Iyana Malik, BSN, RN; Randall Reves, MD

During one of my medical school clinical rotations in Colorado, a patient presented with months of dyspnea, hemoptysis, fevers, night sweats, and weight loss. The patient’s chest CT showed findings suggestive of miliary tuberculosis (TB). When I discussed including TB on my differential diagnosis, my suggestion was dismissed with the counterargument that TB was unlikely in Colorado and unlikely in this patient, and no further assessment of risk factors was pursued. This experience motivated me to explore how TB epidemiology influences diagnosis and management, potentially minimizing TB in the differential.

TB is the deadliest infectious disease in the world, consistently ranking among the top 10 causes of death. Globally, more than 10 million people develop active TB each year and over 1 million die. Estimates show that one-third of those with TB never get diagnosed or treated. Because 90% of the global TB burden occurs in Asia, Africa, and Latin America, TB is often described as a “third-world disease,” which minimizes its impact on this country. After the U.S. TB resurgence of the 1980s, the annual number of cases in the U.S. was declining until 2024 when it surpassed 10,000 for the first time in a decade. Colorado reported over 100 cases in 2025, double the incidence in 2022. This shows that TB has not disappeared.

These concerns led me to question why a patient with TB-like symptoms was not evaluated for TB. Risk assessment and screening lack precision because they rely on broad epidemiologic categories and proxies such as country of birth, race, primary language, homelessness, and incarceration. While associated with increased exposure, these factors are applied in ways that use identity as a shortcut for risk. We need stronger evidence-based recommendations that move beyond general characteristics and go toward individualized risk stratification.

Medical providers must advocate for research to improve TB risk assessment, diagnostics, and treatment as it is a vital domestic and public health responsibility. Despite TB’s enormous global and rising local burden, research in these areas has remained stagnant.

On March 24, 1882, Dr. Robert Koch presented his discovery of Mycobacterium tuberculosis and methods to culture it. That date is now recognized as World TB Day. Microscopic detection using acid-fast staining (AFB) became the standard diagnostic test, remains widely used, and is still the only available test in many resource-limited countries.

The diagnostic testing we use for TB remains antiquated and often produces results that providers cannot fully rely on. Hospitals require airborne isolation until three consecutive sputum AFB smears are negative. For physicians, limited airborne isolation rooms may contribute to hesitation in including TB in the differential. Sputum microscopy has limited sensitivity and cultures are slow, taking up to six weeks. Molecular tests have marginally improved sensitivity and can detect drug resistance more rapidly, but access continues to be limited in many regions. However, even with a negative result, these tests do not rule out TB. The TB skin test and interferon-gamma release assays cannot distinguish latent from active disease, and false positives and negatives occur in around 20% of cases.

Therapeutic advancements for TB have been few and far between. The standard treatment for drug-susceptible TB has remained largely unchanged for decades. Rifampin, introduced in the 1960s, is still a cornerstone. Despite the toxicities, and adherence challenges of our current TB therapy, only three new TB drugs have been approved in the past 50 years, none replacing the current regimen. The next step forward is replacing the current regimen. For an organism identified in the 19th century and prevalent for millennia, this lack of innovation is abysmal.

This research stagnation is not due to scientific limitations but economic neglect. Only 24% of the pledged $5 billion has gone to TB research. TB disproportionately afflicts low-income countries and disadvantaged communities with limited market power and pharmaceutical investment. This differs from HIV testing and treatment, which have become highly reliable within weeks of exposure, illustrating the disparities that exist in research prioritization despite its smaller global burden.

The appeal for action is urgent. Providers serve an important role in prompting research and innovation. When diagnostic testing is uncertain, detection is delayed, patients suffer, and diseases spread. Medical professionals must champion policy change and increased research funding. Academic institutions should prioritize TB research, professional societies should reevaluate risk assessment guidelines, and providers should partner with public health departments to limit disease spread.

In health care, I have noticed that what we highlight in training and research sends a message about whose lives are valued. With the recent rise in TB cases in Colorado and the U.S., we must commit to eliminating TB rather than discounting it as a “third-world” issue. Medical professionals must use their influence to ensure that no disease is neglected simply because its burden falls on people with lower socioeconomic status.