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.

SMART4TB is proud to launch CABLab, a self-paced online curriculum for people looking to increase their knowledge to engage more deeply–or for the first time!–in TB advocacy and research. Built in collaboration with our regional Community Advisory Board partners, Afrocab, APCASO, and Eurasian Community for Access to Treatment (ECAT), CABLab covers a broad spectrum of topics, from vaccines to research fundamentals.

Through a mix of articles, videos, and interactive materials, along with opportunities for digital interaction and sharing, CABLab provides a forum where interested advocates can come together to continue expanding their TB knowledge.

CABLab will be launching in English on November 20, 2024, with French and Russian translations available in early 2025 but you can start registering now. We hope to expand to more languages in the coming years.

Register for CABLab HERE.

 

 

SMART4TB and the BETTER Project co-hosted a two-day meeting in Johannesburg last week to address the growing issue of expanded resistance to TB drugs. Bedaquiline, clofazimine, delamanid, linezolid, and pretomanid are the backbones of shorter, safer, more effective regimens for rifampin-resistant TB. However, resistance to them poses enormous challenges for affected individuals and the clinicians and programs who treat them.

Leading front-line clinicians, affected community members, and representatives from national TB programs convened to share experiences and develop best practices for this rising concern. They discussed the complicated decision-making process involved in treating and receiving treatment for a type of TB with limited options. This involved weighing the side effects and risks against the goals for the person living with TB, the physician, and the national TB program. They concluded that structured approaches to care for people living with expanded resistance to TB drugs should include:

• Timely access to genomic sequencing to identify drug-resistance mutations to enable early detection of expanded resistance to guide treatment;
• Wraparound care with holistic counseling and shared decision-making between the healthcare provider and person living with expanded drug resistance;
• Urgent development of equitable programs, developed in consultation with key affected communities, for pre-approval access to new drugs. These programs should include both clinical trials and compassionate use. The BETTER Project stands ready to provide clinical support to these programs and calls on drug developers and donors to prioritize this work; and
• Data collection using common elements and existing shared platforms to capture the extent of expanded resistance and outcomes to inform evidence-based policymaking.

SMART4TB and BETTER will produce a clinical field guide in the coming months, further detailing the above practices. If you are interested in receiving the field guide and learning more about our joint efforts, sign up for SMART4TB updates or follow us on LinkedIn. We will also distribute the field guide on our website and through TB listservs. If you are a provider treating expanded DR-TB, please contact Jen Furin at jenniferfurin@gmail.com and if you are a survivor and want to share your story, please contact Rekha Radhakrishnan at rradhak5@jh.edu.

Studies led by local, early-career researchers are linked to national public health priorities 

BALTIMORE AND SOWETO, September 9, 2024 —The Supporting, Mobilizing, and Accelerating Research for Tuberculosis Elimination (SMART4TB) Consortium is proud to announce the launch of two innovative operational research projects to improve TB prevention and early treatment in contacts of people with TB. The studies, funded by the U.S. Agency for International Development (USAID), followed a call for proposals from South African investigators to develop concepts for advancing the South African National TB Program’s research priorities.

“We’re thrilled to advance these important, locally developed concepts, all while nurturing the growth of early career investigators,” said Dr. Neil Martinson, executive director of the Perinatal HIV Research Unit in Soweto, South Africa and SMART4TB Consortium member.

The first study, Participatory Approaches to Strengthen Implementation of Contact Tracing and Treatment for TB or PACT-TB, will characterize barriers and enablers to delivering contact tracing and treatment services in Khayelitsha, Western Cape, and using participatory research methods, will co-develop interventions to increase contact tracing, testing and treatment. “TB Proof is passionate about partnering with communities affected by TB to advance implementation of the latest research,” remarked Ingrid Schoeman, PACT-TB lead and director of TB Proof, an advocacy organization started in 2012 by health workers who developed occupational TB. “And as a TB survivor myself, the chance to lead a research project to improve TB detection and prevention in people who are at high risk from close contact with TB is especially meaningful.”

The second study, led by Thobani Ntshiqa, a PhD candidate affiliated with the Aurum Institute, will evaluate the prognostic value of tuberculosis infection tests in predicting progression of infection to active TB disease among people who have close household contact with someone with TB. “TB preventive therapy uptake is stubbornly low in South Africa, with only 6% of household contacts of people with TB starting treatment,” noted Ntshiqa. “Predicting the progression of tuberculosis infection to active disease would help triage, prioritize and optimize the delivery of preventive therapy strategies among household contacts in high TB and HIV burden settings.”

A call for proposals released in December 2023 solicited applications for innovative operational research related to TB prevention, treatment and care to assist and support the National TB Program’s Research Priorities for TB in South Africa. The call targeted investigators who received their most recent degree within the last 10 years or are new to TB research. SMART4TB received more than 10 applications, which were carefully reviewed by a panel of 16 independent reviewers, representing SMART4TB technical experts, leaders from research and policy organizations and a South African member of Afrocab, one of SMART4TB’s regional community advisory boards.

“Both of these projects reflect some of our country’s biggest challenges in TB and their results will influence our strategies for detection and prevention going forward,” said Professor Norbert Ndjeka, chief director: TB Control & Management at the National Department of Health in South Africa.

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The SMART4TB Consortium brings together experts in TB tools development, implementation science, capacity strengthening, civil society engagement and policy translation. Led by Johns Hopkins University, consortium members include University of California, San Francisco, Elizabeth Glaser Pediatric AIDS Foundation, KNCV Tuberculosis Foundation, and Treatment Action Group.

SMART4TB is made possible by the support of the American people through the United States Agency for International Development (USAID). The contents of this press release are the sole responsibility of SMART4TB and do not necessarily reflect the views of USAID, the United States Government or consortium collaborators or members.

Prioritizing scalable, point-of-care testing, five companies seek to produce the next major diagnostic advancement in TB

BALTIMORE, JULY 8, 2024 — Supporting, Mobilizing, and Accelerating Research for Tuberculosis Elimination (SMART4TB) is pleased to announce a collaboration with Sherlock Biosciences in developing their oral, swab-based point-of-care molecular test for TB. Sherlock joins the four companies, Boditech Med, Co-Diagnostics, Nuclein and Molbio Diagnostics, announced in January 2024 in receiving a first phase of SMART4TB funding and technical assistance to advance their novel tests with the hope of closing key TB diagnosis gaps. Among some of the traits that make Sherlock’s technology promising for TB diagnostics is ease of use, including the intended ability to self-collect the sample, and no need for extensive lab or storage infrastructure to complete the test. These features are especially important in reaching people in diverse, resource-limited healthcare settings where TB is often diagnosed.

Sherlock, and the previously announced developers, were selected by a panel of 11 TB and diagnostics experts from academic institutions and the United States Agency for International Development (USAID). Characteristics and data from this first phase will be evaluated by a similar group of experts, including affected community members, and those that meet key criteria will move into the next phase of funding to prepare for clinical assessment.

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The SMART4TB Consortium brings together experts in TB tools development, implementation science, capacity strengthening, civil society engagement and policy translation. Led by Johns Hopkins University, consortium members include University of California, San Francisco, Elizabeth Glaser Pediatric AIDS Foundation, KNCV Tuberculosis Foundation, and Treatment Action Group. SMART4TB is made possible by the support of the American people through the United States Agency for International Development (USAID). The contents of this press release are the sole responsibility of SMART4TB and do not necessarily reflect the views of USAID, the United States Government or consortium collaborators or members.

Locally driven research is at the centerpiece of months-long USAID-funded program to continue building local capacity for tuberculosis research 

BALTIMORE, April 25, 2024 — Supporting, Mobilizing, and Accelerating Research for Tuberculosis Elimination (SMART4TB) is excited to welcome the second cohort of Early Stage Investigator (ESI) scholars. This year’s cohort reflects the depth and diversity of early career researchers, with a total of 50 scholars representing six countries in Africa and Asia. Simultaneously, SMART4TB is admitting 12 scholars from the first cohort to Phase II of the ESI program, a rigorous fellowship that hones in on researchers’ specific projects.

“This year’s cohort of Early Stage Investigators were impressive, reflecting the diverse background and interests of global researchers,” said Robert Bollinger, the Raj and Kamla Gupta Professor of Infectious Diseases at Johns Hopkins University. “It’s incredibly gratifying to meet new scholars and progress some of the scholars we trained last year into the next phase and see their research interests mature and solidify.”

Now in its second year, the first phase of the Early Stage Investigator program, is a 10-week intensive curriculum delivered by some of the world’s leading TB researchers. Topics include developing a research question and concept paper for a research proposal, engaging communities, designing a research study as well as reviewing and discussing their country’s current National Tuberculosis Program priorities. The countries represented in this new cohort include Nigeria, the Philippines, South Africa, Uganda,Vietnam and Zambia.

This Early-Stage Investigators’ Program creates unique opportunities for further enhancing the quality of locally led research by bringing investigators into direct contact with top-notch knowledge sources in TB research and education,” said Degu Jerene, a senior epidemiologist and team lead at KNCV Tuberculosis Foundation. “The program builds on what countries have started, paving the way to a sustainable model of capacity strengthening.”

After successful completion of Phase I of the program, scholars can apply to Phase II where they progress to the SMART4TB fellowship program that includes specific courses to help convert their research concept into a fully developed high quality TB research proposal. They receive mentorship from both a local and an internationally experienced SMART4TB faculty research co-mentor. Fellows also have access to strategic technical support consultations, including data management, biostatistics, research ethics, study design, implementation science and community engagement from SMART4TB experts. This year’s SMART4TB Phase II fellowship participants represent Mozambique, the Philippines, South Africa, and Zambia.

Márcia Chiluvane, a SMART4TB fellow from Mozambique described her experience as an ESI scholar. “The highlight was developing a research proposal that can address the challenges highlighted by my country’s National Tuberculosis Program. On this journey, I was surrounded and supported by a remarkable network of colleagues and mentors, both national and international, with vast expertise in tuberculosis.”

“The Early Stage Investigator program really speaks to the need for comprehensive mentorship for researchers early in their careers,” said Philip Hopewell, professor of medicine emeritus at University of California, San Francisco. “The research and ideas they produce will undoubtedly inform the field and strengthen local capacity in sustainable ways that will benefit future generations.”

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The SMART4TB Consortium brings together experts in TB tools development, implementation science, capacity strengthening, civil society engagement and policy translation. Led by Johns Hopkins University, consortium members include University of California, San Francisco, Elizabeth Glaser Pediatric AIDS Foundation, KNCV Tuberculosis Foundation, and Treatment Action Group.

The ADAPT for Kids study will evaluate accuracy of non-sputum tuberculosis diagnostic tests in children

BALTIMORE, February 15, 2024 — The Assessing Diagnostics at Point-of Care for Tuberculosis (ADAPT) for Kids study has enrolled its first participants at Instituto Nacional de Saúde (INS), Mozambique. ADAPT for Kids is evaluating promising TB diagnostic tests for children to inform World Health Organization (WHO) policy and ultimately provide children better, more accurate tests. The first tests studies will be tongue swab tests in children under 15 years, including children living with HIV. The study is led by Supporting, Mobilizing, and Accelerating Research for Tuberculosis Elimination (SMART4TB) consortium.

TB is a leading cause of death in children, and almost all (96%) childhood TB deaths occur in children not on treatment due to missed diagnosis. Pediatric TB is underdiagnosed, in part because existing tests don’t work well in children. “Better tools for diagnosis at the point-of-care means a faster start to treatment, which is vital to ending these senseless TB deaths in children,” said Dr. Nilesh Bhatt, ADAPT for Kids investigator and global clinical research director at the Elizabeth Glaser Pediatric AIDS Foundation.

ADAPT for Kids will enroll children less than 15 years old with TB symptoms and risk factors, including children living with HIV. One of the first tests the study will evaluate utilizes tongue swabs to detect TB. Traditional TB tests rely on sputum, which is difficult for children to produce. “A tongue swab test would be a game changer, making TB diagnosis easier for both children and health systems to process and turn around,” said Dr. Celso Khosa, ADAPT for Kids investigator and director of the Centro de Investigação e Treino em Saúde da Polana Caniço (CISPOC) at Mozambique’s INS. ADAPT for Kids will generate critical evidence not just on test accuracy, but also on usability and acceptability among healthcare workers, critical components to ensuring effective tests are adopted by health systems and countries.

“Improving diagnostics is at the center of how we reach the ultimate goal of ending TB in Mozambique,” said Dr. Benedita Jose, the National TB program director in Mozambique. “We are excited to focus on children with this study and help get them access to the same cutting edge diagnostic technology that we look at for other populations.”

“SMART4TB is proud that the ADAPT for Kids study was developed and implemented in parallel and in collaboration with the ADAPT study in adults,” said Dr. Devan Jaganath, ADAPT for Kids investigator and assistant professor of Pediatrics at University of California, San Francisco. “Pediatric TB research too often lags behind, and SMART4TB is dedicated to closing research gaps for children by making sure we’re evaluating similar promising diagnostic technology in kids.” To further ensure standardized, high-quality evidence for children, ADAPT for Kids also is coordinating with the pediatric site with the U.S. National Institute of Allergy and Infectious Diseases-funded The Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network).

A second ADAPT for Kids site at Mulago National Referral Hospital in Uganda, will be launched in the first half of 2024. Each site anticipates enrollment of 200-250 children per year.

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The SMART4TB Consortium brings together experts in TB tools development, implementation science, capacity strengthening, civil society engagement, and policy translation. Led by Johns Hopkins University, consortium members include University of California, San Francisco, Elizabeth Glaser Pediatric AIDS Foundation, KNCV Tuberculosis Foundation, and Treatment Action Group. SMART4TB is a cooperative agreement with the United States Agency for International Development (USAID), made possible by the generosity of the American people.The findings in this publication do not necessarily represent the views of the U.S. Agency for International Development or the U.S. Government.