One day of new, shorter experimental MDR-TB treatment. Current medicines require patients to swallow more than 20 pills a day. (TB Alliance)

SA may hold key to curing world's rising drug-resistant TB epidemic

Dr Francesca Conradie
New drug combinations tested in the country may be a lifeline to those with TB most unlikely to survive it.

Tuberculosis (TB) remains the top killer of South Africans, figures from Statistics South Africa show.

The World Health Organisation (WHO) says we bear the burden of more than 450000 new cases of TB a year, placing us among the ranks of countries hardest hit by the disease. Almost 20000 people were diagnosed in 2015 with multidrug-resistant TB (MDR-TB) or infections that did not respond to at least two of the most potent drugs used to treat the disease, isoniazid and rifampicin, according to the WHO.

Worse, 730 people were diagnosed with extensively drug-resistant TB (XDR-TB), a type of TB that cannot be treated by either the most commonly used TB treatments or an entire class of antibiotics known as fluoroquinolones. XDR-TB also won’t respond to at least one of the three injectable drugs used to treat TB when initial treatment fails.

“Normal” TB, known to doctors as drug-sensitive TB, is not hard to cure. WHO data indicate a treatment success rate of 83% for this type of TB.

But if you catch drug-resistant TB – as was the case in nearly 80% of XDR-TB cases in KwaZulu-Natal in one US Centres for Disease Control study – your options plummet. Treatment choices for drug-resistant TB bring much lower cure rates, can last two years or more and can result in kidney damage and hearing loss.

Only one in five patients who have MDR-TB are diagnosed, and only half will be successfully treated, research from WHO’s Global Tuberculosis Report 2016 shows. This proportion drops to less than one in three among people with XDR-TB.

Patients need shorter, less toxic and more effective treatments. And this is where South Africa steps in.

Until 2013, no new TB drugs had come on to the market in 50 years. But now two new drugs have been registered for the treatment of drug-resistant TB: bedaquiline and delamanid. Hot on their heels is another novel drug called pretomanid, which is being tested by TB Alliance, an international research and development nonprofit.

The national TB programme of South Africa has provided bedaquiline to more than 4000 patients. As of February, the international humanitarian organisation Doctors Without Borders found that South African patients now make up more than half of those patients who have received pretomanid globally.

A small pilot project will start providing delamanid to patients in the country this month.

We’re also finding new ways to use older drugs to treat drug-resistant TB, including linezolid, an antibiotic previously reserved to help patients ward off serious infections in intensive care units. Clofazimine, an old leprosy drug, is also finding a new life as part of our arsenal.

But adding one drug to our existing treatment regimens doesn’t go far enough, fast enough. We need to take the new drugs and test them in combinations to produce more effective treatment regimens more quickly.

Research studies using this approach are underway in South Africa. The first, called the STREAM 1 trial, will test whether patients with drug-resistant TB can be treated with a shorter nine-month course of drugs instead of the usual two years. Supported by the United States Agency for International Development and the British Medical Research Council, the results of STREAM 1 will be available in 2018.

The STREAM 2 trial, which began in March last year, will look at what role bedaquiline can play in bringing drug-resistant TB treatment times down from 24 months to nine or, with the help of a few months of daily injections, even six months.

And because both bedaquiline and delamanid can disrupt patients’ heart rhythms, a study by the AIDS Clinical Trial Group research network is looking at what effect the two drugs might have on patients if combined as part of a shorter treatment.

We're also working with the TB Alliance to unlock the potential of more medicines on the horizon. In a study conducted among roughly 120 patients from 10 trial sites in Tanzania, Uganda and South Africa, about half these patients had MDR-TB and were given a new combination of bedaquiline and pretomanid alongside older TB drugs, moxifloxacin and pyrazinamide. The other half had normal TB and were given standard treatment.

Much to everyone's surprise, the MDR-TB patients were TB-free sooner than their peers. There is hope that this combination will be able to treat all but the world's most drug-resistant cases of TB and South Africa is again taking a leading role in helping to confirm this.

Finally, new drug combinations may also be a lifeline to those with TB most unlikely to survive it.

In the 72-person Nix-TB study, high-risk patients who had failed or could not complete MDR-TB treatment were given a combination of bedaquiline, pretomanid and linezolid. This amounted to 27 tablets a week – or about the number of pills these patients would normally be required to take daily under conventional treatment. Nix-TB patients were also spared the traditional daily injections that can leave people deaf.

The study found that the vast majority of patients were no longer infectious after four months of treatment and were TB-free after just six months, according to findings presented at the international Conference on Retroviruses and Opportunistic Infections.

South Africa now sits at the intersection of cutting-edge research and the next wave of drug-resistant TB infections. With the right tools in hand and the political will to invest in using them properly, in the near future we might be able to rid ourselves of TB.

Francesca Conradie is a clinical adviser for the nonprofit organisation Right to Care

Have something to say? Tweet or Facebook us on @Bhekisisia_MG

Tuberculosis (TB)