Tuberculosis

The TBnet registry is a multinational, prospective tuberculosis registry established by the Tuberculosis Network European Trialsgroup (TBnet e.V.) to collect and analyze long-term data from TB patients across Europe. Its purpose is to centralize data on TB epidemiology, prevention, diagnosis, and treatment to improve care, support research, and ultimately help eliminate TB. The registry captures risk factors, diagnostic details (e.g., microbiology, imaging, drug resistance), treatment data, side effects, outcomes, and late complications.

RIFA-REAL is a prospective observational longitudinal study evaluating the safety, feasibility, and effectiveness of rifapentine-based shorter treatment regimens for drug-susceptible tuberculosis (DS-TB) and tuberculosis infection (TBI) under routine programmatic conditions in Kazakhstan. The study enrolls three cohorts: patients with DS-TB receiving the 4-month isoniazid-rifapentine-moxifloxacin-pyrazinamide regimen (2HPMZ/2HPM), patients with DS-TB receiving the standard 6-month isoniazid-rifampicin-pyrazinamide-ethambutol regimen (2HRZE/4HR), and individuals with TBI receiving the 1-month rifapentine-isoniazid regimen (1HP). Participants include people living with and without HIV. The study is conducted across four regions of Kazakhstan and is funded through the Western-Eastern European Partnership Initiative on HIV, Viral Hepatitis and TB (WEEPI) grant. Findings will inform national TB policy and contribute to global evidence on programmatic implementation of rifapentine-based regimens.

Epstein Barr Virus (EBV) or Cytomegalovirus (CMV) infection results in significant morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients. HSCT patients often face opportunistic infections due to the immunosuppressive state during transplantation. Antimicrobial drugs are usually used for prophylactic purposes and for treatment after early detectable infections. Unfortunately, some patients develop resistance to such drug treatment. In addition to HSCT patient, immune compromised patient may also be victim to opportunistic infections. Many infections can be effectively managed by functional immune recovery. In this study, the safety and efficacy of microbial-specific cytotoxic T lymphocytes (CTLs) will be investigated.

Background: \- Tuberculosis (TB) is an infectious disease that affects numerous people worldwide. Researchers are interested in actively recruiting individuals with TB for research and treatment studies. Objectives: \- To collect blood and other samples to study the natural history of tuberculosis. Eligibility: \- Individuals 2 years of age and older who have either active or latent tuberculosis. Design: * Latent TB patients: Participants will have a single study visit with a physical examination and medical history, and will provide blood samples for testing. * Active TB patients: Participants will have an initial visit with a physical examination and medical history, and will provide blood samples for testing. Participants will also provide sputum samples if required, and may have an optional skin punch biopsy to collect a sample of skin tissue for study. * Treatment for active TB will be provided as part of this protocol. * Active TB participants may be asked to return for study visits every 1-2 months while receiving treatment....

Current tuberculosis (TB) treatment is effective (works well), but it takes a long time to cure TB. This study will evaluate if TB treatment with a higher dose of rifampicin, one of the TB medicines, and shorter TB treatment duration is as effective and safe as the standard, TB treatment (with the usual rifampicin dose and usual duration). This study hopes to find a better shorter treatment that works as well as the current treatment (standard of care). This could benefit children worldwide who are getting TB treatment. Children 3 months to less than 10 years of age who have drug-susceptible TB (can be successfully treated with standard TB medicines) are eligible for this study.

The A5414 study will evaluate whether treatment for drug-susceptible pulmonary tuberculosis (TB) can be tailored according to a participant's risk of an unfavorable outcome. Participants will be assigned to lower-risk or higher-risk groups using baseline characteristics and then randomized within each group to receive either standard TB treatment or an investigational rifapentine- and moxifloxacin-containing regimen. The study will evaluate whether shorter treatment durations may be used in lower-risk participants and whether the investigational regimen may improve outcomes in higher-risk participants. Safety and tolerability will also be evaluated.

This study aims to find the proposed dose of Rifapentine (RPT) taken once daily with Isoniazid (INH) for 28 days to prevent tuberculosis (TB). The study will take place at multiple locations and children under 13 years old will be divided into two groups: one group will include children without HIV, and the other group will include children with HIV who are on antiretroviral treatment. Up to 144 children will participate, and participants in each group will be followed for 24 weeks.

The French Tuberculosis Cohort is a prospective, national, multicenter, low-intervention study including subjects aged 18 years and older with tuberculosis disease for which inpatient treatment is initiated. The goal of this observational study is to follow-up and anti-tuberculosis treatment will be provided according to current French recommendations. Participants will provide sociodemographic, clinical, biological, radiological and bacteriological data at various protocol visits at 2 days, 1 and 2 weeks, 2 months, at the end of treatment, 12 and 24 months. Consenting participants will have samples collected at scheduled visits for the establishment of a biobank. This will include blood, urine, breath and hair samples. The positive mycobacterial strains will constitute a specimen bank.

A Phase I, Double-Blind, Randomized, Placebo Controlled Trial to Evaluate Safety and Immunogenicity of Lipovaxin Tuberculosis Vaccine (Bio Farma) in Healthy Populations Aged 18-40 Years in Indonesia

Tuberculosis (TB) is a global pandemic that despite successful treatment and bacterial eradication can cause chronic ill health, such as pulmonary impairment after tuberculosis (PIAT) and cardiovascular disease (CVD). A recent Phase 2b double-blind randomised-controlled clinical trial shows that adjunctive doxycycline therapy is safe, accelerates resolution of inflammation, suppresses tissue damaging enzyme activity and decreases pulmonary cavity volume (1). We aim to determine if adjunctive doxycycline can reduce PIAT and improve cardiovascular outcomes in a fully powered Phase III trial of 8 weeks of adjunctive doxycycline alongside standard pulmonary TB (PTB) treatment. The investigators hypothesize that doxycycline inhibits tissue destruction in patients with PTB and thereby leads to improved lung function after treatment. Specific aims 1. To assess improvement in lung function as measured by forced expiratory volume (FEV1) predicted in PTB patients given doxycycline versus placebo. 2. To investigate whether doxycycline will hasten the resolution of pulmonary cavities measured by CT thorax 3. To investigate whether doxycycline can suppress inflammatory markers including matrix metalloproteinases 4. To investigate whether doxycycline can accelerate time to sputum conversion 5. To evaluate the effect of doxycycline on cardiovascular outcomes such as the incidence of acute coronary syndrome (ACS) and pulmonary hypertension 6. To investigate whether doxycycline improves TB drug concentrations in sputum and plasma. 7. To assess the safety profile of doxycycline with concurrent standard anti-tuberculous treatment.

This study, titled "Effect of Mycobacterial Infection on Immune Status" (EMIIS), investigates the immune-driven mechanisms of mycobacterial infections, focusing on the dynamic immune characteristics of multidrug-resistant tuberculosis (MDR-TB), nontuberculous mycobacterial (NTM) infections, and tuberculous pleurisy. Mycobacterial infections (including the Mycobacterium tuberculosis complex and nontuberculous mycobacteria) remain a major global public health threat. EMIIS is a single-center, randomized, single-blind,prospective study. The study recruited 120 participants, divided into groups of healthy individuals/community-acquired pneumonia patients, active pulmonary tuberculosis patients, latent tuberculosis infection patients, tuberculous pleurisy patients, and nontuberculous mycobacteria patients. Blood samples were collected from all groups within 3 days before treatment and 2-3 months after treatment. Pleural effusion samples were additionally collected from the tuberculous pleurisy group within 3 days before treatment and 2 months after treatment. Exhaled breath condensate (EBC) was collected from the nontuberculous mycobacteria group. Utilizing mass cytometry (CyTOF) and multi-dimensional indicators, the study aims to elucidate the immune-driven mechanisms of mycobacterial infections and provide new strategies for individualized treatment.

Sepsis, a life-threatening condition due to a dysregulated response to infection, is the leading cause of global mortality and is frequently driven by tuberculosis (TB) and drug-resistant bacteria in sub-Saharan Africa, particularly among people living with HIV. The prevailing standard of care in the region, ceftriaxone alone, is insufficient as it does not address TB, drug-resistant bacteria, or adrenal insufficiency, which is common in HIV-related sepsis. Therefore, the investigators propose a randomized 2x2 factorial clinical trial to compare 28-day survival from sepsis between study participants who along with a standard of care that includes immediate conventional anti-TB treatment receive 1) hydrocortisone to treat septic shock and 2) rifampin, isoniazid, levofloxacin and linezolid to treat TB and other drug-resistant bacteria in order to deliver important and scalable knowledge that may alter the standard of care for sepsis in HIV endemic settings of sub-Saharan Africa. Improving understanding of the physiology and treatment alternatives for HIV related critical illness globally will have reciprocal benefit for health in the U.S.

While drug-susceptible tuberculosis (TB) disease in children currently requires four to six months of treatment, most children may be able to be cured with a shorter treatment of more powerful drugs. Shorter treatment may be easier for children to tolerate and finish as well as ease caregiver strain from managing treatment side effects and supporting children over many months. The primary objective of this study is to evaluate if a 2-month regimen (including isoniazid (H), rifapentine (P), pyrazinamide (Z) and moxifloxacin (M)) is as safe and effective as a 4- to 6-month regimen (isoniazid, rifampicin (R), pyrazinamide, ethambutol (E)) in curing drug-susceptible TB disease in children under 10 years old. The study is also evaluating the safety of the HPZM in children with and without HIV.

Public understanding of tuberculosis (TB) is shaped by sociocultural norms, educational background, and personal experiences. Misconceptions about TB transmission, disease severity, and treatment side effects are widespread, contributing to stigma and fear of social rejection. Such stigma can lead individuals to conceal their diagnosis, limiting access to support, engagement with healthcare, and overall health literacy. TB-related stigma is recognised as a significant barrier to ending the global TB epidemic, affecting quality of life and access to care. Yet in high-income, low-incidence (HILI) countries like the UK, its prevalence, influence, and lived impact remain largely unexplored. Where stigma appears in research, it is often treated as an emerging theme, leaving a critical gap in understanding how individuals with TB, or those caring or supporting them, experience and respond to it. This study adopts a Constructivist Grounded Theory (CGT) approach to examine TB-related stigma in depth. CGT allows the research to explore how people living with TB make sense of, interpret, negotiate, and resist stigma, capturing the dynamic and contextual ways it shapes their lives, identities, and interactions with healthcare systems. By investigating these meaning-making processes, the study aims to illuminate how stigma operates in the UK, providing insights to inform future stigma-reduction interventions, communication strategies, and supportive healthcare practices, ultimately benefiting patients, communities, and the NHS.

To reduce the burden of TB worldwide through more accurate, faster, simpler, and less expensive diagnosis of TB Every year, more than 3 million people with TB remain undiagnosed and 1 million die. Better diagnostics are essential to reducing the enormous burden of TB worldwide. The Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) brings together experts in TB care, technology assessment, diagnostics development, laboratory medicine, epidemiology, health economics and mathematical modeling with highly experienced clinical study sites in 10 countries.

TB is the single biggest infectious cause of death (1.5 million died in 2018), killing more HIV-positive people than any other disease, and is arguably the most important poverty-related disease in the world. TB's estimated incidence in Africa has been declining over recent years but progress is slow and plateauing. To avert stagnation, truly innovative and ambitious technologies are needed, especially those that improve case finding and time-to-diagnosis as, in mathematical models based on the TB care cascade framework, interventions that accomplish this will have the most impact on disrupting population-level transmission, including when deployed at facilities where patients are readily accessible. Critically, these interventions (triage tests) must promote access to confirmatory testing (e.g., Xpert MTB/RIF Ultra) by enabling patients to be referred rapidly and efficiently during the same visit. The investigators will optimise and evaluate a technology that, aside from the investigators early case-controlled study to show feasibility, is hitherto not meaningfully investigated for TB. This gap is alarming given, on one hand, the enormity of the TB epidemic and the need for a triage test and, on the other hand, promising proofs-of-concept that demonstrate high diagnostic accuracy of cough audio classifier for respiratory diseases such as pneumonia, asthma. pertussis, croup, and COPD. In some cases, these classification systems are CE-marked, awaiting FDA-approval, and subject to late-stage clinical trials. This demonstrates the promise of the underlying technological principle. CAGE-TB's innovation is further enhanced by: applying advanced machine learning methods that the team have specifically developed for TB patient cough audio analysis, use of mixed methods research - drawing from health economics, implementation science, and medical anthropology - to inform product design and assess barriers and facilitators to implementation, and uniquely for a TB diagnostic test, its potential deployment as a pure mHealth (smartphone-based) innovation that mitigates many barriers that typically jeopardise TPP criteria fulfilment.

Background: Most people with tuberculosis (TB) feel better after starting treatment. But for some people, the opposite happens. They may feel better at first, but then suddenly get worse. This is a paradoxical reaction. Researchers want to better understand what causes this reaction and what happens after someone has it. Objective: To learn about paradoxical reactions to TB treatment. Eligibility: Adults 18 and older diagnosed with confirmed or suspected TB and currently on treatment for at least 2 weeks, with or without signs/symptoms of a paradoxical inflammatory reaction. Design: Participants will be screened with a physical exam and medical history. They will give blood and urine samples. Eligible participants will visit either the NIH Clinical Center or the Mexico Clinic sites 3 times over 6 to 18 months. Each visit will take 7 hours to complete; visits may be scheduled over more than 1 day. Participants may have more visits if their TB symptoms change. Participants will give blood, urine, and sputum samples. They will have adverse event assessments. They will have 2 to 3 positron emission tomography/computed tomography (PET/CT) scans. PET/CT scans make pictures of the inside of the body. For this, participants will lie on a table that slides into a donut-shaped scanner. They will get a small amount of radioactive dye through an IV, which is a small plastic tube placed in a vein in the arm using a needle. Participants may have optional apheresis at the NIH site only. For this, blood is taken from a needle in one arm. White blood cells are separated from the rest of the blood. The rest of the blood is returned through a needle in the other arm.

The incidence of tuberculosis has decreased over the last 2 years on the national territory (6.4/100,000 inhabitants) but remains twice as high in Ile de France where it is increasing with an increase of almost 10% in the number of cases. reported between 2015 and 2017 . the notification rate of tuberculosis disease for the year 2020 was 14.3 cases per 100,000 inhabitants (i.e. 1757 cases declared) which is more than double that found at the national level . As the disease is multifocal, patients are likely to be hospitalized in different departments with variable care and compliance support offered. One of the major issues is compliance with treatment. Indeed, INVS data (2008-2014) report a percentage of treatment completed in pulmonary tuberculosis of 73% . Among these cases, 20% had a potentially unfavorable outcome, including 45% lost to follow-up, which creates a risk of relapse and contagiousness for those around them. The latest data reported in 2022 over the period 2014-2018 seem to show an increase in treatment completeness but completeness remains variable from one region to another and from one year to another Using Public Health France data, the investigator were able to collect the proportion of completeness of treatment at Saint Antoine hospital, which is 60% over the period 2014-2016 (Public Health France, unpublished data). In more recent work carried out within the department retrospectively between 2019-2021, the investigator compared treatment outcomes depending on whether or not patients benefit from ETP support and it is 66% among patients without it. benefited, thus confirming the data from Public Health France over a more recent period.. In this context, several other studies have shown the interest of a therapeutic education program on the completeness of the treatment.

Tuberculosis (TB) is one of the leading causes of infectious disease worldwide. The diagnosis of TB typically relies on microbiological evidence of the presence of Mycobacterium tuberculosis (MTB) or histological features of the host immune response to MTB in the infected organs. The diagnosis can be enhanced by performing molecular diagnostic tests (e.g. polymerase chain reaction, PCR) on the clinical specimens obtained. Expectorated sputum is usually the first sample sent for MTB culture for suspected pulmonary TB (PTB), which is the most common type of TB. However, this can be particularly challenging for paediatric patients and elderly patients with poor coughing techniques or effort. While for extrapulmonary TB (EPTB), which contributes to 10-20% of TB cases, with TB pleuritis and lymphadenitis as the most common types, invasive investigations are usually required for obtaining clinical specimens of good quality for MTB culture or histological examination. The invasiveness of procedures (e.g. pleural biopsy, lymph node biopsy) and inadequate sensitivity of diagnostic tests could hinder the diagnosis of EPTB. The long turnaround time of MTB culture also creates a challenge for timely diagnosis. Blood sampling for MTB culture or PCR, although non-invasive, has low diagnostic yields. All these urges for non-invasive, rapid and accurate diagnosis of TB. The standard duration of TB treatment is 6 months, with a longer duration up to 12 months required for certain types of EPTB or in patients with underlying comorbidities (e.g. diabetes mellitus). Treatment monitoring and surveillance for relapses are typically based on a composite of clinical symptoms, sputum MTB culture status, and radiographical appearance. All these domains have their drawbacks, including subjective reporting (clinical symptoms), long turnaround times (sputum MTB culture status), and a lack of diagnostic sensitivity (changes in radiographical appearance in PTB). These clinical unmet needs may be overcome if a non-invasive molecular test could accurately quantify the burden of MTB in the body. Recently, it was reported that the level of MTB cfDNA in plasma can be measured by the CRISPR-TB assay. However, the data were derived mainly from the paediatric patient group and did not evaluate the possibility of latent TB infection (LTBI). This new technology remains explorative at the moment. Our group has developed a metagenomic sequencing-based assay for measuring the level of MTB cell-free DNA (cfDNA) in plasma. We hypothesize that this new plasma MTB cfDNA assay has the potential to diagnose active TB disease, treatment monitoring and surveillance monitoring by serially measuring the MTB cfDNA level in the plasma. Similar technology may also be applicable to urine, which requires prospective validation.

This study is a non-randomized observation and comparison of immune response between bacteriologically confirmed TB patients under treatment cohort who received COVID-19 vaccine (n=54) vs healthy individuals (n=54). Each participant will receive single or double doses of one of COVID-19 vaccines (Pfizer-BioNTech COVID-19 vaccine, AstraZeneca vaccine or Janssen Ad26.COV2.S COVID-19 vaccine) in the deltoid muscle of the non-dominant arm. Study Duration approximately 1 year. The main focus of this study is to compare the humoral and cellular immunological responses of the COVID-19 vaccines between bacteriologically confirmed TB patients under treatment vs healthy individuals. This study is funded by the Wellcome Trust. The grant reference number is 220211/A/20/Z.

The purpose of this study is to integrate elements from existing interventions developed by our team into a single intervention (QUIT-AD), designed to improve smoking cessation and favorable HIV/TB treatment outcomes among individuals with HIV and/or TB in Cape Town, South Africa. If feasibility, acceptability, and preliminary efficacy are demonstrated, the intervention will be ready for large-scale effectiveness/implementation testing. This program will has the potential to dramatically improve public health by increasing the smoking quit rate and facilitating favorable HIV/TB treatment outcomes among patients with HIV and/or TB in resource limited South African settings.

The Decide-TB project aims to generate evidence for the implementation of a comprehensive Treatment Decision Algorithms (TDA) based approach for TB in children living in high TB burden and resource-limited countries, at District Hospital (DH) and Primary Health Centre (PHC) levels, and to facilitate the integration of this evidence within practices and policies. This programmatic pilot led by the National TB Programs (NTP) will test a TDA-based approach integrating TB screening, diagnosis, treatment decision-making, and disease severity assessment for shorter treatment eligibility, for use at a lower level of healthcare. This TDA-based approach will be evaluated in a hybrid effectiveness implementation study based on a pragmatic stepped wedge cluster-randomized trial. The Decide TB project will be implemented at the district level, targeting five districts in each country. Each cluster in a district will be made up of one district hospital and six primary health centers. The study will develop a Clinical Decision Support System (CDSS) to operationalize the use of TDAs, and strengthen District Health Information Systems (DHIS2) to collect individual data, which will contribute to monitoring and evaluation, clinical mentoring, and supervision by the country's NTPs.

Despite being a curable and preventable disease, tuberculosis still represents a major global health problem. It is estimated that 10.8 million people contracted tuberculosis in 2023, with an incidence of 134 per 100,000 inhabitants. In 2023, there were 1.25 million deaths, confirming this disease as a leading cause of death and the leading cause of death from a single infectious agent. It is a disease that primarily affects adults in their most productive years, with significant repercussions on family budgets. The aim of this study is to identify and characterize the demographic, epidemiological, microbiological, clinical, and radiological variables of the tuberculosis population that has come to our hospital's attention, as an exemplary population in a low-endemic setting. This study also aims to develop a tuberculosis risk score aimed at early differentiation between patients requiring respiratory isolation and those with negligible tuberculosis risk, and to improve diagnostic accuracy.

This cluster-randomized trial in Uganda will evaluate the effectiveness and implementation of a novel, peer-led TB education and counseling strategy to improve outcomes among persons with tuberculosis (TB) with and without HIV/AIDS and assess the social-behavioral mechanisms underlying the observed treatment effects.

The study design will be a randomized controlled trial. The data will be collected from Gulab Devi Teaching Hospital, Lahore. 34 kids aged 8 to 14 years will be randomly assigned either to an experimental group or a control group. The intervention group includes the active Cycle of Breathing technique with balloon-blowing therapy for 3 days. The control group includes the active cycle of breathing technique. Sputum secretion will be measured by 'sputum measurement cups." Dyspnea will be measured by the "Modified Borg dyspne Scale," and functional capacity will be measured by the "6-Minute Walk Test." Data will be analyzed through SPSS version 25.0.