Medupi

Tuberculosis (TB), a curable and preventable disease, continues to be a global health crisis, especially in low- and middle-income countries like India. More than 10 million people fell ill with TB in 2021, with India accounting for approximately 2.5 million of these cases. 1.5 million people lost their lives, and 40% weren't even diagnosed. Primarily due to the limitations of current testing methods and their inadequate delivery mechanisms.

There are three main types of active TB testing today:

1. Microscopy: This conventional method is relatively affordable at $1 per test, but its sensitivity is only around 50%. While microscopy centers are widespread and easily accessible, the low sensitivity leads to a high rate of missed diagnoses.

2. PCR/NAAT (Nucleic Acid Amplification Tests): These tests offer high sensitivity of around 95%, making them highly reliable. However, each test costs approximately $20, making it financially unviable for mass testing, especially in resource-limited settings.

3. AI on X-rays: These tests offer a sensitivity of around 75% at a cost of $4 per test. Despite their potential, the practicalities of field deployment and the limited specificity of X-rays make them a less than ideal solution.

Companies developing these tests have focused on product improvement but have overlooked the critical aspect of delivery mechanisms. The expectation that patients will commute to a facility to access these tests is unrealistic, especially for stigmatized diseases like TB. To ensure testing accessibility, diagnostics must reach people where they are, enabling immediate treatment initiation.

Moreover, to break the cycle of TB transmission, the testing approach should allow for over-testing over the long-term (10+ years). This approach means testing not only symptomatic individuals but also entire communities regularly. This strategy is the only way to prevent community transmission and eventually eradicate TB.

Present testing methods do not support such an approach:

a) Despite financial viability, microscopy’s low sensitivity makes it unsuitable for mass testing.

b) NAAT's high costs make it impossible to implement widespread testing over an extended period.

c) Portable X-rays are challenging to conduct in the field, and their inherent limitations in specificity make them unsuitable for initiating treatment.

Furthermore, the existing infrastructure heavily favors microscopy, which accounts for 2/3 of all tests globally. The inertia of such an entrenched system cannot be overlooked, and any new diagnostic tool that can integrate with this infrastructure is more likely to be adopted.

Every extra minute per test is crucial. For example, a 60-minute NAAT test on a 4-at-once machine running 12 hours a day can conduct only 48 tests a day. In contrast, a 3-minute screening run for 8 hours a day by a single worker can perform 160 tests a day. This increased capacity is essential for over-testing and isolating potential cases to prevent outbreaks.

The challenge, therefore, lies in finding a testing solution that is not only highly sensitive and affordable but also integrates well with the existing infrastructure, supports large-scale and rapid testing, and can be delivered to the patient's doorstep. 

Our solution, the Medupi system, is a diagnostic device that employs polarimetric optical imaging to detect Tuberculosis (TB). The device, portable and fast, is designed to function on-site, removing the need for patients to travel to a testing center.

The Medupi system comprises two elements: a reader device (platform) and a disposable cartridge. The cartridge processes the biological sample, while the reader interprets the sample and provides the results.

Here's how it works:

1. A sputum sample, traditionally used for TB testing, is collected from the patient and placed in the reusable cartridge.

2. This cartridge is then inserted into the Medupi reader. 

3. The reader reads the sample in a couple of minutes.

4. Once the processing is complete, the results are displayed on the reader device. A positive result indicates the presence of TB bacteria, while a negative result indicates the absence of the bacteria.

One of the key features of Medupi is its cost-effectiveness. Our reusable cartridges are reagent-free and cost only $2 each. Additionally, they are designed to be compatible not only with our Medupi reader but also with existing microscopy systems. This adaptability enables the easy integration of our cartridges into existing health infrastructure, making the transition to more efficient and sensitive TB testing seamless.

Our reader device is priced at $2000, making it a cost-effective solution for extensive testing in resource-limited settings.

Medupi's rapid processing time and portability make it an ideal solution for over-testing in high-risk communities. It allows for a large number of people to be tested quickly and regularly, enabling the prompt isolation of positive cases and preventing further transmission.

In our ongoing field study in India, our cartridges have demonstrated 100% sensitivity match with GeneXpert in TB patients also living with HIV, but at a significantly lower cost. While making diagnostics affordable and accessible, Medupi empowers communities to foster trust and built last mile delivery mechanisms to effectively combat TB and other infectious diseases.

Data collected from the devices can be pushed into a central surveillance database daily, informing optimized interventions and allocation of resources such as micro-quarantines, and active screening efforts. 

Medupi primarily serves populations that are most vulnerable and disproportionately affected by Tuberculosis (TB). These include homeless populations, residents of urban slums, labor force populations, people living with HIV, and rural communities, including tribal communities. Each of these groups faces unique challenges that contribute to delayed diagnosis and treatment, increasing the spread and severity of TB within these populations.

1. Homeless populations: Homeless populations, whether in developing nations like India or developed ones like the US, face higher risks of TB. This group is four times more likely to contract TB due to their living conditions and limited access to healthcare. Medupi, with its portability and ease-of-use, can bring diagnostics directly to them, reducing the barriers to TB diagnosis and treatment.

2. Urban Slums: Populations in urban slums, including migrant and factory workers, often lack proper healthcare facilities. Medupi can provide quick and accurate TB diagnostics in these densely populated areas, aiding in the rapid initiation of treatment and reducing transmission.

3. Labor force populations: Occupations in the labor force often correlate with delayed care-seeking behavior due to economic constraints. By providing instant testing and immediate treatment enrollment, Medupi addresses this critical challenge.

4. People living with HIV: Individuals with HIV, including sex workers, typically have a lower TB bacteria load, making detection more challenging. Medupi's enhanced sensitivity for low bacteria load makes it particularly suitable for this population.

5. Rural and Tribal Communities: These communities often live in hard-to-reach areas, with many resorting to self-medication and delayed care-seeking behavior. Medupi's portability allows for in-home testing and immediate treatment initiation, bypassing the need for multiple visits by health workers.

By starting our rollout in India, a country with the highest TB burden and an ambitious goal to be TB-free by 2025, we can make a significant impact on the global TB landscape. Our existing partnerships with study partners, non-profit organizations, and universities in India, combined with potential collaborations with health officials and agencies worldwide, will allow us to refine and improve Medupi's effectiveness and reach.

Future field studies planned for South Africa will further our understanding of Medupi's applicability in different contexts, contributing to our goal of making TB diagnostics accessible and effective for all, regardless of their location or socioeconomic status. Medupi's potential to revolutionize TB diagnostics lies in its ability to reach and serve those who need it most, offering a solution that aligns with the urgency of the TB crisis and the global commitment to eradicate TB by 2030.

Drizzle Health's founding team is composed of Bonolo Mathekga and Digvijay Singh. Bonolo and Digvijay were born and raised in South Africa, and India respectively. We have been personally affected by the plight of TB in our home countries in various ways. This has been the primary force driving us to work on developing solutions to address TB, from the onset of our careers. We have firsthand experiences working with Community Care Workers (CCWs) on the ground in South Africa, and India, as they go door-to-door providing TB services to their communities. We have collectively spent over 200 hours conducting stakeholder interviews with CCWs, community leaders, government officials, doctors, nurses, TB patients and their families. Throughout all of these experiences, we have grown to have a deep appreciation for the work that CCWs do, not only for TB, but for HIV/AIDS, as well as non-communicable diseases too. CCWs are the unspoken backbone of healthcare systems in LMICs, which is a sharp contrast to systems in more developed nations. Digvijay and I feel passionate about creating technologies that will help make them more effective at the very important work that they do. 

Throughout our design process, we have held numerous design sprints, ideation sessions and co-creation sessions with different stakeholders involved in the TB care pathway, right from CCWs to epidemiologists. We are also constantly engaging with our partners in India, South Africa and the US, to get feedback on our design process. We're currently working towards hosting a virtual listening session with CCWs, TB patients, and researchers in South Africa to learn how reimbursement for CCWs works, as well as how the on-going Covid-19 pandemic is affecting active TB case finding at a community level.  

We're currently running a pilot study in Chennai, India for 100 people (58 of them have been tested with 100% sensitivity) using our cartridge for microscopy. (25 positives, 16<Ct<30, HIV co-infection, GeneXpert comparator)

In addition, we currently finalizing (due to start in the next few weeks) the following:

1. An all-comers walk-in pilot study (endpoint : 50 positive cases). Likely will test 250 patients. Prospective sites : Jaipur, Rajasthan OR Delhi 

2. Two in-community screening pilots, where community care workers will tag geolocations of suspect patients when collecting their samples, to help visualize community transmission. Prospective sites : Tribal region in Madhya Pradesh AND Pune, Maharashtra 

Technical:

1. We're looking for partners and advisors in local manufacturing and regulatory (esp. India, South Africa)

2. We're looking to develop a more robust monitoring and evaluation system as we increase the number people we test.

3. We're looking for friends and team members passionate about global health, who're practical idealists, and bring skills in program management, mechanical and optical engineering, regulatory and quality systems and submissions, and B2B sales.

4. We're looking for local partners in the US to pilot our community diseases surveillance systems at city public health levels. 

Financial:

1. We're looking to fundraise (SAFEs, and grants) and are looking for advisors who can help navigate the right partners and channels.

Medupi's innovation lies in its potential to transform the tuberculosis (TB) diagnostic landscape by addressing the most critical gaps in current testing methods. It introduces a novel approach to TB testing that combines affordability, rapid results, portability, and ease of use, all of which are essential in low-and-middle income countries (LMICs) that bear the majority of the global TB burden.

The key elements that make Medupi innovative are:

1. Affordability: The high cost of Nucleic Acid Amplification Tests (NAAT), such as GeneXpert, and the infrastructural requirements associated with them limit their uptake and accessibility, especially in primary health centers (PHCs) in LMICs. Medupi, on the other hand, is a low-cost system, making it accessible to a broader population. We've reduced per test cost by 10 times.

2. Rapid Results: Current diagnostic tests take hours or even days to deliver results. Apart from intrinsic working principles, it is also caused by overload. 1 center with 1 GeneXpert mini can only test 12 patients/day for example. Medupi provides results within minutes, enabling faster initiation of treatment and reducing the time during which patients can spread the disease. We can do upto 40 times more tests in the same time.

3. Portability and Ease of Use: Medupi's compact size and simple operation make it suitable for use at all levels of the healthcare system, including by community care workers (CCWs) who can bring TB diagnostics directly to patients' homes. This addresses the problem of limited access to diagnostic centers, particularly in rural areas. Importantly, this allows for a more proactive approach to seek patients, as opposed to wait for them to show up while community transmission happens.

4. Improved Sensitivity: While SSM has a sensitivity of about 50%, the use of Medupi increases sensitivity to over 90%, enhancing the reliability of TB diagnosis.

Moreover, Medupi could potentially transform the TB diagnostic market by making advanced, accurate, and quick TB testing a norm rather than a luxury. It can democratize access to quality TB diagnostics and contribute significantly to the global effort to eradicate TB. The technology behind Medupi could also be adapted for other high priority diseases in the future, further expanding its impact.

In the short term, over the next two years, our primary impact goals revolve around improving the TB diagnosis and notification rates, and accelerating the initiation of correct treatment for patients. Specifically, we aim to:

1. Increase the number of bacteriologically confirmed TB cases: With the use of Medupi's cartridges, we anticipate a significant improvement in the sensitivity of TB diagnosis, which will lead to more confirmed TB cases.
2. Increase TB notification rates: Medupi's ease of use and rapid results should encourage increased testing, leading to higher notification rates.
3. Ensure patients get correctly diagnosed the first time: By enhancing diagnostic accuracy, we aim to minimize misdiagnoses, reducing the need for repeat testing and the associated stress for patients.
4. Ease of accessibility encourages more people to get tested: With our cartridge sales, we plan to make TB testing more accessible, particularly in underserved areas, thus encouraging more people to get tested.
5. Reunite patients with their test results: With faster, more accurate testing, patients can get their results sooner, allowing for quicker intervention and better patient management.
6. Initiate patients on TB treatment: By facilitating faster and more accurate diagnosis, we aim to hasten the initiation of appropriate treatment for TB patients.

In the longer term, over the next 2-5 years, our goals expand to encompass a broader impact on the TB landscape, leveraging the complete Medupi system. We aim to:

1. Create a positive impression of the healthcare system: By ensuring that any presumptive TB patients get correctly diagnosed upon accessing public healthcare, we can instill confidence in the system and process.
2. Decrease TB incidence rates and deaths: With widespread use of Medupi, we expect to see a tangible reduction in TB incidence and mortality rates.
3. Increase population coverage in active tracing efforts: With our portable, easy-to-use system, we can reach more people, particularly in hard-to-reach areas, thus expanding the coverage of active TB tracing efforts.
4. Reduce TB stigma: By providing faster relief from signs and symptoms, we hope to reduce the stigma associated with TB.
5. Reduce incidence rate of multi/extreme-drug resistant TB: Improved monitoring of active TB cases can aid in the timely detection and management of drug-resistant TB cases.
6. Establish TB outbreak surveillance: With real-time data collection and analysis, we aim to establish an efficient surveillance system for TB outbreaks.

We will achieve these goals by conducting TB testing at point of care settings using our products, working alongside community care workers and lab technicians, and reporting the results to both the patients and the national TB registry in a timely manner. We are actively collaborating with our existing partners for the mass production of our cartridges and are in the process of seeking new partnerships for the manufacturing of our Medupi reader system. Our phased approach, starting with small pilots and gradually expanding, will allow us to optimize our operations while achieving our impact goals.

We are working towards the UN's SDG Target 3.3 of ending the TB epidemic by 2030. Progress made towards achieving this goal will be measured by monitoring the reported TB incidence rates (called TB notification coverage in India) , following the implementation of our technology. Additionally, the number of bacteriologically confirmed TB cases, and the number of patients that are initiated on anti-TB drugs are all key performance indicators which we will be closely monitoring. 

Our ultimate goal is to contribute towards eradicating TB in India by 2025. This ambitious plan will be realized through a series of immediate and future goals that we have laid out.

However, it's crucial to understand that combating TB isn't a straightforward process. It's not just about testing and treating; it's a multi-layered issue that needs a holistic approach. Better TB drugs, treating latent TB infections (people who have TB bacteria but aren't yet sick), developing a TB vaccine, and introducing non-health interventions, like improved living conditions, are all part of the broader strategy.

To give you an idea of what we're aiming for, let's look at some numbers from India's National Strategic Plan to End TB. According to this plan, increasing active TB case finding (that is, actively looking for and diagnosing TB) by 25% by 2025 could reduce the number of new TB cases to 170 per 100,000 people. If we can increase active case finding even more - say by 30%, 70%, or 90% - we could bring the new cases down to 148, 120, or even just 44 per 100,000 people, respectively.

Now, let's take Rajasthan as an example. This is a state where we already have established partnerships. Rajasthan is home to approximately 81.2 million people and carries about 7% of India's total TB burden. Currently, about 89% of confirmed TB cases are diagnosed using traditional methods like sputum smear microscopy (SSM), X-rays, and TB culture.

Here's where our technology comes in. If we replace just 30% of the tests currently conducted at primary health centers (PHCs) with our rapid, accurate technology, we could correctly diagnose an estimated 44,954 TB patients in our first year of operation alone. This would be a substantial step towards our ultimate goal of a TB-free India.

In short, our technology is one piece of the puzzle, but a critical one. It's part of a larger strategy to increase active TB case finding, which is a key factor in reducing the overall number of TB cases and, ultimately, eradicating the disease.

The cartridge is powered by our polymer system that concentrates TB causing bacteria to one spot. The TB-capturing cationic polymer system, poly diallyldimethylammonium chloride (pDADMAC) has previously been shown to have a high affinity for mycobacterium [1-4].

The reader makes use of a polarization imaging technique to probe the microstructural and optical information of TB bacterial colonies [5]. The system processes and reads unique bacterial signatures from the cartridge, which are then processed and analyzed by comparing it to an existing library of bacterial signatures, leading to a positive or negative TB test result.

[1] Albert H, Ademun PJ, Lukyamuzi G, et al. Feasibility of magnetic bead technology for concentration of mycobacteria in sputum prior to fluorescence microscopy. BMC infectious diseases

2011;11:125.

[2] Liu J, Sun ZQ, Pei H, et al. Increased case finding of tuberculosis from sputum and sputum deposits after magnetic bead concentration of mycobacteria. Journal of microbiological methods

2013;93:144-7.

[3] Wilson S, Lane A, Rosedale R, Stanley C. Concentration of Mycobacterium tuberculosis from sputum using ligand-coated magnetic beads. Int J Tuberc Lung Dis 2010;14:1164-8.

[4] Tadesse M, Aragaw D, Rigouts L, Abebe G. Increased detection of smear-negative pulmonary tuberculosis by GeneXpert MTB/RIF(R) assay after bleach concentration. International journal of mycobacteriology 2016;5:211-8.

[5] Badieyan, Saeedesadat, et al. "Detection and discrimination of bacterial colonies with Mueller matrix imaging." Scientific reports 8.1 (2018): 1-10.

As a team, we firmly believe in acknowledging our differences in race, color, sexual orientation, gender identity, religion, disability, age, genetic information, veteran status, ancestry, and national or ethnic origin. It is only by acknowledging what makes us different, that we are able to truly embrace and celebrate our diversity. These differences govern how we uniquely experience the world, and motivate our decisions on when and how we access healthcare, the type of diseases endemic in our communities, and the medications available to us. 

Our goal is to fight TB and the destruction it is causing millions of lives around the globe each year. We understand that this is a fight where we need all the help we can get and need to rely on the best of each other.

The team's co-founders have differing backgrounds. Digvijay is an Indian national, hailing from the national capital region. Bonolo is South African and named the product Medupi, a Sepedi word that means gentle rain. Medupi is considered a blessing, as it is pleasant rain that soaks parched land, yielding a plentiful harvest. This aligns well with what we imagine equitable healthcare to look like. Rain affects everyone, regardless of socio-economic status, cultural, and identity-based human attributes. Similarly, our goal is to make healthcare accessible to everyone, regardless of socio-economic status, cultural, and identity-based human attributes. 

This spirit is reflected in our current team and extended team, and will guide us as we expand. 

Our primary business model is straightforward: we charge per Medupi reader device and per testing cartridge. 

We plan to sell each cartridge for $2, a price significantly lower than the $20 typically associated with cartridges for Nucleic Acid Amplification Tests (NAATs). This price aligns with guidelines set by the Foundation for Innovative New Diagnostics (FIND) and the World Health Organization's (WHO) Target Product Profiles. At scale, the cost of goods sold (COGS) for each cartridge falls under $0.25.

We intend to sell each Medupi reader device for $2000, also significantly lower the $10000 associated with NAATs (subject to the results of pricing discussions with stakeholders). At scale, the COGS for the reader falls below $500.

Over the next one to three years, our main customer is the Government of India, both at state and central levels. The Indian government is committed to eradicating TB in the country by 2025, a goal that is both urgent and politically significant. Diagnostic tools like our Medupi system play a critical role in achieving this goal, and the government has allocated substantial resources to this effort.

According to the National Strategic Plan to End TB in India 2020 report, India will need to conduct six times more tests, and over 90% of the population will need to be screened. This would cost $4.5 billion if done using NAAT over five years. By contrast, conducting the same number of tests using our device would cost only $300 million over five years. This drastic cost reduction would enable the government to increase funding for treatment and expand testing to include all symptomatic individuals, contact tracing, door-to-door screening, active case finding, and monitoring of drug-resistant cases.

Based on our current projections, we aim to sell 1 million cartridges and 100 Medupi readers by the end of 2024. Our total addressable market consists of the 8.2 million microscopy-based tests and 2.3 million NAAT-based tests conducted in India, a market that the government estimates will grow five times in size. We plan to start with pilot programs in two states before expanding to other states and eventually the national TB program. The number of new TB patients in India was about 1.9 million in 2021, while globally, there were about 10 million patients.

Our business model is not only sustainable but also transformative for the TB diagnosis landscape. We look forward to partnering with the MIT SOLVE community to navigate regulatory channels and garner support for our mission of making TB diagnostics accessible and affordable.

We're currently bootstrapping, as planned, to finish phase I (i.e. collect field efficacy data at YRG, Chennai). We're already engaging with grant funders as we transition towards Phase II activities. Towards our bootstrapping strategy, our company has been and continues to provide consulting services to the National Institutes of Health's (NIH) Rapid Acceleration of Diagnostics (RADx) initiative.

From a product perspective, the strategy is to pursue separate approval paths for the cartridge and the whole Medupi system. The cartridge is a relatively simpler and lower cost product that we already have a lot of buy in for. It also has a lower regulatory burden, as per the Central Drugs Standard Control Organization's (India's medical devices regulatory body) guidelines and has extreme utility for the equipment used by the Indian TB program now, and for the foreseeable future. The Indian government, in 2021, released an essential equipment list enumerating equipment it seeks to procure for health centers at every level - this includes microscopy equipment for TB at various levels, indicating that apart from a strategy focused on NAAT, the government is actively procuring and putting infrastructure in place for microscopy.

Since the cartridge readily works with microscopy, and dramatically increases performance, we see it as a low barrier first product that will bring in revenue in the short term, while we work on the engineering, regulatory and production scale-up phases for the Medupi reader and approvals for the overall Medupi system. 

Towards our bootstrapping strategy, our company has been and continues to provide consulting services to the NIH's RADx initiative, with the contract profits fueling our development costs.

The company and the project raised and continues to use grants and resources from Halcyon, Acumen, VentureWell, The Johns Hopkins Alliance for Healthier World, Autodesk Technology Impact program, Ballard Spahr BASE program, and the Technology Accelerator Fund at the Center for Bioengineering Innovation and Design. 

Non-dilutive external funds raised total over $80,000.