Scientists Discover a Cure for the Deadliest Strain of Tuberculosis

TSAKANE, South Africa — When Tsholofelo Msimango joined a clinical trial of new tuberculosis drugs, she was 20 years old and weighed just 57 pounds.

Stricken with a deadly strain of tuberculosis, Ms. 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.

“I cried the whole way in the ambulance,” she recently recalled. “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, who became the trial’s fifth enrolled patient, is now tuberculosis-free. She is healthy at 103 pounds, and has a young son.

The trial she joined, nicknamed Nix-TB, is small — it has enrolled only 109 patients. But experts are already calling the preliminary results groundbreaking. The three-drug regimen tested on Ms. Msimango has shown a 90 percent success rate against a deadly plague: extensively drug-resistant tuberculosis, better known as XDR-TB.

On Wednesday, the Food and Drug Administration effectively endorsed the Nix-TB regimen by approving the last of its three drugs, pretomanid, for XDR-TB patients as long as it is used with the other two previously approved ones, bedaquiline and linezolid.

Usually, the World Health Organization eventually adopts approvals made by the F.D.A. or its European counterpart, meaning the regimen could soon come into use worldwide.

Tuberculosis has now surpassed AIDS as the world’s leading infectious cause of death, and the 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 the XDR strain, but very few of those who do survive it.

The death rate was about 80 percent. 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 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. “I had a patient who tried to commit suicide because of the tinnitus — ringing in his ears,” said Dr. Pauline Howell, a tuberculosis researcher who runs the Nix trial at Sizwe.

“Some get hallucinations,” Dr. Howell said. “I had one patient who tried to cut open his skin because he thought bugs were crawling under it. I’ve had patients who became wheelchair-bound because of the vertigo.”

Patients can go deaf over a weekend, she said, or the nerves in their feet and hands can wither until they can no longer walk or cook. Some develop disrupted cardiac rhythms, which can trigger heart attacks.

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 negative-pressure air 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.

“I’m used to public calls by activists for rapid approval to provide new options,” he said. “I’m not used to calls against a new drug. It’s like we’re forgetting that we’re facing a lethal disease.”

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.

Sahred From Source link Science

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