Johannesburg
Here in the waiting room of Helen Joseph Hospital, a cough never sounds like just a cough. It’s more like the audio accompaniment for a glimpse at what may be the most sustained medical catastrophe of our time. A throng of new patients are spectral figures, the latest victims of what public-health officials dub a “co-epidemic” of tuberculosis and HIV. The patients’ off-white masks flutter whenever they break into that distinctive guttural bark, followed by a raspy rattle in the throat. Linger long enough in this room and you’ll hear prayers offered: “Please, Jesus, let this be a case of ordinary tuberculosis.” Rising numbers of patients are infected with strains of Mycobacterium tuberculosis resistant to commonly used medications. Treatment, then, will be longer, more punishing, and less effective.
Although largely unnoticed by the public in the United States and Western Europe, where TB and HIV are relatively well-controlled, the co-epidemic rages on across great swaths of Asia, Eastern Europe, Latin America, and Africa. In 2013 alone, these twin scourges took the lives of an estimated 2.6 million people, who died of one infection, or the other, or both.
Nine million people contracted TB in 2013 (1.1 million of them also HIV-positive), and nearly half a million new infections that year involved drug-resistant strains, according to the World Health Organization. The ongoing, uncontrolled spread of multidrug-resistant tuberculosis (MDR TB) also threatens to upend the public-health systems in South Africa and 21 other counties.
Against this grim backdrop, there’s a $1.7 billion shortfall worldwide in funds needed for the prevention, diagnosis, and treatment of TB. Investment in research on vaccines and new treatments remains at paltry levels. The scale of suffering and dying is alarming enough, but public-health advocates worry about the potential for wider consequences, since one in three of us hosts a latent, or inactive, form of tuberculosis, and 37 million are HIV-positive.
“You know, Ebola is only a plane ride away,” one of the doctors at the hospital told me shortly after I arrived for a visit on a cool autumn morning. “Like Ebola, untreatable TB is only a plane ride away, too. So I’m quite surprised by the apparent lack of a sense of urgency about this everywhere but here.”
The Patient
In a corridor that links the hospital’s HIV clinic to its TB treatment center, I met a patient who has been fighting both illnesses for the past six years. “This sickness has been hunting me,” Babsy Raphoto told me. “TB, you know, it eats your strength.” She’s a 45-year-old black woman with a pleasant, oval-shaped face, dressed in a bright pink-and-blue blouse. “And there’s been so many TBs!” Raphoto exclaimed. “I’ve had it three times so far.”
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The hospital itself is a sprawling public-health facility perched on the edge of South Africa’s largest city and named for an icon in the struggle against apartheid. TB infection control had a history of struggle, too. That history included mass dormitory-style housing for mine workers, high rates of incarceration, and scant healthcare for the black majority. Those conditions fueled elevated rates of infection for generations. When the postapartheid government fumbled its early response to a burgeoning HIV epidemic, tuberculosis also boomed.
“I used to think: ‘What have I done wrong?’” Raphoto confided, and I knew from talking to other patients that it was common for those who’d contracted these diseases to blame themselves. The short answer to her question is that it was merely geography and chance—having had the bad luck to come of age amid the intersection and burgeoning spread of two infectious diseases.
Raphoto’s first two bouts with TB were extrapulmonary cases: the first time an attack on her stomach, the second on her lymphatic system (tuberculosis often strikes in organs besides the lungs). Then, in a stunning double whammy, she tested positive for HIV, which was how she discovered that her longtime partner (now an ex-boyfriend) had other romantic attachments. “When I got sick, he didn’t want me,” she said.
Between illnesses, Raphoto always returned to work—she had a teenage daughter to raise, school fees to pay, and unfulfilled ambitions of her own. After apartheid fell, she’d seized the new opportunities suddenly open to blacks, working for a prominent media company and then landing a job as assistant to the CEO of the country’s largest bank. As with millions of her contemporaries, however, the drive for political liberation and economic advancement was blunted by the need to engage in a different kind of struggle—the fight for freedom from disease.
At the end of 2011, tuberculosis “gave me a break!” Raphoto said, speaking of the disease as if it had a mind of its own. Two years later, with her life and career finally back on track, she contracted TB again. This time, she was infected with a more pernicious strain, one resistant to the two drugs most commonly used against it.
The treatment for multidrug-resistant TB proved orders of magnitude more difficult. Her doctor estimates that patients who complete the two-year course of treatment have to swallow up to 14,600 pills and endure daily intramuscular injections for six months. “Aw, if you could only know that pain!” Raphoto said. “Every day you touched your bum and asked yourself, ‘Where is there even a little spot left to be injected?’”
The pain from injectable medications helps explain the high dropout rate worldwide from treatment for MDR TB. So do the severe side effects, including high levels of psychotic reaction and loss of hearing.
Raphoto credited three people with her survival through this travail: her daughter and her sister, both of whom ferried her back and forth to the hospital for years, and her doctor. “I am alive today because of Dr. Berhanu,” she told me. On this fall morning, she had arrived early for her appointment to learn whether she’d been cured once again, this time of MDR TB.
The Doctor
When I visited the clinic last May, the doctor in charge was gathering data for a report on how her patients had fared. Dr. Rebecca Berhanu is a 36-year-old internist who manages research and treatment at TB Focal Point, an innovative collaboration with the Health Ministry managed by the NGO Right to Care and funded by the US government. “It’s patients like Babsy who keep me going,” Berhanu said. Then we were interrupted by a phone call; Berhanu took down a batch of statistics and looked pretty grim as she set down the phone. “The data is just so bad—really disappointing,” the doctor said.
The latest survey revealed that only 40 percent of patients treated for drug-resistant tuberculosis at TB Focal Point had completed a full course of the treatment. This made survivors a distinct minority, in spite of the intensive effort mounted by nurses, counselors, and doctors. About one in four patients—26 percent—had died during the course of treatment, and another 30 percent were “lost to follow-up,” which meant nobody in the clinic knew what happened to them. This is how drug-resistant strains of infection spread across the country, and also across borders.
The results were doubly disappointing because South African health officials had responded to the crisis with a high sense of urgency, unlike their counterparts in Russia and India, for example. “South Africa is actually moving faster than anybody else,” Berhanu pointed out. She thought the health minister, Dr. Aaron Motsoaledi, had demonstrated visionary leadership by embracing the diagnostic tool known as GeneXpert, which allows for speedier and more accurate diagnosis, and moving toward a system of decentralized care, which had worked in places like Peru. The national government pledged to end the co-epidemic altogether by 2035.
These ambitions butted up against sobering realities. In 2015, the waiting room here, like those of so many clinics and hospitals around the country, was filled with patients complaining of psychotic breaks, balance disorders, and deafness from medications being used in the scaled-up campaign against TB.
Continued use of these drugs has placed doctors in a precarious position with their own patients. “We have to tell them, ‘OK, you might go deaf and the odds are it won’t work, but otherwise you’re certain to die of TB.’ So which would you choose?” Berhanu said, raising her eyes to the ceiling. Then, looking at me dead on, as if I were one of her patients: “Well, would you rather go deaf—or die?”
A relatively new drug called bedaquiline was approved by South African authorities for “compassionate use” in cases where patients suffer severe side effects under the old regimen. For doctors in the clinic, however, bedaquiline’s regulatory approval was mainly an advance in theory, since few doses actually arrived. “It’s so discouraging and so frustrating—we need to move a lot faster in getting new drugs to these patients,” Berhanu said.
Her very next patient exemplified the point. Frans Ndou, a construction worker, was a slight man of medium height who’d been diagnosed with MDR TB six months earlier. Placed on the standard treatment that Raphoto had already described to me, he’d swiftly suffered debilitating side effects, including excruciating pains in his legs and feet, a psychotic break, and deafness. “My ears used to work, but because of the medicine—which they said would cure me—these ears won’t work. While you are talking, I have to follow your lips to see what you’re saying,” he told me. The doctor stopped the injections and applied right away for the new drug. For half a year, both patient and doctor were left hanging. Berhanu was anxious to get her hands on the new treatment, because a few weeks later she was scheduled to begin a one-year leave after receiving a fellowship in infectious disease at the University of North Carolina. The experience had left her patient suspicious of the entire enterprise of modern medicine: Why couldn’t they cure the disease in a way that would prevent it from coming back? “I don’t want to admit it, but I might run away,” he said when the doctor left the room. (He was later placed on bedaquiline and reported marked improvement.)
Berhanu was born in Ethiopia and went to colleges and medical school in the United States, so she’s no stranger to the global class divide in medicine. Still, she found it infuriating that it would be so hard to get her hands on a few new drugs easily available to her colleagues in the United States, Western Europe, Japan, and South Korea. In cities like Chicago, where I live, the drug is stocked but rarely used because there are so few cases of MDR TB. There were only 96 such cases nationwide in 2013, compared to more than 14,000 in South Africa the same year (and 6,242 cases of extremely drug-resistant tuberculosis, or XDR TB, from 2004 to 2012).
“It’s the haves and the have-nots, right there!” Berhanu said. It also seemed unconscionable that doctors had to rely on archaic treatments in the first place: The two most commonly used drugs in first-line treatment were developed in the 1950s. Few new medications have been developed for a disease that afflicts tens of millions.
Part of the reason, she thought, had to do with the fact that nearly all the suffering and dying occurs in poor and middle-income countries. This means prices on newly introduced drugs are likely to be negotiated downward, as they had been in the case of HIV drugs. Besides, there’s a much higher profit margin for drugs that treat chronic conditions.
“So the problem with producing new treatments for tuberculosis…?” I started to ask. “Is that it’s curable,” Berhanu replied before I could finish. “Nobody’s interested in treating a curable disease anymore. If you’re developing new drugs, you want to produce something for a chronic condition that everybody has in richer countries, like antidepressants for seasonal-affect disorder or remedies for insomnia.” In richer markets, it’s easier to charge a premium.
Global inequality reveals itself in other ways. In cities like Chicago, patients diagnosed with MDR TB are hospitalized or placed in isolation at home for at least two weeks, away from children and immune-compromised adults, like those infected with HIV. Patients are assigned social workers and nurses who visit their homes, offer support, and give injections. In June, a traveler from India who flew to Chicago and was subsequently diagnosed with XDR TB was airlifted to an isolation ward in a facility operated by the National Institutes of Health and treated at a reported cost of $480,000.
In South Africa, where there are only 2,500 beds set aside for those with drug-resistant diseases, patients are often sent home with well-meaning advice tailored more to a person in Chicago than to someone in Johannesburg. “Our advice, like the medical advice anywhere, is to sleep with open windows in separate rooms,” Berhanu said. “But people are living four, five, and six in one-room shacks!” Exposure to adults at their most infectious is one of the reasons so many children are dying of TB undiagnosed, untreated, and unreported.
Many of Berhanu’s patients had little money for food or transport and walked long distances to and from the hospital in excruciating pain. For the first time, there was a hint of despair in the doctor’s voice. “You always think, you know, ‘What if it was me?’” she said.
The doctor wondered what it would take for drug manufacturers, policy-makers, and the public to register the scale of this disaster. In the middle of the 19th century, tuberculosis caused a third of all deaths in the industrialized world. Would the rest of the world wake up only if the contagion spread? From her vantage point at the heart of contagion, Berhanu thought there was still a whisper of a chance to contain it, but only if more effective, shorter-term, and less painful treatments arrived soon.
The Big Picture
In its annual report last year, the World Health Organization (WHO) noted signal achievements: an estimated 37 million lives saved since 2000 through improved access to diagnosis and treatment for TB and declining mortality rates. These advances demonstrated that a more concerted campaign might make more of a difference. The biggest obstacles are failure of the imagination and will on the part of national governments, including those of middle-income, high-burden countries like Brazil, Russia, India, and China. An annual budget of $8 billion was needed for detection, diagnosis, and treatment, but only $6.3 billion had been raised. Another $2 billion was desperately needed for research and development on new drugs and treatment regimens.
While the prevalence rate (the proportion of the world’s population with active TB infection) fell, the world population had also grown. So, after a long incremental decline, the numbers of people affected by the co-epidemic seemed to have crept back up in recent years: More people died of TB and HIV in 2013 than in 2012. (WHO releases its latest survey, covering 2014, early in October.)
“They love to talk about all the supposed good news,” Mark Harrington told me in mid-September. He’s the hyperkinetic executive director of Treatment Action Group (TAG), the New York–based organization that successfully pressed for greater investment in AIDS research, speedier testing of new medications, and a more patient-centric approach to new treatments during the early years of the HIV epidemic. Now, it struck him, dozens of drugs are available for treating HIV, but only a paltry few are ready to be deployed against tuberculosis.
In 2002, when the Global Fund to Fight AIDS, Tuberculosis and Malaria was formed with seed money from the Bill and Melinda Gates Foundation (which also supported TAG), promising new research was launched into TB vaccines and cures. Then a major vaccine trial failed, and pharmaceutical conglomerates abandoned the field. “What we thought was a renaissance turned into a spark of light before a return to the dark ages,” Harrington said. “It’s been a massive failure of political will and a failure of science.” (And a significant failure of journalism, too, because the scope of the suffering and the political implications of the burden on developing countries hasn’t received adequate coverage.)
One under-celebrated bright spot was the creation of a nonprofit drug-development organization called TB Alliance. Formed in 2000, it became a key player in research on combination therapies that mix old and new drugs in novel ways. The alliance headed three out of six major studies under way on new drugs for the treatment of TB. It’s also a pioneer in clinical trials on combinations of old, repurposed, and new drugs to develop better standards of care for TB patients, including Nix-TB, a trial to test the efficacy of bedaquiline and two other drugs in treating patients with XDR TB.
Dr. Mel Spigelman, CEO of the TB Alliance, emphasized the need for “a truly short-course, simple, affordable, and well-tolerated universal-treatment regimen.” Derek Ambrosino, spokesman for the alliance, said it was the “realities of patients’ experiences” that led to research on drug regimens that could be taken orally.
Back at Helen Joseph Hospital, Babsy Raphoto arrived early for her appointment to review her most recent laboratory results. Finally, some good news: In the latest sample of her sputum and X-ray, there was no sign of TB infection. “Today, I’m healed!” Raphoto declared. “I’m proud to say TB can be cured!”
When the doctor reminded her that she could take off her mask in the examining room, the patient froze. The mask, it seemed, had become part of her identity. Untying it slowly, she drew the mask down into her lap. The transformation was stunning: Masked, she’d looked drawn and fidgety, her eyes narrow and darting. Now, unlike the frail new patients down the hallway, she unveiled wonderfully clear skin stretched over full cheeks. “Overall, it’s six years of being sick with TB,” Raphoto said. “That’s why, back home, they are saying I’m the strongest woman ever!”
As she rose to leave the examining room and fetch her sister, she listed to one side because of a balance disorder from the drugs. She worried that her halting walk made her look like a drunk. Raphoto felt so eager now to do normal things again—leave the house, go into town, shop in a mall, and work. So she tried to imagine her body completely freed from her long bondage to disease. Her African name is Busisiwe, which means “lucky girl” in Zulu. “I am alive!” she announced, like a broadcaster delivering breaking news. She repeated herself even more forcefully: “Can you believe it? I am alive!”
