Paving the Way for the Next Generation of TB Researchers: Jonathan Golub, PhD

“The TB epidemic is different in India than it is in South Africa and Brazil.”

Dr. Jonathan Golub, Professor of Medicine, Epidemiology and International Health at the Johns Hopkins Bloomberg School of Public Health began his work in India when he found himself at the confluence of a needs-based issue and a bureaucratic problem.

“About 10 or 12 years ago I had a project on tuberculosis and diabetes that had been funded to be done in Brazil, but we were having trouble with the IRB process there. I often joke that, had it not been for the IRB issues, I would be exclusively working there, and I wouldn’t be in India,” Dr. Golub said. “Because it was a TB-diabetes project, and diabetes and TB are bigger problems in India compared to Brazil, we decided to bring the study over. We started the project first at Byramjee Jeejeebhoy Government Medical College, and then we expanded to DY Patil when we needed to recruit more patients. The study went very well, and I really enjoyed working there.”

He noted that their study had several interesting findings. He said that up until this research, most TB-diabetes studies showed that patients with tuberculosis and diabetes had worse tuberculosis outcomes, but they did not find the same magnitude of difference between tuberculosis patients with and without diabetes, a surprising misalignment with the literature.

Tuberculosis & Diabetes

“We had a combined outcome where we looked at people who had died, relapsed, or failed treatment. Most prior reports said there was a difference in these outcomes. However, our results showed that among people who had diabetes, there was only an increase in early mortality—people dying during TB treatment. That was important, but we just weren’t powered to show that association. That’s the most important finding from our project.”

“A reason why we think we didn’t see all the outcomes that we had expected between people with diabetes and those without diabetes, is that at that time, the drug regimen for TB was only given in India three times a week, as opposed to daily,” he said. “So, there were a lot of people in our study who were getting sub-therapeutic levels of drugs during TB treatment, and that’s probably why the outcomes were worse than expected for everybody, as opposed to just being worse for the people with diabetes. The national treatment guidelines changed toward the end of the study though.”

He and his team also assessed the study as a cohort, following patients who received metformin for their diabetes while they had tuberculosis and found that people on metformin had a 50 percent reduction in mortality, showing a need for concurrent treatment.

“It’s interesting. When I speak to people in India, they’ll tell me that everybody is being screened for diabetes, but they’re not necessarily getting treated for their diabetes once diagnosed. Screening is important, but treatment is necessary. Unfortunately, our study hasn’t changed anything just yet,” Dr. Golub said.

“The team that we work with in India is just a machine, and things get done.”

Dr. Golub and his team noticed that there had been no trials looking at strategies to find recurrent tuberculosis, or tuberculosis among people who have completed treatment. To fill this gap in research, his team opened a non-inferiority trial in coordination with the India National TB Elimination Program (NTEP) and input from the World Health Organization (WHO), called TB Aftermath, with Dr. Vidya Mave and Dr. Kakrani, Dr. MS Barthwal, and others at DY Patil.

The purpose of the NIH-funded TB Aftermath study was to compare strategies to find people with recurrent tuberculosis, while also understanding the costs associated with the strategies and the implementation issues as well.

Though not the primary objective of TB Aftermath, during this study, they realized that children and the rest of the household should be receiving preventive therapy. Many times, they are not. “India is at the forefront of developing technology, but implementation of some basic strategies remains a challenge. Getting their household contacts preventive therapy is hugely important,” Dr. Golub said. “India has a lot of TB, and despite preventive therapy being a recognized proven effective strategy, there’s not as much preventive therapy happening as there should be, which is true almost everywhere in the world.”

“I’m happy that much of my portfolio is moving towards India. I still want to do work in other high incidence settings, but because of the team in India and how smoothly things tend to go once a study is up and running, it’s really a great place to work,” he said.

“I’m very interested in working with TB survivors.”

Dr. Golub explains that he’s passionate about studying the comorbidities that are associated with tuberculosis, particularly when it comes to diabetes, tobacco, alcohol, malnourishment, and pulmonary impairment. This led him to start a new study called TB PuRe, a NIH-funded clinical trial that provides patients with pulmonary rehabilitation during tuberculosis treatment.

“Almost 25-50 percent of people with TB have pulmonary impairment at the end of TB treatment. Most of the few studies that have been done wait until the end of TB treatment to assess if patients are impaired, and then try to provide them pulmonary rehabilitation. It’s a lot more difficult to engage a person after they’ve completed TB treatment,” he explained. “What we’re aiming to do is get them at the time of TB diagnosis and give them pulmonary rehabilitation while you have them for the six months of TB treatment.”

He noted that another priority for India is finding the estimated millions of people with tuberculosis that go undiagnosed each year. “Ours is a small study, trying to diagnose these recurrent TB cases, but there needs to be bigger studies to figure out how to best find these missing TB cases, likely in the slums and other high-risk populations,” he said.

“I’m not a physician, so I don’t treat patients, but it’s important to me to go on household visits. On a visit back in May of 2023, I went on one of our TB Aftermath visits, and it was quite interesting to go to a participant’s home. It was amazing to see how engaged they are with the team. They treat them as if they were friends. They are happy to have them there, welcome them into their home, and offer them tea while they’re sitting there interviewing them for an hour. It was really nice to see.” Most recently, the TB Aftermath team had the opportunity to present the TB Aftermath results to the NTEP, who were quite enthusiastic about the project. “This is why we do the work we do,” Dr. Golub said, “To provide evidence for countries to use to change their policies for the better.”

“I’ve been informally talking to a lot of TB survivors from around the world to get a sense of what their needs are post-TB completion because I do think that’s a very forgotten aspect of TB,” Dr. Golub said. “It’s getting a lot of attention in the last several years from the perspective of post-TB lung disease, which is kind of what our TB PuRe study, and to some extent TB Aftermath, are about. We want to improve the health of people with TB so they can live productive, healthy lives following their battle with TB.”

“Training is something that I’m passionate about, and that’s why I’m excited to work on this.”

Dr. Golub explains that he’s done many forms of training when it comes to tuberculosis and research. Most prominently by teaching the course and Jeopardy clue “Epidemiological Basis for Tuberculosis Control,” at Johns Hopkins for the past 20 years. It was originated by Dr. George Comstock in the 1960s and co-instructed for many years by Dr. Richard Chaisson. He’s currently turning it into an online course for RePORT International, a multinational consortium comprising country-level and cross-national tuberculosis research efforts in Brazil, China, India, Indonesia, Philippines, and Uganda that are linked through the implementation of a common protocol for data and specimen collection and are poised to address critical tuberculosis research needs; the consortium is supported by the U.S. NIH and respective participating governments.

He also led a Fogarty program for 11 years with Brazil where he brought a dozen researchers each year who took courses in epidemiology and biostatistics and worked on developing research projects. This morphed into developing training programs in South Africa and India.

At SMART4TB, he co-leads the technical area for implementation and operational research, which has him working with early-stage investigators in several countries. With the JHU Tuberculosis Research Advancement Center (TRAC), he’s the head of the developmental core, which gets to distribute grants to early-stage investigators, while also aiding ESIs in developing K and R grant applications.

“We reach a lot of TB researchers worldwide and try to provide as much training and training materials as possible to the early-stage investigators. This has evolved for me over the last several years as I’m getting older in my career,” he said. “It’s become even more important to me to give back and help train the next generation.”