Tuberculosis Prevention, Control, and Elimination

Tuberculosis (TB) is a preventable and, in most cases, curable disease. Nonetheless, it remains a formidable public health challenge, killing more than 1.25 million people in 2023. The world's most prevalent human infection, it has affected humans across millennia and killed more people than any other disease throughout history. Long considered an infection without a known cause or treatment, disease understanding has rapidly progressed. Robert Koch discovered the Mycobacterium tuberculosis bacterium (Mtb) in 1882, and, just over 100 years later, its complete genome sequence was mapped. Today, continued advancements in diagnostics, treatment, implementation science, epidemiological techniques, global cooperation, and research, amongst others, offer optimism for the prevention, control, and elimination of TB. The causative agent of TB, (Mtb), is a solely human pathogen, spread primarily via inhaling aerosolized droplets from an infected person. Adolescents and adults account for the majority of transmissions. Although tuberculosis most commonly infects the lungs, it is a multisystemic infection that can present with highly variable clinical findings. Of those infected with Mtb, 5% to 10% of untreated, healthy, immunocompetent individuals develop TB disease. The emergence of multiple drug-resistant TB (MDR-TB) raises the specter of untreatable illness and increasing years of life lost, particularly in low-income nations already grappling with underfunded healthcare systems. In 1993, the World Health Organization (WHO) declared TB a global emergency when an HIV-driven increase in incidence reversed decades of progress toward global TB control. In 2015, the WHO set an ambitious goal to reduce TB incidence by 90% by 2035.[WHO. End TB 2022.] However, the world is unlikely to reach its 2035 target, particularly after the devastating impacts of the COVID-19 pandemic on TB rates and recent withdrawals of political will and funding. A renewed, concerted public health effort is required to reach global and national TB elimination and eradication goals.[WHO. End TB 2022.][WHO. GTBR 2024.] TB elimination refers to preventing disease in a specific geographic area; eradication is the permanent global elimination of disease cases and transmission. Suspected or confirmed TB disease is a condition reportable to local or state public health officials.  TB prevention, control, and elimination efforts face significant clinical- and systems-level challenges. Clinically, no effective vaccine exists across the age spectrum. TB infection (TBI) is asymptomatic and may last decades before the onset of TB disease. TB disease often presents with nonspecific symptoms that go unnoticed, facilitating high transmission rates. The Mantoux or tuberculin skin test (TST), developed in 1909, was the only available option to screen for TBI until recently, despite its known limitations in sensitivity, specificity, and the inability to differentiate TBI from TB disease. Historically, long and complex antibiotic treatment regimes, with a heavy pill burden and frequent side effects, present patient adherence difficulties. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB further complicates treatment, necessitating specialized care and robust public health and health infrastructure. Systems factors compound the clinical challenges. Poverty, overcrowding, malnutrition, war, and lack of public health infrastructure and universal access to healthcare perpetuate TB transmission, while global inequities hinder the distribution of newer diagnostic and treatment tools. Huge disparities in TB risk continue within and across countries. While decreased income inequality has reduced the rates of TB in low-incidence countries, TB is increasingly a disease of the marginalized in these areas. Globally, families affected by TB are often left impoverished. Long latency indicates a sustained need for control efforts over an extended period. Healthcare providers will require ongoing training to maintain a high index of suspicion for TB and to exercise strong clinical judgment in differentiating TBI from TB disease appropriately. As case numbers wane, diagnostic tools, treatments, surveillance approaches, policies, and legislation must adapt. With competing health and social priorities, continued political support, funding, global collaboration, accountability, and equitable access to healthcare resources will be essential for TB control efforts. Today, advancements in science provide hope for eliminating and eventually eradicating TB. Rapid interferon gamma-release assays (IGRAs) and nucleic acid amplification tests (NAATs) create a new global diagnostic landscape. AI-assisted technologies offer a cost-effective approach to screening for undiagnosed TB disease in high-prevalence populations. The recent addition of new or repurposed antibiotics and shorter treatment regimes offers patients increased opportunities for successful treatment completion. In resource-rich settings, whole genome sequencing (WGS) adds to the tools for antimicrobial resistance (AMR) detection and understanding TB transmission dynamics. Researchers are developing promising candidates for TB vaccines that can prevent the progression to TB disease. In the United States (US), the TB Centers of Excellence provide readily available expert advice to clinicians. Civil societies, patients, stakeholders, and advocacy groups play critical roles in improving patients' access to care and maintaining pressure on governments to clearly define and develop global and national goals, strategies, roles, funding, and mechanisms for accountability. This activity focuses on the activities necessary for TB prevention, control, and elimination. Critically, the multiple roles and activities clinicians, the interprofessional team, and others can undertake to strengthen patient-centered and public health care, surveillance and reporting, program development, health and healthcare research, and advocacy, among others, contribute to ending TB as a human pathogen. As WHO Director-General Tedros Adhanom Ghebreyesus stated, "We have an opportunity that no generation in the history of humanity has had: the opportunity to write the final chapter in the story of tuberculosis." Until TB is eradicated, it remains a risk everywhere. This paper uses the terminology' TB infection' and 'TB disease' instead of 'latent TB' and 'active TB', respectively, as recommended by Menzies. The WHO defines TBI as "a state of persistent immune response to stimulation by Mtb antigens with no evidence of clinically manifest TB disease."  The term' latent TB' is inconsistent with the underlying pathology of TBI, in which viable mycobacteria are held in fluctuating degrees of containment by host defenses. Guidelines from organizations such as the WHO and national health departments (eg, Canadian Tuberculosis Standards) increasingly use this terminology.[WHO. End TB 2022.] Refer to StatPearls' related activities "Tuberculosis Overview" and "Latent Tuberculosis" for further information on the treatment and management of TBI and TB disease.