Multi-drug-resistant tuberculosis has been a growing problem in India for years. Now an even more extreme strain of the deadly disease -- resistant to all of the drugs normally used to treat it -- is causing concern. WSJ's Natacha Butler reports from Mumbai.
MUMBAI—India's slow response to years of medical warnings now threatens to turn the country into an incubator for a mutant strain of tuberculosis that is proving resistant to all known treatments, raising alarms of a new global health hazard.
"We finally have ended up with a virtually untreatable strain" of tuberculosis in India, said Dr. Zarir Udwadia, one of the country's leading TB authorities.
In December, Dr. Udwadia reported in a medical journal that he had four tuberculosis patients resistant to all treatment. By January, he had a dozen cases, then 15.
A government backlash began immediately. Anonymous health-ministry officials denied the reports through media outlets. They accused Dr. Udwadia and his colleagues of starting a panic. A Mumbai city health official seized patient samples for verification in government labs.
In April, the government quietly confirmed the strain, according to internal Indian health-ministry documents reviewed by The Wall Street Journal.
Spread of the strain could return tuberculosis to the fatal plague that killed two-thirds of people afflicted, before modern treatments were developed in the 1940s, said Dr. Mario Raviglione, director of the Stop TB Department of the World Health Organization. The WHO is now assisting India to combat the strain.
Tuberculosis Strains Raise Concern in India
Chiara Goia for The Wall Street Journal
Ganga Jatolia, and her mother, Geeta, inside their small house in the Chembur neighborhood of Mumbai.
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The number of known cases in India is small but geographically dispersed. Dr. Udwadia's patients are in Mumbai, at the P.D. Hinduja National Hospital & Medical Research Center. In the high-tech hub of Bangalore, St. John's National Academy of Health Sciences has seen six cases. And in New Delhi, the All India Institute of Medical Sciences has confirmed another two, said officials at the institutions.
"While this handful of cases is worrying, it's just the tip of the iceberg," said Dr. Soumya Swaminathan, of India's National Institute for Research in Tuberculosis. For treatments, Dr. Udwadia said, "We've got nothing."
Ashok Kumar, head of India's tuberculosis-control program, said the government was "seriously addressing" the widening drug-resistance problem. However, he refuted Dr. Udwadia's description of a "totally drug-resistant" TB strain—not because there is a treatment, but because the term isn't internationally recognized and a new cure could be discovered.
Dr. Kumar said Dr. Udwadia and his hospital should have reported the cases to local health authorities, instead of an international medical journal. Public concern about drug-resistant TB, he said, "is not a well-founded fear."
Tuberculosis, a communicable, airborne disease that usually attacks the lungs, is mostly found in pockets of deep poverty around the world. Healthy, well-fed people are less likely to contract the disease when exposed.
India has the largest number of the world's cases—2.3 million of the nearly nine million people afflicted annually—and it is the country's most fatal infectious illness. Government authorities estimated about 100,000 of India's patients have drug-resistant strains, which researchers say can mutate into forms increasingly immune to more and more medicines.
For years, India was praised for having the world's most ambitious TB treatment program, with 640,000 people who dispense medicines and 13,000 centers for diagnosis.
But the program is strained. TB patients, for example, are treated by village nurses, who also supervise most other health programs, said Dr. Swaminathan. Nurses often don't have time to monitor TB patients, who must take medicines for months. Many patients quit early.
The government has promised to expand its treatment system by 2017, with the goal of quickly diagnosing and treating drug-resistant TB cases.
Experts, however, doubt India can keep its promise with the $230 million earmarked for each of the next four years, given the high cost of diagnostic equipment and the drugs needed to battle resistant strains.
In most of the country, India pays only for standard TB treatment, which medical authorities say is useless against the antibiotic-resistant strains. In fact, experts said, antibiotics that don't kill the disease provide favorable conditions for mutation of new, stronger strains.
Experts of the World Health Organization met in Geneva to discuss untreatable TB in March, according to documents reviewed by the Journal. They decided against creating a "totally drug-resistant" category because the condition was difficult to confirm in a lab. Some participants also worried about the psychological effect on patients if their illness was declared "totally drug resistant."
Camilla Rodrigues, lab chief at Hinduja Hospital where most of India's cases have been found, said the strain's total drug resistance was indeed difficult to confirm in a lab. But, she said, it was easily confirmed in clinical practice: Four of 15 patients whose lab tests showed the strain have died, despite aggressive treatment. The hospital has since stopped publicly reporting its cases.
The Indian cases are the latest and most serious in a steady increase in resistance to tuberculosis drugs around the world. The first reports of so-called totally drug resistant TB came from Italy in 2007. Two years later, researchers in Iran reported patients who failed to respond to any known TB drugs.
Many countries have reported multidrug-resistant TB, which the WHO defines as a strain resistant to the two most powerful drugs. A smaller group of patients have extensively resistant TB—a strain resistant to most of the 12 known treatments—with survival rates that vary according to the quality of medical care.
The New England Journal of Medicine this month published a study showing 10% of TB patients in China had multidrug-resistant strains.
For almost two decades, Dr. Udwadia and his colleagues have been diagnosing patients with increasingly resistant TB, warning the strains could spiral out of control.
In 1996, he delivered a lecture on the topic at the American College of Chest Physicians conference in San Francisco. In 2003, he published a paper in the New York Academy of Sciences reporting that multidrug-resistant TB was rampant among patients he saw at his hospital.
India's TB program for years focused on treating regular strains. Patients who didn't improve received the same treatment for longer but with one more antibiotic. The regimen had virtually no chance of defeating resistant strains, experts said.
"It serves merely to amplify resistance over a further eight months, allowing drug-resistant TB to spread," Dr. Udwadia wrote this year in Thorax, the respiratory medicine journal published by the British Thoracic Society.
Dr. Udwadia, 51 years old, trained in Mumbai's public hospitals, where TB is rampant, and at City Hospital in Edinburgh, where researchers first combined medicines for a cure.
He returned to Mumbai in 1991, and tuberculosis has since been the focus of his practice and research. He has a small office at the end of a long, gray corridor on the third floor of the clinic building at the Hinduja National Hospital.
On a recent Monday, a line of a dozen patients in saris, burqas and kurta pajamas stretched down the corridor from his doorway. Dr. Udwadia sat by an open window to reduce the chance of infection but wore no surgical mask with his patients. He whipped medical records and X-rays out of yellow envelopes, studied them, scrawled notes and then tossed them in a pile on the floor. He saw 50 patients in less than two hours.
Tall and lean, with a dome of black hair, the doctor spoke to patients in rapid-fire English and Hindi. Most were poor—fruit vendors, rickshaw drivers. A young doctor with drug-resistant TB entered his office trembling. Dr. Udwadia chided him, "Get a grip, doctor. You, of all people, have to stay positive."
Dr. Udwadia beamed at 16-year-old Dinesh Jatolia, who came with his mother. The boy, who has an extensively resistant strain, filled out his white T-shirt with broad shoulders and muscular arms. The teenager has gained eight pounds since Dr. Udwadia last saw him, a sign his treatment was working.
Dinesh's mother was eager to ask about her daughter, who was at home suffering with the same strain. "Is there any hope for Ganga?" she asked.
"I can never say there's no hope," Dr. Udwadia said. "But your son is much better off than your daughter."
In a corner of the family's home in the Chembur neighborhood, 19-year-old Ganga used her pencil-thin arms to push herself up from a low bed during a visit in April. Beside her were sacks filled with the soles of chappals, Indian slippers her parents assemble for less than one cent a pair. The family income is $60 a month.
On a shelf is a photograph of Ganga's older brother, who died this year of TB. Last year, an older sister died of the disease.
Their mother, Geeta Jatolia, sold her gold jewelry to buy $6,000 worth of TB medicines for the two dead children because the Indian government only paid to treat patients with the regular strain. The family has been spending its entire monthly income on medicines for the two surviving children. They borrow money from neighbors and friends to buy food.
Having seen two children die, Mrs. Jatolia said, "We try to make the medicines the first priority."
Tuberculosis has long been a global killer. Traces were found in the skeletons of Egyptian mummies. There are records of the disease from Hippocrates, the Indian Rig Veda and ancient Chinese texts. At the start of the 19th century, tuberculosis was the main cause of death in most of Europe.
After the discovery of the antibiotic streptomycin in the 1940s, followed later by chemotherapy agents, researchers created a combination of treatments called modern short-course chemotherapy. TB could now be cured in six months.
The disease continued to thrive in countries like India, where people are weakened by malnutrition. A challenge everywhere is keeping patients on their medicines, which can have side effects of nausea and loss of feeling in the limbs.
Drug-resistant tuberculosis develops when patients fail to complete the full treatment or don't take strong enough medicines. If TB isn't attacked with the right medicines long enough to kill it, the bacteria mutates.
In the U.S. and most western European countries, patients are tested for resistant strains at their initial diagnosis. India has continued to test for and treat only the regular strain of tuberculosis in most of the country.
In 2006, Dr. Udwadia and colleagues at Hinduja National Hospital reported India's first cases of extensively drug-resistant TB, the variety afflicting Dinesh Jatolia and his siblings. That year, India announced it would expand its TB program to tackle multidrug-resistant strains and two years later began building a network of labs to diagnose them.
India has so far built 37 of the labs and is treating 5,000 patients with multidrug-resistant TB—a fraction of those afflicted with the strain, said Dr. Kumar.
The government waited to tackle resistant strains largely because India didn't have labs able to diagnose those varieties. It also made sense, Dr. Kumar said, to focus first on treating the more than two million patients who could be cured for about 500 rupees each, or $9, he said. Treating drug-resistant TB costs at least 100,000 rupees, or $1,800.
The WHO has since 2010 urged India to buy machines that can test patients for drug-resistant TB in two hours, rather than waiting through months of failed treatments. Not properly diagnosing TB strains, said Dr. Raviglione of the WHO, "is why we've progressed very little in fighting drug resistance,"
The diagnostic machines cost about $70,000 and each patient test is about $16, said Dr. Raviglione, which includes a discount negotiated by the WHO.
The machines are in pilot programs and if they work, Dr. Kumar said, India will buy more.
Dr. Udwadia said he was worried they would come too late: "We're chasing the snowball down the hill."
During a visit this month, the Jatolia family's house was quiet. Mrs. Jatolia sat in one corner. Ganga's metal-frame bed, where the girl had spent months fighting to breathe, was empty.
"Ganga died four days ago," Mrs. Jatolia said. In a last effort to save her daughter, she put Ganga in a hospital, mortgaging the family's two-room home to pay the bill.
"We've sold everything we had, we've borrowed money on everything we owned," she said, "and all we have to show for it is three dead children."
—Shreya Shah contributed to this article.
Write to Geeta Anand at email@example.com