TBnet Newsletter March 2021

Updated: Mar 25


1. Reminder: today March 25th, join the discussion on TB advocacy in Europe @ 16:00 CET

Panel: Jess Potter, TBnet, Paul Thorn and Kseniia Shchenina, TBpeople https://www.tbnet.eu/post/tbnet-webinar-in-march


2. World TB Day Blog

Each year we use the date Robert Koch gave his historic presentation, demonstrating that TB was an infectious disease caused by Mycobacterium tuberculosis, to re-focus the World’s attention on this important condition. This year, as all eyes turned to focus on another global killer, advocacy in the field of TB is even more important. There has been a dramatic under-diagnosis of TB, particularly affecting high incidence countries. TB services have been interrupted impacting healthcare provision, laboratory work and drug supply. Funding of TB treatment and human resources are insufficient and the commitments of the High Level Meetings on TB from recent years are not being fulfilled.

When we consider what advocacy is – the attempt to influence institutions, politics, policies and practices to bring about change – TBnet is an active contributor in efforts to tackle TB across Europe. Established in 2006, TBnet is a pan-European network of healthcare professionals and scientists whose aim is to promote quality TB care through research and education.

Over the years our network has grown into a multinational, multi-disciplinary consortium comprising more than 650 participants. Let’s look at how we have been contributing to the fight against TB:


Research

TBnet members are able to rapidly elicit views, practises, and experiences using the network to steer general and scientific debate. This has produced detailed analyses of inequalities in drug prices and drug availability, access to diagnostics, and "best practises" in clinical care. Using the full network ensures that these rapid appraisals encompass a wide variety of clinical settings, making them a robust basis for practical guidelines. With over 60 peer-reviewed publications and an expanding number of expert-led consensus statements on topics where evidence is lacking, TBnet plays an influential role in guiding improvements in TB care.


Training

Another key component of TBnet’s work is education and this programme has two key flagship events. The yearly European Advanced Course on Clinical Tuberculosis is an in-depth course for physicians and public health experts, organised by TBnet and renowned international partners. It provides state-of-the art knowledge on the clinical management of TB, and connects health professionals from a large number of European countries.

TBnet Academy brings together aspiring and established TB clinicians and academics from across Europe. This gathering facilitates the exchange of knowledge and importantly experience – experience shared by people working at different stages of their career as well as the varied contextual experience of working in different regions across Europe.

These educational activities facilitate the dissemination of knowledge and improvements in best practice as well as fostering trans-national collaborations and capacity building.


Advocacy

In recent years there has been a more explicit focus on advocacy including collaboration with organisations of people who have personal experience of TB like "TakeThatTB" (Germany) and "TB people" (Eastern Europe and Central Asia). We organized several meetings focussing on healthcare inequalities, the needs of people with TB experience and disadvantaged groups like some migrants. TBnet Academies have been hosted by organizations in European countries with a heavy burden of TB such as Moldova, Ukraine, Russia, Armenia and Romania. They always include speakers from the local community of people affected by TB and an events designed to raise local awareness about TB. Through social media, TBnet is also more able to share knowledge and experience with the general public.

Advocacy can be undertaken on a range of scales and across a variety of contexts. Often, when it comes to campaigning to effect change, we think of protests such as storming the stage at the Union Conference demanding J&J reduce the price of bedaquiline. We think of organisations who lobby politicians to change the law so that people affected by TB can get access to some subsistence support, which has recently been achieved in Romania. Or perhaps we think of work with local, national and international media designed simply to draw attention to the fact that TB remains a global killer. However, advocacy can occur on a far smaller scale – a scale everyone can commit to. We all have the power to push for change, each and every day, through all of our interactions. By listening to the experiences of people affected by TB we can learn what is important to them. By speaking up we can help centre these voices and concerns in our research questions, our research design, our education and our clinical practice.

For some scientists and researchers, advocacy might not be seen as part of our job. Indeed, it may even be considered in conflict with our perception of objectivity in relation to the validity of our work. However, if advocacy in TB is the campaign to challenge the inequitable structures which both contribute to and sustain the prevalence of TB in our societies; if to be a TB advocate is to strive to improve care for every single person affected by TB and, ultimately, to eliminate the disease all together; perhaps there is an argument that not only are we all advocates, but it is also necessary if we are to do our jobs effectively.

Contributed by:

Jessica Potter MBBCh PhD

Honorary Clinical Lecturer, Queen Mary University of London

TBnet SC member, Advocacy


3. TBnet Clinical Research Collaborations with the European Respiratory Society.

TBnet administration has been for many years supported by the European Respiratory Society (ERS) TBnet - Clinical Research Collaboration (CRC). This support comes to an end just a month before we hope to have signed off another major grant application.

The first CRC was proposed as a collaboration between the ERS and TBnet via Giovanni B Migliori and Christoph Lange to support European research in tuberculosis. Working together, they produced some of the fundamental components of TBnet which remain to this day:

1. A concern for patients to benefit from clinical research in tuberculosis across Europe

2. Creating new international collaborations among young researchers – the TBnet Academy

3. A regular clinical teach-in to enable the best and most up-to-date transfer of scientific knowledge to best clinical practice – the European Advanced Course in Clinical Tuberculosis.

The outcome for the first six years was a Framework 7 EU grant, which enabled the first CRC in tuberculosis to extend its scientific contributions.

Originally, CRCs acted as a support for an umbrella of studies led by individual members of the CRC Steering Committee, with the TBnet label recognizing collaborations of three or more countries working together. Many of the most important contributions of the CRC were projects based on the free commitment of time and effort by individual physicians, aware of the limited funding opportunities for tuberculosis and the tremendous need within Eastern Europe, especially regarding the increasing problem of MDR-TB. A consistent administration for TBnet provided a bedrock on which to build advances in tuberculosis care. TBnet is therefore very grateful for this support of the ERS to enable physicians to fulfil their potential in otherwise adverse circumstances.

MDR-TB continues to threaten the elimination of tuberculosis in Europe. Our studies over the past six years were instrumental in revealing the inequalities of access to diagnostic tests, inadequate isolation facilities and infection control for staff, insufficient capacity for treating MDR-TB and difficulties in the provision of new drug regimens and independent advice for their use across Europe. An important revision in treatment definitions, placing a relapse-free period at the end of treatment as a pivotal requirement in assessing treatment outcomes (NEJM 2016; 375:1103-5), has been widely accepted. Consensus documents have promoted safe clinical care.

We now hope to push forwards, addressing the needs for patients to have effective treatment for as short a time as possible but sufficient in duration to be sure of a cure. We thank all those physicians who have contributed their time and energy free of charge to this aim, physicians who exemplify the best of motivations, the care of their patients and the desire to see the treatment of difficult tuberculosis improve continuously.

Contributed by:

Graham Bothamley, Homerton University Hospital, Queen Mary University of London and London School of Hygiene and Tropical Medicine, TBnet SC member, Past Chair

Lorenzo Guglielmetti, MSF and French Natuional reference Centre for Mycobacteria, TBnet SC member, Clinical trials


4. Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model

Can RNA tell you if cure from TB has been achieved and there won't be a TB relapse later?

A 22-gene RNA transcriptomic model has been developed by an international team (including several active TBnet members) led by Dr Jan Heyckendorf from Research Center Borstel, Germany. This model accurately predicts clinical outcomes in tuberculosis patients. Application of the model on independent cohorts of patients in Germany and Romania suggests that treatment duration can be shortened in many multidrug-resistant tuberculosis (MDR-TB) patients. The model can become a useful treatment monitoring tool that will tell the clinician when to finish anti-TB treatment; and in many MDR-TB patients, it may be earlier than standard 20 months.

The paper can be found here:

https://erj.ersjournals.com/content/early/2021/01/28/13993003.03492-2020

To validate the model in a large prospective cohort of MDR-TB patients, a non-inferiority randomised clinical trial (ClinicalTrials.gov ID: NCT04783727) has just started at Research Center Borstel. Several international centres will join the trial later. The patients will be randomly assigned to one of two study arms: in the control arm, the patients will receive a standardised World Health Organization recommended 20 months treatment while in the experimental arm the treatment duration will be guided by the RNA transcriptomic signature-based model. All patients will be followed-up over the entire course of anti-TB treatment and one year after the end of therapy. Treatment outcomes and level of TB relapse and survival will be compared between the experimental and control arms. The efficacy of biomarker-guided treatment therapy will be assessed by a comparison of the proportions of favourable study outcome between two arms.

More details on the clinical trial: https://clinicaltrials.gov/ct2/show/NCT04783727

Contributed by:

Irina Kontsevaya, PhD, Postdoctoral Researcher at Research Center Borstel, Germany

TBnet SC member, Diagnostics


5. Link to the record of TBnet Clinical Webinar from February (panel discussion and the presentation of Guy Thwaites)

https://www.tbnet.eu/post/tbnet-february-webinar-record




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