Superbug From India Spread Far and Fast, Study Finds

An antibiotic-resistant gene originally discovered in bacteria from India was found 8,000 miles away in a remote Arctic environment, according to a new study. Researchers believe the gene, found in bacteria in the soil of a Norwegian archipelago, made the trek in less than three years, highlighting the speed with which antibiotic resistance can spread on a global scale.

Antibiotic resistance is a persistent and growing global health concern. At least 700,000 people die globally each year from antibiotic-resistant infections, according to a 2014 report from the British government. As some bacteria have evolved to fight off even last-resort treatments, that number is on track to increase as much as 10-fold in the coming decades, according to the report.

These so-called superbugs have spread through hospitals and health-care facilities due to overuse of antibiotics in medicine and in farming. But they also crop up throughout the environment via water and food, carried in the guts of animals or humans, researchers say. Resistance without human intervention continuously occurs as bacteria evolve genes to compete with each other—a process millions of years older than humans. All of these factors make it difficult for scientist to track exactly how some antibiotic-resistant genes emerge and proliferate.

“We’re trying to understand these other factors that come into play,” said David Graham, an ecosystems engineer at Newcastle University in the U.K. and lead researcher on the study. “If we don’t know the pathways, we can’t come up with the right solutions.”

Dr. Graham and his team collected soil samples from eight locations in Svalbard, a Norwegian island chain in the Arctic Ocean. The team chose an isolated area with minimal human impact to discount human antibiotic use. The team then analyzed the DNA from the bacteria and other organisms in the dirt.

“The arctic is a perfect microcosm for studying pathways,” said Clare McCann, an environmental engineer at Newcastle University in the U.K. and first author on the study. “You can very quickly and easily discount any human use there.”

Researchers found 131 genes linked to antibiotic resistance. That level of genetic diversity isn’t unusual, says Dr. Graham, though two genes and their high abundance specifically caught the team’s attention. The gene called pncA creates resistance to the tuberculosis drug pyrazinamide. The other gene produces the notorious “superbug” protein NDM-1.

The findings were published Sunday in the journal Environment International.

New Delhi metallo-beta-lactamase-1, or NDM-1, makes some certain gut bacteria resistant to the last-resort group of antibiotics known as  carbapenems. Since its discovery in 2008, NDM-1 has spread to over 100 countries, including the U.S. “This is a gene that’s causing havoc in hospitals,” said Gerry Wright, the director of the Institute for Infectious Disease Research at McMaster University in Canada, who wasn’t involved with the study.

The gene was found only in soil samples that had high nutrient levels, reflecting the presence of plants and animal feces, meaning that NDM-1 was most likely transported to the environment via animals or other mechanisms, the researcher said, rather than having developed there on its own.

Superbug From India Spread Far and Fast, Study Finds

Researchers were analyzing samples that had been collected in 2013. NDM-1 emerged in Indian groundwater in 2010, so researchers believe that the gene made the 8,000 mile journey to the Arctic in just three years. “This gene has spread around the world so incredibly fast,” said Dr. Wright. “It’s something that’s not surprising to me, but it should be frightening to everybody.”

It isn’t just the speed that concerns scientists; it is also the location. “What’s terrible is that we’re talking about a really remote place, a place that we don’t think of as a hotbed of antibiotic resistance,” said Martin Blaser,  the chairman of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria, who wasn’t involved in the research. “This is really bad news.”

Researchers can’t exactly say how the superbug gene arrived in the Arctic, though it may have been picked up in the guts of migratory seabirds. Although NDM-1 won’t harm humans while it is in the soil, the finding is important for those who track how genes spread.

“This moves us forward in our quest to understand the global distribution of these genes,” said Jill Mikucki, an assistant professor of microbiology at the University of Tennessee, who wasn’t involved in the research.

The gene pncA seemed to have developed in the Arctic on its own, researchers say, because it was found in all of the soil samples regardless of nutrient level. Because the gene is resistant to tuberculosis drugs, researchers believe there is the potential to find a tuberculosis-fighting antibiotic in the soil that may have prompted the resistance to develop. “If there is a gene out there with resistance, there is almost certainly an organism that can counterbalance that,” said Dr. Graham.

Finding undiscovered antibiotics in soil is a possibility–that is how the first antibiotics were discovered, and researchers are currently working to pull undiscovered antibiotics from dirt. But as of right now, the evolutionary struggle with antibiotic resistance is one that modern medicine is losing. “We really rely on antibiotics, and this resistance thing is only going in one direction. It’s getting worse,” said Dr. Wright. “You can run, but you can’t hide.”




This article was originally published in The Wall Street Journal. Read the original article.

Scientists Are Teaching the Body to Accept New Organs

It was not the most ominous sign of health trouble, just a nosebleed that would not stop. So in February 2017, Michael Schaffer, who is 60 and lives near Pittsburgh, went first to a local emergency room, then to a hospital where a doctor finally succeeded in cauterizing a tiny cut in his nostril.

Then the doctor told Mr. Schaffer something he never expected to hear: “You need a liver transplant.”

Mr. Schaffer had no idea his liver was failing. He had never heard of the diagnosis: Nash, for nonalcoholic steatohepatitis, a fatty liver disease not linked to alcoholism or infections.

The disease may have no obvious symptoms even as it destroys the organ. That nosebleed was a sign that Mr. Schaffer’s liver was not making proteins needed for blood to clot. He was in serious trouble.

The news was soon followed by another eye-opener: Doctors asked Mr. Schaffer to become the first patient in an experiment that would attempt something that transplant surgeons have dreamed of for more than 65 years.

If it worked, he would receive a donated liver without needing to take powerful drugs to prevent the immune system from rejecting it.

Before the discovery of anti-rejection drugs, organ transplants were simply impossible. The only way to get the body to accept a donated organ is to squelch its immune response. But the drugs are themselves hazardous, increasing the risks of infection, cancer, high cholesterol levels, accelerated heart disease, diabetes and kidney failure.

Within five years of a liver transplant, 25 percent of patients on average have died. Within 10 years, 35 to 40 percent have died.

“Even though the liver may be working, patients may die of a heart attack or stroke or kidney failure,” said Dr. Abhinav Humar, a transplant surgeon at the University of Pittsburgh Medical Center who is leading the study Mr. Schaffer joined. “It may not be entirely due to the anti-rejection meds, but the anti-rejection meds contribute.”

Kidneys in particular may be damaged. “It is not uncommon to end up doing a kidney transplant in patients who previously had a lung or liver or heart transplant,” Dr. Humar added.

Patients usually know about the drugs’ risks, but the alternative is worse: death for those needing livers, hearts or lungs; or, for kidney patients, a life on dialysis, which brings an even worse life expectancy and quality of life than does a transplanted kidney.

In 1953, Dr. Peter Medawar and his colleagues in Britain did an experiment with a result so stunning that he shared a Nobel Prize for it. He showed that it was possible to “train” the immune systems of mice so that they would not reject tissue transplanted from other mice.

His method was not exactly practical. It involved injecting newborn or fetal mice with white blood cells from unrelated mice. When the mice were adults, researchers placed skin grafts from the unrelated mice onto the backs of those that had received the blood cells.

The mice accepted the grafts as if they were their own skin, suggesting that the immune system can be modified. The study led to a scientific quest to find a way to train the immune systems of adults who needed new organs.

Dr. Peter Medawar, around 1960, when he won the Nobel Prize for studies of the immune system.CreditBettmann, via Getty Images

Dr. Peter Medawar, around 1960, when he won the Nobel Prize for studies of the immune system.CreditBettmann, via Getty Images

That turned out to be a difficult task. The immune system is already developed in adults, while in baby mice it is still “learning” what is foreign and what is not.

“You are trying to fool the body’s immune system,” Dr. Humar said. “That is not easy to do.”

Most of the scientific research so far has focused on liver and kidney transplant patients for several reasons, said Dr. James Markmann, chief of the division of transplant surgery at Massachusetts General Hospital.

Those organs can be transplanted from living donors, and so cells from the donor are available to use in an attempt to train the transplant patient’s immune system.

Far more people need kidneys than need any other organ — there are about 19,500 kidney transplants a year, compared with 8,000 transplanted livers. And those transplanted kidneys rarely last a lifetime of battering with immunosuppressive drugs.

“If you are 30 or 40 and get a kidney transplant, that is not the only kidney you will need,” said Dr. Joseph R. Leventhal, who directs the kidney and pancreas transplant programs at Northwestern University.

Another reason to focus on kidneys: “If something goes wrong, it’s not the end of the world,” Dr. Markmann said. If an attempt to wean patients from immunosuppressive drugs fails, they can get dialysis to cleanse their blood. Rejection of other transplanted organs can mean death.

The liver intrigues researchers for different reasons. It is less prone to rejection by the body’s immune system. When rejection does occur, there is less immediate damage to the organ.

And sometimes, after people have lived with a transplanted liver for years, their bodies simply accept the organ. A few patients discovered this by chance when they decided on their own to discard their anti-rejection drugs, generally because of the expense and side effects.

An estimated 15 to 20 percent of liver transplant patients who have tried this risky strategy have succeeded, but only after years of taking the drugs.

In one trial, Dr. Alberto Sanchez-Fueyo, a liver specialist at King’s College London, reported that as many as 80 percent could stop taking anti-rejection drugs. In general, those patients were older — the immune system becomes weaker with age. They had been long-term users of immunosuppressive drugs and had normal liver biopsies.

But the damage caused by immunosuppressive drugs is cumulative and irreversible, and use over a decade or longer can cause significant damage. Yet there is no way to predict who will succeed in withdrawing.

The more researchers learned about the symphony of white blood cells that control responses to infections and cancers — and transplanted organs — the more they began to see hope for modifying the body’s immune system.

Many types of white blood cells work together to create and control immune responses. A number of researchers, including Dr. Markmann and his colleague, Dr. Eva Guinan of the Dana-Farber Cancer Institute, chose to focus on cells called regulatory T lymphocytes.

These are rare white blood cells that help the body identify its own cells as not foreign. If these regulatory cells are missing or impaired, people can develop diseases in which the body’s immune system attacks its own tissues and organs.

The idea is to isolate regulatory T cells from a patient about to have a liver or kidney transplant. Then scientists attempt to grow them in the lab along with cells from the donor.

Then the T cells are infused back to the patient. The process, scientists hope, will teach the immune system to accept the donated organ as part of the patient’s body.

“The new T cells signal the rest of the immune system to leave the organ alone,” said Angus Thomson, director of transplant immunology at the University of Pittsburgh Medical Center.

Dr. Markmann, working with liver transplant patients, and Dr. Leventhal, working with kidney transplant patients, are starting studies using regulatory T cells.

At Pittsburgh, the plan is to modify a different immune system cell, called regulatory dendritic cells. Like regulatory T cells, they are rare and enable the rest of the immune system to distinguish self from non-self.

One advantage of regulatory dendritic cells is that researchers do not have to isolate them and grow them in sufficient quantities. Instead, scientists can prod a more abundant type of cell — immature white blood cells — to turn into dendritic cells in petri dishes.

“It takes one week to generate dendritic cells,” Dr. Thomson said. In contrast, it can take weeks to grow enough regulatory T cells.

The regulatory T cells also have to remain in the bloodstream to control the immune response, while dendritic cells need not stay around long — they control the immune system during a brief journey through the circulation.

“Each of us is taking advantage of a different approach,” Dr. Markmann said. “It is not clear yet which is best. But the field is at a fascinating point.”

What about patients who already had an organ transplant? Is it too late for them?

“I get asked that question almost every day I am seeing patients,” Dr. Leventhal said.

For now, the answer is that it is too late. These patients are not candidates for these new strategies to modify the immune system. But researchers hope that situation will change as they learn more.

When Michael Schaffer, the Pittsburgh patient, was told that he needed a liver and that he could be the first patient in the group’s clinical trial, he shrugged. “Someone has to be first,” he said.

Mr. Schaffer began a search to find a living donor, a close relative willing to undergo a major operation to remove a lobe of liver — or a stranger whose cells were compatible and who was willing to donate.

The Pittsburgh scientists told him how to proceed. Ask immediate family, then relatives, friends and colleagues. If that failed, he would have to start advertising with fliers and posts on Facebook.

Mr. Schaffer is one of eight brothers. Four were older than 55, too old to safely undergo removal of part of their liver. The three younger brothers were in poor health.

He moved on to nieces and nephews. Three agreed to donate, and one, Deidre Cannon, 34, who was a good match, went forward with the operation.

It took place on Sept. 28, 2017. Afterward, Mr. Schaffer was taking 40 pills a day to prevent infections and to tamp down his immune system while his body learned to accept the new organ.

But now he has tapered down to one pill, a low dose of just one of the three anti-rejection drugs he started with. And doctors hope to wean him even from that.

His case may be intriguing, but he is just one patient. The scientists plan to try the procedure on 12 more patients and, if it succeeds, to expand the study to include many more patients at multiple test sites.

For Mr. Schaffer, it has all been worthwhile. He is active, working with a teenage grandson to replace the tiles on his kitchen floor. He shovels snow and mows lawns as a favor for his neighbors, and helps take care of his grandchildren after school.

“My goal is to live to be 100 and get shot in bed by a jealous husband,” Mr. Schaffer said.



This article was originally published in The New York Times. Read the original article.

How a shampoo bottle is saving young lives

ON HIS first night as a trainee paediatrician in Sylhet, Bangladesh, Mohamad Chisti (pictured above) watched three children die of pneumonia. Oxygen was being delivered to them, through a face mask or via tubes placed near their nostrils, using what is called a basic “low-flow” technique which followed World Health Organisation (WHO) guidelines for low-income countries. But it was clearly failing. He decided to find a better way.

Last year 920,000 children under the age of five died of pneumonia, making it the leading killer of people in that age group. This figure is falling (in 2011 it was 1.2m), but it still represents 16% of all infant deaths. Such deaths are not, however, evenly distributed. In Bangladesh pneumonia causes 28% of infant mortality.

Pneumonia is a result of bacterial, viral or fungal infection of the lungs. Its symptoms of breathlessness result from a build-up of pus in the alveoli. These are tiny sacs, found at the ends of the branching airways within the lungs, that are richly infused with capillary blood vessels. They are the places where oxygen enters the bloodstream and carbon dioxide leaves it. Stop the alveoli doing their job and a patient will suffocate.

Pneumonia is particularly threatening to malnourished children—which many in Bangladesh are. First, malnourishment debilitates the immune system, making infection more likely. Second, to keep its oxygen levels up and its CO2 levels down, a child with pneumonia breathes faster and faster. But this takes a lot of energy, so undernourished infants do not have the ability to keep such an effort up for long. Dr Chisti’s device is designed to reduce the effort required to breathe, and to do so cheaply. (The reason for the WHO’s recommended approach in poor countries is that the sort of ventilator routinely available in the rich world costs around $15,000. But low-flow oxygen delivery does not reduce the effort required to breathe.)

His invention was inspired by something he saw while visiting Australia. On this trip he was introduced to a type of ventilator called a bubble-CPAP (continuous positive airway pressure), which is employed to help premature babies breathe. It channels the infant’s exhaled breath through a tube that has its far end immersed in water. The exhaled breath emerges from the tube as bubbles, and the process of bubble formation causes oscillations of pressure in the air in the tube. These feed back into the child’s lungs. That improves the exchange of gases in the alveoli and also increases the lungs’ volume. Both make breathing easier.

At about $6,000, standard bubble-CPAPs are cheaper than conventional ventilators. But that is still too much for many poor-country hospitals. However, after a second piece of serendipitous inspiration, when he picked up a discarded shampoo bottle that contained leftover bubbles, Dr Chisti realised he could probably lash together something that did the same job. Which he did, using an oxygen supply (which is, in any case, needed for the low-flow oxygen delivery method), some tubing and a plastic bottle filled with water. And it worked.

In 2015 he and his colleagues published the results of a trial that they had conducted in the institution where he practises, the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research. This showed that the method had potential. The hospital now deploys it routinely and the number of children who die there from pneumonia has fallen by three-quarters. That means the survival rate in the Dhaka Hospital is today almost on a par with that of children treated in rich-world facilities, using conventional ventilators.

Dr Chisti says that, as well as saving lives, his device has cut the hospital’s spending on pneumonia treatment by nearly 90%. The materials needed to make his version of a bubble-CPAP ventilator cost a mere $1.25. The device also consumes much less oxygen than a conventional ventilator. In 2013 the hospital spent $30,000 on supplies of the gas. In 2017 it spent $6,000.

The idea is spreading. Dr Chisti and his team are about to start trials of the new ventilator in a group of hospitals in Ethiopia. If it works as well there as it does in Dhaka, it will surely be taken up elsewhere. All in all, the Chisti bottle-based ventilator shows what can be achieved by stripping an idea down to its basic principles. Effectiveness, it neatly demonstrates, need not always go hand in hand with high tech.



This article was originally published in The Economist. Read the original article.