TSAKANE, South Africa – When she joined a trial for new drugs for tuberculosis, the dying young woman weighed just 57 kilograms.
Stunned by a deadly strain of the disease, she was mortally horrified. Local nurses told her that the hospital in Johannesburg, to which she was to be transferred, was very far away – and infected with monkeys of rope.
"I cried all the way in the ambulance," recalled Tsolofelo Msimango recently. "They said I would live with monkeys and the sisters were not good there and the food was bad and there was no way I could go back. They told my parents to take out the insurance because I was going to die. ”
The trial he joined was small – it enrolled only 109 patients – but experts called the preliminary results innovative. Ms. Msimango's drug regimen tested showed a 90 percent success rate against the deadly plague, a drug-resistant tuberculosis.
On Wednesday, the Food and Drug Administration effectively endorsed the approach, approving the latest of the three drugs used in the scheme. Usually, the World Health Organization accepts approvals made by the F.D.A. or its European counterpart, which means that the treatment may soon come into use worldwide.
Tuberculosis now has surpassed AIDS as the leading infectious cause of death in the world, and the so-called XDR strain is the highest in mortality, it is resistant to all four families, anti-four commonly used to fight the disease.
Only a small proportion of the 10 million tuberculosis infected each year receive this type, but very few survive it.
There are approximately 30,000 cases in over 100 countries. Three-quarters of those patients die before they are even diagnosed, experts say, and among those receiving typical treatment, the cure rate is only 34 percent.
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The treatment itself is extremely difficult. The typical regimen in South Africa requires up to 40 pills a day, taken up to two years.
Other countries rely on even older regimens that include daily injections of antibiotics that can have detrimental side effects, including deafness, kidney failure and psychosis.
But in the study, Ms. Msimango joined, nicknamed Nix-TB, patients took only five pills a day for six months.
The pills contain only three medicines: Pretomanide, Bedaquilin and Linezolid. (Someday, the whole regimen can come with just one pill, as HIV medicines do, says an expert.)
Until recently, some advocacy groups opposed the approval of Pretomanid, saying the drug needed from additional tests. But other tuberculosis experts say the situation is so desperate that risks have to be taken.
p. Gerald Friedland, one of the discoverers of XDR-TB and now an emergent professor at Yale Medical School, called Nix a "wonderful test" that could revolutionize treatment: "If it works as good as it looks, we should do it now.
A killer appears
The news that tuberculosis has developed has evolved a new horrifying strain first broke in 2006 when doctors at a global AIDS conference learned of a doomed group of tuberculosis patients in Ferry Tugela, a rural South African city.
Of the 53 patients in whom the strain was detected, 52 died – most within one month of diagnosis. They were relatively young: the average age is 35.
Many have never been treated for tuberculosis before, which means they have caught the drug-resistant strain from others who have been infected and have not developed it, such as have failed to take drugs. There are several healthcare professionals who are thought to have been taken by patients.
Within months, South Africa realized that there were cases of lethal infection in 40 hospitals. Worried, W.H.O. officials have called for worldwide testing.
The results show that 28 countries, including the US, had a deadly strain, XDR-TB, and that two-thirds of the cases were in China, India and Russia. It took a much longer time to determine how widespread it is in Africa, as most countries there could not do sophisticated testing.
H.I.V., The AIDS-causing virus helped to drive the epidemic. Anyone infected with it is 25 times more likely to get tuberculosis, according to W.H.O. But many victims, including Ms. Msimango, catch this type of tuberculosis without ever having H.I.V.
"From 2007 to 2014, we threw the kitchen sink over it," says Dr. Francesca Conradi, a researcher at the University of the Witwatersran, Johannesburg, and director of the Knicks Process.
The mortality rate was about 80 percent. Sometimes drugs kill patients. In other cases, patients died from the disease because they could not tolerate the medication and stopped taking it.
Tuberculosis germs dig deep into the lungs and barricade themselves inside lumps of dead cells. Breaking these nodes and destroying all the bacteria inside requires taking medicines for months.
Almost all antibiotics cause nausea and diarrhea. But some, especially injections, are far more difficult for patients.
"Some are hallucinating," says Dr. Pauline Howell, a tuberculosis researcher who ran the Nicks trial at Sizwe at Tropical Diseases Hospital in Johannesburg, where Ms. Msimango was being treated. "I had a patient who tried to cut his skin because he thought bugs were crawling underneath."
Medicines can leave patients in wheelchairs with dizziness or deaf for just one weekend. The nerves in the legs and arms can dry out 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 strayed close to death because the drugs were too much for her.
When she was 19, she said she had gotten drug-resistant tuberculosis from another young woman – her mother's temporary homeless daughter.
Her mother generously welcomed the young woman and told her daughter to share her bed, a common arrangement in cities such as Czakane. "A few weeks after she left, I started coughing," said Msimango.
"She did not tell us that she had drug-resistant tuberculosis and had a malfunction," she added, using a generic term for non-treatment.
In the beginning, Ms. Msimango put herself in the hospital and took her pills under her mother's keen eye. But they made her feel so awful that she secretly spat them out and slipped them between the cushions on the couch when her mother wasn't looking.
After failing twice in failure, she was transferred to Sizwe, terrified that she would die on her own.
No masks, no doctors
Although located in the largest city in South Africa, Sisve hosts ape, with wild peacocks and random mongoose. It has long been at the forefront of South Africa's protracted battle against tuberculosis.
The hospital sits on an isolated hilltop hill 10 miles from downtown. It was built by the British in 1895 as Ritfontein Hospital to shelter victims of infectious diseases such as leprosy, smallpox and syphilis.
Gandhi volunteered there during the bubonic plague epidemic of 1904, and Archbishop Desmond Tutu was ill with tuberculosis there in his youth.  In 1996, with the raging AIDS epidemic, the WHO declared that South Africa had the worst tuberculosis epidemic in the world: 350 cases per 100,000 citizens.
This finding shocks the government using outdated approaches to the disease. Diagnoses were made by X-rays that were less accurate than sputum tests and doctors hospitalized each patient.
I visited shortly after the 1996 announcement and the situation inside Ritfontein was troubling. In the men's ward, dozens of tuberculosis patients lie on baby beds only two feet away; those with drug-resistant strains slept with patients of the usual type.
No one wore a mask and no doctor was on duty. At night, the patients shut them down and heated the heat and the room became a lethal incubator. A return visit this month showed that much more than the name has changed (Sizwe means means "nation" in Zulu).
The former men's ward is now a mostly empty meeting room. Patients with non-drug-resistant tuberculosis are treated at home, and even those with partially drug-resistant strains are usually hospitalized only briefly.
Patients with XDR-TB rest in a hill compartment, and golf carts transport these too weak to walk. Each patient has a separate room and bathroom, oxygen and lung suction doors, a TV and large windows and a door to the lawn outside.
The building has a complex ventilation system but is often destroyed so the policy is to keep all doors and windows open as much as possible, said Dr. Rihanna Lou, the hospital's chief executive officer.
Patients can work in the garden, play pool or football and participate in sewing, beads or other crafts, which
But the months of isolation required for treatment can be difficult. "Our children are scattered, they are falling apart!" A patient gave his name only when Samantha called for group therapy, which turned into a complaint.
"My children's father is in prison," she said. "My firstborn son was arrested for robbing people on the street. It wouldn't happen if I was home!
The counselor interrupted to say, "We understand your dissatisfaction. But if we release you, we take the risk. You're not healthy. You can still expose people to your illness. Therefore, you will stay at least four months.
The regimen successfully tested in Sizwe is called BPaL, a transcript of the three drugs that it includes: Bedaquilin, Pretomanide, and Linezolid.
BPaL's regime is "bold because it is three drug killers instead of two killers plus some supportive," says Dr. Howell .
Most regimes, she explained, rely on two serious drugs that can destroy them. bacterial walls and include others that have fewer side effects but only stop the tuberculosis bacteria from multiplying.
But even the new treatment poses dangers.
Short-term use of linezolid for severe hospital-acquired infections causes few problems, but use for many weeks against tuberculosis can kill the nerves in the legs, making it difficult to walk, or it can suppress the bone marrow where blood cells are made. (To find the ideal dose of linezolid, Nix researchers began a new trial, ZeNix.)
F.D.A. approved Bedaquilin for use in 2012 against multidrug-resistant tuberculosis (the XDR strain is an even more lethal subgroup), and in 2015 W.H.O. followed suit. By Wednesday, Pretomanid was in dispute, though in June F.D.A. The Advisory Committee voted 14 to 4 to approve it.
Some advocacy groups claim that the drug has been tested too little.
"Pretomanide looks like a promising drug, but it's rushing forward and we don't want to see F.D.A. cut the approval band, "said Lindsey McKenna, co-director of the tuberculosis project in the treatment group, in July,
her organization and others have asked the F.D.A. first, ask for more rigorous drug tests.
Pretomanid is not owned by a drug company but by TB Alliance, a New York-based NGO seeking new treatments.
Dr. Mel Spiegelman, the president of the union, argues that a full clinical trial will be impractical and unethical.
"Put yourself in a patient position," he said. "I suggest choosing between three drugs with 90 percent of treatment and 20 or more with less chance of cure – who would agree to randomization?"
Such an experiment would cost $ 30 million and take another five years , he added: "This is a very poor use of scarce resources."
"There is no Survival here"
Innocent Makamu, 32, was confronted with a hospital two years ago when he chose to join the Knicks process in 2017.
Like Ms. Msimango, he had also received drug-resistant tuberculosis from a roommate. A plumber, he had shared a room on a faraway construction site with a carpenter.
"He was too much on the bottle," said Mr. Makamu. He continued to fail.
Shortly afterwards, he began to feel tired and lose his appetite. Doctors at the hospital near his home diagnosed him with tuberculosis and gave him 29 daily pills and a daily injection.
"That was deep in my stomach," he said. "I couldn't sit properly. It hurts every day. "
At the hospital, he watched two other hospital patients wither and die because they could not adhere to the regimen. "I thought, 'Oh, there's no survival here. "
Subsequently, further tests revealed that he had complete XDR-TB.
Some patients out there who were on standard 40 pill regimens discouraged it. "They said, 'They use you as guinea pigs,'" he said. "Even the nurses thought about it."
But he found the possibility of taking only five pills in six months very tempting, so he volunteered. Within a month he can say that it works.
"Then the patients who called us guinea pigs wanted to take the pills for study," he said.