Childhood tuberculosis: Integrating tools for improved diagnosis and vaccines
Lead Research Organisation:
MRC Unit the Gambia
Department Name: Vaccinology Theme
Abstract
Tuberculosis still causes significant disability and death in many countries in the world, including half a million deaths in children each year. The diagnosis of TB is more difficult in children, as often it cannot be confirmed by "gold standard" methodology, which means showing presence of the TB bacilli in a patient, usually in their sputum. This is rarely possible in children, since they have fewer bacteria, often don't cough up sputum and still get very sick. They often don't receive treatment in time or not at all. Apart from looking for the TB bacilli, we hence use other more indirect tools to make a diagnosis, including observations of TB cases in the community and evidence that the host's immune system has been exposed to TB (patient) by doing a skin test. There are new technologies which can now be applied to blood samples of patients to see if their immune system expresses a characteristic "signature" of TB. However, these have not been used in children yet.
TB often occurs in households, which is where children are particularly likely to catch it from an infected adult. But not everyone gets it when exposed to a coughing "index case", which is the coughing person with active TB. It is likely that many factors like the organism in question, the conditions of the household and also the responses of the immune system of the individual child play a role. We have a large gap in our understanding of the transmission, susceptibility and what kind of immunity is needed to fend off the TB bacteria. This is why we have so far failed to make a better vaccine than the current vaccine, BCG, which is not fully protective. If we understand the mechanisms that underlie susceptibility and protection, this would be very useful for any trials of new vaccines, but also for the diagnosis, as we could look for specific markers associated with TB disease and protection. Such markers could also be used in vaccine or treatment trials, instead of purely relying on the bacteriologically confirmed cases, which is the current approach. This approach is very costly since it needs a very large number of children to participate in vaccine or treatment trials, as most of them will never show up with confirmation by bacteria and yet get sick with what we think is TB.
In our project, we will develop and test novel approaches by using new methods in the microbiology and immunology laboratory and have brought together a strong team of internal and external experts to be able to use all the state-of-the art available methodology.
In particular, we want to evaluate some of the new technologies to diagnose TB on the "signature" it leaves in the body and to use a statistical approach to bring together the individual pieces of the jigsaw that makes up TB diagnosis in children. We will also study children who do and do not get TB after exposure to the bacillus in their household, as the group who does not contract the disease or infection might hold the key to what is really protective against TB. This knowledge will be very important for making an improved vaccine, which can essentially mimic such protective mechanisms. With the help of more advanced statistical analysis of all the factors that contribute to a TB diagnosis we would like to come up with algorithms for the diagnosis that are just or nearly as good as the gold standard. We wish to conduct this project in the Gambia, where there is still a lot of TB. Thanks to the MRC Unit in The Gambia, we benefit from all the tools in the lab and field to collect samples and data for a very comprehensive assessment of every case.
Our long-term goal with this project is to enable the research community to develop a better diagnostic approach to childhood TB and understand how we should design the ideal vaccine against TB.
TB often occurs in households, which is where children are particularly likely to catch it from an infected adult. But not everyone gets it when exposed to a coughing "index case", which is the coughing person with active TB. It is likely that many factors like the organism in question, the conditions of the household and also the responses of the immune system of the individual child play a role. We have a large gap in our understanding of the transmission, susceptibility and what kind of immunity is needed to fend off the TB bacteria. This is why we have so far failed to make a better vaccine than the current vaccine, BCG, which is not fully protective. If we understand the mechanisms that underlie susceptibility and protection, this would be very useful for any trials of new vaccines, but also for the diagnosis, as we could look for specific markers associated with TB disease and protection. Such markers could also be used in vaccine or treatment trials, instead of purely relying on the bacteriologically confirmed cases, which is the current approach. This approach is very costly since it needs a very large number of children to participate in vaccine or treatment trials, as most of them will never show up with confirmation by bacteria and yet get sick with what we think is TB.
In our project, we will develop and test novel approaches by using new methods in the microbiology and immunology laboratory and have brought together a strong team of internal and external experts to be able to use all the state-of-the art available methodology.
In particular, we want to evaluate some of the new technologies to diagnose TB on the "signature" it leaves in the body and to use a statistical approach to bring together the individual pieces of the jigsaw that makes up TB diagnosis in children. We will also study children who do and do not get TB after exposure to the bacillus in their household, as the group who does not contract the disease or infection might hold the key to what is really protective against TB. This knowledge will be very important for making an improved vaccine, which can essentially mimic such protective mechanisms. With the help of more advanced statistical analysis of all the factors that contribute to a TB diagnosis we would like to come up with algorithms for the diagnosis that are just or nearly as good as the gold standard. We wish to conduct this project in the Gambia, where there is still a lot of TB. Thanks to the MRC Unit in The Gambia, we benefit from all the tools in the lab and field to collect samples and data for a very comprehensive assessment of every case.
Our long-term goal with this project is to enable the research community to develop a better diagnostic approach to childhood TB and understand how we should design the ideal vaccine against TB.
Technical Summary
Tuberculosis causes significant morbidity and mortality in children worldwide. Bacteriological confirmation of TB in children is rare and lack of suitable alternative diagnostics is a major bottleneck to progress in identifying patients in need of treatment and in clinical trials of new vaccines and therapies. The MRC Unit, The Gambia can make a significant contribution in this field, since it has a track record in TB research, established data collection tools and state-of-the art laboratory facilities. Suitable cohorts of children with TB disease, infected and controls can be predicted. Our team of local and international investigators will further develop and evaluate existing and new tools based on both host immune response and microbiology and work with new external collaborators, who are highly experienced in statistical analysis. We will test samples from TB-affected children (exposed, infected or diseased) identified in household cohorts by using a combined approach of host and pathogen signatures and cellular and molecular methods, such as GeneXpert and biosignatures. We will characterise host responses associated with protection against infection in TB-exposed children who remain uninfected and who can serve as a model for protective immunity. We will expand our existing epidemiological database to include the epidemiological and microbiological context of household transmission and its impact on host responses. We will develop a novel statistical approach to design prediction algorithms for the diagnosis of childhood TB. Translation to Policy: Integration of measurable host responses into diagnostic algorithms will inform not only the diagnosis of the individual patient but also facilitate clinical trials of new vaccines and drugs. Understanding of protective immune mechanisms will guide vaccine design. Epidemiological datasets that link TB exposure, infection and disease can serve as a model for public health and TB control.
Planned Impact
Tuberculosis remains a global emergency and affects and continues to kill adults and children in large numbers worldwide.
Our project proposal has been developed to address a critical bottleneck for patient management and clinical trials of new vaccines and drugs alike: a) the problem of accurate diagnostics for tuberculosis (TB) in children and b) the absence of markers of protection which can be used as endpoints for TB vaccine trials. This bottleneck is widely acknowledged by the scientific community and international TB program officers, and remains at the center of international research efforts. This was highlighted in the special supplement to the Journal of Infectious Disease, published on World TB Day 2012 and dedicated to basic research but also implementation obstacles for TB globally.
Without a better diagnostic approach, which doesn't exclusively rely on bacteriological confirmation, children are not likely to be included in any studies of improved treatment for TB, and any ongoing vaccine trials will continue to require large and expensive cohorts of patients to be followed prospectively over a long period of time. This is prohibitively expensive and will preclude the evaluation of promising vaccine candidates as there simply are not enough field sites available that can provide both sizeable paediatric cohorts and have the laboratory and clinical capacity to follow them up in clinical trials.
Our research program will impact on areas of discovery, development and delivery within childhood tuberculosis. All of these are required and have merit in driving forward the agenda to improve the diagnosis and treatment of individual cases of TB in children and ultimately also facilitate clinical trials for new treatments and vaccines.
Discovery: the identification of new biomarkers and host/pathogen signatures will drive the development of point-of care tests for TB by identifying new leads in either metabolomics, cytokine or gene signatures, which are amenable to further development with the help of industry partners and not-for profit organisations such as FIND/PATH. To understand mechanisms of protection against infection opens up a key avenue for vaccine design and evaluation, as ultimately, only a TB vaccine that prevents infection and disease will have the desired public health impact for TB control.
Development: we expect that the evaluation of recently identified biosignatures from adult populations will confirm preliminary results also in children and will then stimulate the development of more user-friendly versions of assays, including translation into nanotechnological and lateral flow-based assays, again partnering with industry in the future.
Delivery: The assessment of impact of epidemiological components for household transmission and the analysis of additional laboratory assays built into the diagnostic algorithms will lend support for the planning of interventions and mobilisation of resources for policy makers in TB and the national TB programs in a variety of settings, depending on resources available. The aim of this particular objective is to develop further policy links and share the algorithms and toolbox concept with our partners in NLTP in resource-poor and -rich settings. We anticipate that these algorithms could be tailored according to available resources and require to be evaluated in a variety of populations (+/- HIV). We will then liaise with experts in cost-effectiveness analysis (i.e. Imperial College Business school, HPA, WHO) to quantify the potential need for resources, depending on the algorithm chosen. This will allow the TB program decision makers to develop more appropriate predictions of impact depending on the settings that wish to adapt them.Through close links between our research and the National Leprosy and TB program (NLTP), the experience in The Gambia will inform international TB control efforts via communication channels such as the StopTB partnership and WHO.
Our project proposal has been developed to address a critical bottleneck for patient management and clinical trials of new vaccines and drugs alike: a) the problem of accurate diagnostics for tuberculosis (TB) in children and b) the absence of markers of protection which can be used as endpoints for TB vaccine trials. This bottleneck is widely acknowledged by the scientific community and international TB program officers, and remains at the center of international research efforts. This was highlighted in the special supplement to the Journal of Infectious Disease, published on World TB Day 2012 and dedicated to basic research but also implementation obstacles for TB globally.
Without a better diagnostic approach, which doesn't exclusively rely on bacteriological confirmation, children are not likely to be included in any studies of improved treatment for TB, and any ongoing vaccine trials will continue to require large and expensive cohorts of patients to be followed prospectively over a long period of time. This is prohibitively expensive and will preclude the evaluation of promising vaccine candidates as there simply are not enough field sites available that can provide both sizeable paediatric cohorts and have the laboratory and clinical capacity to follow them up in clinical trials.
Our research program will impact on areas of discovery, development and delivery within childhood tuberculosis. All of these are required and have merit in driving forward the agenda to improve the diagnosis and treatment of individual cases of TB in children and ultimately also facilitate clinical trials for new treatments and vaccines.
Discovery: the identification of new biomarkers and host/pathogen signatures will drive the development of point-of care tests for TB by identifying new leads in either metabolomics, cytokine or gene signatures, which are amenable to further development with the help of industry partners and not-for profit organisations such as FIND/PATH. To understand mechanisms of protection against infection opens up a key avenue for vaccine design and evaluation, as ultimately, only a TB vaccine that prevents infection and disease will have the desired public health impact for TB control.
Development: we expect that the evaluation of recently identified biosignatures from adult populations will confirm preliminary results also in children and will then stimulate the development of more user-friendly versions of assays, including translation into nanotechnological and lateral flow-based assays, again partnering with industry in the future.
Delivery: The assessment of impact of epidemiological components for household transmission and the analysis of additional laboratory assays built into the diagnostic algorithms will lend support for the planning of interventions and mobilisation of resources for policy makers in TB and the national TB programs in a variety of settings, depending on resources available. The aim of this particular objective is to develop further policy links and share the algorithms and toolbox concept with our partners in NLTP in resource-poor and -rich settings. We anticipate that these algorithms could be tailored according to available resources and require to be evaluated in a variety of populations (+/- HIV). We will then liaise with experts in cost-effectiveness analysis (i.e. Imperial College Business school, HPA, WHO) to quantify the potential need for resources, depending on the algorithm chosen. This will allow the TB program decision makers to develop more appropriate predictions of impact depending on the settings that wish to adapt them.Through close links between our research and the National Leprosy and TB program (NLTP), the experience in The Gambia will inform international TB control efforts via communication channels such as the StopTB partnership and WHO.
Organisations
- MRC Unit the Gambia (Lead Research Organisation)
- West African Network for TB, AIDS and Malaria (Collaboration)
- UCSF Medical Center (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- University of Bamako (Collaboration)
- UNIVERSITY OF JOS (Collaboration)
- UNIVERSITY OF OXFORD (Collaboration)
- National Institute for Medical Research, Tanzania (Collaboration)
- University of San Francisco (Collaboration)
- Boston Children's Hospital (Collaboration)
- Ludwig Maximilian University of Munich (LMU Munich) (Collaboration)
- Liverpool School of Tropical Medicine (Collaboration)
- University Cheikh Anta Diop de Dakar (Collaboration)
- UNIVERSITY OF LIVERPOOL (Collaboration)
- UNIVERSITY OF BRITISH COLUMBIA (Collaboration)
Publications
Afolabi MO
(2015)
A multimedia consent tool for research participants in the Gambia: a randomized controlled trial.
in Bulletin of the World Health Organization
Snow KJ
(2020)
Adolescent tuberculosis.
in The Lancet. Child & adolescent health
Whittaker E
(2018)
Age-related waning of immune responses to BCG in healthy children supports the need for a booster dose of BCG in TB endemic countries.
in Scientific reports
Basu Roy R
(2019)
An Auto-luminescent Fluorescent BCG Whole Blood Assay to Enable Evaluation of Paediatric Mycobacterial Responses Using Minimal Blood Volumes.
in Frontiers in pediatrics
Le Doare K
(2015)
Anti-group B Streptococcus antibody in infants born to mothers with human immunodeficiency virus (HIV) infection.
in Vaccine
Tapia MD
(2015)
Antibody Persistence 1-5 Years Following Vaccination With MenAfriVac in African Children Vaccinated at 12-23 Months of Age.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Togun T
(2020)
Anticipating the impact of the COVID-19 pandemic on TB patients and TB control programmes.
in Annals of clinical microbiology and antimicrobials
Tientcheu LD
(2016)
Association of slow recovery of Mycobacterium africanum-infected patients posttreatment with high content of Persister-Like bacilli in pretreatment sputum.
in International journal of mycobacteriology
Grassly NC
(2015)
Biological challenges to effective vaccines in the developing world.
in Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Togun TO
(2018)
Biomarkers for diagnosis of childhood tuberculosis: A systematic review.
in PloS one
Mendy J
(2018)
Changes in Mycobacterium tuberculosis-Specific Immunity With Influenza co-infection at Time of TB Diagnosis.
in Frontiers in immunology
Hemingway C
(2017)
Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function.
in PloS one
Graham SM
(2015)
Clinical Case Definitions for Classification of Intrathoracic Tuberculosis in Children: An Update.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Idoko OT
(2015)
Community Perspectives Associated With the African PsA-TT (MenAfriVac) Vaccine Trials.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Bojang AL
(2016)
Comparison of TB-LAMP, GeneXpert MTB/RIF and culture for diagnosis of pulmonary tuberculosis in The Gambia.
in The Journal of infection
Togun TO
(2015)
Contribution of Xpert® MTB/RIF to the diagnosis of pulmonary tuberculosis among TB-exposed children in The Gambia.
in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Owolabi OA
(2020)
Delay in the diagnosis of pulmonary tuberculosis in The Gambia, West Africa: A cross-sectional study.
in International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
Tientcheu LD
(2014)
Differences in T-cell responses between Mycobacterium tuberculosis and Mycobacterium africanum-infected patients.
in European journal of immunology
Tientcheu LD
(2015)
Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment.
in Genes and immunity
Elliott TO
(2015)
Dysregulation of Apoptosis Is a Risk Factor for Tuberculosis Disease Progression.
in The Journal of infectious diseases
Roca A
(2015)
Ebola: a holistic approach is required to achieve effective management and control.
in The Journal of allergy and clinical immunology
Lowe DM
(2015)
Effect of Antiretroviral Therapy on HIV-mediated Impairment of the Neutrophil Antimycobacterial Response.
in Annals of the American Thoracic Society
Van Leth F
(2014)
Embracing the challenges of HIV-TB co-infection in children.
in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Martellet L
(2015)
Ethical Challenges and Lessons Learned During the Clinical Development of a Group A Meningococcal Conjugate Vaccine.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Kampmann B
(2018)
Evaluating UK National Guidance for Screening of Children for Tuberculosis. A Prospective Multicenter Study.
in American journal of respiratory and critical care medicine
Kampmann B
(2015)
Factors influencing innate immunity and vaccine responses in infancy.
in Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Garand M
(2018)
Functional and Phenotypic Changes of Natural Killer Cells in Whole Blood during Mycobacterium tuberculosis Infection and Disease.
in Frontiers in immunology
Seddon JA
(2015)
HIV and tuberculosis in children: biology meets epidemiology.
in The lancet. HIV
Tientcheu LD
(2016)
Host Immune Responses Differ between M. africanum- and M. tuberculosis-Infected Patients following Standard Anti-tuberculosis Treatment.
in PLoS neglected tropical diseases
Pollock L
(2013)
How to use: interferon ? release assays for tuberculosis.
in Archives of disease in childhood. Education and practice edition
Andreas NJ
(2015)
Human breast milk: A review on its composition and bioactivity.
in Early human development
Egere U
(2017)
Identifying children with tuberculosis among household contacts in The Gambia.
in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Coulter F
(2017)
IL-17 Production from T Helper 17, Mucosal-Associated Invariant T, and ?d Cells in Tuberculosis Infection and Disease.
in Frontiers in immunology
Bah S
(2017)
Immune oxysterols: Role in mycobacterial infection and inflammation
in The Journal of Steroid Biochemistry and Molecular Biology
Piot P
(2019)
Immunization: vital progress, unfinished agenda.
in Nature
Gehre F
(2013)
Immunogenic Mycobacterium africanum strains associated with ongoing transmission in The Gambia.
in Emerging infectious diseases
Tientcheu LD
(2017)
Immunological consequences of strain variation within the Mycobacterium tuberculosis complex.
in European journal of immunology
Egere U
(2017)
In reply.
in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Mackenzie GA
(2015)
Increased disease due to Haemophilus influenzae type b: population-based surveillance in eastern Gambia, 2008-2013.
in The Pediatric infectious disease journal
Fletcher HA
(2013)
Inhibition of mycobacterial growth in vitro following primary but not secondary vaccination with Mycobacterium bovis BCG.
in Clinical and vaccine immunology : CVI
Egere U
(2016)
Isoniazid preventive treatment among child contacts of adults with smear-positive tuberculosis in The Gambia.
in Public health action
Nkereuwem E
(2022)
Making a case for investing in post-tuberculosis lung health in children.
in The Lancet. Respiratory medicine
Turkova A
(2017)
Management of child MDR-TB contacts across countries in the WHO European Region: a survey of current practice.
in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Turkova A
(2014)
Management of paediatric tuberculosis in leading UK centres: unveiling consensus and discrepancies.
in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Lange C
(2014)
Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement.
in The European respiratory journal
Williams B
(2013)
Management of pediatric contacts of multidrug resistant tuberculosis in the United Kingdom.
in The Pediatric infectious disease journal
| Description | Assistance to the National TB program |
| Geographic Reach | National |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | The training program in childhood tuberculosis which was established through my program grant has led to a doubling of the notification of cases of childhood TB in the country. It has also led to the request for our involvement to assist the National Leprosy and TB Program of The Gambia in their preparation for the application for funding to the Global Fund. This request for funding was granted and now also includes more provision of services for children. |
| Description | Book chapter in new book on childhood TB |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | I am the author of the chapter on immunology in the new book on childhood and adolescent TB recently published by Starke and Donaldson- this textbook is virtually the only available textbook and to be asked to author a chapter pays tribute to my international standing in the field. |
| Description | Participation in NIH workshop on reserach agenda for latent TB infection- represnted paediatric components |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Membership of a guideline committee |
| Guideline Title | NIH Classification of childhood TB |
| Description | Update of classification for childhood TB |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in clinical guidelines |
| Impact | The definitions for childhood TB have facilitate the notifications of the condition to the WHO and the rise of age-disaggregated data in the reports to the Who has been phenomenal. The reporting of childhood TB in The Gambia rose by 60% since I initiated the childhood TB research program. |
| Description | CHILDHOOD 'OMICS' AND MYCOBACTERIUM TUBERCULOSIS-DERIVED BIOSIGNATURES (COMBO) FOR TB DIAGNOSIS IN HIGH HIV PREVALENCE SETTINGS |
| Amount | $1,503,586 (USD) |
| Funding ID | R01AI152161 |
| Organisation | National Institute of Allergy and Infectious Diseases (NIAID) |
| Sector | Public |
| Country | United States |
| Start | 04/2020 |
| End | 03/2025 |
| Description | GCRF |
| Amount | £580,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2017 |
| End | 04/2019 |
| Description | German Government- BMBF- International collaborations |
| Amount | € 2,000,000 (EUR) |
| Organisation | German Federal Ministry of Education and Research |
| Sector | Public |
| Country | Germany |
| Start | 07/2016 |
| End | 06/2021 |
| Description | HOST PROTEOMIC BIOSIGNATURES FOR A URINE-BASED DIAGNOSIS OF PULMONARY TUBERCULOSIS IN CHILDREN |
| Amount | $209,400 (USD) |
| Funding ID | K23HL153581 |
| Organisation | National Heart, Lung, and Blood Institute (NHLBI) |
| Department | Candidate gene Association Resource (CARe) |
| Sector | Academic/University |
| Country | United States |
| Start | 09/2020 |
| End | 08/2025 |
| Description | MRC Program grant |
| Amount | £2,000,000 (GBP) |
| Organisation | MRC Harwell |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 01/2013 |
| End | 01/2018 |
| Description | NIH- Biomarkers for Childhood TB |
| Amount | $2,500,000 (USD) |
| Organisation | National Institutes of Health (NIH) |
| Sector | Public |
| Country | United States |
| Start | 02/2020 |
| End | 01/2024 |
| Description | NIH- Biomrker Award PI Levin |
| Amount | $2,000,000 (USD) |
| Organisation | National Institutes of Health (NIH) |
| Sector | Public |
| Country | United States |
| Start | 01/2018 |
| End | 12/2023 |
| Description | Networks of Excellence EDCTP |
| Amount | € 3,066,638 (EUR) |
| Organisation | Sixth Framework Programme (FP6) |
| Department | European and Developing Countries Clinical Trials Partnership |
| Sector | Public |
| Country | Netherlands |
| Start | 03/2017 |
| End | 03/2020 |
| Description | UKRI-GCRF |
| Amount | £150,000 (GBP) |
| Organisation | United Kingdom Research and Innovation |
| Department | Global Challenges Research Fund |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2020 |
| End | 03/2021 |
| Description | Validation of Biomarkers of Pediatric TB and further development for use in diagnosis of childhood TB |
| Amount | $1,000,208 (USD) |
| Funding ID | R01AI128765-02 |
| Organisation | National Institutes of Health (NIH) |
| Sector | Public |
| Country | United States |
| Start | 12/2016 |
| End | 11/2021 |
| Description | WANETAM- network |
| Amount | € 2,000,000 (EUR) |
| Organisation | European Commission H2020 |
| Sector | Public |
| Country | Belgium |
| Start | 04/2018 |
| End | 04/2022 |
| Title | reporter gene mycobacteria |
| Description | I generated a new generation of reporter-gene tagged mycobacteria in my lab which facilitates studies of host/pathogen interaction |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | new assay for high throughput of drug screening set up |
| Title | R4KA database |
| Description | 4-country research database for implementation of the project, data integrity and data sharing on a regular basis |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | No |
| Impact | able to share data across the platform of the study and enable data quality control |
| Title | database for TB contacts in households |
| Description | This database links index cases and contacts affected by tuberculosis |
| Type Of Material | Database/Collection of data |
| Year Produced | 2013 |
| Provided To Others? | Yes |
| Impact | The set up of the database in The Gambia is also a useful tool for the TB research at Imperial College and has been shared in an anonymised way with all ethical approvals |
| Description | British Columbia University |
| Organisation | University of British Columbia |
| Department | Department of Pediatrics |
| Country | Canada |
| Sector | Academic/University |
| PI Contribution | provided support for field sample collections and vaccinations, plus laboratory facilities |
| Collaborator Contribution | access to protocols |
| Impact | publication, presentation at international meeting, visibility |
| Start Year | 2014 |
| Description | COMBO-NIH grant |
| Organisation | UCSF Medical Center |
| Country | United States |
| Sector | Hospitals |
| PI Contribution | We are co-investigators on this NIH award and will be contributing samples and data and experience |
| Collaborator Contribution | This new grant on which we are co-investigators will discover new biomarkers for childhood TB diagnosis It is a 5-year project |
| Impact | not yet |
| Start Year | 2020 |
| Description | GCRF Foundation Award partner |
| Organisation | National Institute for Medical Research, Tanzania |
| Department | NIMR Mbeya Research Centre |
| Country | Tanzania, United Republic of |
| Sector | Academic/University |
| PI Contribution | Grant Facilitates Recruitment site for childhood GCRF grant, MRC Gambia provides training |
| Collaborator Contribution | sample collection, policy development |
| Impact | ongoing |
| Start Year | 2017 |
| Description | GCRF Foundation Award partner |
| Organisation | University of Jos |
| Country | Nigeria |
| Sector | Academic/University |
| PI Contribution | Grant Facilitates Recruitment site for childhood GCRF grant, MRC Gambia provides training |
| Collaborator Contribution | Recruitment of patients and biosamples for collaborative childhood TB work |
| Impact | capacity building , research skills |
| Start Year | 2017 |
| Description | GCRF Foundation award partner |
| Organisation | University of Bamako |
| Country | Mali |
| Sector | Academic/University |
| PI Contribution | Grant Facilitates Recruitment site for childhood GCRF grant, MRC Gambia provides training |
| Collaborator Contribution | Able to recruit patients to collaborative project |
| Impact | ongoing |
| Start Year | 2017 |
| Description | IMPALA |
| Organisation | Liverpool School of Tropical Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Collaboration on assessment of child lung health |
| Collaborator Contribution | Training and expertise |
| Impact | new collaboration |
| Start Year | 2018 |
| Description | Jos |
| Organisation | University of Jos |
| Department | Department of Paediatrics |
| Country | Nigeria |
| Sector | Academic/University |
| PI Contribution | We engaged Dr Ebonyi as our partner in the research project and devised the protocol and data system to be implemented on site. We shared our training materials |
| Collaborator Contribution | The partners in Jos have enabled implementation of the GCRF work and facilitated close links with the Nigerian National TB Control Program and have led training activities in Nigeria for chidlhood TB as well as informed documentation of implementation of IPT. |
| Impact | derived documents now used in National TB programs |
| Start Year | 2017 |
| Description | Levy Lab |
| Organisation | Boston Children's Hospital |
| Department | Levy Laboratory |
| Country | United States |
| Sector | Hospitals |
| PI Contribution | set up of systems vaccinology research for studies of EPI vaccines |
| Collaborator Contribution | bioinformatics support |
| Impact | several publications and a grant submission to the nIH |
| Start Year | 2014 |
| Description | NIH grant for biomarkers of chidlhood TB diagnostics |
| Organisation | University of San Francisco |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | this recently awarded NIH grant will allow us ot contribute stored samples form the MRC program grant and GCRF award to the validation of childhood TB diagnostic markers and to prospectively recruit a new cohort of children with TB and community controls |
| Collaborator Contribution | The grant is led by the colleagues from the University of San Francisco and we are research partners with a sub contract. |
| Impact | none yet |
| Start Year | 2020 |
| Description | Oxford Vaccine Group |
| Organisation | University of Oxford |
| Department | Oxford Vaccine Group |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | mutual engagement in Vaccinology research |
| Collaborator Contribution | joint supervision of PhD student |
| Impact | new collaboration |
| Start Year | 2014 |
| Description | Tanzania |
| Organisation | National Institute for Medical Research, Tanzania |
| Department | NIMR Mbeya Research Centre |
| Country | Tanzania, United Republic of |
| Sector | Academic/University |
| PI Contribution | Identification of children in households affected by TB through protocols, data collection tools and teaching |
| Collaborator Contribution | recruitment of children affected by TB and samples for biomarker studies |
| Impact | samples currently undergoing evaluation for novel diagnostics |
| Start Year | 2017 |
| Description | UCAD |
| Organisation | University Cheikh Anta Diop de Dakar |
| Country | Senegal |
| Sector | Academic/University |
| PI Contribution | Professor Mboup and Professor Gaye are partners in our West African Global Health Research initiative and a number of members of their respective departments are now involved in our research |
| Collaborator Contribution | exchange of ideas and potential for join grant applications |
| Impact | scientific workshops |
| Start Year | 2016 |
| Description | UKRI-GCRF award for partenrship in chidlhood TB sequelae (just awarded) |
| Organisation | University of Liverpool |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This GCRF grant is held by my postdoc Dr Togun and myself at MRCG@LSHTM. We have small salary portions on it only as overall garnt small and money needed for the activities- hence we give time in lieu to set up this new collaboration to establish a platform to study lung outcome in chidlren who are/were affected by TB |
| Collaborator Contribution | This GCRF award has established a partnership with Dr Kevin Mortimer at Liverpool University and his team. The grant is held at MRC Gambia at teh LSHTM. Whilst he has a small salary contribution, his team is contributing in kind in order to set things up for the more substantial application next year. |
| Impact | not yet |
| Start Year | 2020 |
| Description | UNiversity of Bamako |
| Organisation | University of Bamako |
| Country | Mali |
| Sector | Academic/University |
| PI Contribution | Identification of children in households affected by TB through protocols, data collection tools and teaching |
| Collaborator Contribution | Implementation of contact tracing for children with TB via the National TB program sample collections for biomarker evaluations |
| Impact | Implementation of contact tracing for children with TB via the National TB program |
| Start Year | 2017 |
| Description | University of Jos, Nigeria |
| Organisation | University of Jos |
| Department | Department of Paediatrics |
| Country | Nigeria |
| Sector | Academic/University |
| PI Contribution | A paediatrician form Jos is developing a research project under my supervision and received funding via Imperial College in 2016. He is now also a collaborator on the Foundation GCRF award |
| Collaborator Contribution | set up of validators cohorts for childhood TB research |
| Impact | Foundation Award MRC |
| Start Year | 2015 |
| Description | University of Munich |
| Organisation | Ludwig Maximilian University of Munich (LMU Munich) |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Collaborative grant award from the German ministry to conduct research into lung sequelae of TB |
| Collaborator Contribution | LMU is the grant holder and chose my TB program at MRC and the TBCC as a partner site in this 5-counry multicentre study. |
| Impact | the study is just starting, the website is being developed |
| Start Year | 2016 |
| Description | WANETAM network |
| Organisation | West African Network for TB, AIDS and Malaria |
| Country | Senegal |
| Sector | Charity/Non Profit |
| PI Contribution | The WANETAM network is an EDCTP funded network across partners in West Africa. My group leads the TB workpackage which has created a platform for the conduct of childhood TB research and funds research and career development for paediatricians and NLTP in the region to invest in better diagnosis and management of childhood TB. Most activities are led by my post doc Dr Toyin Togun who achieved his PhD under the original program grant form MRC to myself, I therefore see this as an impactful outcome. |
| Collaborator Contribution | Partners in 7 West African countries are making contributions by dedication time and personnel to the aim of the network package, which is to achieve better diagnosis and management of childhood TB in the region. |
| Impact | ongoing, only started in 2019, training delivered, all Ethics through in all countries, MSc student appointed, database designed and shared- now recruiting |
| Start Year | 2019 |
| Description | metabolomics |
| Organisation | Imperial College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | new collaboration on metabolomics analysis for TB samples |
| Collaborator Contribution | equipment and analysis capabilities available to me |
| Impact | analysis ongoing |
| Start Year | 2014 |
| Title | Patent for TB biomarker signature |
| Description | this patent application is a direct result of the work conducted on my MRC program grant. it protects a diagnostic biosignature for childhood TB which can now be taken forward for further evaluation and potentially developed into a POC test. |
| IP Reference | P10280GB |
| Protection | Patent application published |
| Year Protection Granted | 2016 |
| Licensed | No |
| Impact | only just filed |
| Description | Community sensitisation events |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Participants in your research and patient groups |
| Results and Impact | The community sensitisation events are regularly conducted to inform past, present and future participants in our research on the results of previous studies and upcoming new research studies and clinical trials. They serve as a link to the community decision makers and are well supported by community members and MRC researchers. Increased participation in clincial trials and ongoign research |
| Year(s) Of Engagement Activity | 2010,2011,2012,2013,2014 |
| Description | Engagement with local schoolchidlrne aroufn TB in the community |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Several schools have been invited to workshops and information sessions at the MRC Unit to talk about TB, the symptoms, stigma-related issues- these activities are led by a member of our team, Dr Owalabi, who also received small funding for Public engagement from the LSHTM. |
| Year(s) Of Engagement Activity | 2019,2020 |
| Description | INMIS media interveiw |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | as part of the International Symposium for neonatal and maternal immunisations hick I organised in The Gambia I gave a television interview to the national media which was broadcasted on the same day |
| Year(s) Of Engagement Activity | 2015 |
| Description | Kick of meeting Mali , Bamako University |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Kick off meeting for the GCRF award engaged University of Bamako practitioners and the National TB program |
| Year(s) Of Engagement Activity | 2017 |
| Description | Lancet personal profile |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Type Of Presentation | Paper Presentation |
| Geographic Reach | International |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Personal Profile in The Lancet entitled" Professor Beate Kampmann: Advocate for Childhood Tuberculosis" invitations to present work at various international meetings |
| Year(s) Of Engagement Activity | 2012 |
| Description | Open Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Type Of Presentation | Poster Presentation |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Increased interest in science and Medicine by Gambian schoolkids. Gives an overview of what MRC does and the specific projects within TB. Promotes school attachees and training by MRC for capacity building in Gambia. |
| Year(s) Of Engagement Activity | Pre-2006,2006,2008,2009,2010,2011,2012,2013 |
| Description | TB conference |
| Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
| Part Of Official Scheme? | Yes |
| Type Of Presentation | Keynote/Invited Speaker |
| Geographic Reach | International |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Mycobacterium tuberculosis... can we beat it? Organised by Euroscion. London, UK, March 21st, 2013. Published in: Arundhati Maitra and Sanjib Bhakta, Mycobacterium tuberculosis Can we beat it? A Euroscicon conference 2013. Virulence 4:6, 499-503; August 15, 2013 Education of UK/europe on the TB epidemic in Africa. Importance of developing rapid TB tests. |
| Year(s) Of Engagement Activity | 2013 |
| Description | Union TB meeting 2013 |
| Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
| Part Of Official Scheme? | Yes |
| Type Of Presentation | Keynote/Invited Speaker |
| Geographic Reach | International |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Adetifa I., Sutherland J, Hill P, Kampmann B. New Evidence for Computer-Aided Detection of Tuberculosis, Paris-Oral presentation (October 2013) Networking and strengthening collaborations. Discussion with experts on use of computer technology for TB diagnosis. |
| Year(s) Of Engagement Activity | 2013 |
| Description | Union TB meeting 2014 |
| Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
| Part Of Official Scheme? | Yes |
| Type Of Presentation | poster presentation |
| Geographic Reach | International |
| Primary Audience | Participants in your research and patient groups |
| Results and Impact | Discussion and networking. Discussions with researchers from other TB-endemic countries |
| Year(s) Of Engagement Activity | 2014 |
| Description | World TB Day community activities |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | For the World TB day on March 24th we coordinated joint activities with the NLTP of The Gambia in a coastal community. Schoolchildren and lay audience as well as healthcare workers and patents participated. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.mrc.gm/mrc-unit-tb-research-world-tb-day-celebration/ |
| Description | World TB Day in conjucntion with National TB Program the Gambia |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Each year our team collaborated with the National TB program in teh Gambia to stage events around World TB Day and to give visibility to all of the TB control activities. These events are always attended by national TV and radio and written up in national newspapers as well as publicised via the mRC comms channels. World TB Day is an international event. |
| Year(s) Of Engagement Activity | 2019,2020 |