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The WHO AMR Technology landscape

Debi Boeras presents an overview of the WHO AMR technology landscape and discusses how they could be leveraged to build back a stronger AMR response.
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DEBI BOERAS: In this step, we will go through the AMR technology landscape, the types and methods of diagnostics, the diagnostic systems, and different products currently available. In 2019, WHO published the AMR technology landscape, describing the types of pathogen detection and host response markers. The report focuses on commercially available diagnostics to combat AMR. Specifically, diagnostics that improve clinical syndromic management of patients to reduce the overprescription of antibiotics that can be performed at primary and secondary care facilities in low and middle-income countries, and are targeted at pathogens primarily related to community-acquired infections and secondarily to bacterial infections that are most frequently Acquired In Hospitals– HAIs– and to help distinguish bacterial from non-bacterial infections.
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For pathogen detection, test techniques can include microscopy, culture plus identification, immunoassays for the detection of pathogen proteins, molecular assays for the detection of pathogen nucleic acids, and sequencing. Post-responsive markers can be antibodies or markers of inflammation such as C-Responsive Protein, CRP. There are three types of tests used by health care professionals to determine the best course of action for patient treatment. An ID test identifies the microorganism, and combined with antimicrobial susceptibility testing can help assess the effectiveness of antimicrobial agents in killing or inhibiting the growth of the microbe. Antimicrobial resistance testing can detect the genes that encode resistance, and combined with an ID test could help assess resistance, except that a negative ART result does equal susceptibility.
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The organism may be resistant to the antimicrobials through a mechanism not covered by the ART, or the genotypic method may not detect emerging resistance patterns for which the genotype has not been identified. Since the AMR technology landscape has provided detailed information on different types of technology for AMR, we will not repeat any technology information here. Instead, we would like to provide some guidance on the advantages and disadvantages for the types of diagnostic methods to detect pathogens and resistance. This table shows that. Phenotypic tests, which are culture-based, can be low cost and can guide treatment, but require a lab with the capacity to perform culture. And the results generally take 48 to 72 hours.
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Genotypic tests are based on molecular amplification techniques, which are highly sensitive and specific. Resistant genes can be detected in as little as two to four hours. The presence of a resistant genotype against an antibiotic is useful in informing clinicians pretty quickly what not to prescribe. Note, though, that it does not tell us that the resistance gene is expressed or not. These tests also require a lab, are costly, and can only detect resistance genes we know. Proteomic tests measure byproducts of a pathogen or its resistance genes, such as a protein or toxin. It takes as little as 30 minutes and are available as point of care tests.
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The presence of the byproducts of a resistance gene means that the gene is expressed and clinicians should avoid prescribing that antibiotic. Reliable information on the burden of AMR is dependent on testing and the quality of data available. Diagnostics, software, and data management applications are key in capturing and processing the data needed. A key consideration for a laboratory is the choice of equipment to perform testing. A major consideration is whether to purchase open or closed diagnostic systems. The choice is often based on what testing is required, testing volume, facility available to accommodate the smooth running of the equipment, funding, and technical capacity available. In general, the advantages and disadvantages of open and closed systems are as follows.
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Open diagnostic systems use manufacturer-specific reagents, and also allow for the use of reagents from other manufacturers, as well as the ability for laboratories to develop their own tests, what is referred to as laboratory-developed tests. These are sometimes referred to as open polyvalent platforms. Closed or proprietary diagnostic systems are those which use manufacture-specific reagents only. Data systems can also be open or closed. Open are usually produced as a result of open collaboration and source codes are public, while closed or proprietary systems are owned by a few individuals or a company. In general, open systems may allow for building resiliency into the lab networks, as they may be faster at adapting and evolving to meet new requirements over time.
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The advantages to open systems are more flexibility, may be easily modified to suit additional needs that may arise, no one owns the system, and is usually less expensive. Increased competition and increased access to multiple products, easier to sustain as just a qualified programmer can be able to look after the software. Disadvantages are they are more prone to quality issues and vulnerable to manipulation. They do not come with extensive support. Since they are not made for any specific person or setting, they may not be user-friendly. And they can require self-validation by the user.
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The next few slides, we will go through some options for open systems for AMR, because as previously mentioned, open systems can allow for more flexibility with testing and allow for more than one type of test. Here we see three different products for manual testing. Users can develop their own testing protocols and perform testing with their choice of reagents. Note that these instruments run the PCR aspect of tests. Users must separately process the specimens to extract the nucleic acid that is the sample for the PCR test. The Roche LightCycler instrument is a real-time, high-throughput PCR system with many functionalities and multiplex capabilities. ThermoFisher’s Applied Biosystems is another high-throughput, automated instrument, allowing up to 480,000 reactions.
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And the BioRad CFX Opus is similar network-connected, real-time PCR detection system with cloud connectivity. The BD Max system featured here is an automated system that offers simple implementation and a standardised workflow with both closed system and open system reagent capabilities. The closed system menu of tests is shown here. Being fully automated, there’s no visual interpretation of results required, and they can test up to 24 samples with different assays across a wide range of specimen types. When processing 24 samples, it takes 15 minutes of hands-on time, and results are in under three hours.
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Here you see a sampling of the suite of reagents available on this system in an open system format. This allows users to extract nucleic acid from different specimen types with an automatic transfer to the PCR assay. Users add their choice of primers probes for the assay based on their pathogen and targets of interest. The Abbott m2000 RealTime System pictured here is a highly flexible platform with automated sample extraction, and offers open-mode protocols for general purpose extraction on the m2000sp. The system is also comprised of the m2000 RealTime PCR thermal cycler reader instrument. At the completion of the automated sample preparation protocol, the operator seals and manually transfers the PCR plate to the Abbott m2000 RT for nucleic acid detection.
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It has a larger footprint for labs, but offers a barcode reader and flexible sample processing. Sample IDs and processing status for each specimen are electronically transferred to the m2000 RT from the m2000sp and linked to the PCR plate ID. In comparison, closed systems offer automated testing, requiring less technical expertise and minimal hands-on time. Sample in, answer out. They provide greater control over quality in such that the developer validates the system and the tests. They provide access to training and technical support from the company and enhance data security. The disadvantages are that these systems are made for a specific purpose and the users cannot modify them.
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There is much more control from the developer and manufacturer, so when something goes wrong, it is not possible for the user to troubleshoot so easily. The system often requires software updates, and all of this leads to increased costs.
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The next few slides, I will show you a few examples of closed systems currently available for AMR that can be performed outside of laboratory settings by non-laboratory staff. The Cepheid Gene Expert platform provides a suite of various platform types with varying footprints. Random access avoids batching samples and time to results is approximately 45 minutes, with only two minutes of hands-on time. Their suite of applications covers health care-associated infections, respiratory infections, and sexual health. The BioFire Film Array is based on a two-stage nested multiplex PCR and comes with reagents dried in a plastic pouch. It can test 16 pathogens in one run. The menu includes a respiratory panel, a gastrointestinal panel, a biothreat panel and blood culture ID, and carbapenemase-resistant enterobacteriaceae.
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This system also offers data connectivity to support reporting. The last product shown here is the Abbott ID NOW point-of-care molecular platform, based on nucleic acid isothermal amplification technology. It has been widely used for COVID testing and can also test for other respiratory infections with a chlamydia and gonorrhoea test in clinical trials and C. difficile in development.

In 2019, WHO published a landscape of diagnostics against antibacterial resistance, gaps and priorities.

In this step, Dr. Debi Boeras goes through the types and methods of diagnostics, the diagnostic systems, and different products currently available.

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Diagnostics for AMR: Building Back Better from the COVID-19 Pandemic

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