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TB-related research

UCL-TB spans almost every department of the School of Life and Medical Sciences at UCL, with research across basic science, microbiology, translational medicine, epidemiology and beyond.

Adherence to treatment

Developing effective drug regimens is just one part of effective TB treatment. The course of treatment is long, may cause side effects, and non-adherence can lead to new antibiotic resistance.  The same is true of treating latent TB, when individuals have no symptoms. Supporting people in taking their full course of treatment, and understanding reasons for non-adherence, are therefore important.

Example outputs: 

  • Health and illness beliefs in adults with tuberculosis infection during the COVID-19 pandemic in the UK. (2024) Kilic, A., Clarke, A. L., Moon, Z., Hamada, Y., Chan, A. H. Y., Rahman, A., Layton, C., Griffiths, C. J., Zenner, D., Powell, E., Kunst, H., Lipman, M., Mandelbaum, M., Papineni, P., Tattersall, T., Duong, T., Abubakar, I., Rangaka, M. X., and Horne, R. Dialogues Health 4, 100162: https://doi.org/10.1016/j.dialog.2023.100162.
  • Forgiveness is the attribute of the strong: Nonadherence and regimen shortening in drug-sensitive tuberculosis. (2023) Stagg, H. R., Thompson, J. A., Lipman, M. C. I., Sloan, D. J., Flook, M., and Fielding, K. L. Am J Respir Crit Care Med 207, 193-205: https://doi.org/10.1164/rccm.202201-0144OC.
  • Evaluating the effect of short-course rifapentine-based regimens with or without enhanced behaviour-targeted treatment support on adherence and completion of treatment for latent tuberculosis infection among adults in the UK (RID-TB: Treat): protocol for an open-label, multicentre, randomised controlled trial. (2022) Rangaka, M. X., Y. Hamada, T. Duong, H. Bern, J. Calvert, M. Francis, A. L. Clarke, A. Ghanouni, C. Layton, V. Hack, E. Owen-Powell, J. Surey, K. Sanders, H. L. Booth, A. Crook, C. Griffiths, R. Horne, H. Kunst, M. Lipman, M. Mandelbaum, P. J. White, D. Zenner and I. Abubakar. BMJ Open 12(9): e057717 https://doi.org/10.1136/bmjopen-2021-057717
  • "You have to change your whole life": A qualitative study of the dynamics of treatment adherence among adults with tuberculosis in the United Kingdom. (2021) Karat, A. S., A. S. K. Jones, I. Abubakar, C. N. J. Campbell, A. L. Clarke, C. S. Clarke, M. Darvell, A. T. Hill, R. Horne, H. Kunst, M. Mandelbaum, B. G. Marshall, C. McSparron, A. Rahman, H. R. Stagg, J. White, M. C. I. Lipman and K. Kielmann. J Clin Tuberc Other Mycobact Dis 23: 100233 https://doi.org/10.1016/j.jctube.2021.100233
  • All nonadherence is equal but is some more equal than others? Tuberculosis in the digital era. (2020) Stagg, H. R. et al. ERJ Open Res 6(4) https://doi.org/10.1183/23120541.00315-2020
  • IMPACT study on intervening with a manualised package to achieve treatment adherence in people with tuberculosis: protocol paper for a mixed-methods study, including a pilot randomised controlled trial.  (2019) Stagg, H. R.et al.  BMJ Open 9(12): e032760 https://doi.org/10.1136/bmjopen-2019-032760
  • Measuring and reporting treatment adherence: What can we learn by comparing two respiratory conditions? (2020) Tibble, H. et al. Br J Clin Pharmacol https://doi.org/10.1111/bcp.14458

Projects: IMPACT, RID-TB

People: Ibrahim Abubakar, Rob Horne, Marc Lipman, Lele Rangaka  

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Arts and humanities

TB has been part of the fabric of life in the UK for many centuries, and therefore has a presence in our culture, which we are keen to explore.

People: John Mullan

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Behavioural research

Example outputs:

  • IMPACT study on intervening with a manualised package to achieve treatment adherence in people with tuberculosis: protocol paper for a mixed-methods study, including a pilot randomised controlled trial.  (2019) Stagg, H. R.et al.  BMJ Open 9(12): e032760 https://doi.org/10.1136/bmjopen-2019-032760

Projects: IMPACT, RID-TB

People: Rob Horne

See also: Adherence to treatment

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Biology of host and pathogen

See sub-themes: Genomics; Drug Development, Gene regulation; Immunology; Pharmacology

People: Kristine Arnvig, Francois Balloux, Sanjib Bhakta, Frank Kloprogge, Gillian Tomlinson, Lucy van Dorp

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Biomarkers

The body is complex, and infection and our immune response to it are complex processes that we only partly understand.  However, we can now collect enormous amounts of information about the activity going on in our bodies, and use computers to identify signatures that are found (for example) in a group of people with known disease, but not in people we know not to be infected.  These signatures can then be used as biomarkers for disease in people of unknown status.  For example, this approach is analysing mRNA expression in the blood for biomarker signatures that identify people who don’t yet have clinical TB, but in whom TB bacteria that were latent/inactive have now become active. In addition, we are investigating TB-specific cytokine profiles that may aid to distinguish between latent and active TB, as well as functional T cell profiling. 

Example outputs:

  • Blood RNA biomarkers for tuberculosis screening in people living with HIV before antiretroviral therapy initiation: a diagnostic accuracy study. (2024) Mann, T., Gupta, R. K., Reeve, B. W. P., Ndlangalavu, G., Chandran, A., Krishna, A. P., Calderwood, C. J., Tshivhula, H., Palmer, Z., Naidoo, S., Mbu, D. L., Theron, G., and Noursadeghi, M. Lancet Glob Health 12, e783-e792: https://doi.org/10.1016/S2214-109X(24)00029-9.
  • Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers. (2024) Schiff, H. F., Walker, N. F., Ugarte-Gil, C., Tebruegge, M., Manousopoulou, A., Garbis, S. D., Mansour, S., Wong, P. H. M., Rockett, G., Piazza, P., Niranjan, M., Vallejo, A. F., Woelk, C. H., Wilkinson, R. J., Tezera, L. B., Garay-Baquero, D., and Elkington, P. JCI Insight 9 https://doi.org/10.1172/jci.insight.173273.
  • Diagnosis and biomarkers for ocular tuberculosis: From the present into the future. (2023) Ludi, Z., Sule, A. A., Samy, R. P., Putera, I., Schrijver, B., Hutchinson, P. E., Gunaratne, J., Verma, I., Singhal, A., Nora, R. D., van Hagen, P. M., Dik, W. A., Gupta, V., and Agrawal, R. Theranostics 13, 2088-2113: https://doi.org/10.7150/thno.81488.
  • Evaluation of host protein biomarkers by ELISA From whole lysed peripheral blood for development of diagnostic tests for active tuberculosis. (2022) Garlant, H. N., K. Ellappan, M. Hewitt, P. Perumal, S. Pekeleke, N. Wand, J. Southern, S. V. Kumar, H. Belgode, I. Abubakar, S. Sinha, S. Vasan, N. M. Joseph and K. E. Kempsell. Front Immunol 13: 854327 https://doi.org/10.3389/fimmu.2022.854327
  • Blood transcriptomic biomarkers for tuberculosis screening: time to redefine our target populations? (2021) Gupta, R.K. and M. Noursadeghi. Lancet Glob Health https://doi.org/10.1016/S2214-109X(21)00088-7
  • Exploring a combined biomarker for tuberculosis treatment response: protocol for a prospective observational cohort study. (2021) Kloprogge, F., I. Abubakar, H. Esmail, V. Hack, H. Kunst, T. D. McHugh, M. Noursadeghi, J. Surey, S. Tiberi and M. Lipman. BMJ Open 11(7): e052885 https://doi.org/10.1136/bmjopen-2021-052885
  • New insights into the limitations of host transcriptional biomarkers of tuberculosis. (2021) Noursadeghi, M. and R. K. Gupta. Am J Respir Crit Care Med 204(12): 1363-1365 https://doi.org/10.1164/rccm.202109-2146ED

People: Ibrahim Abubakar, Rishi Gupta, Isobella Honeyborne, Maddy Noursadeghi,  Marc Tebruegge

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Capacity development & training

Most TB is found in the Global South, where overall scientific infrastructure and support is most insecure for multiple historical and economic reasons.  We strongly support the idea that these countries should be enabled to develop high quality science with highly trained workforces.  We are both part of large programmes explicitly aiming to improve capacity development, and we also bring capacity development into other work wherever we can. As a university, we see the importance of academic and practical education, and have expertise in delivering it.  This includes supporting individuals to visit UCL for varying periods of time, carrying out workshops in London and abroad, training laboratory workers in diagnostic laboratories, and being part of bigger capacity development programmes.

Example outputs:

Projects: PanACEA; UK-Korean partnership for a TB cohort

People: Frank Kloprogge, Tim McHugh, Ali Zumla 

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Clinical management

Although standard treatments are published for patients with TB, working with individual patients to apply those treatments is a long process that is often far from smooth.  TB as a disease is different in every patient in terms of where the infection is active, whether the bacteria are resistant to any antibiotics, how the patient responds to drugs they are given, their personal situation, and other complicating conditions or factors.  Treatment is long, and many of these factors may change, while stopping the treatment early may lead to new drug resistance developing. All this happens in the context of a changing NHS and Social Services with limited resources. Clinical management is therefore never routine, and developing processes that are flexible and robust enough is challenging.

Example outputs:

People: Hanif Esmail, Marc Lipman, Ilaria Motta, Maddy Noursadeghi, Jess Potter, Emily Shaw, Conor Tweed, Jacqui White

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Clinical trials

The way we can improve treatment for TB, and be confident that it will be safe and effective, is through stringent clinical trials.  For TB, which is a disease that can be slow to develop and to treat, where the drug resistance patterns are changing, and manifests most in the poorest parts of the world, these trials are particularly challenging. They involve a large team of people with different skills over a long period of time, so are costly, and those we run have to be carefully selected.  The MRC Clinical Trials Unit at UCL – which formed originally as the MRC Tuberculosis Research Unit in 1948 has an unprecedented track record in TB trials.  As well as their leadership, management,  statistical and analysis expertise, they work with others at UCL who carry out TB microbiology and train and monitor participating laboratories, and an army of people throughout the world who recruit and work with the trial participants.  UCL also works with other trial sponsors such as the Global TB Alliance, and the University of Stellenbosch.

Sub-themes: Clinical trial design, Drug-resistant TB, Paediatric TB

Example outputs:

  • Ascertainment bias in TB treatment trials: Can systematic assessment of objective endpoints solve it? (2023) Mitnick, C. D., and Nunn, A. J. Am J Respir Crit Care Med 207, 1269-1270: https://doi.org/10.1164/rccm.202303-0430ED.
  • Baseline and acquired resistance to bedaquiline, linezolid and pretomanid, and impact on treatment outcomes in four tuberculosis clinical trials containing pretomanid. (2023) Timm, J., Bateson, A., Solanki, P., Paleckyte, A., Witney, A. A., Rofael, S. A. D., Fabiane, S., Olugbosi, M., McHugh, T. D., and Sun, E. PLOS Glob Public Health 3, e0002283: https://doi.org/10.1371/journal.pgph.0002283.
  • Clinical outcomes in children living with HIV treated for non-severe tuberculosis in the SHINE Trial. (2024) Chabala, C., Wobudeya, E., van der Zalm, M. M., Kapasa, M., Raichur, P., Mboizi, R., Palmer, M., Kinikar, A., Hissar, S., Mulenga, V., Mave, V., Musoke, P., Hesseling, A. C., McIlleron, H., Gibb, D., Crook, A., Turkova, A., and team, S. t. Clin Infect Dis https://doi.org/10.1093/cid/ciae193.
  • Clinical trials of tuberculosis vaccines in the era of increased access to preventive antibiotic treatment. (2023) Rangaka, M. X., Frick, M., Churchyard, G., Garcia-Basteiro, A. L., Hatherill, M., Hanekom, W., Hill, P. C., Hamada, Y., Quaife, M., Vekemans, J., White, R. G., and Cobelens, F. Lancet Respir Med 11, 380-390: https://doi.org/10.1016/S2213-2600(23)00084-X.
  • Economic evaluation of shortened, bedaquiline-containing treatment regimens for rifampicin-resistant tuberculosis (STREAM stage 2): a within-trial analysis of a randomised controlled trial. (2023) Rosu, L., Madan, J. J., Tomeny, E. M., Muniyandi, M., Nidoi, J., Girma, M., Vilc, V., Bindroo, P., Dhandhukiya, R., Bayissa, A. K., Meressa, D., Narendran, G., Solanki, R., Bhatnagar, A. K., Tudor, E., Kirenga, B., Meredith, S. K., Nunn, A. J., Bronson, G., Rusen, I. D., Squire, S. B., Worrall, E., and Collaborators, S. S. H. E. E. Lancet Glob Health 11, e265-e277: https://doi.org/10.1016/S2214-109X(22)00498-3.
  • A flexible multi-metric Bayesian framework for decision-making in Phase II multi-arm multi-stage studies. (2024) Dufault, S. M., Crook, A. M., Rolfe, K., and Phillips, P. P. J. Stat Med 43, 501-513: https://doi.org/10.1002/sim.9961.
  • Implementation challenges and lessons learned from the STREAM clinical trial-a survey of trial sites. (2023) Patel, L. N., Gurumurthy, M., Bronson, G., Sanders, K., and Rusen, I. D. Trials 24, 51: https://doi.org/10.1186/s13063-023-07068-8.
  • A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis. (2023) Dierig, A., Hoelscher, M., Schultz, S., Hoffmann, L., Jarchow-MacDonald, A., Svensson, E. M., Te Brake, L., Aarnoutse, R., Boeree, M., McHugh, T. D., Wildner, L. M., Gong, X., Phillips, P., Minja, L. T., Ntinginya, N., Mpagama, S., Liyoyo, A., Wallis, R. S., Sebe, M., Mhimbira, F. A., Mbeya, B., Rassool, M., Geiter, L., Cho, Y. L., and Heinrich, N. Trials 24, 382: https://doi.org/10.1186/s13063-023-07354-5. (2023) Dierig, A., Hoelscher, M., Schultz, S., Hoffmann, L., Jarchow-MacDonald, A., Svensson, E. M., Te Brake, L., Aarnoutse, R., Boeree, M., McHugh, T. D., Wildner, L. M., Gong, X., Phillips, P., Minja, L. T., Ntinginya, N., Mpagama, S., Liyoyo, A., Wallis, R. S., Sebe, M., Mhimbira, F. A., Mbeya, B., Rassool, M., Geiter, L., Cho, Y. L., and Heinrich, N. Trials 24, 382: https://doi.org/10.1186/s13063-023-07354-5.
  • Radiographic characteristics of rifampicin-resistant tuberculosis in the STREAM stage 1 trial and their influence on time to culture conversion in the short regimen. (2024) Chiang, C. Y., Bern, H., Goodall, R., Chien, S. T., Rusen, I. D., Nunn, A., and Collaborators, S. S.-s. BMC Infect Dis 24, 144: https://doi.org/10.1186/s12879-024-09039-z.
  • Short oral regimens for pulmonary rifampicin-resistant tuberculosis (TB-PRACTECAL): An open-label, randomised, controlled, phase 2B-3, multi-arm, multicentre, non-inferiority trial. (2023) Nyang'wa, B. T., Berry, C., Kazounis, E., Motta, I., Parpieva, N., Tigay, Z., Moodliar, R., Dodd, M., Solodovnikova, V., Liverko, I., Rajaram, S., Rassool, M., McHugh, T., Spigelman, M., Moore, D. A., Ritmeijer, K., du Cros, P., Fielding, K., and team, T.-P. Lancet Respir Med: https://doi.org/10.1016/S2213-2600(23)00389-2.
  • Standards for clinical trials for treating TB. (2023) du Cros, P., Greig, J., Alffenaar, J. C., Cross, G. B., Cousins, C., Berry, C., Khan, U., Phillips, P. P. J., Velasquez, G. E., Furin, J., Spigelman, M., Denholm, J. T., Thi, S. S., Tiberi, S., Huang, G. K. L., Marks, G. B., Turkova, A., Guglielmetti, L., Chew, K. L., Nguyen, H. T., Ong, C. W. M., Brigden, G., Singh, K. P., Motta, I., Lange, C., Seddon, J. A., Nyang'wa, B. T., Maug, A. K. J., Gler, M. T., Dooley, K. E., Quelapio, M., Tsogt, B., Menzies, D., Cox, V., Upton, C. M., Skrahina, A., McKenna, L., Horsburgh, C. R., Dheda, K., and Marais, B. J. Int J Tuberc Lung Dis 27, 885-898: https://doi.org/10.5588/ijtld.23.0341.
  • T-wave morphology abnormalities in the STREAM stage 1 trial. (2024) Hughes, G., Young, W. J., Bern, H., Crook, A., Lambiase, P. D., Goodall, R. L., Nunn, A. J., and Meredith, S. K. Expert Opin Drug Saf 23, 469-476: https://doi.org/10.1080/14740338.2024.2322116.

Projects: NC009, PARADIGM4TB (UNITE4TB-01), SimpliciTB, STREAM 2.0, TB-CHAMP, TB-PRACTECAL, ZeNix; (MRC-CTU TB project page)

People: Suzanne Anderson, Robindra Basu Roy, Angela Crook, Hanif Esmail, Diana Gibb, Ruth Goodall, Tim McHugh, Sarah Meredith, Ilaria Motta, Andrew Nunn, Lele Rangaka, Anna Turkova, Conor Tweed 

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Comorbidities of TB

Just as HIV and TB often go together (see separate section below), there are other conditions that associate strongly with progression of TB disease.  These include for example diabetes, smoking, and parasite co-infections.

Example outputs:

  • Association of diabetes, smoking, and alcohol use with subclinical-to-symptomatic spectrum of tuberculosis in 16 countries: an individual participant data meta-analysis of national tuberculosis prevalence surveys. (2023) Hamada, Y. et al. EClinicalMedicine 63, 102191: https://doi.org/10.1016/j.eclinm.2023.102191.
  • Tobacco smoking clusters in households affected by tuberculosis in an individual participant data meta-analysis of national tuberculosis prevalence surveys: Time for household-wide interventions? (2024) Hamada, Y. et al. PLOS Glob Public Health 4, e0002596: https://doi.org/10.1371/journal.pgph.0002596.

People: Yohhei Hamada, Lele Rangaka  

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Diagnostics

Despite many technical advances in diagnostics in the last two decades diagnosing TB is often challenging, especially in children. Existing tests have suboptimal sensitivity, which means that many TB patients have false-negative results. Diagnosing TB in children has additional challenges, as collecting adequate samples is often difficult and most children have paucibacillary disease (meaning that few mycobacteria are present in their clinical samples, making it hard to detect them). We are conducting studies on existing immune-based TB tests, including the tuberculin skin test and interferon-gamma release assays, and are working towards designing novel immunological TB tests that perform better across all age groups.

Example outputs:

  • Are mRNA based transcriptomic signatures ready for diagnosing tuberculosis in the clinic? - A review of evidence and the technological landscape. (2022) Hamada, Y., A. Penn-Nicholson, S. Krishnan, D. M. Cirillo, A. Matteelli, R. Wyss, C. M. Denkinger, M. X. Rangaka, M. Ruhwald and S. G. Schumacher. EBioMedicine 82: 104174 https://doi.org/10.1016/j.ebiom.2022.104174
  • Diagnosis and biomarkers for ocular tuberculosis: From the present into the future. (2023) Ludi, Z., Sule, A. A., Samy, R. P., Putera, I., Schrijver, B., Hutchinson, P. E., Gunaratne, J., Verma, I., Singhal, A., Nora, R. D., van Hagen, P. M., Dik, W. A., Gupta, V., and Agrawal, R. Theranostics 13, 2088-2113: https://doi.org/10.7150/thno.81488.
  • Diagnostic accuracy of a three-gene Mycobacterium tuberculosis host response cartridge using fingerstick blood for childhood tuberculosis: A multicentre prospective study in low-income and middle-income countries. (2024) Olbrich, L., Verghese, V. P., Franckling-Smith, Z., Sabi, I., Ntinginya, N. E., Mfinanga, A., Banze, D., Viegas, S., Khosa, C., Semphere, R., Nliwasa, M., McHugh, T. D., Larsson, L., Razid, A., Song, R., Corbett, E. L., Nabeta, P., Trollip, A., Graham, S. M., Hoelscher, M., Geldmacher, C., Zar, H. J., Michael, J. S., Heinrich, N., and RaPaed, T. B. c. Lancet Infect Dis 24, 140-149: https://doi.org/10.1016/S1473-3099(23)00491-7.
  • Diagnostic accuracy of QuantiFERON-TB Gold Plus assays in children and adolescents with tuberculosis disease. (2020) Soler-Garcia, A. et al.  J Pediatr 223: 212-215 e211 https://doi.org/10.1016/j.jpeds.2020.02.025
  • Evaluation of serological assays for the diagnosis of childhood tuberculosis disease: a study protocol. (2024) Neudecker, D., Fritisch, N., Sutter, T., Lu, L., Lu, P., Tebruegge, M., Santiago-Garcia, B., and Ritz, N. BMC Infect Dis 24, 481: https://doi.org/10.1186/s12879-024-09359-0.
  • Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers. (2024) Schiff, H. F., Walker, N. F., Ugarte-Gil, C., Tebruegge, M., Manousopoulou, A., Garbis, S. D., Mansour, S., Wong, P. H. M., Rockett, G., Piazza, P., Niranjan, M., Vallejo, A. F., Woelk, C. H., Wilkinson, R. J., Tezera, L. B., Garay-Baquero, D., and Elkington, P. JCI Insight 9 https://doi.org/10.1172/jci.insight.173273.
  • Phenotype versus genotype discordant rifampicin susceptibility testing in tuberculosis: Implications for a diagnostic accuracy. (2024) Qadir, M., Faryal, R., Khan, M. T., Khan, S. A., Zhang, S., Li, W., Wei, D. Q., Tahseen, S., and McHugh, T. D. Microbiol Spectr 12, e0163123: https://doi.org/10.1128/spectrum.01631-23.
  • Tuberculosis-associated hemophagocytic lymphohistiocytosis: diagnostic challenges and determinants of outcome. (2024) Kurver, L., Seers, T., van Dorp, S., van Crevel, R., Pollara, G., and van Laarhoven, A. Open Forum Infect Dis 11, ofad697: https://doi.org/10.1093/ofid/ofad697.
  • Tuberculosis disease in children and adolescents on therapy with antitumor necrosis factor-a agents: A collaborative, multicenter Paediatric Tuberculosis Network European Trials Group (ptbnet) study. (2020) Noguera-Julian, A. et al. Clin Infect Dis 71(10): 2561-2569 https://doi.org/10.1093/cid/ciz1138

Projects:

  • SimpliciTB
  • TB-PRACTECAL
  • ZeNix
  • Comparison of Cepheid Xpert MTB/XDR and GenoScreen Deeplex Myc-TB for MDR and XDR M. tuberculosis (Giovanni Satta).  

People: Tim McHugh, Yohhei Hamada, Lele Rangaka, Giovanni Satta,  Marc Tebruegge

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Digital health

Example outputs:

  • Digital approaches to reducing TB treatment loss to follow-up. (2023) Oeser, C., Rangaka, M. X., and Abubakar, I. Int J Tuberc Lung Dis 27, 432-437: https://doi.org/10.5588/ijtld.23.0027.
  • Knowledge, attitudes, and behaviors on utilizing mobile health technology for TB in Indonesia: A qualitative pilot study. (2020) Aisyah, D. N. et al. Front Public Health 8: 531514 https://doi.org/10.3389/fpubh.2020.531514
  • Management and control of tuberculosis control in socially complex groups: a research programme including three RCTs. (2020) Story, A., et al. Programme Grants for Applied Research 8(9) https://doi.org/http://doi.org/10.3310/pgfar08090

Projects:

People: Hanif Esmail, Andrew Hayward, Patty Kostkova, Rachel McKendry, Al Story 

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Drug development

After the success of early drugs against TB, starting in the 1940s with streptomycin, there was a long period where no new antibiotics were developed, due to lower priority, cost and time to develop these, and lack of biological understanding. The rise of antibiotic resistance has shown this to be short-sighted, and at last there is a renewed pipeline of drugs, some of which have moved into clinical use.  We are looking for novel drugs, coming both from the biology, and also from direction of large collections of chemical derivatives.

Example outputs:

  • Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition. (2018) Danquah, C. A. et al.. Sci Rep 8(1): 1150 https://doi.org/10.1038/s41598-017-18948-w
  • BacPROTACs targeting Clp protease: a promising strategy for anti-mycobacterial drug discovery. (2024) Bonjorno, A. F., Pavan, A. R., Fernandes, G. F. S., Scarim, C. B., Castagnolo, D., and Dos Santos, J. L. Front Chem 12, 1358539: https://doi.org/10.3389/fchem.2024.1358539.
  • Carprofen elicits pleiotropic mechanisms of bactericidal action with the potential to reverse antimicrobial drug resistance in tuberculosis. (2020) Maitra, A. et al. J Antimicrob Chemother 75(11): 3194-3201 https://doi.org/10.1093/jac/dkaa307
  • Cell wall peptidoglycan in Mycobacterium tuberculosis: An Achilles' heel for the TB-causing pathogen. (2019) Maitra, A., T. Munshi, J. Healy, L. T. Martin, W. Vollmer, N. H. Keep and S. Bhakta. FEMS Microbiol Rev 43(5): 548-575 https://doi.org/10.1093/femsre/fuz016
  • Characterization of the MurT/GatD complex in Mycobacterium tuberculosis towards validating a novel anti-tubercular drug target. (2021) Maitra, A., S. Nukala, R. Dickman, L. T. Martin, T. Munshi, A. Gupta, A. J. Shepherd, K. B. Arnvig, A. B. Tabor, N. H. Keep and S. Bhakta. JAC Antimicrob Resist 3(1): dlab028 https://doi.org/10.1093/jacamr/dlab028
  • Co-delivery of D-LAK antimicrobial peptide and capreomycin as inhaled powder formulation to combat drug-resistant tuberculosis. (2023) Shao, Z., Chow, M. Y. T., Chow, S. F., and Lam, J. K. W. Pharm Res 40, 1073-1086: https://doi.org/10.1007/s11095-023-03488-y.
  • Ertapenem and Faropenem against Mycobacterium tuberculosis: in vitro testing and comparison by macro and microdilution. (2020) Gonzalo, X. et al. BMC Microbiol 20(1): 271 https://doi.org/10.1186/s12866-020-01954-w
  • Improving the potency of N-Aryl-2,5-dimethylpyrroles against multidrug-resistant and intracellular mycobacteria. (2020) Touitou, M. et al. ACS Med Chem Lett 11(5): 638-644 https://doi.org/10.1021/acsmedchemlett.9b00515
  • Liposome-siderophore conjugates loaded with moxifloxacin serve as a model for drug delivery against Mycobacterium tuberculosis. (2024) Maringolo Ribeiro, C., Augusto Roque-Borda, C., Carolina Franzini, M., Fernanda Manieri, K., Manaia Demarqui, F., Leite Campos, D., Temperani Amaral Machado, R., Cristiane da Silva, I., Tavares Luiz, M., Delello Di Filippo, L., Bento da Silva, P., Cristina Oliveira da Rocha, M., Nair Bao, S., Masci, D., Fernandes, G. F. S., Castagnolo, D., Chorilli, M., and Rogerio Pavan, F. Int J Pharm 655, 124050: https://doi.org/10.1016/j.ijpharm.2024.124050.
  • Polymersomes eradicating intracellular bacteria. (2020) Fenaroli, F. et al. ACS Nano 14(7): 8287-8298 https://doi.org/10.1021/acsnano.0c01870
  • Pre-clinical tools for predicting drug efficacy in treatment of tuberculosis. (2022) Margaryan, H., D. D. Evangelopoulos, L. Muraro Wildner and T. D. McHugh. Microorganisms 10(3) https://doi.org/10.3390/microorganisms10030514
  • Prediction of lung exposure to anti-tubercular drugs using plasma pharmacokinetic data: Implications for dose selection. (2022) Muliaditan, M., D. Teutonico, F. Ortega-Muro, S. Ferrer and O. Della Pasqua. Eur J Pharm Sci 173: 106163 https://doi.org/10.1016/j.ejps.2022.106163
  • Role of whole-genome sequencing in characterizing the mechanism of action of para-aminosalicylic acid and its resistance. (2020) Satta, G. et al. Antimicrob Agents Chemother 64(9) https://doi.org/10.1128/AAC.00675-20
  • Synergistic combination of antimicrobial peptide and isoniazid as inhalable dry powder formulation against multi-drug resistant tuberculosis. (2024) Shao, Z., Tam, K. K., Achalla, V. P. K., Woon, E. C. Y., Mason, A. J., Chow, S. F., Yam, W. C., and Lam, J. K. W. Int J Pharm 654, 123960: https://doi.org/10.1016/j.ijpharm.2024.123960.
  • Tuberculosis drug discovery: challenges and new horizons. (2022) Fernandes, G. F. S., A. M. Thompson, D. Castagnolo, W. A. Denny and J. L. Dos Santos. J Med Chem 65(11): 7489-7531 https://doi.org/10.1021/acs.jmedchem.2c00227
  • See also Tuberculomucin in 'Host-directed therapies', below

Projects:

  • Inhibitors of cell-wall peptidoglycan as novel anti-TB drugs

People: Sanjib Bhakta, Dimitris Evangelopoulos, Tim McHugh, Mat Todd

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Drug-resistant TB

Antibiotics are one of the cornerstones of the modern world, curing once-fatal diseases, and this is true for TB.  Yet resistance to these antibiotics develops  - in the case of M. tuberculosis, through the bacteria acquiring mutations in their chromosomes one at a time.  Reducing the risk of this happening is one major reason that TB is always treated with combination drug therapy. With TB the problem is worsened by the long period of treatment and side effects of drugs, which can lead to patients not completing their full courses. It is an aspect of TB that affects almost everything else: diagnosis, clinical management, and drug development to name a few.

People and sub-themes:

Example outputs:

  • Bedaquiline resistance in drug-resistant tuberculosis HIV co-infected patients. (2020) Nimmo, C. et al. Eur Respir J 55(6) https://doi.org/10.1183/13993003.02383-2019
  • Carprofen elicits pleiotropic mechanisms of bactericidal action with the potential to reverse antimicrobial drug resistance in tuberculosis. (2020) Maitra, A. et al. J Antimicrob Chemother 75(11): 3194-3201 https://doi.org/10.1093/jac/dkaa307

Projects: SimpliciTB, STREAM 2.0, TB-CHAMP, TB-PRACTECAL, ZeNix

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Gene regulation

Although we have known the genetic structure of Mycobacterium tuberculosis for over 20 years, much of its biology relates to how and when genes are switched on and off, but our understanding of the underlying mechanisms remains incomplete.  The development of high-throughput sequencing (HTS) techniques, has revealed the abundance and importance of regulatory RNAs such as small RNAs and so-called riboswitches in bacterial gene expression control, and we can now monitor expression of all genes in an effort to understand their role in different activity states and in different locations within the host.

Example outputs:

  • Premature termination of transcription is shaped by Rho and translated uORFS in Mycobacterium tuberculosis. (2023) D'Halluin, A., Polgar, P., Kipkorir, T., Patel, Z., Cortes, T., and Arnvig, K. B. iScience 26, 106465: https://doi.org/10.1016/j.isci.2023.106465.
  • The Mycobacterium tuberculosis sRNA F6 Modifies Expression of Essential Chaperonins, GroEL2 and GroES. (2021) Houghton, J. et al. Microbiol Spectr 9, e0109521: https://doi.org/10.1128/Spectrum.01095-21.
  • Coupling of peptidoglycan synthesis to central metabolism in mycobacteria: Post-transcriptional control of CwlM by aconitase. (2020) Bancroft, P. J. et al. Cell Rep 32(13): 108209 https://doi.org/10.1016/j.celrep.2020.108209
  • Riboswitches: choosing the best platform.  (2019) Arnvig, K. B.  Biochem Soc Trans 47(4): 1091-1099 https://doi.org/10.1042/BST20180507

People: Kristine Arnvig

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Genomics

Sequencing the entire genome of M. tuberculosis has in recent years changed from a major enterprise, to being quick and a fraction of the previous cost.  Studying the genomes of M. tuberculosis strains can identify likely drug resistance, detect local outbreaks, identify sub-strains with particular properties, inform on genotypic predictors of disease pathology, tell us how drug resistance develops and spreads, and inform us about human history. 

Example outputs:

  • Ancient and recent differences in the intrinsic susceptibility of Mycobacterium tuberculosis complex to pretomanid. (2022) Bateson, A., J. Ortiz Canseco, T. D. McHugh, A. A. Witney, S. Feuerriegel, M. Merker, T. A. Kohl, C. Utpatel, S. Niemann, S. Andres, K. Kranzer, F. P. Maurer, A. Ghodousi, E. Borroni, D. M. Cirillo, M. Wijkander, J. C. Toro, R. Groenheit, J. Werngren, D. Machado, M. Viveiros, R. M. Warren, F. Sirgel, A. Dippenaar, C. U. Koser, E. Sun and J. Timm. J Antimicrob Chemother 77(6): 1685-1693 https://doi.org/10.1093/jac/dkac070
  • Association between bacterial homoplastic variants and radiological pathology in tuberculosis. (2020) Grandjean, L. et al. Thorax 75(7): 584-591 https://doi.org/10.1136/thoraxjnl-2019-213281
  • Challenges in defining the functional, non-coding, expressed genome of members of the Mycobacterium tuberculosis complex. (2022) Stiens, J., K. B. Arnvig, S. L. Kendall and I. Nobeli. Mol Microbiol 117(1): 20-31 https://doi.org/10.1111/mmi.14862
  • Detection of a historic reservoir of bedaquiline/clofazimine resistance-associated variants in Mycobacterium tuberculosis. (2024) Nimmo, C., Ortiz, A. T., Tan, C. C. S., Pang, J., Acman, M., Millard, J., Padayatchi, N., Grant, A. D., O'Donnell, M., Pym, A., Brynildsrud, O. B., Eldholm, V., Grandjean, L., Didelot, X., Balloux, F., and van Dorp, L. Genome Med 16, 34: https://doi.org/10.1186/s13073-024-01289-5.
  • Dynamics of within-host Mycobacterium tuberculosis diversity and heteroresistance during treatment. (2020) Nimmo, C. et al. EBioMedicine 55: 102747 https://doi.org/10.1016/j.ebiom.2020.102747
  • The effect of M. tuberculosis lineage on clinical phenotype. (2023) Du, D. H., Geskus, R. B., Zhao, Y., Codecasa, L. R., Cirillo, D. M., van Crevel, R., Pascapurnama, D. N., Chaidir, L., Niemann, S., Diel, R., Omar, S. V., Grandjean, L., Rokadiya, S., Ortitz, A. T., Lan, N. H., Ha, D. T. M., Smith, E. G., Robinson, E., Dedicoat, M., Nhat, L. T. H., Thwaites, G. E., Van, L. H., Thuong, N. T. T., and Walker, T. M. PLOS Glob Public Health 3, e0001788: https://doi.org/10.1371/journal.pgph.0001788.
  • Emergence of phenotypic and genotypic antimicrobial resistance in Mycobacterium tuberculosis. (2022) Kloprogge, F., J. Ortiz Canseco, L. Phee, Z. Sadouki, K. Kipper, A. A. Witney, N. Stoker and T. D. McHugh. Sci Rep 12(1): 21429 https://doi.org/10.1038/s41598-022-25827-6
  • From Theory to Practice: Translating Whole-Genome Sequencing (WGS) into the Clinic. (2018) Balloux, F. et al. Trends Microbiol 26(12): 1035-1048 https://doi.org/10.1016/j.tim.2018.08.004
  • Genome-wide association with uncertainty in the genetic similarity matrix. (2023) Wang, S., Ge, S., Sobkowiak, B., Wang, L., Grandjean, L., Colijn, C., and Elliott, L. T. J Comput Biol 30, 189-203: https://doi.org/10.1089/cmb.2022.0067.
  • Genomic signatures of pre-resistance in Mycobacterium tuberculosis. (2021) Torres Ortiz, A., J. Coronel, J. R. Vidal, C. Bonilla, D. A. J. Moore, R. H. Gilman, F. Balloux, O. M. Kon, X. Didelot and L. Grandjean. Nat Commun 12(1): 7312 https://doi.org/10.1038/s41467-021-27616-7
  • Mapping the phylogeny and lineage history of geographically distinct BCG vaccine strains. (2023) Elton, L., Kasaragod, S., Donoghue, H., Safar, H. A., Amankwah, P., Zumla, A., Witney, A. A., and McHugh, T. D. Microb Genom 9: https://doi.org/10.1099/mgen.0.001077.
  • Mycobacterium tuberculosis and whole-genome sequencing: how close are we to unleashing its full potential? (2018) Satta, G. et al. Clin Microbiol Infect 24(6): 604-609 https://doi.org/10.1016/j.cmi.2017.10.030.
  • Phenotype versus genotype discordant rifampicin susceptibility testing in tuberculosis: Implications for a diagnostic accuracy. (2024) Qadir, M., Faryal, R., Khan, M. T., Khan, S. A., Zhang, S., Li, W., Wei, D. Q., Tahseen, S., and McHugh, T. D. Microbiol Spectr 12, e0163123: https://doi.org/10.1128/spectrum.01631-23.
  • Population-level emergence of bedaquiline and clofazimine resistance-associated variants among patients with drug-resistant tuberculosis in southern Africa: a phenotypic and phylogenetic analysis. (2020) Nimmo, C. et al. Lancet Microbe 1(4): e165-e174 https://doi.org/10.1016/S2666-5247(20)30031-8
  • Relevance of genomic diversity of Mycobacterium tuberculosis complex in Africa. (2022) Osei-Wusu, S., I. D. Otchere, P. Asare, F. Ntoumi, A. Zumla, A. Asante-Poku and D. Yeboah-Manu. Int J Infect Dis 124 Suppl 1: S47-S49 https://doi.org/10.1016/j.ijid.2022.03.016
  • Role of whole-genome sequencing in characterizing the mechanism of action of para-aminosalicylic acid and its resistance. (2020) Satta, G. et al. Antimicrob Agents Chemother 64(9) https://doi.org/10.1128/AAC.00675-20
  • Whole genome sequencing and prediction of antimicrobial susceptibilities in non-tuberculous mycobacteria. (2022) Solanki, P., M. Lipman, T. D. McHugh and G. Satta. Front Microbiol 13: 1044515 https://doi.org/10.3389/fmicb.2022.1044515

Projects:

People: Kristine Arnvig, Francois Balloux, Linzy Elton, Louis Grandjean, Frank Kloprogge, Tim McHugh, Camus Nimmo, Lucy van Dorp, Giovanni Satta

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HIV and TB

The HIV epidemic brought about a surge in TB cases in countries throughout the world, with both low and high pre-existing rates of TB.  TB - a disease largely controlled by cellular immunity - is much more likely to develop in people who have a deficiency in their cellular immunity, as is the case with untreated HIV infection. 

Example outputs: 

  • Blood RNA biomarkers for tuberculosis screening in people living with HIV before antiretroviral therapy initiation: a diagnostic accuracy study. (2024) Mann, T., Gupta, R. K., Reeve, B. W. P., Ndlangalavu, G., Chandran, A., Krishna, A. P., Calderwood, C. J., Tshivhula, H., Palmer, Z., Naidoo, S., Mbu, D. L., Theron, G., and Noursadeghi, M. Lancet Glob Health 12, e783-e792: https://doi.org/10.1016/S2214-109X(24)00029-9.
  • Clinical outcomes in children living with HIV treated for non-severe tuberculosis in the SHINE Trial. (2024) Chabala, C., Wobudeya, E., van der Zalm, M. M., Kapasa, M., Raichur, P., Mboizi, R., Palmer, M., Kinikar, A., Hissar, S., Mulenga, V., Mave, V., Musoke, P., Hesseling, A. C., McIlleron, H., Gibb, D., Crook, A., Turkova, A., and team, S. t. Clin Infect Dis https://doi.org/10.1093/cid/ciae193.
  • Screening for tuberculosis infection and effectiveness of preventive treatment among people with HIV in low-incidence settings. (2024) van Geuns, D., Arts, R. J. W., de Vries, G., Wit, F., Degtyareva, S. Y., Brown, J., Pareek, M., Lipman, M., and van Crevel, R. AIDS 38, 193-205: https://doi.org/10.1097/QAD.0000000000003747.

Projects:

  • Clonal and functional T cell determinants of protection and pathogenesis in tuberculosis (Mahdad Nousadeghi, Benny Chain, Hans Stauss, Alasdair Leslie and Andreas Tiffeau-Mayer) Link

People: Marc Lipman, Mahdad Noursadeghi

Host-directed therapies

Classically we think of treating bacterial disease with antibiotics – molecules that kill or damage the bacteria, and ideally don’t affect the patient at all. A complementary approach is to use molecules that modulate the host’s immune response. An effective immune response aims to kill pathogen but not its own cells. Pathology caused by infectious agents can either be a direct effect of the pathogen, or arise indirectly from an inappropriate immune response that causes damage. Host-directed therapies, therefore, can both be developed to stimulate the immune response, and dampen autoimmune damage depending on what is needed.

Example outputs:

Projects: 

  • Tuberculomucin - a substance first developed by Dr Friedrich Weleminsky in the early part of the 20th century (Friedrich Weleminsky, Ueber die Bildung von Elweiss und Mucin durch Tuberkelbacillen,  Berliner klinische Wochenschr 28 (1912): 1-8. Translated by Stephanie Eichberg (SE)).  Long term TB culture following his protocol has resulted in a product similar in characteristics to that described by Weleminsky and testing of its efficacy is planned. Reeves, CA; Tuberculomucin: a forgotten treatment for tuberculosis, (2014)  The Transactions of the Medical Society of London 131 pp. 106-112, available at UCL Discovery

People: Dimitris Evangelopoulos, Gabriele Pollara, Judy Weleminsky, Ali Zumla

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Immunology

Example outputs:

  • Advances in development of new tuberculosis vaccines. (2023) da Costa, C., Onyebujoh, P., Thiry, G., and Zumla, A. Curr Opin Pulm Med 29, 143-148: https://doi.org/10.1097/MCP.0000000000000950.
  • Aggregated Mycobacterium tuberculosis enhances the inflammatory response. (2021) Rodel, H. E., I. Ferreira, C. G. K. Ziegler, Y. Ganga, M. Bernstein, S. H. Hwa, K. Nargan, G. Lustig, G. Kaplan, M. Noursadeghi, A. K. Shalek, A. J. C. Steyn and A. Sigal. Front Microbiol 12: 757134 https://doi.org/10.3389/fmicb.2021.757134
  • Anaerobe-enriched gut microbiota predicts pro-inflammatory responses in pulmonary tuberculosis. (2021) Naidoo, C. C., G. R. Nyawo, I. Sulaiman, B. G. Wu, C. T. Turner, K. Bu, Z. Palmer, Y. Li, B. W. P. Reeve, S. Moodley, J. G. Jackson, J. Limberis, A. H. Diacon, P. D. van Helden, J. C. Clemente, R. M. Warren, M. Noursadeghi, L. N. Segal and G. Theron. EBioMedicine 67: 103374 https://doi.org/10.1016/j.ebiom.2021.103374
  • Analysis tools to quantify dissemination of pathology in zebrafish larvae. (2020) Stirling, D. R. et al. Sci Rep 10(1): 3149 https://doi.org/10.1038/s41598-020-59932-1
  • Bacillus Calmette-Guerin skin reaction predicts enhanced mycobacteria-specific T-cell responses in infants: A post hoc analysis of a randomized controlled trial. (2022) Pittet, L. F., N. Fritschi, M. Tebruegge, B. Dutta, S. Donath, N. L. Messina, D. Casalaz, W. A. Hanekom, W. J. Britton, R. Robins-Browne, N. Curtis and N. Ritz. Am J Respir Crit Care Med 205(7): 830-841 https://doi.org/10.1164/rccm.202108-1892OC
  • Defining discriminatory antibody fingerprints in active and latent tuberculosis. (2022) Nziza, N., D. Cizmeci, L. Davies, E. B. Irvine, W. Jung, B. A. Fenderson, M. de Kock, W. A. Hanekom, K. Franken, C. L. Day, T. H. M. Ottenhoff and G. Alter. Front Immunol 13: 856906 https://doi.org/10.3389/fimmu.2022.856906Exaggerated IL-17A activity in human in vivo recall responses discriminates active tuberculosis from latent infection and cured disease. (2021) Pollara, G., C. T. Turner, J. Rosenheim, A. Chandran, L. C. K. Bell, A. Khan, A. Patel, L. F. Peralta, A. Folino, A. Akarca, C. Venturini, T. Baker, S. Ecker, F. L. M. Ricciardolo, T. Marafioti, C. Ugarte-Gil, D. A. J. Moore, B. M. Chain, G. S. Tomlinson and M. Noursadeghi. Sci Transl Med 13(592) https://doi.org/10.1126/scitranslmed.abg7673
  • Immunobiology of tubercle bacilli and prospects of immunomodulatory drugs to tackle tuberculosis (TB) and other non-tubercular mycobacterial infections. (2022) Daniel, C. and S. Bhakta. Immunobiology 227(3): 152224 https://doi.org/10.1016/j.imbio.2022.152224
  • Investigating neutrophil cell death in TB pathogenesis. (2021) Fisher, K. L., K. Rajkumar-Bhugeloo, D. Moodley, T. Mpotje, D. Ramsuran, T. Ndung'u and M. J. Marakalala. Gates Open Res 5: 175 https://doi.org/10.12688/gatesopenres.13472.2
  • Mycobacterium tuberculosis senses host Interferon-gamma via the membrane protein MmpL10. (2022) Ahmed, M., J. Mackenzie, L. Tezera, R. Krause, B. Truebody, D. Garay-Baquero, A. Vallejo, K. Govender, J. Adamson, H. Fisher, J. W. Essex, S. Mansour, P. Elkington, A. J. C. Steyn and A. Leslie. Commun Biol 5(1): 1317 https://doi.org/10.1038/s42003-022-04265-0
  • NIX-mediated mitophagy regulate metabolic reprogramming in phagocytic cells during mycobacterial infection. (2021) Mahla, R. S., A. Kumar, H. J. Tutill, S. T. Krishnaji, B. Sathyamoorthy, M. Noursadeghi, J. Breuer, A. K. Pandey and H. Kumar. Tuberculosis (Edinb) 126: 102046 https://doi.org/10.1016/j.tube.2020.102046
  • The paradox of immune checkpoint inhibition reactivating tuberculosis. (2022) Ahmed, M., L. B. Tezera, P. T. Elkington and A. J. Leslie. Eur Respir J https://doi.org/10.1183/13993003.02512-2021
  • Tissue-resident-like CD4+ T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung. (2021) Ogongo, P., L. B. Tezera, A. Ardain, S. Nhamoyebonde, D. Ramsuran, A. Singh, A. Ng'oepe, F. Karim, T. Naidoo, K. Khan, K. J. Dullabh, M. Fehlings, B. H. Lee, A. Nardin, C. S. Lindestam Arlehamn, A. Sette, S. M. Behar, A. J. Steyn, R. Madansein, H. N. Kloverpris, P. T. Elkington and A. Leslie. J Clin Invest 131(10) https://doi.org/10.1172/JCI142014
  • Tribbles1 is host protective during in vivo mycobacterial infection. (2024) Hammond, F. R., Lewis, A., Pollara, G., Tomlinson, G. S., Noursadeghi, M., Kiss-Toth, E., and Elks, P. M. Elife 13 https://doi.org/10.7554/eLife.95980.
  • Understanding the tuberculosis granuloma: The matrix revolutions. (2021) Elkington, P., M. E. Polak, M. T. Reichmann and A. Leslie. Trends Mol Med https://doi.org/10.1016/j.molmed.2021.11.004
  • Validation of proteins associated with pathological damage in human tuberculosis granulomas: Study protocol. (2023) Mpotje, T., More, J., Rajkumar-Bhugeloo, K., Moodley, D., and Marakalala, M. J. Wellcome Open Res 8, 139: https://doi.org/10.12688/wellcomeopenres.19226.1.

Projects:

  • Clonal and functional T cell determinants of protection and pathogenesis in tuberculosis (Mahdad Noursadeghi)

People: Lucy Bell, David Lowe, Jackson Marakala, Mahdad Noursadeghi, Gabriele Pollara, Hans Stauss, Gillian Tomlinson

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Latent and sub-clinical TB

When people are infected with M. tuberculosis, if not cleared by the immune response, the bacteria will most often stay in the body – often the lungs – in a quiescent state.  At some point, which could be soon after infection or many years later, it can reactivate to cause disease.  Only 10% of infections move to disease, so most infection is latent.  Identifying people with latent infection, and those where the bacteria are starting to reactivate but not yet clinically apparent, is an important part of controlling disease. However this is not only technically difficult, but it also raises issues of what is appropriate to do, and often requires engaging with particular at-risk communities.

Example outputs: 

  • Association of diabetes, smoking, and alcohol use with subclinical-to-symptomatic spectrum of tuberculosis in 16 countries: an individual participant data meta-analysis of national tuberculosis prevalence surveys. (2023) Hamada, Y., Quartagno, M., Law, I., Malik, F., Bonsu, F. A., Adetifa, I. M. O., Adusi-Poku, Y., D'Alessandro, U., Bashorun, A. O., Begum, V., Lolong, D. B., Boldoo, T., Dlamini, T., Donkor, S., Dwihardiani, B., Egwaga, S., Farid, M. N., Celina, G. G. A. M., Mae, G. G. D., Husain, M. M., Ismail, F., Kaggwa, M., Kamara, D. V., Kasozi, S., Kaswaswa, K., Kirenga, B., Klinkenberg, E., Kondo, Z., Lawanson, A., Macheque, D., Manhica, I., Maama-Maime, L. B., Mfinanga, S., Moyo, S., Mpunga, J., Mthiyane, T., Mustikawati, D. E., Mvusi, L., Nguyen, H. B., Nguyen, H. V., Pangaribuan, L., Patrobas, P., Rahman, M., Rahman, M., Rahman, M. S., Raleting, T., Riono, P., Ruswa, N., Rutebemberwa, E., Rwabinumi, M. F., Senkoro, M., Sharif, A. R., Sikhondze, W., Sismanidis, C., Sovd, T., Stavia, T., Sultana, S., Suriani, O., Thomas, A. M., Tobing, K., Van der Walt, M., Walusimbi, S., Zaman, M. M., Floyd, K., Copas, A., Abubakar, I., and Rangaka, M. X. EClinicalMedicine 63, 102191: https://doi.org/10.1016/j.eclinm.2023.102191.
  • Beyond latent and active tuberculosis: A scoping review of conceptual frameworks. (2023) Zaidi, S. M. A., Coussens, A. K., Seddon, J. A., Kredo, T., Warner, D., Houben, R., and Esmail, H. EClinicalMedicine 66, 102332: https://doi.org/10.1016/j.eclinm.2023.102332.
  • Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise. (2024) Coussens, A. K., Zaidi, S. M. A., Allwood, B. W., Dewan, P. K., Gray, G., Kohli, M., Kredo, T., Marais, B. J., Marks, G. B., Martinez, L., Ruhwald, M., Scriba, T. J., Seddon, J. A., Tisile, P., Warner, D. F., Wilkinson, R. J., Esmail, H., Houben, R., and International Consensus for Early, T. B. g. Lancet Respir Med https://doi.org/10.1016/S2213-2600(24)00028-6.
  • Clinical trials of tuberculosis vaccines in the era of increased access to preventive antibiotic treatment. (2023) Rangaka, M. X., Frick, M., Churchyard, G., Garcia-Basteiro, A. L., Hatherill, M., Hanekom, W., Hill, P. C., Hamada, Y., Quaife, M., Vekemans, J., White, R. G., and Cobelens, F. Lancet Respir Med 11, 380-390: https://doi.org/10.1016/S2213-2600(23)00084-X.
  • Discovery and validation of a personalized risk predictor for incident tuberculosis in low transmission settings. (2020) Gupta, R. K. et al. Nat Med 26(12): 1941-1949 https://doi.org/10.1038/s41591-020-1076-0
  • Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-alpha inhibitor initiation in children in Spain. (2023) Calzada-Hernandez, J., Anton, J., Martin de Carpi, J., Lopez-Montesinos, B., Calvo, I., Donat, E., Nunez, E., Blasco Alonso, J., Mellado, M. J., Baquero-Artigao, F., Leis, R., Vegas-Alvarez, A. M., Medrano San Ildefonso, M., Pinedo-Gago, M. D. C., Eizaguirre, F. J., Tagarro, A., Camacho-Lovillo, M., Perez-Gorricho, B., Gavilan-Martin, C., Guillen, S., Sevilla-Perez, B., Pena-Quintana, L., Mesa-Del-Castillo, P., Fortuny, C., Tebruegge, M., and Noguera-Julian, A. Eur J Pediatr 182, 307-317: https://doi.org/10.1007/s00431-022-04640-3.Exaggerated IL-17A activity in human in vivo recall responses discriminates active tuberculosis from latent infection and cured disease. (2021) Pollara, G. et al. Sci Transl Med 13(592) https://doi.org/10.1126/scitranslmed.abg7673
  • Isoniazid preventive therapy completion between July-September 2019: A comparison across HIV differentiated service delivery models in Uganda. (2024) Mugenyi, L., Namuwenge, P. M., Ouma, S., Bakashaba, B., Nanfuka, M., Zech, J., Agaba, C., Mijumbi Ojok, A., Kaliba, F., Bossa Kato, J., Opito, R., Miya, Y., Katureebe, C., and Hirsch-Moverman, Y. PLoS One 19, e0296239: https://doi.org/10.1371/journal.pone.0296239.
  • Latent tuberculosis infection care. (2022) Gaskell, K. M., T. D. Pillay, J. Brown, M. Belton, S. O. Mepham, D. A. Moore and M. Lipman. Clin Infect Dis https://doi.org/10.1093/cid/ciac582
  • Reevaluating progression and pathways following Mycobacterium tuberculosis infection within the spectrum of tuberculosis. (2023) Horton, K. C., Richards, A. S., Emery, J. C., Esmail, H., and Houben, R. Proc Natl Acad Sci U S A 120, e2221186120: https://doi.org/10.1073/pnas.2221186120.
  • The relationship between social risk factors and latent tuberculosis infection among individuals residing in England: a cross-sectional study. (2020) Lule, S. A. et al. BMJ Glob Health 5(12) https://doi.org/10.1136/bmjgh-2020-003550
  • Screening for tuberculosis infection and effectiveness of preventive treatment among people with HIV in low-incidence settings. (2024) van Geuns, D., Arts, R. J. W., de Vries, G., Wit, F., Degtyareva, S. Y., Brown, J., Pareek, M., Lipman, M., and van Crevel, R. AIDS 38, 193-205: https://doi.org/10.1097/QAD.0000000000003747.
  • Subclinical tuberculosis disease - a review and analysis of prevalence surveys to inform definitions, burden, associations and screening methodology. (2020) Frascella, B. et al. Clin Infect Dis https://doi.org/10.1093/cid/ciaa1402

Projects: RID-TB

People: Ibrahim Abubakar, Hanif Esmail, Rishi Gupta, Marc Lipman, Maddy Noursadeghi, Gabriele Pollara, Lele Rangaka, Marc Tebreugge, Asad Zaidi, Ali Zumla 

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Long-term consequences of TB

It's common to regard TB as cured once treatment has been completed, with bacterial infection eliminated.  However, as with many serious illnesses, the person who has been 'cured' may be left with a variety of physical, psychological and personal effects that may continue to be seriously debilitating.  These might includes issues such as managing life with severely compromised lungs, post-traumatic stress, and potentially catastrophic financial consequences.

People: Marc Lipman

Marginalised populations

Like many health conditions, TB is more prevalent in populations who have fewer resources and less access to healthcare.  Furthermore, the long periods needed for treatment means that mobile populations of all sorts experience challenges accessing diagnosis and sustaining engagement with treatment. To improve TB prevention and care among these populations we conduct research focussing on migrants, people who have experienced homelessness, war and incarceration.

Example outputs:

  • Barriers and enablers to implementing tuberculosis control strategies in EU and European Economic Area countries: a systematic review. (2021) Conroy, O., F. Wurie, S. M. Collin, M. Edmunds, G. de Vries, K. Lonnroth, I. Abubakar, S. R. Anderson and D. Zenner. Lancet Infect Dis 21(9): e272-e280 https://doi.org/10.1016/S1473-3099(21)00077-3
  • High burden of childhood tuberculosis in migrants: a retrospective cohort study from the Thailand-Myanmar border. (2022) Carroll, A., B. Maung Maung, W. P. P. Htun, W. Watthanaworawit, M. Vincenti-Delmas, C. Smith, P. Sonnenberg and F. Nosten. BMC Infect Dis 22(1): 608 https://doi.org/10.1186/s12879-022-07569-y
  • Integrated screening of migrants for multiple infectious diseases: Qualitative study of a city-wide programme. (2020) Eborall, H. et al. EClinicalMedicine 21: 100315 https://doi.org/10.1016/j.eclinm.2020.100315
  • "It's too hard" - the management of latent TB in under-served populations in the UK: a qualitative study. (2022) Gray, A. T., J. Surey, H. Esmail, A. Story and M. Harris. BMC Health Serv Res 22(1): 1464 https://doi.org/10.1186/s12913-022-08855-w
  • Optimising tuberculosis care for refugees affected by armed conflicts. (2022) Castro, K. G., Ditiu, L., Sahu, S., Ntoumi, F., Tiberi, S., O'Kane, C. M., Akkerman, O., Manika, K., Mwaba, P., Davies Forsman, L., Petersen, E., Aklillu, E., Azhar, E. I., Cirillo, D. M., Migliori, G. B., Abbara, A., and Zumla, A. Lancet Respir Med 10, 533-536: https://doi.org/10.1016/S2213-2600(22)00104-7.
  • Outcomes of a residential respite service for homeless people with tuberculosis in London, UK: A cross-sectional study. (2023) Crosby, L., Lewer, D., Appleby, Y., Anderson, C., Hayward, A., and Story, A. Perspect Public Health 143, 89-96: https://doi.org/10.1177/17579139221093544.
  • Protocol for a systematic review of treatment adherence for HIV, hepatitis C and tuberculosis among homeless populations. (2020) Johnson, L. et al. Syst Rev 9(1): 211 https://doi.org/10.1186/s13643-020-01470-y
  • Psychosocial support interventions to improve treatment outcomes for people living with tuberculosis: A mixed methods systematic review and meta-analysis. (2023) Maynard, C., Tariq, S., Sotgiu, G., Migliori, G. B., van den Boom, M., and Field, N. EClinicalMedicine 61, 102057: https://doi.org/10.1016/j.eclinm.2023.102057.
  • Screening for latent tuberculosis in migrants-status quo and future challenges. (2024) Petersen, E., Al-Abri, S., Al-Jardani, A., Memish, Z. A., Aklillu, E., Ntoumi, F., Mwaba, P., Wejse, C., Zumla, A., and Al-Yaquobi, F. Int J Infect Dis 141S, 107002: https://doi.org/10.1016/j.ijid.2024.107002.
  • A systematic review of tuberculosis detection and prevention studies in prisons. (2022) Haeusler, I. L., A. Torres-Ortiz and L. Grandjean. Glob Public Health 17(2): 194-209 https://doi.org/10.1080/17441692.2020.1864753
  • Tackling TB in migrants arriving at Europe's southern border. (2021) Gosce, L., E. Girardi, K. Allel, D. M. Cirillo, L. Barcellini, G. Stancanelli, A. Matteelli, H. Hagphrast-Bidgoli and I. Abubakar. Int J Infect Dis 113 Suppl 1: S28-S32 https://doi.org/10.1016/j.ijid.2021.02.103
  • Reply: Tuberculosis screening in migrants to the EU/EEA and UK. (2023) Zenner, D., Cobelens, F., and Abubakar, I. Eur Respir J 62: https://doi.org/10.1183/13993003.01535-2023.
  • Tuberculosis surveillance in Romania among vulnerable risk groups between 2015 and 2017. (2022) Munteanu, I., N. Cioran, R. van Hest, I. Abubakar, A. Story, D. Chiotan, G. de Vries and B. Mahler. Ther Clin Risk Manag 18: 439-446 https://doi.org/10.2147/TCRM.S347748
  • World tuberculosis day 2023 - Reflections on the spread of drug-resistant tuberculosis by travellers and reducing risk in forcibly displaced populations. (2023) Rodriguez-Morales, A. J., Abbara, A., Ntoumi, F., Kapata, N., Mwaba, P., Yeboah-Manu, D., Maeurer, M., Dar, O., Abubakar, I., and Zumla, A. Travel Med Infect Dis 53, 102568: https://doi.org/10.1016/j.tmaid.2023.102568.

Projects:

People: Ibrahim Abubakar, Rob Aldridge, Andrew Hayward, Lele Rangaka, Emily Shaw, Al Story 

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Non-tuberculous mycobacteria (NTM)

Although TB, caused by Mycobacterium tuberculosis and other highly related organisms in what is called the M. tuberculosis complex, may be considered the most important disease caused by mycobacteria, other mycobacteria do cause significant human disease. These are grouped essentially as ‘everything that is not tuberculosis or leprosy: non-tuberculous mycobacteria (NTM).  These mycobacteria, such as M. abscessus  and M. avium, survive in the environment or other animals, and disease in humans is usually opportunistic.  However these infections are increasingly common and are seen in people who are generally not thought of as being at risk of such infections. NTM infections can be debilitating, and hard to diagnose and treat. Our work looks at both at how these bacteria (including M. abscessus, M. avium, M. marinum and M. ulcerans) cause disease, and how infections can be effectively managed in patients.

Example outputs:

  • Carprofen elicits pleiotropic mechanisms of bactericidal action with the potential to reverse antimicrobial drug resistance in tuberculosis. (2020) Maitra, A. et al. J Antimicrob Chemother 75(11): 3194-3201 https://doi.org/10.1093/jac/dkaa307
  • Cross-transmission is not the source of new Mycobacterium abscessus infections in a multicenter cohort of cystic fibrosis patients. (2020) Doyle, R. M. et al. Clin Infect Dis 70(9): 1855-1864 https://doi.org/10.1093/cid/ciz526
  • Current and future management of non-tuberculous mycobacterial pulmonary disease (NTM-PD) in the UK. (2020) Lipman, M. et al. BMJ Open Respir Res 7(1) https://doi.org/10.1136/bmjresp-2020-000591
  • Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. (2019) Dedrick, R. M. et al. Nat Med 25(5): 730-733 https://doi.org/10.1038/s41591-019-0437-z
  • Interferon-Gamma release assays differentiate between Mycobacterium avium complex and tuberculous lymphadenitis in children. (2021) Martinez-Planas, A. et al. J Pediatr 236: 211-218 e212 https://doi.org/10.1016/j.jpeds.2021.05.008
  • Mycobacterium abscessus in cystic fibrosis. (2021) Brugha, R. and H. Spencer. Science 372(6541): 465-466 https://doi.org/10.1126/science.abi5695
  • Mycobacterium ulcerans-specific immune response after immunisation with bacillus Calmette-Guerin (BCG) vaccine. (2021) Pittet, L. F. et al. Vaccine 39(4): 652-657 https://doi.org/10.1016/j.vaccine.2020.11.045
  • The mycobactin biosynthesis pathway: A prospective therapeutic target in the battle against tuberculosis. (2021) Shyam, M. et al. J Med Chem 64(1): 71-100 https://doi.org/10.1021/acs.jmedchem.0c01176
  • Mycobactin Analogues with Excellent Pharmacokinetic Profile Demonstrate Potent Antitubercular Specific Activity and Exceptional Efflux Pump Inhibition. (2022) Shyam, M. et al. J Med Chem 65(1): 234-256 https://doi.org/10.1021/acs.jmedchem.1c01349
  • Non tuberculous mycobacteria pulmonary disease: patients and clinicians working together to improve the evidence base for care. (2021) Lipman, M., H. Kunst, M. R. Loebinger, H. J. Milburn and M. King. Int J Infect Dis 113 Suppl 1: S73-S77 https://doi.org/10.1016/j.ijid.2021.03.064
  • The problem of Mycobacterium abscessus complex: Multi-drug resistance, bacteriophage susceptibility and potential healthcare transmission. (2023) Dedrick, R. M., Abad, L., Storey, N., Kaganovsky, A. M., Smith, B. E., Aull, H. A., Cristinziano, M., Morkowska, A., Murthy, S., Loebinger, M. R., Hatfull, G. F., and Satta, G. Clin Microbiol Infect 29, 1335 e1339-1335 e1316: https://doi.org/10.1016/j.cmi.2023.06.026.
  • Rare mycobacteria and HIV in children: Two case reports. (2022) Johnson, S. M., Pinera, C., Whittaker, E., Kirkhope, N., Kon, O. M., Satta, G., Balcells, M. E., and Foster, C. Clin Drug Investig 42, 541-547: https://doi.org/10.1007/s40261-022-01153-7.
     

Projects:

  • Cell-wall and Iron-acquisition mechanisms in Mycobacterium abscessus (Sanjib Bhakta)
  • European Non-tuberculouS Mycobacterial Lymphadenitis in childrEn (ENSeMBLE) study (Marc Tebruegge)
  • Evolution of mycobacterial drug resistance (Naomi Fuller, Tim McHugh)
  • M. abscessus rapid diagnosis of resistance with whole genome sequencing (Giovanni Satta, Garth Dixon)
  • M. abscessus new treatment options, including bacteriophages (Giovanni Satta)
  • Post-transcriptional regulation in M. abscessus (Kristine Arnvig)
  • The Hollow-Fibre Model of M. abscessus disease to test new antibiotics and combination therapy (Steve Morris-Jones, Giovanni Satta)

People: Ibrahim Abubakar, Kristine Arnvig, Sanjib Bhakta, Helen Booth, Hanif Esmail, Naomi Fuller, Frank Kloprogge, David Lowe, Marc Lipman, Tim McHugh, Rob Miller, Giovanni Satta, Helen Spencer, Marc Tebruegge, Gillian Tomlinson, Jacqui White

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Paediatric tuberculosis

As with many branches of medicine, paediatric TB is a specialist aspect of TB control and clinical care.  Standard clinical trials exclude children, and specific trials have to be carried out to determine what is safe and efficacious. The recent SHINE trial, which involved UCL staff in the MRC CLinicat Trials Unit at UCL, was a recent highlight, in that it directly impacted on children, and allowed many of them to be treated for shorter periods. This was rapidly incorporated by WHO into receommendations for programmatic treatment of children with TB.

Example outputs:

Publications

  • Artificial intelligence in paediatric tuberculosis. (2023) Naidoo, J., Shelmerdine, S. C., Charcape, C. F. U., and Sodhi, A. S. Pediatr Radiol 53, 1733-1745: https://doi.org/10.1007/s00247-023-05606-9.
  • Clinical outcomes in children living with HIV treated for non-severe tuberculosis in the SHINE Trial. (2024) Chabala, C., Wobudeya, E., van der Zalm, M. M., Kapasa, M., Raichur, P., Mboizi, R., Palmer, M., Kinikar, A., Hissar, S., Mulenga, V., Mave, V., Musoke, P., Hesseling, A. C., McIlleron, H., Gibb, D., Crook, A., Turkova, A., and team, S. t. Clin Infect Dis https://doi.org/10.1093/cid/ciae193.
  • Clinical standards for drug-susceptible TB in children and adolescents. (2023) Chiang, S. S., Graham, S. M., Schaaf, H. S., Marais, B. J., Sant'Anna, C. C., Sharma, S., Starke, J. R., Triasih, R., Achar, J., Amanullah, F., Armitage, L. Y., Aurilio, R. B., Buck, W. C., Centis, R., Chabala, C., Cruz, A. T., Demers, A. M., du Preez, K., Enimil, A., Furin, J., Garcia-Prats, A. J., Gonzalez, N. E., Hoddinott, G., Isaakidis, P., Jaganath, D., Kabra, S. K., Kampmann, B., Kay, A., Kitai, I., Lopez-Varela, E., Maleche-Obimbo, E., Malaspina, F. M., Velasquez, J. N., Nuttall, J. J. C., Oliwa, J. N., Andrade, I. O., Perez-Velez, C. M., Rabie, H., Seddon, J. A., Sekadde, M. P., Shen, A., Skrahina, A., Soriano-Arandes, A., Steenhoff, A. P., Tebruegge, M., Tovar, M. A., Tsogt, B., van der Zalm, M. M., Welch, H., and Migliori, G. B. Int J Tuberc Lung Dis 27, 584-598: https://doi.org/10.5588/ijtld.23.0085.
  • Diagnostic accuracy of a three-gene Mycobacterium tuberculosis host response cartridge using fingerstick blood for childhood tuberculosis: a multicentre prospective study in low-income and middle-income countries. (2023) Olbrich, L., Verghese, V. P., Franckling-Smith, Z., Sabi, I., Ntinginya, N. E., Mfinanga, A., Banze, D., Viegas, S., Khosa, C., Semphere, R., Nliwasa, M., McHugh, T. D., Larsson, L., Razid, A., Song, R., Corbett, E. L., Nabeta, P., Trollip, A., Graham, S. M., Hoelscher, M., Geldmacher, C., Zar, H. J., Michael, J. S., Heinrich, N., and RaPaed, T. B. c. Lancet Infect Dis https://doi.org/10.1016/S1473-3099(23)00491-7.
  • Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-alpha inhibitor initiation in children in Spain. (2023) Calzada-Hernandez, J., Anton, J., Martin de Carpi, J., Lopez-Montesinos, B., Calvo, I., Donat, E., Nunez, E., Blasco Alonso, J., Mellado, M. J., Baquero-Artigao, F., Leis, R., Vegas-Alvarez, A. M., Medrano San Ildefonso, M., Pinedo-Gago, M. D. C., Eizaguirre, F. J., Tagarro, A., Camacho-Lovillo, M., Perez-Gorricho, B., Gavilan-Martin, C., Guillen, S., Sevilla-Perez, B., Pena-Quintana, L., Mesa-Del-Castillo, P., Fortuny, C., Tebruegge, M., and Noguera-Julian, A. Eur J Pediatr 182, 307-317: https://doi.org/10.1007/s00431-022-04640-3.
  • Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial. (2022) Turkova, A., H. Waalewijn, M. K. Chan, P. D. J. Bollen, M. F. Bwakura-Dangarembizi, A. R. Kekitiinwa, M. F. Cotton, A. Lugemwa, E. Variava, G. M. Ahimbisibwe, U. Srirompotong, V. Mumbiro, P. Amuge, P. Zuidewind, S. Ali, C. M. Kityo, M. Archary, R. A. Ferrand, A. Violari, D. M. Gibb, D. M. Burger, D. Ford, A. Colbers and O. T. Team. Lancet HIV 9(9): e627-e637 https://doi.org/10.1016/S2352-3018(22)00160-6
  • Evaluating pediatric tuberculosis dosing guidelines: A model-based individual data pooled analysis. (2023) Galileya, L. T., Wasmann, R. E., Chabala, C., Rabie, H., Lee, J., Njahira Mukui, I., Hesseling, A., Zar, H., Aarnoutse, R., Turkova, A., Gibb, D., Cotton, M. F., McIlleron, H., and Denti, P. PLoS Med 20, e1004303: https://doi.org/10.1371/journal.pmed.1004303.
  • Evaluation of serological assays for the diagnosis of childhood tuberculosis disease: a study protocol. (2024) Neudecker, D., Fritisch, N., Sutter, T., Lu, L., Lu, P., Tebruegge, M., Santiago-Garcia, B., and Ritz, N. BMC Infect Dis 24, 481: https://doi.org/10.1186/s12879-024-09359-0.
  • Fluoroquinolone preventive therapy for children exposed to MDR-TB. (2022) Gureva, T., A. Turkova, E. Yablokova, P. Smirnova, O. Sveshnikova, O. Zolotaya, E. Nikishova, E. Heldal, S. Hinderaker, J. A. Seddon and A. Mariandyshev. Int J Tuberc Lung Dis 26(2): 171-173 https://doi.org/10.5588/ijtld.21.0443
  • Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis. (2022) Gafar, F., R. E. Wasmann, H. M. McIlleron, R. E. Aarnoutse, H. S. Schaaf, B. J. Marais, D. Agarwal, S. Antwi, N. D. Bang, A. Bekker, D. J. Bell, C. Chabala, L. Choo, G. R. Davies, J. N. Day, R. Dayal, P. Denti, P. R. Donald, E. Engidawork, A. J. Garcia-Prats, D. Gibb, S. M. Graham, A. C. Hesseling, S. K. Heysell, M. I. Idris, S. K. Kabra, A. Kinikar, A. K. Hemanth Kumar, A. Kwara, R. Lodha, C. Magis-Escurra, N. Martinez, B. S. Mathew, V. Mave, E. Mduma, R. Mlotha-Mitole, S. G. Mpagama, A. Mukherjee, H. M. Nataprawira, C. A. Peloquin, T. Pouplin, G. Ramachandran, J. Ranjalkar, V. Roy, R. Ruslami, I. Shah, Y. Singh, M. G. G. Sturkenboom, E. M. Svensson, S. Swaminathan, U. Thatte, S. Thee, T. A. Thomas, T. Tikiso, D. J. Touw, A. Turkova, T. Velpandian, L. M. Verhagen, J. L. Winckler, H. Yang, V. Yunivita, K. Taxis, J. Stevens, J. C. Alffenaar and T. B. D. Global Collaborative Group for Meta-Analysis of Paediatric Individual Patient Data in Pharmacokinetics of Anti. Eur Respir J https://doi.org/10.1183/13993003.01596-2022
  • High burden of childhood tuberculosis in migrants: a retrospective cohort study from the Thailand-Myanmar border. (2022) Carroll, A., B. Maung Maung, W. P. P. Htun, W. Watthanaworawit, M. Vincenti-Delmas, C. Smith, P. Sonnenberg and F. Nosten. BMC Infect Dis 22(1): 608 https://doi.org/10.1186/s12879-022-07569-y
  • Host, technical, and environmental factors affecting QuantiFERON-TB Gold In-Tube performance in children below 5 years of age. (2022) Velasco-Arnaiz, E., M. Batllori, M. Monsonis, A. Valls, M. Rios-Barnes, S. Simo-Nebot, A. Gamell, C. Fortuny, M. Tebruegge and A. Noguera-Julian. Sci Rep 12(1): 19908 https://doi.org/10.1038/s41598-022-24433-w
  • Inadequate Lopinavir concentrations with modified 8-hourly Lopinavir/Ritonavir 4:1 dosing during rifampicin-based tuberculosis treatment in children living with HIV. (2023) Chabala, C., Turkova, A., Kapasa, M., LeBeau, K., Tembo, C. H., Zimba, K., Weisner, L., Zyambo, K., Choo, L., Chungu, C., Lungu, J., Mulenga, V., Crook, A., Gibb, D., McIlleron, H., and team, S. t. Pediatr Infect Dis J 42, 899-904: https://doi.org/10.1097/INF.0000000000004047.
  • Performance of QuantiFERON-TB Gold Plus assays in paediatric tuberculosis: A multicentre PTBNET study. (2023) Buonsenso, D., Noguera-Julian, A., Moroni, R., Hernandez-Bartolome, A., Fritschi, N., Lancella, L., Cursi, L., Soler-Garcia, A., Kruger, R., Feiterna-Sperling, C., Sali, M., Lo Vecchio, A., Scarano, S., Hernanz Lobo, A., Espiau, M., Soriano-Arandes, A., Cetin, B. S., Brinkmann, F., Ozere, I., Baquero-Artigao, F., Tsolia, M., Milheiro Silva, T., Bustillo-Alonso, M., Martin Nalda, A., Mancini, M., Starshinova, A., Ritz, N., Velizarova, S., Ferreras-Antolin, L., Gotzinger, F., Bilogortseva, O., Chechenyeva, V., Tebruegge, M., Santiago-Garcia, B., and ptbnet, Q. F. T. P. s. g. Thorax 78, 288-296: https://doi.org/10.1136/thorax-2022-218929.
  • Pharmacokinetics of first-line drugs in children with tuberculosis, using World Health Organization-recommended weight band doses and formulations. (2022) Chabala, C., A. Turkova, A. C. Hesseling, K. M. Zimba, M. van der Zalm, M. Kapasa, M. Palmer, M. Chirehwa, L. Wiesner, E. Wobudeya, A. Kinikar, V. Mave, S. Hissar, L. Choo, K. LeBeau, V. Mulenga, R. Aarnoutse, D. Gibb and H. McIlleron. Clin Infect Dis 74(10): 1767-1775 https://doi.org/10.1093/cid/ciab725
  • Shorter treatment for nonsevere tuberculosis in African and Indian children. (2022) Turkova, A., G. H. Wills, E. Wobudeya, C. Chabala, M. Palmer, A. Kinikar, S. Hissar, L. Choo, P. Musoke, V. Mulenga, V. Mave, B. Joseph, K. LeBeau, M. J. Thomason, R. B. Mboizi, M. Kapasa, M. M. van der Zalm, P. Raichur, P. K. Bhavani, H. McIlleron, A. M. Demers, R. Aarnoutse, J. Love-Koh, J. A. Seddon, S. B. Welch, S. M. Graham, A. C. Hesseling, D. M. Gibb, A. M. Crook and S. T. Team. N Engl J Med 386(10): 911-922 https://doi.org/10.1056/NEJMoa2104535
  • Shorter Treatment for Tuberculosis in Children. Reply. (2022) Turkova, A., M. Palmer and D. M. Gibb. N Engl J Med 386(25): 2439-2440 https://doi.org/10.1056/NEJMc2204561
  • Towards accurate point-of-care tests for tuberculosis in children. (2022) Vaezipour, N., N. Fritschi, N. Brasier, S. Belard, J. Dominguez, M. Tebruegge, D. Portevin and N. Ritz. Pathogens 11(3) https://doi.org/10.3390/pathogens11030327
  • Treatment and outcome in children with tuberculous meningitis: A multicenter Pediatric Tuberculosis Network European Trials Group study. (2022) Thee, S., R. Basu Roy, D. Blazquez-Gamero, L. Falcon-Neyra, O. Neth, A. Noguera-Julian, C. Lillo, L. Galli, E. Venturini, D. Buonsenso, F. Gotzinger, N. Martinez-Alier, S. Velizarova, F. Brinkmann, S. B. Welch, M. Tsolia, B. Santiago-Garcia, R. Schilling, M. Tebruegge, R. Kruger and T. B. M. S. G. ptbnet. Clin Infect Dis 75(3): 372-381 https://doi.org/10.1093/cid/ciab982
  • Tuberculosis disease in immunocompromised children and adolescents: a pTBnet multi-centre case-control study. (2024) Rodriguez-Molino, P., Tebruegge, M., Noguera-Julian, A., Neth, O., Fidler, K., Brinkmann, F., Sainz, T., Ivaskeviciene, I., Ritz, N., Brito, M. J., Milheiro Silva, T., Chechenieva, V., Serdiuk, M., Lancella, L., Russo, C., Soler-Garcia, A., Navarro, M. L., Krueger, R., Feiterna-Sperling, C., Starshinova, A., Hiteva, A., Hoffmann, A., Kalibatas, P., Lo Vecchio, A., Scarano, S. M., Bustillo, M., Blazquez Gamero, D., Espiau, M., Buonsenso, D., Falcon, L., Turnbull, L., Colino, E., Rueda, S., Buxbaum, C., Carazo, B., Alvarez, C., Dapena, M., Piqueras, A., Velizarova, S., Ozere, I., Gotzinger, F., Pareja, M., Garrote Llanos, M. I., Soto, B., Rodriguez Martin, S., Korta, J. J., Perez-Gorricho, B., Herranz, M., Hernandez-Bartolome, A., Diaz-Almiron, M., Kohns Vasconcelos, M., Ferreras-Antolin, L., and Santiago-Garcia, B. Clin Infect Dis https://doi.org/10.1093/cid/ciae158.
  • Utility of esophageal ultrasound-guided biopsy of mediastinal lymph nodes in diagnosis of childhood tuberculosis. (2022) Cohen, J. M., M. Banks, O. M. Kon and S. Eisen. Pediatr Infect Dis J 41(5): e246-e248 https://doi.org/10.1097/INF.0000000000003498
  • The value of the second QuantiFERON-TB Gold-Plus antigen tube at diagnosis and at treatment completion in Spanish children with tuberculosis. (2023) Soler-Garcia, A., Gamell, A., Monsonis, M., Korta-Murua, J. J., Espiau, M., Rincon-Lopez, E., Rodriguez-Molino, P., Perez-Porcuna, T., Bustillo-Alonso, M., Santiago, B., Tebruegge, M., Noguera-Julian, A., and Network, Q. F.-P. S. G. o. t. S. P. T. R. Pediatr Infect Dis J: https://doi.org/10.1097/INF.0000000000004058.
  • Variation in initial health assessment of unaccompanied asylum-seeking children: a cross-sectional survey across England. (2022) Nezafat Maldonado, B., A. J. Armitage and B. Williams. BMJ Paediatr Open 6(1) https://doi.org/10.1136/bmjpo-2022-001435

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Projects: 

People: Diana Gibb, Marc Tebreugge, Anna Turkova

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Pharmacology

Determining the best combinations and levels of drugs for TB treatment to effectively kill bacteria, and minimise side effects, is challenging. By investigating the relationship between how much drug is used and how effective they are  (the pharmacokinetic-pharmacodynamic relationships), we can optimise the combinations of drugs that we use to treat TB. We use two approaches: the first is the hollow-fibre laboratory model, in which we investigate drug effects of treatment combinations against M. tuberculosis in a controlled way by mimicking antibiotic profiles to human conditions. A second approach is to evaluate antibiotic effects of drug combinations in the context of the whole body and immune system using data from patients.

Example outputs:

  • Can phenotypic data complement our understanding of antimycobacterial effects for drug combinations?  (2019) Kloprogge, F. et al.  J Antimicrob Chemother 74(12): 3530-3536 https://doi.org/10.1093/jac/dkz369
  • Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial. (2022) Turkova, A., H. Waalewijn, M. K. Chan, P. D. J. Bollen, M. F. Bwakura-Dangarembizi, A. R. Kekitiinwa, M. F. Cotton, A. Lugemwa, E. Variava, G. M. Ahimbisibwe, U. Srirompotong, V. Mumbiro, P. Amuge, P. Zuidewind, S. Ali, C. M. Kityo, M. Archary, R. A. Ferrand, A. Violari, D. M. Gibb, D. M. Burger, D. Ford, A. Colbers and O. T. Team. Lancet HIV 9(9): e627-e637 https://doi.org/10.1016/S2352-3018(22)00160-6
  • Emergence of phenotypic and genotypic antimicrobial resistance in Mycobacterium tuberculosis. (2022) Kloprogge, F. et al. Sci Rep 12(1): 21429 https://doi.org/10.1038/s41598-022-25827-6
  • Evaluation of pharmacokinetic-pharmacodynamic relationships and selection of drug combinations for tuberculosis. (2021) Muliaditan, M. and O. Della Pasqua. Br J Clin Pharmacol 87(1): 140-151 https://doi.org/10.1111/bcp.14371
  • Exploring a combined biomarker for tuberculosis treatment response: protocol for a prospective observational cohort study. (2021) Kloprogge, F et al.. BMJ Open 11(7): e052885 https://doi.org/10.1136/bmjopen-2021-052885
  • Editorial: The evolution in pharmacology of infectious diseases: 2022. (2024) Porta, E. O. J., Saffaei, A., and Kalesh, K. Front Pharmacol 15, 1386077: https://doi.org/10.3389/fphar.2024.1386077
  • Inadequate Lopinavir concentrations with modified 8-hourly Lopinavir/Ritonavir 4:1 dosing during rifampicin-based tuberculosis treatment in children living with HIV. (2023) Chabala, C., Turkova, A., Kapasa, M., LeBeau, K., Tembo, C. H., Zimba, K., Weisner, L., Zyambo, K., Choo, L., Chungu, C., Lungu, J., Mulenga, V., Crook, A., Gibb, D., McIlleron, H., and team, S. t. Pediatr Infect Dis J 42, 899-904: https://doi.org/10.1097/INF.0000000000004047
  • Longitudinal pharmacokinetic-pharmacodynamic biomarkers correlate with treatment outcome in drug-sensitive pulmonary tuberculosis: A population pharmacokinetic-pharmacodynamic analysis. (2020) Kloprogge, F., et al. Open Forum Infect Dis 7(7): ofaa218 https://doi.org/10.1093/ofid/ofaa218
  • Pharmacokinetics of first-line drugs in children with tuberculosis, using World Health Organization-recommended weight band doses and formulations. (2022) Chabala, C., A. Turkova, A. C. Hesseling, K. M. Zimba, M. van der Zalm, M. Kapasa, M. Palmer, M. Chirehwa, L. Wiesner, E. Wobudeya, A. Kinikar, V. Mave, S. Hissar, L. Choo, K. LeBeau, V. Mulenga, R. Aarnoutse, D. Gibb and H. McIlleron. Clin Infect Dis 74(10): 1767-1775 https://doi.org/10.1093/cid/ciab725
  • Population pharmacokinetics and pharmacodynamics of investigational regimens' drugs in the TB-PRACTECAL clinical trial (the PRACTECAL-PKPD study): a prospective nested study protocol in a randomised controlled trial. (2021) Nyang'wa, B. T., F. Kloprogge, D. A. J. Moore, A. Bustinduy, I. Motta, C. Berry and G. R. Davies. BMJ Open 11(9): e047185 https://doi.org/10.1136/bmjopen-2020-047185

Projects:

People: Oscar Della Pasqua, Diana Gibb, Frank Kloprogge, Anna Turkova

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Policy engagement

Many different policies - at local, national and international levels – shape the experiences of people and communities affected by tuberculosis and are a major method of public health governance. Exploring how policy is constructed and investigating the impacts of particular policies are an important focus of research. In addition, engaging with politics, policy-makers from an advocacy perspective is an important tool in the global work to End TB. Our work brings a critical perspective to policy analysis. In addition we work with UK Academics and Professionals to End TB to help bridge the gap between research and healthcare experiences and policy-makers.

Our projects:

  • A qualitative study exploring the impact of TB policies across Western Europe and barriers to success.
  • Access to TB medicines webinar series

Example outputs:

 

People: Ilaria Motta, Jess Potter

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