Using laboratory data to categorise CD4 laboratory turn-around-time performance across a national programme

Background and objective: The National Health Laboratory Service provides CD4 testing through an integrated tiered service delivery model with a target laboratory turn-around time (TAT) of 48 h. Mean TAT provides insight into national CD4 laboratory performance. However, it is not sensitive enough to identify inefficiencies of outlying laboratories or predict the percentage of samples meeting the TAT target. The aim of this study was to describe the use of the median, 75th percentile and percentage within target of laboratory TAT data to categorise laboratory performance.   Methods: Retrospective CD4 laboratory data for 2015–2016 fiscal year were extracted from the corporate data warehouse. The laboratory TAT distribution and percentage of samples within the 48 h target were assessed. A scatter plot was used to categorise laboratory performance into four quadrants using both the percentage within target and 75th percentile TAT. The laboratory performance was labelled good, satisfactory or poor.   Results: TAT data reported a positive skew with a mode of 13 h and a median of 17 h and 75th percentile of 25 h. Overall, 93.2% of CD4 samples had a laboratory TAT of less than 48 h. 48 out of 52 laboratories reported good TAT performance, i.e. percentage within target > 85% and 75th percentile ≤ 48 h, with two categorised as satisfactory (one parameter met), and two as poor performing laboratories (failed both parameters).   Conclusion: This study demonstrated the feasibility of utilising laboratory data to categorise laboratory performance. Using the quadrant approach for TAT data, laboratories that need interventions can be highlighted for root cause analysis assessment

Analysis of HIV disease burden by calculating the percentages of patients with CD4 counts <100 cells/µL across 52 districts reveals hot spots for intensified commitment to programmatic support

Background. South Africa (SA)’s Comprehensive HIV and AIDS Care, Management and Treatment (CCMT) programme has reduced new HIV infections and HIV-related deaths. In spite of progress made, 11.2% of South Africans (4.02 million) were living with HIV in 2015. Objective. The National Health Laboratory Service (NHLS) in SA performs CD4 testing in support of the CCMT programme and collates data through the NHLS Corporate Data Warehouse. The objective of this study was to assess the distribution of CD4 counts 500 cells/µL (as an HIV-positive ‘wellness’ indicator). Methods. CD4 data were extracted for the financial years 2010/11 and 2014/15, according to the district where the test was ordered, for predefined CD4 ranges. National and provincial averages of CD4 counts 500 cells/µL were calculated. Data were analysed using Stata 12 and mapping was done with ArcGIS software, reporting percentages of CD4 counts 500 cells/µL by district. Results. The national average percentage of patients with CD4 counts 500 cells/µL (by 57%). District-by-district analysis showed that in 2010/11, 44/52 districts had >10% of CD4 samples with counts 500 cells/µL. In contrast, in 2014/15, the highest percentages of CD4 counts 500 cells/µL were also noted. Conclusions. The percentages of CD4 counts <100 cells/µL highlighted here reveal districts with positive change suggestive of programmatic improvements, and also highlight districts requiring local interventions to achieve the UNAIDS/SA National Department of Health 90-90-90 HIV treatment goals. The study further underscores the value of using NHLS laboratory data, an underutilised national resource, to leverage laboratory test data to enable a more comprehensive understanding of programme-specific health indicators

Analysis of HIV disease burden by calculating the percentages of patients with CD4 counts

Background. South Africa (SA)’s Comprehensive HIV and AIDS Care, Management and Treatment (CCMT) programme has reduced new HIV infections and HIV-related deaths. In spite of progress made, 11.2% of South Africans (4.02 million) were living with HIV in 2015.Objective. The National Health Laboratory Service (NHLS) in SA performs CD4 testing in support of the CCMT programme and collates data through the NHLS Corporate Data Warehouse. The objective of this study was to assess the distribution of CD4 counts &lt;100 cells/µL (defining severely immunosuppressed HIV-positive patients) and &gt;500 cells/µL (as an HIV-positive ‘wellness’ indicator).Methods. CD4 data were extracted for the financial years 2010/11 and 2014/15, according to the district where the test was ordered, for predefined CD4 ranges. National and provincial averages of CD4 counts &lt;100 and &gt;500 cells/µL were calculated. Data were analysed using Stata 12 and mapping was done with ArcGIS software, reporting percentages of CD4 counts &lt;100 and &gt;500 cells/µL by district.Results. The national average percentage of patients with CD4 counts &lt;100 cells/µL showed a marked decrease (by 22%) over the 5-year study period, with a concurrent increase in CD4 counts &gt;500 cells/µL (by 57%). District-by-district analysis showed that in 2010/11, 44/52 districts had &gt;10% of CD4 samples with counts &lt;100 cells/µL, decreasing to only 17/52 districts by 2014/15. Overall, districts in the Western Cape and KwaZulu-Natal had the lowest percentages of CD4 counts &lt;100 cells/µL, as well as the highest percentages of counts &gt;500 cells/µL. In contrast, in 2014/15, the highest percentages of CD4 counts &lt;100 cells/µL were noted in the West Rand (Gauteng), Vhembe (Limpopo) and Nelson Mandela Bay (Eastern Cape) districts, where the lowest percentages of counts &gt;500 cells/µL were also noted.Conclusions. The percentages of CD4 counts &lt;100 cells/µL highlighted here reveal districts with positive change suggestive of programmatic improvements, and also highlight districts requiring local interventions to achieve the UNAIDS/SA National Department of Health 90-90-90 HIV treatment goals. The study further underscores the value of using NHLS laboratory data, an underutilised national resource, to leverage laboratory test data to enable a more comprehensive understanding of programme-specific health indicators.

Performance verification of the new fully automated Aquios flow cytometer PanLeucogate (PLG) platform for CD4-T-lymphocyte enumeration in South Africa

<div><p>Background</p><p>The National Health Laboratory Service (NHLS) offers wide-scale CD4 testing through a network of laboratories in South Africa. A new “load and go” cytometer (Aquios CL, Beckman Coulter), developed with a PLG protocol, was validated against the predicate PLG method on the Beckman Coulter FC500 MPL/CellMek platform.</p><p>Methods</p><p>Remnant routine EDTA blood CD4 reference results were compared to results from two Aquios/PLG instruments (n = 205) and a further n = 1885 samples tested to assess daily testing capacity. Reproducibility was assessed using Immunotrol^TM and patient samples with low, medium, high CD4 counts. Data was analyzed using GraphPad software for general statistics and Bland-Altman (BA) analyses. The percentage similarity (%Sim) was used to measure the level of agreement (accuracy) of the new platform versus the predicate and variance (%SimCV) reported to indicate precision of difference to predicate.</p><p>Results</p><p>205 samples were tested with a CD4 count range of 2–1228 cells/μl (median 365cells/μl). BA analysis revealed an overall -40.5±44.0cells/μl bias (LOA of 126.8 to 45.8cells/μl) and %Sim showing good agreement and tight precision to predicate results (94.83±5.39% with %SimCV = 5.69%). Workflow analysis (n = 1885) showed similar outcomes 94.9±8.9% (CV of 9.4%) and 120 samples/day capacity. Excellent intra-instrument reproducibility was noted (%Sim 98.7±2.8% and %SimCV of 2.8%). 5-day reproducibility using internal quality control material (Immunotrol™) showed tight precision (reported %CV of 4.69 and 7.62 for Normal and Low material respectively) and instrument stability.</p><p>Conclusion</p><p>The Aquios/PLG CD4 testing platform showed clinically acceptable result reporting to existing predicate results, with good system stability and reproducibility with a slight negative but precise bias. This system can replace the faded XL cytometers in low- to medium volume CD4 testing laboratories, using the standardized testing protocol, with better staff utilization especially where technical skills are lacking. Central monitoring of on-board quality assessment data facilitates proactive maintenance and networked instrument performance monitoring.</p></div

PLG/CD4 protocol on Aquios CL cytometer.

<p>PLG/CD4 gating strategy applied for the Aquios CL cytometer platform, represented by 8 histograms (H1-8). H2 selects all CD45 positive white cells, from which all CD4 bright lymphocytes are gated (in H3) for reporting of an absolute CD4 count, while a CD4% of lymphocytes value is derived from H4. H6 and H7 indicate the bead population, currently used as an internal control measure of instrument stability.</p

Summary of results from manufacturer provided daily quality control material (Immunotrol^TM Normal and Low) for 12 consecutive days, where target value and range refers to package insert values.

<p>Summary of results from manufacturer provided daily quality control material (Immunotrol^TM Normal and Low) for 12 consecutive days, where target value and range refers to package insert values.</p

External quality assessment results.

<p>Radar graphs summarizing the results obtained with external quality assessment samples for absolute CD4 counts (left, including 10 trials, each with a low and a normal CD4 count on each respective trial) and CD4% of lymphocytes (right), both indicated by solid blue lines revealing the performance of the Aquios in relation to the respective 10 supplied retrospective trial pool means. The solid red lines indicate the acceptable 2 standard deviation range, while the interrupted black line represents the average overall performance (ideal) of the pooled results (at an SDI of zero).</p

Summary of samples tested using the predicate FC500 MPL/CellMek PLG platform and comparative statistics against the Aquios PLG platform.

<p>Summary of samples tested using the predicate FC500 MPL/CellMek PLG platform and comparative statistics against the Aquios PLG platform.</p