Drug resistance may spawn new diseases

Two alarming reports have been published this year in medical journals, highlighting the emergence of resistance to antimicrobials (drugs used to treat infections due to bacteria, viruses and fungi etc). A recent study in The Lancet Microbe discusses the intercontinental spread of antimicrobial-resistant Salmonella typhi, the bacterium causing typhoid fever. Earlier in January, The Lancet had carried another study, “Global burden of bacterial antimicrobial resistance in 2019: A systemic analysis”. Bacteria become resistant to antimicrobial agents when changes in them cause the drugs to be ineffective in killing them. These two reports bring to the fore an impending disaster which seems to have been ignored due to the raging Covid-19 pandemic.

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The typhoid study is the largest one of its kind looking at genomic sequencing of the typhoid bacteria isolated from 2016 to 2019 from Bangladesh, Nepal, Pakistan and India. The researchers explored 3,489 newly sequenced isolates from these countries together with over 4,000 strains from 1905 to 2018 from more than 70 countries to study the emergence of antimicrobial resistance (AMR) and how it spread to different geographical areas. It was found that genetic mutations in the organism resulted in resistance to commonly used antibiotics like ciprofloxacin and erythromycin. In the last 30 years, resistance spread nearly 200 times, both within a continent and to other continents. South Asia remained the largest (90%) hub of mutations and the source of spread, which occurred within countries of South Asia, and from South Asia to South East Asia and Southern Africa. There was spread to Europe and the Americas too.

The results have far-reaching implications. First, it makes treatment of a common problem difficult with patients needing tests to see the efficacy of different antibiotics. The failure rates of treatment go up, so does the cost. Resultantly, there is an increase in the duration of hospitalisation and the death rate. Secondly, the spread of resistant strains to different countries and even continents calls for a change in epidemiological control strategies which need to become global, rather than country or region specific. Thirdly, the emergence of extremely resistant strains calls for expanding preventive measures, including typhoid vaccines in typhoid-endemic countries.

The second study published earlier this year looked at the global burden of AMR with estimates from over 200 countries and over 20 bacterial pathogens. It was deduced that in 2019, close to 4.95 million deaths across the world were attributed to AMR with the low resource countries being the most affected. Nearly three-fourth of these deaths were linked to only six bacteria, with Escherichia coli being the most prevalent. The biggest contributor to such infections was lower respiratory tract infections, called pneumonia in common parlance. Sub-Saharan Africa was the worst affected followed by South Asia, with Australia being the least affected. The data show that it is imperative to have location/country-specific burden of AMR so that policy decisions are tailor-made accordingly. A fact which is worrisome for India is that it figured with very high prevalence of resistance to the six of the key bacteria when compared to other countries.

Some organisms can become resistant to multiple antimicrobials and can evolve into “super bugs”, and some organisms can transfer resistant genes to other organisms, which can affect other antibiotic treatments. What causes AMR? Over-prescription or misuse of antibiotics is the foremost cause. With non-judicious use of antibiotics, the susceptible organisms adapt to them with genetic changes, resulting in loss of efficacy. According to a 2016 study by the United States’ Centres for Disease Control and Prevention (CDC), at least 30% of antibiotic prescriptions in that country were unnecessary with the most often prescribed antibiotics being those for viral flu, sore throat or sinus infections. In India, this percentage is likely to be manifold higher. Unauthorised quacks and pharmacists randomly issue antibiotics to patients seeking them without any prescription. For every cough or diarrhoea or abdominal pain, some antibiotic is prescribed. Even in hospitals, antimicrobials are prescribed in a knee-jerk reaction, virtually for every indoor admission.

Substandard or poor quality medicines are equally responsible, especially in resource constrained countries. Disease-causing bacteria exposed to sub-therapeutic doses of antimicrobials lead to mutations in the former. More worrisome is the fact that unjustified or sub-optimal antimicrobials can cause class resistance, i.e., resistance to the whole category of drugs rather than one particular agent. Some years ago, a study had found that one in eight antibiotics and one in five antimalarials used in poor countries were substandard. Other causes of AMR include inadequate laboratory testing to identify the appropriate antimicrobial agent, poor compliance by the patient in completing the intended treatment or even switching antibiotics. To add to these are unhygienic conditions in public hospitals, lack of surveillance, limited access to second or third-line antibiotics and indiscriminate use of antibiotics in poultry and animals.

Contamination of human environment is also being recognised as an important factor in AMR. Antibiotics reach the environment via urine and faeces from humans and domestic animals, through improper disposal of drugs and hospital waste, and direct environmental contamination in some industries. In the environment, there is admixing of human and animal microbiota, giving ample opportunity to microbes to acquire and transfer antimicrobial resistance to each other. One extreme example is the use of an antibiotic Colistin which has been used for decades as an additive in livestock feed for promoting growth and treating intestinal infections. Such animals become a source of Colistin-resistant microbes which wreak havoc in serious human infections since Colistin is a last-resort drug for the treatment of infections by multi-drug-resistant Gram-negative bacteria. The environment thus has a role both in the evolution and transmission of resistance, a fact that has not been given due importance.

It is time India woke up to the spectre of AMR looming large. We need strong regulatory systems to ensure antibiotics are prescribed and dispensed rationally, that quality control in their production is enforced and surveillance programmes are initiated to detect and monitor AMR. We need better equipped laboratories and testing facilities apart from state and region specific data collection. Public health education programmes are needed, starting at ground level. It is time we address the role of environment and the connection between antimicrobial use in humans and animals. The ICMR initiative on Antimicrobial Resistance Surveillance and Research Network leaves much to be desired. We could also implement the system of Infectious Diseases Units in our hospitals like in Europe and USA where the usage of higher antibiotics is done in a controlled and supervised manner.