On the occasion of the EndTB trial site launch in Khayelitsha, Dr. Eric Goemaere reflects on how far the medical response to DR-TB has come in two decades, and where it must still go.
At the recent opening ceremony of the newest site to join the five-country expand new drug markets for TB (endTB) clinical trial in Khayelitsha (a large urban settlement just outside Cape Town), the audience heard how the trial aims to revolutionize treatment for drug-resistant tuberculosis (DR-TB) by eliminating the daily injectable antibiotic which causes irreversible hearing loss in up to 60% of patients.
I found myself thinking back to the earlier revolution in diagnosing DR-TB, and how this has helped to dramatically change attitudes towards people affected by the disease. During my first visits with MSF to South Africa in 1999, I witnessed the country’s rapidly growing DR-TB epidemic first-hand in Khayelitsha, which was and remains one of the highest TB and DR-TB burden settings in the world.
The dominant but incorrect view of the World Health Organization (WHO) at the time was that DR-TB was the ‘fault’ of the individual themselves through not taking their treatment properly, or to a lesser extent because of health service issues, including bad quality drugs or wrong prescriptions.
Patients with DR-TB were seen as ‘defaulters’ who participated in creating their own disease, and were therefore stigmatized and stripped of their right to dignity and appropriate care without discrimination. Typically they were confined to hospitals, or locked up in sanatoriums, often against their will.
Acquired versus transmitted DR-TB
This misconception meant that preventing DR-TB acquisition was the priority, not treatment. The existing treatment was believed to be sufficient, which in turn dis-incentivized the development of new tools to fight DR-TB.
At the same time, before it was actively researched, DR-TB was essentially a medical blind spot. The extent of drug-resistant TB was under-estimated across the African continent and elsewhere. Until the end of the 1990s, the WHO’s annual DR-TB reports spoke of ‘hot spots’ while identifying South Africa and Egypt as the main, if not the only DR-TB hotspots in Africa. In fact, they were some of the few places in Africa then testing for TB drug resistance.
In the early 2000s, a decision was finally taken to tackle the extent of the problem. This was after it emerged that many parts of Eastern Europe had high rates of DR-TB, mainly in prisons but not exclusively, and evidence was emerging of high DR-TB rates from areas with high numbers of patients also living with HIV. TB overwhelmingly attacks people living with HIV, and in South Africa, the untreated nature of the HIV epidemic until around 2007 led to a proliferation of all forms of TB. In Khayelitsha, the HIV/TB co-infection rate was found to be around 70 percent.
New diagnostic tools – first liquid cultures, followed years later by genotypic detection – burst onto the scene. It was a revolution because there was now proof that people had transmitted DR-TB – people who had never been infected with TB before were found to have DR-TB. By 2011, South Africa was going all out to identify how big their DR-TB epidemic was, with a nation-wide rollout of nearly 800 GeneXpert machines. GeneXpert allowed drug-resistance (to rifampicin) to be diagnosed almost instantly and in decentralised labs, which avoided weeks of waiting for culture results from central laboratories. Today, the WHO estimates there are 19,000 new DR-TB cases a year in South Africa (WHO, 2017).
Diagnosis had a significant impact on the DR-TB response. Within a few years, the world started to realise the scale of the problem, which perversely also made the pharmaceutical market for DR-TB more lucrative.
DR-TB patients fight back
The courageous decision of MSF’s first DR-TB patients from Khayelitsha to speak out, as well as MSF’s involvement in South Africa’s HIV activism movement are some of the reasons the approach to treating DR-TB has changed so much, both in South Africa and elsewhere. DR-TB is very stigmatizing. Ten years ago, with DR-TB patients being blamed for their condition, it was unheard of for a patient to dare raise their voice. But DR-TB patients like Phumeza Tisile from Khayelitsha, who went permanently deaf from her daily kanamycin injections, have become powerful public advocates for better treatment. Others started to say, ‘Doctor don’t give me this injectable anymore because I don’t want to go deaf like Phumeza.’
Today you have DR-TB survivors who don’t feel ashamed to say they want a less toxic shorter treatment and care that is more respectful of their basic rights, what we call a ‘patient-centred approach’. In 2014, Phumeza – then cured of XDR-TB after two years of treatment - delivered 50,000 signatures on the DR-TB manifesto at the World Health Assembly, calling on members to radically improve DR-TB care.
Moving on from injectables
Today, MSF’s Khayelitsha project along with others in the province offers treatment close to patients’ homes, or even at home from ‘treatment supporters’. Clinicians explain to patients what their treatment options are, and include patients in the discussion as part of a ‘bilateral treatment contract’.
Yet for MSF, despite these improvements, DR-TB care remains inadequate. When you ask patients what their major obstacle is to completing treatment, the majority will complain about the painful daily injectable they have to receive for at least six months. Getting rid of the injectable would be a real game changer for DR-TB care as it would certainly improve adherence to treatment, which would impact positively on treatment success rates.
Now that new DR-TB drugs like bedaquiline and delamanid have come to the market, getting rid of the injectable is not a pipe dream anymore but rather a possibility, even for the most resistant strains of TB. If the endTB trial achieves its ambitious aim of finding one or hopefully several new treatment regimens that are demonstrably safe and effective as well as being short and all-oral, meaning no injection, it could indeed stimulate the next revolution in DR-TB treatment. It would also take forward the on-going revolution in DR-TB diagnosis and thinking about DR-TB that we have already witnessed.
Expand new drug markets for TB (endTB) is a partnership between Partners in Health, Médecins Sans Frontières, Interactive Research & Development and financial partner UNITAID. Epicentre, Harvard Medical School and the Institute of Tropical Medicine Antwerp are partners of the clinical trial.
As of May 2018, there are 98 patients enrolled across five countries, namely Georgia, Kazakhstan, Lesotho, Peru and South Africa. For more information go to: www.endtb.org/clinical-trial