The World Health Organization (WHO) reports that tuberculosis (TB), an airborne illness caused by bacteria, affects more than 10 million people annually and kills 1.5 million people each year, marking it as a top deadly infectious disease.

First discovered in 1720, diagnosis can take several weeks, during which patients risk spreading the disease to others or become grievously ill in the interim. To this day, an efficient and rapid diagnostic test still doesn’t exist.

A student researcher in the Wallace H. Coulter Department of Biomedical Engineering hopes to change this and improve screenings for tuberculosis.

Ph.D. candidate Sarah Ali is one of six recipients of the Young Investigators Award given by the American Society of Tropical Medicine and Hygiene (ASTMH), a non-profit organization dedicated to improving global health. The award recognizes the work of emerging scientists pursuing careers in various aspects of tropical disease research.

“I have always wanted to be a part of research that can directly impact the lives of those in need,” Ali said. “Working with infectious diseases was a new pathway that would allow me to make such an impact.”

Ali works as a graduate assistant in the lab of Asst. Prof. Aniruddh Sarkar, whose research focuses on developing technologies to reduce healthcare disparities with a specific focus of infectious disease diagnostics. In just her first year in the Ph.D. program, after graduating in 2022 with a bachelor’s in biomedical engineering from Florida Institute of Technology, Ali’s research centers around developing point-of-care (POC) diagnostics for infectious diseases, specifically TB.

“My research proposed the multiplexed probing of antibody titer and Fc receptor response to increase diagnostic efficiency for TB,” said Ali.

While effective treatment exists for TB, diagnosis remains a challenge. Due to the incredibly hardy nature of the bacteria (Mycobacterium tuberculosis), TB can persist in the body for years. Current TB diagnostics can take up to 6 weeks to produce results. Without certainty, recommending a patient to initiate TB treatment can be challenging as the regimen can take up to 9 months.

Ali’s hope is to improve screenings in populations from low- to middle-income countries as well as optimize TB diagnostics for HIV coinfected pediatric TB patients who have a high risk of TB mortality.

“The fact that we still have not been able to eradicate this disease is very telling of its complexity and the extensive scientific knowledge and expertise needed in the fight against TB,” she said.

In the realm of infectious disease diagnostics, many POC tools have relied on antibody titer, a test that measures the level of antibodies in a blood sample and reflects the history of the body’s immune responses. However, Ali suggests that antibody titer may not be the optimal route for TB diagnostics. “Due to the complex nature of TB”, she explains, “titer by itself fails to differentiate between the two major diagnostic categories for TB—active TB and latent TB.”

Active TB patients, who are the biggest public health concern, are symptomatic and can spread TB to others. Though latent TB patients are asymptomatic and often unaware they even have tuberculosis, their diagnosis is also of significant importance as they can transition to active TB cases.

“My research proposed the multiplexed probing of antibody titer and Fc receptor response to increase diagnostic efficiency for TB,” said Ali.

Ali’s research is particularly novel because no other POC TB diagnostics currently exist that differentiate between active and latent TB.

“This method not only quantifies the amount of antibody present but also the ‘quality’ of those antibodies,” Ali explained. “This unique multiplexed biomarker is then applied to a novel diagnostic platform developed by Dr. Sarkar’s lab to allow for the fast, sensitive, and low-cost diagnosis of TB.”

Not only is the method that Ali uses in her research significantly cheaper, it’s also faster. And there’s another reason why Ali’s research is such a game changer: the diagnostics developed not only meets but also surpasses the standards set by World Health Organization (WHO).

“Our diagnostics currently surpasses these standards and approaches the reference lab standards, AUC>0.9. This is a major accomplishment for the Sarkar lab and me personally,” she said.

As promising as her research is, Ali says that it was not without its frustrations. Recounting a period of uncertainty, Ali shared, “I spent that first semester buried in research attempting to find a biomarker that worked to distinguish between Active TB and Latent TB. Nothing was working.”

She eventually came to a point where starting over became a necessity. After a much-needed break over Christmas, Ali realized that a period of re-evaulation is just what she needed to move forward.

“I just needed to clear my head and think. What exactly was not working? How exactly was I planning and conducting these experiments,” she said.

As a researcher navigating new territory, she questioned what the next step in the process was. The most challenging part, she remembers, was identifying which factors were impeding the performance of the diagnostic.

“Eventually my biggest internal struggle was explaining exactly why the changes I made to the experiment allowed for such improved performance,” Ali said. “I was so worried that things weren’t really working. But as I tested more and more patients, my skepticism was squashed.”

With added support from Sarkar, and a not-so-small amount of patience and perseverance, she came upon the crucial step in the experiment that changed everything.

“I went from multiple failed experiments to a series of successful and incredibly surprising outcomes.”

She added, “It’s important to be kind to yourself as a scientist and acknowledge when a break is needed and that taking a break doesn’t make you a poor scientist. It might in fact make you a smart one.”

Winning the Young Investigators Award came as a surprise to Ali. She was sitting among other researchers and fellow young scientists, hearing their exemplary work be recognized and celebrated when her name was also called. The recognition represents an important milestone in Ali’s research journey.

“It means a lot to me that my work was acknowledged by such senior scientists in this field, and it inspires me to keep moving forward and developing myself into a seasoned scientist capable of adding productively to the scientific and non-scientific community,” said Ali. “I feel empowered to continue my work (going through the good and the bad) to play the role that I can in improving the lives of those with TB.”