World Tuberculosis Day 2024 theme “Yes! We can end TB” can be made a reality through concerted global efforts that advance detection, diagnosis, and treatment of tuberculosis infection and disease

Every year, World Tuberculosis (TB) Day is commemorated on March 24 and is targeted at raising public and political awareness of TB, a preventable and treatable disease. World TB Day commemorates the day in 1882 when Professor Robert Koch announced his discovery of the microbial cause of TB, the TB bacillus, Mycobacterium tuberculosis. Despite effective TB treatment being available for over 65 years, TB today causes 1.3 million deaths yearly, mostly in low- and middle-income countries. Drug-resistant TB is the leading cause of death owing to antimicrobial resistant disease in the world today and is a growing global health security threat, with hundreds of thousands of people affected every year [1World Health Organization. Global tuberculosis report 2023, https://www.who.int/publications-detail-redirect/9789240083851; 2023 [accessed 27 February 2024].Google Scholar]. It is in this dismal global situation that “Yes! We can end TB!” is the World Health Organization (WHO) and STOP TB Partnership's theme for World TB Day [1World Health Organization. Global tuberculosis report 2023, https://www.who.int/publications-detail-redirect/9789240083851; 2023 [accessed 27 February 2024].Google Scholar]. This theme remains the same as that of World TB Day 2023 to emphasize and deliver a message of hope to those who continue to be affected. Critical to highlight on this day will be the provision of the required global funding to enable faster uptake of new WHO management recommendations for finding, diagnosing, and effectively treating infections and all cases of clinical TB using new and updated WHO recommendations and guidelines [2World Health Organization. WHO consolidated guidelines on tuberculosis: module 1: prevention: tuberculosis preventive treatment 2020, https://www.who.int/publications-detail-redirect/9789240001503; 2020 [accessed 27 February 2024].Google Scholar, 3World Health Organization. WHO consolidated guidelines on tuberculosis: module 2: screening: systematic screening for tuberculosis disease 2021, https://www.who.int/publications-detail-redirect/9789240022676; 2021 [accessed 27 February 2024].Google Scholar, 4World Health Organization. WHO consolidated guidelines on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection, 2021 update 2021, https://www.who.int/publications-detail-redirect/9789240029415; 2021 [accessed 27 February 2024].Google Scholar, 5World Health Organization. WHO consolidated guidelines on tuberculosis: module 4: treatment: drug-resistant tuberculosis treatment 2020, https://www.who.int/publications-detail-redirect/9789240007048; 2020 [accessed 27 February 2024].Google Scholar]. Although global efforts to combat TB have saved an estimated 75 million lives since 2000, the COVID-19 pandemic, coupled with conflicts across Europe, Africa, and the Middle East [6Casco N Jorge AL Palmero DJ Alffenaar JW Fox GJ et al.Global Tuberculosis Network and TB/COVID-19 Global Study GroupLong-term outcomes of the global tuberculosis and COVID-19 co-infection cohort.Eur Respir J. 2023; 622300925https://doi.org/10.1183/13993003.00925-2023Crossref Scopus (7) Google Scholar,7TB/COVID-19 Global Study GroupTuberculosis and COVID-19 co-infection: description of the global cohort.Eur Respir J. 2022; 592102538https://doi.org/10.1183/13993003.02538-2021Crossref Scopus (64) Google Scholar] and poor socioeconomic conditions, have reversed years of progress that was being made by global efforts to control and eventually end TB. The deteriorating global economic situation, with rising cost of living and reduction of budgets for national health programs, has disproportionately affected the poorest and disadvantaged, the very populations who are most affected by TB. Moreover, access to available WHO-recommended TB diagnostics and treatment regimens remains a major challenge, especially in low- and middle-income countries, where 80% of the annual TB caseload occurs. The United Nations General Assembly (UNGA) convened its second High-Level Meeting (HLM) on the fight against TB on September 22, 2023 to revisit the global targets established for 2018-2022 during the first meeting and to develop new targets up to 2027. Member states at the meeting endorsed a political declaration that reaffirms global commitments to end TB by 2030. The targets of the first United Nations HLM sought to treat at least 40 million individuals with TB worldwide from 2018 to 2022, addressing the TB needs of 3.5 million children, providing treatment for 1.5 million individuals with drug-resistant TB, and initiating TB preventive treatment (TPT) for at least 30 million people. The new global targets for 2023-2027 are more ambitious [1World Health Organization. Global tuberculosis report 2023, https://www.who.int/publications-detail-redirect/9789240083851; 2023 [accessed 27 February 2024].Google Scholar]. These include achieving 90% of patients having access to quality-assured diagnosis and treatment, 90% of individuals at risk of developing disease having access to TPT, 100% of people with TB having access to health and social benefits packages, raising 22 billion US$ for research, and developing a new vaccine against TB. In this special International Journal of Infectious Diseases issue to commemorate World TB Day, we present nine reports covering several of these aspects. We discuss several prevention issues. Prevention starts with vaccines [8da Costa C Benn CS Nyirenda T Mpabalwani E Grewal HMS Ahmed R et al.Perspectives on development and advancement of new tuberculosis vaccines.Int J Infect Dis. 2024; https://doi.org/10.1016/j.ijid.2024.106987Abstract Full Text Full Text PDF Scopus (2) Google Scholar]. There have been no new TB vaccines available since the introduction of the bacille Calmette–Guerin vaccine over a century ago. Encouragingly, several promising TB vaccine candidates are currently being evaluated in phase II and III clinical trials [8da Costa C Benn CS Nyirenda T Mpabalwani E Grewal HMS Ahmed R et al.Perspectives on development and advancement of new tuberculosis vaccines.Int J Infect Dis. 2024; https://doi.org/10.1016/j.ijid.2024.106987Abstract Full Text Full Text PDF Scopus (2) Google Scholar]. In parallel, we describe the immunology approaches to design vaccines and immune diagnostic tests for TB [9Panda S Kearns K Cheng C Arlehamn CSL. From antigens to immune responses: shaping the future of TB detection and prevention.Int J Infect Dis. 2024; https://doi.org/10.1016/j.ijid.2024.106983Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar]. The screening strategies are reported in terms of political commitments, as the Prevention and Systematic Screening Initiative, which is a new approach to technical assistance, focused on prevention and systematic screening, to end TB in the WHO European Region by 2030 [10Dadu A Yedilbayev A Migliori GB Ahmedov S Falzon D den Boon S et al.PASS to End TB in Europe: accelerated efforts on prevention and systematic screening to end tuberculosis in the WHO European Region by 2030.Int J Infect Dis. 2024; https://doi.org/10.1016/j.ijid.2024.02.023Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar,11World Health Organization. Gearing up towards ending TB in Europe: regional workshop on prevention and systematic screening (PASS-to-EndTB), https://www.who.int/europe/news-room/events/item/2023/10/30/default-calendar/gearing-up-towards-ending-tb-in-europe–regional-workshop-on-prevention-And-systematic-screening-(pass-to-endtb); 2023 [accessed 27 February 2024].Google Scholar]. Screening procedures and TPT are also discussed, with a focus on persons moving from high- to low-TB endemic countries [12Petersen E Al-Abri S Al Jardani A Memish ZA Aklillu E Ntoumi F et al.Screening for latent tuberculosis in migrants – status quo and future challenges.Int J Infect Dis. 2024; 107002Abstract Full Text Full Text PDF Scopus (1) Google Scholar]. This highlights the importance of identifying persons with TB infection and ensuring they receive TPT to prevent the re-activation of latent TB infection (LTBI) toward TB disease, leading to further transmission. In addition to screening migrants, South Korea developed a highly successful program for LTBI screening. This intervention has contributed to an annual 5.2% reduction in TB incidence between 2011 and 2016 through the screening of community workers, including daycare centers for children, kindergarten, and schools [13Go U Park M Kim UN Lee S Han S Lee J et al.Tuberculosis prevention and care in Korea: evolution of policy and practice.J Clin Tuberc Other Mycobact Dis. 2018; 11: 28-36https://doi.org/10.1016/j.jctube.2018.04.006Crossref PubMed Scopus (69) Google Scholar]. Although TB mainly affects the lungs, it can also affect other organs. When people with pulmonary TB cough, sneeze, or spit, TB bacilli are propelled and spread through the air and respiratory droplets. A person in close contact needs to inhale only a few mycobacteria to become infected. About a quarter of the global population (around 2 billion people) is estimated to have an immune response against TB and are likely to have TB infection. Most people with LTBI will not go on to develop TB disease and some will clear the infection. People showing an immune response against TB bacteria have a 5-10% lifetime risk of falling ill with TB disease during their whole life span. Those with compromised immune systems, such as people living with HIV, malnutrition, or diabetes, or using tumor necrosis factor inhibitor therapies or tobacco, have a higher risk of falling ill [14Cantini F Niccoli L Capone A Petrone L Goletti D. Risk of tuberculosis reactivation associated with traditional disease modifying anti-rheumatic drugs and non-anti-tumor necrosis factor biologics in patients with rheumatic disorders and suggestion for clinical practice.Expert Opin Drug Saf. 2019; 18: 415-425https://doi.org/10.1080/14740338.2019.1612872Crossref PubMed Scopus (44) Google Scholar,15Goletti D Pisapia R Fusco FM Aiello A Van Crevel R. Epidemiology, pathogenesis, clinical presentation and management of TB in patients with HIV and diabetes.Int J Tuberc Lung Dis. 2023; 27: 284-290https://doi.org/10.5588/ijtld.22.0685Crossref PubMed Scopus (12) Google Scholar]. Screening is done by standardized interferon-γ release assays and skin tests [16Alonzi T Repele F Goletti D. Research tests for the diagnosis of tuberculosis infection.Expert Rev Mol Diagn. 2023; 23: 783-795https://doi.org/10.1080/14737159.2023.2240230Crossref PubMed Scopus (9) Google Scholar, 17Kontsevaya I Cabibbe AM Cirillo DM DiNardo AR Frahm N Gillespie SH et al.Update on the diagnosis of tuberculosis.Clin Microbiol Infect. 2023; https://doi.org/10.1016/j.cmi.2023.07.014Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 18Goletti D Delogu G Matteelli A Migliori GB. The role of IGRA in the diagnosis of tuberculosis infection, differentiating from active tuberculosis, and decision making for initiating treatment or preventive therapy of tuberculosis infection.Int J Infect Dis. 2022; 124: S12-S19https://doi.org/10.1016/j.ijid.2022.02.047Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar], the new one based on the intradermal inoculation of ESAT-6 and CFP-10, which are M. tuberculosis-specific antigens compared with those included in the tuberculin skin test [16Alonzi T Repele F Goletti D. Research tests for the diagnosis of tuberculosis infection.Expert Rev Mol Diagn. 2023; 23: 783-795https://doi.org/10.1080/14737159.2023.2240230Crossref PubMed Scopus (9) Google Scholar, 17Kontsevaya I Cabibbe AM Cirillo DM DiNardo AR Frahm N Gillespie SH et al.Update on the diagnosis of tuberculosis.Clin Microbiol Infect. 2023; https://doi.org/10.1016/j.cmi.2023.07.014Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 18Goletti D Delogu G Matteelli A Migliori GB. The role of IGRA in the diagnosis of tuberculosis infection, differentiating from active tuberculosis, and decision making for initiating treatment or preventive therapy of tuberculosis infection.Int J Infect Dis. 2022; 124: S12-S19https://doi.org/10.1016/j.ijid.2022.02.047Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar]. The challenges of these new skin tests are also covered here [19To KW Rui Z Lee SS. Is the new TB antigen-based skin test ready for use as an alternative to TST/IGRA for TB diagnosis? A narrative review.Int J Infect Dis. 2024; Abstract Full Text Full Text PDF Google Scholar]. Finally, we report an overview of experimental non-sputum diagnostic and biomarkers assays for TB disease detection and progression to disease. Non-sputum tests can be very important for diagnosing extra-pulmonary TB or pulmonary TB in those unable to expectorate, such as children, or in immunocompromised subjects where the sputum M. tuberculosis load can be very low. A test based on the Actiphage technology to detect M. tuberculosis DNA in the blood is described [20Rees C Swift B Haldar P. State of art of the detection of M. tuberculosis during TB infection by blood tests using the phage technology.Int J Infect Dis. 2024; https://doi.org/10.1016/j.ijid.2024.106991Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar] as useful for TB diagnosis and identifying those with TB infection that may progress to TB disease [21Verma R Swift BMC Handley-Hartill W Lee JK Woltmann G Rees CED et al.A novel, high-sensitivity, bacteriophage-based assay identifies low-level Mycobacterium tuberculosis bacteremia in immunocompetent patients with active and incipient tuberculosis.Clin Infect Dis. 2020; 70: 933-936https://doi.org/10.1093/cid/ciz548Crossref PubMed Scopus (28) Google Scholar,22Kim JW Bowman K Nazareth J Lee J Woltmann G Verma R et al.PET-CT-guided characterisation of progressive, preclinical tuberculosis infection and its association with low-level circulating Mycobacterium tuberculosis DNA in household contacts in Leicester, UK: a prospective cohort study.Lancet Microbe. 2024; 5: e119-e130https://doi.org/10.1016/S2666-5247(23)00289-6Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar]. An alternative and potentially complementary approach for the detection of progressors to TB disease is by measuring host inflammation [23Källenius G Correia-Neves M Sundling C. Diagnostic markers reflecting dysregulation of the host response in the transition to TB disease.Int J Infect Dis. 2024; https://doi.org/10.1016/j.ijid.2024.106984Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar]. Host immune responses can be measured by a proteomic and transcriptomic assessment that can detect increasing immune activation associated with TB disease progression several months before the onset of clinical disease [24Tabone O Verma R Singhania A Chakravarty P Branchett WJ Graham CM et al.Blood transcriptomics reveal the evolution and resolution of the immune response in tuberculosis.J Exp Med. 2021; 218e20210915https://doi.org/10.1084/jem.20210915Crossref PubMed Scopus (32) Google Scholar,25Scriba TJ Penn-Nicholson A Shankar S Hraha T Thompson EG Sterling D et al.Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.PLoS Pathog. 2017; 13e1006687https://doi.org/10.1371/journal.ppat.1006687Crossref PubMed Scopus (149) Google Scholar]. The potential importance of new methodologies for defining the latency stage of TB infection based on the detection of M. tuberculosis DNA in CD34+ cells in the blood of subjects with TB infection is discussed [26Martineau AR Chandran S Palukani W Garrido P Mayito J Reece ST et al.Towards a molecular microbial blood test for tuberculosis infection.Int J Infect Dis. 2024; https://doi.org/10.1016/j.ijid.2024.106988Abstract Full Text Full Text PDF Scopus (2) Google Scholar,27Repele F Alonzi T Navarra A Farroni C Salmi A Cuzzi G et al.Detection of Mycobacterium tuberculosis DNA in CD34+ peripheral blood mononuclear cells of adults with tuberculosis infection and disease.Int J Infect Dis. 2024; 106999Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar]. These methodologies could help to better understand TB pathogenesis and may allow specific targeting of the patients who require TPT. To achieve global TB control and eventually elimination, we need several actions: increased investments to accelerate the promising new TB vaccines pipeline, implementation of new immune strategies for better vaccine design, new therapies and/or therapy regimens, new diagnostic tests, implementation of prevention through screening using standardized old and new diagnostic tests for TB infection detection [28Migliori GB Wu SJ Matteelli A Zenner D Goletti D Ahmedov S et al.Clinical standards for the diagnosis, treatment and prevention of TB infection.Int J Tuberc Lung Dis. 2022; 26: 190-205https://doi.org/10.5588/ijtld.21.0753Crossref PubMed Scopus (44) Google Scholar], implementation of the non-sputum diagnostic tests for TB disease, and implementation of tests for the identification of those progressing toward TB disease to better target those needing therapy.