Respiratory infections
Lead Research Organisation:
University College London
Department Name: UNLISTED
Abstract
Respiratory infections are infections that affect people’s breathing. They are the biggest cause infectious disease deaths worldwide. A quarter of the world’s population is estimated to have latent tuberculosis (TB). Latent TB is a TB infection without symptoms. One in ten people with latent TB will develop active TB (TB with symptoms) in their lifetime. People who are older or who have illnesses such as HIV or diabetes are at higher risk of developing active TB. To address this global public health problem, we have expanded our range of TB trials to cover the full spectrum of disease. We have new studies of
• Diagnostics (tools for diagnosing TB)
• TB preventative therapy
• Shorter and simpler treatments for different types of TB in adults and children.
Respiratory infections caused by bacteria are extremely common. They are increasing in high-income countries. They are a major driver of antibiotic use and thus antimicrobial (drug) resistance. We need better evidence to inform prescribing guidelines. To help with this, we have a number of trials aiming to work out the best dose and duration of antibiotics for children and adults with bacterial respiratory infections.
In response to the SARS-Cov-2 pandemic, we have developed a number of treatment trials. These trials use our expanded global influenza network. The trials cover the patients severely ill in intensive care, hospitalised patients with mild-moderate infection and in those with early disease at risk of progression. Embedded substudies are exploring the timing and number of doses of SARS-Cov-2 vaccine needed in those who have been hospitalised with COVID-19.
• Diagnostics (tools for diagnosing TB)
• TB preventative therapy
• Shorter and simpler treatments for different types of TB in adults and children.
Respiratory infections caused by bacteria are extremely common. They are increasing in high-income countries. They are a major driver of antibiotic use and thus antimicrobial (drug) resistance. We need better evidence to inform prescribing guidelines. To help with this, we have a number of trials aiming to work out the best dose and duration of antibiotics for children and adults with bacterial respiratory infections.
In response to the SARS-Cov-2 pandemic, we have developed a number of treatment trials. These trials use our expanded global influenza network. The trials cover the patients severely ill in intensive care, hospitalised patients with mild-moderate infection and in those with early disease at risk of progression. Embedded substudies are exploring the timing and number of doses of SARS-Cov-2 vaccine needed in those who have been hospitalised with COVID-19.
Technical Summary
Respiratory infections continue to cause the greatest number of infectious disease deaths worldwide. A quarter of the world’s population is estimated to have latent tuberculosis, with a 10% lifetime risk of developing active TB, further increased by co-morbidities such as HIV or diabetes mellitus and exacerbated by the effects of aging. In response to this public health emergency, in this quinquennium, we have expanded our portfolio of tuberculosis trials to cover the full spectrum of disease, with new studies of latent tuberculosis diagnostics and tuberculosis preventative therapy, as well as addressing antimicrobial resistance through trials testing shortened treatment (improving adherence) and more effective regimens for both drug-sensitive and drug-resistant tuberculosis disease. Paediatric tuberculosis has historically been neglected, particularly in terms of identifying the right drug doses and appropriate formulations. We have been at the forefront of international activity in this area, conducting a programme of relevant phase III paediatric tuberculosis trials in Africa and Asia, ensuring that children are represented in research.
Bacterial respiratory infections are extremely common, and estimated to be increasing in high-income countries, making them a major driver of antibiotic use and thus antimicrobial resistance. Better evidence is needed to inform prescribing guidelines. Antibiotic trials pose numerous methodological challenges which our programme is addressing. For example, the relatively weak evidence base for treating pneumonia in both adults and children, particularly regarding choice of drug, dose and duration means that appropriately designed trials addressing questions about narrowing and shortening of antibiotic treatment courses need to be undertaken. We have developed a new trial design to directly estimate the optimal duration of antibiotic treatment, whose first large-scale application will be in a trial in paediatric pneumonia in LMIC.
In response to the SARS-Cov-2 pandemic, and utilising and expanding on our global influenza network, built in 2009 in response to the influenza A H1N1 pandemic, we are playing a leading role in the international response. We are testing the most promising antiviral candidates and immunomodulating agents (including passive immunotherapy using convalescent plasma and immunoglobulin) for treatment across the disease spectrum.
Bacterial respiratory infections are extremely common, and estimated to be increasing in high-income countries, making them a major driver of antibiotic use and thus antimicrobial resistance. Better evidence is needed to inform prescribing guidelines. Antibiotic trials pose numerous methodological challenges which our programme is addressing. For example, the relatively weak evidence base for treating pneumonia in both adults and children, particularly regarding choice of drug, dose and duration means that appropriately designed trials addressing questions about narrowing and shortening of antibiotic treatment courses need to be undertaken. We have developed a new trial design to directly estimate the optimal duration of antibiotic treatment, whose first large-scale application will be in a trial in paediatric pneumonia in LMIC.
In response to the SARS-Cov-2 pandemic, and utilising and expanding on our global influenza network, built in 2009 in response to the influenza A H1N1 pandemic, we are playing a leading role in the international response. We are testing the most promising antiviral candidates and immunomodulating agents (including passive immunotherapy using convalescent plasma and immunoglobulin) for treatment across the disease spectrum.
Organisations
- University College London (Lead Research Organisation)
- Foundation for Innovative New Diagnostics (FIND) (Collaboration)
- World Health Organization (WHO) (Collaboration)
- UNIVERSITY OF LEICESTER (Collaboration)
- Medical Research Council of South Africa (MRC) (Collaboration)
- ST GEORGE'S UNIVERSITY OF LONDON (Collaboration)
- National Institute of Allergy and Infectious Diseases (NIAID) (Collaboration)
- Stellenbosch University (Collaboration)
- The Global Alliance for TB Drug Development (Collaboration)
- Bill & Melinda Gates Foundation (Collaboration)
- London School of Hygiene and Tropical Medicine (LSHTM) (Collaboration)
- The Walter and Eliza Hall Institute of Medical Research (WEHI) (Collaboration)
- Radboud University Nijmegen (Collaboration)
- National Institutes of Health (NIH) (Collaboration)
- University of Cape Town (Collaboration)
People |
ORCID iD |
Publications
Abeywickrema M
(2022)
COVID-19 vaccine results might inform malaria vaccine strategies.
in The Lancet. Infectious diseases
ACTIV-3/Therapeutics For Inpatients With COVID-19 (TICO) Study Group
(2022)
Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial.
in The Lancet. Infectious diseases
ACTIV-3/TICO LY-CoV555 Study Group
(2021)
A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19.
in The New England journal of medicine
ACTIV-3/TICO Study Group
(2022)
The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19.
in Annals of internal medicine
ACTIV-3/TICO Study Group
(2022)
Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.
in Annals of internal medicine
Barratt S
(2021)
Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT.
in Health technology assessment (Winchester, England)
Basu Roy R
(2021)
Defeating Paediatric Tuberculous Meningitis: Applying the WHO "Defeating Meningitis by 2030: Global Roadmap".
in Microorganisms
Bawa T
(2022)
Inpatient COVID-19 vaccination rollout: Improving access to vaccination.
in Clinical medicine (London, England)
Butler M
(2021)
Functional Neurological Disorder After SARS-CoV-2 Vaccines: Two Case Reports and Discussion of Potential Public Health Implications.
in The Journal of neuropsychiatry and clinical neurosciences
Butler M
(2021)
Considerations for causality assessment of neurological and neuropsychiatric complications of SARS-CoV-2 vaccines: from cerebral venous sinus thrombosis to functional neurological disorder.
in Journal of neurology, neurosurgery, and psychiatry
Chabala C
(2022)
Pharmacokinetics of First-Line Drugs in Children With Tuberculosis, Using World Health Organization-Recommended Weight Band Doses and Formulations.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Chaudhry Z
(2021)
Short durations of corticosteroids for hospitalised COVID-19 patients are associated with a high readmission rate
in Journal of Infection
Cohen-Stavi CJ
(2022)
BNT162b2 Vaccine Effectiveness against Omicron in Children 5 to 11 Years of Age.
in The New England journal of medicine
Conradie F
(2022)
Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis.
in The New England journal of medicine
Curnow E
(2023)
Multiple imputation of missing data under missing at random: compatible imputation models are not sufficient to avoid bias if they are mis-specified.
in Journal of clinical epidemiology
Douin DJ
(2022)
Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery.
in American journal of respiratory and critical care medicine
Ejo M
(2021)
Effectiveness of GenoType MTBDRsl in excluding TB drug resistance in a clinical trial.
in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Emary KRW
(2021)
Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial.
in Lancet (London, England)
Fidler S
(2023)
Booster Vaccination Against SARS-CoV-2 Induces Potent Immune Responses in People With Human Immunodeficiency Virus.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Flaxman A
(2021)
Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002).
in Lancet (London, England)
Frascella B
(2021)
Subclinical Tuberculosis Disease-A Review and Analysis of Prevalence Surveys to Inform Definitions, Burden, Associations, and Screening Methodology.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Gafar F
(2023)
Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.
in The European respiratory journal
Gafar F
(2023)
Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.
in The European respiratory journal
Glavin D
(2021)
COVID-19 Encephalitis with SARS-CoV-2 Detected in Cerebrospinal Fluid Presenting as a Stroke Mimic.
in Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
Goodall RL
(2022)
Evaluation of two short standardised regimens for the treatment of rifampicin-resistant tuberculosis (STREAM stage 2): an open-label, multicentre, randomised, non-inferiority trial.
in Lancet (London, England)
Gray A
(2021)
Following Guidelines for Drug-Resistant Tuberculosis: "Yes, it's a challenge"
in Frontiers in Tropical Diseases
Grundmann A
(2023)
Fewer COVID-19 Neurological Complications with Dexamethasone and Remdesivir.
in Annals of neurology
Gureva T
(2022)
Fluoroquinolone preventive therapy for children exposed to MDR-TB.
in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Heath PT
(2021)
Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine.
in The New England journal of medicine
ITAC (INSIGHT 013) Study Group
(2022)
Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial.
in Lancet (London, England)
Kloprogge F
(2021)
Exploring a combined biomarker for tuberculosis treatment response: protocol for a prospective observational cohort study.
in BMJ open
Kokebu DM
(2022)
Failure or relapse predictors for the STREAM Stage 1 short regimen for RR-TB.
in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Laher F
(2022)
HIV Prevention in a Time of COVID-19: A Report from the HIVR4P // Virtual Conference 2021.
in AIDS research and human retroviruses
MacPherson P
(2021)
Before the whistle blows: developing new paradigms in tuberculosis screening to maximise benefit and minimise harm
in Wellcome Open Research
Menni C
(2021)
Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study.
in The Lancet. Infectious diseases
Mentzer AJ
(2023)
Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection.
in Nature medicine
Molloy SF
(2022)
Multiplicity adjustments in parallel-group multi-arm trials sharing a control group: Clear guidance is needed.
in Contemporary clinical trials
Moran E
(2021)
Persistent SARS-CoV-2 infection: the urgent need for access to treatment and trials.
in The Lancet. Infectious diseases
Munro APS
(2022)
Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial.
in The Lancet. Infectious diseases
Murray DD
(2021)
Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).
in medRxiv : the preprint server for health sciences
Murray DD
(2022)
Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).
in Clinical trials (London, England)
Nguyen H
(2021)
Compassionate use of REGN-COV2 in the treatment of COVID-19 in a patient with impaired humoral immunity.
in Clinical infection in practice
Related Projects
| Project Reference | Relationship | Related To | Start | End | Award Value |
|---|---|---|---|---|---|
| MC_UU_00004/01 | 01/04/2021 | 31/03/2026 | £5,186,000 | ||
| MC_UU_00004/02 | Transfer | MC_UU_00004/01 | 01/04/2021 | 31/03/2026 | £4,446,000 |
| MC_UU_00004/03 | Transfer | MC_UU_00004/02 | 01/04/2021 | 31/03/2026 | £4,999,000 |
| MC_UU_00004/04 | Transfer | MC_UU_00004/03 | 01/04/2021 | 31/03/2026 | £5,315,000 |
| MC_UU_00004/05 | Transfer | MC_UU_00004/04 | 01/04/2021 | 31/03/2026 | £3,107,000 |
| MC_UU_00004/06 | Transfer | MC_UU_00004/05 | 01/04/2021 | 31/03/2026 | £2,889,000 |
| MC_UU_00004/07 | Transfer | MC_UU_00004/06 | 01/04/2021 | 31/03/2026 | £2,369,000 |
| MC_UU_00004/08 | Transfer | MC_UU_00004/07 | 01/04/2021 | 31/03/2026 | £2,270,000 |
| MC_UU_00004/09 | Transfer | MC_UU_00004/08 | 01/04/2021 | 31/03/2026 | £2,160,000 |
| Guideline Title | WHO guidelines on vaccines, JCVI guidelines on vaccines |
| Description | AZD1222 vaccine implemented worldwide |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in clinical guidelines |
| Impact | At the end of 2021 AstraZeneca COVID-19 vaccine AZD1222 has been administered to over 2 billion people and estimated to have presented 50 million cases of COVID-19 and helped save more than 1 million lives. Two thirds of the utilisation of this vaccine has been in low and middle income countries. |
| Description | Citation in WHO guidelines on vaccines in COVID-19 |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in other policy documents |
| Impact | Ability to give heterologous boost vaccines |
| URL | https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance |
| Guideline Title | Rapid communication on updated guidance on the management of tuberculosis in children and adolescents |
| Description | TB treatment shortening for non-severe drug-susceptible TB in children |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in clinical guidelines |
| Impact | The expected impact is improved quality of life of children with non-severe TB (estimated 2/3 of 1 million every year) and their families due to shortened treatment plus substantial cost savings in TB programmes (estimated $17 per child) that an be spend for improving screening and diagnostics in childhood TB. |
| URL | https://www.who.int/publications/i/item/9789240033450 |
| Description | (ORCHESTRA) - Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic: ORCHESTRA |
| Amount | € 21,799,690 (EUR) |
| Funding ID | 101016167 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | 12/2020 |
| End | 11/2023 |
| Description | An International Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of Anti-Coronavirus Hyperimmune Intravenous Immunglobulin for the Treatment of Adult Outpatients in Early Stages of COVID-19 (INSIGHT 012) |
| Amount | $33,785,252 (USD) |
| Organisation | University of Minnesota |
| Sector | Academic/University |
| Country | United States |
| Start | 06/2021 |
| End | 12/2023 |
| Description | An International Observational Study of Outpatients with COVID-19 (INSIGHT 011) |
| Amount | $15,934,529 (USD) |
| Funding ID | An International Observational Study of Outpatients with COVID-19 (INSIGHT 011) |
| Organisation | University of Minnesota |
| Sector | Academic/University |
| Country | United States |
| Start | 04/2021 |
| End | 06/2022 |
| Description | EDCTP Clinical Trial Grant (PediCAP) |
| Amount | € 6,997,078 (EUR) |
| Funding ID | RIA2017MC-2023 |
| Organisation | Sixth Framework Programme (FP6) |
| Department | European and Developing Countries Clinical Trials Partnership |
| Sector | Public |
| Country | Netherlands |
| Start | 04/2019 |
| End | 03/2023 |
| Description | Evaluation of the Feasibility and Reproducibility of 2 Point-of-Care Tests for SARS-Co-V-2 Antibodies (INSIGHT 017) |
| Amount | $1,279,369 (USD) |
| Organisation | University of Minnesota |
| Sector | Academic/University |
| Country | United States |
| Start | 11/2021 |
| End | 06/2023 |
| Description | SARS-CoV-2 vaccination strategies in previously hospitalized and recovered COVID-19 patients (INSIGHT 016) |
| Amount | $5,305,476 (USD) |
| Organisation | University of Minnesota |
| Sector | Academic/University |
| Country | United States |
| Start | 07/2021 |
| End | 12/2022 |
| Description | VERDI: SARS-coV2 variants Evaluation in pRegnancy and paeDIatrics cohorts |
| Amount | € 10,000,000 (EUR) |
| Funding ID | VERDI - 101045989 - GAP-101045989 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | 11/2021 |
| End | 10/2025 |
| Description | Collaboration with Global Alliance for TB Drug Development |
| Organisation | The Global Alliance for TB Drug Development |
| Country | Global |
| Sector | Private |
| PI Contribution | MRC CTU at UCL contribute to the design of new studies and have responsibilities for efficacy analyses for all phase 2/3 clinical studies sponsored by the Global Alliance for TB Drug Development. This collaboration began in 2007, with the REMoxTB trial. In 2017, UCL become a member of the TB Alliance Stakeholder Association (SHA). |
| Collaborator Contribution | MRC CTU at UCL contribute to the design of new studies and have responsibilities for efficacy analyses for all phase 2/3 clinical studies sponsored by the Global Alliance for TB Drug Development. This collaboration began in 2007, with the REMoxTB trial. In 2017, UCL become a member of the TB Alliance Stakeholder Association (SHA). |
| Impact | Publications from the REMoxTB Consortium. |
| Start Year | 2007 |
| Description | Development of a global consensus statement for Early TB Disease |
| Organisation | Bill and Melinda Gates Foundation |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | The Radio+ TB project focuses on the management on people with early TB disease who fall between current definitions of active and latent TB. To move the research agenda forward it is critical to recognise the limtations of this active/latent paridigm which is increasingly recognised but is leading to confusion. I co-led and co-chaired the scientific organising committee in the efforts to build a global consensus in this area. We brought together a group of 60 stakeholders at a face to face meeting Cape Town to acheive this. Stakeholders included WHO, FIND, NIH, Gates, Wellcome, National TB Programmes, TB advocates and a wide range of academics from both low and high income settings. Our research team led on the scoping review and the initial Delphi process that fed into the consensus building process. As part of the meeting there was also a workshop held on the the implications for clinical trial design which I co-led. |
| Collaborator Contribution | Meeting was co-led with partner from LSHTM and WEHI and organisation was assisted by partners from UCT, Stellenbosch and South African MRC. Partners form NIH and BMGF sat on the steering commitee and provided financial support for thr meeting along with the Wellcome Centre for Infectious Disease Research at University of Cape Town. |
| Impact | 1. Scoping Review 2. Symposium and Consensus meeting 3. Position Paper (being written) |
| Start Year | 2022 |
| Description | Development of a global consensus statement for Early TB Disease |
| Organisation | London School of Hygiene and Tropical Medicine (LSHTM) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | The Radio+ TB project focuses on the management on people with early TB disease who fall between current definitions of active and latent TB. To move the research agenda forward it is critical to recognise the limtations of this active/latent paridigm which is increasingly recognised but is leading to confusion. I co-led and co-chaired the scientific organising committee in the efforts to build a global consensus in this area. We brought together a group of 60 stakeholders at a face to face meeting Cape Town to acheive this. Stakeholders included WHO, FIND, NIH, Gates, Wellcome, National TB Programmes, TB advocates and a wide range of academics from both low and high income settings. Our research team led on the scoping review and the initial Delphi process that fed into the consensus building process. As part of the meeting there was also a workshop held on the the implications for clinical trial design which I co-led. |
| Collaborator Contribution | Meeting was co-led with partner from LSHTM and WEHI and organisation was assisted by partners from UCT, Stellenbosch and South African MRC. Partners form NIH and BMGF sat on the steering commitee and provided financial support for thr meeting along with the Wellcome Centre for Infectious Disease Research at University of Cape Town. |
| Impact | 1. Scoping Review 2. Symposium and Consensus meeting 3. Position Paper (being written) |
| Start Year | 2022 |
| Description | Development of a global consensus statement for Early TB Disease |
| Organisation | Medical Research Council of South Africa (MRC) |
| Country | South Africa |
| Sector | Public |
| PI Contribution | The Radio+ TB project focuses on the management on people with early TB disease who fall between current definitions of active and latent TB. To move the research agenda forward it is critical to recognise the limtations of this active/latent paridigm which is increasingly recognised but is leading to confusion. I co-led and co-chaired the scientific organising committee in the efforts to build a global consensus in this area. We brought together a group of 60 stakeholders at a face to face meeting Cape Town to acheive this. Stakeholders included WHO, FIND, NIH, Gates, Wellcome, National TB Programmes, TB advocates and a wide range of academics from both low and high income settings. Our research team led on the scoping review and the initial Delphi process that fed into the consensus building process. As part of the meeting there was also a workshop held on the the implications for clinical trial design which I co-led. |
| Collaborator Contribution | Meeting was co-led with partner from LSHTM and WEHI and organisation was assisted by partners from UCT, Stellenbosch and South African MRC. Partners form NIH and BMGF sat on the steering commitee and provided financial support for thr meeting along with the Wellcome Centre for Infectious Disease Research at University of Cape Town. |
| Impact | 1. Scoping Review 2. Symposium and Consensus meeting 3. Position Paper (being written) |
| Start Year | 2022 |
| Description | Development of a global consensus statement for Early TB Disease |
| Organisation | National Institute of Allergy and Infectious Diseases (NIAID) |
| Country | United States |
| Sector | Public |
| PI Contribution | The Radio+ TB project focuses on the management on people with early TB disease who fall between current definitions of active and latent TB. To move the research agenda forward it is critical to recognise the limtations of this active/latent paridigm which is increasingly recognised but is leading to confusion. I co-led and co-chaired the scientific organising committee in the efforts to build a global consensus in this area. We brought together a group of 60 stakeholders at a face to face meeting Cape Town to acheive this. Stakeholders included WHO, FIND, NIH, Gates, Wellcome, National TB Programmes, TB advocates and a wide range of academics from both low and high income settings. Our research team led on the scoping review and the initial Delphi process that fed into the consensus building process. As part of the meeting there was also a workshop held on the the implications for clinical trial design which I co-led. |
| Collaborator Contribution | Meeting was co-led with partner from LSHTM and WEHI and organisation was assisted by partners from UCT, Stellenbosch and South African MRC. Partners form NIH and BMGF sat on the steering commitee and provided financial support for thr meeting along with the Wellcome Centre for Infectious Disease Research at University of Cape Town. |
| Impact | 1. Scoping Review 2. Symposium and Consensus meeting 3. Position Paper (being written) |
| Start Year | 2022 |
| Description | Development of a global consensus statement for Early TB Disease |
| Organisation | The Walter and Eliza Hall Institute of Medical Research (WEHI) |
| Country | Australia |
| Sector | Academic/University |
| PI Contribution | The Radio+ TB project focuses on the management on people with early TB disease who fall between current definitions of active and latent TB. To move the research agenda forward it is critical to recognise the limtations of this active/latent paridigm which is increasingly recognised but is leading to confusion. I co-led and co-chaired the scientific organising committee in the efforts to build a global consensus in this area. We brought together a group of 60 stakeholders at a face to face meeting Cape Town to acheive this. Stakeholders included WHO, FIND, NIH, Gates, Wellcome, National TB Programmes, TB advocates and a wide range of academics from both low and high income settings. Our research team led on the scoping review and the initial Delphi process that fed into the consensus building process. As part of the meeting there was also a workshop held on the the implications for clinical trial design which I co-led. |
| Collaborator Contribution | Meeting was co-led with partner from LSHTM and WEHI and organisation was assisted by partners from UCT, Stellenbosch and South African MRC. Partners form NIH and BMGF sat on the steering commitee and provided financial support for thr meeting along with the Wellcome Centre for Infectious Disease Research at University of Cape Town. |
| Impact | 1. Scoping Review 2. Symposium and Consensus meeting 3. Position Paper (being written) |
| Start Year | 2022 |
| Description | Development of a global consensus statement for Early TB Disease |
| Organisation | University of Cape Town |
| Country | South Africa |
| Sector | Academic/University |
| PI Contribution | The Radio+ TB project focuses on the management on people with early TB disease who fall between current definitions of active and latent TB. To move the research agenda forward it is critical to recognise the limtations of this active/latent paridigm which is increasingly recognised but is leading to confusion. I co-led and co-chaired the scientific organising committee in the efforts to build a global consensus in this area. We brought together a group of 60 stakeholders at a face to face meeting Cape Town to acheive this. Stakeholders included WHO, FIND, NIH, Gates, Wellcome, National TB Programmes, TB advocates and a wide range of academics from both low and high income settings. Our research team led on the scoping review and the initial Delphi process that fed into the consensus building process. As part of the meeting there was also a workshop held on the the implications for clinical trial design which I co-led. |
| Collaborator Contribution | Meeting was co-led with partner from LSHTM and WEHI and organisation was assisted by partners from UCT, Stellenbosch and South African MRC. Partners form NIH and BMGF sat on the steering commitee and provided financial support for thr meeting along with the Wellcome Centre for Infectious Disease Research at University of Cape Town. |
| Impact | 1. Scoping Review 2. Symposium and Consensus meeting 3. Position Paper (being written) |
| Start Year | 2022 |
| Description | Development of a global consensus statement for Early TB Disease |
| Organisation | University of Stellenbosch |
| Country | South Africa |
| Sector | Academic/University |
| PI Contribution | The Radio+ TB project focuses on the management on people with early TB disease who fall between current definitions of active and latent TB. To move the research agenda forward it is critical to recognise the limtations of this active/latent paridigm which is increasingly recognised but is leading to confusion. I co-led and co-chaired the scientific organising committee in the efforts to build a global consensus in this area. We brought together a group of 60 stakeholders at a face to face meeting Cape Town to acheive this. Stakeholders included WHO, FIND, NIH, Gates, Wellcome, National TB Programmes, TB advocates and a wide range of academics from both low and high income settings. Our research team led on the scoping review and the initial Delphi process that fed into the consensus building process. As part of the meeting there was also a workshop held on the the implications for clinical trial design which I co-led. |
| Collaborator Contribution | Meeting was co-led with partner from LSHTM and WEHI and organisation was assisted by partners from UCT, Stellenbosch and South African MRC. Partners form NIH and BMGF sat on the steering commitee and provided financial support for thr meeting along with the Wellcome Centre for Infectious Disease Research at University of Cape Town. |
| Impact | 1. Scoping Review 2. Symposium and Consensus meeting 3. Position Paper (being written) |
| Start Year | 2022 |
| Description | Evaluation of the use of face mask sampling for TB |
| Organisation | University of Leicester |
| Department | Department of Health Sciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | As a result of the award we developed a new collaboration with University of Leicester to evaluate a novel diagnostic test they have developped to capture Mycobacterium tuberculosis within espiratory secretions within a face mask. This came about as we had a prospective cohort in Malawi as a result of the funding and led to oportunities to evaluate more novel diagnostics prosepectively |
| Collaborator Contribution | They have provided prototype face mask samplers for the study at cost and suppoted with the training of the site to undertake this work and with analysis |
| Impact | Nil yet |
| Start Year | 2021 |
| Description | INSIGHT network |
| Organisation | National Institutes of Health (NIH) |
| Country | United States |
| Sector | Public |
| PI Contribution | Membership of the INSIGHT group network has been enabled for me through my MRC Respiratory funding. This in turn has led me to be involved in future COVID and respiratory projects. The first project which brought in funding was ACTT/TICO which I was able to be PI of at my clinical site (Guy's and St Thomas' NHS Foundation Trust) and this brought in funding to enable our participation in international trials. It was matched in kind by local CRN funding through NIHR. |
| Collaborator Contribution | The INSIGHT network is a global network. It would not be possible without this collaboration. |
| Impact | Publications as per my publication log on remdesivir and baricitinib. |
| Start Year | 2021 |
| Description | St George's University of London |
| Organisation | St George's University of London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | MRC CTU at UCL is leading on design and statistical aspects of randomised trials in the fields of antibiotic treatment/antimicrobial resistance in children and neonates. |
| Collaborator Contribution | The team at SGUL provide clinical leadership to the programme of trials. |
| Impact | Multiple grants to conduct trials and observational studies, leading to peer reviewed publications, with further impacts to come. Multidiscplinary, including clinical medicine, statistics, trial management, laboratory management. |
| Start Year | 2015 |
| Description | UNITE4TB Academia and Industry United Innovation and Treatment for Tuberculosis |
| Organisation | Radboud University Nijmegen |
| Country | Netherlands |
| Sector | Academic/University |
| PI Contribution | UCL leads the trial design and statistical analysis of a new consortium for clinical drug and regimen development for TB. UNITE4TB will address the major challenge of defining new anti-TB drugs and regimens for the 21st century. The consortium will create a platform for conducting innovative Phase 2A, and Phase 2B/C clinical trials that can reliably and efficiently identify, anti-TB drug regimens at the optimal durations with the best chance of success in definitive, large-scale, Phase 3 trials. |
| Collaborator Contribution | With financial support from the Innovative Medicine Initiative (IMI) in Europe and the German Federal Ministry of Research and Education (BmBF), the UNITE4TB Consortium will begin work in 2021. With a total budget of 185 million euros, 22 European academic institutions, 3 research institutions from the United States and South Africa, 2 European Federation of Pharmaceutical Industries and Association (EFPIA) members and 2 Associated Partners (APs) from Germany, this will be the largest collaboration on clinical TB drug development in the history of the European Union. |
| Impact | None yet |
| Start Year | 2021 |
| Description | WHO collaboration on Global Survey of National TB Program on approach to systematic screening for TB |
| Organisation | Foundation for Innovative New Diagnostics (FIND) |
| Country | Switzerland |
| Sector | Charity/Non Profit |
| PI Contribution | Our research focuses on developing new approaches to identifying patients at risk of developing TB that can be identified through systematic screening. In order to find out what current practices are globally for this population what what the perceived challeges are we approached the WHO and FIND suggesting this global survey which they supported. |
| Collaborator Contribution | The WHO and FIND have helped by co-developing the survey and providing contacts for national TB programmes globally. |
| Impact | 1. Survey o completed by 63 National TB Programmes representing >80% of Global TB burden 2. Webinar held for National TB Programmes to feed back results attended by representatives of over 32 countries 3. Accepted abstract and oral presentation at the 52nd World Conference on TB and Lung Disease |
| Start Year | 2021 |
| Description | WHO collaboration on Global Survey of National TB Program on approach to systematic screening for TB |
| Organisation | World Health Organization (WHO) |
| Department | Global TB Program |
| Country | Switzerland |
| Sector | Public |
| PI Contribution | Our research focuses on developing new approaches to identifying patients at risk of developing TB that can be identified through systematic screening. In order to find out what current practices are globally for this population what what the perceived challeges are we approached the WHO and FIND suggesting this global survey which they supported. |
| Collaborator Contribution | The WHO and FIND have helped by co-developing the survey and providing contacts for national TB programmes globally. |
| Impact | 1. Survey o completed by 63 National TB Programmes representing >80% of Global TB burden 2. Webinar held for National TB Programmes to feed back results attended by representatives of over 32 countries 3. Accepted abstract and oral presentation at the 52nd World Conference on TB and Lung Disease |
| Start Year | 2021 |
| Title | Oral antibiotic step-down with amoxicillin or co-amoxiclav for varying duration of total antibiotic treatment |
| Description | Oral antibiotic step-down with amoxicillin or co-amoxiclav for varying duration of total antibiotic treatment for paediatric community acquired pneumonia in Africa. WHO currently recommends long-term intravenous antibiotic treatment for hospitalised children with severe/very severe pneumonia, leading to long stays and greater risks of nosocomial acquisition of other drug-resistant bacteria. There are no data on the use of oral amoxicillin or co-amoxiclav as "step-down" treatment once children are well enough to take oral rather than intravenous medications, and there are no data on optimal duration of total antibiotic treatment. Shorter treatment could reduce pressure for the development of antimicrobial resistance, reduce side-effects and enable children to be discharged sooner. EDCTP have funded a large RCT in South Africa, Uganda, Zambia and Zimbabwe to address this question. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Late clinical evaluation |
| Year Development Stage Completed | 2019 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| UKCRN/ISCTN Identifier | ISRCTN63115131 |
| Impact | Trial ongoing |
| Description | Briefing paper: Shorter treatment for children with minimal TB |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | This briefing paper looks at evidence from the SHINE trial, the first randomised controlled trial to assess the length of treatment needed for children with minimal TB. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.mrcctu.ucl.ac.uk/media/2057/shine-briefing-paper-220222.pdf |
| Description | COVAC1 Participant Webinar |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Study participants or study members |
| Results and Impact | We held a participant webinar in order to share the results of the dose-ranging part of the COVAC1 trial. COVAC1 evaluated a new type of vaccine candidate against SARS-CoV2 - it was a self-amplifying RNA vaccine. We evaluated 6 different doses for safety and immunogenicity. We held the webinar to explain the results before they were in the public domain on the Lancet pre-print server. The participants were very engaged, had lots of questions - some of which were difficult to answer. Participants were very interested to see their immune responses and we agreed to provide these, having emphasised that they were not to be used to make clinical decisions. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.imperial.ac.uk/news/222553/self-amplifying-rna-covid-19-vaccine-technology-safe/ |
| Description | Consensus meeting and symposium on Early TB disease |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | 60 stakeholders including WHO, FIND, NIH, Gates, South African MRC, National TB Programme Leads, TB advocates and acaademic attended consensus meeting to determine research framework for early TB disease, terminology and definitions |
| Year(s) Of Engagement Activity | 2022 |
| Description | Oral presentation 52nd World conference on Lung Health on NTP survey |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Oral absract presentation given by clinical fellow on the study reporting the findings from the survey of National TB Programmes |
| Year(s) Of Engagement Activity | 2022 |
| Description | PTBNET meeting: Invited talk "TB treatment shortening: are we there yet?" 23-24 Sep 2021 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Presented overview of the recent TB treatment shortening trials with focus on the SHINE trial results. |
| Year(s) Of Engagement Activity | 2021 |
| Description | SHINE Infographic |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | This infographic summarises the results of the SHINE trial. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.mrcctu.ucl.ac.uk/news/news-stories/2022/march/treatment-time-for-children-with-minimal-t... |
| Description | SHINE animated abstract |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | This animated abstract summarises the results of the SHINE trial. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://vimeo.com/474730726/e10e0b621c |
| Description | SHINE film |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | In 2020 an estimated 1.1 million children fell ill with tuberculosis (TB) globally. A quarter those children are estimated to have died, despite the fact that TB is treatable. This film shows how a ground-breaking multi-country randomised controlled clinical trial, co-ordinated by MRC-CTU at UCL and published in the New England Journal of Medicine, has already led to changes in WHO guidelines and will make treatment easier for children with TB. The full length version includes a discussion about implementing the trial results. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://vimeo.com/645164426/251c376917 |
| Description | Symposium at World TB meeting on Lung Health |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I co-led and chaired symposium on early/subclinical TB at the World Conference on Lung Health. The 2022 symposium had 2 talk on the work relating to the grant |
| Year(s) Of Engagement Activity | 2021,2022 |
| Description | WHO TB Guidelines Group Meeting Preparatory webinar: Invited talk Shorter Treatment for Non-severe Tuberculosis in African and Indian children |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Invited talk: Shorter treatment for non-severe tuberculosis in African and Indian children. Presented results of the SHINE trial to the WHO Guidelines Development Group. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Webinar on TB screening: Policies, Practices, Opportunities and Challenges |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | We conducted a survey of 63 National TB programmes as a part of the grant to explore policies, practices and challenges around TB screening. We then held a webinar to feed the results back to the NTP |
| Year(s) Of Engagement Activity | 2022 |