Consumption, phthisis, the white plague - a killer by any other name, tuberculosis (TB) has stalked humanity since at least the ice age. Today, the disease - passed from those who are actively sick to others through airborne droplets - is the leading infectious disease killer globally.
Still, for decades, the fight against TB has been frozen in time, even as the bacteria that causes it has become more resistant. The world's only TB vaccine protects young infants and children but dates back to Prohibition.
National Institutes of Health (NIH) support has enabled scientists from UC San Francisco and others from around the country to chart a new course. Three UCSF experts break down some of the biggest developments in the field and the promise that lies ahead.
The ultimate ambition is to get to regimens that are weeks, not months, long, and offer patients more treatment options so that medicines work for their lives."
Treatment
The Goldilocks era? Shorter, kinder and more efficient
For decades, TB treatment was long and painful. Roughly 1 in 8 cases of TB globally are resistant to standard medicine. Until just a few years ago, treating these cases involved handfuls of daily pills for two years or longer, including months of regular injections. Medicines left many nauseous and vomiting, and some with permanent hearing loss and kidney damage. Even then, cure was not assured. Today, the worst forms of TB can be cured with just three or four drugs taken orally in six months.
Similarly, the treatment time for drug-susceptible TB has nearly halved, dropping to just four - thanks to a landmark 2021 study co-led by UCSF scientists . The work followed in the footsteps of School of Pharmacy professor Rada Savic , PhD. A co-director of the UCSF Center for Tuberculosis , Savic pioneered pharmacology studies that were among the first to suggest it was possible to shave months off treatment without compromising care.
And a quicker cure is a more effective cure, explains UCSF's Institute for Global Health Sciences Executive Director Payam Nahid , MD, MPH.
"People are more likely to finish shorter treatment courses, which makes them more effective and guards against the development of drug resistance," he says. "Symptoms improve more quickly and people become less infectious sooner, reducing new infections."
Earlier this year, Nahid helped develop new American TB guidelines to make shorter treatment available to more people. These guidelines are now being used to fight the current Kansas TB outbreak.
And even better cures are on the horizon, Nahid says. The pipeline for experimental drugs is larger than ever and features entirely new types of medicines.
"The ultimate ambition is to get to regimens that are weeks, not months, long, and offer patients more treatment options so that medicines work for their lives."
Part of this, Nahid predicts, will be a shift towards a Goldilocks, or just right approach to treatment.
"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," he continues. "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."
Previous treatment: Previous TB treatment involved handfuls of daily pills for two or more years, alongside regular injections. Medicines caused nausea, and sometimes permanent hearing loss and kidney damage.
Treatment today: Today, the most severe cases of TB can be cured with an updated regimen of just three or four drugs taken orally in six months. Images by John-Michael Maas, TB Alliance
Diagnosis
Leveraging advances made during COVID-19 pandemic
Imagine a room full of rows of technicians perched at lab benches and hunched over microscopes. For hours on end, these microscopists peer through their lenses looking for TB's tell-tale rod shaped bacteria on tiny blue-stained test samples to diagnose TB.
In more than half of TB diagnostic units in high-burden countries, this is what TB testing looks like. It's not too different from how TB was first discovered more than a century ago, explains UCSF Center for TB's Adithya Cattamanchi , MD. Cattamanchi is also UC Irvine's division chief of pulmonary diseases and critical care medicine.
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."
Other forms of testing need sophisticated laboratories or expensive molecular diagnostics not always available. All of them require patients to cough up phlegm from deep within their lungs for sampling, which is nearly impossible for children and the very sick. It's why millions of people go undiagnosed each year.
"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," he tells UCSF News. "Many TB survivors live with chronic lung disease even after being cured."
Cattamanchi is working with scientists at UCSF and partners around the world to revolutionize TB testing to, one day, put fast reliable TB testing within communities' reach.
"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, including Cattamanchi, are also investigating how to improve existing experimental urine-based tests and, eventually, develop TB blood tests.
TB's Great Mystery
Why some people get sick and not others
TB illness may seem like a game of chance. Although many people are exposed to the bacteria that cause TB each year, only about 1 in 10 get sick. No one really knows why.
Assistant Professor of Medicine Sara Suliman , PhD, MPH, is working to solve this mystery. The answer lies partly in what scientists call biomarkers - or measurable, biological changes in our bodies that can be used to diagnose illness, predict disease progression or gauge a vaccine response.
... there are different types of TB patients who would benefit from different types of treatment."
"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 that we can use that to develop an intervention to reduce that risk."
Currently, medicine cures TB with antibiotics that kill the bacteria itself. The discovery of a TB biomarker could pave the way for treatments focused not on the germs but instead us, so that are immune system can better control the infection. And it will help usher in a new era in 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."
