Breaking silos to step up the fight against AMR
Antimicrobial resistance (AMR) is an emerging challenge across healthcare, agriculture, livelihoods, food industry, and environment. AMR claims nearly 7,00,000 lives globally, and at this rate is set to claim nearly 10 million deaths by 2050! With expanding populations and the resultant increase in man-animal conflict, zoonotic transmissions are being reported more frequently. Indiscriminate use of antibiotics in animals through feeds, water or therapeutic purposes find their way to humans through meat, poultry and diary. Adding to this is the environmental pollution of soil and water due to unregulated dumping of chemicals and antibiotics by pharmaceutical industry, or agricultural practices. In the past few years, climate change has further aggravated this issue as previously non-pathogenic microbes have shown association in pathogenic mechanisms.
Breaking the silos
The COVID-19 pandemic set a new normal in many contexts. Due to the urgency of the situation, on the one hand, R&D was accelerated with many consortiums and agencies working together to identify the infecting virus, design cost-effective diagnostics, identify drugs targets and screen new or repurposed drugs; on the other hand, many agencies came together to scale-up production and deploy PPEs, ventilators etc. The cohesive collaboration was a first of its kind, not just for India but across the world. Active sampling and surveillance efforts, using genomics, were made to attempt close monitoring of the emerging strains for timely decision-making. For the first time, scientific research and public health interventions by Government went hand-in-hand, in near real-time. The same approach needs to be pursued to prevent the foreseeable AMR epidemic.
Programming Initiative on Antimicrobial Resistance (JPI AMR), New Drugs for Bad Bugs (ND4BB), Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X), BEAM (Biotech companies in Europe combating Anti Microbial Resistance) Alliance and the Coalition for Epidemic Preparedness Innovations (CEPI)are a few organizations and aggregator networks that have committed their resources to fund solutions for AMR. In India, many other partners, like WHO, FIND, PATH etc. are working with state and central government agencies on AMR in high priority pathogens. Collectively, much can be achieved.
Global and National Efforts to combat AMR
WHO & CDC have put forth the priority pathogen list. These pathogens are important in the context of high infection rates and high rate of resistance development against current antimicrobials. The Global Action Plan (GAP) suggested a framework for combating AMR through critical aspects like awareness, surveillance, R&D, etc through inter-sectoral collaborations. Each country adapted this document to contextualize an action plan suited locally. India’s National Action Plan (NAP) for AMR aims to act as the framework for consolidating efforts to combat this emergent threat in India. The key interventional areas are:
- Improve awareness and understanding of antimicrobial resistance
2. Strengthen knowledge through surveillance and research
3. Reduce the incidence of infection
4. Optimize the use of antimicrobial agents in health, animal and food sectors
5. Promote investments for AMR Activities, research and innovations
6. Strengthening India’s leadership on AMR
Improve awareness and understanding of antimicrobial resistance
A major factor in controlling AMR is prevention at source. The un-regulated use of antibiotics in poultry, animal farms, and agricultural use has been a challenge to measure, let alone regulate. Awareness of people engaged in these sectors on AMR and how it can be avoided is paramount to prevent a flush of antibiotics unknowingly entering our food and water sources.
Strengthen knowledge through surveillance and research
Actual disease burden of different high risk & high priority diseases is still not available. This challenges the assumptions on which the solutions are developed, and their market potential. Epidemiological and surveillance data thus becomes important. Genomics can be used in big way for the surveillance of AMR, appropriate use of antibiotics, vaccine development etc. Socio-geographical conditions, along with climatic variables, need to also be mapped to predict the spread of infections. This will require data collation, management, analytics and access to be managed centrally.
Reduce the incidence of infection
Prevention of infections is perhaps the most important intervention that can save lives, and huge economic costs. Although appropriate hygiene and sanitation parameters in public health, animal health and food sectors cannot be emphasized enough, the development and use of vaccines to locally circulating pathogen strains and preventatives can avoid many potential infections.
Proactive surveillance and monitoring mechanisms against high incidence infections, that maybe epidemic in different parts of the country, can lead to timely preventive strategies to control the spread. This is especially true for LMICs which have a fragmented healthcare system. Additionally, diagnostics for pathogen identification at point of care can ensure reduction of treatment duration and the likeliness of cross-infections. In animal husbandry sector and wildlife surveillance, appropriate low-cost testing mechanisms could help in monitoring and curtailing infections in different species that could otherwise lead to zoonotic transmissions.
Optimize the use of antimicrobial agents in health, animal and food sectors
The overuse, misuse as well as lack of access, to quality-assured antimicrobialsis a significant driver in the emergence of antimicrobial resistance. Finding optimal treatment regimens is therefore imperative in ensuring the prolonged effectiveness of these antibiotics. WHO’s integrated Antimicrobial Stewardship toolkit, evidence-based policy recommendations, and tailored country-level support to optimize antimicrobial use through the implementation of antimicrobial stewardship (AMS) programmes have been proposed to achieve this.
Novel strategies to guide the efficient therapeutic use of antimicrobials such as genetic algorithm-based dose recommendations for improved success of eradicating bacteria causing the infections while using less antibiotic than traditional regimens, appropriate diagnostics for pathogen ID and antibiotic sensitivity testing (AST) at point-of-care need to become mainstream.
Promote investments for AMR activities, research and innovations
It is imperative to develop an economic case for sustainable investment that takes account of the needs of all countries, in new medicines, diagnostic tools, vaccines and other interventions. This would include addressing various aspects that impact the development of these interventions.
- Funding
- Regulatory Framework
3. Incentivisation and Market Access
4. Capacity consolidation and optimization
1. Funding: Many public, not-for-profit and philanthropic agencies are coming forward to support AMR initiatives. To name a few, Programming Initiative on Antimicrobial Resistance (JPI AMR) has financed US$ 80 million in pre-clinical trials. New Drugs for Bad Bugs (ND4BB), a European Union Initiative has spent US$ 860 million for funding the entire R and D chain.US-based Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X), with contributions from many philanthropic donors, has invested over US$ 361 million in the last 5 years with a total of $480 earmarked for the period 2016–22. In India, BIRAC has collaborated with Nesta, a UK based innovation charity organization, for creating a pipeline of innovators for the Longitude Prize, in the area of Antimicrobial Resistance (AMR). BIRAC has allocated £200,000 towards the initiative. DBT & BIRAC have also jointly supported innovations for antimicrobials under their AMR mission.
2. Regulatory framework: The Regulatory pathway for new antimicrobials, orphan and repurposed drugs and diagnostics in particular as well as for other therapeutics, vaccines, companion diagnostics, etc have to be streamlined, simplified and harmonized across countries. Review of clinical trial protocols/requirements, regulatory incentives to manage costs and fast-track approvals are some of aspects that need to be looked into. For this strengthening of partnerships and global regulatory networks is essential.
3. Incentivization and Market Access: It is repeatedly acknowledged that commercial models don’t work in AMR due to market failure more than R&D failure so Public-Private Partnership (PPP) Programs need to be prioritized. Start-ups and mid-sized companies account for 90% of innovations in AMR and pull incentives that create a ‘viable market’ for them are required. Novel funding mechanisms, investment instruments and incentives thus need to be worked out and deployed.
4. Capacity consolidation and optimization: High capital expenditure coupled with lack of funding s may deter small scale industries in invest in high-end infrastructure needed for R&D in diagnostics, therapeutics, and vaccines. Access to bio innovation facilities, like C-CAMP, or national high-end laboratory infrastructure like BSL-3 facilities, genome sequencers, animal challenge facility etc. in public laboratories and institutes can enable the same. Anational level repository of well characterized microbial strains that can be accessed by innovators in public and private sectors is a critical need.
Strengthening India’s leadership on AMR
India realizes the gravity of the AMR problem and has supported a well-rounded approach that addresses public health initiatives through collaborative, multi-sectoral and transdisciplinary ‘One Health’ approach at the local, regional, national and global levels. India has a National Action Plan on Antimicrobial Resistance, as well as the Delhi Declaration on Antimicrobial Resistance, which were endorsed at the Inter-Ministerial Consultation on Antimicrobial Resistance in April 2017. Additionally, 3 states have enrolled in the State Action Plans for Containment of Antimicrobial Resistance or SAPCAR. India’s approach to implement AMR containment at the sub-national level through state action plans for containment of AMR is a good example of how other big countries with a federal structure can work towards AMR containment.
India actively engages with the International community on AMR. India contributes to the WHO’s Global Antimicrobial Resistance Surveillance System or GLASS and has been contributing AMR data from the National Centre for Disease Control, Indian Council for Medical Research and GASP (Gonococcal AMR Surveillance Programme) networks.This is important from a global surveillance perspective since India is a high burden country for many infectious diseases, like tuberculosis. Credible surveillance data will enable an understanding of disease spread, prevention and control at a national and international level. On this line, WHO’s global pathogen priority list of antibiotic resistance pathogens is also being adapted as India’s Pathogen Priority List from India’s perspective to incentivise research and development of newer antimicrobials, diagnostics and alternatives.
Advancing the ‘One Health’ approach, the UN Environment Programme (UNEP) and ICMR have recently launched a new collaborative project — ‘Priorities for the Environmental Dimension of Antimicrobial Resistance (AMR) in India’. This marks an important step towards recognizing and addressing the environmental dimension of AMR.
The whole is greater than the sum of its parts
Addressing the diverse and innumerable challenges of AMR will require cohesiveand coordinated efforts. For this, breaking down the functional silosis imperative so that all stakeholders can synchronize their efforts. Individual, disjointed, and often repetitive, efforts have led to fragmented initiatives that have not been able to accelerate many high potential solutions. This strategy needs to be reviewed, revised and re-worked. Convergent platforms and consortia that brings stakeholders and partners such as government, academia, industry, entrepreneurial ecosystems, philanthropies and non-profits together can collectively optimize and amplify the desired outcomes and their impact. Several such multi-stakeholder collaborations have been successfully working together, but there is scope for more such platforms and initiatives to join forces in the global fight against AMR.
Disclaimer: The blog is a compilation of information on a given topic that is drawn from credible sources; however this does not claim to be an exhaustive document on the subject. It is not intended to be prescriptive, nor does it represent the opinion of C-CAMP or its partners. The blog is intended to encourage discussion on an important topic that may be of interest to the larger community and stakeholders in associated domains.
