Dr. Gerald Mazurek completed his internal medicine residency and pulmonology fellowship at UAMS in 1984 and 1986, respectively. Afterward, he completed a UAMS research fellowship focused on the bacteria that causes tuberculosis, Mycobacterium tuberculosis, one of the world’s deadliest pathogens. Since then, he has led a globally impactful research and public health career aimed at tuberculosis control.
It was curiosity and a desire to contribute which prompted Dr. Mazurek’s interest in medical research. His research career began as a UAMS medical student studying immunologic tolerance. His research continued as an internal medicine resident investigating endotoxin-induced lung injury under the guidance of Drs. Roger Bone and Robert Balk in the Division of Pulmonary and Critical Care Medicine. Then, as a pulmonology fellow and subsequently as a research fellow, he worked with faculty mentors Drs. Joseph Bates, Don Cave, Jack Crawford, Richard Ebert, and Kathy Eisenach to develop molecular methods for detecting M. tuberculosis in clinical specimens and for creating DNA fingerprints to identify individual strains of the bacteria. These collaborations led to several pioneering publications describing the use of DNA fingerprinting in the epidemiologic study of tuberculosis. Prior to DNA fingerprinting, there was no reliable way to identify or track the transmission of individual strains of the bacteria. “DNA fingerprinting facilitated dramatic reductions in the nosocomial transmission of the disease and eliminated other unanticipated mechanisms of transmission. It prompted recognition of cross-contamination as a cause of errors in diagnosing tuberculosis,” according to Dr. Mazurek. While it initially took months to create a DNA fingerprint for M. tuberculosis collected from culture, the same information can be obtained now by automated machines in a few hours. Recognition of genetic differences among M. tuberculosis strains remains an important epidemiologic tool for tuberculosis control and is applied to almost all cases of tuberculosis diagnosed in the United States.
After his research fellowship, Dr. Mazurek worked for several academic centers and public health agencies including The University of Texas Health Center at Tyler, the Texas Department of Health, the United States Centers for Disease Control and Prevention (CDC), and the U.S. Public Health Service. Regardless of the sponsoring institution, Dr. Mazurek remained a researcher with a constant focus: addressing deficiencies in the diagnosis and treatment of tuberculosis. His early career work demonstrated the utility of DNA probes in the identification of M. tuberculosis from clinical specimens. This method of identification proved to be a significantly faster and more accurate alternative to the conventional identification methods of culture and biochemical testing. However, this dramatic innovation would not be Dr. Mazurek’s only revolutionary contribution to the diagnosis of tuberculosis.
In 1997, while working for the CDC’s Division of Tuberculosis Elimination, Dr. Mazurek received a challenge from his boss, Dr. Rick O’Brien—to develop a blood test for latent, or asymptomatic, M. tuberculosis infection that could be used in lieu of the hundred-year-old tuberculin skin test. Such a test would ideally allow for quicker and more accurate detection of people who harbor M. tuberculosis. Identifying and treating these people would be crucial to efforts to eliminate the disease. Australian scientists Drs. Jim Rothel and Paul Woods had recently described a blood test to detect cattle infected with Mycobacterium bovis, a pathogen which causes a disease similar to tuberculosis. Their test relied on detecting interferon-gamma, a marker of immune system activation, when blood from cattle was exposed to M. bovis protein antigens. Blood from infected cattle released more interferon-gamma than blood from uninfected cattle. This type of test became known as an interferon-gamma release assay. Dr. Mazurek established a formal collaboration between Drs. Rothel and Woods and the CDC and began tackling the challenges of adapting their techniques to create an interferon-gamma release assay to detect humans withM. tuberculosis infection. The new test measured interferon-gamma release when human blood was exposed to the same purified protein derivative used for the tuberculin skin test.
After development, Dr. Mazurek and his colleagues performed a study in which they compared the new human interferon-gamma release assay to the standard tuberculin skin test. In the conclusion of this 2001 landmark study in JAMA, Dr. Mazurek et al. wrote that “the [interferon-gamma] release assay was comparable with the [tuberculin skin test] in its ability to detect [latent tuberculosis infection], was less affected by [tuberculosis] vaccination, discriminated responses due to nontuberculous mycobacteria, and avoided variability and subjectivity associated with placing and reading the [tuberculin skin test].” Moreover, this new test could be completed in less than twenty-four hours after a single patient visit, whereas tuberculin skin testing required two separate patient visits a few days apart. This data was used to support Food and Drug Administration approval for QuantiFERON-TB, the first blood test for M. tuberculosisinfection. Building on the potential for interferon-gamma release assays, Dr. Mazurek and his collaborators sought better antigens. They recognized that, unlike the skin test which required injection of the antigen, the response to multiple antigens could be assessed by interferon-gamma release assays with blood from a single puncture and without the need for prior antigen safety studies. Increased accuracy with interferon-gamma release assays using manufactured antigens and more sensitive analytic methods was reported in their 2004 clinical trial. Further refinements yielded successively better tests: the QuantiFERON-TB Gold Test, the QuantiFERON-TB Gold In-Tube, and then the QuantiFERON-TB Gold Plus. In the latter two tests, antigens were included in the tube used to collect blood to reduce test complexity, facilitate automation, increase reliability of results, and ultimately facilitate use in rural locations. The latter test is one of two interferon-gamma release assays that are now the preferred screening test for M. tuberculosis infection.
Dr. Mazurek also studied improved treatments for tuberculosis. He collaborated on clinical trials which led to the acceptance of rifapentine and shorter treatment regimens for active tuberculosis disease and latent M. tuberculosisinfection. The use of rifapentine allowed treatment to be shortened from nine months to three months in some cases. Other notable work throughout Dr. Mazurek’s career includes deployments with the U.S. Public Health Service to various states and countries for hurricane relief, influenza control, Ebola response, and COVID-19 threats.
When reflecting on his education, career, and his numerous mentors, Dr. Mazurek says, “Hard work, luck, and prayer got me into and through medical school at UAMS, but clinical mentoring by Drs. Bill Stead, Richard Ebert, Joe Bates, and Robert Abernathy fueled my interest in tuberculosis.” Dr. Mazurek also notes the importance of UAMS microbiology professor and later CDC collaborator, Dr. Jack Crawford, in his career.
To this day, Dr. Mazurek remains affiliated with UAMS medical students, residents, fellows, and faculty through intermittent clinical work at the John L. McClellan Memorial Veterans’ Hospital. This collaboration is thanks to Drs. Larry Johnson and Manish Joshi, Professors in the Division of Pulmonary and Critical Care Medicine. Dr. Mazurek adds, “I sincerely thank Dr. Johnson and Dr. Joshi for the opportunity to work at my alma mater and for the opportunity to exchange ideas related to tuberculosis diagnosis and treatment over the past fifteen years.”