Diagnostics innovations that could shape the AMR landscape

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In recent years, antimicrobial resistance (AMR) has emerged as a global public health and economic concern. According to a study published in The Lancet, an estimated 1.27 million succumbed to bacterial AMR in 2019. The World Health Organization (WHO) has declared AMR as one of the top 10 global public health threats facing humanity. This challenge calls for innovative, multidisciplinary solutions to prevent, detect, and treat AMR.

Unmet needs

Antimicrobial-resistant microbes can be found in people, animals, plants, and the environment. Indiscriminate use of antibiotics in agriculture, livestock, and medicine is a major driving factor in the emergence of AMR. Such indiscriminate use exerts selection pressure, causing microbes to acquire resistance genes that can then spread to other bacteria. The high burden of infectious diseases compounded by inadequate healthcare and poor sanitation systems further thrust AMR in low-to-middle-income countries. Making matters worse is the lack of data available on the extent of AMR.

The key to tackling AMR is a holistic and integrated approach that addresses issues end-to-end. It comprises innovations to promote antibiotic stewardship, improve AMR surveillance with better diagnostics and data management, encourage diagnosis-based clinical decisions, and ensure good animal and environmental health. Perhaps, at the heart of such an approach is rapid and affordable point-of-care diagnostics.

Fast and accurate diagnosis of pathogens, even the ability to distinguish bacterial and viral infections, can help reduce the misuse of antimicrobials. Further, determining the antibiotic susceptibility of pathogens in a sample is critical in choosing the right antimicrobial for treatment, thereby checking further development of AMR. But such diagnostic tests are limited, especially in low-to-middle-income countries with high AMR burden. Besides, the type and volume of samples for diagnostics can vary depending on the context: from saliva to blood, urine, feces, soil, or water. Moreover, infections involving different microbes in the same sample add to the complexity of the problem.

Addressing the unmet needs

It is no surprise that many countries have charted national initiatives to check AMR through innovations in diagnostics. For instance, the Indian Council of Medical Research (ICMR) established India’s AMR surveillance and research network in 2013, and the initiative considers access to appropriate diagnosis a top priority. One of the strategic priorities of India’s National Action Plan on AMR 2017–2021 was to promote investments for AMR research and innovations through new diagnostics.

There is a real need for rapid, easy-to-use diagnostic tests that can accurately detect the pathogen and guide appropriate treatement as conventional methods, while precise, require trained personnel and are time-consuming.

In this direction, several innovative AMR diagnostic technologies are emerging globally. For instance, Day Zero Diagnostics, a Boston-based start-up, is developing a fully integrated sample prep and sequencing technology, which leverages machine learning in order to provide pathogen ID and resistance gene information direct from whole blood in less than 8 hrs. Considering the rapid expansion of sequencing capabilities since the start of the COVID-19 pandemic, solutions like this could expand access to existing sequencing capacity for AMR-focused testing. Additionally, Baebies, a North Carolina-based company, is leveraging their FINDER platform and capabilities for processing small sample volumes in order to provide bacterial infection confirmation and AMR results from blood cultures of neonatal patients in less an hour. Such rapid tests, when accurate, can significantly increase the patient’s chances of survival during sepsis. Avails Medical’s proposed flagship product, Avails eAST, is an electronic antibiotic susceptibility testing device that could fit into the current laboratory workflow and rapidly detect the susceptibility of pathogens in blood using biosensors. These start-ups along with many others, including India-based Module Innovations, have been funded by Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X).

Some startups incubated at C-CAMP in India have been developing new platforms to screen for antimicrobial-resistant pathogens. These include Spotsense, Module Innovations, Achira Labs, Papyrus Diagnostics, and RapidDx Technologies. Their products range from detecting microbes in food, clinical samples, and urinary tract infections to neonatal sepsis.

Spotsense has a diagnostic pacifier platform, Spittle, to screen for diseases in newborn babies using saliva, including a rapid diagnostic test for neonatal sepsis. Neonatal sepsis is one of the leading causes of infant death within the first year of life. It could be treated if detected early and accurately.

Module Innovations is developing nanofiber strips that change color upon detecting enterohemorrhagic bacteria in food and clinical samples. They now have devices called EcoSense and Usense to detect E. coli and specific pathogens that cause urinary tract infections, respectively. Achira Labs’ Bug Check is a rapid diagnostic technology that detects microbes and antimicrobial resistance genes in urinary tract infections. Papyrus Diagnostics has a paper-based antibiotic susceptibility test called Papyrus, which detects antimicrobial-resistant pathogens. RapidDx has also developed a microfluidics-based platform technology called rPASA for fast screening of different pathogens. In less than 5 hours, rPASA can directly identify antibiotics that could work against pathogens in a clinical sample. These technologies may enable physicians to decide on the choice of antibiotics based on diagnosis, thereby preventing the emergence of AMR.

Funding and support

The success of these and other upcoming ideas relies on good funding and technical support. To this end, CARB-X has invested almost $500M to support therapeutics, preventatives, and diagnostic innovations to detect bacterial infections and antimicrobial resistance or drug susceptibility with the support of a large of pool of expert advisors and accelerators, like FIND and C-CAMP. The recent CARB-X funding call includes funding for rapid diagnostics to rapidly diagnose and detect antibiotic-sensitive or resistant gonorrhea infections. Gonorrhea is a sexually transmitted disease, caused by Neisseria gonorrheae, a major public health concern with over 80 million infections worldwide in 2020 for which the last line of effective therapy is losing effectiveness as XDR cases have already been detected. In addition, the call includes funding opportunities for oral therapeutics, vaccines for neonatal sepsis, and other gonorrhea products. Entities can express interest in all 3 themes by October 31, 2022, January 30, 2023, or May 1, 2023, all by 23:59 ET. In an effort to support the growth and success of the diagnostic ecosystem in India, CARB-X is sponsoring a product development webinar series starting Monday, November 7 and runs through Friday, December 9. If you would like to register or learn more, please visit the CARB-X website or click here.

Sources:

  1. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext
  2. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance#:~:text=Antimicrobial%20resistance%20(AMR)%20is%20a,public%20health%20threats%20facing%20humanity.
  3. https://www.thelancet.com/action/showPdf?pii=S2666-5247%2821%2900303-7
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047147/
  5. https://iamrsn.icmr.org.in/index.php/diagnostic/amr-diagnostic
  6. https://cdn.who.int/media/docs/default-source/antimicrobial-resistance/amr-spc-npm/nap-library/national-action-plan-on-amr-(india).pdf?sfvrsn=9f396e90_1&download=true
  7. https://www.ccamp.res.in/amr-carbx
  8. https://carb-x.org/carb-x-news/carbx-convenes-next-decade/
  9. https://www.who.int/news-room/fact-sheets/detail/multi-drug-resistant-gonorrhoea

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.

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