Clinical Research Directory

Mycobacterial and Opportunistic Infections in HIV-Negative Thai and Taiwanese Patients Associated With Autoantibodies to Interferon-gamma

Opportunistic infections are caused by bacteria, mycobacteria, fungi or viruses that do not normally cause infections in people with healthy immune systems. Some of these infections can cause public health concerns, especially in areas with limited access to treatment. People who acquire opportunistic infections usually have diseases that affect their immune systems, such as human immunodeficiency virus (HIV), or do not have enough white blood cells to fight the infection. However, some people acquire opportunistic infections even though they have normal amounts of white blood cells and are free from known diseases that harm their immune systems. This study will investigate some of the reasons that otherwise healthy people get opportunistic infections to learn more about why some people are more likely to have them. This study will include up to 210 HIV-negative males and females older than 18 years of age who have opportunistic infections. The patients will be drawn from multiple sites in Thailand and Taiwan including Khon Kaen University Hospital, Siriraj Hospital, Ramathibodi Hospital, National Taiwan University Hospital, National Cheng-Kung University Hospital Patients will undergo an initial evaluation that will include a physical examination, medical history, and blood and urine testing. Additional tests will be conducted if the researchers consider that the tests are medically necessary to treat the opportunistic infection; the results of the tests will be reviewed and saved for study purposes. Depending on the severity of the infection, the initial evaluation may take more than 1 day to complete. After the evaluation, patients will be given standard and appropriate medicines to treat the infections. Patients will return for follow-up visits to allow researchers to monitor their condition and to assess how well the patient is responding to the treatment. Patients will be evaluated by the study researchers at least once a year for 2 years following the initial treatment.

Shortened Regimen for Drug-susceptible TB in Children

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.

Feasibility of the Application of a New Six-month Treatment for Multidrug-resistant Tuberculosis (MDR-TB) Patients in France (FAST-MDR)

The FAST-MDR trial is an externally-controlled, multicentre trial with one prospective arm, evaluating the non-inferiority of the effectiveness of BPaLM in the interventional arm versus the effectiveness of the long, conventional regimen in a French historical cohort of MDR-TB patients (2006-2022). In light of recent WHO recommendations suggesting using BPaLM as a first choice for routine MDR-TB treatment and of the expected benefits of BPaLM over the standard treatment, there will be no internal comparator arm in the study.

Blood Tuberculosis DNA Levels to Monitor Tuberculosis Treatment

Tuberculosis (TB) is a leading infectious cause of death worldwide. Current strategies for monitoring TB treatment response are culture dependent and insensitive. New methods of assessing treatment response in vivo could inform new drug development and other treatment strategies. Cell-free DNA (cfDNA) - small circulating fragments of DNA - is widely used in maternofetal medicine and oncology for diagnosis and assessment of treatment response. This study aims to investigate whether pathogen derived Mycobacterium tuberculosis-specific cfDNA (Mtb-cfDNA) can be used to monitor TB treatment response. This feasibility study will take place at Mae RaMat TB Center in Thailand and includes two study groups: 1. Assay Development and Validation 2. Longitudinal Assessment of Mtb-cfDNA levels

Evaluation of PATHFAST-LAM as a Tuberculosis Treatment Monitoring Tool in Kenya

Tuberculosis (TB) can be treated; however, the standard 6-month treatment is long and challenging for many patients, and 10-20% still don't recover well by the end of treatment. Thus, it's important to regularly check if the treatment is working to help patients get better and prevent drug-resistant TB from developing. It can, however, be especially hard to check if TB treatment is working in places with limited resources. Traditional methods, such as testing sputum samples for microscopy and culture, have limitations. Lipoarabinomannan (LAM) is a substance that is found in the cell wall of the bacteria that cause TB, which can be used as an indicator for TB diagnosis and treatment monitoring. The PATHFAST TB LAM Ag test is a fully automatic machine that checks for LAM in sputum. It could offer a faster and more accurate way to see if TB treatment is working. This study aims to find out how helpful the PATHFAST-LAM test is in monitoring TB treatment progress among Kenyan TB patients. The primary objective of this study is to assess whether changes in sputum LAM levels can help predict unfavorable results. In this study, investigators will recruit adult patients diagnosed with pulmonary TB from multiple healthcare facilities in Nairobi, Kenya. Investigators will follow them during their TB treatment and collect sputum and urine samples at the beginning of treatment, then, every week for the first month, every two weeks for the next two months, and monthly for months 3-6. Investigators will use the PATHFAST-LAM test to measure LAM levels in sputum and urine. Since there are no previous studies that have evaluated the relationship between sputum LAM and treatment outcome, investigators will do an initial analysis with 30 participants, and based on that, investigators will determine the final number of participants needed for our study. It is expected that sputum LAM decreases when the treatment is successful and remains positive (does not decrease) when treatment is unsuccessful, with patients experiencing unfavorable results. How LAM decreases during the earlier course of TB treatment may be useful in predicting patients' outcomes. The results of this study could provide a faster and effective way for monitoring TB treatment. This could contribute to improved patient outcomes and help reduce the global burden of TB.

Diagnosis of Tuberculosis in Swiss Children

1. The primary objective is to improve the sensitivity of novel immunodiagnostic tests for detection of TB disease in children. 2. The secondary objective is to determine biomarkers that discriminate children with TB infection and disease.

Characteristics and Outcomes of TB and HIV Co-infections

People Living with HIV (PLHIV) are prone to several opportunistic infections depending on the degree of immunosuppression as well as infections prevalent in their geographic area/country. These include a wide variety of mycobacterial diseases, fungal infections, bacterial pneumonias, pneumocystis jirovecii pneumonia, cryptococcal infections, toxoplasmosis etc. Tuberculosis remains the most common opportunistic infection in the developing countries like South Africa and India. HIV and tuberculosis (TB) are two of the most challenging infections faced by the humanity. HIV is the most important risk factor for progression of latent Mycobacterium tuberculosis (MTB) to active disease. The most common cause of death among PLHIV is tuberculosis. These two infections place immense burden on health care systems worldwide. During the last two decades, sustained research and public health initiatives on prevention and therapeutic advances have allayed morbidity and mortality due to HIV and TB to a large extent, however more needs to be done. Globally, an estimated 10 million people fell ill with TB and an estimated 1.4 million people died of TB in 2018 (1.2 million among HIV negative and 251 000 among HIV positive people). There were around 37.9 million PLHIV worldwide in 2018. In the pre-antiretroviral therapy (ART) era, nearly one-third of HIV/AIDS (acquired immune deficiency syndrome) related deaths were due to TB. Wider availability of ART has reduced the mortality of HIV-associated TB significantly, but it still remains high compared to HIV-uninfected individuals. The mortality risk with HIV TB coinfection accounts for approximately 25% of global HIV/AIDS deaths every year. This study aims to investigate characteristics and outcomes of TB and HIV co-infections in Upper Egypt.

New Strategies for Assessment of the Persistence of Viable Bacilli in Latent and Active Tuberculosis

Current diagnostic tools such as interferon gamma release assay (IGRA) and purified protein derivative (PPD) can not distinguish patients with latent tuberculosis infection (LTBI) and persistence of live mycobacteria. This inability to rule out living mycobacteria in patients investigated for LTBI leads to unnecessary and potentially harmful treatment regimes all around the globe. The goal of this observational study is to identify candidate biomarkers for viable bacilli in latent tuberculosis in order to decrease the use of unnecessary and ineffective antibiotic treatment.