The emergence of drug resistance is threatening the control of tuberculosis in South Africa and other parts of the world. Researchers from K-RITH and the Broad Institute of MIT and Harvard have traced the roots of extensively drug-resistant TB (XDR TB) in KwaZulu-Natal (KZN) to the late 1950s. Their findings, published in the journal PLOS Medicine, have vital implications for the way we understand how XDR strains are spread, and the management and treatment of TB in South Africa and elsewhere in the world.

In XDR, the bacteria that causes TB has become resistant to nearly all anti-TB drugs and is virtually untreatable. The largest outbreak of XDR TB in history was first detected in KZN in 2005 at the Church of Scotland Hospital in Tugela Ferry and XDR TB is now found throughout the province. Up until now it was not known where it came from.

In collaboration with scientists at CAPRISA, the National Health Laboratory Service and the SA Medical Research Council, the researchers used whole genome sequencing – a method that can work out the entire genetic code of individual strains of bacteria – and dating analysis to trace the origin of XDR TB in KZN. They found that the mutations in the TB bacteria that cause drug resistance emerged in 1957, soon after the first antibiotics to treat the disease became available. Since then, every time a new drug has been introduced the TB bacteria has successfully developed resistance to it. By the 1980s, the microbe had evolved to multi drug-resistant status (MDR) and by the mid-1990s it had mutated to XDR. This means that the massive problem of drug resistance in South Africa is not due to recent challenges in TB control and developed well before the explosive HIV epidemic in the 1990s, which had previously thought to be the cause of XDR TB in KZN.

During the process of tracing the Tugela Ferry XDR strain, researchers also found many other strains of drug resistant TB that were evolving independently of each other. Vitally, scientists discovered that the first drug all the strains develop resistance to is the antibiotic isoniazid. This was the key step that started the evolution towards XDR. When doing rapid tests for MDR and XDR TB, most hospitals and clinics in South Africa currently only test for resistance to the drug rifampicin. Researchers believe that if we are going to halt the process of further evolution to new resistance, there should also be mandatory screening for isoniazid resistance.

“If we want to turn off the tap to generating new drug resistant strains of TB, we have to screen for isoniazid resistance as well,” said K-RITH scientist Dr Alex Pym, a lead author on the research paper.

“There is some real hope for treating XDR as this year the National TB Control Programme was able to get access to the first new TB drug developed in 40 years – called bedaquiline – and there are others in the pipeline. But unless we use these new drugs extremely carefully the XDR TB bacteria will continue its relentless evolution and the new drugs will become useless,” he added.