Active clinical trials for "Tuberculosis"

The study involves use of isoniazid and cotrimoxazole as strategies for preventing infections in HIV-infected children and reducing mortality. Cotrimoxazole is well known to reduce mortality and infections in HIV-infected children and is currently the recommended standard of care. However, isoniazid has only been studied in HIV-infected adults (in whom it has been shown to substantially reduce the incidence of tuberculosis). In a randomised controlled study of isoniazid in HIV-infected children, the investigators found that INH reduced mortality and tuberculosis incidence in excess of 50%; the data safety monitoring board recommended termination of the placebo arm given the beneficial effects of INH. The investigators therefore aim to follow-up these children to compare the long term impact of two different INH and CTX preventive regimens (daily versus thrice weekly) on morbidity, mortality, adherence and incidence of adverse reactions. The investigators also aim to investigate the efficacy, safety and tolerability of INH compared with placebo for prevention of TB in children receiving HAART as the benefit in this group is unknown.

The purpose of this study is to evaluate the safety profile of an adjuvanted TB subunit vaccine administered at 0 and 2 months.

This is a three-arm, open-label individually randomised controlled clinical trial investigating the benefits of the diagnostic use of broad-spectrum antimicrobials during the diagnostic process for tuberculosis (TB) and the risk of antimicrobial resistance. Adults (≥18 years) presenting to primary care with TB symptoms will, after excluding acute illness, be randomised (1:1:1) to receiving azithromycin, amoxicillin or standard care. Diagnostic accuracy will be ascertained by comparing self-reported response to treatment on Day-8 to results of mycobacteriology tests (MTB culture, smear microscopy and Xpert/MTB/RIF). Antimicrobial resistance will be ascertained by comparing arms with respect to incidence of resistant Streptococcus pneumonia carriage cultured from nasopharyngeal swabs collected on Day-28. Clinical benefit will be ascertained by comparing clinical outcomes by Day-29.

The proposed study will randomize adults (18 years of age or older) with pulmonary MDR-TB with sputum that contains M. tuberculosis that is isoniazid and rifampin resistant by MTBDRplus and fluoroquinolone susceptible by MTBDRsl HIV seropositive (with or without antiretroviral therapy) or negative (but not unknown) and Karnofsky score of >60 at sites in Moldova, Peru, and the Philippines. Patients with MDR-TB will be randomized to oral regimen of delamanid (DLM), linezolid (LZD), levofloxacin (LFX) and pyrazinamide (PZA) for 24, 32, 40, 48 or 56 weeks or World Health Organization (WHO) standard of care MDR-TB regimen (9-month "modified Bangladesh" regimen or WHO standard MDR-TB regimen). Primary Objective 1. Determine the shortest duration of the delamanid-containing oral regimen that is non-inferior to the blended WHO standard regimen. Secondary Objective Define the safety and tolerability of the oral delamanid, linezolid, levofloxacin and pyrazinamide regimen. Determine if baseline PZA susceptibility is associated with shorter time to non-inferior treatment duration. Identify the relationship between delamanid and linezolid serum drug levels and time to sputum culture conversion among patients on the delamanid-containing oral regimen. Identify the relationship between delamanid and linezolid serum drug levels and occurrence of adverse events among patients on the delamanid-containing oral regimen.

Drug-resistance is a major challenge for tuberculosis (TB) care programs. The new WHO guideline recommends adding levofloxacin in previously treated patients with isoniazid-resistant rifampicin-susceptible TB. The investigators believe that such a retreatment regimen may result in acquired resistance to fluoroquinolone, the core drug of multidrug-resistant TB (MDR-TB) regimen, and thus threaten the effectiveness of the fluoroquinolone-based MDR-TB treatment regimen. Therefore the investigators propose to study if regimens strengthened by using high-dose first-line drugs, either a triple dose of isoniazid or a triple dose of rifampicin, are non-inferior to the WHO recommended levofloxacin-strengthened regimen. If one of both high-dose regimens would be non-inferior, it could replace the levofloxacin-strengthened regimen.

Under-diagnosis of TB in children is a critical gap to address. The INPUT study is a multinational stepped-wedge cluster-randomized intervention study aiming to assess the effect of integrating TB services into child healthcare services on TB diagnosis capacities in children under 5 years of age.

Increased health education has the potential to facilitate better use of health care services and to promote early treatment, thus it can strengthen the health care system, and ultimately reduce morbidity and mortality. In this study, we will develop and test the effect of digital health messages related to HIV, Tuberculosis (TB) and Taenia solium cysticercosis/taeniosis (TSCT) (the intervention diseases) in Migoli and Izazi (the intervention villages), in Iringa, Tanzania (TZ). The intervention is planned as follows: A digital platform, providing the intervention villages with digital health messages related to the above-mentioned diseases, will be implemented in TZ in 2019. The platform will be accessible free of charge, through own devices and tablets based in the local Wi-Fi spots in the villages. In the first part of this project, the doctoral research fellow will participate in developing the digital health messages, together with experts from the medical and teaching environments in Tanzania, Norway, Germany and USA. The second part of the PhD-project consists of a cluster non-randomised controlled trial and semi-structured interviews in Tanzania. The digital health messages will be physically shown to the participants in the intervention group. The study is planned to investigate the knowledge related to the intervention diseases, before the intervention, immediately after exposure to the intervention, and at follow-up points throughout one year, after the intervention has been implemented. Semi-structured interviews with clients (users of the intervention) from each of the intervention villages are included, to explore the perception and reception of the intervention. The baseline study and the immediate after survey will take place in Tanzania in Q1 2019, while the other follow-up studies and interviews (3, 6 and 12 months after baseline) will be undertaken throughout one year.

Background: The World Health Organization (WHO) currently recommends household contact investigation for new tuberculosis (TB) patients in low- and middle-income countries, with an emphasis on pediatric contacts. Although the aim of this policy is to find previously undetected TB patients and reduce transmission, such investigations represent a missed opportunity to start contacts without TB on preventive therapy (TPT). The WHO guidelines do not address the optimal implementation of contact investigation. The standard of care (SOC) in most settings, passive referral of pediatric contacts to the clinic by the index TB patient, has largely remained unsuccessful in practice. In 2017, the WHO estimated only 23% of eligible child contacts were started on TB preventive therapy. Household contact investigation has been shown to have a higher yield in active TB case finding, but is labor intensive, and may be challenging to implement in densely populated urban settings or informal settlements/slums. The WHO recently endorsed the use of a new TPT regimen (rifapentine and isoniazid weekly (3HP)) for both children and adults in high burden settings, and the programmatic roll out of this regimen offers the opportunity to simultaneously examine new strategies to improve the identification and treatment of pediatric TB household contacts. Objective: To compare the effectiveness of community-based versus facility-based child contact investigation and delivery of TB preventive care to inform the optimal implementation strategy for investigating pediatric household TB contacts. Study Design: Cluster-randomized trial in 32 clinics (16 clinics per arm) divided equally among South Africa and Ethiopia (8 clinics per arm per country). Methods: Newly diagnosed qualifying TB index patients (determined by South African or Ethiopian National TB guidelines) and participants' household child contacts will be recruited to participate. Local staff, including the relevant nurses and community health workers in the intervention and control clinics, will be trained to conduct contact investigation with a symptom-based approach for all child contacts under 15 years old in home and at the clinic. Data will be collected using routine medical files and then retrospectively abstracted by the research team. Thirty-two primary health clinics will be stratified (by TB case notification and by country) and randomized in 1:1 fashion to either community-based or facility-based delivery of care. Household child contacts under 15 years of age who screen negative for TB disease will be initiated on TPT by a healthcare worker (nurse, community health worker, etc.) either in the home or clinic setting. Children in the intervention arm who screen positive will first be sent to the nurse at the clinic for repeat screening. Children who have a persistently positive screen in the intervention arm and those with a positive screen in the control arm using South Africa's or Ethiopia's pediatric symptom screening tool will be referred to a physician at the district hospital for further investigation of TB disease, as is the standard of care in both settings. Investigators will compare clinic-level outcomes including proportion of household TB contacts under 15 years of age that were screened, initiated on TPT, and who completed TPT, and reasons for not completing TPT including loss to follow up and incident TB disease while on TPT.

This study aims to evaluate the utility of home-based point-of-care TB testing for early diagnosis and linkage to care of household contacts of TB patients, addressing the need for active case finding and early detection of infectious TB. The investigators propose an exploratory study to 1) investigate the acceptability and feasibility of home-based TB testing of household contacts using a new portable GeneXpert point-of-care (PoC) platform, and 2) determine the potential impact of such a home-based testing program on early detection of TB disease and linkage-to-care (LTC).

This is a phase 1 study, in healthy volunteers who have previously been immunized with bacilli Calmette Guerin (BCG), to evaluate the safety and immune responses that develop in the blood and lungs following the administration by aerosol of a new experimental adenovirus-based vaccine for tuberculosis (TB), Ad5Ag85A.