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Background: The International Normalized Ratio (INR) monitors anticoagulant treatment but relies on laboratory-based services. This could limit access to rapid monitoring and increase the diagnostic delay, both of which may be addressed by point-of-care testing (POCT). This study investigated the LumiraDx POC platform for INR monitoring. Methods: INR was measured on recalcified residual venous (n = 94) specimens from Chris Hani Baragwanath Hospital and capillary blood specimens (n = 254) from consenting enrolled participants at Charlotte Maxeke Johannesburg Academic Hospital Anticoagulation clinic, Johannesburg, South Africa. Standard-of-care (SOC) INR was measured on sodium-citrated venous blood using the Sysmex-CS2500 platform (Siemens Healthcare) and Neoplastin-R (Roche Diagnostics and Diagnostica Stago, Paris, France) within 2 h post-venipuncture. Within run, precision was measured using 2 LumiraDx control levels. The statistical agreement of paired INR measurements was also stratified by dosing decision. Results: The precision was within the manufacturer's claim for controls (level 1%CV: 3.63, level 2%CV: 2.24). Accuracy analysis showed a moderate overall agreement compared to the SOC INR results with a correlation coefficient of 0.94 (95% Cl, (0.9267 to 0.9497)). The overall precision (ρ > 0.9) and accuracy (Cb = 0.9842) were good with an absolute bias of 0.07. The 95% confidence intervals for the slope and intercept did not include 1.00 and 0.00, respectively; however, the total calculated error was within the minimal acceptable limits. Conclusion: The LumiraDx INR Test showed a good performance compared to laboratory-based testing and provided opportunity for rapid and patient-centric care. Owing to an increasing positive bias for INR > 3.5, confirmation with laboratory INR measurements may be required. [ABSTRACT FROM AUTHOR]

Background Routine plasma viral load (VL) testing is recommended for monitoring human immunodeficiency virus–infected patients on antiretroviral therapy. In Zambia, VL scale-up is limited due to logistical obstacles around plasma specimen collection, storage, and transport to centralized laboratories. Dried blood spots (DBSs) could circumvent many logistical challenges at the cost of increased misclassification. Recently, plasma separation cards (PSCs) have become available and, though more expensive, have lower total misclassification than DBSs. Methods Using a geospatial model created for optimizing VL utilization in Zambia, we estimated the short-term cost of uptake/correct VL result using either DBSs or PSCs to increase VL access on equipment available in-country. Five scenarios were modeled: (1) plasma only (status quo); (2) plasma at high-volume sites, DBS at low-volume sites; (3) plasma at high-volume sites, PSC at low-volume sites; (4) PSC only; (5) DBS only. Results Scenario 1 resulted in 795 342 correct results due to limited patient access. When allowing for full and partial adoption of dried specimens, access increases by 19%, with scenario 3 producing the greatest number of correct results expected (929 857). The average cost per correct VL result was lowest in the plasma + DBS scenario at $30.90 compared to $31.62 in our plasma + PSC scenario. The cost per correct result of using dried specimens only was dominated in the incremental analysis, due primarily to fewer correct results. Conclusions Adopting the partial use of dried specimens will help achieve improved VL access for patients at the lowest cost per correct result. [ABSTRACT FROM AUTHOR]

The tiered laboratory framework for human immunodeficiency virus (HIV) viral load monitoring accommodates a range of HIV viral load testing platforms, with quality assessment critical to ensure quality patient testing. HIV plasma viral load testing is challenged by the instability of viral RNA. An approach using an RNA stabilizing buffer is described for the Xpert® HIV-1 Viral Load (Cepheid) assay and was tested in remote laboratories in South Africa. Plasma panels with known HIV viral titres were prepared in PrimeStore molecular transport medium for per-module verification and per-instrument external quality assessment. The panels were transported at ambient temperatures to 13 testing laboratories during 2017 and 2018, tested according to standard procedures and uploaded to a web portal for analysis. A total of 275 quality assessment specimens (57 verification panels and two EQA cycles) were tested. All participating laboratories met study verification criteria (n = 171 specimens) with an overall concordance correlation coefficient (ρc) of 0.997 (95% confidence interval (CI): 0.996 to 0.998) and a mean bias of −0.019 log copies per milliliter (cp/mL) (95% CI: −0.044 to 0.063). The overall EQA ρc (n = 104 specimens) was 0.999 (95% CI: 0.998 to 0.999), with a mean bias of 0.03 log cp/mL (95% CI: 0.02 to 0.05). These panels are suitable for use in quality monitoring of Xpert® HIV-1 VL and are applicable to laboratories in remote settings. [ABSTRACT FROM AUTHOR]

The Xpert ® Xpress SARS-CoV-2 and Xpert ® Xpress SARS-CoV-2/Flu/RSV tests were rapidly developed and widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In response to emerging genetic variability, a new SARS-CoV-2 target (RNA-dependent RNA-polymerase) has been added to both tests: Xpert ® Xpress CoV-2 plus and Xpert ® Xpress CoV-2/Flu/RSV plus test. A rapid evaluation of both tests was performed in South Africa, using residual respiratory specimens. Residual respiratory specimens (n = 125) were used to evaluate the Xpert ® Xpress CoV-2 plus test and included 50 genotyped specimens. The Xpert ® Xpress CoV-2/Flu/RSV plus test was assessed using 45 genotyped SARS-CoV-2 specimens, 10 influenza A, 10 influenza B and 20 respiratory syncytial virus specimens. Results were compared to in-country standard-of-care tests. Genotyped specimens tested the performance of the test under pressure from circulating SARS-CoV-2 variants of concern. Reference material was included to assess the test limits and linearity. The Xpert ® Xpress CoV-2 plus test performance compared to reference results across residual respiratory specimens was good (positive percentage agreement (PPA) = 95.2%, negative percentage agreement (NPA) = 95.0%) The Xpert ® Xpress CoV-2/Flu/RSV plus test showed good performance across all residual respiratory specimens (PPA = 100%, NPA = 98.3%). All genotyped variants of concern were detected by both tests. The Xpert ® Xpress CoV-2 plus and Xpert ® Xpress CoV-2/Flu/RSV plus tests can be used to diagnose SARS-CoV-2, and to diagnose and differentiate SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus, respectively. The NPA was lower than the recommended 99%, but was influenced by the low number of negative specimens tested. The variants of concern assessed did not affect test performance. It is recommended that sites perform their own assessments compared to in-country standard-of-care tests.

Currently, the most accurate way to diagnose an active SARS-CoV-2 (COVID-19) infection is through detection of viral RNA using reverse transcription polymerase chain reaction (RT-PCR) test. While RT-PCR tests are the most sensitive for identifying infection, there are significant limitations, such as global access to sufficient test kits, turnaround times (TAT) from specimen collection to test result is often greater than 24 h and the need for skilled operators in accredited laboratories requiring specialized equipment. A rapid test performed at the point of care (POC) could provide a result within an approximate time of 30 min post specimen collection, be performed by a health care worker and comprise a simple workflow, improving both turnaround time and potentially decreasing costs (e.g., transport, cold-chain, skilled laboratory staff, complex equipment). Determining the performance of SARS-CoV-2 RT-PCR tests is, however, easier to assess than antigen-based POCT, as residual clinical specimens (swabs in universal transport media [UTM]) are readily available in laboratory environments, and do not require patient informed consent. Evaluating the performance of POCT requires informed-consent driven studies, with patients required to provide a standard of care specimen as well as study evaluation specimens, which is often not acceptable as nasopharyngeal swabbing can be invasive, clinical field trials are costly and time consuming. Many institutions and regulatory bodies also require preliminary data prior to use in field settings. Therefore, we have developed a method to determine the performance of antigen based POCT that can be used by implementers in national healthcare programs, regulators and rapid test developers. The method investigates both quantitative and qualitative parameters, with the latter providing insights into the capability for implementation and national program uptake., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Molecular technology revolutionized the diagnosis of tuberculosis (TB) with a paradigm shift to faster, more sensitive, clinically relevant patient care. The most recent molecular leader is the GeneXpert MTB/RIF assay (Xpert) (Cepheid, Sunnyvale, CA), which was endorsed by the World Health Organization with unprecedented speed in December 2010 as the initial diagnostic for detection of HIV-associated TB and for where high rates of drug resistance are suspected. South Africa elected to take an aggressive smear replacement approach to facilitate earlier diagnosis and treatment through the decision to implement the Xpert assay nationally in March 2011, against the backdrop of approximately 6.3 million HIV-infected individuals, one of highest global TB and HIV coinfection rates, no available implementation models, uncertainties around field performance and program costs, and lack of guidance on how to operationalize the assay into existing complex clinical algorithms. South Africa's national implementation was conducted as a phased, forecasted, and managed approach (March 2011 to September 2013), through political will and both treasury-funded and donor-funded support. Today there are 314 GeneXperts across 207 microscopy centers; over 8 million assays have been conducted, and South Africa accounts for over half the global test cartridge usage. As with any implementation of new technology, challenges were encountered, both predicted and unexpected. This chapter discusses the challenges and consequences of such large-scale implementation efforts, the opportunities for new innovations, and the need to strengthen health systems, as well as the impact of the Xpert assay on rifampin-sensitive and multidrug-resistant TB patient care that translated into global TB control as we move toward the sustainable development goals.