World TB Day 2023 – ‘Yes! We Can End TB!’

March 24, 2023

Statement of Hugh Auchincloss, M.D., Lakshmi Ramachandra, Ph.D. and Peter Kim, M.D.
National Institute of Allergy and Infectious Diseases
National Institutes of Health

Each year, on March 24, the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, joins people and organizations from around the globe in marking World Tuberculosis Day. On this day, more than 140 years ago, Dr. Robert Koch announced his discovery that most human tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis (Mtb). Although our scientific insight into this disease has grown over the past century, TB is still one of the deadliest infectious diseases on the planet. Today, NIAID joins the world in a message of hope: “Yes! We can end TB!” 

TB is a challenging disease to prevent, and multidrug-resistant (MDR) and extremely-drug resistant (XDR) strains can be difficult to treat. The most recent World Health Organization (WHO) report on TB noted that in 2021 the estimated annual new cases and deaths from TB increased for the first time in more than a decade. The WHO estimates that 10.6 million people fell ill with TB in 2021, and 1.6 million people died. The Centers for Disease Control and Prevention (CDC) estimates that approximately 13 million people in the United States live with latent TB infections. Moreover, according to provisional data, the total number of reported TB cases in the United States rose to 8300 in 2022, an increase of 426 cases from 2021. The symptoms of active TB disease, which can include weakness, weight loss, fever, and (when the infection is in the lungs) coughing and chest pain, can be debilitating, leading to a severe global disease burden. In 2018, this ongoing suffering led NIAID to develop its Strategic Plan for Tuberculosis Research, which emphasizes the use of cutting-edge technology and ongoing research collaborations to further our understanding of TB and develop new tools to prevent and treat TB disease among all those affected by TB, including the most vulnerable populations who continue to face the brunt of this global pandemic

This understanding begins at the molecular level. NIAID’s Immune Mechanisms of Protection Against Mtb (IMPAc-TB) supports comprehensive research on the interaction between the immune system and Mtb to inform future TB vaccine design and development. NIAID’s Tuberculosis Research Units (TBRUs), a collaborative network, supports research on other aspects of the interactions between Mtb and the host’s body. Understanding the mechanisms that allow TB to remain latent and persist in the body will inform scientific efforts to improve methods for identifying people at risk for progression to active TB disease, develop new treatments with shorter durations, and interventions to prevent or improve disease outcomes. In addition, some intramural research initiatives at NIAID are working to identify the best antigens to prompt an immune response against TB, which could serve as the foundation for improved TB vaccines. 

Other major research initiatives are examining how TB is transmitted from person-to-person and the mechanisms that expel the bacteria from the lungs. Recent research supported by NIAID has found that even relaxed breathing, not just coughing, can aerosolize TB bacteria. Studies like these suggest that TB may be transmitted more readily than previously thought, and NIAID is funding researchers to dive deeper into the primary drivers of TB transmission, both at the individual and population levels.

To treat TB patients effectively, healthcare providers must rapidly diagnose patients and ensure they receive an effective drug treatment regimen. NIAID supports multiple programs to improve TB diagnostics, including the “Feasibility of Novel Diagnostics for TB in Endemic Countries (FEND for TB)” centers, which operate clinical sites in 12 countries where TB is endemic. These centers conduct clinical evaluations of new TB assays and validation studies for promising biomarkers. In addition, NIAID plans to fund awards to support the development of new diagnostic technologies to rapidly identify TB drug resistance, including point-of-care diagnostics. Improved drug-susceptibility testing for TB would help healthcare providers determine the most effective drugs to treat individual cases of TB. One of the centers recently provided data from the first clinical evaluation of the Cepheid MTB-HR cartridge as a triage test for people with symptoms of active TB. The results suggested that the cartridge, which uses a droplet of blood via finger stick, meets the WHO criteria for rapidly ruling out TB in patients who have another respiratory disease.

TB is usually treatable with a long course of several antibiotics, and in recent years, researchers have made great strides in improving upon standard treatment regimens to be shorter and less arduous. Standard treatment regimens can be difficult, especially for patients with drug-resistant TB strains. Discovering and developing new TB drugs is a major part of NIAID’s TB research portfolio. A new TB-selective oxazolidinone drug, developed jointly by NIAID and Merck scientists, is now being assessed in a Phase 1 clinical trial by the Gates Medical Research Institute. The drug, designed to be taken once daily by mouth, is expected to be free of the side effects caused by a similar TB drug, linezolid. 

In addition to new drug development, studies suggest that some currently available TB drugs could be used more effectively or efficiently. The “Stratified PatiEnt-Centered Treatment Regimens for Active TB Trial" (SPECTRA TB) study is expected to launch in 2024 and will evaluate different durations for standard treatment regimens and pinpoint circumstances when regimens could be shortened. Another study, ACTG A5409 (RAD TB), will test combinations of new TB drugs to determine which is most effective in treating drug-susceptible TB. Data from the NIAID-supported IMPAACT P1108 study, which tested the safety and tolerability of bedaquiline as a TB therapeutic in children under six years old, informed WHO guidelines on the drug’s use.

NIAID supports global collaboration among TB experts to share knowledge and conduct vital multinational research. For instance, NIAID partners with countries with high TB burdens to run the Regional Prospective Observational Research in Tuberculosis (RePORT) program. RePORT networks all over the world facilitate country-specific research and enable international collaborations, making research advances faster, more cost-effective, and more applicable to global populations who suffer from TB. 

The NIAID TB Portals Program, a global collaboration of clinicians, scientists, and specifically data scientists, provides researchers a virtual open-access repository of high-quality TB imaging, genomic, clinical data and analytical tools. The program includes data from nearly 9,000 tuberculosis patient cases from around the world, allowing scientists to compare patient comorbidities, drug susceptibility testing, and treatment information. Collaborators from 55 sites in 19 countries bring their expertise in medicine, information technology, genomics, and data visualization to the online, open-access platform. The TB Portals Program website also offers the “TB in VR” feature, an immersive educational experience that allows users to explore tuberculosis pathology and learn about antibiotic resistance, by virtually experiencing TB-affected lung structures and protein modifications throughout the course of the disease.  

In addition to new and improved TB treatments, a safe and effective vaccine to prevent TB disease among all ages is urgently needed. The currently available Bacille Calmette-Guérin (BCG) vaccine protects infants without HIV infection and young children against disseminated TB disease and death, but it does not provide long-lasting protection for adults. Recently, a NIAID-supported Phase 1 trial found that a freeze-dried version of the experimental TB vaccine called ID93+GLA-SE was safe and capable of inducing an immune response in healthy adult volunteers. This freeze-dried version of the vaccine has the advantage of being stable at room temperatures, which could make it comparatively easy to transport to remote parts of the world, where refrigeration is challenging. NIAID is also investigating other avenues of vaccine development for TB, including the possibility of an mRNA vaccine.

Looking to the future of TB research, NIAID established a series of new Tuberculosis Research Advancement Centers (TRACs) in 2022, allocating approximately $5.8 million in first-year funding to support the next generation of TB researchers. The TRACs will provide mentoring and funding support for new investigators, opportunities for multidisciplinary and collaborative research, and training in laboratory and clinical settings.

Ending TB on a global scale will require ongoing advances in science and implementation, along with the commitment of researchers, healthcare providers, and community members around the world. Today, as one of the leading funders of TB research, NIAID reaffirms its commitment to easing suffering, saving lives, and lifting the tremendous disease burden TB places upon the world.

Hugh Auchincloss, M.D., is Acting Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Lakshmi Ramachandra, Ph.D., is Chief, Tuberculosis and Other Mycobacterial Diseases Section, Division of Microbiology and Infectious Diseases, NIAID. Peter Kim, M.D., is Director, Therapeutics Research Program, Division of AIDS, NIAID.


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