by Nhu Y. Nguyen (Alaina), PhD
volunteer author for Angels in Medicine
Copyright © 2024 Nhu Y. Nguyen

Last time we learned about Dr. Thuy Le’s inspiration and mentorship that serve as a compass for her journey as a researcher in talaromycosis. (If you missed it, you can read Part 1 here.) Let’s dive deeper in this story to learn about her challenges and achievements.

Challenges to Treatment

One of Dr. Thuy Le’s challenges is that talaromycosis is a neglected fungal infection affecting people with a suppressed immune system, and disproportionately affecting people with advanced HIV disease in Southeast Asia. Patients with talaromycosis often feel ashamed and withdraw from society, partly because 70% of them develop skin lesions with disfiguring facial appearance. By the time they come to the hospital to seek care, they are very sick and at an advanced stage of disease, when treatment is least effective.

Secondly, HIV is a taboo disease, especially in the tight-knit community culture of Vietnam. People may question the reasons for contracting HIV: sexual promiscuity, contact with sex workers, injection drug use, same-gender sex, etc. Illicit drug use, sex work, and sexual activity between same-sex partners are not accepted socially in Vietnam. Therefore, patients are afraid of stigma and discrimination from society and even from their own family. 

Soon these patients become marginalized, difficult to reach and engage into HIV treatment programs. Doctors can treat the acute fungal infection temporarily, but they cannot cure the infection without treating the underlying HIV disease. In Vietnam, 1 in 5 people with advanced HIV disease develop talaromycosis and 1 in 4 of them die within one to two months even with treatment. Despite this, policymakers in Vietnam pay little attention to talaromycosis among HIV patients. Dr. Le says that it is very challenging to care for people who do not have support from their family and society. 

Another challenge is that Mycology, the study of fungi, is a new and emerging research area in Vietnam and Southeast Asia. There are only a handful of clinical microbiologists and researchers who have expertise in Mycology. There is no Mycology Reference Laboratory in Vietnam or Southeast Asia. Dr. Le works on a neglected fungal disease with minimal laboratory support, little local clinical interest, and few government incentives.

Despite these obstacles, her work has substantially improved the diagnosis and treatment of talaromycosis. Not only has she published high-impact papers, but she also works on advocacy to implement new diagnostics and treatment strategies in the clinic to reduce talaromycosis cases and mortality. Her advocacy work includes public, clinical, and policy engagement efforts even though those efforts are unpaid and largely unrecognized by the traditional medical and academic fields.

Challenges Create Opportunities

Challenges nevertheless create opportunities. Dr. Le has recently received fundings from the National Institute of Health (NIH) in the U.S. to develop the Tropical Medicine Research Center (TMRC) at Pham Ngoc Thach University of Medicine in Ho Chi Minh City in Vietnam focused on improving diagnosis and treatment for talaromycosis.

In partnership with the University of Hong Kong, biomedical engineers at Duke University, and biotechnology companies, Dr. Le’s laboratory has successfully developed several new diagnostic tests for talaromycosis. These tests detect protein or nucleic acids released from the fungus and are more sensitive and faster than culture, producing results within hours rather than days to weeks by the current culture method. Her research team is testing these assays in patient samples with the goal of bringing these new diagnostic tests to the market for clinical use in Vietnam and Southeast Asia.

Improving Treatment

When asked about her most memorable patient, Dr. Le told the story of a patient who enrolled in the first-ever clinical trial testing the effect of amphotericin B versus itraconazole for HIV-associated talaromycosis which she led as the Principle Investigator between 2012 and 2017. The patient left her with unforgettable memories. He contracted HIV through intravenous drug use and was gravely ill, but was poor and had no financial support from family. Participation in a clinical trial was his sole avenue for accessing affordable treatment and a chance at survival. 

He was randomized to the more expensive but more toxic drug amphotericin B (which many doctors had avoided). Amphotericin B turned out to be more effective than itraconazole, with a 50% higher chance of survival. Overcoming his illness, he went on to marry and have two children. He keeps in touch with Dr. Le, showing his profound gratitude for the life-saving research on treatment that benefited both him and many others.

After 7 years of testing on 440 HIV-infected people with talaromycosis, Dr. Le’s team discovered that treatment with amphotericin B was better than itraconazole. Dr. Le expresses gratitude to this particular patient and the many others who participated in the clinical trial, contributing to the advancement of medical knowledge and improving treatment for future patients. She says that researchers receive the recognition from running successful trials, but the patients are the true heroes who sacrifice for the acquired knowledge to advance the field and enhance the outcomes for subsequent patients. 

Amphotericin B has now become the standard of care, and all patients are now treated with this drug. Dr. Le’s studies have saved lives! As a result, that clinical trial led to new treatment guidelines in Vietnam, in the United States, and globally. Dr. Le is grateful to the patients in her trials, and maintains that they are the true heroes.

Prevention and Newer Treatments

Beyond her goals in making an early diagnosis of talaromycosis and improving treatment outcomes for patients, Dr. Le is also interested in preventing the infection in the first place. She is currently working on research projects to generate reliable data supporting her screen-and-treat strategy for talaromycosis, similar to early cancer screening and treatment approaches. Her goal is to screen a large population of patients with advanced HIV disease, even when they do not have any symptoms of this fungal infection. If the fungal antigen or DNA is present in their blood, they will be treated to prevent the spread of the infection. This requires public policy, healthcare provider engagement, and high-quality clinical data to support the cost effectiveness of this large-scale screening program. 

Excitingly, her team has been recently funded by the NIH to conduct a seven-year clinical trial in talaromycosis in Vietnam, China, and Thailand to evaluate the safety and efficacy of two new antifungal treatment strategies. One is liposomal amphotericin B, which is a lipid-based formulation of the traditional amphotericin B and is packaged with lipid nano layers to protect it from causing toxicity to human cells; therefore, it leads to fewer adverse effects such as acute kidney injury. Since the liposomal amphotericin B is much safer than the conventional amphotericin B, patients will be treated with a higher dose for a shorter duration (one day versus 14 days). Her goal is to improve safety and improve efficacy.

The other antifungal drug in this trial is flucytosine, which has been used for treatment of cryptococcal meningitis, a fungal infection similar to talaromycosis. Her laboratory-based research at Duke showed that flucytosine has a synergistic interaction with amphotericin B. The team will determine if the combined therapy of flucytosine and amphotericin B will improve safety and efficacy. In brief, her team will test these two interventions to expand treatment options for HIV patients in this seven-year clinical trial in Southeast Asia.

Challenges of an International Career

Dr. Le is a career-driven person and a dedicated, passionate physician-scientist leading a very robust translational and clinical research program. She shares that it takes a deep passion and a unique person to handle all the work she has been doing. She took her six-month old daughter to Vietnam while finishing her Infectious Disease Fellowship at Yale and her PhD degree in Epidemiology at the University of Oxford in the UK. She initially planned to be in Vietnam for one year, but ended up staying for ten years, and now 15 years and counting. Her husband, based in America, visited them three to four times per year during that time and is an understanding and supporting husband.

She is now at Duke University, but still travels extensively to Vietnam to lead the TMRC for Talaromycosis. Her daughter, now 16-years-old, has experienced both the modest and affluent lifestyles in Vietnam and in America, gaining a deep appreciation for her mother’s contributions in both countries. These experiences have enriched her life and are shaping her career choices.

In her humble way, Dr. Le acknowledges that her work has required personal sacrifices, but has resulted in significant contributions to science and medicine. Her research offers hope to many patients suffering from talaromycosis and other fungal diseases worldwide. Despite the challenges, Dr. Le and her family find happiness and fulfillment in their work, making their efforts worthwhile.

About the Author

Nhu Nguyen is a freelance writer based in North Carolina. You can reach her at nyn.alaina@gmail.com.