Phase 2 (community based clinical setting) sensitivity, specificity, and predictive values for the 3 point-of-care tests to detect or exclude anemia.

<p>Phase 2 (community based clinical setting) sensitivity, specificity, and predictive values for the 3 point-of-care tests to detect or exclude anemia.</p

Correlation of the 3 point-of-care assays with values within the dynamic range of the reference Hemoglobin meter in 60 samples in a central laboratory (phase 1), and 100 samples in a community based clinical setting (phase 2).

<p>In phase 1 of the study the STAT-Site had a high failure rate. It seems that this was related to uneven migration of the sample through the sample strip, resulting in the sample migration time exceeding the maximum time specified by the manufacturer.</p

Diagnostic Accuracy of the HemoCue Hb 301, STAT-Site M^Hgb and URIT-12 Point-of-Care Hemoglobin Meters in a Central Laboratory and a Community Based Clinic in Durban, South Africa

<div><p>In South Africa, various point-of-care hemoglobin meters are used. However, the regulatory framework for approval, implementation and oversight of use of point-of-care hemoglobin meters is suboptimal. We assessed the diagnostic accuracy of the HemoCue Hb 301, STAT-Site M^Hgb and URIT-12 point-of-care hemoglobin meters, compared to a central laboratory based reference assay, in a central laboratory and a community based clinic in Durban, South Africa. Differences in performance of the point-of-care assays, compared to the reference assay, were more pronounced in the community based clinic. Results were reasonable for the HemoCue Hb 301, but poor for the STAT-Site M^Hgb and the URIT-12. Poor test performance of point-of-care hemoglobin meters, and inadequate evaluations and oversight in South Africa, leads to suboptimal clinical care and clinical research, and increased costs. There is a need for proper evaluation and quality assurance of point-of-care tests, the results of which should be made widely available to key stakeholders.</p></div

Correlation of the 3 point-of-care assays with values within the dynamic range of the reference hemoglobin meter in 100 samples in a community based clinical setting in phase 2 of the study.

<p>Dots in the blue quadrant indicate that the point-of-care assay missed anemia, i.e., misclassified a finger prick sample as non-anemic where the venous blood sample was classified as anemic according to the reference assay in a central laboratory. Dots in the red quadrant indicate that the point-of-care assay misclassified as anemic a sample that was non-anemic according to the reference assay.</p

Bland-Altman plots comparing the reference laboratory test with the 3 point-of-care assays in phase 1 (left column) and phase 2 (right column).

<p>In phase 1 of the study the STAT-Site had a high failure rate. It seems that this was related to uneven migration of the sample through the sample strip, resulting in the sample migration time exceeding the maximum time specified by the manufacturer.</p

Schematic representation of study results.

<p>163 chronically HIV infected (ARV naïve) individuals (CD4 = 5–1142 cells/ul) were recruited in Durban, South Africa. An RD1-Elispot was performed on PBMC every 3 months for a period of 3–21 months. During the period of follow-up 30 individuals were placed on ARVs and 4 individuals progressed to active TB. Of the 129 individuals who were not placed on ARVs or TB treatment during follow-up, 5 categories of Elispot kinetics were observed: 45 (35%) individuals were consistently negative at each time-point tested, 22 (17%) individuals were consistently positive at each time-point tested, 8 (6%) individuals displayed sustained conversions (three or more positive Elispots after at least one negative Elispot), 11 (9%) individuals displayed transient conversions (one or two positive Elispots between negative plates), and 16 (12%) individuals displayed transient reversions (one or two negative Elispots between positive plates). For 27 (21%) individuals the category is unknown due to either a lack of interpretable results (e.g. SK 179 had indeterminate Elispots at all 3 time points tested), or the absence of either pre-baseline samples or further follow-up to determine if observed reversions and conversions are transient or sustained.</p

Longitudinal comparison of the ex vivo RD1- Elispot and the RD1-qPCR assay.

<p>A highly sensitive assay of RD1-specific IFN-γ production using real time quantitative PCR (qPCR) for two reporters - monokine-induced by IFN-γ (MIG) and the IFN-γ inducible protein-10 (IP10) was compared longitudinally with the ex vivo RD1-Elispot. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037920#pone-0037920-g003" target="_blank">Figure 3A:</a> A head-to–head comparison was performed on 14 individuals on samples from 2 time-points 3 months apart. A significant correlation was observed between fold change on the RD1 qPCR and change in SFC using the RD1-Elispot. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037920#pone-0037920-g003" target="_blank">Figure 3B:</a> Data from SK068. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037920#pone-0037920-g003" target="_blank">Figure 3C:</a> Data from SK036. Top panel displays RD1-Elispot data and bottom-panel displays RD1-qPCR data.</p

Longitudinal MTB-specific T cell profiles and correlation with CD4 count and HIV viral load.

<p>Longitudinal Elispot data from individuals who were not on ARVs for the entire period of follow-up. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037920#pone-0037920-g002" target="_blank">Figure 2A:</a> Examples of responses from 3 individuals who were ex vivo RD1-Elispot positive at all time-points during follow-up. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037920#pone-0037920-g002" target="_blank">Figure 2B:</a> Examples of responses from 3 individuals who displayed an RD1-Elispot conversion that was sustained during follow-up and examples of responses from 3 individuals who displayed a transient RD1-Elispot conversion during follow-up. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037920#pone-0037920-g002" target="_blank">Figure 2C:</a> Examples of responses from 3 individuals who displayed a transient RD1-Elispot reversion during follow-up. Left-hand panel =  Elispot data, right-hand panel  =  CD4 counts and viral loads.</p

Prospective monitoring of RD1- specific IFN-gamma Elispot responses does not predict progression to active TB.

<p>Longitudinal Elispots are shown for SK 169, SK 236, SK325 and SK 351 all of whom progressed to active TB during the follow-up period and 2 of which (SK 325 and SK 351) were also subsequently placed on ARVS. TB Treatment was initiated shortly after diagnosis of active TB. Longitudinal CD4 and viral load data is also shown for all 4 individuals.</p

Data summary for viral load results as determined by the Amplicor v1.5, NucliSens v2.0 and CAP/CTM v2.0 assay.

<p>Data summary for viral load results as determined by the Amplicor v1.5, NucliSens v2.0 and CAP/CTM v2.0 assay.</p