ResistApp dashboard

Antibiotic resistance is a global health threat that causes more than 1,2 million deaths annually. If left unchecked, we face the risk of entering a “post-antibiotic era” in which simple wounds and infections have high mortality rates. Further, the damage caused by resistant infections would be around 100 trillion USD, making antibiotic resistance not only lethal but a threat to the global economy. The extent of the damage caused by antibiotic resistance will depend on how humanity takes action against the problem. 

The monitoring of antibiotic resistance is especially crucial in hospitals as it is oftentimes the centre of outbreaks. One case of antibiotic resistant bacteria outbreak in a hospital is estimated to cost around 1.2 million USD. One example was the regional outbreak in Tuscany, Italy between November 2018 and May 2019. The outbreak was only detected after 22 weeks; meanwhile, 350 cases and 33 deaths were reported within that period. An early warning system would have allowed the hospital to take preventive measures and so limit the spread of infections.

Our solution monitors antibiotic resistance in low to middle-income countries, starting with the Indonesian healthcare sector. Regions such as Indonesia carry the heaviest burden of this health crisis and have consequently become a hotspot for antibiotic resistance. Limited coordination between vital actors in healthcare and government has done very little for the rampant factors causing continued spread of antibiotic resistance. This lack of intervention has allowed for influencing factors such as self-medication, proven by basic national health data showing that around 10% of Indonesian communities kept antibiotics in their homes, and that 86.1% of these antibiotics are obtained without a prescription. If continued, Indonesia is to have an estimated 135,000 deaths caused by antibiotic resistance annually. In instances where health crises are heavily impacted by management and widespread human behaviour, our solution thus proposes a wastewater-based surveillance solution in hospitals to address issues in antibiotic resistance monitoring, wastewater treatment, and the healthcare system simultaneously.

ResistApp is a digital interactive dashboard that shows hospital performance indicators. More specifically, ResistApp displays the levels of pathogens and antibiotic resistance spread in hospital wastewater. Our data-driven surveillance method combines biotechnology with data science by taking hospital wastewater samples to analyse in our lab, then processing them into visual information that can act as an inclusive guide for hospital management and eventually public health policy.

Through ResistApp, users have simplified access to see the number of detected genes associated with antibiotic resistant bacteria and pathogens in each sample, the abundance of detected genes, and a heatmap that shows the resistance gene profiles. This allows users to have in-depth information on the levels of antibiotic resistance from their samples, and to compare the levels of resistance between samples and overtime. In essence, our target users will be able to use the indicators shown in ResistApp to act upon preventative hospital management or policy measures against outbreaks, or improve healthcare performance through finding root causes of mortality and extended hospital stays.

Our innovation consciously utilises wastewater samples because it is not only rich in epidemiological information, but a wastewater-based solution is also the most cost and time-efficient method of surveillance sampling. With only about 100 USD to analyse a wastewater sample representing a subpopulation and fewer permit limitations, our innovation could be the best option for hospitals in low and middle-income countries.

To process the ResistApp dashboards, our innovation design starts from the collection of wastewater samples weekly from each hospital. The process is as follows:

● We collect 1L of wastewater samples from the sewage system of a hospital building every week; The wastewater is collected using an automatic sample collector system and will be picked up and delivered to the laboratory;

● We isolate environmental DNA directly from the wastewater samples using commercial DNA isolation kits which can be automated for scaling up the process; 

● We measure up to 96 genes targeting bacterial pathogens and problematic antibiotic resistance from the environmental DNA samples in parallel using a high-throughput qPCR system, an efficient system;

● The laboratory results are automatically submitted into a cloud system and analysed using ResistApp, our in-house developed software and visualised in an interactive dashboard; 

As such, our own team collects our primary healthcare data based on the process above. Through our unique solution to combine standardised cutting-edge microbiological technology with the best data visualisation techniques, we expect ResistApp to contribute toward improving access to primary health information.

Our solution is preliminarily focusing on subpopulations in low to middle-income countries first as they carry the heaviest burden of infectious diseases. To pilot ResistApp, our solution serves Indonesian subpopulations in Java Island first.

 The Javanese subpopulation of Indonesia is the country’s most populated with roughly 1171 persons per square kilo meter (2021). With 70% of Indonesian pharmacies having reported to dispense antibiotics without prescription (2021), and furthermore with 64% of Indonesian hospitals discharging wastewater directly into receiving water bodies or infiltration wells (2017), the estimated mortality rate caused by this silent pandemic is assumed to be 135,000 per year in Indonesia alone (2021). The dashboard feature offered by ResistApp displays insight into indicators that alert early warning signs of infectious and non-communicable diseases, which will be shareable across information systems in hopes to leverage  preventive health policies with specific guidance. This will not only decrease mortality rates in hospitals but will also prevent outbreaks in surrounding communities that could have been otherwise exposed to the eventual spread of antibiotic resistance in their environment.

This silent pandemic also poses an extreme threat upon the Indonesian primary healthcare system, as the COVID-19 pandemic has already exposed the fragility of the Indonesian healthcare system in being able to provide sufficient staff, stuff, structure, and system. There are severe challenges in hospital productivity that is characterised by an insufficient physician-to-population ratio of 0.38 physicians per 1000 population, 84% of whom experience severe burnout as hospital beds are constantly in full capacity as there is only a mere 1.49 beds for every 1000 Indonesians (2021). Our solution does not only target the surveillance of disease risk-factors, but also hopes to address management issues in Indonesian hospital performance by decreasing patient-related burden.

To create a health-led preventative design against antibiotic resistance, we narrow down our target population by categorising the specific roles our service will directly serve: the scientific community, the healthcare sector, and the wastewater treatment industry. By piloting our solutions in three Indonesian hospital wastewater treatment facilities (RSSA Malang, RSUI Depok, and RSCM Jakarta) between 2020-2022, we determine our explicit impacts through developing future scenarios by the following categories:

1.   The scientific community

• Provide cheap and fast early detection surveillance relative to the current passive surveillance system in hospitals which are from cultured pathogens from patient’s samples;
• Create a research space for an inter-population interaction between our connected surveillance network. As a shareable open interface, this increases efficiency, communication, and access to epidemiological insight between researchers in the scientific community.

2.   The healthcare sector

• There is upwards to 84% in variance of cost differences between control patients and those with resistant infections. As an example, however, it is estimated that the costs of Pneumoniae infection alone exceed 370 USD per patient. The relative cost per patient would thus be decreased by 36 % with ResistApp’s early detection surveillance monitoring, assuming that the patient spends less time in hospitals.
• ResistApp can synthesise costs from multiple sites or surveillance networks. The current method of surveillance in Indonesian hospitals costs 3500 USD per 100 patients, as it is conducted by culturing pathogens from patients. Through ResistApp’s system, this would allow hospitals to only test once from wastewater, which will only cost 100 USD in comparison.
• From a macroeconomic perspective, our early detection surveillance system can also increase labor input, ratio of healthcare labor supply to patients, and even national GDP in the long-term as antibiotic resistance is an economic shock that alters labor supply and productivity. Although it is difficult to quantify with limited resistance data in Indonesia, we take the example of the annual 4.6 billions USD healthcare costs that are expended on antibiotic resistance in the US alone (2021).

3.   The wastewater treatment industry

Currently, hospital wastewater is released into water environments with 60-90 % of antibiotic resistance pollution even after going through the current wastewater treatment facilities (2021). ResistApp informs wastewater treatment facilities regarding the quality of outflow before it is released into water environments. With the high quality information displayed by ResistApp, we expect these wastewater treatments to improve their facilities which in the long-term will encourage standardised treatment facilities through a health-led perspective. This can decrease transmission between humans, animals and the environment.

Our entrepreneurial identity as a team is closely connected to creating innovative biotechnological solutions to public health issues. We are engaged in multiple public health research networks including but not limited to microbiology research, health data science, cancer research, molecular biology and one health policy research. This connects our team to researchers specialising all over geographical locations, including our target population in the Java island, Indonesia. Beyond having cultural and personal proximity as an Indonesian, our team leader herself has notable fellowship among senior researchers in the relevant communities we are serving in this subpopulation of Indonesia. We believe that our identity has provided a strong foundation for our team to build legitimacy in our name as a positive collaborator in Indonesia. It has allowed us to gain access to the resources we needed in our pilot project, including researcher capacity building with the nation’s top universities including the University of Indonesia and the University of Gadjah Mada. 

Our growing network has expanded positively during the duration of ResistApp’s development, as we have also maintained cordial dialogue with government agencies such as the National Research and Innovation Industry and the Indonesian Ministry of Foreign Affairs to push forward bilateral efforts toward creating healthcare innovation. Our proximity to our target population has garnered positive results in aspects of project development, policy discussion, and overall community faith in our innovations. Our active engagement has attracted further success in partnering with PT. Saraswanti Indo Genetech (SIG Laboratory) in Bogor, Indonesia to establish a central laboratory to collect samples to monitor environmental antibiotic resistance. Despite our small operations and only having reached the piloting stage of ResistApp, our efforts continue to encourage fruitful collaboration with actors across communities within our target population. With ongoing support from these actors to further develop ResistApp in our three pilot hospitals (RSSA Malang, RSUI Depok, and RSCM Jakarta), we use this engagement not only to compound our entrepreneurial knowledge for future ResistApp development, but also to maximise the human resources in these Indonesian communities as our direct collaboration has shown us the shared social identity that our team has with our target communities in overcoming epidemiological obstacles.

The funds raised to date, a 600,000 USD Finish government grant to develop and test ResistApp in hospitals in Finland, Indonesia, Thailand, and Nepal, have allowed the validation of the prototype in an operational environment, but it has not yet completed and qualified. Resistomap has explored national funding schemes, but the amount is limited and will not be sufficient to complete the technical validation. The MIT Solve Challenge funding would bridge the gap between the current development stage and the market launch. This will enable the company to reduce project risk and attract further private and corporate investment for successful market penetration and future scale-up.

Risk #1 Technological

While the back-end of ResistApp is currently in the final stages of development, the front-end is still in the very early stage. More user interviews and UX design are still required to ensure that our solution fully addresses the hospitals’ needs.

Contingency plan: To address the technical barriers, we will hire a UX developer and designer to continue developing our monitoring dashboard through user experience design. By doing so, we ensure that our invention fulfilled the hospitals’ needs.

Risk #2 Commercial

Breakthrough technologies may emerge during development. 

Contingency Plan: Our value proposition is extremely strong, and we are already working to secure the necessary IPR portfolio for our protection. The FTO analysis is already done. We will continually review the competing landscape to ensure we will position ourselves as a market leader.

Risk #3 Legal

An open database for sharing the antibiotic resistance levels in hospitals is required. Legal instruments that restrict data sharing could hinder the development of the solution. 

Contingency plan: To address the legal barriers, we are seeking advice on how to address potential restrictions regarding data sharing.

Risk #4 Regulatory

Insufficient data collected from pilot tests for the regulation. 

Contingency Plan: Resistomap has a detailed regulatory strategy and works closely with regulatory experts. The company performs a detailed analysis of the regulatory requirements and ensures that all necessary data is collected during the tests.

Risk #5 Financial

Insufficient funding could limit the range of the pilot tests conducted (e.g., length of wastewater monitoring, number of hospitals included), which would have implications to our goal progress. 

Contingency plan: The budget will be carefully reviewed on a periodic basis to identify any potential deviations from the original plan. Quotations will be requested to ensure an accurate forecast. The management will be proactive in scouting additional funding opportunities and maintain a positive cash flow.

Hospitals are antibiotic resistance (AR) hotspots due to high prevalence of care through hands, use of invasive devices and antibiotic (over)use. However, there is currently no AR monitoring system that could identify emerging threats and long-term trends in hospitals. ResistApp is a new technological revolution that serves as an early warning system that allows hospitals to conduct upfront screening and isolation as preventive measures and limit the spread of infections. ResistApp is unique as it combines and standardises cutting edge microbiological technology with the best visualisation techniques to make the spread of AR understandable and preventable. If scaled globally, ResistApp will prevent AR outbreaks in hospitals worldwide. Resistomap’s solution is the first and only one monitoring AR through the wastewater using culture-independent methods that can potentially provide an efficient alternative to current approaches for monitoring AR and there is no competitor in the private sector doing this.

In the target community we aim to serve in Indonesia, the only monitoring system in place is currently being practiced through passive surveillance by culturing pathogens from patients. This same system of monitoring can also be conveyed to alert hospitals to potential outbreaks. However, this system focuses on a limited number of pathogens, which can restrict the identification of gene profiles often carried by commensal bacteria. Passive surveillance often leads to delayed detection of outbreaks, non-comparable data, and the inability to capture other pathogenic bacteria and AR profiles often carried by commensal bacteria. Currently, AR control in hospitals is mainly carried out in the in-house labs, but not via wastewater monitoring. Some public and university labs occasionally test for AR in wastewater, but it is never continuous, so it does not allow real time control. Both labs do not provide a data dashboard or a digital platform. ResistApp addresses these gaps in surveillance through introducing innovation in offering a continuous wastewater AR monitoring service that provides real time digital access. Although there are other companies in the water sector offer wastewater monitoring, such as Veolia, Biobot, and Kando, we are the first to offer continuous wastewater monitoring for AR. 

1. Scientific publications - eight publications on wastewater monitoring for antibiotic resistance in hospitals

   1. One published scientific publication from Finland, https://www-sciencedirect-com.ezproxyberklee.flo.org/science/article/pii/S0195670121003224

   2. More publications will be produced through the pilot projects that are still ongoing: at least seven more scientific publications (four master thesis from Indonesia and three scientific publications from Indonesia, Thailand, and Nepal)

2. Increasing awareness through social media outreach - since the beginning of our pilot project in Indonesia in 2021, there was a 63% growth in webinar attendees from Indonesia.

3. Introduce ResistApp to more hospitals and municipalities in European and Southeast Asian regions.

4. Contribute to large databases (e.g. GLASS from WHO, UNEP) - currently ResistApp - hospital projects analyzed over 300 samples from Finland and Indonesia, and 100 more samples from Thailand and Nepal by the end of this year. More ResistApp applies in 100 hospitals, to reach 5000 samples.

• Proportion of hospital wastewater outflows with reduced levels of antibiotic resistance genes and resistant pathogenic bacteria

• Incidence rate of outbreaks of antibiotic resistant bacteria in hospitals

• Number of countries with early warning systems for outbreaks of antibiotic resistant bacteria

ResistApp will serve as an early warning system for impending resistant bacteria outbreak by providing evidence-based information to hospitals by monitoring hospital wastewater (Activity). Through ResistApp, users will have in-depth information on the levels of antibiotic resistance from their samples over time. There are three expected outcomes from this activity, which we argue will have positive outcomes to health.

Output 1. Hospitals gain awareness of trends towards possible outbreaks.

Existing antibiotic resistance monitoring in hospitals is only limited to a small number of pathogenic bacteria isolated from patients. This makes it difficult to identify trends on the emergence of antibiotic resistance, which leads to delayed detection of outbreaks. Through ResistApp, hospitals will gain a more complete overview on the presence of antibiotic resistance genes and pathogenic bacteria, which will allow them to identify possible outbreaks at an earlier stage. Hospitals will thus be better prepared to take mitigation measures (Short-term outcome 1), which will lead to decreased outbreaks of antibiotic resistant bacteria in hospitals (Long-term outcome 1).

Output 2. Hospitals gain awareness on the implications of current prescribing practices on the emergence of antibiotic resistance.

The misuse and overuse of antibiotics accelerate the emergence of antibiotic resistance. With the data provided by ResistApp, hospitals will be able to compare the levels of antibiotic resistance with antibiotic use within a specific time period. In this manner, hospitals will gain awareness on the implications of current prescribing practices on the emergence of antibiotic resistance. Hospitals will therefore be encouraged to improve regulations on antibiotic prescribing (Short-term outcome 2), which will lead to optimised use of antibiotics in hospitals (Long-term outcome 2).

Output 3. Hospitals gain awareness of the quality of wastewater outflow released into the environment.

Hospital wastewater is usually treated in wastewater treatment facilities before being released in water environments. Through ResistApp, hospitals will have additional information on the quality of outflow released into the environment. This information is expected to encourage hospitals to improve their wastewater treatment facilities (Short-term outcome 3), which will ensure that local communities have access to water that is safe from antibiotic resistance (Long-term outcome 3).

ResisApp utilizes culture-independent methods and a state-of-the-art technique SmartChip qPCR for the detection and quantification of bacterial genes and antibiotic resistance genes in wastewater. This technique enables 50x more throughput than standard gene quantification methods; however, it requires a PhD-level of understanding to apply and has a high risk of error when used by non-experts. We use 96-validated assays to detect pathogenic bacteria (e.g., Acinetobacter baumannii, Klebsiella pneumonia and Pseudomonas aeruginosa), problematic carbapenem resistance genes (e.g., blaTEM and blaKPC of Class A) and other resistance genes against antibiotics that are used in hospitals (e.g., beta lactams and quinolones). By using culture-independent methods, we will extract all bacterial DNA directly from hospital wastewater and use a high-throughput method for gene quantification, which leads to fast antibiotic resistance monitoring that produces comprehensive data.

ResistApp offers the SmartChip qPCR technology as a standardised service and collects all the resulting data into an open database of gene prevalence and spread. Through ResistApp, users will be able to see the abundance and trend of detected genes, and an early warning system (red line as shown in the layout of the ResistApp dashboard below) for problematic resistance genes. This allows users to have in-depth information on the levels of antibiotic resistance from their samples, and to compare the levels of resistance between hospitals and over time. 

ResistApp dashboard layout plans:

Our team will collect the wastewater samples together with the sanitation unit/waste management unit of the hospital. The other data will be organised by the infectious disease control unit or AMR unit at the hospitals. These units are the main users of ResistApp.

Resistomap accepts and values differences in the team. Our team consists of five women and five men originating from Indonesia, Nepal, Italy, Finland and Sweden. All team members, regardless of background, specialisation and experience, have the opportunity to join one of the parallel projects that cross over the various departments in the company. Involvement is highly encouraged provided that it does not clash with individual tasks and assignments. We also organise a monthly meeting with all team members to build transparency between departments and projects, and to ensure that all members are engaged and included in the direction of the company.

In our pilot project, our small operations exclusively hire women. This is because it is difficult for women in Indonesia to progress in high-skill industries. We also do not discriminate in age or years of research experience, as this pilot project has worked with both junior and researchers alike with different backgrounds and expertise. Our differences have not impaired our productivity, as we rather utilise this as an opportunity to create holistic dialogue. We believe that our recruitment does not only encourage self-development among our members, but also opportunities for future career progression.

The business model consists of the sale of wastewater sample testing for 100 USD per test. Additional services include the automatic sampler installation in the hospital with a one time payment of 4000 USD (optional). Samples are then analysed using a high-throughput qPCR system to detect and quantify antibiotic resistance genes, and these results are then interpreted into meaningful data on antibiotic resistance prevalence in hospitals. Finally, results are delivered via an interactive dashboard to help hospitals identify potential areas for intervention. Resistomap uses a network of distributors to provide ResistApp to hospitals, universities or research institutions, municipalities, and food production. In parallel, barriers to competitors will be raised through patents under development.

Resistomap expects rapid and widespread adoption of ResistApp once the system is completed and qualified and plans to launch an effective communication strategy to accelerate this growth. It will start by focusing on hospitals. With time and experience, we will scale up our customer diversity to encompass universities or research institutions, municipalities, and the food production industry. 

Different types of revenue models will be adopted based on the regions and markets. In Indonesia, ResistApp dashboard will be sold as service contracts to governments for public primary healthcare.   

Since 2019, we received a total of 600,000 USD Finnish government grants (mainly from Business Finland and Finnpartnership), 850,000 USD pre-seed round (Nordic Laboratories) and over one million USD paying customers from universities & research institutes globally (mainly from the UK) for the laboratory services and data analysis that we currently provide. 

We developed the ResistApp to serve a new business model for the subscription-model customers.