By Gardiner Harris, The New York Times, December 3, 2014
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NDM-1 Super Bacteria found in Indian hospitals
AMRAVATI, India — A deadly epidemic that could have global implications is quietly sweeping India, and among its many victims are tens of thousands of newborns dying because once-miraculous cures no longer work.
These infants are born with bacterial infections that are resistant to most known antibiotics, and more than 58,000 died last year as a result, a recent study found. While that is still a fraction of the nearly 800,000 newborns who die annually in India, Indian pediatricians say that the rising toll of resistant infections could soon swamp efforts to improve India’s abysmal infant death rate. Nearly a third of the world’s newborn deaths occur in India.
“Reducing newborn deaths in India is one of the most important public health priorities in the world, and this will require treating an increasing number of neonates who have sepsis and pneumonia,” said Dr. Vinod Paul, chief of pediatrics at the All India Institute of Medical Sciences and the leader of the study. “But if resistant infections keep growing, that progress could slow, stop or even reverse itself. And that would be a disaster for not only India but the entire world.”
In visits to neonatal intensive care wards in five Indian states, doctors reported being overwhelmed by such cases.
“Five years ago, we almost never saw these kinds of infections,” said Dr. Neelam Kler, chairwoman of the department of neonatology at New Delhi’s Sir Ganga Ram Hospital, one of India’s most prestigious private hospitals. “Now, close to 100 percent of the babies referred to us have multidrug resistant infections. It’s scary.”
These babies are part of a disquieting outbreak. A growing chorus of researchers say the evidence is now overwhelming that a significant share of the bacteria present in India — in its water, sewage, animals, soil and even its mothers — are immune to nearly all antibiotics.
Newborns are particularly vulnerable because their immune systems are fragile, leaving little time for doctors to find a drug that works. But everyone is at risk. Uppalapu Shrinivas, one of India’s most famous musicians, died Sept. 19 at age 45 because of an infection that doctors could not cure.
While far from alone in creating antibiotic resistance, India’s resistant infections have already begun to migrate elsewhere.
“India’s dreadful sanitation, uncontrolled use of antibiotics and overcrowding coupled with a complete lack of monitoring the problem has created a tsunami of antibiotic resistance that is reaching just about every country in the world,” said Dr. Timothy R. Walsh, a professor of microbiology at Cardiff University.
Indeed, researchers have already found “superbugs” carrying a genetic code first identified in India — NDM1 (or New Delhi metallo-beta lactamase 1) — around the world, including in France, Japan, Oman and the United States.
Anju Thakur’s daughter, born prematurely a year ago, was one of the epidemic’s victims in Amravati, a city in central India. Doctors assured Ms. Thakur that her daughter, despite weighing just four pounds, would be fine. Her husband gave sweets to neighbors in celebration.
Three days later, Ms. Thakur knew something was wrong. Her daughter’s stomach swelled, her limbs stiffened and her skin thickened — classic signs of a blood infection. As a precaution, doctors had given the baby two powerful antibiotics soon after birth. Doctors switched to other antibiotics and switched again. Nothing worked. Ms. Thakur gave a puja, or prayer, to the goddess Durga, but the baby’s condition worsened. She died, just seven days old.
“We tried everything we could,” said Dr. Swapnil Talvekar, the pediatrician who treated her. Ms. Thakur was inconsolable. “I never thought I’d stop crying,” she said.
A test later revealed that the infection was immune to almost every antibiotic. The child’s rapid death meant the bacteria probably came from her mother, doctors said.
Health officials have warned for decades that overuse of antibiotics — miracle drugs that changed the course of human health in the 20th century — would eventually lead bacteria to evolve in a way that made the drugs useless. In September, the Obama administration announced measures to tackle this problem, which officials termed a threat to national security.
Some studies have found that developing countries have bacterial rates of resistance to antibiotics that are far higher than those in developed nations, with India the global focal point.
Bacteria spread easily in India, experts say, because half of Indians defecate outdoors, and much of the sewage generated by those who do use toilets is untreated. As a result, Indians have among the highest rates of bacterial infections in the world and collectively take more antibiotics, which are sold over the counter here, than any other nationality.
A recent study found that Indian children living in places where people are less likely to use a toilet tend to get diarrhea and be given antibiotics more often than those in places with more toilet use. On Oct. 2, the Indian government began a campaign to clean the country and build toilets, with Prime Minister Narendra Modi publicly sweeping a Delhi neighborhood. But the task is monumental.
“In the absence of better sanitation and hygiene, we are forced to rely heavily on antibiotics to reduce infections,” said Ramanan Laxminarayan, vice president for research and policy at the Public Health Foundation of India. “The result is that we are losing these drugs, and our newborns are already facing the consequences of untreatable sepsis,” or blood infections.
Some health experts and officials here say that these killer bugs are largely confined to hospitals, where heavy use of antibiotics leads to localized colonies.
But India’s top neonatologists suspect the large number of resistant infections in newborns in their first days of life demonstrates that these dangerous bacteria are thriving in communities and even pregnant women’s bodies.
“Our hypothesis is that resistant infections in newborns may be originating from the maternal genital tract and not just the environment,” Dr. Paul said in an interview.
In a continuing study in Delhi at several government-run hospitals that has so far included more than 12,000 high-risk newborns, and was made available to The New York Times, about 70 percent of the babies’ infections were found to be immune to multiple powerful antibiotics, confirming the results of earlier and smaller studies.
Doctors interviewed in hospitals across India said that a large number of the infections they found in newborns were resistant to many antibiotics. Awareness of the problem has begun to grow, with Indian medical associations calling for efforts to reduce unnecessary antibiotic use. But there is keen sensitivity here to any alert to the dangers. A 2010 discovery of a New Delhi “superbug” caused intense controversy because of fears that publicity would threaten India’s profitable medical tourism industry. Government officials have stopped some studies of the problem, Dr. Walsh said.
The effects of antibiotic-resistant bacteria on treating disease in India could be enormous. Tuberculosis is just one example of the challenges doctors face. India has the world’s largest number of cases, and recent studies using the latest genetic tests have shown that as many as 10 percent of untreated patients in places as far apart as Mumbai and Sikkim have resistant infections. These patients are catching resistant bugs at home, not hospitals, making the epidemic very difficult to control, Dr. Soumya Swaminathan, director of the National Institute for Research in Tuberculosis, said in an interview.
“It’s startling and very worrying,” Dr. Swaminathan said. Unless the government makes profound and drastic changes, tuberculosis in India may soon become untreatable, she said.
Although resistant bugs are everywhere here, hospitals have become factories for untreatable “superbugs.” A government program that pays women to have babies in hospitals has in 10 years more than doubled the share of hospital-born babies to 82 percent, but the government did little to increase hospital capacity to deal with the crush. Maternity wards often have two and three women in each bed, allowing infections to spread rapidly.
Besides being desperately crowded, many hospitals are unhygienic, allowing the bugs to flourish. A Unicef survey of 94 district hospitals and health centers in Rajasthan last year found that 70 percent had possibly contaminated water and 78 percent had no soap available at hand-washing sinks, while 67 percent of toilets were unsanitary.
Doctors across India have responded to the sanitation crisis in hospitals by giving antibiotics freely.
In Haryana, for instance, almost every baby born in hospitals in recent years was injected with antibiotics whether they showed signs of illness or not, Dr. Suresh Dalpat, deputy director of child health in the state of Haryana, said in an interview. “Now, with proper training, we are bringing that down.”
All those drugs create resistant bacteria that find their way into hospital sewage, which is mostly dumped untreated into rivers, canals and pits in the surrounding community where pregnant women can become infected.
The most frequent causes of resistant newborn infections in India are bacteria like Klebsiella and Acinetobacter, which are found in untreated human waste. Such bacteria rarely infect newborns in developed nations, said Dr. Paul.
India and other developing nations are by no means alone in threatening the future of antibiotics. Overuse of the drugs in chicken, hog and cattle farms in the United States has led to the rise of resistant strains there, and research has shown that as much as half of antibiotic prescriptions in the United States are unnecessary.
The Centers for Disease Control and Prevention estimated last year that two million people are sickened by resistant bacteria every year in the United States and 23,000 die as a result. But efforts to crack down on inappropriate antibiotic use in the United States and much of Europe have been successful, with prescriptions dropping from 2000 to 2010. That drop was more than offset, however, by growing use in the developing world.
Global sales of antibiotics for human consumption rose 36 percent from 2000 to 2010, with Brazil, Russia, India, China and South Africa accounting for 76 percent of that increase. In India, much of that growth has been driven by private doctors who deliver about 90 percent of care here and are often poorly trained. Much of these doctors’ income comes from drug sales.
Just as worrisome has been the rapid growth of India’s industrialized animal husbandry, where antibiotics are widespread. Most large chicken farms here use feed laced with antibiotics banned for use in animals in the United States. A New Delhi science group recently found antibiotic residues in 40 percent of chicken samples tested.
But the effects in children are perhaps the most heart-wrenching. After her baby’s death a year ago, Ms. Thakur, 21, was soon pregnant again. She gave birth on Sept. 21 to a baby girl. On a visit shortly after the baby’s birth, Ms. Thakur was shivering from a severe infection while staying in a home with no toilet or running water. She nursed her tiny infant, Khushi, under a small shrine with pictures of Durga and Krishna.
Nearly two months later, she reported that she and the baby were fine.
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