A Beacon of Hope: Brooklyn Chest Hospital’s Paediatric TB Research Hub Flourishes
Soft toys, infectious giggles, and the vibrant energy of children fill the wards of Brooklyn Chest Hospital, a testament to the dedicated staff and researchers driving world-class work at its paediatric tuberculosis research hub. This facility, a crucial clinical site for the Desmond Tutu TB Centre, is marking a decade of significant contributions, offering a glimpse into pioneering new treatment trials and the compassionate care provided to its young patients.
Brooklyn Chest Hospital, a sprawling complex of buildings set against the industrial backdrop of Paarden Island in Cape Town, is a place of bright colours and comforting sounds. The paediatric wards are a cheerful sight, with metal cots lining walls adorned with whimsical murals of giraffes and marine life. The air, even at midday, carries the lingering aroma of lunch, a small comfort in a place that can be a long-term home for many.
The hospital is equipped with approximately 300 beds in total, dedicated to patients requiring extended stays for complicated or severe forms of tuberculosis. For children, this can include challenging conditions like TB meningitis and multidrug-resistant TB. The dedicated paediatric unit boasts 40 beds, currently housing 31 children. Depending on the severity of their illness and their social circumstances, a child’s stay can range from two months to, in rare instances, over three years.
Compassionate Care Beyond Medication
Within these wards, the focus extends far beyond medical treatment. In one room, Noxolo Mlata, an educator, engages a group of children aged three to six with a reading session, their small fingers eagerly pointing to colours on the pages. Nearby, nurse Goodness Ngubane gently feeds a young boy in a wheelchair, his excitement palpable as he interacts with her.
Importantly, staff members in the wards do not wear masks, as the young patients are not considered an infection risk. Sister Anastasia Cornelius explains that children ranging from three months to twelve years old are admitted to this unit. Adolescents are typically transferred to the adult wards. She points to the boy being cared for by Ngubane, noting, “We have one boy who is 13 years old, because he is small for his age with special needs. He has been here for more than three years and is cured of TB meningitis, but his family cannot take care of him. He will need a special home.”
Cornelius cradles a toddler, her voice filled with affection. “This one is very intelligent. She arrived two days ago from Red Cross [War Memorial Children’s Hospital]. When her mum left yesterday, she was crying, but now she is doing well.” Another child clutches a unicorn soft toy, while Ngubane receives a shower of kisses from a lively young boy.
In a sunlit playroom, a woman tenderly feeds an infant nestled in her lap. While parents are welcome to visit, overnight stays are not permitted. “We love them so much, all of them,” Cornelius affirms. “They need a particular level of care; it’s not just about money and [medication] adherence, they need love and understanding, kindness.” The staff are actively establishing a dedicated reading room and are seeking volunteers to read to the children on weekends.
A Hub for Global TB Research Excellence
A short walk from the wards leads to a modest prefab building, the nerve centre of groundbreaking scientific endeavours. Brooklyn Chest Hospital serves as a key clinical site for the Desmond Tutu TB Centre, affiliated with Stellenbosch University, and has emerged as a premier international hub for paediatric TB research. The centre’s vital work has directly influenced World Health Organisation (WHO) guidelines for treating TB in children and adolescents.
One significant impact is the WHO’s recommendation for a shortened treatment course of just four months for children aged three months to sixteen years with non-severe TB, a reduction from the previous six months. Severe TB in children is defined as life-threatening disease, encompassing conditions like TB meningitis or TB affecting critical organs. This shorter regimen not only benefits young patients and their caregivers but also alleviates pressure on public health resources. The SHINE trial (Shorter Treatment for Minimal Tuberculosis in Children), which involved 1,204 young participants across four countries, provided crucial evidence for this WHO recommendation. The Desmond Tutu TB Centre played a pivotal role in implementing the South African arm of the trial, enrolling 315 participants in Cape Town, including some from Brooklyn Chest Hospital.
In South Africa, the adoption of the four-month treatment for non-severe TB was officially incorporated into the National Department of Health’s 2024 guidelines. Dr. Norbert Ndjeka, a leading TB official within the department, confirmed this shift.
At the Desmond Tutu TB Centre’s on-site offices, research clinician Dr. Susan Purchase elaborates on the complexities of treating young patients. “Many of the children in these wards don’t have severe TB but they have social problems at home, so they don’t actually have a caregiver who is able to give them medicine,” she explains. “Some may have TB meningitis, which is a severe form of TB that requires a higher level of care. TB meningitis can have terrible consequences where a child is left quite disabled for life, and they will need specific care.” TB meningitis occurs when the protective membranes surrounding the brain become inflamed due to a TB infection.
Reflecting on the Desmond Tutu TB Centre’s research unit, established ten years ago on the hospital grounds, Purchase highlights their initial focus on pharmacokinetics – understanding how drugs move through the body. “We were testing all these adult drugs in children of different ages to try and work out the correct dosing,” she states. “Because you think: ‘Oh well, if a child weighs half what an adult weighs, you can give them half the dose,’ but that’s not at all true. They have [structurally and functionally] different livers and kidneys and they process the medications differently.”
A notable achievement of the centre has been the evaluation of the dosing and safety of bedaquiline and delamanid in children. These relatively new TB drugs have revolutionized the treatment of multidrug-resistant TB in adults. The research confirmed their safety and efficacy across all age groups of children, leading to their inclusion in the WHO’s 2022 guidelines for paediatric TB treatment.
The DTTC PK unit, located at Brooklyn Chest TB Hospital, comprises a 30-person research team dedicated to designing and executing highly specialized clinical trials. Their work explores the pharmacokinetics, safety, and acceptability of key drugs and regimens used in paediatric TB treatment.
Ten years ago, Purchase notes, patients with drug-resistant TB were treated with amikacin, a highly toxic antibiotic. “Injected every day for six months or more, this was a problem in itself, as it’s a painful injection, but then it also caused about a third of the kids to go deaf. So that was a huge issue to try and test hearing, but testing hearing in young children is also not easy, it’s subtle”. Amikacin and another injectable antibiotic, kanamycin, were also known to cause hearing loss in many adults.
The introduction of bedaquiline approximately a decade ago ushered in a safer, all-oral treatment regimen. This shift allowed for home-based treatment, reducing hospital stays and eliminating amikacin-related hearing loss. Despite these advancements, treatment remains challenging. Purchase mentions that most young patients take a combination of four or five different tablets daily, often requiring them to be crushed.
Her own research has focused on “the acceptability of these kind of medicines for young children,” a significant hurdle given that the drugs are frequently “appallingly bitter” despite taste-masking efforts. She has observed that children as young as three years old learn to swallow the tablets, recognizing it as a preferable alternative to the unpleasant taste.
The Diagnostic Puzzle of Paediatric TB
Diagnosing TB in children presents a far greater challenge than in adults, according to Purchase. “We call it a puzzle because you need lots of different pieces to fit together. It’s a combination of first asking about their symptoms; adults cough blood, they sweat and they lose weight, whereas children might just not grow along their curve as you would expect them to.”
A major complicating factor in identifying childhood TB is the reliance on sputum samples, typically coughed up from the lungs. Children often struggle to produce these samples on demand, limiting the diagnostic value of standard TB tests. “You can’t ask a one-year-old to cough into a sputum bottle, so then we do gastric aspirates for children, we actually pass a nasogastric tube into their stomach to aspirate what they swallow,” Purchase explains. This method works because children frequently cough up phlegm from their lungs, which they then swallow.
In light of the difficulties in obtaining sputum samples, significant research has been dedicated to exploring alternative methods, such as stool samples and tongue swabs. While research in these areas continues, the WHO already recommends the use of stool samples in its guidelines, though the evidence for their sensitivity is not as robust as for sputum. “Stool samples are most useful in HIV-positive patients,” says Purchase. “But it’s not a good diagnostic tool. And we also have used urine but it’s mainly effective in people who have quite a depressed immune system from HIV. So it’s not a useful tool in the average child.”
Purchase expresses greater optimism regarding the potential of tongue swabs, noting that while currently being tested in adults, they are not yet evaluated in children. “It would be a huge advantage if we could simply just do a quick swab and within a few hours you could have a result, that would be a game changer. But we’re not there quite yet,” she states.
Although chest X-rays are primarily considered a screening tool rather than a definitive diagnostic method for TB, they have seen a resurgence in recent years with the development of portable X-ray units for community-based screening. However, paediatric diagnostics often lag behind. Purchase points out that interpreting children’s X-rays is more difficult than those of adults.
The Desmond Tutu TB Centre is currently involved in new research exploring automated chest X-ray readings for children. “So that nurses and junior doctors in resource-limited areas can actually get an image read by AI, rather than needing a pulmonologist [a doctor who specialises in the lungs] or someone with lots of experience in reading children’s x-rays,” she explains.
Complementing this effort, a study led by Professor James Seddon of the Desmond Tutu TB Centre, published in The Lancet Child & Adolescent Health in 2023, analysed data from 4,718 children with pulmonary TB across 12 countries. The study aimed to develop a data-driven algorithm to assist front-line health workers in clinical treatment decisions. These findings were also incorporated into the 2022 WHO guidelines for paediatric TB treatment. As researchers strive to bridge the diagnostic gap for TB in children, clinicians continue to piece together information from various sources to make informed decisions.
A Groundbreaking Collaboration with South Korea
The investigation continues at the Desmond Tutu TB Centre’s headquarters on Stellenbosch University’s medical campus, adjacent to Tygerberg Hospital. Inside her office, Professor Anneke Hesseling works in proximity to a large photograph of the late Archbishop Desmond Tutu. The centre, founded in 2003, found its official patron in Tutu in 2004, a personal connection given his own childhood experience with TB.
As the director of the Desmond Tutu TB Centre for the past decade, Hesseling has navigated significant challenges, particularly following funding cuts from the United States, which previously accounted for approximately 70% of the centre’s funding through National Institutes of Health grants. Over the past year, the centre has actively sought new collaborations, with promising opportunities emerging in Korea and Japan.
Hesseling excitedly describes a “cutting-edge trial” they have designed in collaboration with “wonderful Korean colleagues” from the Korean National Institute of Health. This collaboration, initiated last year, focuses on an adult multidrug-resistant TB trial.
The study will investigate delpazolid, a new antibiotic developed in South Korea, primarily intended for treating multidrug-resistant TB. Hesseling expresses hope that delpazolid will eventually replace linezolid, a currently used but highly toxic antibiotic for drug-resistant TB. The initial phase of testing will involve adults, followed by trials in children.
“The current drug we use is linezolid and it’s very, very toxic in everyone, so people get peripheral neuropathy. They go blind, they get bone marrow suppression,” she states. “[Delpazolid] just looks much safer, so it’s super exciting. It’s also interesting learning to collaborate with a completely different culture and language, I mean our conference calls with our Korean colleagues, half of the conversation is in Korean, which we don’t understand, so we have to just politely wait…”
Hesseling emphasizes that this World TB Day is a celebration of resilience for the centre. “The last year has been a bit rough, but things are looking up,” she shares. “This World TB Day will be a celebration of what we have actually not only survived, but how we’ve thrived, and how resilient we are. We’re not being bitter, not being angry. It’s a celebration of how much we can do as a team. How much resources we actually have if we work together well, how many new collaborations, new opportunities.”
