Innovations: MSF mini-lab

Before reading the article below, please watch this short video from Médecins Sans Frontières on the Mini-Lab access blue-print:

Source: Jean-baptiste Ronat, Chief Scientific officer, Mini-Lab project; 20/10/2020

Introduction

Antimicrobial resistance represents a threat to global health-care systems^{[1], [2]}. Low-resource settings (LRS) especially struggle to diagnose and effectively treat bacterial pathogens ^[3]–[5]. Quality and coverage of Clinical Bacteriology Laboratory in LRS are complicated by a lack of infrastructure and expertise ^[3], especially in laboratory facilities where quality assurance procedures, skilled personnel, laboratory supplies, and adequate and functioning equipment are all in short supply ^[4]–[8]. Furthermore, the rolling-out of clinical bacteriology laboratories (CBL) in LRS raises numerous challenges, including procurement constraints, product stability and availability of qualified personnel ^[6]. Automated systems are restricted due to their high costs and high maintenance requirements, molecular-based methods for identification (ID) and antibiotic resistance testing (ART) are too costly and not yet ready to replace phenotypical methods for antibiotic susceptibility testing (AST), and whole genome sequencing (WGS) is not yet applicable in the diagnostic setting in LRS ^[9].

In 2016, Médecins Sans Frontières (MSF) asked whether high-quality clinical bacteriology can be implemented in the most remote, challenging, and underserved areas of the world to improve treatment and surveillance of antimicrobial resistant infections ^{[10], [11], [12]}. Previously, mobile laboratory solutions have focused on outbreak investigations and used containers, truck platforms, or pelican suitcases to transport and store minimally adapted laboratory equipment and consumables. Most mobile laboratory solutions use expensive molecular technologies that demand skilled technicians and are focused on single pathogen detection^[13].

Médecins Sans Frontières response to tackle AMR challenges:

To tackle the problem of AMR, MSF has created in 2015 a dedicated task force to develop and implement a control program including infection prevention and control (IPC) measures, antimicrobial stewardship, and the strengthening of CBLs capacity in the field. As a tool to achieve these goals, MSF, in collaboration with other partners, has developed the Mini-Lab, a transportable, self-contained, quality assured, stand-alone CBL adapted to low-resource settings. The Mini-Lab is conceived to respond to LRS constraints:

• It is based on the concept that clinical bacteriology laboratory in LRS should be patient-directed and guided by clinical reality ^[8].
• It is designed to be operated by lab technicians non-expert in microbiology.
• It is based on the idea that a CBLs for LRS should be well-conceived, cost-effective and built-for-purpose, not an “entry-level” version of its counterpart in high resource settings ^[6].
• It uses conventional simple and affordable culture-based technologies and quality-assured oriented AST, considered sufficient to improve patient care and to provide adequate surveillance data, while contributing to the control of hospital-acquired infections ^{[7], [11]}.

The Mini-Lab focuses on diagnostics of bloodstream infections and urine tract infections, for the moment, using manual (i.e. automatic equipment-free) techniques and providing preliminary results by pathogens group classification, followed by full-pathogen identification by biochemical testing and AST by ready-to-use broth micro- dilution method and include a microbiology expert system that interprets all results, warn laboratory technician and provide valuable information to clinicians with regard to the organism or treatments. The panel of antibiotics has been specifically chosen to meet MSF field needs, the WHO Model List of Essential Medicines ^[14] and the GLASS recommended surveillance indicators ^[15], for both treatment and surveillance purposes.

Blueprint to make this solution available to stakeholders involved in medical care and antibiotic resistance surveillance in LRS:

After several years of development and evaluation on the field, MSF is starting the deployment of Mini-Lab in the field (8 sites plan in 2022), meanwhile, several stakeholders outside of MSF believe that this solution might benefit other partners willing to have access to simplified bacteriology for clinical or surveillance purpose. However there are barriers to overcome and to address:

• MSF is not a manufacturer or business-driven organisation and have support of several well-known organisations (DNDI, GARP, FIND) that have expertise of the different go to market strategies to apply to this type of solution and are supporting us in the development of a business model that could be applied keeping “MSF principles.”
• We have some of the unique logistic capacity in humanitarian actors that provide proper and efficient supply management with the supply centre we have around the world, such as MSF Logistique in Bordeaux, France, that is for now the assembler of this Mini-Lab and cannot distribute this product outside of the Non-Governmental Organization area. Therefore in our approach to make this product available we would need to partners with subsidiaries organisations that have the capacity to assemble and distribute the product outside of MSF’s logistique mandate.
• Despite the simplicity of the concept it does require a stringent supply management system and when entering the countries would need to obtain all the legal registration in order to penetrate properly a target country market. As well, while the Mini-Lab has been largely tested inside MSF for usability and robustness, further evaluation should be done by future partners outside of MSF to evaluate ease of integration into their clinical/surveillance practice.

The reflection around the provision of this solution outside of MSF is still ongoing as it has been delayed due to COVID and the necessity to focus on the deployment of MSF for the moment in possible business model we are exploring three access pillars :

• Turn key solution: in this approach we could provide a fully equipped solution as described above with all reagents, training, equipment through a network of suppliers with capacity of after-sale service, onsite training and supply sustainability in the desired country.
• Adapted turn-key solution: this approach would require that we provide a service to a partner that would like to install several Mini-Labs in a region, country, etc. we would then, as a service provider, adapt the solution together to local supply possibilities and hence provide the capacity to the partner to build its own Mini-Lab and supply management adapted to its constraints.
• Lessons learned: In this 5-year development journey we have learned so much and have compiled the scientific information in order for future developer interested in adapting technologies to LRS to share our know-how, hence facilitating their work. A complete list of our article are presented below^{[6], [11], [16], [17]} and others are to come. We are as well looking to make available freely all the Standard Operating Procedures, documents, training, e-learning we have created on a web page we are considering to launch next year under a Creative Common licence.

An interesting by-product of Mini-Lab Development that could benefit others:

Finally, during the development of the Mini-LIMS, the Laboratory Information Management System specific to Mini-Lab, we have worked with the Boston-based WHO Collaborating Centre for Surveillance of Antimicrobial Resistance, developers of the well-known WHONET microbiology data management and analysis system, in order to incorporate into our Mini-LIMS WHONET’s unique capacity to interpret Zone Inhibition Diameters or Minimal Inhibition Concentration values into understandable clinical categories with all the complexity of drug-organism interpretation specificities and expert rules and more than 30 years of expertise. To do so, MSF and the WHONET team have partnered to develop a table-driven approach for breakpoints, organisms lists, expert and intrinsic resistance rules, etc., originally available inside WHONET, in order to ease the transfer of this state-of-the-art test interpretation engine into our Mini-LIMS. Through this collaboration, we realised first of all that this work could benefit other LIMS developers in the short-term interested in the field of Antibiotic Resistance surveillance for Low- and Middle-Income Countries. And in the long-term, we believe that an international collaborative effort could benefit from this initial work to build a sustainable maintenance and support strategy. Therefore, we are now looking to make available to all, this table-driven approach to antimicrobial susceptibility test interpretation that could be maintained by a community of voluntary experts around the world.