Multi-omics and behaviour data-driven AMR mitigation.

This study utilizes rural bus transit system, drinking water and wastewater to profile AMR and their promoters in districts of Karnataka and Puducherry. The hyperlocal antibiogram will be introduced in taluk/district healthcare setup. A retrospective longitudinal mixed-method survey, pre- & post-introduction of antibiogram, will be conducted to measure impact.

Team Lead is Dr. Prashantha Hebbar, CEO & Research Scientist at Meta Biosciences Pvt. Ltd., Manipal, Karnataka.

Previous observations found a shift from first-line therapeutic agents to broad-spectrum antibiotics such as carbapenems and aminoglycosides leading to increased resistance in rural areas [doi:10.1017/ash.2023.162]. The risk of resistant bacteria spreading from animals to humans has been also observed. There is an increased resistance to colistin, which is a commonly used antibiotic in animal husbandry, observed in humans [PMID:31219080]. In milk samples collected from dairy buffaloes from the Dharwad and Bengaluru districts in Karnataka, methicillin resistance in S. aureus and coagulase-negative Staphylococci were observed [PMID:26588070, PMID:31219076]. In Mangalore district, 41% of sewage samples exhibited resistance to tetracycline which is commonly used in animal husbandry [http://dx.doi.org.ezproxyberklee.flo.org/10.22207/JPAM.12.4.27]. The National Action Plan (NAP) on AMR of India focuses on clinically relevant pathogens as identified by WHO, primarily in tertiary-care academic centres. However, there is a glaring gap in the program guidelines that do not provide local AMR trends at the taluk/district level. This study outcome will guide antimicrobial use through taluk/district-specific antibiogram in healthcare setups of human and animal communities. Further, AMR promoter profiles help mitigate AMR at its origin through sanitization and responsible use of chemicals in the agriculture sector.

The study focuses on serving the state, physicians, people and farming animal communities, farmer community and rural development, assessing the impact of the solution and improving quality of life, directly and indirectly.

1. The area-specific antibiogram at the taluk and district level will help clinicians provide more rapid and precise empirical treatment based on the patient's clinical presentations reducing healthcare costs, hospitalization, morbidity and mortality rate among patients.
2. Veterinarians, aquatic, agriculture and horticulture can benefit by quick diagnosis of diseases. This will help farmers in reducing animal healthcare costs.
3. The list will educate the rural population on maintaining hygiene, safe drinking water bodies, and sanitization of the area (WASH). Information about chemicals and heavy metals responsible for the transformation of strains into resistant strains from this study can be used to prevent regular exposure of microbes to mutagens from public places.

This study will engage with clinicians, pharmacists and veterinarians to collect state-wide AMR and treatment behaviour data before and after antibiogram introduction. The study will further engage with the Ministry of Rural Development and Panchayath Raj (RDPR) and a large self-help group organization comprising 5.4 million active members to implement policies regarding hygiene and rural development for mitigating AMR.

This study will benefit Karnataka with a population of 64.1 million, of which 38.67% live in urban and 61.33% in rural and Puducherry with 1.6 million population. While this study has several benefits, the creation of taluk/district-specific antibiogram and enforcing it in human and animal healthcare setups are the most important objectives of this proposal. This will improve patient outcomes, reduce microbial resistance and decrease spread of multi-drug resistant infections in humans and animals. Due to lack of hyperlocal antibiogram, patients are not treated with precise antibiotics, as a result of which increased AMR, prolonged hospital stays, increased financial burden and increase in morbidity and mortality are seen. The same is true from a veterinary perspective. Cattle rearing is the main source of income for the state farmers. When cattle die due to infections, psychological distress and depression encourage these farmers to withdraw from farming life. Hence, hyperlocal antibiograms indirectly benefit the farming community. Further, the state has not yet implemented NAP-AMR, even though NAP was introduced in 2017. This could be due to lack of fund allocation to states. This study will contribute policies to create awareness about WASH in rural communities through SHOs to mitigate AMR (Supplementary-Figure-6).

The policies formed from the outcome of this study will be implemented through engaging administrative representatives from relevant ministries. Meta Biosciences has consulted the Karnataka Innovation and Technology Society (KITS) to support this initiative. KITS has agreed to form an apex committee comprising representatives of all stakeholder ministries to create a platform for engaging with all stakeholders to implement the policies in the state. This work requires permission from KSRTC to allow sample collection in buses, RDPR to use municipal administration and Grama panchayath (i.e., rural admin body) for earmarking sewage sites. Further, SHOs will be utilized to enforce various policies at the grassroots level. Their participation will enforce rural development in three dimensions such as rural health, farming and animal husbandry and WASH. Further, implementing antibiogram in healthcare setups requires engagement with Health & Family Welfare and Animal Husbandry and Fisheries ministries. To reach every clinician including private ones and to bring awareness on the judicious use of antibiotics, associations such as the Karnataka state branch of the Indian Medical Association (IMA) and Karnataka Government Medical Officers Association (KGMOA) will be informed (Supplementary-Figure-6). 

In first year of the study, upon approval from KSRTC, sample collection will be carried out for next 8 months from MTS. Additionally, the team will collect data on the AMR treatment behaviour of clinicians, pharmacists, and veterinarians in each district at fixed intervals.

Sewage sites will be earmarked based on AMR trend seen in bus routes at the end of first year and second year, after consulting with district's administrative machinery. AMR, heavy metal, and chemical compound profiling in MTS, and water samples will be completed by the end of year two, alongside conduction of focus group discussions and stakeholder meetings. In the second half of the second year, the construction of hybrid genomes and the detection of AMR will be completed. Additionally, AMR promoters will be analyzed using machine learning methods. Finally, segregation of AMR will be based on their habitat.

In the third year, antibiogram and policy implementation strategies will be created for each district, with input from the health and animal husbandry ministries. Post-antibiogram AMR treatment behaviour and its impact in reducing indiscriminate use of antibiotics will be measured. SHOs will be consulted to bring awareness about appropriate antibiotic use and WASH policies in rural communities.

The value of using MTS as a system for identification of AMR, finding the correlation of AMR in two buses per route, and establishing AMR promoters such as heavy metals from vehicle exhaust and their interaction with temperature and precipitation for evolution and propagation of AMR -are success indicators in year-1. Further, establishing a panel-based retrospective longitudinal survey among clinicians, pharmacists and veterinarians to gather antibiotics prescription behaviour at regular intervals is yet another success indicator from an impact measurement perspective.

In year-2, using MTS as a tool for shrinking the area of sampling to refine the AMR origin hotspots will be detected if there is a correlation between MTS and sewage site AMR patterns and abundance, setting a precedence for future studies.

Further, gathering information about multi-sector challenges from conventional sources using focus groups and write-shops, creating awareness using SHOs and measuring the impact of hyperlocal antibiogram implementation on changes in prescription practices through surveys, are indicators of success in year-3.  

Often, swabbing the handrails captures less amount of sample. That may not yield good DNA quantity and quality. To maintain a well-distributed microbiome in a bus environment, four handrails will be sampled using two swab kits. Half of each swab will be used for one handrail and the samples will be pooled. Further, from each route at least two buses will be swabbed to overcome false positive routes.

To facilitate a platform for data collection of clinical behaviour survey at regular intervals before and after antibiogram introduction, focus group and stakeholder meetings, sharing of hyperlocal antibiogram to clinicians, pharmacists and veterinarians at each district, enable AMR origin and transmission tracking via GIS interface, spread AMR-centric WASH policy awareness among SHO active groups, a mobile app will be developed in local language. Since primary and secondary healthcare facilities do not maintain records of the antibiotics prescribed and AST results, the survey relies on the memory of the medical professionals. Hence, follow-up questions will be presented to the same set of individuals every 3 months.

The study requires approval and engagement with many ministries. An apex committee formation and engagement of representatives from relevant ministries may overcome the barrier. 

In 2017, the central government launched the National Action Plan (NAP) on AMR. However, like in many other states, the implementation of this plan was delayed in Karnataka due to lack of funds and the COVID-19 pandemic.

Meta Biosciences brings experience in implementation of multi-omics in population health. Proposing a solution to mitigate AMR and contribute to transformational change in the health of rural communities through policies and enforcement is one of our prime objectives.

In this regard, we pitched an idea to capture AMR through rural MTS of Karnataka with MetaSub. We are grateful to the MetaSub consortium for supporting this effort with partial funding and adding Meta Biosciences to their network of associates.

Since then, we have consulted with many stakeholders in this multi-sectoral challenge, including KITS, to create a platform to engage with administrative representatives of ministries. We have also indirectly consulted the Health, RDPR ministries, and SHOs.

We believe that Trinity Challenge’s mission of AMR mitigation and bringing transformative change in society aligns perfectly with our objective. We value the inclusivity of small companies to play a responsible role in societal change. Often, small companies are kept away from such financial support.

We would like to collaborate with Shri Kshethra Dharmasthala Rural Development Project (SKDRDP) as they have a vast network of SHGs in Karnataka. We would also like to collaborate with a software development company for the development of a mobile app.

The Global Health Network- https://amr.tghn.org/funding/