Can Pan-TB shorter regimens be a promising hope for ending TB in India by 2025 in ongoing COVID-19 era?
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ABSTRACT:
SUBMITTER: Prasad R
PROVIDER: S-EPMC9221684 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
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Can Pan-TB shorter regimens be a promising hope for ending TB in India by 2025 in ongoing COVID-19 era?
Prasad Rajendra R Singh Abhijeet A Gupta Nikhil N
The Indian journal of tuberculosis 20220623 4
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Project description:Most ongoing and planned TB therapeutic trials are focused on shortening the duration of treatment while giving less consideration to other aspects of TB care that are important to people with TB. Here we argue that other variables besides duration of TB treatment should also be considered when developing new TB treatment regimens, including drug toxicity, time spent in monitoring and overall quality of life while on therapy. We examine the specific use of linezolid in treatment-shortening trials for drug-susceptible TB and propose additional endpoints that should be prioritised in TB treatment studies.
| S-EPMC10446660 | biostudies-literature
Project description:IntroductionPeople living with multidrug-resistant tuberculosis currently have few options for effective treatment and cure. Regimens that are available are toxic, may involve injections and take up to 2 years to complete treatment, with success rates as low as 50%. The TB-PRACTECAL trial is evaluating shorter, more tolerable regimens of oral drugs; we detail the substudy within this trial, PRACTECAL-PRO, which aims to evaluate patient experiences and perspectives on treatment, to understand outcomes more fully.Methods and analysisWe are conducting a mixed-methods evaluation within both investigational and standard of care arms within the TB-PRACTECAL trial, using sequential quality of life (QoL) surveys and in-depth interviews. Data collection involves the Short Form 12 (SF-12) and St George's Respiratory Questionnaire (SGRQ), collected at up to four fixed timepoints, from baseline, to up to 12 months later. Healthy volunteers will be surveyed to establish locally relevant controls. We will also purposively sample participants for qualitative data collection and analysis, to provide rich explanation of QoL scores. The study will be implemented in all six TB-PRACTECAL study sites in Uzbekistan, South Africa and Belarus. QoL surveys will be scored and analysed according to SF-12 and SGRQ developers' manuals. Differences between scores at baseline and later timepoints will be evaluated as well as graphical exploration of group score trajectories of investigational and standard of care arms.Ethics and disseminationEthics approval was obtained from the Médecins Sans Frontières Ethics Review Board. Local ethics approval has been obtained in Uzbekistan, Belarus and South Africa. Results of the substudy will be shared with local health authorities, the WHO and submitted for publication in a peer-reviewed journal.Trial registration numberNCT03942354; Pre-results.
| S-EPMC8422308 | biostudies-literature
Project description:BackgroundWe aimed to determine the prevalence of pulmonary TB amongst the adult population (≥15 years) in 2016 in Kenya.MethodA nationwide cross-sectional survey where participants first underwent TB symptom screening and chest x-ray. Subsequently, participants who reported cough >2weeks and/or had a chest x-ray suggestive of TB, submitted sputum specimen for laboratory examination by smear microscopy, culture and Xpert MTB/RIF.ResultThe survey identified 305 prevalent TB cases translating to a prevalence of 558 [95%CI 455-662] per 100,000 adult population. The highest disease burden was reported among people aged 25-34 years (716 [95% CI 526-906]), males (809 [(95% CI 656-962]) and those who live in urban areas (760 [95% CI 539-981]). Compared to the reported TB notification rate for Kenya in 2016, the prevalence to notification ratio was 2.5:1. The gap between the survey prevalence and notification rates was highest among males, age groups 25-34, and the older age group of 65 years and above. Only 48% of the of the survey prevalent cases reported cough >2weeks. In addition, only 59% of the identified cases had the four cardinal symptoms for TB (cough ≥2 weeks, fever, night sweat and weight loss. However, 88.2% had an abnormal chest x-ray suggestive of TB. The use of Xpert MTB/RIF identified 77.7% of the cases compared to smear microscopy's 46%. Twenty-one percent of the survey participants with respiratory symptoms reported to have sought prior health care at private clinics and chemists. Among the survey prevalent cases who reported TB related symptoms, 64.9% had not sought any health care prior to the survey.ConclusionThis survey established that TB prevalence in Kenya is higher than had been estimated, and about half of the those who fall ill with the disease each year are missed.
| S-EPMC6306266 | biostudies-literature
Project description:Tools for effective TB control have been available for years. Case finding, active medications, case management and directly observed therapy are the foundations for the management of TB. The current TB epidemic, centered in resource-limited settings is fueled by the HIV-1 epidemic. Lack of ability to diagnose and treat drug-resistant TB has led to development of more extensive patterns of resistance. Among the currently available drugs, there is reason to hope that rifamycins paired with fluoroquinolones will lead to shorter treatment regimens for drug-susceptible TB. As the result of novel public-private collaborations and investments of resources, new drugs are being developed. These include TMC207, already shown to have activity early in the treatment of multidrug-resistant TB and others that are likely to be active against persistor organisms, and have the prospect to dramatically shorten treatment courses for active and latent TB. Given that these drugs have novel mechanisms of action, combinations have the prospect to be highly active even against multidrug-resistant organisms.
| S-EPMC3647464 | biostudies-literature
Project description:Immunotherapy with chimeric antigen receptor-engineered T cells (CAR-T) has revolutionized the treatment landscape of relapsed/refractory B-cell malignancies. Nonetheless, the use of autologous T cells has certain limitations, including the variable quality and quantity of collected effector T cells, extended time of cell processing, limited number of available CAR cells, toxicities, and a high cost. Thanks to their powerful cytotoxic capabilities, with proven antitumor effects in both haploidentical hematopoietic stem cell transplantation and adoptive cell therapy against solid tumors and hematological malignancies, Natural Killer cells could be a promising alternative. Different sources of NK cells can be used, including cellular lines, cord blood, peripheral blood, and induced pluripotent stem cells. Their biggest advantage is the possibility of using them in an allogeneic context without major toxic side effects. However, the majority of the reports on CAR-NK cells concern preclinical or early clinical trials. Indeed, NK cells might be more difficult to engineer, and the optimization and standardization of expansion and transfection protocols need to be defined. Furthermore, their short persistence after infusion is also a major setback. However, with recent advances in manufacturing engineered CAR-NK cells exploiting their cytolytic capacities, antibody-dependent cellular cytotoxicity (ADCC), and cytokine production, "off-the-shelf" allogeneic CAR-NK cells can provide a great potential in cancer treatments.
| S-EPMC9367380 | biostudies-literature
Project description:IntroductionCurrent treatment regimens for multidrug-resistant tuberculosis (MDR-TB) are long, poorly tolerated and have poor outcomes. Furthermore, the costs of treating MDR-TB are much greater than those for treating drug-susceptible TB, both for health service and patient-incurred costs. Urgent action is needed to identify short, effective, tolerable and cheaper treatments for people with both quinolone-susceptible and quinolone-resistant MDR-TB. We present the protocol for an economic evaluation (PRACTECAL-EE substudy) alongside an ongoing clinical trial (TB-PRACTECAL) aiming to assess the costs to patients and providers of new regimens, as well as their cost-effectiveness and impact on participant poverty levels. This substudy is based on data from the three countries participating in the main trial.Methods and analysisPrimary cost data will be collected from the provider and patient perspectives, following economic best practice. We will estimate the probability that new MDR-TB regimens containing bedaquiline, pretomanid and linezolid are cost-effective from a societal perspective as compared with the standard of care for MDR-TB patients in Uzbekistan, South Africa and Belarus. Analysis uses a Markov model populated with primary cost and outcome data collected at each study site. We will also estimate the impact of new regimens on prevalence of catastrophic patient costs due to TB.Ethics and disseminationEthical approval has been obtained from the London School of Hygiene & Tropical Medicine and Médecins Sans Frontières. Local ethical approval will be sought in each study site. The results of the economic evaluation will be shared with the country health authorities and published in a peer-reviewed journal.Trial registration numberClinicalTrials.gov Registry (NCT04207112); Pre-results.
| S-EPMC7549492 | biostudies-literature
Project description:BackgroundChina has the third-largest burden of tuberculosis (TB) cases in the world with great challenges towards ending TB. Primary health care (PHC) sectors play a critical role in TB prevention and control in communities under the Chinese integrated TB control model. However, there is a lack of comprehensive review of research evidence on TB control in PHC sectors under the integrated TB control model in China.MethodsThis review was conducted following the PRISMA guidelines. Articles published from 2012 to January 2022 were searched from four international and three Chinese databases. Studies conducted inside mainland China and relevant with TB control service in PHC sectors under the integrated model were included. After study selection, data extraction, and quality assessment, the meta-analysis was performed with RevMan using a random-effect model.When I2 was more than 50%, subgroup analysis was performed to explore possible reasons for heterogeneity. We also conducted a post hoc sensitivity analysis for outcomes after meta-analysis by exclusion of studies with a high risk of bias or classified as low quality.ResultsForty-three studies from 16 provinces/municipalities in China were included in this review, and most studies included were of medium quality. PHC sectors in East China delivered TB control service better overall than that in West China, especially in tracing of patients and TB case management (TCM). In meta-analyses, both the pooled arrival rate of tracing and pooled TCM rate in East China were higher than those in West China. TB patients had a low degree of willingness to receive TCM provided by healthcare workers in PHC sectors nationwide, especially among migrant TB patients. There were 9 studies reporting factors related to TB control service in PHC sectors, 6 (2 in East and 4 in West China) of which indentified several characteristics of patients as associated factors. The context of PHC sectors was demonstrated to influence delivery of TB control service in PHC sectors in 5 studies (3 in East, 1 in Middle and 1 in West China). Most studies on strategies to promoting TB control services in PHC sectors were conducted in East China and some of these studies identified several online and offline interventions and strategies improving patients' treatment compliance [pooled OR (95% CI): 7.81 (3.08, 19.19] and awareness of TB [pooled OR (95% CI): 6.86 (2.16, 21.72)].ConclusionIt is of urgent need to improve TB control in PHC sector in China, particularly in West China. Formative and implementation research with rigorous design are necessary to develop comprehensive, context-specific, and patient-centered TB control strategies to promote ending TB in China.
| S-EPMC10785344 | biostudies-literature
Project description:Minimal conditioning or even no conditioning would be the preferred preparation for most gene therapy applications for nonmalignant diseases. However, reduced intensity conditioning (RIC) regimens in patients with nonhematologic malignancies have not led to long-term engraftment unless a selective advantage was present for the transplanted donor cells. Similar findings have also been observed in a number of large animal studies. Inadequate myelosuppression levels were thought to be responsible for the outcomes. To address this issue several innovative protocols in small animals have been presented with selective hematopoietic myelosuppression and less systemic toxicity. Such protocols promised to curb the transplant-related morbidity and mortality in myeloablative conditioning and provide effective long-term engraftment, especially in patients with gene-corrected autografts. In the present study we have tested some of these promising RIC regimens in nonhuman primates, a clinically relevant large animal model. Our data suggest that transient myelosuppression induced by anti-c-Kit antibody in conjunction with low-dose irradiation may lead to long-term engraftment, albeit at low levels. The animals with busulfan conditioning with or without anti-c-Kit that received gene-modified autologous transplants with green fluorescent protein expression had similar myelosuppression, but failed long-term engraftment and despite immunosuppressive treatment had all the hallmarks seen previously in similar models without immunosuppression. Our preliminary data expand current knowledge of RIC and emphasize the need to explore whether specific and directed myelosuppression alone is adequate in the absence of microenvironmental modulation, or whether innovative combinations are necessary for safe and effective engraftment.
| S-EPMC4270134 | biostudies-literature
Project description: Not available
| S-EPMC1198044 | biostudies-literature
Project description:Despite current control efforts, global tuberculosis (TB) incidence is decreasing slowly. New regimens that can shorten treatment hold promise for improving treatment completion and success, but their impact on population-level transmission remains unclear. Earlier models projected that a four-month regimen could reduce TB incidence by 10% but assumed that an entire course of therapy must be completed to derive any benefit. We constructed a dynamic transmission model of TB disease calibrated to global estimates of incidence, prevalence, mortality, and treatment success. To account for the efficacy of partial treatment, we used data from clinical trials of early short-course regimens to estimate relapse rates among TB patients who completed one-third, one-half, two-thirds, and all of their first-line treatment regimens. We projected population-level incidence and mortality over 10 years, comparing standard six-month therapy to hypothetical shorter-course regimens with equivalent treatment success but fewer defaults. The impact of hypothetical four-month regimens on TB incidence after 10 years was smaller than estimated in previous modeling analyses (1.9% [95% uncertainty range 0.6-3.1%] vs. 10%). Impact on TB mortality was larger (3.5% at 10 years) but still modest. Transmission impact was most sensitive to the proportion of patients completing therapy: four-month therapy led to greater incidence reductions in settings where 25% of patients leave care ("default") over six months. Our findings remained robust under one-way variation of model parameters. These findings suggest that novel regimens that shorten treatment duration may have only a modest effect on TB transmission except in settings of very low treatment completion.
| S-EPMC4015982 | biostudies-literature