Childhood tuberculosis (TB), while impacting nearly a million children across the globe, isn’t as well diagnosed and is likely under or overtreated compared with TB in adulthood. The Shortened Regimen for Drug-Susceptible TB in Children (SMILE-TB) trial, led by the SMART4TB Consortium, and funded by the U.S. government, is focused on addressing this critical population, evaluating a shorter treatment regimen for children with pulmonary and lymph node tuberculosis. When children are diagnosed and treated quickly and effectively, it can have an enormous impact on their future and their caregivers. SMILE-TB is currently enrolling participants in Uganda, Indonesia, and Zambia, where local researchers are seizing this opportunity to improve treatment and care.

Dr. Chishala Chabala is a pediatrician and lecturer at the University of Zambia and the principal investigator of the SMILE-TB trial in Zambia.

How did you come to the field of TB and specifically, pediatric TB?
I’ve worked on TB for 20 years, starting out as a provincial TB coordinator in Southern Zambia and seeing the impact of TB in clinics, particularly people with HIV and TB. As a pediatrician, it was glaring how neglected TB in children was. We saw so many changes in treatment for adults based on trials, but such little attention was given to children, so that motivated me.

What is the potential for the SMILE-TB trial to impact children living with TB, their caregivers, and families? It’s potentially a game-changer; the standard treatment was six months, then it was reduced to four months based on the results of the SHINE trial (Shorter Treatment for Minimal Tuberculosis in Children) and now, in SMILE-TB, we’re looking at two months, encompassing  pulmonary and lymph node TB.

The current treatment requires going to a facility for the duration of the treatment, which is a big cost, both for the family and the health service. Parents sometimes have to take off work for several days and the longer you are taking medication, the more potential for side effects and adverse events. We also know that when a child presents with TB, more often than not there is another person in the house who has TB so caring for the child and adult makes it difficult. With shorter treatment, you know that you are saving costs for the family, and you are reducing side effects for the child.

What is unique about the TB epidemiology in Zambia?
Zambia is a high-burden TB country, we have high rates of HIV infection and high rates of TB in children who are malnourished. This trial gives us an opportunity to look at children with added health complexities, including taking a lot of medication (in the case of HIV and TB) and managing their nutrition. What we learn in Zambia will be applicable to similar settings in sub-Saharan Africa.

Why is research like this important to pursue right now?
Typically, these types of trials are done in adults, and we have to extrapolate from those results what to do with children. With SMILE-TB, we are providing answers that adult treatment trials can’t answer. As healthcare spending goes down, we can show that when we invest in children, when we invest in research, we can make a big impact.

Dr. Bwendo Nduna is the Senior Medical Superintendent Arthur Davison Children’s Hospital and an investigator of the SMILE-TB trial in Ndola, Zambia.

How did you come to the field of TB and specifically, pediatric TB?
I had an interest in neonatology and infectious diseases as a medical student and a strong interest in research because as I was doing my specialization, most of our learning was through evidence-based practices. You start to learn how children are managed throughout the world, and you are learning how to provide the best standard of care. When you look at TB diagnosis in children, it’s difficult to make. Even an experienced clinician will toil around and have difficulty and that worried me. The first battle is that you must convince the parent that the child has TB, and then when you start the treatment, it’s so long.

When I started out, it was common to start a child on first line antibiotic treatment, switch to second line antibiotics when there was a poor response, by the time you get to the third line you start to worry that it’s TB. That would mean six months of “imprisonment” on medication. Parents would then be worried about how long they will be in the hospital, how many injections they will get, and things like that.

When the various healthcare workers I’ve trained to manage pediatric TB see me at the grocery store, they think of TB, and I take it as a sign of how passionate I am about this work.

What is the significance of the SMILE-TB study in Ndola? What is the study’s potential for children living with TB, caregivers, and their families?
I’m so excited, whenever you think of pill burdens, it’s huge. A child who has HIV is already taking so many pills, and then you give them a diagnosis of TB and now they are swallowing even more pills for a long duration. I want to make life easier for these children and get them the shortest, most effective therapy.

I always say, we have to improve the quality of this child’s life, the dignity of the patient. It’s a game changer, and it opens other avenues for research and collaboration. A child being unwell is not a natural thing. You see the catastrophic costs of patients who have TB, and this trial has the potential to lessen all of that. It’s such a welcome thing.

Crucial treatment-shortening trial with potential to dramatically improve care for one of the most dangerous forms of TB begins enrollment in Mongolia

The U.S. government-funded Supporting, Mobilizing, and Accelerating Research for Tuberculosis Elimination (SMART4TB) consortium is excited to announce that The Program for Rifampicin-Resistant Disease with Stratified Medicine for TB (PRISM-TB) trial, led by investigators from University of California, San Francisco, has launched at the National Center for Communicable Diseases in Ulaanbaatar, Mongolia with 10 participants enrolled. PRISM-TB (ClinicalTrials.gov NCT06441006) is one of three randomized, controlled trials aiming to optimize TB therapeutics and provide life-saving benefits for the millions suffering from the leading infectious disease killer in the world.

PRISM-TB is a two-stage trial that evaluates a stratified medicine approach to shortening drug-resistant TB treatment with bedaquiline, pretomanid, linezolid and moxifloxacin (BPaLM) to three or four months from a standard of six months. “PRISM-TB is an exciting opportunity to move away from a one-size-fits-all approach and evaluate a more personalized approach that we hope keeps people on treatment and helps them return to their lives faster,” said Bazarragchaa Tsogt, principal investigator for the trial at the National Center for Communicable Diseases.

It is estimated that 390,000 people develop drug-resistant TB each year; this form of TB does not respond to first-line treatments and consequently, is difficult and expensive to treat. Current standard treatments for drug-resistant TB are six to nine months; shorter treatment has the potential to make it easier for more people to complete treatment, to reduce the length of potentially difficult side effects, to ease burden on TB programs and to allow people return to healthy, productive lives faster. PRISM-TB will enroll 200 participants, including adults, adolescents, pregnant and lactating women and people living with HIV, and randomize them into standard treatment, four months of BPaLM, or a stratified arm of three or six months of BPaLM, depending on individual risk factors. The treatment stratification uses an algorithm based on factors demonstrated to be associated with TB outcomes like age, sex, HIV status, bacterial load in sputum and presence of cavitary lung disease to determine if a participant receives shorter or longer treatment.

“PRISM-TB will not only generate crucial data that we hope can inform guidelines and improve treatment in the U.S. and around the world, but we are employing a first-ever risk-benefit analysis with a desirability of outcome ranking at the end of Stage One to select the optimal treatment for Stage Two,” said Dr Gustavo Velásquez, PRISM-TB principal investigator and assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine and the Center for Tuberculosis at University of California, San Francisco. “We believe these unique trial elements in addition to including priority populations such as adolescents and pregnant women will both optimize treatment and improve access.”

PRISM-TB trial drug donations include bedaquiline by Johnson & Johnson and pretomanid by Viatris/Mylan Pharmaceutical Private Limited. In addition to Mongolia, the PRISM-TB trial plans to open in clinical sites in Peru and Uganda soon. SMART4TB anticipates preliminary analysis in 2027.

Seasoned global health leader brings over 26 years of expertise in complex, multi-stakeholder projects 

Baltimore, January 16, 2025 — Leader in combatting global infectious diseases Kelly Curran is joining USAID-funded Supporting, Mobilizing, and Accelerating Research for Tuberculosis Elimination (SMART4TB) as Project Director on January 27.  

Former senior director for HIV and Infectious Diseases at Jhpiego, Curran’s career spans a variety of global health’s most pressing issues, from women’s health to HIV, COVID-19, and mpox, working with key stakeholders including country ministries of health, donors, multilateral agencies, researchers, clinicians and affected communities. Driven by a passion for transforming global health on the ground, Curran’s roles have involved designing and implementing effective multi-country programs, leading multidisciplinary teams, directing operations, and conducting research with life-saving results.  

“Kelly Curran has an extraordinary record of developing and implementing programs that have changed the trajectory of population health in countries afflicted with high burdens of communicable diseases and health inequities,” said Richard Chaisson, SMART4TB chief of party and professor of medicine and public health at Johns Hopkins University.  

“SMART4TB will benefit enormously from the depth of experience and innovative problem solving that Kelly has brought to some incredibly complex challenges,” said Payam Nahid, SMART4TB senior research advisor and Haile T. Debas distinguished professor of global health and executive director of the UCSF Institute for Global Health Sciences. “Her knowledge, passion, and energy will undoubtedly drive us forward in exciting new ways.” 

Curran’s most recent role involved overseeing the $391 million PEPFAR/USAID-funded Reaching Impact, Saturation and Epidemic control project, which is focused on supporting national HIV, COVID-19, mpox, and Marburg virus responses. In this project, she helped introduce 3HP TB preventive treatment for people living with HIV, and long-acting HIV prevention products in low- and middle-income countries with nurse-led service delivery models.  

“The global responses to COVID-19, HIV, and malaria show that we can change the course of an epidemic when scientific advances in diagnostics, therapeutics and prevention reach the people who need them most,” said Curran. “I am thrilled to join the SMART4TB team, and the global TB response, at this pivotal moment when so much scientific progress is being made against the world’s leading infectious disease killer.”   

Curran comes to SMART4TB at an exciting moment, as several multi-country treatment trials, vaccine preparedness, airborne infection control, and operational research projects are launching.  

Several promising tuberculosis (TB) vaccine candidates are in late-stage clinical trials and have the potential to accelerate the global community’s efforts to curb and ultimately end the disease. But vaccines can only save lives and prevent transmission if they are widely used, making preparation for the rollout of a TB vaccine critical. SMART4TB is proud to introduce the TB vaccine preparedness repository, which will facilitate coordination of research taking place on adult and adolescent TB vaccine preparedness.

The repository tracks completed, ongoing, and planned projects from across the globe, focusing on research that examines preparation for a new TB vaccine. The repository is updated semi-annually, with stakeholders reporting on ongoing and planned projects. If you would like to be added to this list, or have projects to add to the repository, or a question, please contact Joeri Buis at joeri.buis@kncvtbc.org.

Visit the repository HERE.