The panTB-HM clinical trial has begun patient recruitment in South Africa, with first patient dosed on 28 July 2023. This trial is a historic milestone in the quest to revolutionise tuberculosis (TB) treatment and improve outcomes for all TB patients.

The panTB-HM trial addresses the World Health Organisation (WHO) target profile for new TB regimens that can be administered without prior knowledge of rifampicin susceptibility, the marker for multi-drug resistant TB. The panTB-HM trial is designed as a phase 2c trial, aligning with WHO recommendations for TB regimen development.

The trial's primary objective is to assess the proportion of patients with durable, non-relapsing cure, representing a pivotal step in advancing TB treatment paradigms. The goal is a more effective, shorter-duration TB treatment that protects lung function during and after treatment.

The innovative regimen contains new TB drugs bedaquiline and pretomanid and the experimental new oxazolidinone sutezolid. Extensive preclinical studies and phase 1 and 2 clinical trials of sutezolid demonstrated excellent safety over up to three months of daily oral dosing, a substantially better safety profile than other oxazolidinones used in TB regimens (i.e., linezolid).

Even after successful treatment with standard drug regimens, many TB survivors endure persistent lung conditions, such as bronchiectasis and fibrosis, that gradually erode lung function. The panTB-HM trial incorporates N-acetylcysteine (NAC), a repurposed host-directed WHO essential medicine. NAC is used to protect both the liver and lung from oxidative damage, preserving lung function and accelerating the eradication of MTB infection by replenishing glutathione (GSH).

Tuberculosis remains a formidable global health challenge, causing significant morbidity, mortality, and socio-economic consequences. In 2021, WHO estimated 10.6 million cases of TB worldwide and >500,000 of these patients had multi-drug resistant TB. TB continues to be the global infectious disease with the highest mortality rate, with 1.6 million deaths in 2021, topped only by pandemic COVID.

The panTB-HM trial is a collaboration led by The Aurum Institute, with Prof Robert Wallis as Aurum Institute Chief Scientific Officer and Principal Investigator of the trial. The consortium includes academic institutions Ludwig-Maximilians-Universitaet Muenchen (Germany) Stellenbosch University (South Africa), and Stichting Katholieke Universiteit-Radboudumc (Netherlands); clinical trial sites include Wits Health Consortium`s Clinical HIV Research Unit (South Africa) and National Institute for Medical Research in Mbeya (Tanzania, United Republic of); the consortium also includes a corporate collaborator, Sequella Inc (United States).

The trial is funded by the European & Developing Countries Clinical Trials Partnership (EDCTP), grant number RIA2019AMR-264.

Clinical Trial Registration Information Sites:

Pan African Clinical Trials Registry: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=24206

South African Clinical Trials Registry: https://sanctr.samrc.ac.za/TrialDisplay.aspx?TrialID=6986

ClinicalTrials.gov:https://www.clinicaltrials.gov/study/NCT05686356?term=panTBHM&rank=1

About The Aurum Institute

The Aurum Institute is a proudly African organisation working to advance health science and innovation to create a healthier world for future generations. We partner with governments, the private sector and civil society to design and deliver high-quality care and treatment to people in developing communities. https://www.auruminstitute.org/

For the latest information and updates on the panTB-HM trial, please visit our official website at https://pantb-hm.org/.

For media inquiries and additional details, please contact:

Don Mudzengi Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

As the United Nations High-Level Meeting (UNHLM) on TB approaches, a new report from the Lancet Commission on tuberculosis releases recommendations, providing a path forward to turn the tide on this preventable, treatable and curable disease.

For the first time in 20 years there has been an increase in TB deaths — rising from 1.4 million in 2019 to 1.6 million in 2021 — as COVID-19 erased years of reduction in TB mortality rates. Moreover, there has been a troubling decline in the number of people diagnosed with TB, estimating that one-third of people were undiagnosed and untreated in 2022. The COVID pandemic had a significant impact on the ability of global health systems to prevent, screen and treat TB. COVID-19 quickly and substantially disrupted TB response efforts as diagnostic infrastructure was diverted away from TB programs and shutdowns led to reduced access to TB treatment services. In almost all high TB burden countries, COVID-19 resulted in health worker shortages and burnout, further diminishing health systems’ capacity to provide essential TB services. COVID-19 also had a negative effect on many countries’ abilities to invest in health, with precious resources for health programs being diverted to respond to COVID and economic disruptions impacting governments’ abilities to prioritize health moving forward.

“Progress on fighting TB has been stalled, but we can and must get back on track. As this new critical report states, we must focus on a new menu of tools that have the potential to revolutionize TB prevention, diagnosis and treatment.” stated Dr. Eric Goosby, Commission co-Chair, UCSF Professor of Medicine and former UN Special Envoy on Tuberculosis.

Lancet Commission Report Endorses New Menu of Tools New treatment regimens and several late-stage vaccine candidates present an incredible opportunity to make major inroads in preventing TB deaths. Recommendations put forth by the Commission include:

• Immediate scale-up in access to molecular diagnostics and AI-assisted chest x-ray technology.
• Sustained investments in research and development to accelerate progress on new tools including non-sputum-based tests such as tongue swabs, urine-based antigen tests and improved screening tools, all of which are faster and more accurate than sputum tests, which can take one to eight weeks to provide results.
• Addressing malnutrition as a major risk factor for TB with more than a third of annual TB incidence attributable to undernutrition — especially in Southeast Asia. Recent research illustrates the positive impact of giving food baskets to patients with TB and their closest contacts. In a large study in India, better nutrition in patients with TB reduced incidence of infection by nearly 50 percent while reducing mortality among those treated for TB by nearly 60 percent.
• Endorsement of the 1/4/6x24 campaign, an effort to bring new, shorter, safe and effective TB regimens to as many countries as possible by 2024. Specifically, the report outlines recommendations for ensuring access to one-month regimen or once-weekly for TB prevention, four months for drug-sensitive TB, and six months treatment regimen for drug-resistant TB.

“The newer, shorter 1/4/6 TB treatment regimens can have a huge impact on adherence and efficacy,” said Soumya Swaminathan, Commission Co-chair and former World Health Organization Chief Scientist. “To maximize the impact of these significant treatment breakthroughs, we need more countries adopting the new treatment paths faster. Adjunct therapies like nutritional support can also go a long way in reducing deaths due to TB.”

Economic Cost of Inaction - Recommendations for The Global Fund to Fight AIDS, TB and Malaria

The cost of inaction on TB is massive. More than 27 million lives and over $13 trillion in economic losses will result if there is a business-as-usual trajectory between now and 2050. A recent estimate commissioned by the STOP TB Partnership proposes a near-term target of US$15 billion a year, rising to US$20 billion in 2025, to end TB by 2030. This estimate takes into account lost ground due to COVID-19 and acceleration in the development of new tools.

Donor financing plays a significant role in funding TB resources in many low- and middle-income countries. TB receives less funding from the Global Fund compared to HIV and malaria even though TB accounts for 61 percent of global deaths caused by the three diseases. The report recommends that the Global Fund allocate more money to TB based on disease burden and cost-effectiveness. It also suggests prioritising the increase in TB support for low-income countries with higher TB mortality.

This new report is a follow-up to the 2019 Lancet Commission on tuberculosis. The first report outlined a blueprint for reaching the goals set by the first UNHLM in 2018. While progress has been made in some areas, the targets of the UNHLM have not yet been achieved. Some African countries have sustained declines in TB mortality, but more than seven million people have died from TB in the past five years, emphasizing the urgency to accelerate efforts.

This year’s UNHLM on TB is taking place on September 22 and presents a critical opportunity to mobilise political will and resources to scale up new technology, emphasising affordability and availability.

“TB advocates and survivors like me know there aren’t a lot of opportunities to shed light on this disease despite its impact on so many people across the world. We are demanding that countries step up and prioritize the funding and technology that will get us to a TB-free world,” said Nandita Venkatesan, TB survivor champion and journalist.

 In addition to holding a High-Level Meeting on TB, additional meetings will focus on Pandemic Preparedness and Response (PPR) and Universal Health Coverage (UHC). The Commission highlights several areas where aligning global TB efforts with the PPR and UHC agendas would be mutually beneficial, emphasising that investing in PPR should be synergistic with efforts to end TB.

The Lancet Commission received support from the United States Agency for International Development through Supporting, Mobilising, and Accelerating Research for Tuberculosis Elimination, a five-year cooperative agreement that aims to transform TB prevention and care.

Aurum Institute Ghana announced this week that it is a winner of a Grand Challenges grant – an initiative fostering innovation to solve pressing global health and development problems and funded by the Bill & Melinda Gates Foundation. Nana Kofi Quakyi, MPH will pursue an innovative global health and development research project focused on Catalyzing Equitable Artificial Intelligence (AI) Use, titled AI-powered Decision Support for Antibiotic Prescribing in Ghana.

When harnessed equitably and responsibly, AI has incredible potential to help solve some of the world’s toughest challenges and reduce global inequity. Supporting AI research in low- and middle-income countries (LMICs) will help ensure that AI technology is tailored to local health, education, agricultural and other contexts and designed with the needs of the world’s most vulnerable at the center.

The project addresses the urgent public health challenge of antimicrobial resistance (AMR) in Ghana. Its goal is to address this problem by creating an unconventional AI-powered clinical decision support tool. This tool will offer personalised recommendations for prescribing antibiotics, considering factors like patient information, treatment environment, antimicrobial resistance patterns, and Ghana's national drug policy. Through refining a sophisticated large language model with data from Ghanaian experts, the tool will provide real-time interactivity to prescribers. It will offer tailored guidance and adaptive suggestions based on the local clinical and policy context.

This innovative approach aligns with Ghana's National Action Plan for Antimicrobial Use and Resistance. This plan emphasises comprehensive strategies that include behavioral changes, like our Clinical Decision Support Tool, to combat AMR. Our technology aims to bridge the gap between knowledge and action, promoting responsible antibiotic prescribing practices in line with the local healthcare situation. Nana Kofi Quakyi became a Programme Manager at Aurum Institute Ghana in 2021. His role involves enhancing access to new technologies, treatments, and diagnostics in Ghana. He also leads efforts to generate evidence regarding their feasibility and acceptability.

Nana Kofi Quakyi’s project is one of nearly 50 Grand Challenges Catalyzing Equitable Artificial Intelligence (AI) Use grants announced by the Gates Foundation to support LMICs in harnessing AI’s power for good and to solve the urgent need for LMIC participation in the co-creation process of this technology as it rapidly evolves. The project’s findings will contribute to building an evidence base for testing AI large language models (LLMs) that can fill wide gaps in access and equitable use of these tools.  Each of these grants represents an opportunity to solve or mitigate a real challenge experienced by communities, researchers and/or governments in low- and middle-income countries.

To receive funding, Nana Kofi Quakyi and other Grand Challenges winners submitted their concepts which outlined their bold idea in response to the Catalyzing Equitable Artificial Intelligence (AI) Use request for proposals. More than 1,300 proposals were submitted from around the world.

About Grand Challenges

Grand Challenges stem from the idea from over a century ago that crowdsourcing a defined set of unsolved problems can spark innovation and accelerate progress. The Bill & Melinda Gates Foundation and its Grand Challenges funding partners use Challenges – launched in 2003 as open requests for grant proposals – to focus attention and effort on solving pressing global health and development problems for those most in need. Together they have awarded over 3600 grants engaging a diverse pool of problem solvers in over 100 countries and fostering a global innovation ecosystem where it will have the most impact. The foundation and its Grand Challenges partners will continue to launch RFPs to support innovators from around the world in tackling the hardest, most urgent, Grand Challenges. To learn more, visit grandchallenges.org. 

About The Aurum Institute

The Aurum Institute is a proudly African organisation working to advance health science and innovation to create a healthier world for future generations. We partner with governments, the private sector and civil society to design and deliver high-quality care and treatment to people in developing communities. https://www.auruminstitute.org/

About The Aurum Institute Ghana

Aurum Institute Ghana is an African Public Benefit Organization whose mission is to improve the health of people and communities living in poverty through innovation in global health research, systems, and delivery. The Aurum Institute Ghana operates in Ghana as a local Non- Governmental Organization (NGO) registered under Companies Code of 1963, Act 179 and licenced by the Social Welfare Department. It is an affiliate of Aurum Institute South Africa which is a not-for-profit company and a leading healthcare organisation. It is rooted in Africa and is dedicated to researching, supporting, and implementing innovative, integrated approaches to global health.  In Ghana, it is collaborating with the Ghana Health Service (GHS) in research, programme implementation and capacity building. https://www.auruminstitute.org/what-we-do/aurum-international/aurum-institute-ghana

For more information, contact:

Nana Kofi Quakyi, This email address is being protected from spambots. You need JavaScript enabled to view it., +233 244 501 809

George Amoo Adjei, This email address is being protected from spambots. You need JavaScript enabled to view it., +233 307 007 109

Kanya Ndaki, This email address is being protected from spambots. You need JavaScript enabled to view it., +27 83 298 610

Combination intervention found to be cost-effective in averting illness and deaths in high-risk groups

• People living in close contact with a person with TB disease are at highest risk of infection, and account for a significant percentage of the 10.6 million new TB infections each year.
• Analysis shows that implementing a combined strategy of identifying household contacts and providing TB preventive treatment is cost-effective and would cut deaths by 35% among household contacts of all ages and people living with HIV by 2035.
• Additionally, because TB diagnosis is so low among children under five – just over 3 in 10 children with TB are identified – contact tracing and prevention would have an outsized impact on reducing child death from TB.
• TB prevention and contact tracing can be delivered cost effectively thanks, in part, to the significant price reductions in short-course therapy achieved in recent years. With further decreases in price and by improving the efficiency and integration of contact tracing into disease responses, the intervention could benefit from greater cost savings and public health benefit.
• As world leaders prepare for the second United Nations High-Level Meeting on TB this September, up-front multi-stakeholder commitment and financial backing is urgently needed to reap the massive rewards of preventing TB illness and death.

Johannesburg/Geneva, 18 July 2023 – A new study published today in  found that the lives of 850,000 people could be saved by 2035 if short-course tuberculosis (TB) preventive treatment is provided to people living with HIV and contacts of individuals newly diagnosed with TB. 700,000 of those lives saved would be among children aged 15 years and younger.

The study, co-authored by researchers from Johns Hopkins University, the Aurum Institute and global health agency Unitaid, also found the combined intervention of contact tracing and TB prevention to be broadly cost-effective for household contacts of all ages. The impact was particularly high among children under the age of five who face higher risks of death.

“Tuberculosis remains the world’s deadliest infectious disease, despite being preventable and curable,” said Professor Gavin Churchyard, Group Chief Executive Officer of the Aurum Institute. “Although progress has been made in preventing TB among people living with HIV, we’ve lagged behind in keeping family members—especially children—free of the disease when a parent becomes sick. This new study, we hope, provides the evidence needed to massively scale up the use of TB preventive treatment among those individuals at risk of developing TB.”

TB preventive therapy has made enormous strides in recent years: new shorter treatment regimens can clear TB infection before it develops into active disease with a once-weekly treatment over twelve weeks, called 3HP, or a daily treatment over one month, called 1HP. And a series of negotiations led by Unitaid, the Aurum Institute, and partners have reduced the price of treatment by more than 70% since 2017.

About one-quarter of the world’s population is infected with TB and at risk of developing active disease, which causes severe illness. The World Health Organization recommends TB preventive treatment for those at highest risk of infection, including people living with HIV and household contacts of people with TB. The first United Nations High-Level Meeting in 2018 set targets to accelerate efforts to end TB as a global health threat, including a goal to reach at least 30 million people with TB preventive treatment.

Only the target to reach people living with HIV was attained, and a corresponding decrease in the number of TB cases and deaths occurred within this population during the COVID-19 pandemic. In contrast, TB cases and deaths increased in all other populations over the same period.

“The imperative for TB prevention is clear,” said Vincent Bretin, Director of Results at Unitaid. “This cost-effectiveness analysis proves that preemptively reaching all at-risk individuals – even when it requires the logistical hurdles of going into communities to find those who may not be actively seeking care – is not just ethically sound. It is a smart investment capable of making an enormous impact on the fight to end TB worldwide.”

The study found that providing 3HP through contact tracing, in which the household members of a person diagnosed with TB are identified, assessed, and treated, could yield an estimated 13% cumulative reduction in the number of contacts developing TB through 2035 and an estimated 35% cumulative reduction in deaths.  

Among children under five, the combination of 3HP with contact tracing showed to have a profound impact on the child TB burden overall, helping to drive up the identification of active disease in addition to preventing new infections. The impact on missing cases among this population was so substantial that the intervention would save more lives by treating TB disease and infection than the number of new infections prevented.

The study is the first to provide comparable evidence on the cost-effectiveness of short-course TB preventive treatment for people living with HIV and household contacts in three age groups (< 5, 5-14, and ≥ 15 years old), using consistent methods for all four populations. This provides a clear justification to support policy change and implementation of the life-saving approach where coverage is lagging.

“At the moment, too many family members of people diagnosed with TB are slipping through the cracks and too many lives are being lost,” said Tess Ryckman, faculty member at Johns Hopkins University and lead author of the study. “To finally make a significant dent in the TB epidemic, we need stronger recommendations in favor of TB prevention for household contacts along with a significant boost in resources. The stakes are too high not to act now.”

Despite the cost-effectiveness of TB preventive treatment, the researchers note that the absolute cost of scale up will be substantial. External funding—with an explicit plan to bridge to domestic support as TB burden declines—will be needed, as well as a further decrease in the price of the drug rifapentine, the key cost driver in short TB prevention regimens.

####

NOTES FOR EDITORS:

The analysis is based on modelling of 29 countries representing a range of income levels, geographic regions, and HIV and TB incidence expected to be applicable to other countries with high burdens of TB.

Burundi, Bangladesh, Brazil, Congo DRC, Ethiopia, Ghana, Haiti, Indonesia, India, Kenya, Cambodia, Liberia, Lesotho, Mongolia, Mozambique, Malawi, Namibia, Pakistan, Rwanda, Somalia, Eswatini, Thailand, Tajikistan, Timor-Leste, Tanzania, Uganda, South Africa, Zambia, Zimbabwe.

Information on the Unitaid-funded IMPAACT4TB Project

The IMPAACT4TB project has been working towards delivering transformational change in the accessibility and use of TB preventive treatment since 2018. Funded by Unitaid and led by the Aurum Institute with a consortium of partners, the project seeks to establish 3HP and 1HP as affordable, quality-assured, less toxic therapies suitable for wide introduction in countries most affected by TB.

Since its inception, IMPAACT4TB has:

• Reduced the price of 3HP from US$72 in 2017 to US$14.25 today
• Increased procurement of 3HP from 35,000 patient courses in 2017 to more than 4 million in 2022
• Improved supply security by bringing two new generic manufacturers into the market
• Helped surpass UN HLM prevention targets for people living with HIV
• Generated the missing evidence to enable people with HIV on first-line treatments to safely take short-course TB preventive treatment

By June 2022, 78 countries were using new short-course TB preventive treatments.

Figures on TB preventive treatment

According to the World Health Organization’s 2022 Global TB Report, the total number of people living with HIV and household contacts of people diagnosed with TB who were provided with TB preventive treatment increased from 1 million in 2015 to 3.6 million in 2019. There was a significant decrease in 2020 to 3.2 million, probably reflecting disruptions to health services caused by the COVID-19 pandemic.

The majority of all groups receiving TB preventive treatment are people living with HIV. TB preventive treatment among household contacts continues to represent a significant gap.

Global number of people provided with TB preventive treatment, 2015-2021

Contacts for the media

Kanya Ndaki, This email address is being protected from spambots. You need JavaScript enabled to view it., +27 83 298 6100

Hervé Verhoosel, This email address is being protected from spambots. You need JavaScript enabled to view it., +33 6 22 59 73 54  

About Unitaid

Unitaid is a global health agency engaged in finding innovative solutions to prevent, diagnose and treat diseases more quickly, cheaply and effectively, in low- and middle-income countries. Its work includes funding initiatives to address major diseases such as HIV/AIDS, malaria and tuberculosis, as well as HIV co-infections and co-morbidities such as cervical cancer and hepatitis C, and cross-cutting areas, such as fever management. Unitaid is hosted by the World Health Organization.

About the Aurum Institute

The Aurum Institute is a proudly African organisation working to advance health science and innovation to create a healthier world for future generations. We partner with governments, the private sector and civil society to design and deliver high-quality care and treatment to people in developing communities.