by Nhu Y. Nguyen (Alaina), PhD
volunteer author for Angels in Medicine
Copyright © 2024 Nhu Y. Nguyen
I first met Dr. Thuy Le in 2009 when I was an undergraduate intern at the Oxford University Clinical Research Unit (OUCRU) based in the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. At that time, she was a physician and a junior faculty member in Infectious Diseases from Yale University who received a Fogarty International Clinical Research Fellowship, awarded by the National Institutes of Health (NIH), to conduct her PhD project about HIV infection at the OUCRU-Vietnam. I was impressed by her kindness, critical thinking, work ethic, and most importantly, her outstanding research about the global HIV epidemic.
Fifteen years later, destiny has brought us together as we now both live in North Carolina. I had a precious opportunity to learn about her current research through an interesting interview about her career and current work.
Diagnosing and Treating a Dangerous Fungus
Dr. Thuy Le is an Associate Professor of Medicine, Associate Professor of Molecular Genetics and Microbiology at Duke University School of Medicine, Co-Director of the Clinical Core of the Duke Center for AIDS Research, and Co-Director of the Tropical Medicine Research Center (TMRC) for Talaromycosis in Vietnam.
She is in charge of an international research program based in the TMRC, concentrating on developing efficient and effective diagnostic methods and treatments of talaromycosis – a life-threatening invasive fungal infection caused by the fungus Talaromyces marneffei that is endemic in Southeast Asia (including Vietnam and Thailand) and China. Her work is predominantly in Vietnam, but she also has research partners in Thailand and China where she visits her patients at times. She has been a key leader driving multiple NIH grants to advance a pipeline of novel diagnostics for talaromycosis at the TMRC in Vietnam.
Talaromycosis, a severe infection, affects people with weakened immune systems, especially patients with advanced HIV disease. Strikingly, the mortality is very high, as one in three patients dies despite anti-fungal treatments because of two reasons.
First, it is difficult to catch this fungus unless the patients are at the advanced stage where the infection spreads from the lung to multiple organs and into the bloodstream; therefore, by the time the lab can isolate and grow this fungus for identification, the patients have already developed advanced disease and anti-fungal treatments are least effective at that time.
Second, the traditional diagnostic methods of growing the fungus in cell culture take up to 28 days for detection and are poorly sensitive, so the patients may already be dead by the time the diagnostic results are available.
Dr. Thuy Le and her team have been tirelessly working on development of new methods to diagnose this infection by detecting a protein antigen (toxin) that is being excreted in the patients’ bloodstream during infection in a speedy and accurate manner. Significantly, it has been shown that the novel techniques can detect this toxin up to four months before the fungus is grown and identified by the traditional method. It is critical to rapidly detect the presence of this fungus because the earlier the detection, the better the treatment outcome for patients.
Another aspect of her work is to improve therapeutic treatments, because the current drugs are either toxic or difficult to get absorbed into the bloodstream. Her team has been developing diagnostic tests as well as safe and effective anti-fungal drugs for talaromycosis at Duke University and in collaboration with pharmaceutical companies in the United States; these tests and drugs will be then used for HIV patients in clinical trials in Vietnam.
Making a Difference
Inspiration and mentorship are critical for every successful individual, and Dr. Thuy Le is not an exception. Her passion in this significant work stems from the fact that she was born and grew up in Vietnam before she immigrated into the US with her family.
“I am from Vietnam, and I have always wanted to do global health research and infectious diseases,” Dr. Le said. In fact, when she was a medical fellow at Yale University, she decided to come to Vietnam initially to work on HIV drug resistance. Observing those HIV patients in pain due to the lethal infection of talaromycosis, and learning that there is not much known about this disease and there is no efficient way to diagnose or treat it, inspired her to take the lead to improve these two particular issues, diagnosis and treatment of talaromycosis. “I wanted to make a difference,” Dr. Le emphasized.
In particular, there are two special persons that made a remarkable inspiration for her career path in this field. The first one is also her first Vietnamese patient, who was a 19-year-old farmer at the time. The patient did not know that she had HIV when she first came to the hospital with horrific skin lesions. It was dramatic for Dr. Le to see such a young woman with this severe fungal infection of talaromycosis.
Dr. Le and her medical team were able to treat her successfully at that time and the patient did well after all. This first patient really triggered Dr. Le’s curiosity to dive deeper into this area to make a positive and significant impact on the health of those patients.
Exceptional Mentorship
The second person that made a huge difference in her career is her mentor, Dr. Jeremy Farrar, Director of the Oxford University Clinical Research Unit based in the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, where she was a fellow at the time. He was a visionary leader who allowed her to pursue her research interest and encouraged her to launch a clinical trial for treatments of this fungal disease.
When she told him that there was no clinical study done on treatments for this infection and we did not know the best drug for it, Dr. Farrar suggested that she conduct a clinical trial by herself.
“I was shocked at the suggestion”, Dr. Le said, because the idea of running a clinical study in Vietnam by an Infectious Disease fellow or even a junior faculty in the US was beyond her. Dr. Farrar showed her his confidence in her ability, and gave her a sample clinical trial protocol for severe influenza so that she was able to learn to write the first clinical trial protocol for treatment of talaromycosis on her own. Furthermore, Dr. Farrar encouraged her to go an extra mile by writing and submitting a grant to secure financial support for her own study.
It turned out that her project was one of the top four clinical trials, out of the total 130 applications worldwide, that was funded by the Wellcome Trust – a global charitable foundation established in the UK in 1936. It was no doubt that Dr. Le became a principal investigator of a multi-center study from a fellow thanks to her mentor’s guidance and motivation. She was grateful to insist that Dr. Jeremy Farrar was the one that taught her to think big, fueled her research passion, and showed her the ropes of how to pursue her goals. Indeed, he was a mentor that made a significant impact on Dr. Le’s career.
Every journey has its own ups and downs as the black and white keys on a piano make beautiful songs. In Part II, we will learn about Dr. Thuy Le’s challenges and advancements of her clinical study of this fungal infection.
About the Author
Nhu Nguyen is a freelance writer based in North Carolina. You can reach her at nyn.alaina@gmail.com.