Use of people power and technology solutions to address AMR in LMICs

Resistance to antibiotics is multifactorial. We will gather new data on antibiotic consumption in LMICs using an App and 'citizen science', increase antimicrobial authenticity using counterfeiting tracking managed from smartphones, and determine the roles of hospitals and agriculture in the sustainability of AMR in LMICs, with obvious antibiotic stewardship issues.

Prof Sandeep Verma, Head, Gangwal School of Medical Sciences and Technology, IIT Kanpur, is the Team Lead. Principal Investigator, DST Center of Excellence in Antimicrobial Resistance, IIT Kanpur.

Antimicrobial Resistance (AMR) is a complex medical challenge where drug-resistant organisms rapidly spread through combinations of inappropriate antibiotic use in human and animal health, liberal community access, and poor quality of the drugs. Countering AMR requires coordinated efforts to ensure effectiveness of chemotherapeutic treatments. AMR is particularly challenging in LMICs due to healthcare inequity, limited resources, and lack of knowledge. We will address the Trinity Challenge through data-driven solutions:

• Data-driven genomics: Collaborations will be established for the analysis of genomes and resistomes found in hospital environments (e.g. hospital outflows).  A similar approach will be taken at two veterinary sites (Kashmir and Uttar Pradesh) to map antibiotic usage, and environment samples will be collected for bacterial genomics and antibiotic traces by mass spectrometry methods.

• App-driven data collection: A smart phone App will be developed to collect data on community antibiotic usage - source of drug, whether prescribed, treatment of medical conditions and management of leftover drugs.

• Anti-counterfeiting tools: WHO estimates that 1 in every 10 doses of antibiotics in LMICs is counterfeited. Addressing distribution and purchase of counterfeit medicines will decrease rates of AMR and improve treatment outcomes. A smartphone approach using cost-effective packaging tracing and anti-tampering technology will be deployed.

Our solutions address three main questions regarding AMR which also indicates the target audience for our consideration:

1. Who are the major contributors to AMR (community, hospitals and agriculture)? Here the data collected and generated will be spread over different locations as well as in smaller communities, for tighter data control.
2. Why and how are antimicrobials used in LMIC without prescription controls and how much usage is supported by a qualified health practitioners providing a prescription? The IIT Kanpur community (<25,000) will be requested to download the App on their mobile phones to beta test the innovation. In addition, we have existing partnerships in adjacent rural communities which are accessible through a platform- Asha. These target audience will be connected and followed to understand their needs and develop appropriate technology-driven solutions.
3. If ‘fake’ antimicrobials are at least partly responsible for AMR, then can packaging authenticity and anti-tampering be increased to prevent their use? Our 3D tamper-proof tool will serve a large section of pharma.
4. University of Melbourne is currently generating a E. coli One Health
   data set – humans, animals, environment in the state of Victoria – this will be a very useful dataset for our project to train initial models.

AMR is a global problem which ignores geographical boundaries. There is profound public good in understanding the source(s) and key drivers maintaining AMR; such an understanding will help craft focused responses, and ultimately limit infections caused by highly resistant pathogens.  In turn, a reduction in AMR should ensure better health outcomes especially in LMICs, which suffer from higher burdens of infectious diseases. The development of new resources e.g. an App for collecting data on antibiotic use should have an important educational component, a technology deployed around anti-counterfeiting technologies should ensure the poorer members of LMICs enjoy higher quality antimicrobials while being empowered to immediately determine that the drugs are authentic or counterfeited with the help of their mobile smartphones. Identification of One Health drivers will also deliver solutions for public good given the fact the many LMICs are agrarian economies with great disparities in economic situations. Thus, the four verticals offer public good in the form of:

1. Data-driven knowledge via AI/ML algorithms - which source(s) contribute
2. Multilingual antibiotic app as a product - open source app
3. Tamper-proof 3D printed anti-counterfeit labels as a product
4. One Health paradigm - service to human health and agriculture sector, replacement of antibiotic feed additives

Depending on the results of the genomics surveys, it may be that agricultural use of antimicrobials comes under much greater scrutiny.  While there is clear evidence of ‘growth promoting’ activity from the liberal use of antibiotics in agriculture, there are significant downsides too in the form of AMR.  There are cost-effective alternatives e.g. vaccines to prevent antibiotic-treated diseases in production animals, if there is top-down pressure to develop them for agricultural use.   The spread and use of substandard , fraudulent medicines, contributed by spurious manufacturers, have a significant impact on AMR in LMICs. Our innovation to bring in tamper proof IoT-enabled tags to identify counterfeit drugs will offer an affordable technology to screen and monitor antibiotic packaging through any handheld smartphone. This approach will also give data on the hotspots of spurious drugs and an opportunity for prevention through information and empowerment. The use of smartphone Apps to discover how much antibiotic use is unprescribed or used to address conditions where they will inherently have poor efficacy. Tighter and more accountable stewardship of antimicrobials should benefit communities, and also lower rates of AMR, as the most appropriate, rather than the cheapest, antimicrobials are used.

The scaling of our interventions will provide considerable opportunities for education and training. Stewardship of antimicrobials requires participation from manufacturers, pharmacists, doctors and other healthcare professionals, and the consumers. As data collection, and the novel interpretations planned, begin to resolve where AMR is sustained in the community,the proposed education programs can be developed and implemented. These might include better training of pharmacists in dealing with patients, in designing and deploying simple diagnostic protocols that better align antibiotic use with conditions, with regular sample collection and deeper, AI-driven analysis of pathogens and their encoded ‘resistome’. LMICs need support to establish these approaches but there are considerable gains to be had, for example in moving farmers off antibiotic classes that share resistance mechanisms. Stopping agricultural resistance to antibiotic classes used in humans, which might be transferred from innocuous rural settings into highly intensive medicine in large hospitals, must be avoided. We are also looking for collaboration with larger businesses who could take our successful solutions to more global implementation. While two approaches are more academic in nature leading not only to publications but also policy changes, the other two (App and 3D Labels) have the potential to be scaled for maximum impact.

1. Data-driven Surveillance: We will endeavor to create a robust surveillance system for monitoring antibiotic use, resistance patterns, and the spread of resistant strains through data-driven approaches. We will evolve a data-driven antibiotic stewardship program for optimal antibiotic use. Measurable reduction in overall incidence of AMR-related infections, clinical complications, and number of deaths, using data-driven approaches across LMICs.
2. AMR Mobile App: Best way to measure the success in this vertical will be high levels of end-user engagement as measured by monthly active users (MAUs) of the App, incorporate innovative features in App such as AR/VR and gamification to increase user engagement, and potentially covering geographic coverage in both urban and rural areas, and across different regions and LMICs.
3. Anti-counterfeiting Tools: Successful outcomes of AMR anticounterfeiting effort will require development of advanced and reliable authentication (open) technologies on antibiotic packaging, reduction in the incidence of counterfeit antimicrobial drugs, and adoption of technology by pharma giants.

It is anticipated that eventual success of this Trinity Challenge solution will lead to adoption of One Health AMR approach, across human health, animal health, and environmental sectors. LMICs will serve as living laboratories to execute our proposed ideas and leverage these further with due refinements.

The key headwinds to dealing with AMR are economic and cultural.  In LMICs where access to antimicrobials is relatively free, increasing scrutiny on how such drugs are obtained will place a potentially unwanted focus on community pharmacies where drugs are sold.  Equally, consumers in such settings expect to be able to buy antimicrobials when they believe they are necessary.  The only effective management of this environment requires greater regulatory oversight and education and training of both retailers and consumers.  This might involve simple materials that explain how the drugs work, and what the consequences can be of unfettered use. Even in the most developed economies, antibacterials are still prescribed for viral infections; practice can change with education and management of expectations.  Unless some constraints are ultimately placed on drug availability, inappropriate use is likely and AMR will continue to occur.  

Checko technology will combine multiple anti-counterfeiting measures using a layered approach, to enhance tamper-proof security of antibiotic packaging. Its patented 3D printing technology and unique tracking codes will permit monitoring of fraudulent antibiotic packing and rapidly identify and report irregularities to stakeholders, physicians, pharmaceutical companies, and regulators, to maintain safe supply chains to effectively combat counterfeit antibiotics.

One of the biggest barriers existing in LMICs are the fragmented healthcare systems compounded  by challenges in communication and collaboration among different healthcare providers such as wellness centers, primary and community health centers and tertiary care hospitals. Such a fragmented landscape and unavailability of effective technology solutions makes it extremely difficult to implement standardized protocols for antibiotic dispensation and follow-up. Moreover, LMICs have economic barriers that translate to lack of proper prescriptions, follow-up; prevalence of fraudulent drugs adds to resistance. Lack of AMR data and modeling in LMICs, regulated antibiotic procurement, and effective diagnostic tools, are huge barriers.

We believe that the Trinity Challenge provides an avenue to deploy innovative technology expertise at IIT Kanpur, combined with the deep medical biology and agricultural science capabilities of the University of Melbourne, and the leading large scale regional, medical service delivery of CMC Vellore, SKAUST (India). Our interventions will deploy a One Health approach for understanding sources of AMR in LMICs. These challenges require interventions that include new data collection and analysis to help understand contributions of key AMR factors but, as importantly, education and tracking in a large community that has almost unfettered access to inexpensive antimicrobials increasing the AMR burden. 

The Indian Institute of Technology at Kanpur is a leading Indian technology research and teaching institution.  It has recently partnered with the University of Melbourne, which has a global top 50 medical school (QS 24, THES 37) in establishing the Gangwal School of Medical Sciences and Technology (GSMST).  This project provides an excellent opportunity for collaborative research, for technology transfer and the catalysis of innovative new ventures in the area of AMR. GSMST has collaboration with Amrita University, Kochi, a big university in Southern India which also has access to their hospital and patient data. The group (Prof Bipin Nair/Prof Geetha Kumar) has expertise in antimicrobial (bio)therapeutics with small molecules and phages. There is an ongoing collaboration with Central Drug Research Institute, India, which has a huge repository of MDR pathogens and the possibility of using them for genomics data (Dr Sidharth Chopra). There is an important existing collaboration with Helmholtz-Zentrum für Infektionsforschung (Prof Alexander Titz) against AMR and multiresistant pathogens of infectious diseases.We would strive to leverage existing relationships with national and global technology companies in LMICs that are aligned to AMR objectives. Melbourne Medicine has a strong partnership in clinical and laboratory medicine with CMC Vellore.