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Scientists discover new cure for the deadliest strain of tuberculosis

TSAKANE, South Africa – When she joined an experiment with new tuberculosis drugs, the dying young woman weighed only 57 kilos.

Knitting with a deadly strain of the disease, she became mortally terrified. Local nurses told her that the Johannesburg hospital to which she had to be transferred was very far away – and infected by the recruit monkeys.

"I cried all the 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 poor and there was no way to come back. They told my parents to fix the insurance for me to die. ”

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

The study she joined was small – it registered only 109 patients – but experts call the preliminary results groundbreaking. The drug regimen tested on Msimango has shown a 90 percent success rate against a deadly plague, including drug-resistant tuberculosis.

On Wednesday, the Food and Drug Administration approved the alignment and approved the newest of the three drugs used in the regimen. The World Health Organization usually adopts approvals made by F.D.A. or its European counterpart, which means that treatment could soon be implemented 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 mortality. It is resistant to all four families of antibiotics commonly used to fight the disease.

Only a small fraction of the 10 million people infected with tuberculosis each year get this type, but very few of them survive it.

There are approximately 30,000 cases in over 100 countries. Three-quarters of these patients die before they are even diagnosed, experts believe, and among those who receive typical treatment, the cure rate is only 34 percent.

"From 2007 to 2014, we threw the sink on it," Dr. Francesca Conradie, researcher at the University of the Witwatersrand, Johannesburg and head of the Nix trial.

The death rate was about 80 percent. Sometimes the drugs killed patients. In other cases, the patients died of the disease because they could not tolerate the drugs and stopped taking them.

Tuberculosis greens dig deep into the lungs and barricade themselves in clumps of dead cells. Breaking down these knots and killing all the bacteria inside requires taking drugs for months.

Almost all antibiotics cause nausea and diarrhea. But some, especially the injections, are much tougher for patients.

"Some people get hallucinations," Dr. Pauline Howell, a tuberculosis researcher conducting the Nix trial at Sizwe Tropical Diseases Hospital in Johannesburg, where Msimango was being treated. "I had a patient who tried to cut his skin because he thought bugs were crawling under it."

The drugs can leave patients in wheelchairs with scams or deaf people in just one weekend. Nerves in feet and hands can wither until they can no longer walk or cook. One of Dr. Howell's patients suffered so much from ringing in his ears that he tried to commit suicide.

Mrs. Msimango also wrestled near 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 parishes like Tsakane. "A few weeks after she left, I started coughing," Msimango said.

"She had not told us she had drug-resistant tuberculosis and had fallen," she added, using a common term for dropping out of treatment.

First Msimango received her injections in a hospital and took her pills under her mother's watchful eye. But they made her feel so awful that she secretly expelled them and stuffed them between the cushions when her mother didn't look.

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

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

The former men's department is now a mostly empty meeting hall. Patients with tuberculosis that are not drug resistant are treated at home, and even those with partially drug resistant strains are usually only briefly admitted.

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

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

Patients can work in the garden, play pool or football and take courses in sewing, beads or other crafts that can help them make money when they come out.

But the months of isolation needed for treatment can be tough. "Our children are scattered, they fall apart!" A patient who gave his name only when Samantha cried at a group therapy session that turned into an airing of complaints.

"My child's father is in prison," she said. “My firstborn son is arrested for robbing people on the street. It wouldn't happen if I was home! "

The counselor interrupted to say:" We understand your frustration. But if we let you go, we take a risk. You're not healthy. You can still expose people to your illness. That is why you will stay at least four months. ”

The treatment successfully tested at Sizwe is called BPaL, in brief for the three drugs it includes: bedaquiline, pretomanide and linezolid.

The BPaL regime is "bold, as it is three killers instead of two killers plus some supportive ones," Dr. Howell .

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

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

"Put yourself in a patient's position," he said. "Offered a choice between three drugs with 90 percent cure and 20 or more with less chance of cure – who would approve randomization?"

Such a trial would cost $ 30 million and take another five years, he added: "It's a very poor use of scarce resources."

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

Like Msimango, he had also caught drug-resistant TB from a roommate . He had shared a plumber with a carpenter in a remote building site.

"He was too much on the bottle," Makamu said. "He kept going out."

Soon thereafter, he began to feel 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 looked at two other inpatients who wither and die because they couldn't adhere to the treatment. "I thought," Oh, there's no survival here. "

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

Some patients there who were in the standard 40 pill rules counteracted him. "They said, 'They use you as guinea pigs,'" he said. "Even the nurses thought so." month he could say it worked.

"Then the patients who called us" guinea pigs "- they wished they had taken the research pills," he said.

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