TSAKANE, South Africa – When Tsholofelo Msimango joined a clinical trial of new tuberculosis drugs, she was 20 years old and weighed 57 pounds.
Stricken with a deadly strain of tuberculosis, Msimango was terrified. She was to be transferred to Sizwe Tropical Diseases Hospital in Johannesburg. The nurses in the township here told her that it was far away and infested with vervet monkeys. “They told my parents to fix the insurance because I would die,” she said.
Five years later, Msimngo, the trial’s fifth enrolled patient, is now tuberculosis-free. She is healthy and has a young son.
Tuberculosis has now surpassed AIDS as the world’s leading infectious cause of death, and the strain that Msimango had — known as XDR-TB — is the ultimate in lethality. It is resistant to all four families of antibiotics typically used to fight the disease. Only a tiny fraction of the 10 million people infected by TB each year get the strain, but very few of those who do survive it.
Three-quarters of those patients die before they even receive a diagnosis, experts believe, and among those who get typical treatment, the cure rate is only 34%.
A typical regimen in South Africa requires up to 40 daily pills, taken for up to two years. Other countries rely on even older regimens that include daily injections of antibiotics that can cause deafness, kidney failure and psychosis.
But the new Nix-TB regimen — hailed by experts as groundbreaking and recently endorsed by the FDA — requires only five pills a day for a mere six months. The three-drug regimen has shown a 90% success rate. Its drugs — linezolid, bedaquiline and pretomanid — are not without side effects, but most are manageable, according to the doctors running the trial.
Some drug-access groups had opposed pretomanid’s approval, saying it needed further testing. Other TB experts argued that the situation is still so desperate that risks had to be taken.
Dr. Gerald Friedland, one of the discoverers of XDR-TB and now an emeritus professor at Yale’s medical school, called Nix “a wonderful trial” that could revolutionize treatment: “If this works as well as it seems to, we need to do this now.”
News that tuberculosis had evolved a terrifying new strain first broke in 2006, when doctors at a global AIDS conference learned of a doomed group of tuberculosis patients in Tugela Ferry, a rural South African town.
Of the 53 patients in whom the strain had been detected, 52 were dead — most within a month of diagnosis. The median age was 35.
In the early years, XDR-TB was a death sentence. Doctors tried every drug they could think of, from those used to treat leprosy to those for urinary tract infections.
“From 2007 to 2014, we threw the kitchen sink at it,” said Dr. Francesca Conradie, director of the Nix trial.
The death rate was about 80%. Sometimes the drugs killed patients. In other cases, patients died because they could not tolerate the drugs and stopped taking them.
Tuberculosis germs burrow deep into the lungs and barricade themselves inside clumps of dead cells. Breaking those nodules and killing all the bacteria inside requires taking drugs for months.
Nearly all antibiotics cause nausea and diarrhea. But some, especially the injections, are far tougher. “Some get hallucinations,” Dr. Pauline Howell said. “I had one patient who tried to cut open his skin because he thought bugs were crawling under it.”
Patients can go deaf over a weekend, she said, or the nerves in their feet and hands can wither. Some develop disrupted cardiac rhythms, which can trigger heart attacks.
Yet even the new treatment poses hazards. Short-term use of linezolid causes few problems, but use for many weeks can kill nerves in the feet, making it hard to walk, or can suppress the bone marrow where blood cells are made.
Some advocacy groups argued that one of the drugs in the cocktail, pretomanid, had been too little tested. “We don’t want to see the FDA lower the bar for approval,” said Lindsay McKenna of the Treatment Action Group, an advocacy organization.
Her organization and others had asked the FDA to first demand a head-to-head comparison of pretomanid against delamanid, a related drug, and a randomized clinical trial in thousands of patients of the Nix regimen versus another used by the WHO.
Pretomanid is not owned by a drug company but by the TB Alliance, a nonprofit based in New York.
Dr. Mel Spigelman, the alliance’s president, had argued that a full clinical trial would be impractical and unethical. He said, “Offered a choice between three drugs with a 90% cure rate, and 20 or more with less chance of cure — who would consent to be randomized?”
Dr. Mario Raviglione, who ran the WHO’s tuberculosis programs for 14 years and is on the TB Alliance’s board, said, “I’m used to public calls by activists for rapid approval to provide new options. I’m not used to calls against a new drug. It’s like we’re forgetting that we’re facing a lethal disease.”