How the Ganga Is Contributing to Increasing Antibiotic Resistance Worldwide

14 November, 2017

In his book River of Life, River of Death: The Ganges and India’s Future, Victor Mallet traces the journey of the river from source to mouth. Mallet, the former South Asia bureau chief for the Financial Times, writes in the book that “Indians are killing the Ganges with pollution, and that the polluted Ganges, in turn, is killing Indians.” The book includes chapters on the history of the Ganga, the distressing fate of the river in Varanasi, the extent of the toxicity of its waters, as well as its significance in the country’s water crisis. In the following extract from the book, Mallet describes the Ganga as a “Superbug river”—host to bacterial genes that expose the water’s users to infectious diseases that are resistant to modern antibiotics. The journalist discusses the role the Ganga and its tributary Yamuna play in the spread of blaNDM-1—a bacterial gene that codes for a protein called NDM-1, or New Delhi metallo-beta-lactamase, and whose presence can make the carrier highly resistant to antibiotics. Mallet writes that the spread of the gene is a political issue that is closely connected to the Ganga’s state, its sacred position among Hindus, and to India’s sanitation problem.

Vipin Vashishtha, a paediatrician in Bijnor, a town in Uttar Pradesh on the Ganges, described his horror when babies starting dying in his hospital in 2009 because bacterial acquisition of blaNDM-1 had made infections resistant to antibiotics. “What I found out was that there is a deadly epidemic going on. And very few of us have any clue ... The bacteria in our water, sewage, soil, even the bacteria within us—they are all immune to nearly all antibiotics.”

But what might a patient’s death from a superbug infection in a hospital in New York or London have to do with India, let alone the Ganges—particularly if the victim has never travelled to south Asia? The answer is that the NDM genes that make bacteria highly drug-resistant are being spread across the country in humans and other animals, and through sewers, streams, and rivers, and are ultimately transported onward in people’s guts to every part of the world.

This is a politically sensitive matter, of course. Some Indian officials and doctors were furious with The Lancet for naming the new NDM gene in 2010 after New Delhi, the Indian capital, and the origins of this particular part of the drug-resistance problem are less important now that such genes have spread around the world. But both Indian and international scientists accept that South Asia has been one epicentre of the crisis and agree that India (soon to overtake China as the world’s most populous nation) urgently needs to improve hygiene and build toilets and effective sewage treatment plants. It also needs to curb the misuse and overuse of antibiotics that accelerate the evolution of drug-resistant strains of bacteria.

Of all the academic papers on antibiotic resistance that I examined, the most arresting on the subject of the Ganges was written by scientists based in India and the UK and carried the less than catchy title: “Increased waterborne blaNDM-1 resistance gene abundances associated with seasonal human pilgrimages to the upper Ganges River.” It confirms that NDM-1 genes are found in the Yamuna River, a Ganges tributary that runs through Delhi, and in the main stream of the Ganges River. It also shows that high levels of the gene are associated with high levels of faecal coliform bacteria and therefore with the flow of human waste into rivers. More significantly, the samples demonstrate that the (relatively) pristine reaches of the upper Ganges near Haridwar suffer surges of bacterial pollution and, in turn, blaNDM-1 pollution during visits by thousands of urban Indians during the May–June pilgrimage season. Devout Hindus, in other words, are unwittingly spreading diseases, and antibiotic resistance to diseases, in the very river to which they have come to pay homage.

The Ganges is a much-abused river at least in part because Hindus are reluctant to believe its holy waters can be sullied. Even foreign visitors are inclined to assume, wrongly, that the water of the upper Ganges is safe. The Ganges–Yamuna paper blames increased exposure to NDM-1 in the upper Ganges partly on the fact that pilgrims presume water quality to be good and fail to consider the impact of their own mass visits. Its data suggest that the average visiting pilgrim, because he or she is likely to come from Indian cities where NDM genes are more prevalent, harbours well over twenty times as many NDM-1 genes as local residents. “As such, pilgrimage areas may act as ‘hot spots’ for the broader transmission of blaNDM-1 and other ARG [antibiotic resistant genes], especially considering bathing and water consumption occur in Ganges waters and exposed visitors return home after their visit to the region,” it concludes.

This prompted me to call David Graham, one of the co-authors of the paper and the man who then informed me that both he and I were likely to have NDM-1 genes in our guts. Graham told me he had worked for more than 15 years on the effects of trace contaminants in the environment.

Studying almost anything in river water is complicated nowadays because humans pour in so many different types of pollutants that it is hard to find out precisely which ingredient is affecting what and how. “Big rivers are different than little streams. It’s very, very difficult to explicitly—with no ambiguity—show cause and effect,” says Graham. “We could have gone [downstream] to Varanasi and come up with a sensational paper that was really very, very scary.” Instead, intrigued by the prevalence of antibiotic resistance in India and Pakistan, and inspired by the suggestions of Ziauddin Shaikh from India, who was then one of his post-doctoral researchers, Graham started studying the Haridwar pilgrimage sites on the Ganges in 2012. Graham and Shaikh have been sampling the river twice a year since then. “The political implications of this are very substantial,” says Graham. “They’ve got to stop open defecation. If they are seeing anything like this at other places along the Ganges, they have got to stop it ... In some places within India I think things are maybe hopeless. But if we can create beacons of hope along the river, that will create some social momentum.”

Shaikh became an assistant professor at the department of biochemical engineering and biotechnology at the Indian Institute of Technology in Delhi, one of the country’s elite academic institutions. “We have to increase the number of treatment plants and improve the operation of existing treatment plants,” he said. After three years of Ganges sampling, “we can see the signature pattern for antibiotic resistance genes and how they are getting stored in the environment ... In Rishikesh and Haridwar it’s showing an increase in trend.” TR Sreekrishnan, the head of the department and another co-author of the study, said: “The only route it can enter the water is through faecal contamination ... If you do not properly treat the waste before it’s discharged into the rivers you are not only contaminating the water, you are also assisting the proliferation of antibiotic resistance.”

The global spread of NDM-1 since its discovery less than a decade ago has been startlingly quick. The first-known human carrier of the gene was a 59-year-old diabetic Swedish hospital patient of Indian origin who caught a urinary tract infection on a trip to India in 2009. He had been treated in Ludhiana and Delhi for an abscess on his buttocks and underwent surgery. As described in The Lancet, the infection was caused by a strain of the Klebsiella pneumoniae bacterium that was resistant to antibiotics because of the presence of a previously unknown bacterial gene that codes for NDM-1.

The suggestion that Indian hospitals—a cheap destination for medical tourists from around the world—were the source of the problem prompted a predictably angry reaction at the time from some Indian doctors and government officials. A few even suggested a Western conspiracy to undermine the Indian economy. “We feel this is economically motivated,” said Dr Raman Sardana, secretary of the Hospital Infection Society India.

Yet hospitals, with their combination of sick people and multiple drug regimes, are known to be ideal breeding grounds for the accelerated evolution of pathogens. A hospital in Delhi conducted a study in 2010 and found 22 patients carrying bacteria with NDM-1 genes in three months; others were soon identified elsewhere in India and in Pakistan. India’s poor sanitation and the abuse of antibiotics (drugs can easily be obtained without a doctor’s prescription and patients frequently fail to complete a course of medicine, encouraging the survival and proliferation of resistant strains of disease) only deepen the crisis. The two problems together “make India a perfect system for the spread of antibiotic resistance,” says David Livermore, professor of medical microbiology at the University of East Anglia in the UK. “India and Pakistan are the first countries where this kind of resistance has got real traction.”

Ramanan Laxminarayan of the Public Health Foundation of India, an expert on the topic, said India had a “perfect storm” to produce highly pathogenic strains of bacteria, in the form of a “large pharmaceutical industry, high background rates of infectious diseases, and an affluent population that can afford antibiotics.”

Tim Walsh of Cardiff University, another microbiology professor who co-authored the report in The Lancet, says India’s political and medical establishment is in denial about the scale of the problem, despite some good research in the country. One reason, he suggests, is that Indian hospitals do not want to put off patients from abroad: more than three million “medical tourists” visit the country each year. Walsh says he has not been welcome in India since heled the 2010 study.

Bacterial infections resistant to most antibiotics because of the NDM-1 gene are now found in hospitals all over the world. The victims include those who have travelled to India for cosmetic surgery, US soldiers who fought in Afghanistan, and returning holidaymakers.

The main “reservoirs” of bacteria with NDM-1 nevertheless remain in the Indian subcontinent, the Middle East, and the Balkans. In 2011, Walsh and others published another study in The Lancet. They found bacteria containing the NDM-1 gene in nearly a third of the surface water samples they tested in New Delhi, and even in two of the fifty drinking-water samples. The gene, furthermore, was found in 11 species of bacteria where it had not been previously reported, including Shigella boydii and Vibrio cholerae, which can cause dysentery and cholera respectively. The point, now well established, is that even if blaNDM-1 was originally selected and detected in the ideal conditions of a hospital, it is now widespread in the environment, including in Indian rivers such as the Ganges.

This is an extract from River of Life, River of Death: The Ganges and India’s Future by Victor Mallet, published by Oxford University Press. The extract has been condensed.