View clinical trials related to Tuberculosis.
Filter by:The purpose of this study is to assess the safety and immunogenicity of two doses of the TB vaccine administered according to a 0, 1 month schedule. In, addition, blood samples collected at different time points after vaccination will be analysed to see when exactly genes are activated by the vaccine using an assay called mRNA expression profiling. The different methods for mRNA expression profiling using whole blood samples versus Peripheral Blood Mononuclear cell(s) (PBMCs), will also be compared.
This study is a randomized control trial assessing the impact of a simple evidence-based protocol for the treatment severe sepsis with hypotension in Zambia. This is a follow-up study to the Simplified Severe Sepsis Protocol (SSSP) study. The intervention protocol consists of a scheduled fluid regimen, early blood culture and antibiotics, and dopamine and blood transfusion when necessary. It is hypothesized that the protocol will significantly decrease in-hospital mortality in patients with severe sepsis and hypotension.
This is a cluster Tuberculosis (TB) randomized trial in which enhanced case finding (ECF) strategy will be compared to passive TB case reporting in The Gambia. And that the impact of ECF on community and household transmission of TB will also be assessed. The hypothesis is a cluster randomized trial of an enhanced case finding (ECF) strategy will increase TB case notifications in The Gambia and reduce TB burden in the study area in a cost effective manner. The impact of ECF on community and household transmission of TB will also be assessed. The investigators hope this trial will contribute to this evidence base. The timing alongside a nationwide TB prevalence survey is particularly of benefit as that would provide a baseline for disease burden against which the investigators may be able to compare case notification or case detection in selected clusters
Hypothesis That improving vitamin D status among TB patients will speed the pace of bacteriological cure, and will enhance immune responses to TB infection
Rationale: The Bacille Calmette-Guérin (BCG) vaccine protects children against disseminated tuberculosis (TB) including TB meningitis and miliary TB, but efficacy against pulmonary TB is inconsistent among children and adults. Administration of live attenuated BCG to infants known to be HIV infected is contraindicated by the World Health Organization (WHO), due to the risk of serious vaccine adverse events (BCG disease. Developing countries, which lack capacity for integration of early infant HIV testing with infant vaccination schedules, have not fully implemented the WHO guidelines on BCG vaccination of HIV exposed infants. Newborn infants of HIV infected mothers continue to receive routine BCG before HIV infection has been excluded. Clinical trials of new viral-vectored TB vaccines, including MVA85A, a modified vaccinia virus Ankara (MVA) vaccine expressing the Mycobacterium tuberculosis antigen 85A, have to date enrolled infants who were already vaccinated with routine BCG at birth. However, TB vaccination regimens that depend on newborn BCG will remain unsafe for HIV infected infants. Infants of HIV infected mothers, who constituted 29% of babies born in South Africa in 2009, would benefit from a new TB vaccination strategy, in which BCG is delayed until after HIV infection has been excluded. These HIV exposed infants also have greater increased risk of TB disease. Testing the safety and immunogenicity of MVA85A vaccine prime, followed by selective delayed BCG boost, in HIV exposed newborns, is a critical step towards delivery of a new TB vaccine regimen that is safe and effective for all infants, regardless of HIV exposure. Study Design: Double blinded, randomised, controlled trial. HIV exposed infants will be randomised 1:1 to receive single dose, intradermal MVA85A vaccine or Candin® control at birth. The first 60 infants enrolled in the trial will form a pilot safety cohort for formal Data Monitoring & Ethics Committee (DMEC) safety review. Thereafter, safety and immunogenicity outcomes will be measured in all infants. Study Population: Infants (n=340) born to HIV infected mothers receiving antiretroviral therapy (ART) or Prevention of Mother to Child Transmission (PMTCT) prophylaxis. Sites: Worcester (University of Cape Town) and Khayelitsha (Stellenbosch University), South Africa Study Intervention: Newborn infants will receive 1 x 108 pfu MVA85A vaccine or Candin® control by intradermal injection. Infants confirmed HIV uninfected by HIV PCR will receive BCG Vaccine SSI at 8 weeks of age. Infants confirmed HIV infected by HIV PCR will not receive BCG. Primary specific aims: To evaluate the safety of MVA85A given at birth to HIV exposed uninfected infants. To evaluate the safety of BCG given at 8 weeks of age to HIV exposed uninfected infants, using an MVA85A prime and BCG boost strategy. Secondary specific aims: To evaluate the immunogenicity of MVA85A given at birth to HIV exposed uninfected infants. To evaluate the immunogenicity of BCG given at 8 weeks of age to HIV exposed uninfected infants, using an MVA85A prime and BCG boost strategy. Safety endpoints: Local, regional, and systemic adverse events (AEs) and serious adverse events (SAEs). Immunology endpoints: Frequencies of CD4 and CD8 T cells producing any of 4 cytokines (IL-17, IFN-γ, TNF-α, or IL-2), or polyfunctional combinations of these cytokines simultaneously, following stimulation with antigen Ag85A or BCG, measured by whole blood intracellular cytokine assay (WB-ICS). Specific proliferative capacity of CD8 and CD4 T cells that produce any of the three cytokines (IFN-γ, TNF-α, and/or IL-2) or combinations of these cytokines simultaneously, measured by a novel whole blood 6-day lymphoproliferative flow cytometric assay (WB-prolif). Relative proportions and absolute numbers of peripheral blood myeloid and lymphoid cell subsets, measured directly ex vivo by flow cytometry. Study groups: The first 60 infants enrolled in Study Group 1 will undergo intensive safety evaluation, followed by DMEC review of Day-28 safety data. The DMEC will make a formal recommendation on continuation of enrollment and/or changes to the protocol, based on this safety review. Study Groups 2-5 will be evaluated for clinical safety and immunology outcomes. Statistical Analysis: Cumulative 12-month incidence of local, regional, and systemic AEs, by category, will be compared for HIV exposed uninfected subjects receiving MVA85A vaccine or Candin® control at birth. The sample size has 90% probability of detecting an SAE with a true occurrence rate of 1.5% in infants receiving MVA85A vaccine and 80% power to detect a 15% difference in the rate of non-serious AEs (20% compared to 35%) between the two study arms (p<0.05). Multivariate models will be built to explore longitudinal immunological data and identify independent associations with MVA85A vaccination and covariates of interest.
Tuberculosis (TB) continues to be one of the most serious bacterial infections worldwide and therefore new improved diagnostic tests are needed to help doctors in diagnosing TB. The new skin test is named C-Tb. Like the current tuberculin skin test, PPD, the C-Tb test is injected just under the skin and will, when positive, show redness and/or swelling at the injection site while a negative test will leave no reactions. The investigators hope that this new C-Tb skin test will be more precise (specific) than the PPD test, as the PPD test e.g. may show a reaction if the person tested is BCG vaccinated. The aim of this trial is to test the C-Tb skin test in volunteers suspected of having TB disease. With focus on age, HIV status and CD4 count the following analyses are done (in an overall perspective): - To compare the C-Tb test to a blood test, the QuantiFERON test. - To compare the C-Tb test to the PPD test that is currently being used. - To assess the safety of the C-Tb test.
The aims of this project are to: 1. To evaluate the pharmacokinetics of first line antituberculosis drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) when applying the 2010 WHO/IUATLD dosing guidelines across pediatric populations (0-12 years of age, HIV infected and uninfected, and with varied nutritional status) in Cape Town, South Africa and Blantyre, Malawi. 2. To evaluate an 8-hourly weight band-based dosing strategy for lopinavir/ritonavir using the commercially available lopinavir/ritonavir (4:1 ratio) in children in South Africa receiving rifampicin-based antituberculosis treatment. 3. To evaluate the pharmacokinetics of nevirapine in children in Malawi receiving rifampicin-based antituberculosis treatment.
The objective of this randomized, controlled trial is to determine if adding a protein-calorie supplement (PCS) to the standard treatments for tuberculosis (TB) and HIV will improve health outcomes. The investigators will enroll 180 HIV-positive women with newly diagnosed active TB and without prior anti-retroviral therapy (ART). At baseline, the investigators will conduct dietary interviews, measure body composition, randomize subjects to receive a PCS (plus micronutritional supplements [MNS]) or control (MNS only) for the 6-month duration of anti-TB therapy (ATT) plus an additional 2 mos (8 mos total). Subjects will be followed monthly and have CD4 counts at baseline, 2, 8 and 12 months. At 2 months (i.e., at the end of the 4 drug intensive phase of TB treatment and start of the 2 drug continuation phase), all subjects will be started on anti-retroviral therapy (ART) based on Tanzanian Ministry of Health guidelines (currently: AZT/3TC/efavirenz). The primary endpoint will be change in CD4 count after 8 months (i.e., at end of PCS/MNS intervention and 2 months after completion of ATT).
Tuberculosis (TB) continues to be the most important bacterial infection worldwide and therefore new improved diagnostic tests are needed to help doctors in diagnosing TB. We are investigating a new skin test named C-Tb. Like the current tuberculin skin test (PPD), the C-Tb test is injected just under the skin and will, when positive, show redness and/or swelling at the injection site while a negative test will leave no reactions. The aim of this trial is to test the C-Tb skin test in volunteers. The volunteers are divided into four groups: - Negative control group: Must have no history of exposure to a person with tuberculosis disease. - Occasional contact: Must be in contact with a person with tuberculosis disease between 6 hours/week and 6 hours/day - Close contact: Must be in close contact with a person with tuberculosis disease for more than 6 hours/day for at least five days - Positive control group: Must have a confirmed tuberculosis disease within the last 3 years. The goals of this clinical trial are: - To compare the C-Tb test to a blood test, the QuantiFERON test. - To compare the C-Tb test to the PPD test that is currently being used. - To assess the safety of the C-Tb test.
This is a prospective cohort study of persons tested for latent tuberculosis infection at either high risk for exposure to Mycobacterium tuberculosis or high risk for progression to tuberculosis disease. The study will assess the relative performance and cost of three diagnostic tests for latent tuberculosis infection (tuberculin skin test, QuantiFERON-TB Gold In-Tube, and T-SPOT.TB) and will examine the rates of positive results among the cohort. This study will also determine the risk and rate of progression to active TB disease, overall and by the results of the three tests.