World Tuberculosis Day 2024

It was on 24 March 1882 that Dr Robert Koch announced his discovery of the bacillus responsible for tuberculosis.

Published on 20 March 2024

The theme of World TB Day 2024

The theme of this year is « Yes! we can end TB! ». In 2024, the focus is on implementing the commitments made by Heads of State at the United Nations Meeting in 2023 to eradicate tuberculosis as quickly as possible.

Impact of tuberculosis

Mortality remains high

An estimated 10.6 million people worldwide will have developed tuberculosis (TB) by 2022: 5.8 million men, 3.5 million women and 1.3 million children. TB is the second leading cause of infectious disease deaths worldwide, behind COVID-19 and before AIDS. A total of 1.3 million people died of TB in 2022 (167,000 of whom also had HIV infection). Ending the TB epidemic by 2030 is one of the health challenges included in the United Nations’ sustainable development goals.

Multidrug-resistant tuberculosis: a public health threat

Multidrug-resistant tuberculosis is a public health crisis and remains a health security threat threat. Only around two out of five people with drug-resistant TB had access to treatment in 2022.

The ANRS MIE commitment

To guarantee progress in reducing TB-related morbidity and mortality, it is necessary to maintain sufficient levels of funding over time. The ANRS MIE is committed to fighting TB by funding research projects and leading coordinated action groups composed of experts in the field.

To mark World TB Day, the ANRS MIE is presenting some of the major research projects currently underway, in particular on the management of TB in pregnant women and young children, and the search for new dual antibiotics or bio-inspired molecules to combat multidrug-resistant TB.

TB in pregnant women and infants in the early stages of life: interview with Prof. Philippe Vande Perre

Bio-inspired molecules in the fight against tuberculosis: interview from Dr. Hedia Marrakchi

New dual antibiotics: interview from Dr. Olivier Neyrolles

Olivier Neyrolles, Institute of Pharmacology and Structural Biology UMR 5089 CNRS-University of Toulouse

Can you give us an update on the current state of therapeutic approaches under development?

The development of the first antibiotics between 1940 and 1960 was a major contributor to the fight against tuberculosis. The same agents were used for 40 years, without any other antibiotic being identified to reinforce the treatment. Several of these drugs are still in use today, but their extensive use and toxicity have led to the emergence of antibiotic-resistant TB bacilli (Mycobacterium tuberculosis, also known as Koch’s bacillus). The beginning of the 21st century has seen a resurgence of enthusiasm about research in the field, with the identification of three new molecules (bedaquiline, pretomanid and delamanide).

This has led to the development of new therapeutic combinations that are effective against multidrug-resistant tuberculosis. However, more compounds are needed to enable doctors to personalise treatment based upon patients’ clinical profiles. The pipeline of compounds currently in clinical trials is relatively rich, but there is no room for complacency, given the complexity and selectivity of the steps required for these compounds to make their way into the general pharmacopoeia. In addition, much remains to be done to reduce the duration of treatment, which is still too long, and to limit the risk of relapse. It is therefore necessary to constantly investigate new antibacterial modes of action.

The scientific community is increasingly interested in new therapeutic approaches. Can you explain what dual antibiotics are?

Various new therapeutic approaches are explored, including antivirulence molecules, molecules thatstimulate host defences, molecules that inhibit bacterial dormancy (a source of relapse), molecules that stimulate the action of other antibiotics (or “boosters”), and molecules that block antibiotic efflux pumps. Dual antibiotics combine at least two of these mechanisms. For example, bedaquiline blocks adenosine triphosphate (ATP), the source of energy in the cell, and stimulates the infected host innate immunity, promoting the elimination of the bacillus by two independent mechanisms.

You have just published work on a dual-acting antibiotic. Can you explain how this work is innovative?

In this publication (1), researchers, including Alain Baulard’s team at the Institut Pasteur in Lille, have shown that the dual-acting agent is able to make bacteria hyper-sensitive to the antibiotic ethionamide (even those resistant to this antibiotic) and to block bacterial virulence by preventing it from secreting the EsxA and EsxB proteins, which are very harmful to the patient’s immune system.

With its relatively simple chemical structure (like bedaquiline), this compound can act through two independent mechanisms. It is a safe bet that the tuberculosis bacillus will find it more difficult to protect itself from this dual action, thereby limiting the risk of resistance emergence – a ‘nightmare’ scenario for therapists and their patients.

(1) Gries R, Chhen J, van Gumpel E, Theobald SJ, Sonnenkalb L, Utpatel C, Metzen F, Koch M, Dallenga T, Djaout K, Baulard A, Dal Molin M, Rybniker J. Discovery of dual-active ethionamide boosters inhibiting the Mycobacterium tuberculosis ESX-1 secretion system. Cell Chem Biol. 2023 S2451-9456(23)00436-1.

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