Drug-resistant tuberculosis (DR-TB) poses a significant global health challenge, marked by its high mortality rate, the exorbitant cost of treatment and the risk of transmission. In the year 2021 alone, an estimated 450 000 DR-TB cases were reported worldwide, resulting in 191 000 fatalities.
South Africa reportedly grapples with one of the highest DR-TB patient burdens globally, yet merely 50% of these patients commence treatment.
Dr Brigitta Derendinger, a researcher at Stellenbosch University’s Faculty of Medicine and Health Sciences, embarked on a comprehensive study that highlights the looming threat DR-TB poses to the World Health Organisation’s (WHO) END-TB strategy, an initiative that aims to eliminate tuberculosis globally by the year 2035.
Also read: Reducing the stigma of suicide this World Suicide Prevention Day
According to Stellenbosch University, Dr Derendinger’s research highlights the pressing need for innovative and expedited methods for diagnosing DR-TB, which are essential for curtailing transmission, improving treatment and ultimately saving lives. She also delved into characterising the programmatic emergence of resistance to bedaquiline, a groundbreaking TB drug and the first of its kind in nearly four decades.
Bedaquiline plays a vital role in injectable-free regimens for DR-TB.
Dr Derendinger points out that commonly used tests for TB diagnosis, such as Xpert MTB and RIF Ultra, still necessitate a second sputum sample to confirm resistance to rifampicin, a frequent TB treatment, and to diagnose resistance to second-line drugs.
Also, MTBDRplus and MTBDRsl, two molecular tests backed by the WHO, are used regularly to confirm DR-TB diagnoses and find out if the patient is resistant to other drugs.
She observes, ‘Since the roll-out of Xpert, Ultra and MTBDRplus in South Africa, the time from the initial diagnosis of multi-drug-resistant TB to when the patient starts to receive treatment has shortened, but this process is still long.’
Furthermore, in many high-TB-burden countries, there is reportedly a severe shortage of biosafety facilities and infrastructure for DNA extraction and additional molecular testing. Consequently, there is an urgent need to expedite the diagnostic process and enhance rapid molecular methods to reduce reliance on second sputum samples.
Cape {town} Etc discount: Appreciate the beauty of Cape Town with a 60-minute cruise for R155 (valued at R310). Get it here.
To address these challenges, Dr Derendinger extracted DNA from used Xpert cartridges (known as cartridge extract, CE) that would otherwise be discarded by laboratories. From this single cartridge extract, she conducted both first-line (MTBDRplus) and second-line (MTBDRsl) TB drug tests. This approach not only expedited DR-TB diagnosis but also eliminated the need for collecting a second specimen.
‘We* have identified ways to reduce the need for the collection of a second sputum sample, thereby potentially reducing the time it takes to make a diagnosis from weeks to a few days. A quicker diagnosis will mean that patients can be placed on treatment sooner,’ Dr Derendinger stated.
The research demonstrated the value of adjusting a parameter used in MTBDRplus and MTBDRsl tests. This adjustment enhanced the diagnosis of DR-TB in more patients and facilitated their timely placement on effective treatment regimens.
Regarding bedaquiline, Dr Derendinger highlighted its rapid scale-up but lamented the lack of widespread TB drug testing. The WHO recommends such testing for all bedaquiline recipients to monitor their treatment, but this is not consistently practised in South Africa, with only a few centralised laboratories possessing the necessary capacity.
This deficiency allegedly contributes to diagnostic delays.
Explore Cape Town and its surroundings with these incredible deals on cars for under 100k. Find car listings here.
‘Clinical bedaquiline resistance is emerging, but the data is scarce, especially in settings where patients are more likely to experience delays and drug shortages, receive less support and are monitored even less than patients on clinical trials,’ said Dr Derendinger.
There is therefore an imperative to optimise established molecular DR-TB tests and develop new ones to monitor resistance to innovative drugs like bedaquiline. This will be crucial in reducing delayed diagnoses and the ongoing transmission of drug-resistant tuberculosis.
Dr Derendinger’s findings have reportedly had a significant impact on influencing WHO training materials and contributing to global laboratory performance and quality assessments.
*Dr Derendinger acknowledges Dr Rouxjeane Venter from the Division of Molecular Biology and Human Genetics at Stellenbosch University for her valuable contributions to this research.
Also read:
One organ donor extends the lives of four recipients in the Western Cape
Picture: Anna Shvets / Pexels