Tackling TB: all hands on deck

During 2017, 1.6 million people died from tuberculosis (TB). This is according to the World Health Organization’s (WHO) Global Tuberculosis Report released last year. In 2017, TB resulted in 22 000 deaths among HIV-negative South Africans and 56 000 deaths among those with HIV. With at least 330 people dying daily, TB is the leading natural cause of death in the country.

The University of Cape Town’s (UCT) Institute of Infectious Disease and Molecular Medicine (IDM), based within the Faculty of Health Sciences, is a leading research centre on infectious disease in Africa.

“Unfortunately, we have a high burden of TB in this country, and Cape Town is a heavily TB-burdened city with high rates of HIV co-infection,” says Professor Valerie Mizrahi, director of the IDM. “However, we have a strong group of TB researchers in the IDM and elsewhere in the university.

“Our research groups have established outstanding clinical and laboratory capabilities for investigating new ways to intervene in TB by working at the intersection of the laboratory, clinic and community. We are able to bring many disciplines to bear on this problem.”

The IDM covers the full spectrum of TB research – something for which UCT is recognised internationally. “We work along the entire continuum: from fundamental research on the biology of Mycobacterium tuberculosis – the causative agent of TB – through to preclinical and clinical research.

“We have a high burden of TB in this country, and Cape Town is a heavily TB-burdened city with high rates of HIV co-infection.”

“Our researchers are particularly well known for their work on understanding the progress from infection to disease; for evaluating new interventions, in particular vaccine candidates and new diagnostics; and for novel biomarker discovery,” says Mizrahi. Biomarkers are used in medicine as measurable indicators of disease.

The cost of care

The health economics of TB cannot be ignored. There’s a substantial cost, often carried by impoverished families, to support a relative living with the disease. A report cited in The Economist shed some light on the cost of TB treatment and care: Treating a case of drug-resistant TB can be eight to 25 times more expensive than treating a case of drug-sensitive TB. In the next 35 years, multi-drug resistant TB could cost the global economy USD16.7 trillion.   

Mizrahi estimates that of the research revenue raised by members of the IDM, at least 20 to 30% supports research on TB. This includes a major focus on HIV-associated TB.

Up close and personal

It’s an alarming reality that working in what seems to be the epicentre of TB means engaging with more patients daily than institutions in the north do in a year. It is estimated that at least eight out of every 10 South Africans have been infected with the TB bacterium.

“We don’t need to be inspired here to work on TB because we see it daily”, adds Mizrahi. “In a room of students and staff in the IDM, many would have been affected in some way by TB.” The Student Development and Support Committee for the UCT Faculty of Health Sciences reports that about seven students contract TB annually.

“We need a suite of new tools to control TB more effectively and have the kind of impact on the epidemic that’s needed to meet the ambitious targets set in the WHO’s End TB Strategy.”

For Mizrahi the disease is up close and personal. “Both my mother and father had TB.” A reality which she thinks offers the institution an edge. “It’s sobering, yet inspiring to work on a disease with such urgent unmet needs.

“We need a suite of new tools to control TB more effectively and have the kind of impact on the epidemic that’s needed to meet the ambitious targets set in the WHO’s End TB Strategy. And we here, at UCT, are part of a global community of researchers in active pursuit of those, namely, diagnostics, biomarkers, drugs and vaccines.”

Leading-edge research

Working under the umbrella of the IDM are the South African Tuberculosis Vaccine Initiative (SATVI), the Wellcome Centre for Infectious Disease Research in Africa (CIDRI-Africa) and the Desmond Tutu HIV Centre (DTHC), among others. In 2018, these groups announced some major research findings that have brought hope to the field.

SATVI and DTHC examined whether a new vaccine (H4:IC31) or re-administration of the childhood vaccine BCG could protect adolescents from infection by M. tuberculosis. They found that sustained infection could be prevented by revaccinating patients with the currently available BCG vaccine, providing proof-of-concept for the researchers’ trial design, which was novel, and highlighting the crucial question of whether BCG revaccination of TB-uninfected populations could have a long-term impact on the disease.

“I’d like to see a world free of TB in my lifetime.”

SATVI and CIDRI-Africa worked together on a study of a new TB vaccine, currently known by the code M72/AS01E. It was found to cut the rate of TB lung disease in adults by more than half.

In February this year, the Desmond Tutu HIV Foundation launched its Aerobiology TB Research Facility in Masiphumelele. The site is surrounded by 23 000 residents in the informal settlement. The building houses internationally renowned UCT researchers and scientists, as well as support staff whose work forms part of the TB project in collaboration with the IDM. The Desmond Tutu HIV Foundation, the Bill and Melinda Gates Foundation and the South African Medical Research Council sponsor this work.

Maintaining awareness, speaking out and destigmatising the problem are important, says Mizrahi. “South Africa, with its high disease burden, gives us a special responsibility to play a leading role in tackling this problem… What we still haven’t gotten quite right is how to advocate more powerfully for TB in the way that has been done for HIV/AIDS.

“Advocacy plays a crucial role in heightening public awareness and keeping the disease at the forefront of people’s minds.

“We need to do better. We need new tools. I’m proud to be part of a research enterprise that’s contributing so significantly to global efforts to control TB.” Mizrahi concludes, “I’d like to see a world free of TB in my lifetime.”