University of the Witwatersrand: SA research leads to new WHO guidelines for improved TB treatment

The World Health Organization (WHO) has announced key changes to the treatment of drug-resistant tuberculosis (DR-TB), a significant development which will benefit patients with DR-TB in SA and globally. Treatment time has been slashed from 18 months to six, the number of pills reduced from 23 a day to 23 per week, painful injections eliminated and side-effects reduced.

The research also revealed that nine out of every ten patients treated with the new regimen will be cured, offering hope to those who have DR-TB. Through an early access programme, some DR-TB patients in SA are already benefiting from the new regimen.

Under the leadership of Dr Norbert Ndjeka, recently appointed by SA’s National Department of Health as chief director of TB, much of this pivotal research was conducted by the University of the Witwatersrand and the Clinical HIV Research Unit (CHRU) as part of clinical trials including the Nix-TB and ZeNix studies conducted by the Global TB Alliance. The trials mostly conducted in SA produced robust data which changed international policy.

Dr Ndjeka explains, “The new WHO guidelines allow almost all forms of DR-TB to be treated with either BPaLM (a combination of bedaquiline, pretomanid, linezolid and moxifloxacin) or BPaL (bedaquiline, pretomanid and linezolid). We welcome the WHO announcement which facilitates rapid implementation of the new regimen.”

Pretomanid first received regulatory approval in August 2019 for the treatment of certain forms of highly drug-resistant TB. BPaL was most recently evaluated in TB Alliance’s ZeNix trial. The BPaLM regimen was evaluated in the successful TB-PRACTECAL trial, sponsored by Médecins Sans Frontières, in which CHRU participated under the leadership of Dr Mohammed Rassool.

Dr Francesca Conradie, an infectious diseases researcher in the School of Clinical Medicine at Wits, executive director of CHRU’s Isango Lethemba TB research unit and principal investigator of the Nix-TB and ZeNix clinical trials, says, “The timing has been lightning speed from the findings of the clinical trials to the adoption by the WHO of the treatments tested. This achievement speaks to South Africa’s TB programme and Dr Ndjeka’s visionary approach to addressing TB, which includes a strong focus on rigorous research. Under his leadership, we have been delivering this treatment to those that need it most under the BPaL clinical access programme since March 2021.”

Dr Conradie is also the principal investigator of the BPaL clinical access programme in SA which is funded by USAID.

“The treatment of drug resistant TB has been a rapidly changing field in the last 10 years and new medicines for DR-TB have been rapidly incorporated into the South African national TB programme,” she adds.

Professor Shabir Mahdi, Dean of the Faculty of Health Sciences and Professor of Vaccinology at Wits, says, “In this centenary year of the University of the Witwatersrand, our researchers continue to produce ground-breaking research of international importance and more so for South Africa and Africa. The findings from this study will inform treatment programmes across the world, make treatment of the deadly scourge of TB more tolerable for patients, improve outcomes for patients and relieve pressure on health systems.”

Conradie explains that the updates announced by the WHO include shorter novel six-month all-oral regimens for the treatment of multidrug and rifampicin-resistant TB (MDR/RR-TB), with or without additional resistance to fluoroquinolones (pre-XDR-TB). The new regimen consists of only three or four medications, namely, bedaquiline, pretomanid, and linezolid, with the addition of moxifloxacin.

“In addition, based on data from SA’s national TB programme, the WHO has also recommended an alternative 9-month all-oral regimen for the treatment of MDR/RR-TB. In this regimen an older drug, ethionamide has been replaced with a newer drug, linezolid. Ethionamide has many side effects that often deter patients from completing their treatment.”

According to the WHO, TB remains a threat to global public health and is one of the leading infectious causes of death globally. In 2020, an estimated ten million people developed TB and 1.5 million died from the disease. Owing to the impact of Covid-19, TB incidence could increase globally in 2022 and 2023.

“South Africa has once again delivered trailblazing research which will improve outcomes for patients with DR-TB in South Africa and internationally. This accomplishment has inspired us to continue our work in addressing the TB burden through research that produces better and shorter treatments that can cure the disease,” concludes Dr Ndjeka.

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