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OPINION: New research and implementing lessons from COVID-19 are key to SA’s future TB intervention plans

Our health systems endured a heavy – often invisible – cost during the COVID-19 pandemic. While the country was focused on the battle against this pandemic, long-fought gains against other infectious diseases were being rolled back.

And none more so than with tuberculosis.

The Lancet notes that South Africa has one of the highest tuberculosis (TB) burdens in the world, with 304 000 people developing TB in 2021, bringing the country’s incidence rate to 513 per 100 000, according to the World Health Organization’s Global TB Report released recently. In South Africa, the TB epidemic is largely driven by the high HIV prevalence rate, with the disease estimated to kill more people living with HIV (33 000) than those who were HIV negative (23 000) in 2021.

Earlier this year, more than 2 000 healthcare workers labouring to end tuberculosis gathered for the 7th South African Tuberculosis conference to share results from research findings, advocate for implementation of effective strategies with policy makers, and collaboratively plan for the road ahead. Conference delegates included researchers, government & policy makers, community-based health workers, health planners, and civil society activists/advocates.

The conference provided a realistic assessment of the progress and the challenges in TB control, and of the direction which TB control and research plans should now take to achieve South Africa’s tuberculosis prevention and treatment objectives. A few months down the line, we need to keep the momentum going and implement lessons from the COVID-19 pandemic, including pooling our limited resources and increasing the pace to find a TB-preventative vaccine.

Data alerts

Data presented at the conference showed the devastating impact of the COVID-19 pandemic on the uptake of TB prevention, diagnosis, and treatment interventions, dashing all hopes of achieving the global target to end the TB pandemic by 2030

Data from the World Health Organization presented at the conference showed that globally deaths from TB were on the increase from 1.4 million in 2019 to 1.5 million in 2020. This may be attributed to the fact that far fewer people were diagnosed with TB or provided with treatment because of the lockdown and a decline in funding.

Conference chairperson Professor Willem Hanekom highlighted in his opening session that delegates aim to get TB control back on track and that this was only possible if “diverse stakeholders from civil society, government, academia, and the non-governmental sector work together.”

What does tuberculosis control mean? It centres on collectively focusing on four broad themes – pathogenesis of TB-pathogen and host; treatment, and prevention interventions such as drugs, vaccines, and diagnostics; implementation science and health systems; and understanding social and community context. The path to success in managing and achieving TB control requires scientists, service providers, and stakeholders to place their efforts and resources in all four of these areas.

Since South Africa moved out of the COVID-19 lockdown in mid-2022, there has been a recovery in TB testing according to the Department of Health’s Dr Norbert Ndjeka, but this was not enough. The trajectory to ending TB must address – finding people with undiagnosed TB through increasing testing within at-risk population groups, linking and retaining people within care programmes, reducing stigma and promoting family and community support.

Indeed, a dominant theme of the conference was finding the missing TB cases. Dr Limakatso Lebina, from the African Health Research Institute (AHRI), presented data, which showed that between 100 000 to 250 000 people are not diagnosed, evaluated, or initiated on TB treatment. The reasons for this are varied. Many never see health workers, but even when they do, they might not be screened for TB symptoms, and might not have a molecular test requested by the healthcare worker. Often, results of tests fall through the cracks and are not being given back to the patient, or the patient is not being initiated on treatment. In some cases, healthcare workers omit to obtain a sample for a TB diagnosis.

Lebina called for increased community-based, community-led TB screening and testing together with implementing the National Health Insurance scheme. This approach will make services more accessible, reduce patient-born costs through social assistance, and enhance patient empowerment/education to increase demand for TB testing.

Questions about sub-clinical TB

As highlighted at the conference, implementation science and programmes come against the backdrop of scientific developments that are changing our understanding of TB and breaking down our traditional framework for thinking about the disease. We must unlearn ineffective strategies and learn implementation of new strategies.

Along these lines, AHRI’s Dr Emily Wong provided a compelling argument for increased research into understanding sub-clinical TB because the current two-state theory of TB being either active TB disease or latent infection has become outdated. The recent research is proposing two additional states, that of incipient and sub-clinical TB, which we need to learn more of, but which could be key to controlling TB.

Data from several studies have shown that sub-clinical TB, where people are asymptomatic – could be a larger problem with as many as 50% of prevalent TB being sub-clinical. People with asymptomatic TB have no reason to go to clinics, thus remaining undetected, infectious, and therefore driving the burden of disease, as was the case with COVID-19 in South Africa. Dr Wong called for research into establishing a treatment regime for sub-clinical TB to prevent overtreatment, undertreatment, and even mis-categorisation.

There remain many unanswered questions such as the extent to how infectious sub-clinical TB might be, how to screen, identify, and manage subclinical TB. Data is needed from prospective research across multiple settings to guide clinicians and patients diagnosed with sub-clinical TB and to maximise our understanding of the basic science and immunology of TB.

Another exciting area of research is the search for a new TB vaccine. As pointed out by Dr Angelique Luabeya of the South African Tuberculosis Vaccine Initiative (SATVI), the COVID-19 pandemic resulted in a whopping 172 vaccines for COVID-19 moving into clinical trials by September 2022. By comparison, there are only 14 TB vaccines currently in clinical research. Since the development of the BCG vaccine a century ago, no new TB vaccines have reached the market.

More efforts are needed for TB vaccine research to increase the number and diversity of vaccine candidates. This was highlighted at an mRNA technology discussion by Prof Glenda Gray, CEO of SAMRC who stated that with the high prevalence of HIV and TB in South Africa, the mRNA platform provides an opportunity for scientists to use their skills and knowledge in HIV, TB, and COVID-19 to expand on vaccine development and access.

Looking ahead

COVID-19 has been a major setback to both TB control and TB research efforts, but we can claw back the grounds we have lost and progress further if we work collaboratively and efficiently implement lessons from HIV and COVID-19 research and interventions.

Getting this right is critical.

One place where we can start getting this right is in South Africa’s key strategy document for TB and HIV – the National Strategic Plan (NSP) for HIV, STI’s and TB. The new NSP is currently being developed under the leadership of the South African National AIDS Council (SANAC) but collaboration from a wide variety of stakeholders will be needed to make the new NSP a success at implementation level.

A second and related plan in which we must get it right is the Department of Health’s TB recovery plan. Here too, we will need active collaboration from many stakeholders to ensure the plan is successfully implemented.

Among others, active collaboration means sharing of existing resources, skills, and infrastructure set up for HIV and COVID-19 research. We must also continue to build on and develop partnerships with private and public collaborators at a local and international level while at the same time enhancing the existing expertise in South Africa.

25th November 2022 | Kelvin Vollenhoven and Neetha Morar

*Vollenhoven is Communications manager at the South African Tuberculosis Vaccine Initiative, a participant in the 2018 Stop TB Working Group on new Vaccines Advocacy Program and a SAHTAC steering committee member. Morar is Senior Research Manager of HIV, and other Infectious Diseases Research Unit (HIDRU), South African Medical Research Council (SAMRC) and SAHTAC Steering Committee Member

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