Clinical Research Directory

Isoniazid-Related Hepatotoxicity in Clinical Practice: Incidence and Predictors

The objective of this observational study is to determine how frequently isoniazid (INH) causes liver injury (hepatotoxicity) in adults treated for tuberculosis (TB) or latent tuberculosis infection (LTBI) and to understand which factors increase this risk. The study also aims to describe how hepatotoxicity is managed in real-world clinical practice and whether treatments such as corticosteroids can improve liver function tests. The main questions this study aims to answer are: * How frequently does INH-induced hepatotoxicity occur in adults treated for TB or LTBI? * What demographic, clinical, microbiological, or lifestyle factors increase the risk of developing hepatotoxicity? * How do different management strategies, including treatment modification or the use of corticosteroids, affect liver recovery and completion of TB/LTBI therapy? This study does not involve experimental treatments. Researchers will analyze information already collected during routine clinical care, both retrospectively (from 2020 to 2025) and prospectively (2026-2028). There is no comparison group, but participants may have different clinical profiles or treatments, which will be compared to understand risk factors and outcomes. Participants will: * Receive standard treatment for tuberculosis or LTBI, including isoniazid, as prescribed by their treating physicians. * Undergo routine assessments, such as blood tests, microbiology, imaging, and clinic visits, as part of their regular care. * Their clinical data will be recorded in the study database to analyze liver function trends, treatment changes, and outcomes. The study will contribute to improving understanding of INH-induced hepatotoxicity and supporting safer and more effective treatment strategies for tuberculosis and LTBI.

Evaluation of a Novel Microbiological Diagnostic Test for Latent Mycobacterium Tuberculosis Infection

Tuberculosis (TB) is an infectious disease that is caused by bacteria (bugs). The infection is passed on when a patient with active lung TB coughs bugs into the air, which are then breathed in by an uninfected person. In 90% of people who get infected, the TB infection remains dormant and the person never falls ill with active TB disease. However, 10% of people with dormant TB infection will eventually go on to develop active TB disease at some time in the future, with symptoms such as cough and weight loss. Dormant TB infection can be treated with a 3-month course of antibiotics, which prevent the infection from becoming active and causing problems in the future. However, existing tests for dormant TB rely on detecting the body's immune response to infection, rather than detecting the TB bugs themselves. Because the immune response doesn't go away when dormant TB is treated, existing tests for dormant TB do not change from positive to negative after antibiotic treatment. Thus, clinicians can't know if antibiotic treatment of dormant TB infection was successful or not. Moreover, existing tests can't distinguish the 90% of people with dormant TB infection who will never develop active TB (and who don't need antibiotics) from the 10% who will go on to fall ill with active TB at some point in the future (who do need antibiotics). So the investigators end up giving antibiotics to many more people than we need to. Recently, a group of scientists in Germany have developed a sensitive new blood test that was able to detect very small numbers of TB bugs in the blood of just seven people with dormant TB infection. This finding has created a lot of excitement in the TB field, as nobody has been able to find TB bugs in people with dormant infection before. Our research study will evaluate this new blood test in a larger group of 100 people, with and without dormant TB infection, to see if the findings from Germany are really true. If they are, then this could lead to the development of a more accurate test for dormant TB infection in the future.

Burden of Tuberculosis Among Pregnant and Postpartum Women in Guinea-Bissau

This study aims to address critical diagnostic and data gaps in tuberculosis (TB) care among pregnant and postpartum women in Guinea-Bissau, a high-burden, resource-limited setting. Recognising that current TB screening during antenatal care (ANC) relies largely on unstructured symptom questions, the study will integrate more systematic and innovative approaches into routine maternal health services. The project will implement the Bandim TBscore II as a structured triage tool to classify symptom severity and guide referrals. To strengthen diagnostic capacity, two novel tools will be evaluated: stool-based GeneXpert testing (a method recommended in children and explored here as a feasible alternative for pregnant women) and artificial intelligence-powered chest X-ray interpretation software designed to enhance TB detection where radiological expertise is lacking. The study will also generate comprehensive, population-based data on TB and TB infection (TBI) among pregnant, postpartum women and women of reproductive age in Guinea-Bissau. The results are intended to inform health policy, both locally and in high-income countries, by providing evidence to improve TB screening protocols and care for this vulnerable group. Ultimately, the study seeks to develop scalable strategies that can be replicated across low- and middle-income countries to advance maternal and child health and support global TB eradication efforts.

Shorter and Safer Treatment Regimens for Latent TB

Our study rationale is based on: 1. Tuberculosis Preventive Treatment (TPT) is given to healthy people and needs to be safe; 2. Tuberculosis Preventive Treatment (TPT) with shorter regimens are superior with respect to acceptance, completion, and costs; 3. 4 months of Rifampin 10mg/kg (4R10) is the safest regimen, but is completed by \<80% of patients; 4. The safety of 2 months of Rifampin 20mg/kg (2R20) is similar to that of 4 months of Rifampin 10mg/kg (4R10), but completion is a concern; 5. 1-month regimens have promising efficacy; 6. Safety and tolerability must be carefully assessed with comparisons to 4 months of Rifampin 10mg/kg (4R10), and head-to-head with each other. OBJECTIVES: The investigator will use a Bayesian adaptive Phase 2 randomized open-label trial design to test at least three experimental Tuberculosis Preventive Treatment (TPT) regimens to identify at least one regimen of ≤2 months duration that has non-inferior safety, completion, and tolerability in adults and children relative to the reference Tuberculosis Preventive Treatment (TPT) regimen. The shortest, safest, and best tolerated regimen identified in this Phase 2 trial will be tested for effectiveness and efficacy in a Phase 3 trial. Specific Tuberculosis Preventive Treatment (TPT) regimens (All are daily and self-administered) Reference: Rifampin at a dose of 10 mg/kg/day for 4 months (4R10); Experimental: 1) Rifampin at 20 mg/kg/day for 2 months (2R20); (2) one month Levofloxacin and Rifapentine (1LP). At a later stage a 3rd experimental regimen will be selected and added: one another novel 1-2-month regimen identified from pre-clinical and clinical studies. When selected, this will be explained fully including preliminary data on safety and efficacy in an amended protocol and consent - which will be submitted for ethics and regulatory approval at that time).

Window Prophylaxis for Pediatric Tuberculosis Prevention Trial

The goal of this cluster-randomized controlled trial is to evaluate the effectiveness of tuberculosis preventive treatment (TPT) administered during the "window period" to prevent new Mycobacterium tuberculosis infections in children and adolescents. The main question it aims to answer is: Can immediate TPT reduce the incidence of IGRA conversions in children and adolescents who are household contacts of a newly diagnosed pulmonary tuberculosis patient? Researchers will compare the incidence of new tuberculosis infections-measured by IGRA conversion at 12 weeks-between participants who receive immediate TPT while still uninfected (baseline IGRA-negative) and those who receive standard care, in which TPT is not offered to IGRA-negative contacts. Participants will be: 1. Tested for M. tuberculosis infection using the Interferon-Gamma Release Assay (IGRA), specifically the QuantiFERON-TB Gold Plus, at enrollment and after 12 weeks of follow-up. 2. Take weekly isoniazid and rifapentine for 12 weeks if: 1. They are assigned to the intervention arm (regardless of baseline IGRA result), or 2. They are in the control arm and test IGRA-positive at baseline. Additionally, participants from the control arm who experience an IGRA conversion at 12 weeks (following the primary outcome assessment) will also receive TPT, as per standard of care.