The Fight Against TB Was Frozen in Time, Until Now. See Its Future

Tuberculosis (TB), known historically as consumption, phthisis, or the white plague, has plagued humanity since the ice age. This airborne disease, spread through droplets from actively sick individuals, remains the leading infectious disease globally, causing 1.25 million deaths in 2023.

Despite its long history, progress in combating TB has been slow, even as the bacteria causing it becomes increasingly resistant. The current TB vaccine, which only protects young infants and children, dates back to the Prohibition era.

Thanks to support from the National Institutes of Health (NIH), scientists from UC San Francisco and other institutions nationwide are pioneering new approaches to TB treatment. Experts are focusing on shorter treatment regimens and expanded patient options to improve outcomes.

Shorter Treatment Durations

Traditional TB treatment has been lengthy and arduous. Approximately one in eight TB cases worldwide exhibit resistance to standard medications. Until recently, these cases required numerous daily pills and regular injections for two years or more, leading to nausea, vomiting, hearing loss, and kidney damage. Even with this intensive treatment, a cure was not guaranteed. Today, severe TB cases can be cured with a six-month regimen of three or four oral drugs.

The treatment duration for drug-susceptible TB has also been nearly halved, thanks to a pivotal 2021 study co-led by UCSF scientists. This work built upon the research of School of Pharmacy professor Rada Savic, PhD, co-director of the UCSF Center for Tuberculosis, whose pharmacology studies suggested that treatment could be shortened without compromising care.

UCSF’s Institute for Global Health Sciences Executive Director Payam Nahid, MD, MPH, emphasizes that quicker cures are more effective. "People are more likely to finish shorter treatment courses, which makes them more effective and guards against the development of drug resistance," he stated. "Symptoms improve more quickly and people become less infectious sooner, reducing new infections."

Earlier this year, Nahid contributed to the development of new American TB guidelines promoting shorter treatment regimens, which are currently being used to manage the TB outbreak in Kansas. The experimental drug pipeline is expanding with innovative medicines, promising even better cures in the future.

Nahid predicts a shift towards a more tailored approach to treatment. He explains, "An enormous amount of work at UCSF has shown that the world is currently treating many patients with tuberculosis with regimens and durations that are needed to cure the minority 20% who have severe forms of the disease. Eighty percent could actually be treated with much shorter regimen and possibly even fewer drugs. I think more of that differentiation will emerge in the next five years."

Revolutionizing TB Testing

Current TB diagnostic methods often rely on technicians examining stained test samples under microscopes for TB bacteria. This process, largely unchanged since the discovery of TB over a century ago, remains prevalent in high-burden countries, according to UCSF Center for TB’s Adithya Cattamanchi, MD, also UC Irvine’s division chief of pulmonary diseases and critical care medicine.

Alternative testing methods require sophisticated laboratories or expensive molecular diagnostics, which are not always accessible. All existing methods require patients to produce phlegm samples, a difficult task for children and the severely ill, leading to millions of undiagnosed cases annually.

Cattamanchi notes, "TB can be a debilitating illness: The longer it goes undiagnosed, the more delays there are in treatment, the more damage it causes to the lungs. Many TB survivors live with chronic lung disease even after being cured." He and his colleagues are working to develop rapid and reliable TB tests that can be implemented within communities.

"We’re leveraging the diagnostic advances made during COVID for TB, in particular, easy-to-use and low-cost swab-based molecular testing," he explains. "We’ve identified best practice methods for collecting and processing swabs. Now, we’re working with product developers to adapt those for their testing platforms." UCSF researchers are also exploring improvements to urine-based tests and developing TB blood tests.

Understanding TB Susceptibility

Although many people are exposed to TB bacteria, only about 1 in 10 develop the disease. Assistant Professor of Medicine Sara Suliman, PhD, MPH, is researching the underlying reasons for this variability, focusing on biomarkers – measurable biological changes that can indicate illness, predict disease progression, or assess vaccine response.

"The question that my lab is trying to answer is twofold: One, can we find biomarkers markers that could act almost like a crystal ball to tell us who among the people exposed to TB is at high risk of developing the disease," Suliman explains. "The second is, we can use that to develop an intervention to reduce that risk?"

Currently, TB is treated with antibiotics that target the bacteria. The discovery of TB biomarkers could lead to treatments that enhance the immune system's ability to control the infection, marking a shift towards stratified care. "Stratified medicine, which groups similar patients, is one step before precision medicine, or care based on the individual," she says. "My dream is to move away from this one-size-fits-all approach and towards an understanding that there are different types of TB patients who would benefit from different types of treatment."