Leading in TB research earns Prof Keertan Dheda the 2023 Alan Pifer Award

The week Professor Keertan Dheda accepted his Alan Pifer Award was a busy one. He had just returned from out-of-town research site visits and on the day of the award ceremony, he was on call at Groote Schuur Hospital’s ICU. He arrived at the event having just submitted a lengthy NIH funding proposal – having made the deadline with less than a minute to spare. Despite his demanding responsibilities, he stepped away to address attendees of the University of Cape Town’s (UCT) annual Research Celebration held on 4 December 2024. It was here that he reflected on the decades of impactful clinical research that earned him this prestigious recognition.

Addressing the audience at the UCT’s Neuroscience Institute, Professor Dheda humbly deflected individual praise during his acceptance speech. Instead crediting the award to the collective efforts of his dedicated team, all united by a single mission: reducing the burden of tuberculosis (TB) in vulnerable communities.

“I have to emphasise that I am a figurehead representing a very large group of people and much of the credit and hard work must be attributed to them rather than myself,” he said.

The Alan Pifer award is a prestigious prize, awarded annually by the vice-chancellor, to honour exceptional research dedicated to advancing societal welfare. Created in memory of Alan Pifer, a renowned philanthropist and former president of the Carnegie Corporation, the award celebrates his enduring legacy. Pifer dedicated his career to championing social justice and uplifting historically marginalised communities, with a strong focus on advocating for women's rights.

“I don’t know how all [of] you do it, to bring us the glory that you bring to UCT combined with all of the work you do for science, research and impact,” the Vice-Chancellor, Professor Mosa Moshabela said when conferring the award.

While Dheda’s work is firmly rooted in academic excellence and scientific innovation, its hallmark remains societal impact – a focus also recently recognised by the Academy of Science of South Africa (ASSAf) when he received the 2024 Science-for-Society Gold Medal. Striving to direct his influence toward reducing the TB burden in vulnerable communities is a constant intention of his work.

Why respiratory medicine research?

For Dheda, who is a global leader in TB research based at UCT’s Faculty of Health Sciences and a member of the Institute of Infectious Disease and Molecular Medicine (IDM), the journey began during his medical training. As a student at Baragwanath Hospital and later as a young doctor at King Edward Hospital, Dheda witnessed firsthand the devastation caused by undiagnosed TB. He was particularly struck by the tragic deaths of young people – a loss often caused by misdiagnosis at the time.

“It was obvious at that early stage that many people with TB (more than 60% we now know) cannot produce adequate sputum and yet this was the predominant way in which we attempted to make the diagnosis,” Dheda explained.

This is what would spawn his interest in the field of respiratory medicine and later his groundbreaking research. Today, he is the named inventor and co-inventor on nine patents related to new TB diagnostics and therapeutics, one of which has been developed as a user-friendly test for extra-pulmonary tuberculosis – a form of TB that affects areas beyond the lungs, such as the bones, joints, kidneys and the brain.

Advancing global TB research and saving lives

As the director of the Centre of Lung Infection and Immunity (CLII) and the CLII Clinical Trials Unit at the UCT Lung Institute, Dheda has spent two decades influencing policy – both locally and globally. One of his team’s most noteworthy contributions was a landmark trial that catalysed the World Health Organization’s (WHO) first guidelines on when and how to use urine TB lipoarabinomannan (LAM) tests.

“I am particularly proud of this work, which demonstrated mortality reduction using urine LAM in hospitalised TB patients with advanced HIV,” Dheda reflected. This study not only led to WHO’s endorsement and the large-scale rollout of the test in Africa but is also estimated to have saved 40 000 lives per year on the continent alone.

Dheda and his team are renowned for revolutionising active case finding, a model that brings TB screening and diagnosis to the community rather than waiting for patients to self-report to healthcare facilities. Using battery-operated DNA diagnostics within a mini-mobile clinic, their scalable approach has already screened over 150 000 people across four countries. Looking ahead to 2025, they aim to take this innovation further by launching mini mobile clinics across South Africa’s major cities, supported by the Global Fund.

His work has also been pivotal in understanding and addressing drug-resistant TB – one of the greatest and poorly understood challenges in the global fight against the disease – and that contributes 25% of the total global cost of anti-microbial resistance due to any organism.

“TB afflicts the most vulnerable from our communities.”

Importantly, Dheda’s work has challenged long-standing assumptions about the origins of drug resistance. For many years, patients were often ‘blamed’ for developing resistance due to presumed non-compliance or improper use of medication. However, his team demonstrated that drug resistance is rather driven by the poor penetration of certain antibiotics (e.g. fluoroquinolones) into TB cavities – areas where the bacteria thrive and are protected.

“Some drugs are naturally prone to developing resistance because they cannot effectively penetrate TB cavities,” Dheda explained. This finding has reshaped thinking around drug development and treatment protocols for resistant TB.

Giving communities a better fighting chance

In 2014, Dheda took his dedication to fight TB a step further by founding FreeOfTB, a non-profit organisation (NPO) aimed at raising funds to fight South Africa’s “diseases of poverty”: TB, HIV and pneumonia.

TB is the leading infectious cause of death worldwide and South Africa is among the WHO’s list of high-burden TB countries. Despite being a middle-income country, unemployment and extreme inequality fuel the TB crisis. This disease is closely linked to poverty and is worsened by poor nutrition and overcrowded living conditions, which are common in South Africa.

“TB afflicts the most vulnerable from our communities,” Dheda said, also acknowledging the scarcity of charitable organisations and by extension funding dedicated to fighting the disease.

Since its inception, FreeOfTB has made considerable contributions to the fight against TB. In recent years, the NPO has been focused on providing urine-based TB diagnostic tests to healthcare facilities that could not procure them. Beyond diagnostics, the organisation runs community-based education projects during their case-finding studies to raise awareness about TB and improve early detection. They recently donated a new blood gas machine to the Brooklyn Chest TB Hospital, enabling patients to be prescribed lifesaving oxygen when they are discharged home.

During one of their case finding studies, after recognising a critical gap at the Brooklyn Chest TB Hospital, FreeOfTB is in the process of building a library for patients, particularly children. “[This] will enormously improve the lives of patients, especially the children who can spend a large part of time hospitalised,” he said. Last week, they donated a new snooker table and table tennis board to establish a recreational centre at the hospital.

Dheda is also a professor in Mycobacteriology and Global Health at the London School of Hygiene and Tropical Medicine where he has contributed expertise to several seminal studies as part of ensuring that TB solutions are affordable and made available.

Looking into the future: TB prevention and improved care

Dheda is optimistic that the most significant breakthrough in TB eradication will come from preventative measures, particularly a TB vaccine. His team is currently working on an inhaled formulation of the TB vaccine, bacille Calmette-Guérin (BCG) – being designed as a dry powder inhaler – and that has the potential to make a massive dent on the global TB burden.

“Animal studies have been very promising,” he shared. “We’re already in the second phase of this work, where we’ve challenged healthy individuals with live mycobacteria in the form of BCG. In the next phase, we hope to advance the inhaled formulation. This approach could be pivotal in reducing TB cases and we’re incredibly excited about its potential impact.”

Reflecting on these groundbreaking initiatives, Dheda added, “it is a privilege to be at the forefront of research that not only advances scientific knowledge but also delivers real-world solutions to those most affected by TB.”