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Background: Diagnostic sensitivities of point-of-care SARS-CoV-2 assays depend on specimen type and population-specific viral loads. Evaluation of these assays require "direct" specimens from paired-swab studies rather than more accessible residual specimens in viral transport media (VTM). Methods: Residual VTM and limit-of-detection studies were conducted on Abbott ID NOW™ COVID-19, Quidel Sofia 2™ SARS Antigen FIA, and DiaSorin Simplexa™ COVID-19 Direct assays, with cycle threshold (CT) adjustments to approximate direct-specimen testing based on gene-target doubling each PCR cycle. Logistic regression was used to model assay performance by specimen CT. These models were applied to CT distributions of symptomatic and asymptomatic populations presenting to emergency services to predict the percentage of specimens that would be detected by each assay. A 96-sample paired-swab study was conducted to confirm model results. Results: When using direct nasopharyngeal samples and fit with either VTM or limit-of-detection data, percent positivities for ID NOW (symptomatic 94.9%/97.4%; asymptomatic 88.4.0%/89.6%) and Simplexa (symptomatic 97.8%/97.2%; asymptomatic 91.1%/90.8%) were predicted to be similar. Likewise, percent positivities for ID NOW with direct nasal specimens (symptomatic 77.8%; asymptomatic 64.5%) and, fit with VTM data, Sofia 2 with direct nasopharyngeal specimens (symptomatic 76.6%, asymptomatic 60.3%) were similar. The paired-swab study comparing direct nasopharyngeal specimens on ID NOW and nasopharyngeal VTM specimens on Simplexa showed 99% concordance. Conclusions: Assay performance can be modeled as dependent on viral load, fit using laboratory bench study results, and adjusted to account for direct-specimen testing. When using nasopharyngeal specimens, direct testing on Abbott ID NOW and VTM testing on DiaSorin Simplexa have similar performance. [ABSTRACT FROM AUTHOR]

Placement of pathology and laboratory medicine (PALM) services requires balancing efficiency (maximizing test volume) with equitable urban-rural access. We compared the association between population density (proxy for efficiency) and travel time to the closest facility (proxy for equitable access) across levels of Tanzania's public sector health system. We linked geospatial data for Tanzania from multiple sources. Data on facility locations and other geographic measures were collected from government and non-governmental databases. We classified facilities assuming increasing PALM availability by tier: (1) dispensaries, (2) health centres, (3) district hospitals and (4) regional/referral hospitals. We used the AccessMod 5 algorithm to estimate travel time to the closest facility for each tier across Tanzania with 500-m resolution. District-level average population density and travel time to the closest facility were calculated and presented using medians and interquartile ranges. Spatial correlations between these variables were estimated using the global Moran's I and bivariate Local Indicator of Spatial Autocorrelation, specifying a queen's neighbourhood matrix. Spatial analysis was restricted to 171 contiguous districts. The study included 5406 dispensaries, 675 health centres, 186 district hospitals and 37 regional/referral hospitals. District-level travel times were shortest for Tier 1 (median: [IQR]: 45.4 min [30.0-74.7]) and longest for Tier 4 facilities (160.2 min [107.3-260.0]). There was a weak spatial autocorrelation across tiers (Tier 1: -0.289, Tier 2: -0.292, Tier 3: -0.271 and Tier 4: -0.258) and few districts were classified as significant spatial outliers. Across tiers, geographic patterns of populated districts surrounded by neighbours with short travel time and sparsely populated districts surrounded by neighbours with long travel time were observed. Similar spatial correlation measures across health system levels suggest that Tanzania's health system reflects equitable urban-rural access to different PALM services. Longer travel times to hospital-based care could be ameliorated by shifting specialized diagnostics to more accessible lower tiers. [ABSTRACT FROM AUTHOR]

Objectives: Serologic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has experienced a changing landscape of available assays coupled with uncertainty surrounding performance characteristics. Studies are needed to directly compare multiple commercially available assays.Methods: Residual serum samples were identified based on SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing, clinical test results, and collection dates. Serum samples were analyzed using assays from four different manufacturers: DiaSorin anti-SARS-CoV-2 S1/S2 IgG, EUROIMMUN anti-SARS-CoV-2 IgG ELISA, Roche Elecsys anti-SARS-CoV-2, and Siemens SARS-CoV-2 Total antibody assays.Results: Samples from SARS-CoV-2 RT-PCR-positive patients became increasingly positive as time from symptom onset increased. For patients with latest sample 14 or more days after symptom onset, sensitivities reached 93.1% to 96.6%, 98.3%, and 96.6% for EUROIMMUN, Roche, and Siemens assays, respectively, which were superior to the DiaSorin assay at 87.7%. The specificity of Roche and Siemens assays was 100% and superior to DiaSorin and EUROIMMUN assays, which ranged from 96.1% to 97.0% and 86.3% to 96.4%, respectively.Conclusions: Laboratories should be aware of the advantages and limitations of serology testing options for SARS-CoV-2. The specificity and sensitivity achieved by the Roche and Siemens assays would be acceptable for testing in lower-prevalence regions and have the potential of orthogonal testing advantages if used in combination. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the effect of diabetes on sickle hemoglobin (HbS) measurement on two common clinical hemoglobin separation platforms.Methods: We performed a method comparison between the Bio-Rad Variant II high-performance liquid chromatography (HPLC) and Sebia Capillarys 2 Flex Piercing capillary electrophoresis (CE) using clinical specimens from 38 patients without hemoglobin variants and 57 patients with sickle cell trait (AS) (HbA1c%, 4.1%-15.4%). We investigated the effect of intermethod Hb% differences on result interpretation by a panel of expert clinical observers.Results: In diabetic specimens, HPLC undermeasured HbS% up to 7.4% vs CE, due to S1c eluting closely with A0 in HPLC. This increased concern for underlying α-thalassemia in diabetic patients with AS based on HPLC results. HPLC P2% was linearly related to HbA1c% and can be a screen for diabetic AS samples.Conclusions: Glycosylation can interfere with HbS% measurement by HPLC. Susceptible specimens should be identified and preferentially analyzed via CE. [ABSTRACT FROM AUTHOR]

Introduction: M-protein quantification is routinely performed by demarcating serum protein electrophoresis (SPE) regions. However, quantification of β-migrating M-protein is hindered by overlapping nonimmunoglobulin protein. Immunosubtraction (ISUB) on capillary electrophoresis is a method currently used qualitatively to subtract out (and therefore highlight) immunoglobulin isotypes in serum, thus reducing the masking effect of normal serum proteins. This study expands on traditional ISUB by developing a quantitative immunosubtraction (qIS) methodology. Methods: qIS is achieved by estimating the monoclonal class-specific immunoglobulin contribution to the SPE region containing the M-protein. We conducted a recovery study by use of serial dilutions from 3 patients with β-region M-proteins (n = 22), performing SPE and ISUB on each dilution. We visualized the difference between the ISUB electrophoresis trace and the involved ISUB isotype-subtracted trace to distinguish M-protein and background polyclonal immunoglobulins, which was demarcated independently by 3 pathologists. The M-protein contribution to the β-region was calculated and applied to the β-region protein concentration producing the quantitative M-protein concentration, while minimizing contamination by nonimmunoglobulin or polyclonal immunoglobulin proteins. Results: Using a quality target of 25% error, we determined that our analytical measurable range spanned the maximum concentration tested (0.81 g/dL) to 0.05 g/dL. Passing--Bablok regression between qIS and the expected M-protein produced a slope of 1.04 (95% CI, 0.94-1.09), r = 0.99. Total CV was 4.8% and intraclass correlation between pathologists was 0.998. Discussion: qIS promises quantification of β-migrating M-proteins at concentrations an order of magnitude lower than traditional SPE methodology, allowing earlier detection of increasing or decreasing M-protein. [ABSTRACT FROM AUTHOR]

The article focuses on three approaches to creating an essential diagnostics list.

Objectives: A recent survey of laboratories in Kampala, Uganda, demonstrated that only 0.3% of laboratories (3/954) met international quality standards. To benchmark laboratory quality throughout the rest of sub-Saharan Africa (SSA), we compiled a list of SSA laboratories meeting international quality standards. Methods: Accrediting bodies were queried via online registries or direct communication in May 2013. Results: There were 380 laboratories accredited to international standards in SSA. Ninety-one percent were in South Africa. Thirty-seven of 49 countries had no laboratories accredited to international quality standards. Accredited laboratory density (per million people) in South Africa, Namibia, and Botswana were similar to those in many European countries. Single variable linear regression showed a correlation between accredited laboratory density and health expenditures per person (adjusted R² = 0.81, P < .001). Conclusions: Most SSA countries do not have an accredited clinical laboratory. For those that do, there is a strong correlation between country-specific accredited laboratory density and per-capita health expenditures. [ABSTRACT FROM AUTHOR]