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.

Significant investment in technology marks major advance in point-of-care testing, the highest priority diagnostic need for TB prevention and care 

BALTIMORE, January 9, 2024 — Supporting, Mobilizing, and Accelerating Research for Tuberculosis Elimination (SMART4TB) is excited to announce Boditech Med, Co-Diagnostics, Nuclein and Molbio Diagnostics as partners in developing oral swab-based, point-of-care molecular TB tests.

“The United States Agency for International Development’s (USAID) strategic investment in diagnostics technology for TB is an area ripe for innovation,” said Claudia Denkinger, head of the Division of Infectious Diseases and Tropical Medicine at University Hospital Heidelberg. “COVID-19 showed us that with the right incentives, many developers could utilize technology they were already working on to create efficient, scalable tests for different diseases. We have a similar ambition for TB, and this investment marks a vital step in the right direction.”

According to the World Health Organization’s ​​2023 Global Tuberculosis Report, 10.6 million people fell ill with tuberculosis  (TB) in 2022; 3.1 million were not reported because they were either not diagnosed or were diagnosed and not linked to care. Rapid molecular TB testing through platforms such as GeneXpert and Molbio has been an important advancement for TB by providing faster, more accurate diagnoses, including the detection of drug resistance. However, these tests largely still rely on sputum samples, which can be difficult to produce, and require infrastructure that challenges their use in a range of places where people seek care. To effectively treat people in settings where they are more likely to visit, healthcare providers need a test that is fast, accurate and can be conducted in any clinical setting.

“Rapid tests at the point of care for a person with TB is a game-changer. From the perspective of people with TB, it means getting a faster diagnosis and planning for potential treatment. From the clinician’s and program’s perspective, rapid, point-of-care testing can reach more people and improve the entire cascade of care, from prevention through treatment to contract tracing,” said Adithya Cattamanchi, chief, Division of Pulmonary Diseases and Critical Care Medicine at University of California, Irvine.

Developers were selected by a panel of 11 TB and diagnostics experts from academic institutions,USAID and​​ prominent organizations. The developers already have point-of-care molecular platforms in pre-commercialization or commercialization phase. In this effort, SMART4TB will provide financial and technical support to help adapt their technology to TB, and clinical support and regulatory guidance to help bring the final product to communities affected by TB.

“We’re excited about these partners because of the innovation they showed in their applications,” said Yuka Manabe, director at the Center for Innovative Diagnostics for Infectious Diseases at Johns Hopkins University School of Medicine. “We believe they have a high chance of success in bringing a test to market on an aggressive timeline and ultimately, bringing TB care close to many more people.”

This project has three development phases, from prototype to a design-locked clinically evaluated test. Partners selected for the first phase will only move to the next phase if their test meets designated standards and will be evaluated by a series of experts, including affected community members.

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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.

The ADAPT study will collaborate with global partners in this space as part of the largest-ever coordinated effort to further TB diagnostic development

BALTIMORE, November 7, 2023 — The USAID-funded Supporting, Mobilizing, and Accelerating Research for Tuberculosis Elimination (SMART4TB) award is excited to announce enrollment of study participants in Nigeria, Zambia and the Philippines in the Assessing Diagnostics at Point-of Care for Tuberculosis (ADAPT) study. This study seeks to identify and assess promising novel point-of-care TB tests that do not rely on sputum. The study will generate evidence to inform World Health Organization (WHO) review and ultimately, uptake of new, effective diagnostic tests in TB high-burden countries.

“Better diagnostics that work where patients seek care are key to finding the 3.1 million people with TB who go undiagnosed each year,” said Adithya Cattamanchi, chief, Division of Pulmonary Diseases and Critical Care Medicine at University of California, Irvine. “Our goal with this study is to evaluate tests that are easier on patients and that could produce fast, reliable results in diverse healthcare settings.”

Partnering with the U.S. National Institute of Allergy and Infectious Diseases-funded The Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network), Feasibility of Novel Diagnostics for TB (FEND-TB), FIND and Unitaid-funded DriveDx4TB, ADAPT will first rigorously evaluate the performance of Tongue Swab Xpert Ultra and Truenat MTB Plus, two WHO-endorsed rapid molecular tests for TB to determine whether they are an effective alternative method for diagnosing TB. SMART4TB is partnering with the Zankli Research Centre at Bingham University in Nigeria, De La Salle Medical and Health Sciences Institute (DLSMHSI) in the Philippines and Centre for Infectious Disease Research in Zambia (CIDRZ). Across these sites, the study will enroll 900 participants who present to health clinics with a cough for two or more weeks and/or have TB risk factors plus a positive World Health Organization (WHO)-recommended TB screening test, including key populations such as close contacts of people with TB, adolescents and people living with HIV.

“The difference a tongue swab test could make for patients—particularly young people and people living with HIV, who struggle to produce sputum—cannot be underestimated, influencing everything from their likelihood of getting tested to moving them more rapidly towards treatment options,” said John Bimba, director of the Zankli Research Centre.

“We need diagnostics tests that are user friendly. Healthcare settings for TB can vary widely and one of the goals with any new test is how well our staff is able to repeatedly conduct it. We will be looking at that closely with both tests,” said Charles Yu, former vice chancellor for research services and a professor at the College of Medicine of the De La Salle Medical Health and Sciences Institute.

“Rapid, low-cost and accurate tests can play a major role in ending TB in Zambia. We are looking forward to seeing the results and hope this study plays a role in transforming TB care globally,” said Monde Muyoteta, program director for TB at the Centre for Infectious Disease Research in Zambia.

Researchers expect to have initial results from the study to share in March 2024.

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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.

NEW YORK CITY, September 25, 2023 — Following the United Nations (UN) High-Level Meeting on the fight against Tuberculosis, the Supporting, Mobilizing, and Accelerating Research for Tuberculosis Elimination (SMART4TB) Consortium welcomes the UN’s commitments to ending tuberculosis (TB), particularly through advancing research and access for neglected populations. In a week in which health systems and public health coordination took the global center stage, the overwhelming need for cutting edge research that is effective and responsive to the needs of affected communities was a critical theme. Member states committed to mobilizing $5 billion for TB research per year by 2027 and affirmed the right of all people to “enjoy and share the benefits of research and innovation.”

“We are heartened to see countries uniting in recommitting to end TB, and especially in asserting the importance of research, access and affordability of evidence-based tools to achieve ambitious goals,” said SMART4TB chief of party, Dr. Richard Chaisson, professor of medicine at Johns Hopkins University School of Medicine. “Making good on these commitments is vital. SMART4TB stands ready to support countries in their realization throughout our research and policy activities.”

SMART4TB’s key research areas include diagnostics, therapeutics, vaccine preparedness and strengthening research capacity. Among the current and planned consortium activities that will support commitments made by the UN are:

• Assessing point-of-care TB diagnostics to close the diagnosis gap, including for children, through the ADAPT and ADAPT for Kids studies;
• Evaluating the anti-TB drug bedaquiline as preventive treatment for all forms of TB in adults, children and pregnant women (BREACH-TB);

• Improving drug-resistant TB treatment with regimens based on individual baseline risks of poor treatment outcomes (PRISM-TB);
• Testing shorter treatment for children with drug-susceptible TB with a stratified approach (SMILE-TB);
• Ensuring the appropriate inclusion of pregnant women in TB research;

• Developing locally led operational research studies in partnership with country missions and research stakeholders;

• Supporting engagement and innovation from the research community in high burden countries through the Early Stage Investigator program, with mentorship and training;
• Centering people and affected communities in all the above, through three regional community advisory boards: AfroCABTreatment Access Partnership (AfroCAB), Asia Pacific Council of AIDS Service Organizations (APCASO) and Eurasian Community for Access to Treatment (ECAT).

SMART4TB welcomes collaboration with partners from affected communities, researchers in high-burden countries, and policymakers at the national and global levels to accelerate the end of TB.

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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.

First study to evaluate bedaquiline, a game changing TB treatment drug, as a shorter, safer regimen for TB prevention

NEW YORK CITY, September 19, 2023 — In the lead up to the second United Nations (UN) High-Level Meeting on Tuberculosis, Supporting, Mobilizing, and Accelerating Research for Tuberculosis Elimination (SMART4TB) announced plans to conduct a transformational multinational study of a one-month treatment regimen to prevent all forms of tuberculosis (TB), including drug-resistant TB.

BREACH-TB (Bedaquiline Roll-Out Evidence in TB Contacts and People Living with HIV to Prevent Tuberculosis) will test whether one month of oral bedaquiline, a potent drug that has revolutionized the treatment of drug-resistant TB, can prevent both drug-resistant (DR) and drug-susceptible (DS) TB in people exposed to either form of TB in their households and in people with HIV infection, including pregnant women and children.

“Developing a short regimen that can prevent both DR- and DS-TB infections from advancing to active TB disease will greatly simplify options for TB preventive treatment (TPT) and ensure that more people exposed to TB in high-burden countries will get and complete treatment, helping to achieve the UN’s goal of Ending the TB Epidemic by 2030,” said SMART4TB chief of party, Dr. Richard Chaisson, professor of medicine at Johns Hopkins University School of Medicine.

TB is a leading infectious killer globally, with an estimated 1.6 million deaths in 2021. In 2018, the first-ever UN High-Level Meeting on TB made ending the disease a global priority and set the target of preventing 30 million new cases between 2018 and 2022. However, less than half of the target was reached. The World Health Organization has prioritized preventive therapy as a key strategy for ending TB.

“The study design of BREACH will allow us to boldly investigate a promising preventive pan-TB regimen—meaning that household contacts, people living with HIV and other key members of TB-affected communities, will be part of a global effort to get us closer to a safe and effective preventive treatment for all,” said Dr. Payam Nahid, SMART4TB’s senior scientific advisor and professor of medicine at the University of California, San Francisco.

Preventive therapy is only successful if the person with latent TB completes the course of medication. However, people with latent TB infections don’t show symptoms of the disease, making it more difficult to keep them on a long, arduous medication schedule solely for prevention. Providers know this and would prefer to offer shorter regimens as a first-line option to ensure they are fully completed. While short-course regimens for DS-TB have been available for several years, individuals exposed to DR-TB can only be treated with longer courses of unproven regimens to prevent development of TB disease.

Approved by the United States Food & Drug Administration in 2012, bedaquiline was the first new drug to be developed for TB in 40 years. It has since become a game-changer in the treatment of DR-TB. The BREACH Study will be the first to evaluate bedaquiline for TB prevention.
SMART4TB is a cooperative agreement with the United States Agency for International Development (USAID), made possible by the generosity of the American people.

“A shorter regimen that fights both drug-resistant and drug-susceptible TB would be a game-changer for those living with TB and get us closer to our shared goal of ending the epidemic by 2030. This clinical trial will lay the foundation for a remarkable innovation in our fight against TB: a single-dose, long-acting injectable medicine,” said Dr. Atul Gawande, USAID assistant administrator for Global Health.

The study is being led by researchers Drs Eric Nuermberger and Sonya Krishnan at Johns Hopkins University. It is slated to begin enrollment in 2024.

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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.