Active clinical trials for "Tuberculosis"

Effective tuberculosis (TB) control requires that people who progress from latent Mycobacterium tuberculosis (MTB) infection (LTBI) to TB disease are identified and treated before they infect others. A prognostic correlate of risk (COR), based on messenger ribonucleic acid (mRNA) expression signatures, which prospectively discriminates between TB cases and healthy controls, has been constructed and validated. Based on published microarray case-control datasets, the COR has 87% diagnostic sensitivity and 97% specificity for prevalent TB disease; and in two nested case-control studies, 70% prognostic sensitivity and 84% specificity for incident TB disease occurring within one year of sampling (HIV uninfected persons). Diagnostic and prognostic performance of the COR has not yet been tested in a prospective cohort. COR+ status is not directly associated with LTBI; and may, or may not, be amenable to preventive therapy. Although effective in the short-term, preventive therapy is not recommended for treatment of LTBI in HIV uninfected adults living in high TB burden countries, due to rapid loss of protection; and treatment burden. A 3-month, 12-dose, once-weekly preventive therapy regimen of high dose Isoniazid (INH) and Rifapentine (3HP) has been recommended as equivalent to 6 months of daily INH for treatment of LTBI in low TB burden countries by the World Health Organization (WHO). A 'screen & treat' strategy, based on serial mass campaigns to provide targeted, short-course preventive therapy only to COR+ persons at highest risk of TB disease, may offer the solution for durable, community-wide protection in high TB burden countries. The efficacy of 3HP for prevention of incident TB disease in COR+ persons has not yet been tested in a clinical trial. Primary Aims Test whether preventive therapy (3HP) reduces the rate of incident TB disease, compared to standard of care (active surveillance), in COR+ persons. Test whether COR status differentiates persons with cumulative prevalent or incident TB disease from persons without TB disease. Secondary Aims Estimate whether COR status differentiates persons at high risk for incident TB disease from persons at low risk for incident TB disease Compare prognostic performance of the COR for incident TB disease with Interferon-gamma release assay (IGRA).

A parallel-group prospective cohort study among adult persons living with HIV/AIDS to study the effect of a new TB diagnostic test, Xpert MTB/RIF on: 1) TB case detection; 2) time to TB diagnosis and TB treatment; 3) presumptive TB patient drop-out from the TB diagnostic "cascade" before starting TB treatment; and 4) loss to follow-up after initiation of TB treatment.

Infection with Mycobacterium tuberculosis remains at epidemic levels globally. Innate and adaptive immune responses evolve as protective mechanisms against mycobacterial infection in humans. Toll-like receptors (TLRs) are transmembrane proteins characterized by an extracellular leucine-rich domain that participates in ligand recognition and an intracellular tail. TLRs are the first defense system to detect potential pathogens, initiate immune responses and form the crucial link between innate and adaptive immune systems. Stimulation of TLR initiates a signaling cascade that involves a number of proteins, such as MyD88 and IL-1 receptor-associated kinase. This signal cascade leads to NF-κB activation, which induce the secretion of pro-inflammatory cytokines. TLR2 is a family of TLR family and has been reported to be the principle mediator of macrophage activation in response to mycobacterium. Growing amounts of data suggest that the ability of certain individuals to respond properly to TLR ligands may be impaired by single nucleotide polymorphisms (SNPs) within TLR genes, resulting in an altered susceptibility to, or course of, infectious disease. The genetic polymorphism of TLR2 (arginine to glutamine substitution at residue 753 (Arg753Gln)) has been associated with a negative influence on TLR2 function, which may, in turn, determine the innate host response to mycobacteria. In addition, another polymorphism (Arg677Trp) of the TLR2 was reported to be associated with susceptibility to tuberculosis in Tunisian patients. Moreover, in Mycobacterium leprosy patients with TLR2 mutation (Arg677Trp), production of IL-2, IL-12, IFN-gamma, and TNF-alpha by M. leprae-stimulated peripheral blood mononuclear cell were decreased compared with that in groups with wild-type TLR2. To date, there have been no studies of the association of SNPs of TLR2 with cytokine profiles and clinical outcomes on M. tuberculosis. We hypothesize that polymorphisms in the TLR2 are associated with : increased prevalence of active pulmonary TB infection, altered levels of pro-inflammatory and anti-inflammatory cytokines in serum, clinical outcomes and presentations. We thus design a prospective case-control study to test this hypothesis. The frequency of TLR2 polymorphisms in both pulmonary TB patients and healthy controls will be determined by polymerase chain reaction-restriction fragment length polymorphism. Serial serum levels of IL-12, IFN-γ, and IL-10 in pulmonary TB patients with or without TLR2 polymorphisms will be measured by enzyme linked immunosorbent assay. Relationships between TLR2 polymorphisms and serum cytokines dynamics or clinical outcomes will be analyzed.

The purpose of this study is to evaluate plasma levels of hepatotoxic anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide plus significant metabolites) among patients on antituberculosis treatment (ATT) and compare the same among those who develop drug induced hepatitis on follow up versus those who do not.

The purpose of this study is to gain a better understanding of how immunity to tuberculosis (TB) is maintained in children. When children get tuberculosis, it is more likely to spread to other parts of the body than when adults get it. This study will compare the blood cells that fight TB in children to the blood cells that fight TB in adults. Children enrolled in this study will have blood drawn on 1 or 2 occasions. Adult participants will be leukapheresed, a process in which blood passes through a machine collecting specific blood cells and returning the remaining blood to the body. An estimated 260 subjects will be enrolled in this study.

TB-Speed SAM is a multicentric, prospective diagnostic cohort study conducted in three countries with high and very high TB incidence (Sierra Leone, Uganda, and Zambia). It aims at assessing several diagnostic tests that could result in the development of a score and algorithm for TB treatment decision in hospitalised children with severe acute malnutrition (SAM).

Maternal infections affect the basal immune status of neonates. One of the possible mechanism is the fetomaternal microchimerism, in which some cells and active substances are exchanged bi-directionally between maternal and fetal circulation through placenta. Even in the absence of a direct (vertical) transmission of pathogens to fetuses, certain infections make the neonates more prone to allergies and some adverse events of early vaccinations. We postulate that the basal immune status of neonates born to HIV and LTBI infected mothers is primed by gestational exposure to immunological active molecules, which could results in an altered response to early BCG vaccination. Transcripts expression identified by RNA sequencing are compared between sets of mother-child and their respective umbilical cord blood, and between groups of infected and non-infected pairs.

This qualitative study is designed to elicit the perspectives of relevant stakeholders to adapt a community-based TB/HIV intervention aimed on providing home-based TB prevention treatment (TPT) initiation for child TB contacts, to design its implementation strategy and, post intervention, to assess lessons learned for future scale up. Participants will include policy makers and health system managers, nurse and physician providers, community health team members, and child caregivers of TB-exposed children. Stakeholders will be asked to participate in two interviews, one prior to the cluster randomized trial assessing this intervention and one after the cluster randomized trial. Trained interviewers will conduct 1-hour semi-structured in-depth interviews that will be audio-recorded, translated and transcribed for thematic analysis using a priori and emergent domains of interest. Free-listing, ranking exercises and cultural consensus will be used to identify context-specific intervention adaptations and implementation strategies.

Introduction: childhood tuberculosis continues to be a major public health problem, despite the fact that the visibility of the epidemic in this population group has increased, studies are still lacking that can resolve the gaps that persist. Objective: To design, implement and evaluate an integrated care strategy for children under five years old household contacts of patients with smear positive pulmonary tuberculosis in Medellín and the Metropolitan Area. Methodology: quasi-experimental study, in which around 300 children household contacts of patients with smear positive pulmonary tuberculosis from Medellín and the Metropolitan Area will be evaluated, who will be recruited in a period of one year. A subgroup of these children, estimated at 85, who require treatment for latent tuberculosis, will be offered to receive treatment for latent tuberculosis under a integrated care strategy that includes some modifications to the currently standardized scheme in Colombia, with rifampicin treatment daily oral route for four months, follow-up under the project scheme with the availability of a nurse, general practitioner, specialists, care by professionals from other disciplines such as social work, psychology, and nutritionist, and the provision of incentives (transport and food assistance). This strategy will be compared with isoniazid treatment according to the standardized scheme in the country, which was received by a cohort of children between 2015 and 2018. The study has the CIB Research Ethics Committee approval. Expected results: this project is expected to contribute with greater local evidence of integrated care strategies that allow greater compliance with treatment for latent tuberculosis in children, so that there is a real impact in the control of childhood tuberculosis and in the reduction of tuberculosis reservoirs in order to achieve the goals proposed by the World Health Organization's End TB Strategy.

The emergence and spread of multi-drug resistant and extensively-drug resistant strains of Mycobacterium tuberculosis (MDR/XDR-TB) have posed a great threat to global TB control and elimination, limiting treatment success rate at worrisome 50% for MDR-TB. Among various factors contributing to the development of drug resistance, low drug exposure is well recognized. To overcome this, either new drugs have to be developed or the dose of currently used therapy be optimized, or both. Fluoroquinolones (levofloxacin and moxifloxacin) and aminoglycosides are important drugs in the MDR-TB treatment regimen. Development of acquired drug resistance to these drugs could complicate and narrow down the available options, and further exacerbate to pre-XDR and XDR-TB. Objective: The main objective of this prospective clinical study is to understand the pharmacokinetics of levofloxacin in MDR-TB patients, receiving standard dosage (750-1250mg) based on the body weight and correlate drug exposure, with treatment outcomes. Study design: A prospective pharmacokinetic study Study population: 20 MDR-TB patients Intervention: Patients receive once daily oral dosing of levofloxacin (750-1250mg) based on the body weight, under MDR-TB treatment regimen of Nepal. Main study parameters/end points: The pharmacokinetic parameters(Vd, CL, AUC etc.) of levofloxacin are the primary end points of the study. The Cmax/MIC and AUC0-24h/MIC ratios are the best predictive parameters for efficacy of levofloxacin treatment and will be estimated. Pharmacokinetics will be evaluated in plasma and in oral fluid