No Local Woe, India's Poor Public Health Feeds Antibiotic Resistance Worldwide

The spread of resistance is more acute in places where antibiotic use is poorly regulated, local pollution is higher and inadequate sanitation is common – conditions that prevail across most of India.

Antibiotic resistance genes from around the world are accumulating in even the most remote locations, such as the Arctic soils, highlighting the pace with which these threats can globalise.

Scientists from Newcastle University have found an antibiotic resistance gene, called the New Delhi metallo-beta-lactamase (blaNDM-1), in soil samples taken in 2013 in Kongsfjorden in the Svalbard archipelago. blaNDM-1 was originally detected in surface seeps in Indian cities in 2011, less than three years prior.

The difference in the climates of these two locations can’t be understated: the remote island in the Arctic has no agriculture or industry, very few people and temperatures low enough to freeze and preserve genetic material.

Metallo-beta-lactamase (NDM) is an enzyme that makes empowers bacteria to resist a broad range of antibiotics. David Graham, one of the Newcastle researchers and an ecosystems engineer, told The Wire that their study “shows how far reaching and how fast resistance can move around the world, which impacts everyone.”

Thankfully, the levels of blaNDM-1 were localised in Kongsfjorden “and posed no health threat” there, according to their published paper. The authors say their findings highlight the value of characterising remote locations that could provide a baseline for estimating the spread of antibiotic resistance around the world.

Also read: Antibiotic Resistant Bacteria Are in Deep Shit – and So Are We

This is not the first time the resistance gene has been found in places away from India. In January 2017, the US Centre for Disease Control (CDC) confirmed the presence of NDM in the body of an American woman who was infected when she was being treated for a thigh-bone fracture in India in 2015. She would die later in 2017.

The CDC report prompted the Drug Controller General of India (DCGI) to issue a notification on January 16, 2017. In it, the DCGI ordered all companies involved in the supply chain to follow guidelines specified in the Drugs and Cosmetics Act on sale of medicines, and directed state drug regulators to act against people selling antibiotics without prescriptions.

Then again, the study also suggests that the spread of blaNDM-1 could be related to factors “that may be equally or more important” than just the direct use of antibiotics.

For example, Graham explained that the spread of resistance appears to be more acute in places where antibiotic use is poorly regulated, local pollution is higher and inadequate sanitation is common. Such conditions allow resistance in one person’s or animal’s faecal matter to enter the environment, exposing residual resistance in their faeces to others.

“Such exposures set off a chain of exposures, which our work indicates can ultimately reach remote places like the Arctic.”

“That resistance genes spread globally is no surprise,” Ramanan Laxminarayan, founder and director, Centre for Disease Dynamics, Economics and Policy (CDDEP), said. However, “we don’t know all the pathways by which they spread, and in this case, it is possibly wild birds that have carried these resistance genes to the Arctic.”

The CDDEP is a public-health research organisation with offices in Washington, DC, and New Delhi.

He added that he wouldn’t “make much of the identification of NDM in the Arctic” and that wasn’t surprising in the least. “The more important thing is to worry about is what is happening in India and to Indian patients.”

Lessons for India

Since the NDM gene was first reported in 2011, there have been several alarm bells going off on the growing problem of antibiotic resistance.

A 2016 paper in the journal PLoS Medicine, coauthored by Laxminarayan, reported that India was the world’s largest consumer of antibiotics for human health in 2010. It also said that 76% of the overall increase in global antibiotic consumption between 2000 and 2010 came from BRICS countries alone.

When access to antibiotics rises, it’s generally good and but can quickly turn simultaneously bad.

Also read: How Researchers Found That Tourists Accidentally Carried a Superbug from India to Paris

According to the study’s findings, Indians consumed 10.7 units of antibiotics per person, compared to China’s 7.5 units and the US’s 22 units. Within the BRICS countries, 23% of the increase in retail antibiotic sales was from India, and up to 57% of the increase in the hospital sector came from China.

The biggest issue with the Indian situation was the availability of carbapenems. This is a class of highly effective and often last-resort antibiotics used for severe- to high-risk bacterial infections. The study said that over-the-counter, nonprescription sales of carbapenems India “are among the highest in the world”, and contribute to growing resistance to these drugs.

A November 2017 scoping paper prepared by the Department of Biotechnology and Research Councils UK-India stated that while antimicrobial resistance is a global public health threat, “nowhere is it as stark as in India”.

According to it, India has some of the highest antibiotic resistance rates among bacteria that commonly cause infections. Additionally, resistance to the class of broad-spectrum antibiotics called fluoroquinolones and the third-generation cephalosporin was over 70% in the Acinetobacter baumannii bacteria.

India has also reported the presence of bacteria that are resistant to colistin, another last-resort antibiotic that doctors around the world believe will replace carbapenems.

Researchers have found such bacteria in India in poultry, livestock, aquaculture, rivers, sewage and hospital drains.

Graham also said that “the problem of environmental spread may be of particular relevance to India because key factors that appear to most influence environmental resistance spread are common in some places.”

He suggested that India pay more attention to curbing antibiotic use along with improving sanitation. The ultimate goal would be to choke the spread of resistance via environmental pathways, especially reducing exposure to wildlife and other “travellers”, which carry resistance around India or, in fact, around the world.

At the same time, the steps that can be taken to contain the spread of the gene are “simple to state, but hard to implement,” Graham said.

The first is to use less antibiotics on a global scale. “However, unless we simultaneously improve sanitation, water quality and food safety around the world, reducing use will likely have limited impact.

“Therefore, containing the spread of this and other genes that can make bacteria highly resistant must be tackled by a multi-pronged approach.”

Also read: An Insider’s Perspective on India’s Failing Public Health System

Laxminarayan is less optimistic: “Not much can be done to contain the spread,” he said. However, he acknowledged that measures to use antibiotics appropriately in both humans and animals to delay the emergence of these genes in the first place could help.

But here again the problem that Graham pointed out arises: the whole world must use such a holistic approach because data unearthed by CDDEP, he said, suggests that resistance migrates fast and easily. “Positive actions of one country will have limited impact unless all countries are also on board.” I.e., all or nothing.

One of the other issues related to resistance, and human and veterinary health in general, is that scientists have almost completely stopped developing new drugs. This is because bacteria become resistant to drugs, old and new, faster than a drug can be developed and introduced into the market. As a result, drug development has become uneconomical for manufacturers.

This is why “we must urgently reduce rates of new resistance evolution, which hopefully will spur new drug development in industry,” Graham said.

The first step in that direction would be delay the resistance genes from spreading within the origin country by providing  better water and sanitation, and improving public health, Laxminarayan said. “If these are not done, then little is possible.”

T.V. Padma is a freelance science journalist.