Dedicoat, Martin
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Biography
Martin is a consultant infectious diseases physician with expertise in tuberculosis (TB) management and care. He holds dual appointments, working both at University Hospitals Birmingham NHS Foundation Trust (UHB) and the UK Health Security Agency's (UKHSA) TB Unit. His research interests include tuberculosis epidemiology and health care for underserved populations.
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Publication Metadata only Distinct blood transcriptomic signature of treatment in latent tuberculosis infected individuals at risk of developing active disease.(Churchill Livingstone, 2021-09-14) Burel, Julie G; Singhania, Akul; Dubelko, Paige; Muller, Julius; Tanner, Rachel; Parizotto, Eneida; Dedicoat, Martin; Fletcher, Thomas E; Dunbar, James; Cunningham, Adam F; Lindestam Arlehamn, Cecilia S; Catanzaro, Donald G; Catanzaro, Antonino; Rodwell, Timothy; McShane, Helen; O'Shea, Matthew K; Peters, Bjoern; Infectious Diseases; Pathology; Medical and Dental; Dedicoat, Martin; O'Shea, Matthew KAlthough only a small fraction will ever develop the active form of tuberculosis (ATB) disease, chemoprophylaxis treatment in latent TB infected (LTBI) individuals is an effective strategy to control pathogen transmission. Characterizing immune responses in LTBI upon chemoprophylactic treatment is important to facilitate treatment monitoring, and thus improve TB control strategies. Here, we studied changes in the blood transcriptome in a cohort of 42 LTBI and 8 ATB participants who received anti-TB therapy. Based on the expression of previously published gene signatures of progression to ATB, we stratified the LTBI cohort in two groups and examined if individuals deemed to be at elevated risk of developing ATB before treatment (LTBI-Risk) differed from others (LTBI-Other). We found that LTBI-Risk and LTBI-Other groups were associated with two distinct transcriptomic treatment signatures, with the LTBI-Risk signature resembling that of treated ATB patients. Notably, overlapping genes between LTBI-Risk and ATB treatment signatures were associated with risk of progression to ATB and interferon (IFN) signaling, and were selectively downregulated upon treatment in the LTBI-Risk but not the LTBI-Other group. Our results suggest that transcriptomic reprogramming following treatment of LTBI is heterogeneous and can be used to distinguish LTBI-Risk individuals from the LTBI cohort at large.Publication Metadata only Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: An observational study(Elsevier, 2022-03-24) Walker, Timothy M; Choisy, Marc; Dedicoat, Martin; Drennan, Philip G; Wyllie, David; Yang-Turner, Fan; Crook, Derrick W; Robinson, Esther R; Walker, A Sarah; Smith, E Grace; Peto, Timothy E A; Infectious Diseases; Medical and Dental; Dedicoat, MartinBackground: Over 10-years of whole-genome sequencing (WGS) of Mycobacterium tuberculosis in Birmingham presents an opportunity to explore epidemiological trends and risk factors for transmission in new detail. Methods: Between 1st January 2009 and 15th June 2019, we obtained the first WGS isolate from every patient resident in a postcode district covered by Birmingham's centralised tuberculosis service. Data on patients' sex, country of birth, social risk-factors, anatomical locus of disease, and strain lineage were collected. Poisson harmonic regression was used to assess seasonal variation in case load and a mixed-effects multivariable Cox proportionate hazards model was used to assess risk factors for a future case arising in clusters defined by a 5 single nucleotide polymorphism (SNP) threshold, and by 12 SNPs in a sensitivity analysis. Findings: 511/1653 (31%) patients were genomically clustered with another. A seasonal variation in diagnoses was observed, peaking in spring, but only among clustered cases. Risk-factors for a future clustered case included UK-birth (aHR=2·03 (95%CI 1·35-3·04), p < 0·001), infectious (pulmonary/laryngeal/miliary) tuberculosis (aHR=3·08 (95%CI 1·98-4·78), p < 0·001), and M. tuberculosis lineage 3 (aHR=1·91 (95%CI 1·03-3·56), p = 0·041) and 4 (aHR=2·27 (95%CI 1·21-4·26), p = 0·011), vs. lineage 1. Similar results pertained to 12 SNP clusters, for which social risk-factors were also significant (aHR 1·72 (95%CI 1·02-2·93), p = 0·044). There was marked heterogeneity in transmission patterns between postcode districts. Interpretation: There is seasonal variation in the diagnosis of genomically clustered, but not non-clustered, cases. Risk factors for clustering include UK-birth, infectious forms of tuberculosis, and infection with lineage 3 or 4. Funding: Wellcome Trust, MRC, UKHSA.Publication Metadata only Disseminated: Mycobacterium abscessus with endocarditis(BMJ Publishing Group, 2024-03-13) Chue, Amy Louise; Braganza Menezes, Darryl; Bhabra, Moninder; Dedicoat, Martin; University Hospitals Birmingham NHS Foundation Trust; Infectious Diseases; Cardiac Surgery; Medical and Dental; Chue, Amy; Bhabra, Moninder; Dedicoat, MartinWe present an uncommon case of endocarditis caused by Mycobacterium abscessus in an immunocompetent patient following a caesarean section. We discuss her turbulent admission course leading to her diagnosis following persistent M. abscessus bacteraemia, medical and surgical management, including a splenectomy and valve resection and repair, and subsequent prolonged course of combination antimicrobials for 24 months post valve surgery. The patient is alive 9 months after completing her treatment and 36 months after her valve surgery. We emphasise the importance of a multidisciplinary team approach in the management of such a complex case.Publication Metadata only Vulnerability and tuberculosis treatment outcomes in urban settings in England: A mixed-methods study(Public Library of Science, 2023-08-17) Berrocal-Almanza, Luis C; Lima, Marcela; Piotrowski, Helen; Botticello, Julie; Badhan, Amarjit; Karnani, Nisha; Kaur, Hanna; Pareek, Manish; Haldar, Pranabashis; Dedicoat, Martin; Kon, Onn Min; Zenner, Dominik; Lalvani, Ajit; Infectious Diseases; General Medicine; Medical and Dental; Nursing and Midwifery Registered; Kaur, Hanna; Dedicoat, MartinBackground: Evidence on factors contributing to poor treatment outcome and healthcare priorities in vulnerable populations affected by tuberculosis (TB) in urban areas of England other than London is needed to inform setting-specific prevention and care policies. We addressed this knowledge gap in a cohort of TB patients and healthcare providers in Birmingham and Leicester, UK. Methods: A mixed-methods study was performed. Logistic regression was used to identify TB patients more likely to have poor treatment outcomes according to clinical and demographic characteristics and social risk factors (SRFs) in a 2013-18 cohort. 25 semi-structured interviews were undertaken in purposely selected individuals (9 patients and 16 healthcare professionals) to glean insights on their healthcare priorities and the factors that contribute to poor treatment outcome. Results: The quantitative cohort comprised 2252 patients. Those who were ≥ 55 years of age, foreign-born from Central Europe, East Asia and Sub Saharan Africa and with MDR-TB were more likely to have poor treatment outcomes. According to patients and healthcare professionals, the factors that contribute to vulnerability to develop TB and poor treatment outcomes include poor working and living conditions, inadequate or absent welfare protection, poor primary healthcare responsiveness, treatment duration and side effects. These factors could be addressed by increased networking, partnership and integration between healthcare and social services and better integration between primary and secondary healthcare. Conclusions: In both cities, being ≥ 55 years of age, having MDR-TB and being of foreign-birth are predictors of unfavourable treatment outcome. Risk of poor treatment outcome and vulnerability seem to be multidimensional. A better understanding of specific vulnerabilities and how they affect patient care pathway is needed to design adequate support programmes.Publication Metadata only Responding to the tuberculosis risk of forced mass migration from Ukraine: A complex challenge with no single solution(BMJ Publishing Group, 2023-09-27) Haldar, Pranabashis; Ahyow, Lauren; Dedicoat, Martin; Infectious Diseases; Medical and Dental; Dedicoat, MartinNo abstract availablePublication Metadata only Practical management of suspected hypersensitivity reactions to anti-tuberculosis drugs(Blackwell Scientific Publications, 2022-02-23) Bermingham, William Hywel; Bhogal, Rashmeet; Arudi Nagarajan, Sowmya; Mutlu, Leman; El-Shabrawy, Reham Mohamed; Madhan, Ramesh; Krishnaswamy, Uma Maheswari; Murali, Mandakolathur Ramaswamy; Kudagammana, Sanath Thushara; Shrestha, Rajeev; Sumantri, Stevent; Christopher, Devasahayam Jesudas; Mahesh, Padukudru Anand; Dedicoat, Martin; Krishna, Mamidipudi Thirumala; University Hospitals Birmingham NHS Foundation Trust; Kanagaroo Care Paediatric Hospital; Zagazig University; JSS AHER; St Johns Medical College; Massachusetts General Hospital; University of Peradeniya; Teaching Hospital Peradeniya; Dhulikhel Hospital Kathmandu University Hospital; Universitas Pelita Harapan; Siloam Academic Hospital Lippo Village; Christian Medical College; University of Birmingham; Infectious Diseases; Medical and Dental; Dedicoat, MartinTuberculosis (TB) is the commonest cause of death by a single infectious agent globally and ranks amongst the top ten causes of global mortality. The incidence of TB is highest in Low-Middle Income countries (LMICs). Prompt institution of, and compliance with, therapy are cornerstones for a favourable outcome in TB and to mitigate the risk of multiple drug resistant (MDR)-TB, which is challenging to treat. There is some evidence that adverse drug reactions (ADRs) and hypersensitivity reactions (HSRs) to anti-TB drugs occur in over 60% and 3%-4% of patients respectively. Both ADRs and HSRs represent significant barriers to treatment adherence and are recognised risk factors for MDR-TB. HSRs to anti-TB drugs are usually cutaneous and benign, occur within few weeks after commencement of therapy and are likely to be T-cell mediated. Severe and systemic T-cell mediated HSRs and IgE mediated anaphylaxis to anti-TB drugs are relatively rare, but important to recognise and treat promptly. T-cell-mediated HSRs are more frequent amongst patients with co-existing HIV infection. Some patients develop multiple sensitisation to anti-TB drugs. Whilst skin tests, patch tests and in vitro diagnostics have been used in the investigation of HSRs to anti-TB drugs, their predictive value is not established, they are onerous, require specialist input of an allergist and are resource-dependent. This is compounded by the global, unmet demand for allergy specialists, particularly in low-income countries (LICs)/LMICs and now the challenging circumstances of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This narrative review provides a critical analysis of the limited published evidence on this topic and proposes a cautious and pragmatic approach to optimise and standardise the management of HSRs to anti-TB drugs. This includes clinical risk stratification and a dual strategy involving sequential re-challenge and rapid drug desensitisation. Furthermore, a concerted international effort is needed to generate real-time data on ADRs, HSRs, safety and clinical outcomes of these interventions.Publication Metadata only Drug-resistant tuberculosis treatments, the case for a phase III platform trial.(World Health Organization, 2024-09-01) Yates, Tom A; Barnes, Samara; Dedicoat, Martin; Kon, Onn Min; Kunst, Heinke; Lipman, Marc; Millington, Kerry A; Nunn, Andrew J; Phillips, Patrick Pj; Potter, Jessica L; Squire, S Bertel; Infectious Diseases; Medical and Dental; Dedicoat, MartinMost phase III trials in drug-resistant tuberculosis have either been underpowered to quantify differences in microbiological endpoints or have taken up to a decade to complete. Composite primary endpoints, dominated by differences in treatment discontinuation and regimen changes, may mask important differences in treatment failure and relapse. Although new regimens for drug-resistant tuberculosis appear very effective, resistance to new drugs is emerging rapidly. There is a need for shorter, safer and more tolerable regimens, including those active against bedaquiline-resistant tuberculosis. Transitioning from multiple regimen A versus regimen B trials to a single large phase III platform trial would accelerate the acquisition of robust estimates of relative efficacy and safety. Further efficiencies could be achieved by adopting modern adaptive platform designs. Collaboration among trialists, affected community representatives, funders and regulators is essential for developing such a phase III platform trial for drug-resistant tuberculosis treatment regimens.Publication Metadata only Identifying opportunities to improve the microbiological diagnosis of tuberculosis in a low endemic urban setting.(Elsevier, 2023-03-09) Clarke, Jenny; Moore, Matthew P; O'Shea, Matthew K; Dedicoat, Martin; Pathology; Infectious Diseases; Medical and Dental; O'Shea, Matthew K; Dedicoat, MartinNo abstract availablePublication Metadata only Anti-tuberculosis drug-induced liver injury(BMJ Publishing Group, 2023-10-27) Lim, Wei Shen; Avery, Anthony; Kon, Onn Min; Dedicoat, Martin; Infectious Diseases; Medical and Dental; Dedicoat, MartinNone availablePublication Metadata only Impact of COVID-19 on NHS tuberculosis services: Results of a UK-wide survey.(Elsevier, 2023-04-11) Morrison, Hazel; Perrin, Felicity; Dedicoat, Martin; Ahmed, Rizwan; Brown, James; Loughenbury, Maria; Paul, Suman; Souto, Miguel; Ward, Richard; Lipman, Marc; Infectious Diseases; Medical and Dental; Dedicoat, MartinNo Abstract Available