$200m TB research programme derailed by US funding cuts

While it is one of the oldest diseases around, TB still kills more people on the planet than any other disease caused by a single infectious agent. The disease is common in developing and middle-income countries such as South Africa, India and Indonesia, but it also occurs in wealthy countries. A recent outbreak in Kansas in the US has been described as “one of the largest” TB outbreaks in US history.

Many in TB circles were excited when, in August 2022, it was announced that the US government was backing a five-year global research programme called SMART4TB. Worth up to $200m, the money would fund a series of clinical trials of new TB treatments and tests — while also helping to build research capacity in developing countries. The money was to come from the US Agency for International Development (USAID).

But in January, recipients of US aid around the world were left reeling when stop-work orders were issued and funding was frozen following US President Donald Trump’s executive order halting US foreign funding for 90 days pending a review for “programmatic efficiencies and consistency with US foreign policy”.

This placed immediate strain on organisations dependent on funding from the US — through the US President’s Emergency Plan for Aids Relief (Pepfar), National Institutes of Health (NIH), the Centers for Disease Control & Prevention (CDC) and USAID. With many potential lifesaving services, like this clinic in Pretoria, having to abruptly close, patients have been left without a way of accessing HIV treatment and other essential health services. Pepfar funds are typically distributed via the CDC or USAID.

In the weeks since, some funding had been temporarily restored through waivers and court orders. However, the reprieve came to an abrupt halt on February 27, when South African organisations reliant on PEPFAR funding through USAID had their grants permanently terminated. The terminations were not limited to South Africa.

One of the biggest TB research grants in history is being axed

One of the many projects that received termination letters is the SMART4TB programme. The project, co-ordinated by Johns Hopkins Medicine, was set to support several important TB studies, some of which were to be conducted in South Africa.

The Global Fund's TB update for April/May 2024 showed that SMART4TB was working with local partners and communities on several key TB trials. These included the ADAPT and ADAPT for Kids studies, which evaluated new TB diagnostic tests in adults and children, including the use of tongue swabs. For TB treatment, SMART4TB was running the SMILE and PRISM trials to test shorter TB regimens — one for children and the other for adults — and the BREACH trial to test a shorter TB prevention treatment for adults.

SMART4TB also aimed to improve TB vaccine preparedness, find ways to interrupt TB transmission, and conduct operational research to improve TB programmes, as outlined in this presentation given to South Africa’s TB Think Tank.

Initially, all SMART4TB’s projects in South Africa, and elsewhere, had been paused but it was confirmed last Friday that the SMART4TB agreement had been terminated by USAID. Whether an earlier waiver for one of the trials would still be in effect wasn’t yet clear.

“The Trump administration [has] terminated SMART4TB … It is devastating to all involved. We are working to determine next steps,” Prof Richard Chaisson, who used to be the chief of party for SMART4TB at Johns Hopkins, tells Spotlight.

The impact

Erica Lessem, the former director of community engagement and policy for SMART4TB, tells Spotlight that their work was an “unprecedented opportunity”, not only due to the size of the award but because of the extensive TB expertise the project brought together.

She describes the way SMART4TB was going to conduct research as “groundbreaking”. It was going to include communities while also focusing on populations that are normally excluded, like children and pregnant and lactating people. “SMART4TB was intended to work on so many important issues in TB that affect not just people in high-burden countries, but Americans as well. And it’s really such a shame to lose the ability to advance that work,” Lessem says.

While the project has accomplished a lot of important things during the past 2½ years that will be useful beyond its closure, Lessem says that stopping the project so abruptly, after all the hard work and the investment of millions of dollars given by US taxpayers, is wasteful.

The impact of this will be felt across multiple areas, including research projects that were about to start but won’t be able to now. “These trials were going to answer some really important outstanding research questions and that is not going to happen now,” Lessem says. Some of the research was set to help answer questions like how regimens for TB prevention could be made shorter and safer, if TB treatment for children could be shortened further, and if TB treatment could move beyond a “one-size-fits-all” approach.

Another important project that had to be halted, according to Lessem, is the BETTER project, a global collaboration of frontline clinicians, civil society and TB policymakers. Together with SMART4TB, the BETTER project had published a clinical field guide for how to treat people living with TB who had “expanded drug resistance” — meaning they had TB which is resistant to some of the new TB drugs like bedaquiline, clofazimine, delamanid, linezolid and pretomanid.

The BETTER project, with funding from SMART4TB, had been working on a more extensive document, recommendations for further research as well as finding pathways to granting access to some of the newer TB drugs currently in development, Lessem says. This is now on hold.

Local projects derailed

One of the five regional SMART4TB hubs was located at Wits University’s Perinatal HIV Research Unit in Soweto. Last year, SMART4TB announced the launch of two operational research projects in South Africa, set to improve TB prevention as well as early treatment in TB contacts.

“That work was going to be immediately relevant to how TB is handled in South Africa,” Lessem says. “I hope they’re able to continue in some other capacity.”

One of these projects was set to be run by the nonprofit TB Proof. The project was “ready to go” before the funding cuts, director Ingrid Schoeman tells Spotlight.

The project would have focused on strengthening the tracing of contacts of people with TB. Schoeman says they were excited about this project as it aims to strengthen the implementation of contact tracing and treatment for TB through participatory approaches in the Khayelitsha and eastern substructure districts in the Western Cape.

The project aimed to “co-develop interventions with health workers, policymakers, TB patients and affected communities, and to create demand for quality TB services at local level”. In this way, Schoeman explains, the project was set to support the implementation of the targeted universal TB testing policy — an approach where everyone who is considered at a high risk for TB is tested instead of only testing when TB symptoms are present.

Schoeman says TB testing and contact tracing overall needs to be expanded as it is the main pillar of South Africa’s TB Recovery Plan, and efforts should be made to test people in their own communities outside of working hours.

“It may sound like it’s not a big deal. But South Africa’s TB Prevalence Survey showed that the majority of people with TB had no TB symptoms, so testing close TB contacts regardless of having TB symptoms is a big advancement in closing TB care cascade gaps,” Schoeman says. “But I’ve seen people waiting too long to get tested [for TB] and without getting treated, one remains infectious, and TB continues to spread in the community.”

She adds that another one of TB Proof’s projects, a partnership with the Stop TB Partnership Challenge Facility for Civil Society project, is also paused. This initiative, which started in 2020, aims to develop TB stigma interventions for people who have been diagnosed with TB.

Many TB programmes disrupted

The USAID funding cuts and uncertainty have already had a significant impact on TB services and research programmes around the world.

A rapid assessment by the Stop TB Partnership, using available data from 12 high-burden countries, shows that many TB services and programmes have been disrupted. The gaps this has caused in TB service delivery, diagnosis and treatment adherence could lead to an increase in transmission and mortality.

South Africa was not included in this assessment, but the conclusion of the report is nevertheless sobering.

It says: “The suspension of US government funding has caused widespread disruptions across multiple aspects of TB response in high-burden countries. While some mitigation measures are being explored, the long-term impact on TB control efforts could be severe if funding is not restored promptly.”

These disruptions will now be compounded by the termination of USAID grants.

Reducing investment in TB has previously led to poor outcomes. A 1998 British Medical Journal article linked the sharp rise in TB cases in the US starting in the late 1980s to funding cuts in the 1970s, problems within New York’s TB control system, and social factors like inequality and the spread of HIV during the 1980s.

Citing this outbreak as an example of the risks and inefficiency of reducing TB services and research, Dr Jennifer Furin, a TB doctor and lecturer at Harvard Medical School in Boston, warned that cutting TB research funding would be disastrous. “When they cut TB work [research and services] in the 1990s, an outbreak occurred in New York City that cost more than a billion dollars to get under control. And many people died,” she told Spotlight before SMART4TB's termination was confirmed. “In fact, the US government — if it cares about security, safety and family — should be investing more in TB.”

Globally, the US government has until now been the largest funder of TB research by some distance. It spent $476m through the CDC, NIH and USAID on TB research in 2023, according to a report by the Treatment Action Group.

*This article was first published by Spotlight – health journalism in the public interest. Sign up to the Spotlight newsletter.