Scientists Discover New Cure for the Deadliest Strain of Tuberculosis


TSAKANE, South Africa — When she joined a trial of new tuberculosis drugs, the dying young woman weighed just 57 pounds.

Stricken with a deadly strain of the disease, she was mortally terrified. Local nurses told her the Johannesburg hospital to which she must be transferred was very far away — and infested with vervet monkeys.

“I cried the whole way in the ambulance,” Tsholofelo Msimango recalled recently. “They said I would live with monkeys and the sisters there were not nice and the food was bad and there was no way I would come back. They told my parents to fix the insurance because I would die.”

Five years later, Ms. Msimango, 25, is now tuberculosis-free. She is healthy at 103 pounds, and has a young son.

The trial she joined was small — it enrolled only 109 patients — but experts are calling the preliminary results groundbreaking. The drug regimen tested on Ms. Msimango has shown a 90 percent success rate against a deadly plague, extensively drug-resistant tuberculosis.

On Wednesday, the Food and Drug Administration effectively endorsed the approach, approving the newest of the three drugs used in the regimen. Usually, the World Health Organization adopts approvals made by the F.D.A. or its European counterpart, meaning the treatment could soon come into use worldwide.

Tuberculosis has now surpassed AIDS as the world’s leading infectious cause of death, and the so-called XDR strain 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 this type, but very few of them survive it.

There are about 30,000 cases in over 100 countries. 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 percent.

“From 2007 to 2014, we threw the kitchen sink at it,’’ said Dr. Francesca Conradie, a researcher at the University of the Witwatersrand, Johannesburg, and director of the Nix trial.

The death rate was about 80 percent. Sometimes the drugs killed patients. In other cases, patients died of the disease, 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 apart 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 on patients.

“Some get hallucinations,” said Dr. Pauline Howell, a tuberculosis researcher who runs the Nix trial at Sizwe Tropical Diseases Hospital in Johannesburg, where Ms. Msimango was treated. “I had one patient who tried to cut open his skin because he thought bugs were crawling under it.”

The drugs may leave patients in wheelchairs with vertigo, or deaf in just a weekend. Nerves in their feet and hands may wither until they can no longer walk or cook. One of Dr. Howell’s patients suffered so much from ringing in the ears that he tried to commit suicide.

Ms. Msimango, too, veered close to death because the drugs were too much for her.

When she was 19, she said, she caught drug-resistant TB from another young woman — the temporarily homeless daughter of a friend of her mother.

Her mother had generously taken in the young woman and had told her daughter to share her bed, a common arrangement in townships like Tsakane. “A few weeks after she left, I started coughing,” Ms. Msimango said.

“She had not told us that she had drug-resistant TB and had defaulted,” she added, using a common term for dropping out of treatment.

At first, Ms. Msimango got her injections at a hospital and took her pills under her mother’s watchful eye. But they made her feel so awful that she secretly spat them out, stuffing them between the sofa cushions when her mother wasn’t looking.

After she defaulted twice herself, she was transferred to Sizwe, terrified that she would die alone.

A return visit this month showed that far more than the name had changed (Sizwe means “nation” in Zulu).

The former men’s ward is now a mostly empty meeting hall. Patients with TB that is not drug-resistant are treated at home, and even those with partially drug-resistant strains are usually hospitalized only briefly.

The XDR-TB patients rest in a ward atop the hill, and golf carts transport those too weak to walk. Each patient has a separate room and bathroom, hookups for oxygen and lung suction, a TV and big windows and a door to the lawn outside.

The building has a sophisticated ventilation system, but it often breaks down, so the policy is to keep all the doors and windows open as much as possible, said Dr. Rianna Louw, the hospital’s chief executive.

Patients can work in the garden, play pool or foosball, and take classes in sewing, beading or other crafts that might help them earn a living when they get out.

But the months of isolation needed for treatment can be tough. “Our children are scattered, they are falling apart!” a patient who gave her name only as Samantha shouted at a group-therapy session that turned into an airing of grievances.

“The father of my kids is in prison,” she said. “My firstborn son is arrested for robbing people in the street. That would not happen if I was home!”

The counselor interrupted to say: “We understand your frustration. But if we discharge you, we are taking a risk. You are not healthy. You can still expose people to your disease. That’s why you will stay a minimum of four months.”

The regimen successfully tested at Sizwe is called BPaL, shorthand for the three drugs it comprises: bedaquiline, pretomanid and linezolid.

The BPaL regimen is “bold, because it’s three killer drugs instead of two killers plus some supportive ones,” Dr. Howell said.

Most regimens, she explained, rely on two harsh drugs that can destroy bacterial walls and include others that have fewer side effects but only stop TB bacteria from multiplying.

Dr. Mel Spigelman, the alliance’s president, had argued that a full clinical trial would be both impractical and unethical.

“Put yourself in a patient’s position,” he said. “Offered a choice between three drugs with a 90 percent cure rate, and 20 or more with less chance of cure — who would consent to randomization?”

Such a trial would cost $30 million and take five more years, he added: “That’s a very poor use of scarce resources.”

Innocent Makamu, 32, was facing two years in the hospital when he chose to join the Nix trial in 2017.

Like Ms. Msimango, he also had caught drug-resistant TB from a roommate. A plumber, he had shared a room at a distant construction site with a carpenter.

“He was too much on the bottle,” Mr. Makamu said. “He kept defaulting.”

Soon afterward, he began feeling tired and lost his appetite. Doctors at the hospital near his home diagnosed tuberculosis, and put him on 29 daily pills and a daily injection.

“It was deep in my bum,” he said. “I couldn’t sit properly. It hurt every day.”

At the hospital, he watched two other inpatients wither and die because they could not stick to the regimen. “I thought, ‘Oh, there is no survival here.’”

Then further tests showed that he had full-blown XDR-TB. He was transferred to Sizwe and offered a spot in the Nix trial.

Some patients there who were on the standard 40-pill regimens discouraged him. “They said, ‘They are using you as guinea pigs,’” he said. “Even the nurses thought that.”

But he found the possibility of taking only five pills for six months very tempting, and so he volunteered. Within a month, he could tell it was working.

“Then the patients who called us ‘guinea pigs’ — they wished they had taken the research pills,” he said.



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