Global Tuberculosis Trends: Rising Cases, Antimicrobial Resistance, and New Hope in Vaccines
Tuberculosis (TB), an infectious disease caused primarily by Mycobacterium tuberculosis, continues to be a major public health challenge in 2025. Despite long-standing global control efforts, TB remains one of the top causes of death from a single infectious agent, surpassing HIV/AIDS in many regions. The disease disproportionately affects low- and middle-income countries, where poverty, undernutrition, and fragile healthcare infrastructures contribute to sustained transmission.
Recent data underscore a worrying trend: TB incidence and mortality have plateaued or even increased in some regions following pandemic-related disruptions, while antimicrobial resistance (AMR) poses a growing obstacle to effective treatment. At the same time, scientific innovation particularly in vaccines and diagnostics offers hope for a transformative shift in prevention and control strategies.
Relevance and Magnitude of Tuberculosis
Globally, tuberculosis (TB) is a problem of enormous dimensions. About one-third of the world’s population is infected by Mycobacterium tuberculosis. Worldwide in 2000 it was estimated that there were about eight million new cases of TB with two million deaths. TB kills more people than any other single infectious agent. Deaths from TB comprise 25% of all avoidable deaths in developing countries. Ninety five percent of TB cases and ninety eight percent of TB deaths occur in developing countries. Seventy five percent of TB cases in developing countries are in the economically productive age group [15-50 years]. Consequently TB impedes economic development in countries with a high incidence of the disease. Moreover, because the disease is not contained by political and geographical borders TB affects industrialized countries and global economic and social development. In developing countries, 3-4 months of family income or up to 20-30% of annual household income can be lost due to TB. The potential cost to a nation due to lost productivity from TB is estimated between 4-7% of GDP. Not only does TB exact a heavy toll in human suffering and economic losses currently, it is increasing every year.
A major contributing factor to the incidence of TB is the dual infection with the human immunodeficiency virus [HIV]. Today, TB is the single biggest killer of people infected with HIV. There are nearly 34 million men, women and children living with HIV in the world today, more than 95% in the developing world where the highest rates of TB infection are found. Today about 15 million people are dually infected with TB and HIV. An estimated 15% of all new cases of TB are also HIV-infected. In many African countries, where TB is often perceived as being synonymous with AIDS, even more than one half of TB patients are HIV-positive. In some countries, the HIV epidemic has led to a tripling or even quadrupling of TB cases over the past ten years. Moreover, TB is the single biggest killer of people infected with HIV, causing about one third of all AIDS deaths.
Global Epidemiological Trends
Rising Incidence and Mortality
Global incidence: In 2023, an estimated 10.8 million people fell ill with TB, representing a 3–4% increase compared with pre-pandemic baselines.
Mortality: Over 1.3 million deaths were attributed to TB in 2023, with a disproportionate burden in sub-Saharan Africa and Southeast Asia.
Regional disparities: While Europe has seen modest declines in TB incidence, high-burden countries such as India, Indonesia, and Nigeria continue to account for nearly 50% of all new cases.
Contributing Factors
Healthcare disruptions: Interruptions in TB diagnostic and treatment services due to COVID-19, conflict, or economic instability have created diagnostic backlogs.
Socioeconomic determinants: Malnutrition, poor housing, and limited access to care exacerbate transmission in vulnerable populations.
Comorbidities: HIV co-infection, diabetes, chronic lung disease, and tobacco use all increase susceptibility and disease severity.
Antimicrobial Resistance in Tuberculosis
Scale of the Problem
Multidrug-resistant TB (MDR-TB), defined as resistance to at least isoniazid and rifampicin, now accounts for ~500,000 cases annually.
Extensively drug-resistant TB (XDR-TB), with additional resistance to fluoroquinolones and second-line injectables, has been increasingly reported across Africa, Asia, and Eastern Europe.
Emerging resistance: Alarmingly, resistance to novel agents such as bedaquiline and linezolid has been documented, threatening last-line treatment options.
Challenges
Complex regimens: MDR/XDR-TB treatments often last 9–18 months, involve multiple toxic drugs, and cost far more than first-line regimens.
Diagnostic gaps: Molecular assays like GeneXpert can detect rifampicin resistance, but full resistance profiling often requires genomic sequencing, which remains inaccessible in many regions.
Therapeutic pipeline: While new targets such as cholesterol-metabolizing enzymes in M. tuberculosis are under study, most candidates remain preclinical.
Innovations in Vaccine Development
Protein-Subunit Vaccines
M72/AS01E has shown ~50% efficacy in preventing active TB among latently infected adults, making it one of the most advanced candidates in the pipeline.
Viral Vector Vaccines
Adenoviral and modified vaccinia Ankara (MVA) vectors are being tested for their ability to induce durable T-cell immunity.
mRNA Vaccines
Mechanism: Deliver TB antigens encoded in mRNA to stimulate robust T-cell responses.
Preclinical results: Mouse studies have demonstrated strong immunity and enhanced protection, particularly when used as a booster after BCG.
Advantages: Rapid design, scalable manufacturing, and adaptability to emerging TB strains.
Global Vaccine Access Initiatives
The WHO-led TB Vaccine Accelerator Council is coordinating financing, regulatory preparedness, and equitable access strategies, recognizing that vaccines must be affordable and globally distributed to have impact.
Global TB control is possible through a well-established strategy known as DOTS. The strategy is based on five elements: political commitment, diagnosis using sputum smear microscopy, standardized short course treatment with direct observation at least in the initial phase, uninterrupted drug supply, and standard recording/reporting with systematic evaluation of treatment outcome. While there is as yet no established strategy for curtailing multi-drug resistant TB [MDR-TB], demonstration projects are being conducted and efforts underway to establish a DOTS+ strategy. The benefits of DOTS are simple and direct: it saves lives; gets people back to school, work and their families; prevents multi-drug resistant TB [MDR-TB]; and minimizes further spread of MDR-TB. DOTS is an effective and affordable strategy for controlling TB and is especially valuable in resource-poor settings. Further, DOTS helps build stronger public health services. Ensuring that diagnosis and treatment are effectively carried out requires well-developed management systems for treatment facilities and laboratories, consistent logistics support, and effective information systems. These components also provide the basic requirements for efficient primary health services.
The DOTS strategy, recommended by WHO and the International Union Against Tuberculosis and Lung Disease (UNION) and subscribed to by the TBCTA, is internationally accepted and has now been adopted by 155 countries worldwide. Important elements of such a system include a network of capable laboratories to guarantee adequate detection of cases and monitoring of treatment outcomes, a recording and reporting system, and a robust logistics system that would ensure a secure supply of drugs. Behind these systems are the requirements of education and training of health care planners and providers, research, and organizational and human resource capacity building.
A number of donors, including USAID, recognize DOTS as one of the most cost-effective of all health interventions and are rigorously promoting its application around the world to avert a large percentage of the global TB burden. For this reason, DOTS can have a tremendous impact on socially excluded and poor people. Each year of life saved through DOTS costs as little as US$3-5. Anti-TB drugs currently cost as little as US$11 per treatment course. Annual costs of a good TB control program are estimated to be about US$0.10 per capita. For example, in the Development Plan 2000-2004 of Vietnam’s National TB Program, total costs of the program (excluding local staff salary costs but including external technical assistance and operational research) are calculated to be US$57.20 per patient.
MDR-TB is defined as resistance to at least two of the most important anti-TB drugs, Isoniazid and Rifampicin, and it occurs when the wrong treatment regimens (dosages or combination of drugs) are prescribed or when the right drugs are taken irregularly or not long enough. MDR-TB is a major challenge to the medical world and a frightening prospect for the future. It is vastly more expensive (over a hundred-fold increase), more likely to be fatal, and is more difficult to treat than drug-susceptible TB, especially in developing countries which are already struggling to provide even basic health services. MDR-TB endangers short-course chemotherapy, as used in DOTS, because the two best drugs are rendered far less effective and because it demands much lengthier treatment. MDR-TB has been found on every continent. Countries with poor TB control programs have a higher prevalence of MDR-TB than countries with good TB control programs.
Several countries have already achieved high cure rates using the DOTS strategy but many more could benefit from its effective application. Since properly applied anti-TB chemotherapy is effective in curing the infectious cases and interrupting the chain of transmission, the best prevention of TB is the cure of infectious cases. DOTS is both a rational strategy and a sound investment.
Important part of the DOTS strategy is political commitment to fund and implement effective national tuberculosis control programs. Therefore it is essential to promote global TB control and avoid the consequences of failure. In addition to DOTS, effective TB control measures require improved access by populations to affordable, equitable, committed and well-organized health delivery and support systems. Strengthening national commitment and organizational and human resource capacity to efficiently manage and deliver high quality health care efficiently is essential to ensure that the time and resources devoted to TB control are sustainable over time. With TB, long-term strategic planning and the application of that plan is necessary to properly develop an effective strategy and implementation plan to achieve a significant reduction in the disease burden.