Debate: Are we prepared for `Resistance'?

"High degree of resistance to antibiotics"

Sunil Gupta, Additional Director, National Centre for Disease Control (NCDC), New Delhi

The problem is no longer restricted to the healthcare sector; it has now emerged as a wider concern involving the animal, food and livestock sectors as well as environmental contamination. The health ministry launched the National Programme on Containment of Antimicrobial Resistance on a pilot basis under the 12th Five Year Plan, which is being coordinated by NCDC.

Under the programme, at least 30 laboratories have been envisaged and 10 labs have already been established to put in place a surveillance system. This year, four to five more labs will be set up in north-eastern states and Himachal Pradesh. The Indian Council of Medical Research (ICMR) has also developed a network of four labs located in premier tertiary care centres in the country. At present, NCDC is analysing data from nine labs for 2015 to determine the magnitude and trends of AMR in different geographical regions of the country. Preliminary analysis shows a reasonably high degree of resistance to antibiotics.

National guidelines for antimicrobial use in infectious diseases were released in February, 2016, which will help all healthcare facilities to formulate their own guidelines, and physicians will be trained accordingly. To strengthen regulation, a separate Schedule H-1 has been incorporated in the Drug and Cosmetic Rules, 1945, to regulate the sale of antimicrobials in the country. About 24 antimicrobials are covered in it. Hospital infection control guidelines have also been formulated, and we are in the process of communicating this to the agencies concerned.

Strengthening AMR surveillance will be our focus for which independent quality assurance agencies like the Indian Association of Medical Microbiologists will be roped in. Besides expanding surveillance labs, more bacterial pathogens would be added in AMR surveillance. Surveillance for antibiotic use patterns in hospitals will be initiated. Trainings will be carried out on antibiotic stewardship for different stakeholders. AMR is a challenging subject that involves multiple diseases and it will take some time to tackle it adequately. The national action plan will be rolled out by May 2017.

 

"Combat measures are inadequate"

Satya Sivaraman, Communications coordinator, ReAct, a Sweden-based non-profit

After a long period of neglect, India has finally woken up to the growing problem of AMR. However, the scale and complexity of the problem is such that these measures are simply inadequate to address the magnitude of the problem. Consider this: India has one of the largest burdens of communicable diseases in the world; the world’s largest incidence of TB, accounting for around a quarter of all new cases reported every year; and, in 2015, the country recorded the largest number of under-five deaths in the world—at 1.3 million—followed by Nigeria and Pakistan. Moreover, rotavirus is the leading cause of under-five deaths due to diarrhoea (146,000 deaths), and pneumococcal pneumonia was the leading cause of under-five deaths due to lower respiratory infections with 393,000 deaths.

The dismal situation of communicable diseases in India is linked to both widespread income poverty as well as poor access to basic resources such as nutrition, water, energy and sanitation facilities. At the same time, due to growing urbanisation and changing lifestyles, the number of diabetes and cardiovascular cases has sharply increased. These require prolonged hospitalisation and often involve surgeries. What makes matters worse is that the country has one of the lowest ratios of healthcare personnel to population in the world, 2.08 per 1,000 population, which is much lower than WHO’s critical shortage threshold of 2.28. According to a study published in The Lancet in 2010, India was the largest consumer of antibiotics in the world, followed by China and the US. These figures do not include antibiotics consumption in the animal and food production sector. There is also no comprehensive policy to restrict non-therapeutic use of antibiotics in the animal farming and food sectors. There is no systematic collection of data on resistance in major pathogen groups either at the national or local levels. Availability of lab facilities and trained personnel to meet this challenge is grossly inadequate. Though we are taking steps to tackle AMR, more innovative measures are needed urgently.

 

"No new antibiotic molecule since 1987"

Kamini Walia, Senior scientist, Division of Epidemiology and Communicable Diseases, Indian Council of Medical Research, New Delhi

The problem of antibiotic resistance has always existed—the first antibiotic Penicillin was discovered in 1928 and cases of Penicillin resistance were reported as early as in the 1940s. Resistance to other antimicrobial agents was reported within a decade of their discovery. It is the combination of factors like negligent broad spectrum antibiotic prescription practices among medical practitioners, non-compliance to the recommended treatment duration, absence of robust regulatory structure for sale of antibiotics and the non-judicious use of antimicrobial agents by populations which are driving AMR. In India, the treatment of infections is often mishandled owing to factors which include lack of appropriate diagnostic support in terms of quality and availability, absence of outbreak reports by any national agency for wider dissemination and the tendency of doctors to continue age-old prescription practices and various socio-economic factors.

We need to strengthen our understanding at multiple levels so that we are able to launch an informed response in each of the gap areas. There is an urgent need to have a correct estimate of the drug resistant infections for which effective and responsive surveillance systems are needed at national and regional levels. ICMR’s surveillance network has brought forth several promising leads and evidence of AMR. The data generated through this network is being used to devise treatment guidelines with the help of clinicians. These guidelines will be helpful in harmonising treatment practices across the tertiary level healthcare institutions in the country.

There are still many gaps in our understanding of the molecular and cellular biology of bacterial resistance, especially how bacteria evolve, acquire and transmit antibiotic resistance and how they adapt to life in human and animal hosts. ICMR, through its various programmes, which include collaborative research with international organisations, is helping us understand naturally occurring resistance mechanisms and targets through advances in genomics, systems biology and structural biology, which could guide development of new diagnostics, potential drug targets and drug molecules.

An early stage of drug development, if supported by scientific studies on resistance development and mechanisms of resistance, will also facilitate the development of dosing regimens. This can help minimise the emergence of resistance to current and new antibiotics, enabling these drugs to be used to best effect, and focus resources on agents that are less likely to fail.

Due to the shortage of new antibiotics being developed, it has become imperative that current treatments are used judiciously by both healthcare professionals and members of the community. Antimicrobial Stewardship Programmes (AMSPs), which are multi-disciplinary, have been demonstrated to optimise antibiotic usage and reduce associated adverse events.

Implementation of strong AMSPs have been helpful in checking the irrational use of antibiotics in many countries which have implemented AMSPs with varying degrees of success. ICMR has also initiated activities to harmonise infection control practices and strengthen AMSP programmes. ICMR’s infection control guidelines, if enforced, will go a long way in reducing infections in hospitals, thus bringing down the rates of drug-resistant infections.

The traditional approach to combat infectious diseases and AMR has been reliance on new drugs and drug combinations as seen in the case of TB and malaria programmes.

But the picture ahead is not very promising as the pipeline of antibiotics is fast drying up and no new antibiotic molecule has been reported since 1987.

 

"Teach farmers to judiciously use antibiotics"

Manjunath Marappan, Co-founder, The Happy Hens Farm, Bengaluru

We have lost our knowledge of traditional natural medicines. I feel farmers should be educated to judiciously use antibiotics and should be taught the difference between using therapeutic and non-therapeutic antibiotics and their impacts on the foodchain and the environment. They should also be taught about the benefits of alternative medicines. At our farm, we do not use any non-therapeutic antibiotics. At present, there is widespread use of antibiotics, so we need a stricter law. The government should also conduct random tests on feed companies and meat processing units to control the use of antibiotics. Ethical and animal-friendly farming should be encouraged along with traditional natural medicines.

 

"India is on the path to successfully confronting resistance"

Ramanan Laxminarayan, Director and Senior Fellow at Washington D.C-based Center for Disease Dynamics, Economics & Policy

In India, common bacterial infections are becoming increasingly difficult to cure because the pathogens that cause them have become resistant to antibiotics. Inappropriate use by patients and healthcare providers, in human medicine as well as animals, is driving antibiotic resistance. The problem is compounded in low-resource settings, where lack of access to quality medicines and diagnostics, weak health systems, and high levels of infectious diseases are everyday challenges.

Fortunately, successful efforts to confront resistance in low-resource settings exist, demonstrating a path forward for India. In South Africa, the Antimicrobial Resistance National Strategy Framework 2014-2024 includes provisions for infection prevention, education, and appropriate use in animals, among others. The framework was developed by the Ministry of Health of South Africa in cooperation with other stakeholders and is supported by public and private sector surveillance of antibiotic resistance, which can guide both policymaking and physician decision-making.

Vietnam also conducts surveillance though a network of hospital labs participating in the Vietnam Resistance Project. Both of these national plans were informed by data from comprehensive situation analyses conducted by Global Antibiotic Resistance Partnership (GARP) working groups. GARP, which is coordinated by the Center for Disease Dynamics, Economics & Policy (CDDEP), has established local policy analysis and policy development capacity related to antibiotic resistance in selected low- and middle-income countries.

India is on the path to successfully confronting resistance. In order to track the current status of antibiotic resistance and use, The Indian Council of Medical Research developed a resistance surveillance network with four hospital laboratories and the National Center for Disease Control developed a surveillance network with 10 hospital laboratories. Aggregated data are available from external repositories, such as Resistance Map, but these datasets are geographically limited and may not include important details, like genetic profiles. Furthermore, no surveillance system currently exists for antibiotic use in human medicine, or use and resistance in animals.

Preventing infections from occurring by improving access to water and sanitation, and increasing immunization coverage, is another proven strategy to reduce the need for antibiotics – and thereby reduce resistance. In December 2014, the Ministry of Health and Family Welfare launched “Mission Indradhanush,” resulting in a 10 percent increase in full immunisation coverage – an unprecedented accomplishment in any country.

To improve the use of antibiotics, nationwide awareness campaign “Medicines with the Red Line,” was introduced in 2016 to educate the public about irrational antibiotic use. All antibiotics are now clearly marked with a red line on their packaging, indicating that they are valuable resources. The Government of India notification of Schedule H1 was introduced to restrict over the counter antibiotic sales, though enforcement has been inconsistent. In 2016, the National Centre for Disease Control published “National Treatment Guidelines for Antimicrobial Use in Infectious Diseases,” to guide the use of antimicrobials in health care facilities.

The drivers of antibiotic resistance that are perhaps most in need of increased attention in India are antibiotic use in animals and the environment. Increased regulation would help to prevent antibiotic residues and resistant bacteria from entering the environment – particularly through wastewater treatment plants around antibiotic production sites. India is a major producer and exporter of antibiotics, and in production sites such as Hyderabad, studies have detected antibiotic residues in higher concentrations than ever before.

Overall, India is on the path to curbing antibiotic resistance, despite the many challenges faced in low-resource settings. Now is the moment to seize energy generated by the World Health Organization (WHO) and other United Nations organizations by consolidating efforts around a strategic action plan that sets the course for the next decade of action. What happens now will determine whether future generations of Indians will have access to affordable, effective antibiotics.