Piloting a national laboratory electronic programme status reporting system in Ekurhuleni health district, South Africa

Background. The National Health Laboratory Service (NHLS) performs ~4 million CD4 tests per annum for the public health sector at 61 CD4 testing laboratories across South Africa. Currently, CD4 laboratory data captured do not differentiate between antiretroviral treatment (ART) and pre-ART care.Methods. A cross-sectional study was undertaken to evaluate a redesigned Comprehensive Care, Management and Treatment of HIV and AIDS (CCMT) request form, incorporating a two-tick collection procedure linking the CD4 test request to patient CCMT programme status. Field testing was undertaken at three health facilities, where healthcare personnel were required to capture whether the CD4 count requested was a ‘first-ever CD4’, ‘CD4 taken previously, not yet in ART care’ or ‘in ART care’. All data were extracted from the NHLS Corporate Data Warehouse and analysed using Microsoft Excel and Stata-12.Results. A substantial increase in the number of request forms with a CCMT programme status (28.1% v. 84.4%) was reported pre- and post-implementation. Post-implementation data (N=1 004) revealed that 30.8% patients were ART naive (‘first-ever CD4’), with 7.4% ‘not yet on ART’ (median CD4 counts of 150 and 328 cells/μL, respectively). Patients on ART comprised 61.9% of the study group (median CD4 count ~346 cells/μL). Sixty percent of patients were aged between 30 and 44 years, and females predominated (male/ female ratio 0.7:1).Conclusions. A simple modification to the CCMT request form can successfully facilitate collection of programme status. For national implementation, it would be advantageous to have a unique patient identifier to further enhance laboratory-based programmatic monitoring and evaluation

Documented higher burden of advanced and very advanced HIV disease among patients, especially men, accessing healthcare in a rapidly growing economic and industrial hub in South Africa: A call to action

Background. Lephalale Municipality in Limpopo Province, South Africa, has seen significant economic and industrial development owing to expansion of the coal mining and power generation sectors. This development has coincided with substantial population growth of 65% between 2001 and 2016, attributable to largely (migrant) males living in the area who, overall, outnumbered females by ~121:100. The local HIV prevalence is reported to be higher than national rates.Objectives. Anonymised National Health Laboratory Service CD4+ data were used to document increasing laboratory services workload and to establish the burden of advanced (CD4+ count <200 cells/µL) and very advanced (<100 cells/µL) HIV disease among adult patients accessing public healthcare in Lephalale between 2006 and 2015.Methods. A cross-sectional design was used to analyse CD4+ laboratory data. CD4+ outcomes were categorised by volumes of tests, year, health facility type, age categories (15 - 19, 20 - 24, 25 - 29, 30 - 34, 35 - 39, 40 - 44, 45 - 49 and >49 years), CD4+ test range (≤50, 51 - 100, 101 - 200, 201 - 350, 351 - 500 and ≥501 cells/µL) and gender. Median CD4+ counts were calculated.Results. Extracted Lephalale data comprised 57 490 CD4+ results, with a mean patient age of 34 years. Considerably fewer male than female patients had CD4+ counts reported (male/female ratio 0.45:1). CD4+ test volumes showed a five-fold escalation over the study period, increasing from 1 458 tests in 2006 to 8 239 in 2015. A considerable burden of advanced and very advanced HIV disease (exceeding 50% of all cases) was noted in 2006/2007; by 2015 the proportion had fallen, but was still high at 27%. The overall median CD4+ count in 2006 (192 cells/µL) confirmed a high burden of advanced disease, with modest improvement to 289 cells/µL by 2015. Between 2006 and 2015, the median CD4+ count for females increased from 204 to 405 cells/µL, while that for males increased from 126 to 285 cells/µL. Age analysis further revealed that men aged <20 years or >25 years, and specifically those aged 30 - 45 years, had up to 44% more advanced HIV disease.Conclusions. Lower median CD4+ counts and a dramatic increase in volumes of CD4+ tests performed from 2007 onwards revealed a high burden of advanced and very advanced HIV disease in patients accessing care in Lephalale. Viewed together with Statistics South Africa census documentation of a disproportionately high number of males compared with females living in the area, these figures suggest that improved systems are urgently needed to encourage and accommodate access to HIV care for male (migrant worker) patients living and working in emerging industrial centres

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 <100 cells/μL (defining severely immunosuppressed HIV-positive patients) and >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 <100 and >500 cells/μL were calculated. Data were analysed using Stata 12 and mapping was done with ArcGIS software, reporting percentages of CD4 counts <100 and >500 cells/μL by district.Results. The national average percentage of patients with CD4 counts <100 cells/μL showed a marked decrease (by 22%) over the 5-year study period, with a concurrent increase in 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 <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 <100 cells/μL, as well as the highest percentages of counts >500 cells/μL. In contrast, in 2014/15, the highest percentages of CD4 counts <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 >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

Use of the Mentzer index will assist in early diagnosis of iron deficiency in South African children

A recent review article by Dr R Thejpal in CME provided a comprehensive update on the diagnosis, treatment and challenges of early diagnosis of iron deficiency in South African children. Although several definitive laboratory tests are readily available in SA National Health Laboratory Service laboratories for diagnosing iron deficiency in both children and adults, laboratory testing is expensive and, as noted previously, regions with a high prevalence of anaemia also have a large burden of infectious diseases that invariably become the laboratory priority in resource-constrained settings.

Piloting a national laboratory electronic programme status reporting system in Ekurhuleni health district, South Africa

Background. The National Health Laboratory Service (NHLS) performs ~4 million CD4 tests per annum for the public health sector at 61 CD4 testing laboratories across South Africa. Currently, CD4 laboratory data captured do not differentiate between antiretroviral treatment (ART) and pre-ART care.Methods. A cross-sectional study was undertaken to evaluate a redesigned Comprehensive Care, Management and Treatment of HIV and AIDS (CCMT) request form, incorporating a two-tick collection procedure linking the CD4 test request to patient CCMT programme status. Field testing was undertaken at three health facilities, where healthcare personnel were required to capture whether the CD4 count requested was a ‘first-ever CD4’, ‘CD4 taken previously, not yet in ART care’ or ‘in ART care’. All data were extracted from the NHLS Corporate Data Warehouse and analysed using Microsoft Excel and Stata-12.Results. A substantial increase in the number of request forms with a CCMT programme status (28.1% v. 84.4%) was reported pre- and post-implementation. Post-implementation data (N=1 004) revealed that 30.8% patients were ART naive (‘first-ever CD4'), with 7.4% ‘not yet on ART’ (median CD4 counts of 150 and 328 cells/µL, respectively). Patients on ART comprised 61.9% of the study group (median CD4 count ~346 cells/µL). Sixty percent of patients were aged between 30 and 44 years, and females predominated (male/female ratio 0.7:1).Conclusions. A simple modification to the CCMT request form can successfully facilitate collection of programme status. For national implementation, it would be advantageous to have a unique patient identifier to further enhance laboratory-based programmatic monitoring and evaluation

Implementation of a new ‘community’ laboratory CD4 service in a rural health district in South Africa extends laboratory services and substantially improves local reporting turnaround time

Background. The CD4 integrated service delivery model (ITSDM) provides for reasonable access to pathology services across South Africa (SA) by offering three new service tiers that extend services into remote, under-serviced areas. ITSDM identified Pixley ka Seme as such an under-serviced district.Objective. To address the poor service delivery in this area, a new ITSDM community (tier 3) laboratory was established in De Aar, SA. Laboratory performance and turnaround time (TAT) were monitored post implementation to assess the impact on local service delivery. Methods. Using the National Health Laboratory Service Corporate Data Warehouse, CD4 data were extracted for the period April 2012 - July 2013 (n=11 964). Total mean TAT (in hours) was calculated and pre-analytical and analytical components assessed. Ongoing testing volumes, as well as external quality assessment performance across ten trials, were used to indicate post-implementation success. Data were analysed using Stata 12. Results. Prior to the implementation of CD4 testing at De Aar, the total mean TAT was 20.5 hours. This fell to 8.2 hours post implementation, predominantly as a result of a lower pre-analytical mean TAT reducing from a mean of 18.9 to 1.8 hours. The analytical testing TAT remained unchanged after implementation and monthly test volumes increased by up to 20%. External quality assessment indicated adequate performance. Although subjective, questionnaires sent to facilities reported improved service delivery. Conclusion. Establishing CD4 testing in a remote community laboratory substantially reduces overall TAT. Additional community CD4 laboratories should be established in under-serviced areas, especially where laboratory infrastructure is already in place.

Endogenous biosynthesis of n-3 long-chain PUFA in Atlantic salmon

A more efficient utilisation of marine derived sources of dietary omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFA) in cultured Atlantic salmon could, amongst other strategies, be facilitated by nutritional strategies that maximise endogenous n-3 LC PUFA synthesis. The objective of the current study was to quantify the extent of n-3 LC PUFA biosynthesis and the resultant effect on fillet nutritional quality in large, market size Atlantic salmon. Four diets were manufactured providing altered levels of dietary omega-3 substrate, namely 18:3n-3, and end-products, namely, 20:5n-3 and 22:6n-3. After 283 days of feeding, fish grew to in excess of 3000g and no differences in growth performance or biometrical parameters were recorded. An analysis of fatty acid composition and in vivo metabolism revealed that post-smolt Atlantic salmon have the potential to endogenously produce n-3 LC PUFA when provided with a substantial amount of dietary omega-3 substrate. Moreover, the extent of endogenous production resulted in fillet levels of n-3 LC PUFA comparable to fish fed a diet with added fish oil. Another major finding was that the presence of abundant dietary omega-3 substrate with the addition of dietary omega-3 end-product (i.e. fish oil) had a positive effect on final fillet levels of n-3 LC PUFA. This was likely the result of the preferential β-oxidation of dietary C18 n-3 PUFA resulting in an apparent conservation of n-3 LC PUFA from catabolism. Ultimately, this study highlights the potential for endogenous synthesis of n-3 LC PUFA to, at least partially, support a substantial reduction, in the amount of dietary fish oil in diets for market sized Atlantic salmon reared in seawater

Tree-Based Methods for Discovery of Association between Flow Cytometry Data and Clinical Endpoints

We demonstrate the application and comparative interpretations of three tree-based algorithms for the analysis of data arising from flow cytometry: classification and regression trees (CARTs), random forests (RFs), and logic regression (LR). Specifically, we consider the question of what best predicts CD4 T-cell recovery in HIV-1 infected persons starting antiretroviral therapy with CD4 count between 200 and 350 cell/μL. A comparison to a more standard contingency table analysis is provided. While contingency table analysis and RFs provide information on the importance of each potential predictor variable, CART and LR offer additional insight into the combinations of variables that together are predictive of the outcome. In all cases considered, baseline CD3-DR-CD56+CD16+ emerges as an important predictor variable, while the tree-based approaches identify additional variables as potentially informative. Application of tree-based methods to our data suggests that a combination of baseline immune activation states, with emphasis on CD8 T-cell activation, may be a better predictor than any single T-cell/innate cell subset analyzed. Taken together, we show that tree-based methods can be successfully applied to flow cytometry data to better inform and discover associations that may not emerge in the context of a univariate analysis