1 signaling during rpoB-H445Y Mtb infection are unknown. In this study, …

The Use Of Comics As A Tuberculosis Learning Medium For Junior High School Students, Budi Utomo, Widati Fatmaningrum, Sulistiawati, Shifa Fauziyah, Teguh Hari Sucipto, Chan Chow Khuen

Folia Medica Indonesiana

Highlights: 1. Comics centered around tuberculosis offer a novel method tailored for specific audiences, specifically children or those of school age, to learn about the disease. 2. The tuberculosis comics feature the etiology, prevention, and treatment of tuberculosis conveyed through their unique design. 3. Comics can be an innovative promotional method to support the preventive campaign against tuberculosis. Abstract As a tropical country, Indonesia continues to grapple with the prevalence of tuberculosis. This study conducted by the Department of Public Health and Preventive Medicine at Universitas Airlangga, Surabaya, Indonesia, presented a novel approach to prevent tuberculosis through measures tailored to …

Bacteriophage Therapy For The Treatment Of Mycobacterium Tuberculosis Infections In Humanized Mice, Fan Yang, Alireza Labani-Motlagh, Jose Alejandro Bohorquez, Josimar Dornelas Moreira, And Additional Authors

School of Medicine Faculty Publications and Presentations

The continuing emergence of new strains of antibiotic-resistant bacteria has renewed interest in phage therapy, however, there has been limited progress in applying phage therapy to multi-drug resistant Mycobacterium tuberculosis (Mtb) infections. In this study, we show that bacteriophage strains D29 and DS6A can efficiently lyse Mtb H37Rv in 7H10 agar plates. However, only phage DS6A efficiently kills H37Rv in liquid culture and in Mtb-infected human primary macrophages. We further show in subsequent experiments that, after the humanized mice were infected with aerosolized H37Rv, then treated with DS6A intravenously, the DS6A treated mice showed increased body weight and improved pulmonary …

Tuberculosis In People Of Ukrainian Origin In The European Union And The European Economic Area, 2019 To 2022, Krista Stoycheva, Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Dominik Zenner, Anca Vasiliu, Marieke Van Der Werf, Christoph Lange

Faculty, Staff and Students Publications

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission.

Tuberculosis In People Of Ukrainian Origin In The European Union And The European Economic Area, 2019 To 2022, Krista Stoycheva, Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Dominik Zenner, Anca Vasiliu, Marieke Van Der Werf, Christoph Lange

Faculty, Staff and Students Publications

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission.

Immunostimulatory Short Non-Coding Rnas In The Circulation Of Patients With Tuberculosis Infection, Justin Gumas, Takuya Kawamura, Megumi Shigematsu, Yohei Kirino

Computational Medicine Center Faculty Papers

Mycobacterium tuberculosis (Mtb) infection is among the world's deadliest infectious diseases. Developing effective treatments and biomarkers for tuberculosis requires a deeper understanding of its pathobiology and host responses. Here, we report a comprehensive characterization of circulating short non-coding RNAs (sncRNAs) in plasma samples from Mtb-infected patients. We achieved this by pre-treating plasma RNAs with T4 polynucleotide kinase to convert all RNA ends to those compatible with sncRNA sequencing. We discovered a global and drastic upregulation of plasma sncRNAs in Mtb-infected patients, with tRNA-derived sncRNAs representing the most dramatically elevated class. Most of these tRNA-derived sncRNAs originated from a limited subset …

A Stool Based Qpcr For The Diagnosis Of Tb In Children And People Living With Hiv In Uganda, Eswatini And Mozambique (Stool4tb): A Protocol For A Multicenter Diagnostic Evaluation, Lucia Carratala-Castro, Willy Ssengooba, Alex Kay, Sozinho Acácio, Joanna Ehrlich, Andrew R Dinardo, Nosisa Shiba, Joachim K Nsubuga, Shilzia Munguambe, Belén Saavedra-Cervera, Patricia Manjate, Durbbin Mulengwa, Busizwe Sibandze, Mangaliso Ziyane, George Kasule, Edson Mambuque, Moorine Penninah Sekadde, Eric Wobudeya, Moses L Joloba, Jan Heyckendorf, Christoph Lange, Sabine Hermans, Anna Mandalakas, Alberto L García-Basteiro, Elisa Lopez-Varela, Stool4tb Global Partnership

Faculty, Staff and Students Publications

BACKGROUND: Tuberculosis (TB) is a major cause of mortality worldwide. Children and people living with HIV (PLHIV) have an increased risk of mortality, particularly in the absence of rapid diagnosis. The main challenges of diagnosing TB in these populations are due to the unspecific and paucibacillary disease presentation and the difficulty of obtaining respiratory samples. Thus, novel diagnostic strategies, based on non-respiratory specimens could improve clinical decision making and TB outcomes in high burden TB settings. We propose a multi-country, prospective diagnostic evaluation study with a nested longitudinal cohort evaluation to assess the performance of a new stool-based qPCR, developed …

Proteome Analysis For Inflammation Related To Acute And Convalescent Infection, Tara K Sigdel, Swastika Sur, Patrick Boada, Suzanne M Mcdermott, Cecilia S Lindestam Arlehamn, Kristy O Murray, Linda K Bockenstedt, Maggie Kerwin, Elaine F Reed, Eva Harris, Ken Stuart, Bjoern Peters, Ana Sesma, Ruth R Montgomery, Minnie M Sarwal

Faculty, Staff and Students Publications

Infectious diseases are a significant burden in global healthcare. Pathogens engage with different host defense mechanisms. However, it is currently unknown if there are disease-specific immune signatures and/or if different pathogens elicit common immune-associated molecular entities to common therapeutic interventions. We studied patients enrolled through the Human Immunology Project Consortium (HIPC), which focuses on immune responses to various infections. Blood samples were collected and analyzed from patients during infection and follow-up time points at the convalescent stage. The study included samples from patients with Lyme disease (LD), tuberculosis (TB), malaria (MLA), dengue virus (DENV), and West Nile virus (WNV), as …

Bayesian Survival Analysis Of Recovery For Tuberculosis Patients In Bulsa Traditional Area, Joseph Akanliksiuk Akan-Nyaatemi, Dioggban Jakperik, Mathias Akamba

Journal of Statistics Applications & Probability

Tuberculosis (TB) is a contagious infection that affect the lungs and caused majorly by a bacterium known as Mycobacterium tuberculosis. The study sought to discover factors that influence recovery of patients using Bayesian Continuous-Time Survival model and the Log-logistic model. The factors that were seen to be linked to treatment outcome are; Age, treatment time, smear results and HIV. It was further realized that, age, HIV and their interactions were significant determinants of TB treatment outcomes in the Bulsa traditional area. The recoveries for males and females were 79.32%, and 87.32% respectively. Also, the recovery for children(100%), adults(81.28%), and aged …

Pharmacokinetic-Pharmacodynamic Evidence From A Phase 3 Trial To Support Flat-Dosing Of Rifampicin For Tuberculosis, Huy X. Ngo, Ava Y. Xu, Gustavo E. Velásquez, Nan Zhang, Vincent K. Chang, Ekaterina V. Kurbatova, William C. Whitworth, Erin Sizemore, Kia Bryant, Wendy Carr, Marc Weiner, Kelly E. Dooley, Melissa Engle, Susan E. Dorman, Payam Nahid, Susan Swindells, Richard E. Chaisson, Pheona Nsubuga, Madeleine Lourens, Rodney Dawson, Radojka M. Savic

Journal Articles: Infectious Diseases

BACKGROUND: The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes.

METHODS: We analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months; TB-related unfavorable outcomes at 9, 12, and 18 months using …

Human Inborn Errors Of Immunity: Tuberculosis, Autoimmunity, And Beyond, Masato Ogishi

Student Theses and Dissertations

Tuberculosis (TB), a multi-organ infectious disease caused by virulent mycobacteria, most predominantly M. tuberculosis, remains one of the deadliest infectious diseases in human history. Bacillus Calmette-Guérin (BCG) vaccine, first implemented medically in 1921, has remained the only available vaccine for TB, although its protective effect is moderate. TB occurs in 5-10% of individuals exposed to those pathogens, while 90-95% remain asymptomatic (i.e.,latent infection or spontaneous clearance). This surprisingly large inter-individual variability has long attracted the attention of human geneticists. Classical twin-based genetic studies have demonstrated the presence of a substantial genetic risk of developing TB disease between monozygotic twins. Later, …

Prevalence Of Non-Communicable Diseases Among Household Contacts Of People With Tuberculosis: A Systematic Review And Individual Participant Data Meta-Analysis, Yohhei Hamada, Matteo Quartagno, Farihah Malik, Keolebogile Ntshamane, Anna Tisler, Sanjay Gaikwad, Carlos Acuna-Villaorduna, Perumal Kannabiran Bhavani, Bachti Alisjahbana, Katharina Ronacher, Lika Apriani, Mercedes Becerra, Alexander L. Chu, Jacob Creswell, Gustavo Diaz, Beatriz E. Ferro, Jerome T. Galea, Louis Grandjean, Harleen M. Grewal, Amita Gupta, Edward C. Jones-López, Léanie Kleynhans, Leonid Lecca, Peter Macpherson, Megan Murray, Diana Marín, Blanca I. Restrepo, Shri Vijay Shivakumar, Eileen Shu, Dhanasekaran Sivakumaran, Luan Nguyen Vo, Emily L. Webb, Andrew Copas, Ibrahim Abubakar, Molebogeng X. Rangaka

Social Work Faculty Publications

Objective: To investigate the prevalence of non-communicable diseases among household contacts of people with tuberculosis.

Methods: We conducted a systematic review and individual participant data meta-analysis. We searched Medline, Embase and the Global Index Medicus from inception to 16 May 2023. We included studies that assessed for at least one non-communicable disease among household contacts of people with clinical tuberculosis. We estimated the non-communicable disease prevalence through mixed effects logistic regression for studies providing individual participant data, and compared it with estimates from aggregated data meta-analyses. Furthermore, we compared age and sex-standardised non-communicable disease prevalence with national-level estimates standardised for …

A Quality-By-Design Approach For The Development Of Inhalable Dry Powders For Tuberculosis (Tb) Treatment, Suyash M. Patil

Theses and Dissertations

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains a pressing concern globally. The emergence of drug-resistant strains and the need for prolonged treatment regimens continue to complicate disease management. Innovative therapeutic strategies are urgently required to enhance treatment efficacy, improve patient adherence, and minimize adverse effects. Toward this, strategies involving use of drug combinations, reducing dosing frequencies, and targeting TB-infected cells are gaining attention. In my dissertation, we explored the combination therapy involving two FDA-approved anti-TB drugs, Bedaquiline (BDQ) and Pretomanid (PTD). The BDQ-PTD combination reduced minimum inhibitory concentration (MIC), compared to individual drugs and demonstrated additive/synergistic effects at 1:4 …

Formulation Development And Characterization Of Isoniazid-Pyridoxine Combination Gummies Using An Extrusion-Based 3d Printer, Aditi Rajendra Holkunde

Electronic Theses and Dissertations

This study aimed to formulate and evaluate Isoniazid-Pyridoxine-loaded gummies for use in a population ranging from pediatric to geriatric and to study the applicability of BIO X 3D printer in printing gummy formulations. Semisolid extrusion (SSE) 3D printing is an emerging technology in personalized medicine. To address clinical multi-dose requirements, SSE has been explored to manufacture new preparations. In this study, Isoniazid (INH) and Pyridoxine Hydrochloride (PDX) were used to make gummy formulations for use in the treatment of Tuberculosis. A suitable semisolid mixture for SSE was prepared and incorporated into the BIO X 3D printer for extrusion-based 3D printing …

Risk-Stratified Treatment For Drug-Susceptible Pulmonary Tuberculosis., Vincent K. Chang, Marjorie Z. Imperial, Patrick P. J. Phillips, Gustavo E. Velásquez, Payam Nahid, Andrew Vernon, Ekaterina V. Kurbatova, Susan Swindells, Richard E. Chaisson, Susan E. Dorman, John L. Johnson, Marc Weiner, Amina Jindani, Thomas Harrison, Erin E. Sizemore, William Whitworth, Wendy Carr, Kia E. Bryant, Deron Burton, Kelly E. Dooley, Melissa Engle, Pheona Nsubuga, Andreas H. Diacon, Nguyen Viet Nhung, Rodney Dawson, Radojka M. Savic, Aids Clinical Trial Group, Tuberculosis Trials Consortium

Journal Articles: Infectious Diseases

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, …

Pyrazinamide Safety, Efficacy, And Dosing For Treating Drug-Susceptible Pulmonary Tuberculosis: A Phase 3, Randomized Controlled Clinical Trial, Ava Y. Xu, Gustavo E. Velásquez, Nan Zhang, Vincent K. Chang, Patrick P. J. Phillips, Payam Nahid, Susan E. Dorman, Ekaterina V. Kurbatova, William C. Whitworth, Erin Sizemore, Kia Bryant, Wendy Carr, Nicole E. Brown, Melissa L. Engle, Nguyen Viet Nhung, Pheona Nsubuga, Andreas Diacon, Kelly E. Dooley, Richard E. Chaisson, Susan Swindells, Radojka M. Savic

Journal Articles: Infectious Diseases

Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/AIDS Clinical Trials Group A5349 represents the largest phase 3 randomized controlled therapeutic trial to date for such an investigation. Objectives: We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure and efficacy and safety outcomes. We aimed to determine pyrazinamide dosing strategies that optimize risks and benefits. Methods: We analyzed pyrazinamide steady-state pharmacokinetic data using population nonlinear mixed-effects models. We evaluated the contribution of pyrazinamide exposure to long-term efficacy using parametric time-to-event models and safety …

Examining Factors Associated With Covid-19 Disruptions To Tuberculosis Services, Tejaswini Dharmapuri Vachaspathi

Public Health Theses

Background: The COVID-19 pandemic posed unprecedented challenges to global health systems, significantly impacting the delivery of essential health services, including tuberculosis (TB) care. It is important to analyze the factors associated with the reductions in TB notifications during the pandemic, with a focus on high TB burden countries, to inform strategies for making TB programs more resilient to health system shocks.

Methods: Amongst 98 selected high-burden countries, a GLM analysis was employed to examine the association between ‘missed’ TB case notifications from 2020 to 2021, and various country-level factors including: COVID-19 mortality estimates, lockdown stringency index, GDP per capita, health …

Epidemiology And Antimicrobial Resistance Of Mycobacterium Spp. In The United Arab Emirates: A Retrospective Analysis Of 12 Years Of National Antimicrobial Resistance Surveillance Data, Jens Thomsen, Najiba M. Abdulrazzaq, Najiba M. Abdulrazzaq, Peter S. Nyasulu, Farida Al Hosani, Maya Habous, Stefan Weber, Fouzia Jabeen, Godfred Antony Menezes, Carole Ayoub Moubareck, Abiola Senok, Dean B. Everett, Adnan Alatoom, Agnes-Sonnevend-Pal, Ahmed Abdulkareem Al Hammadi, Ahmed Elhag Ahmed, Ahmed F. Yousef, Alaa M.M. Enshasy, Amal Mubarak Madhi, Amna Alblooshi, Andreas Podbielski, Anju Nabi, Anup Shashikant Poddar, Arun Kumar Jha, Ayesha Abdulla Al Marzooqi, Bashir Aden, Dean Everett, Deeba Jafri

All Works

Introduction: The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global Mycobacterium tuberculosis (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in the United Arab Emirates (UAE) to 204 per 100,000 in Djibouti. The national surveillance data from the Middle East and North Africa (MENA) region on the epidemiology and antimicrobial resistance trends of TB, including MDR-TB remains scarce. Methods: A retrospective 12-year analysis of N = 8,086 non-duplicate diagnostic Mycobacterium tuberculosis complex (MTB complex) isolates from the UAE was conducted. Data were generated through routine patient care during the 2010–2021 …

Ribosome Hibernation Factor Induces Antibiotic Persisters Of Mycobacterium Tuberculosis In Neutrophil-Rich Lung Lesions, Jamie Corro

Electronic Theses & Dissertations (2024 - present)

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is a prescient global health threat and the leading cause of death by an infectious agent. Treatment of Mtb infection involves administering 2-4 antibiotics for a minimum of 6 months. This extended drug regimen is required to target a subpopulation of persistent bacilli. As their name implies, these bacteria can “persist” by acquiring nonhereditary and transient antibiotic tolerance. Although the precise mechanism is unknown, it’s often attributed to slowing cellular growth and metabolic processes. During zinc deprivation, bacteria can remodel their ribosomes by replacing their zinc-binding paralogues containing the CXXC motif (C+) …

A Transcriptomic Biomarker Predicting Linezolid-Associated Neuropathy During Treatment Of Drug-Resistant Tuberculosis, Nika Zielinski, Dragos Baiceanu, Antonela Dragomir, Jan Heyckendorf, Elmira Ibraim, Niklas Köhler, Christoph Leschczyk, Cristina Popa, Andrea Rachow, Jens Sachsenweger, Patricia Sanchez Carballo, Dagmar Schaub, Hajo Zeeb, Begna Tulu, Andrew R Dinardo, Christoph Lange, Maja Reimann

Faculty, Staff and Students Publications

BACKGROUND: Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation.

OBJECTIVE: We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy.

METHODS: Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was …

Distinct Gene Expression Signatures Comparing Latent Tuberculosis Infection With Different Routes Of Bacillus Calmette-Guérin Vaccination, Richard F Silver, Mei Xia, Chad E Storer, Jessica R Jarvela, Michelle C Moyer, Azra Blazevic, David A Stoeckel, Erin K Rakey, Jan M Tennant, Johannes B Goll, Richard D Head, Daniel F Hoft

2020-Current year OA Pubs

Tuberculosis remains an international health threat partly because of limited protection from pulmonary tuberculosis provided by standard intradermal vaccination with Bacillus of Calmette and Guérin (BCG); this may reflect the inability of intradermal vaccination to optimally induce pulmonary immunity. In contrast, respiratory Mycobacterium tuberculosis infection usually results in the immune-mediated bacillary containment of latent tuberculosis infection (LTBI). Here we present RNA-Seq-based assessments of systemic and pulmonary immune cells from LTBI participants and recipients of intradermal and oral BCG. LTBI individuals uniquely display ongoing immune activation and robust CD4 T cell recall responses in blood and lung. Intradermal BCG is associated …

Safety And Immunogenicity Of An In Vivo Muscle Electroporation Delivery System For Dna-Hsp65 Tuberculosis Vaccine In Cynomolgus Monkeys, Monique Ribeiro De Lima, Ana C. Leandro, Andreia Lamoglia De Souza, Marcio Mantuano Barradas, Eric Henrique Roma, Ana Teresa Gomes Fernandes, Gabrielle Galdino-Silva, Joyce Katiuccia M. Ramos Carvalho, Renato Sergio Marchevsky, John L. Vandeberg

School of Medicine Publications

A Bacille Calmette–Guérin (BCG) is still the only licensed vaccine for the prevention of tuberculosis, providing limited protection against Mycobacterium tuberculosis infection in adulthood. New advances in the delivery of DNA vaccines by electroporation have been made in the past decade. We evaluated the safety and immunogenicity of the DNA-hsp65 vaccine administered by intramuscular electroporation (EP) in cynomolgus macaques. Animals received three doses of DNA-hsp65 at 30-day intervals. We demonstrated that intramuscular electroporated DNA-hsp65 vaccine immunization of cynomolgus macaques was safe, and there were no vaccine-related effects on hematological, renal, or hepatic profiles, compared to the pre-vaccination parameters. No tuberculin …

Targeting Metabolic Switches And Dna Damage Repair For The Treatment Of Human Diseases, Rasangi Chathurika Kankanam Pathirage

Theses & Dissertations

Tuberculosis and Cancer treatments share common challenges due to prolonged therapy, the necessity of combination therapy and severe side effects. Characterization of novel drug targets and identification of new drugs modulating such targets within the context of multidrug treatments will contribute to overcoming current therapeutic challenges.

Tuberculosis (TB) is one of the challenging diseases to treat due to the persistence of Mycobacterium tuberculosis (Mtb) in the dormant phase. Current TB drugs are more effective toward actively dividing bacteria and less effective toward dormant bacteria. The metabolic transition between actively dividing bacteria and dormant bacteria is driven by pivotal metabolic enzymes …

Feasibility, Enablers And Challenges Of Using Timeliness Metrics For Household Contact Tracing And Tb Preventive Therapy In Pakistan, Bushra Jamil, Divya Nair, Pruthu Thekkur, Neelofar Laeeq, Anum Adil, Mohammed Khogali, Rony Zachariah, Selma Dar Berger, Srinath Satyanarayana, Ajay M V Kumar

Department of Medicine

Introduction: Screening household contacts of TB patients and providing TB preventive therapy (TPT) is a key intervention to end the TB epidemic. Global and timely implementation of TPT in household contacts, however, is dismal. We adapted the 7-1-7 timeliness metric designed to evaluate and respond to infectious disease outbreaks or pandemics, and assessed the feasibility, enablers and challenges of implementing this metric for screening and management of household contacts of index patients with bacteriologically-confirmed pulmonary TB in Karachi city, Pakistan.
Methods: We conducted an explanatory mixed methods study with a quantitative component (cohort design) followed by a qualitative component (descriptive …

Synthesis And Characterization Of Pyrazine-Based Prodrugs: A Novel Approach To Combat Multi-Drug Resistant Tuberculosis, Charles Chambers

Chemistry & Biochemistry Theses - Archive

Synthesis and Characterization of Pyrazine-Based Prodrugs: A Novel Approach to Combat Multi-Drug Resistant Tuberculosis Charles Cole Chambers The University of Texas – Arlington, 2023 Supervising Professor: Dr. Joseph Buonomo. The work described in this thesis investigates the development and characterization of a novel prodrug designed to combat multi-drug resistant tuberculosis (MDR-TB), a significant and growing global health challenge. Central to this study is the synthesis of a pyrazine-based prodrug, which innovatively utilizes bicyclic orthoester (BOE) moieties to improve the therapeutic efficacy and safety profile of this tuberculosis treatment. At the core of this research project is the strategic design of …