Childhood TB Sequel
TuberculosisPulmonaryThis study aims to describe the long-term adverse outcomes associated with PTB in children, to describe the evolution of these sequelae, and to determine the epidemiological risk factors associated with these sequelae. The investigators will conduct a prospective cohort study. Children who have completed treatment for PTB will be enrolled. The study visit will be performed in the study clinic, where clinical assessment, spirometry and radiography will be performed. The planned duration of the study is 36 months. Participant enrolment is estimated to begin in March 2022. The estimated date of the last participant enrolled is December 2022.
Evaluation of Point-of-care Ultrasound in Children From 6 Months to 15 Years With Presumptive Tuberculosis...
TuberculosisDiagnosis of tuberculosis (TB) in children is particularly challenging in low and middle-income countries (LMIC), and a high number of children remain undiagnosed and untreated. A delay in diagnosis can lead to an increase in preventable morbidity and mortality. Point-of-care ultrasound (POCUS) is a bedside, non-invasive, inexpensive imaging tool, and TB-focused POCUS has been used and validated for adults with HIV. This study aims to describe the TB-focused POCUS findings for children with presumptive TB aged between 6 months and 15 years old, and to stratify the results per HIV, nutritional status and age. This is a Médecins Sans Frontières (MSF) multicentric study which takes place in Guinea Bissau and South Sudan.
Screening for Tuberculosis in Pregnancy
Latent TuberculosisThe UK has the second highest tuberculosis (TB) incidence in Western Europe. Most active cases occur in migrants due to reactivation of latent TB infection (LTBI) acquired abroad. Screening migrants for LTBI was recently introduced by Public Health England to reduce TB rates and transmission of infectious cases. Newham, which has one of the highest TB rates in London introduced the first large-scale LTBI screening programme for migrants, but it is poorly accessed by pregnant women and screening uptake is low. The issue of how best to screen for TB during pregnancy is important because pregnant/ postpartum women are at particularly high risk of developing TB, and migrants from countries with high TB rates may only interact with healthcare services during pregnancy. Effective strategies are urgently needed to improve screening uptake for LTBI in pregnant migrants. The Antenatal clinic is an attractive location to screen for LTBI because uptake and acceptability of opt-out screening for other infectious diseases (HIV) is high. We will evaluate the uptake, effectiveness and acceptability of routine screening for LTBI in antenatal clinics. Eligible patients are pregnant women who have entered the UK within 10 years from a country with TB rates of >150/100,000. Screening will involve a blood test, taken with other routine antenatal blood tests. We expect that in this setting, screening will be acceptable and uptake will be high. Our main outcome will be to assess the uptake of screening in at least 200 women. Acceptability of screening and understanding barriers of healthcare professionals to test for LTBI are secondary aims. The study will provide important information about a new setting in which to screen pregnant migrants for LTBI and barriers to starting treatment postpartum, which will inform the definitive trial to guide national policy on LTBI screening in antenatal care.
Treatment Shortening of Drug-Sensitive Pulmonary Tuberculosis Using High Dose Rifampicin (Hi-DoRi-3)...
TuberculosisPulmonaryThe purpose of this study is to investigate the effectiveness and safety of the regimen including high dose rifampicin for individualized duration (3 months after Culture Conversion) for the treatment of drug-sensitive pulmonary tuberculosis.
Evaluation of the Efficacy and Safety of a 4-month Daily Regimen (2HZPM/2HPM) for Treatment of Pulmonary...
TuberculosisPulmonaryThe development of efficacious, safe, and shorter treatment regimens could significantly improve TB management and treatment success rates. This prospective, 3-year, single arm study is to evaluate the efficacy and safety of a short-course, 4-month regimen including isoniazid(H), pyrazinamide(P), rifapentine (P), and moxifloxacin(M) (2HZPM/2HPM) for the treatment of drug-susceptible, pulmonary tuberculosis, and compared with a historical control group receiving the standard six-month regimen.
Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drugs During Pregnancy and Postpartum...
HIV InfectionsTuberculosisThe purpose of this study is to evaluate the pharmacokinetic (PK) properties of antiretroviral (ARV) and anti-tuberculosis (TB) drugs administered during pregnancy and postpartum.
Simplified Isoniazid Preventive Therapy Strategy to Reduce TB Burden
TuberculosisHIV/AIDSThe overall objective of this study is to determine if a multi-component implementation intervention (SPIRIT) and additional leadership and management training that targets District Health Officers (DHOs) can increase IPT initiation among HIV-infected persons, as compared to country standard practices, in a cluster randomized trial in Uganda.
Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis
TuberculosisThis study is based on the hypothesis that the pharmacokinetics of anti-tuberculosis drugs in TB children are different from adults. The investigators aim to study the population pharmacokinetics of children receiving the anti-tuberculsis drugs for treatment of TB. In this study, the investigators will detect drug concentration in plasma by using residual blood samples of blood gas analysis and other clinical tests and employ computers for constructing population pharmacokinetic models. In addition, the investigators also want to correlate use of anti-tuberculsis drugs with treatment effectiveness and incidence of adverse effects in children. This novel knowledge will allow better and more rational approaches to the treatment of TB in children. It will also set the foundation for further studies to improve anti-tuberculosis drug therapies for children.
Kharituwe TB Contact Tracing Study
TuberculosisHivThe purpose of this study is to characterize the role of human mobility in fueling TB epidemics and estimate the potential impact of innovative case finding interventions tailored to mobile populations
Evaluation of New Biomarker-based Approaches for Improving the Diagnosis of Childhood Tuberculous...
Tuberculous MeningitisThe rapid diagnosis of tuberculosis (TB) in children remains a serious challenge owing to limitations in the existing diagnostic tests. TB meningitis (TBM), an extrapulmonary form of TB, is the most severe manifestation of paediatric TB. TBM results in high morbidity and mortality in children, despite the availability of chemotherapy, mainly due to diagnostic delay. Most tests required for proper TBM diagnosis including analysis of cerebrospinal fluid (CSF) and brain imaging are not available in resource-limited settings e.g., in most of Africa including South Africa. New tests for TBM are urgently needed. The main goal of this proposal is to develop a point-of-care (POC) diagnostic test for TBM, based on CSF and bloodbiomarkers. Aim 1: Evaluate the diagnostic potentials of 51 host inflammatory biomarkers that the investigators recently identified in CSF and blood samples from children with suspected meningitis in a repository of 100 stored CSF and serum samples using a multiplex platform. After statistical analysis including multi-marker modelling by linear discriminant analysis, random forest, and other modelling techniques, the investigators will select the best combination of up to four biomarkers for incorporation into the prototype diagnostic test (Aim 2). Aim 2: Incorporate the best performing CSF and serum biomarkers into a novel, patented biosensor-based POC diagnostic test. The investigators will develop a multi-biomarker prototype test for detecting up to 4 biomarkers in serum or CSF. Aim 3: Evaluate the newly developed POC test on 300 children prospectively. This will be done at the Tygerberg Academic Hospital. The diagnostic yield of the POC test will be compared to the routine diagnostic tests.