An overview of medical diagnostic laboratories in South Africa that meet the international standard of accreditation: ISO 15189

Accreditation is an official recognition that a facility or laboratory is competent to perform specific tasks and has a documented manual on a Quality Management System (QMS) in place. According to the Accreditation Act 19 of 2006, South African National Accreditation Systems (SANAS) is the only internationally recognised accreditation body in South Africa. The International Organization for Standardization (ISO) standard specifically for medical laboratory accreditation is ISO 15189:2012. This review is designed to bring awareness of accredited and unaccredited medical diagnostic laboratories in SA; to look at the number of accredited, unaccredited laboratories and the rate of accreditation growth; to examine the state of accreditation in South Africa with regard to how many are accredited, suspended or withdrawn; and to highlight the advantages of being an accredited laboratory. It also examines the nonconformances commonly raised during assessment and an overview of accreditation around the world. Upon accreditation, the laboratory is given the right to use the SANAS symbol on patient request forms or results as a confirmation of competency. This has motivated more and more laboratories to be accredited. Diagnostic laboratories contribute much toward the final decisions taken by clinicians to diagnose the patients or treatment; this may be from an accredited or non-accredited laboratory. Since patient care is inextricably linked to pathology testing, every laboratory should engage a premium QMS and be evaluated by an accreditation body to ensure that patients receive a trustworthy report. Accreditation is a voluntary process in South Africa but mandatory in some Western countries. Although some laboratories might lose accreditation along the way, the ratio compared to those accredited is still very small. The fact that a majority remain accredited is a good indication of a well-implemented QMS. The challenges faced by the medical technologist-owned laboratories remain, as they are still not accredited.

Comparison of endocervical swabs to cultured isolates for the detection of antimicrobial resistance determinants in Neisseria gonorrhoeae

Background: The global emergence of antimicrobial resistance (AMR) in Neisseria gonorrhoeae to various antibiotics is a public health concern. To date, there have been no published South African studies that have compared the primary swab to the cultured isolates for the detection of N. gonorrhoeae AMR determinants. This study provides data on such a comparison. Methods: Paired endocervical swabs were collected from 307 pregnant women. The first swab was stored in an Amies charcoal transport media for culture assessment and the second swab was used for the molecular detection of resistant determinants. Specific targets (genes/plasmids/mutations) associated with resistance to penicillin, tetracycline, ciprofloxacin, spectinomycin, cefixime, azithromycin and ceftriaxone were detected from both the cultured isolates and the endocervical swabs. Results: Of the 307 samples tested in this study, only six samples tested positive for culture. A total of 24 samples tested positive for N. gonorrhoeae with the quantitative polymerase chain reaction (qPCR) assay. The six samples which tested positive for culture fell within the qPCR positives group. Since this study was designed to directly compare the culture swabs to the endocervical swabs for the detection of AMR determinants, the current analysis included only the six culture samples and six paired endocervical swab samples (n = 6). All six isolates were resistant to tetracycline and penicillin G while five of the six isolates were resistant to ciprofloxacin. All isolates were susceptible to the remaining antimicrobials. There was a 100% correlation between the cultured isolates and endocervical swabs for detecting the specific AMR determinants, conferring resistance to tetracycline, penicillin G and ciprofloxacin. Conclusion: Based on the findings of this study, tracking emerging patterns of resistance from the molecular level using only the endocervical swabs may serve as an attractive future research direction.

An audit of unnecessary preoperative urea and electrolyte panel tests in patients undergoing major orthopaedic surgery at a quaternary South African hospital

Background: Preoperative urea and electrolyte (U&E) panels are frequently requested for major surgery patients at risk for postoperative acute kidney injury (AKI). There is only one published study that has audited unnecessary preoperative U&E test panel utilisation in major surgery patients at a South African (SA) public sector hospital. This has significant implications for laboratory workloads, healthcare expenditure, and patient-friendly practice in the resource-limited SA public healthcare sector. Objective: To audit preoperative U&E panel requests in a sample of SA patients undergoing major orthopaedic surgery. Methods: We conducted a retrospective audit of adult primary hip arthroplasty patients who attended a quaternary SA hospital. Data on demographics, medical history, preoperative anaesthetic evaluations, operation details, and U&E panel requests were collected from each patient’s medical chart. The National Institute for Health and Care Excellence (NICE) guidelines, based on American Society of Anesthesiologists (ASA) grading and the presence of AKI risk factors, was used to distinguish between necessary and unnecessary preoperative U&E requests. We used descriptive statistics to analyse our study data. Results: Of the 175 patients comprising our study sample, 23 (13.1%) had preoperative U&E panels requested unnecessarily. All 23 patients were otherwise healthy and did not have any AKI risk factors. Conclusion: A small proportion of preoperative U&E test panels in our study sample of major orthopaedic surgery patients were deemed unnecessary. With that being said, there is still room for improvement in practices around preoperative U&E panel requests, which could be achieved through educational, computerised, and audit feedback interventions.

Game of clones: A case of ELANE gene mutation-related neutrope

Mutations in the ELANE gene, which encodes the neutrophil elastase (NE) protein in neutrophils, result in ELANE-related neutropenia. ELANE-related neutropenia encompasses both cyclic neutropenia (CN) and severe congenital neutropenia (SCN), with ELANE mutations seen in a majority of SCN and almost all of CN patients. Clinical history in affected individuals typically reveals recurrent episodes of fever, oral ulcerations and bacterial as well as fungal infections, correlating with periodic oscillations or chronically low levels in the absolute neutrophil count (ANC). ELANE-related neutropenia is characterised by severely low neutrophil counts where ANCs may drop as low as zero. A two-year-old child presented at our hospital with a longstanding history of recurrent bacterial infections and previous admissions at another centre during some of these infectious episodes. Her full blood count demonstrated a markedly low ANC, which was chronic on assessment of her previous results. Decreased granulopoiesis with maturation arrest was seen on her bone marrow and genetic testing for the ELANE gene demonstrated a pathogenic variant of the mutation. Treatment with granulocyte colony-stimulating factor (G-CSF) was initiated.

Establishment of reference intervals of biochemical analytes for South African adults: a study conducted as part of the IFCC global multicentre study on reference values

Objective: This study was conducted as a part of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) global study for establishing reference intervals (RIs) of common laboratory tests for the South African population considering gender, ethnicity, age and body mass index (BMI). Methods: The researchers recruited 1 143 apparently healthy volunteers aged 18–65: 551 African (Afr) and 592 non-African (NAfr) (comprising 383 Caucasian and 209 Mixed Ancestry). Serum samples were measured for 40 chemistry and immunochemistry analytes. The standard deviation ratio (SDR) guided the need for partitioning reference values according to gender, ethnicity and age using a threshold of ≥ 0.4. The latent abnormal values exclusion (LAVE) method was applied to reduce influences of latent diseases before deriving RIs using both parametric and non-parametric methods. Results: Based on SDRsex, males showed higher albumin, uric acid, creatinine, AST, CK and ferritin. Based on SDRRC, Afr compared to NAfr showed (i) higher total protein, amylase, CRP, immunoglobulin G and A and (ii) lower total bilirubin, total cholesterol, low-density lipoprotein cholesterol (LDL-C), ALT and cholinesterase. Both age-related changes in glucose and LDL-C, and BMI-related changes in ALT, ALP and LDH were more prominent in NAfr. RIs were determined according to gender, age and ethnicity. The LAVE method was effective in lowering the upper RI limits (UL) of nutritional markers such as γGT and CRP. Compared to the non-parametric method, the parametric method gave narrower confidence intervals of ULs for analytes with skewed distributions. Conclusion: Establishing RIs by considering ethnicity was essential in many analytes in South Africa. Age and BMI-related changes differed greatly between Afr and NAfr.

Fever in the returning traveller: Dual infection with SARS-CoV-2 and Plasmodium falciparum malaria

Background: More than 90% of the global 400 000 annual malaria deaths occur in Africa. The current SARS-CoV-2 pandemic has resulted in more than 830 000 deaths in its first 10 months. Case presentation: This case describes a patient who had travelled from Mozambique to Cape Town, presented with a mild febrile illness, and was diagnosed with both COVID-19 and uncomplicated Plasmodium falciparum malaria infection. She responded well to malaria treatment and had an uneventful COVID-19 admission. Her blood smear showed a low malaria parasitaemia and a relatively high gametocyte load. Conclusion: We postulate that her clinical course and abnormal smear could well be due to reciprocal disease-modifying effects of the infections. The presenting symptoms of COVID-19 may mimic endemic infectious diseases including malaria, tuberculosis, pneumocystis pneumonia and influenza thus there is a need for clinical vigilance to identify and treat such co-infections.

Evidence for the use of the Alere Afinion™ AS100 for measuring the levels of C-reactive protein in an elderly South African population

Introduction: This study evaluated the performance of the Alere Afinion™ AS100 analyser for the measurement of C-reactive protein (CRP) levels in a population of older adults from South Africa. Methods: This study was a sub-study of the Sexual Health, HIV infection and comorbidity with non-communicable diseases among Older Persons (SHIOP) study. The median age of SHIOP participants was 61 years (interquartile range 12). Serum samples collected through SHIOP were used to measure CRP levels on the Alere Afinion™ AS100 (Point-of-care) and ABX Pentra 400 (reference method), respectively. Bland–Altman analysis and Lin’s concordance correlation coefficients were used to assess the agreement between the two analysers. Results: A total of 183 serum samples were tested in the study. The Alere Afinion™ AS100 median values for CRP were 9.5 mg/L and 11.5 mg/L in women and men respectively (p = 0.275). The ABX Pentra 400 median levels were lower with 5.6 mg/L and 3.6 mg/L for women and men (p = 0.027), respectively. Bland–Altman analysis and linear regression analysis showed an excellent correlation between the Pentra and Afinion analysers, with a Lin’s concordance correlation coefficient of 0.971. The Alere Afinion™ AS100 was able to correctly classify > 90% (165/183) of the CRP results when compared to the ABX Pentra 400. Conclusion: This study showed that the Alere Afinion™ AS100 had an excellent correlation with a standard laboratory method. However, the Afinion™ AS100 did not correlate well at elevated CRP levels. This may not be clinically significant since the cut-points for CVD risk are at much lower levels.

Verification of a rapid von Willebrand factor propeptide assay

Background: Von Willebrand disease (VWD) is the most common inherited bleeding disorder caused by a deficiency or defect in von Willebrand factor (VWF). Quantitative defects include, type 1 VWD and type 3 VWD. Type 1 VWD is either due to decreased synthesis and secretion, or increased clearance of VWF. It is essential to diagnose individuals with increased VWF clearance, as treatment of these patients with 1-deamino-8-D-arginine vasopressin is not effective. Currently, there is one commercial assay that measures von Willebrand factor propeptide (VWFpp) levels. This assay is time consuming to perform. With this research we developed and verified a rapid assay to determine VWFpp levels in patient plasma. Methods: The commercial VWF mouse anti-human VWF propeptide matched antibody pair (clones CLB-Pro 35 and CLB-Pro 14.3) was used in enzyme-linked immunosorbent assays of the commercial and the rapid method. While the CLB-Pro commercial assay uses two-hour incubations, our rapid assay uses 30 minute incubations. We compared our assay to the CLB-Pro commercial assay using twenty type 1 VWD patient plasma. Two samples, the World Health Organization (WHO) 6th International Standard (IS) for factor VIII (FVIII)/VWF and a type 1 VWD patient with increased clearance were also tested four times in duplicate for five consecutive days to determine the inter- and intra-assay precision. Results: Our rapid assay showed equal sensitivity to the CLB-Pro commercial assay by detecting 1.5625% VWFpp. The intra- and interassay CVs of our assay were acceptable according to the Food and Drug Administration guideline of 2018. Conclusion: This rapid enzyme-linked immunosorbent assay (ELISA) is as sensitive and precise as the CLB-Pro commercial assay. Therefore, it can be used to rapidly diagnose patients with increased VWF clearance.

A follow-up audit of the completion of bone marrow specimen request forms at an academic laboratory

Background: In order to ensure that patients receive individualised treatment following bone marrow biopsy, it is necessary for clinicians to provide complete clinical information on bone marrow request forms (BMRFs). An audit of BMRFs six years previously showed poor completion, especially with regard to filling in full blood count results, transfusion history, medication history, information about the clinical examination and HIV status. This lead the laboratory to design a new bone marrow specimen request form. We did a follow-up audit to see if the new form had helped to improve the completion rates. Methods: We compared 400 forms to the 357 that were audited in 2013. The following details were recorded: date and time of collection, patient demographics, requesting doctor’s details, clinical information, current medication, transfusion history and HIV status, and details of the procedure completed by technologists, registrars and pathologists. Results: The 2019 follow-up audit showed significant improvements in the completion of the transfusion history, as well as the clinical examination and HIV status. Registrars and pathologists signed off forms regularly. The completion of patient demographic details, and requesting doctors’ names and telephone numbers worsened. Discussion and conclusion: We recommend that the form be simplified so the requesting doctors only need to tick yes or no, in a tick-box format, if a full blood count has been done in the preceding 24 hours. There needs to be a dedicated space for the hospital and laboratory stickers. Only the name and telephone number of one doctor should be requested. This doctor should preferably be the most senior doctor involved with patient care. All referring laboratories and hospitals will be consulted before updating the form. Unfortunately, it seems that the only way to force the completion of request forms is to introduce an electronic order entry system that does not accept incomplete forms.

Point-of-care testing: is it a paradox in international normalised ratio measurements?

Point-of-care testing (POCT) in haemostasis has shown a steady state increase in the range of tests available with an exponential increase in the number of tests that are performed annually. The most commonly performed test remains the out of hospital measurement of the international normalised ratio (INR). The INR is used to monitor oral anticoagulation therapy (OAT) with vitamin K antagonists. Such drugs include some of the following: warfarin (Coumadin®), phenprocoumon (Marcumar®) and acenocoumarol (Sintrom®, also sold as other brand names). Contrary to laboratory testing, POCT is often performed by general practitioners (GPs), nurses, pharmacists, patients and other healthcare professionals. In many cases these individuals do not have access to the same support mechanisms that exist in the clinical laboratory regarding strict quality control programmes. When an INR test is performed in the clinical laboratory, it has to be accredited, monitored and inspected. Accreditation is also advisable and part of these requirements is to be involved in external quality assessment (EQA). In the case of POCT haemostasis assays, EQA programmes do exist, however these programmes are still relatively few in number. Over the last decade there has been a significant increase in the scope of POCT, particularly in the field of haemostasis. This brief review summarises POCT in haemostasis, highlighting some of its benefits, challenges and future perspectives, especially with regard to the measurement of the INR.