Leapfrogging laboratories: the promise and pitfalls of high-tech solutions for antimicrobial resistance surveillance in low-income settings

Abstract

The scope and trajectory of today’s escalating antimicrobial resistance (AMR) crisis is inadequately captured by existing surveillance systems, particularly those of lower income settings. AMR surveillance systems typically collate data from routine culture and susceptibility testing performed in diagnostic bacteriology laboratories to support healthcare. Limited access to high quality culture and susceptibility testing results in the dearth of AMR surveillance data, typical of many parts of the world where the infectious disease burden and antimicrobial need are high. Culture and susceptibility testing by traditional techniques is also slow, which limits its value in infection management. Here, we outline hurdles to effective resistance surveillance in many low-income settings and encourage an open attitude towards new and evolving technologies that, if adopted, could close resistance surveillance gaps. Emerging advancements in point-of-care testing, laboratory detection of resistance through or without culture, and in data handling, have the potential to generate resistance data from previously unrepresented locales while simultaneously supporting healthcare. Among them are microfluidic, nucleic acid amplification technology and next-generation sequencing approaches. Other low tech or as yet unidentified innovations could also rapidly accelerate AMR surveillance. Parallel advances in data handling further promise to significantly improve AMR surveillance, and new frameworks that can capture, collate and use alternate data formats may need to be developed. We outline the promise and limitations of such technologies, their potential to leapfrog surveillance over currently available, conventional technologies in use today and early steps that health systems could take towards preparing to adopt them.

AMR in low-resource settings: Médecins Sans Frontières bridges surveillance gaps by developing a turnkey solution, the Mini-Lab

“…'Leapfrog' solutions (diagnostic technologies without the infrastructure requirements of systems used in high-income countries) are much needed in these contexts, such as rapid, affordable, and effective point-of-care (POC) diagnostics (especially those that distinguish between viral and bacterial infections) that can identify pathogens and provide antibiotic susceptibility testing (AST). These solutions must be adapted to LMIC constraints, have low maintenance needs, and be able to handle varying heat/humidity levels [28]. Yet, these breakthrough products have not yet materialized, mostly because of market failures and barriers to use [6].…”

A Novel Air-Dried Multiplex High Resolution Melt Assay for the Detection of Extended Spectrum Beta-Lactamase and Carbapenemase Genes

“…This process would eliminate the need for the cold chain, ensure their biological integrity and simplify preparation, as only nuclease-free water and the DNA template would need to be added to resuspend the PCR reagents. 16–18 Typically, this process would be done by lyophilisation of the reagents. Lyophilisation, also called freeze-drying, is the process of the removal of water from a product by volatilization and desorption to increase the lifespan of a product.…”

The importance of molecular diagnostics for infectious diseases in low-resource settings

“…As has been stated before, “PCR is an easy thing to do badly” 2 , and the likelihood of waste, contamination or data misinterpretations from poorly executed molecular tests are the nightmares of even the most forward-thinking diagnostic advocates. WGS might mitigate some PCR limitations.…”

“…Despite their utility and precision, molecular diagnostics were deemed ‘inappropriate’ for decades, as they were considered to be too finicky, contamination-prone, expensive and technically complex to be used where resources are constrained, skills in short supply and infrastructure not up to date. However, traditional culture-based clinical microbiology, typically deemed ‘appropriate’, has been notoriously difficult to sustain at the required quality in lowest-income settings without external support 1 , 2 . Some pathogens are cheap to culture, whereas culture is costly for others.…”

“…There is a pressing need to expand and solidify the molecular biology knowledge-base in low-income countries and to scale up access to external quality assurance. Microfluidics could protect sensitive steps from error, and miniaturization will save on expensive reagents 2 . Deployment of Gene Xpert for the detection of tuberculosis in resource-constrained settings is a case in point 8 and was leveraged for Ebola and SARS-CoV-2 outbreak testing.…”