Active clinical trials for "Tuberculosis"

The purpose of this study is to evaluate safety and immunogenicity of Bacillus Calmette-Guerin (BCG) delivery via Novel Micronjet600 device compared to those via conventional needle.

Tuberculosis (TB) is a highly stigmatized disease, and approximately one-third of the Cambodian population living with TB are undetected. Therefore, it is vital to find these missing cases and promptly link them to care to reduce disease progression and interrupt further transmission. The integration of community-based, peer-driven intervention in TB active case finding (ACF) is relatively novel. In partnership with KHANA, the National Center for Tuberculosis and Leprosy Control (CENAT), and the Cambodia Anti-Tuberculosis Association (CATA), we will conduct a pragmatic cluster randomized controlled trial comparing 1) the ACF with the seed-and-recruit model; 2) ACF targeting household and neighborhood contacts; 3) ACF targeting the older population using mobile screening units; and 4) passive case finding (PCF) approach. The primary outcome will be the case notification rate in the intervention and control districts during the study period. We will also determine additionality, comparing the yield in each arm with its respective historical baseline and the cumulative yield over the implementation period. The secondary outcomes include the number needed to screen to detect one TB case, cost-effectiveness (direct and indirect costs per TB case notified), and the treatment outcome of all people with TB in this study. The project will be carried out over two years in eight operational districts (province name in parenthesis) - Koh Soutin (Kampong Cham), Stong (Kampong Thom), Kanchreach (Prey Veng), Choeung Prey (Kampong Cham), Dambae (Thbong Khmum), Boribo (Kampong Chhnang), Ponhea Leu (Kandal), and Phnom Srouch (Kampong Speu) - in Cambodia. The selection was also based on the number of health centers to increase comparability and generalizability of study findings. This study will randomize currently underserved operational districts (without active intervention at least in the past six months from the implementation date) to receive the interventions (ACF) and PCF as the control. The results from this proposal will enable a nationwide scale-up of an effective intervention that is contextualized and complies with the principles set by the national TB program to find undiagnosed cases and control TB in Cambodia. Also, this project will complement existing ACF programs in Cambodia by expanding ACF to other operational districts that are currently not served by the Global Fund, its implementing partners, and other organizations. Findings from this trial could also potentially inform active case finding strategies in other countries with a high TB burden.

This is a dose escalating and a paired-placebo design study to describe the safety and immunogenicity profile of candidate TB vaccine ChAdOx1 85A given by aerosol inhaled vaccination versus intramuscular (IM) vaccination in adult healthy volunteers. It is postulated that the aerosol inhaled route is practical and feasible and has an acceptable safety profile, comparable to the systemic safety profile of the IM route of administration of ChAdOx1 85A in adult healthy volunteers, and that the aerosol inhaled route of administration will induce greater mucosal immunity and comparable systemic immunity when compared to the IM (systemic) route of administration in these volunteers. Volunteers are followed on a regular basis for safety and immunogenicity, with blood analysis for biological safety tests and immune tests.

TB is a major public health problem and the second most common cause of adult death due to infection in many low-income countries. Despite major efforts to de-centralise services, accessibility to diagnosis is still limited, with one third of the 9 million cases occurring each year being missed by national control programmes. New TB diagnostics suitable for use at the point-of-care are emerging. Some of these are intended for screening purposes, as an initial step to identify individuals who may have TB and should undergo further tests for confirmation. These tests may have high sensitivity, but also give false-positive results (low specificity). Other tests aim to be the confirmatory tests for TB (high specificity), but these tests are often more expensive and complex and are only available in hospital laboratories. As these tests have different purposes, it is likely they would work better in combination in a step fashion to optimise their impact and to develop an efficient diagnostic process. Furthermore, as none of the tests is versatile enough to be used in all settings, test combinations will need to consider the health system context in which they would be used. Our aim is to develop and evaluate rapid and accurate diagnostic approaches for TB that facilitate the initiation of appropriate treatment on the same day of the initial consultation in Africa. The objectives are to Evaluate new diagnostics for TB (including among HIV co-infected individuals) that are suitable at the point-of-care; Develop diagnostic algorithms that streamline and accelerate the diagnosis of TB, allowing patients to reach clinical management decisions within a single clinic visit; Determine the impact of using novel point-of-care diagnostic combinations on the proportion of patients correctly initiating TB treatment within 24-48 hours of first attendance; their potential cost effectiveness The investigators conducted studies in 2016-2018 to accomplish the first two objectives and have identified diagnostic tests that are suitable for low and middle income countries. This document therefore refers to objective 3, which aims to Assess the performance of two diagnostic schemes for the diagnosis of TB when compared to culture. Assess the yield of two diagnostic schemes for the diagnosis of TB when compared to Xpert and Assess the cost of the two diagnostic schemes compared to Xpert.

Tuberculosis (TB) is the prototypical disease of poverty as it disproportionately affects marginalized and impoverished communities. In the US, TB rates are unacceptably high among homeless persons who have a 10-fold increase in TB incidence as compared to the general population. In California, the rate of TB is more than twice the national case rate and recent TB outbreaks have been alarming. Among persons with active TB disease, over 10% die during treatment, with mortality being even higher among homeless persons with TB. While TB can be prevented by treating TB infection (TBI) before it develops into infectious, symptomatic disease, individual factors such as high prevalence of psychosocial comorbidities, unstable housing and limited access to care have led to poor adherence and completion of TBI treatment among homeless persons. Given the complex health disparity factors that affect TBI treatment adherence among homeless persons, this study will assess the feasibility of a theoretically-based novel model of care among persons with TBI and complex chronic illnesses. This study will evaluate an innovative, community-based intervention that addresses critical individual level factors which are potential mechanisms that underlie health disparities in completing TBI treatment among the predominantly minority homeless. The study hypothesis is that improving these conditions, and promoting health by focused screening for TBI, and early detection and treatment for these vulnerable adults will improve TB treatment completion and prevent future TB disease. The proposed theoretically-based health promotion intervention focuses on: 1) completion of TBI treatment, 2) reducing substance use; 3) improving mental health; and 4) improving critical social determinants of TB risk (unstable housing and poor health care access) among homeless adults in the highest TB prevalence area in Los Angeles. A total of 76 homeless adults with TBI will receive this program which includes culturally-sensitive education, case management, and directly observed therapy (DOT) delivery of medication among patients who have been prescribed 3HP (12 weeks treatment for latent TB infection) by a medical provider. This study will determine whether this intervention can achieve higher completion rates than the 65% completion rate among homeless persons reported by previous TB programs.

This is a Phase I/IIa, double-blind, randomized, placebo-controlled, dose- and regimen-finding study in healthy adults with and without LTBI, who are BCG-vaccinated, HIV negative, and have no history or evidence of TB disease. The investigational product is AERAS-456 at 3 dose levels: 5, 15, and 50ug of H56 antigen with 500 nmol IC31. The vaccine is administered by IM injection.

The purpose of this study is to determine the safety, tolerability, and immunogenicity in BCG-vaccinated healthy adult subjects of an investigational vaccine being developed for the prevention of pulmonary tuberculosis.

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.

Tropical fevers have been a diagnostic challenge from the antiquity. Nowadays, despite the availability of good diagnostic capacities, undifferentiated febrile illnesses continue to be a thorny problem for travel physicians. In developing countries, the scarcity of skilled personnel and adequate laboratory facilities makes the differential diagnosis of fevers even more complex. Health care workers must often rely on syndrome-oriented empirical approaches to treatment and might overestimate or underestimate the likelihood of certain diseases. For instance Neglected Tropical Diseases (NTD) contribute substantially to the burden of persistent (more than 1 week) fevers in the Tropics, causing considerable mortality and major disability. These diseases are however rarely diagnosed at primary health care (PHC) level. The difficulty in establishing the cause of febrile illnesses has resulted in omission or delays in treatment, irrational prescriptions with polytherapy, increasing cost and development of drug resistance. In resource-limited settings, clinical algorithms constitute a valuable aid to health workers, as they facilitate the therapeutic decision in the absence of good laboratory capacities. There is a critical lack of appropriate diagnostic tools to guide treatment of NTDs. While clinical algorithms have been developed for some NTDs, in most cases they remain empirical. Besides, they rarely take into account local prevalence data, do not adequately represent the spectrum of patients and differential diagnosis at the primary care level and often have not been properly validated. The purpose of the study is to develop evidence-based Rapid Diagnostic Test (RDT)-supported diagnostic guidelines for patients with persistent fever (≥ 1 week) in the Democratic Republic of the Congo (DRC), Sudan, Cambodia and Nepal.

This Phase I study will be conducted as a randomized, placebo-controlled, double-blind, dose-escalation study in four groups of healthy adult male and female subjects who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection. The study will be conducted at one or two sites located in South Africa. The purpose is to evaluate the safety and immunogenicity of two injections of AERAS 404 prepared with four escalating amounts of antigen in healthy adult male and female subjects who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection.