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India’s bitter pill

Jyotsna Singh | Updated on November 22, 2019 Published on November 22, 2019

Breaking point: When the body is subject to an irrational dosage of antibiotics, its power to control an infection is diminished   -  ISTOCK.COM

How did India become the most drug-resistant nation in the world and what is it doing to combat lethal mutating infections? From draft national medical policies to new pharma regulations and better primary diagnostics, on World Antibiotic Awareness Week, a roundup of the measures unleashed to battle this mass killer

Swaraj Kumar’s death tells a tale. Kumar (name changed) was recently admitted to a super-speciality hospital in New Delhi. He was suffering from pneumonia and, in normal circumstances, would have been cured with a few rounds of antibiotics. Doctors gave him commonly available drugs, and then some of the strongest ones. But nothing worked.

Kumar, they found, was drug resistant — a condition that develops when the body is subject to an irrational dosage of antibiotics, diminishing its power to control an infection. The 60-year-old died of septicemic shock last month.

But his death did not come as a surprise to the doctors treating him. “This is not rare any more,” says Dr Sandeep Nayar, director and head, Centre for Chest and Respiratory Diseases, BLK hospital. “We receive patients with high levels of resistance to antibiotics. Some respond to only last-resort antibiotics; others do not. We end up losing many patients like him.”

On World Antibiotic Awareness Week — marked from November 18 to 24 this year — the lens is again being turned on antibiotic resistance, which has emerged as a major threat to public health across the world. The situation is particularly dire in India, which has the highest antibiotic resistance in the world, according to a recent study by Johns Hopkins School of Medicine, Johns Hopkins Bloomberg School of Public Health and the Center for Disease Dynamics, Economics & Policy, all in the US. India also tops the world in antibiotic consumption per person.

Antibiotics kill the bacteria that infect humans (and animals) with illnesses ranging from tonsillitis to lethal infections such as sepsis. When bacteria develop resistance to antibiotics, the treatment no longer works, and can even lead to death.

Resistance to broad-spectrum antibiotics fluoroquinolones and cephalosporin, used to treat various types of illnesses, is as high as 70 per cent in India for certain bacteria such as E.Coli, which commonly cause diseases such as pneumonia, urinary tract infections and diarrhoea. Even for the antibiotics that are prescribed when all other antibiotics stop working, resistance is found to be high in India. According to the Washington- and New Delhi-based Center for Disease Dynamics, Economics & Policy, resistance to the carbapenem class of antibiotics (usually used for high-risk infections) is 56 per cent in India for the bacteria K. pneumoniae, one of the main causes of pneumonia and lung infection.

It is estimated that antibiotic resistance will kill 10 million people every year by 2050, and cost the world — through loss of life, hospital stay, prolonged treatment and so on — an annual loss of $ 100 trillion.

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The reasons for the high resistance in India are being studied by researchers. One of the factors, health experts rue, is that antibiotics are given to a patient even when they are not needed. For instance, antibiotics do not cure viral infections, but the drugs are often prescribed anyway. Second, unlike in the West, antibiotics are easily available over the counter across the country.

Yet another factor is that many of the drugs are expensive, especially the higher class of antibiotics. If amoxicillin, which is a type of penicillin, costs about ₹100 for a strip of 10, meropenem can cost ₹2,500-3,000. The high costs often prompt patients to discontinue their medicines midway through a course when the symptoms of the disease have disappeared. But the bacteria remain in the body, and are not killed when the same antibiotic is administered later.

“First, resistance reduces the pool of antibiotics from which we can select a rational antibiotic for an individual patient. Second, the higher class of antibiotics is more likely to create toxicity to the liver and kidneys. Sometimes, we have to make the difficult choice of saving the patient at the cost of compromised kidneys. But we think that can be dealt with later. However, if patients do not come to us with resistance, treatment would be so much easier for us and the patients,” Dr Nayar says.

Resistance in Kumar’s body, for instance, was because of the “irrational treatment” — the most common cause of resistance in India — he had earlier received. Before pneumonia, he suffered from allergic rhinitis — inflammation in the nose caused by allergens in the air. It is mostly a viral infection, which antibiotics cannot treat. But he was given antibiotics, and the bacteria finally developed drug resistance.

Clearly, the problem of antibiotic resistance is an overarching issue facing the health system. First, it is not restricted to any one disease, and changing the behaviour of all doctors and healthcare staff is an uphill task. Second, it is not just linked to medicines, but also hygiene practices. To control the spread of infections, adequate facilities for washing one’s hands with clean water are essential. Third, resistance patterns in the country show that bacteria are present in animals, as well as in the soil, water and air. So it is not just a health issue, but calls for collaboration across the board.

There is a general notion that people become resistant to drugs. The truth is, it is the bacterium that is affected. Once people are infected, their immune system gets into action and tries to flush the bacteria out. When that action is not sufficient, the bacteria start to grow. External agents are then required to remove them, and antibiotics come into play. But over the decades, bacteria, for their own survival, have found ways to block the action of antibiotics.

Antibiotics are supposed to kill all the bacteria that have caused an infection. But when they don’t, the leftover bacteria can develop resistance to the drugs and spread into the environment and other human beings. That is the reason a doctor insists that patients finish the entire prescribed course.

“If already resistant bacteria infect a person, then even without prior history of consuming antibiotics, the person will not be cured with a lower class of antibiotics,” warns Dr HS Rehan, head, pharmacology department, Lady Hardinge Medical College (LHMC), New Delhi.

Horror story: The first-line treatment of TB no longer works for a growing number of people   -  THE HINDU/V SREENIVASA MURTHY

 

One disease that has faced the full-blown impact of resistance is tuberculosis (TB). TB is treated with a mix of four or five antibiotics. The first-line treatment of TB has long existed, but doctors are increasingly treating people on whom the medicines do not work any more. Drug-resistant TB is a grave problem in India today.

Take the case of 27-year-old Meera Yadav, a patient of what is known as extremely drug-resistant (XDR) TB. She was 22 when she was diagnosed with multi-drug resistant (MDR) TB. But even after three years of treatment her condition did not improve. The bacteria ate up her right lung, leaving her with only one lung. Later, it was found that she had XDR-TB and had been treated for MDR-TB. In MDR-TB, the bacteria is resistant to a few drugs. In XDR, almost all antibiotics stop working.

“Now I live with only one lung. I have to drain 10 ml of pus every three hours from my lung through a window under my arms. I have been living with this condition for the last three years and doctors are not sure for how much longer this will continue,” she says.

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The overuse of antibiotics is closely related to the promotional strategies of pharma companies producing them. A study by the Nobel Peace Prize-winning organisation Médecins Sans Frontières shows that pharma representatives were a big influence in the small district of Asansol, West Bengal, in asking doctors to prescribe antibiotics.

Realising the extent of the crisis, the World Health Organisation has been pushing countries to develop policies to battle Antimicrobial Resistance (AMR). The Indian government also plans to collaborate with the WHO on AMR. In 2017, India was among the first countries to frame a national action plan on this. But only two states — Kerala and Madhya Pradesh — have come up with action plans so far.

With the National Centre for Disease Control (NCDC) under the ministry of health as the nodal agency, many other ministries have been tasked to draft action plans to control AMR. The Centre plans to involve 11 ministries — including health, agriculture, environment, fisheries and science — to chalk out a nationwide plan. However, India faces lack of data.

“We are lacking sufficient data to come up with rational treatments. The Indian Council of Medical Research (ICMR) is conducting surveillance of drug resistance in 16 hospitals across the country. This will help in generating evidence to guide policy and contain AMR,” says Dr Kamini Walia, senior scientist, division of epidemiology and communicable diseases, ICMR, who also oversees the council’s AMR initiatives.

The problem, experts hold, is that efforts are being made only at the tertiary-care level. “But the main driver of antibiotic resistance are diseases at the primary healthcare level — most of the upper respiratory tract infections and diarrhoea need not be treated with antibiotics, but doctors and informal healthcare providers prescribe them rampantly,” says Nafis Faizi from Jan Swasthya Abhiyan, a health movement body.

On the other hand, Philip Mathew, public health consultant for ReAct Asia Pacific, a global network, warns against the over-reliance on data. He cites the example of the Antibiotic Smart Use Project in Thailand, under which people are given information about, say, how to examine a sore throat and what medicines to take. “People can examine their own throat and decide whether they require antibiotics or not,” Mathew adds. Thailand has also converted its traditional herbal medicines into capsules, which are given to patients who insist on medicines when they do not actually require any.

“India faces similar problems and can adopt this mechanism,” he adds.

At the LHMC and its associated Sucheta Kripalani Hospital, Rehan’s department collects daily data from all other departments and analyses the use of antibiotics in relation to the diseases concerned. “This collection of data itself becomes a deterrent for doctors and they do not prescribe extra antibiotics. As we are also responsible for procuring medicines, this system also helps us in procuring enough medicines, which we give free to our patients,” he says.

If patients get medicines free of cost in a functional public health system, they adhere to the treatment regimen prescribed by the doctors. Data from LHMC show that currently 23 per cent patients receive antibiotics in the hospital, substantially lower than the 35 per cent three years ago.

Another hurdle is the lack of diagnostics. A government hospital or centre can take 48 hours or so to know which antibiotic can work in a given situation. Meanwhile, a patient is given some antibiotics, which may have to be changed once the test results come in. “We need diagnostics that can reduce this time, so that the right antibiotics can be given from the start,” Rehan adds.

Before you pop one: It is projected that two million people in India will die of AMR by 2050   -  ISTOCK.COM

 

To control AMR, point-of-care (POC) diagnostics that can be used in primary health settings are needed. POC testing is mostly performed at or near a place where care is being provided to a patient. But diagnostic companies find laboratory-based tests more profitable. To fill the gap, governments are investing in POC tests. The United Kingdom government has taken an initiative in the form of the Longitude Prize where an effective new test will be awarded 10 million pounds in 2020. The Indian government’s department of biotechnology has funded many Indian start-ups who are vying for the prize.

It is projected that two million people in India will die of AMR by 2050 if urgent steps are not taken. It’s time all hands are on deck to battle a mushrooming mass killer.

Jyotsna Singh is a Delhi-based health writer

‘Over 2,14,000 babies die each year from drug-resistant infections the world over’
  • Half of the antibiotics in use now were developed in the 1950s, stresses Dr Manica Balasegaram, executive director, The Global Antibiotic Research and Development Partnership (GARDP). A not-for-profit research and development organisation based in Geneva, GARDP seeks to deliver new treatments, he tells BLink.
  • AMR is a result of many things gone wrong, starting with the use of antibiotics in animal feed to poor hygiene in hospitals and communities. But what is the role of the pharmaceutical industry in this crisis?
  • The high volume, high price ‘blockbuster’ business model that has traditionally been used by the pharmaceutical industry in the development of new drugs does not work for antibiotics. The research and development of new antibiotics can be risky and is scientifically challenging. As a result, very few new antibiotics have been developed by the pharmaceutical industry over the past decades. This means there is an urgent need to try different approaches, like upfront funding and market entry rewards. So investment is critical. However, incentive programmes to develop new antibiotics and tackle drug resistance must also be driven by public health and patient needs, rather than pure market returns.
  • Ultimately, governments and the public sector must play a part in making the right push-and-pull incentives. GARDP has been set up as such a mechanism to deliver new treatments.
  • What kind of antibiotics are in the pipeline?
  • Pew [a US-based non-profit trust], which has been tracking global antibiotic development, reports that as of June 2019 there were 42 new antibiotics with the potential to treat serious bacterial infections in clinical development. However, it’s important to note that even when new antibiotics are made available, they are often only registered for use in a small number of countries. Research by Kållberg and others (2018) found that 25 new antibiotics that entered the market between 1999 and 2014, only 12 were registered for use in more than 10 countries. GARDP is developing treatments for drug-resistant infections, as well working to ensure these treatments are responsibly and sustainably available for every person who needs them, wherever they live.
  • Most big pharma companies have stopped manufacturing antibiotics...
  • Most pharmaceutical companies are no longer working on the research and development of new antibiotics. Half of all antibiotics used today were discovered during the 1950s. Since that time, discovery and development of new antibiotics has become more complex, time consuming and expensive. New antibiotics that are approved typically have short treatment durations and restrictions on their use to slow the development and spread of resistance. This limits their profitability. So there is a lack of suitable economic models to support urgently needed antibiotics.
  • No country, company or organisation can fix the broken pipeline for antibiotics alone. Developing a pipeline of novel antibiotics and registering them for indications and populations where they are needed most will require new and scaled-up forms of public-private partnerships. GARDP is a not-for-profit working to accelerate the research and development of treatments for drug-resistant infections through a public health-focused portfolio approach. GARDP’s 5 BY 25 goal is seeking to develop 5 new treatments by 2025 to address priority drug-resistant infections.
  • How acute is the problem of lack of antibiotics for children?
  • Globally, infectious diseases such as pneumonia and sepsis are the leading cause of death and disability in children under five. This situation is only worsened by drug-resistant infections. More than 2,14,000 babies die each year from drug-resistant infection. Most of these deaths occur in low- and middle-countries. Children are not small adults and their bodies react differently to antibiotics. It is critical to establish the correct dose for use in children and confirm the safety and effectiveness is the same as in adults. Although most regulatory agencies require pharmaceutical companies to develop plans to evaluate new antibiotics for use in children, these are generally not started until after drugs are registered for use in adults. Many plans are delayed for years after licensing in adults, if they are developed at all. A recent study by Thompson and others (2017) found that of 37 new antibiotics being developed in adults, just two were being studied in children.

Published on November 22, 2019
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