Coordinated Action Tuberculosis

Activities

This Coordinated Action is tasked with:

• Ensuring cross-disciplinary scientific facilitation in order to stimulate high-level research on tuberculosis
• Identifying research priorities and uniting the community around key topics
• Strengthening collaborations and networks, particularly between basic, preclinical and clinical research, and internationally
• Increasing the international visibility of tuberculosis research supported by our agency
• Attracting and supporting the next generation of researchers, in particular to strengthen their role in the organisation and facilitation of events, and help promote their work

Key words: Tuberculosis, Mycobacterium tuberculosis, pathophysiology, host-pathogen interaction, prevention, vaccine, diagnosis, treatment, mortality, public health, basic research, clinical research, extra-pulmonary tuberculosis, latent tuberculosis, treatment resistance, host-targeted therapies, TB-HIV co-infection, immunodepression, pregnant women, children, adolescents, persistence, correlates of protection.

Chair and Co-Chair

Board members

Fight against tuberculosis: the objectives and achievements of the Coordinated action

Interview with the co-chairs of the Coordinated action, Olivier Neyrolles and François-Xavier Blanc.

1.Could you remind us of the reasons behind the creation of the ANRS MIE Coordinated action on tuberculosis?

Olivier Neyrolles. The creation of the Coordinated action (CA) on tuberculosis by the ANRS MIE was motivated by the need to respond to the global health emergency posed by tuberculosis, which remains the deadliest infectious disease, with an estimated 10 million new cases and over 1.2 million deaths by 2023. The situation has been exacerbated by the COVID-19 pandemic, which has disrupted health services, reversing the progress made over the last two decades. In addition, the rise in cases of multidrug-resistant tuberculosis (MDR-TB) represents a major threat to global public health. According to the latest WHO report, around 400,000 people will have developed resistant tuberculosis by 2023. Of these, only 44% were diagnosed and treated, despite a therapeutic success rate of almost 70% for these cases, reflecting an improvement in previous years. The low efficacy of the BCG vaccine against pulmonary forms of the disease and the persistent difficulties in diagnosis and treatment have also highlighted the need for a coordinated strategy to stimulate research and innovation in this field.

France is considered to have a low incidence of tuberculosis, with an average decrease of almost 5% per year for several decades. However, this trend has been interrupted by occasional variations, linked to external events. Some regions have higher incidence rates. French Guiana, Mayotte and Île-de-France are particularly affected. For example, in 2022, French Guiana had a rate of 18.9 cases per 100,000 inhabitants, and Mayotte 13.2 cases per 100,000 inhabitants. Île-de-France accounts for around a third of national cases, with a high incidence in Seine-Saint-Denis. Tuberculosis mainly affects people living in precarious conditions, migrants and the elderly. Homeless people have a particularly high incidence rate, estimated at 170 cases per 100,000 inhabitants. People born outside France are also more affected, with a rate of 34 cases per 100,000 inhabitants.

The creation of the CA has made it possible to bring together a community of researchers, doctors and health professionals to think about and set up projects together on this major public health issue.

François-Xavier Blanc. Historically, the ANRS MIE has already funded several major projects concerning the diagnosis and management of tuberculosis in people living with HIV. The agency has also contributed to the modification of several WHO guidelines in this area. Its field of action consisted almost exclusively of countries with a high prevalence of tuberculosis, particularly in sub-Saharan Africa, South-East Asia and some South American countries. The creation of a CA will obviously significantly broaden this scope: all research into tuberculosis is now potentially eligible for Funding, well beyond co-infection with HIV, and all territories are concerned, including France, where a national cohort of patients should soon see the light of day.

2.What were the group’s initial priorities when it was set up?

Olivier Neyrolles. The priorities defined when the CA was set up included:

• Improving diagnostic tools, particularly for latent, extra-pulmonary forms and vulnerable populations such as children and immunocompromised people.
• The development of new treatments that are shorter and better tolerated, targeting persistent bacteria and multi-resistant mycobacteria.
• The search for new vaccines that are more effective than BCG, requiring a better understanding of the mechanisms of immune protection.
• Strengthening collaboration between basic, preclinical and clinical research, as well as between researchers in the North and South, to create synergies and multidisciplinary approaches.
• Raising the international profile of French tuberculosis research and attracting new generations of researchers.

3.What have been the group’s main achievements since it was set up?

François-Xavier Blanc. The CA Tuberculosis is organised into three working groups: “Tuberculosis in the mother and children”, “Tuberculosis and immunodepression”, and “New treatments and vaccines strategies”. Since its creation, the CA has organised several major scientific events to boost research. An inaugural workshop was held at the end of 2022, bringing together the main players in tuberculosis research in France to encourage exchanges between disciplines (basic, preclinical, clinical) and present the resources available, such as cohorts and biobanks. In 2023, a consolidation symposium provided an opportunity to continue these discussions and refine the group’s strategic directions. Two CA plenary meetings were held in January 2024 and February 2025. At these meetings, the research projects funded by the ANRS MIE are presented by their authors. Workshops are organised on particularly sensitive topics, such as “Latent infection and subclinical tuberculosis: Screening, treatment and follow-up” and “Tuberculosis disease: Treatments, markers of response to treatments and adaptation of treatments to populations” for the 2025 edition. Annual or biannual “Work in Progress” meetings of each working group are also organised. In July 2024, for example, a symposium was held in Lille, organised by the “New treatments and vaccines” WG and the “Société Française de Microbiologie”, at which researchers and clinicians met to discuss basic and pre-translational research, new therapies in particular, epidemiology, resistance to treatments, innovations in diagnostics and host-pathogen interactions in tuberculosis. International symposia are planned to maintain this momentum and raise the profile of French research.

4.Has the group collaborated with international or local partners? If so, what was the impact of these collaborations?

Olivier Neyrolles. The CA TB has actively strengthened both local and international collaborations. Locally, the network has consolidated links between the basic research laboratories (via structures such as the Mycoclub) and clinical centers, facilitating the transfer of knowledge and technologies. Internationally, partnerships have been established with countries heavily affected by tuberculosis (India, South Africa, etc.) to share data, resources (cohorts, biobanks) and strategies for combating the disease. These collaborations have led to advances in the diagnosis, treatment and understanding of the epidemiological dynamics of tuberculosis.

5.In your opinion, what scientific advances have been the most significant in the fight against tuberculosis, supported or facilitated by this Coordinated action?

François-Xavier Blanc. The most significant advances include:

• Repositioning existing compounds for personalized treatments based on patient profiles (children, immunocompromised patients, etc.).
• The development of innovative strategies to target persistent bacteria, either by trying to eliminate them directly or by reactivating them to make them sensitive to conventional treatments.
• The exploration of host-directed therapies to improve the immune response against mycobacteria, or anti-virulence therapies to target the mechanisms of the pathogen required for its infectious cycle.
• Progress in our understanding of immune mechanisms and correlates of protection, essential for the development of more effective vaccines than BCG.

6.What are the priority projects for the coming years?

Olivier Neyrolles. Priority projects include:

• Continuing clinical trials to develop shorter, less toxic treatments, targeting persistent bacteria and adapting treatments to different patient profiles.
• The development of faster, simpler diagnostics, particularly for developing countries, with tests based on biomarkers detectable in bodily fluids.
• Advancing research into innovative vaccines, exploring approaches such as mucosal vaccination.
• The study of co-morbidities, such as diabetes, which influence the progression and management of tuberculosis.

François-Xavier Blanc. Priority projects are selected during calls for proposals by a Scientific Advisory Board that is separate from the CA. The CA therefore has no decision-making power in this area. It tries to bring to light themes that are sometimes neglected, such as those mentioned above, but its role in promoting scientific research stops there. It obviously cannot replace the independent scientific evaluators in charge of the projects submitted to the ANRS MIE during each call for proposals.

7.Do you plan to strengthen existing partnerships or develop new ones?

Olivier Neyrolles. Yes, the CA TB plans to consolidate its current collaborations, in particular by strengthening synergies between researchers in the North and South. For example, a call for proposals was launched in 2024 jointly by the Agency and the South African Medical Research Council (SAMRC) to fund joint projects between French and South African teams. New partnerships will also be sought with international institutions and epidemiology and public health research networks to increase the overall impact of tuberculosis research initiatives.

8.What innovations or avenues of research do you think could transform the fight against tuberculosis soon?

Olivier Neyrolles.

Promising innovations include:

• The development of vaccines with new administration methods, such as mucosal vaccination, which could improve protection against pulmonary forms.
• Host-directed therapies to overcome the persistence of mycobacteria and reduce the duration of treatment.
• The use of biomarkers for early and more accurate diagnosis, adapted to the needs of countries with limited resources.

François-Xavier Blanc. It’s important to remember that tuberculosis is still directly responsible for a high mortality rate worldwide, which in our view is truly unacceptable. The development and availability of more effective diagnostic and/or prognostic tools at reduced cost would transform the fight against tuberculosis, just as automated PCR did more than 10 years ago, making it possible to determine within 2 hours, almost anywhere in the world, whether a patient was suffering from tuberculosis and whether or not there was a suspicion of resistance to rifampin and therefore of multi-drug resistance. Soon, another major advance would be to achieve a very significant reduction in the duration of tuberculosis treatment, which currently still lasts several months and is fraught with certain difficulties. But there is still a lot of work to be done before these results can be achieved. Hence the need to pool our strengths!

9.How can researchers contribute to or take part in Coordinated action?

Olivier Neyrolles. Researchers can get involved by joining the CA TB’s thematic working groups, taking part in organised scientific events (workshops, symposia) and helping to make the most of existing resources (cohorts, biobanks). The CA also encourages the participation of the younger generation of researchers, notably through the creation of an annual Thesis Prize to reward innovative contributions in the field of tuberculosis research.

François-Xavier Blanc. Everyone is welcome. There’s something for everyone. Sharing information and developing collaborations are actively encouraged. So, bring your own skills and an open mind. The easiest way is to join one of the 3 working groups and propose a research topic likely to be of interest to other researchers. After that, it’s time to act and build collaborative projects that will be submitted for funding in the context of competition with the other themes covered by the ANRS MIE. Ultimately, multi-disciplinarity will remain a source of strength and progress, that’s for sure.