eClinicalMedicine

BackgroundTreatment of tuberculosis infection (TBI) is a cornerstone of the WHO End TB Strategy. Two widely recommended short-course regimens--weekly isoniazid plus rifapentine for 12 weeks (3HP) and daily rifampicin for 16 weeks (4RIF)--have not been directly compared in a randomised trial. This study aimed to compare treatment completion between 3HP and 4RIF among individuals with TBI. MethodsWe conducted a multicentre, open-label, parallel-group, randomised controlled trial at seven tubercul...

We present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in adult volunteers aged 18-60. Safety of the vaccine was assessed in 398 volunteers who received two doses of the vaccine (n=298) or placebo (n=100). The studied vaccine has shown good tolerability and safety. No deaths, serious adverse events (AE), or other signifi...

BackgroundLittle is known about the protection following prior infection with different SARS-CoV-2 variants, COVID-19 vaccination, and a combination of the two (hybrid immunity) in adolescents. MethodsWe used national SARS-CoV-2 testing and COVID-19 mRNA vaccination data in England to estimate protection following previous infection and vaccination against symptomatic PCR-confirmed delta and omicron BA.1/BA.2 variants in 11-17-year-olds using a test-negative case-control design. FindingsBy 31 ...

IntroductionCurrent options for treating tuberculosis (TB) that is resistant to rifampicin (RR-TB) are few, and regimens are often long and poorly tolerated. Following recent evidence from the TB-PRACTECAL trial countries are considering programmatic uptake of 6-month, all-oral treatment regimens. MethodsWe used a Markov model to estimate the incremental cost-effectiveness of three regimens containing bedaquiline, pretomanid and linezolid (BPaL) with and without moxifloxacin (BPaLM) or clofazim...

BackgroundBacille Calmette-Guerin (BCG) is the most commonly-used vaccination globally, but multi-country cost-effectiveness analyses are outdated and have not considered sequelae in tuberculosis survivors. A rationale is lacking to guide the size of safety stocks. MethodsFor the 110 countries using universal neonatal BCG vaccination, we used a decision tree model to compare the costs and health benefits of status-quo BCG vaccination for children aged 0-4 years in 2023 to a counterfactual where...

BackgroundActive case finding (ACF) for tuberculosis (TB) can reduce transmission, yet efficient targeting requires high-quality surveillance data. We investigated the potential costs and impact of targeted ACF, guided by local estimates of the annual risk of TB infection (ARTI) derived from Mycobacterium tuberculosis (Mtb) immunoreactivity survey data in children aged <5 years. MethodsUsing mathematical models parameterized with local data, we compared three case-finding approaches across 33 u...

BackgroundLatent TB infection (LTBI) screening and treatment of population groups at high risk for TB is part of Englands Tuberculosis Action Plan, which has succeeded in increasing testing volumes. However, analysis of the cost-effectiveness is hampered by a lack of detailed information on health service costs. MethodsWe surveyed clinics with large volumes of activity, located in the London, West Midlands, South East & South West, and North West England TB Control Board areas. These represent ...

BackgroundIn the current protracted COVID-19 pandemic, SARS-CoV-2 vaccines that have the ability to be used safely and to prevent onset or severe disease are still highly needed. A Phase 1/2 study was conducted in healthy adults and the elderly in Japan to evaluate the immunogenicity, safety, and tolerability of an inactivated whole-virus vaccine (KD-414) that is under development. MethodsIn this double-blind, randomized, placebo-controlled, Phase 1/2 study, adults aged 20 to 64 years and elder...

ObjectiveThanks to the introduction of recent national guidelines for treating herpes simplex virus (HSV) encephalitis health outcomes have improved. This paper evaluates the costs and the health-related quality of life implications of these guidelines. Design and settingA sub-analysis of data from a prospective, multi-centre, observational cohort ENCEPH-UK study conducted across 29 hospitals in the UK from 2012 to 2015. Study participantsData for patients aged [&ge;]16 years with a confirmed ...

BackgroundIn England, hospitalisations and deaths due to SARS-CoV-2 have been falling consistently since January 2021 during the third national lockdown of the COVID-19 pandemic. The first significant relaxation of that lockdown occurred on 8 March when schools reopened. MethodsThe REal-time Assessment of Community Transmission-1 (REACT-1) study augments routine surveillance data for England by measuring swab-positivity for SARS-CoV-2 in the community. The current round, round 10, collected swa...

New infections from the omicron variant of SARS-CoV-2 have been increasing dramatically in South Africa since first identification in November 2021. Despite increasing uptake of COVID-19 vaccine, there are concerns vaccine protection against omicron may be reduced compared to other variants. We sought to characterize a surrogate measure of vaccine efficacy in Gauteng, South Africa by leveraging real-time syndromic surveillance data. The University of Maryland Global COVID Trends and Impact Surve...

Prevalence of SARS-CoV-2 amongst school children in the omicron wave was high leading to a constant exposure of teachers to the virus. A cohort of staff members (n = 28) was recruited from a UK primary school setting. The prevalent variants at the time were Omicron BA.1, BA.4/5 and BA.2: 61% of the cohort reported a lateral-flow-confirmed positive test for SARS-CoV-2 infection in late 2021 or 2022. A mass-standardised quantitative antibody spectrum was measured for both antibody concentration an...

BackgroundThe third wave of COVID-19 in England coincided with the rapid spread of the Delta variant of SARS-CoV-2 from the end of May 2021. Case incidence data from the national testing programme (Pillar 2) in England may be affected by changes in testing behaviour and other biases. Community surveys may provide important contextual information to inform policy and the public health response. MethodsWe estimated patterns of community prevalence of SARS-CoV-2 infection in England using RT-PCR s...

BackgroundAtypical haemolytic uremic syndrome (aHUS) is a rare life-threatening disease. Lifelong treatment with intravenous eculizumab every two/three weeks was recommended but evidence is emerging that patients can stop eculizumab and restart should they relapse. However, little is known about the opinions and needs of aHUS patients on withdrawal. ObjectiveWe aimed to understand the factors that impact on decisions to withdraw from treatment. MethodsWe analysed in-depth telephone interviews ...

BackgroundEmerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) is detected on Drug Susceptibility Testing (DST). Methods and FindingsThe primary ...

BackgroundHigh rates of breakthrough rotavirus gastroenteritis have been reported among Aboriginal children living in rural and remote Australia despite receipt of two doses of oral rotavirus vaccine. Histo-blood group antigens (HBGAs) may mediate rotavirus genotype-dependent differences in susceptibility to rotavirus infection and immune responses to rotavirus vaccination. MethodsHBGA phenotype - Lewis and secretor status - was determined by enzyme immunoassay of saliva samples obtained from A...

RationaleHigh galectin-3 levels predict poor outcomes in patients with COVID-19. Galectin-3 activates monocytes and macrophages which are directly implicated in COVID-19 immunopathology and the cytokine storm. GB0139 is a potent thiodigalactoside galectin-3 inhibitor and may reduce the severe effects of the disease. We report safety and pharmacokinetics and pharmacodynamics of the inhaled galectin-3 inhibitor, GB0139, and assess clinical outcomes and key systemic inflammatory biomarkers in hospi...

BackgroundSeveral clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are nearing completion. The potential benefits of TPT for MDR-TB contacts extend beyond the outcomes that clinical trials can measure. MethodsWe developed an agent-based, household-structured TB and MDR-TB transmission model, calibrated to an illustrative setting in India, the country accounting for 26% of global MDR-TB burden. We simulat...

BackgroundWe report results of immunogenicity, safety and reactogenicity of SOBERANA 02 in a two-dose or three-dose heterologous scheme in adults in a phase IIb clinical trial. MethodThis phase IIb trial was designed as parallel, multicentre, adaptive, double blind, randomized and placebo-controlled. Subjects (N=810) aged 19-80 years were randomized to receive two doses of the recombinant SARS CoV-2 receptor binding domain (RBD) conjugated to tetanus toxoid (SOBERANA 02) and a third dose of dim...

IntroductionStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are a group of severe acute muco-cutaneous blistering disorders with a significant burden of morbidity and mortality. Drugs are commonly identified as potential precipitants of SJS/TEN, although it can be difficult to firmly identify causative agents. Ibuprofen has been proposed as a rare trigger for SJS/TEN and given the widespread use of this non-steroidal anti-inflammatory and significance of reaction, further pha...