National Health Laboratory Service Research Articles

CLINICAL PROFILES AND OUTCOMES OF ADMISSIONS FOLLOWING COVID-19 ADMISSIONS DURING THREE WAVES OF THE PANDEMIC: EXPERIENCE OF A TERTIARY HOSPITAL IN THE EASTERN CAPE PROVINCE OF SOUTH AFRICA.

South Africa was the country worst affected by the Covid-19 pandemic in Africa. There is a paucity of data on the clinical characteristics and mortality of Covid-19 from the Eastern Cape province of South Africa. We report on the demographic and clinical characteristics as well as the mortality of patients admitted to the Covid-19 ward of Nelson Mandela Academic Hospital (NMAH), Mthatha, during three waves of the Covid-19 pandemic in South Africa. We conducted a single centre retrospective observational study of patients admitted for Covid-19 in a tertiary hospital in the rural Eastern Cape of South Africa. Data were collected from patient files, electronic databases and the National Health Laboratory Services (NHLS) database. The outcomes were duration of admission and in-hospital mortality. There were 371 patients admitted across all three waves with a mean age of 52.2 ± 16.3 years. The proportion of females across the three waves is 61.2%. The commonly associated comorbidities, irrespective of the wave, were hypertension, diabetes and HIV infection. The median duration of admission was six days, with an overall mortality of 31%. The mortality for first, second and third wave were 29.3%, 31.5% and 37.9% respectively. Admissions for Covid-19 were predominantly in females and middle-aged. One third of the admitted patients died. Diabetes, hypertension and HIV infection were the most commonly associated comorbidities.

Kidney function in healthcare clients in Khayelitsha, South Africa: Routine laboratory testing and results reflect distinct healthcare experiences by age for healthcare clients with and without HIV.

In South Africa, PLHIV are eligible for free ART and kidney function screening. Serum creatinine (SCr) laboratory test data from the National Health Laboratory Service are collated at the Provincial Health Data Centre and linked with other routine health data. We analysed SCr and estimated glomerular filtration rate (eGFR) results for PLHIV and HIV-negative healthcare clients aged 18-80 years accessing healthcare in Khayelitsha, South Africa and comorbidity profiles at SCr and eGFR testing. 45 640 individuals aged 18-80 years with at least one renal test accessed Khayelitsha public health facilities in 2016/2017. 22 961 (50.3%) were PLHIV. Median age at first SCr and eGFR test for PLHIV was 33yrs (IQR: 27,41) to 36yrs (IQR: 30,43) compared to 49yrs (IQR: 37,57) and 52yrs (IQR: 44,59) for those without HIV. PLHIV first median SCr results were 66 (IQR: 55,78) μmol/l compared to 69 (IQR: 58,82) μmol/l for HIV-negative individuals. Hypertension, diabetes, and CKD at testing were more common in HIV-negative people than PLHIV. HIV, diabetes and tuberculosis (TB) are associated with higher eGFR results; whilst hypertension, being male and older are associated with lower eGFR results. These data reflect testing practices in the Western Cape: younger people without HIV have generally worse kidney function test results; younger PLHIV have generally good test results, and older people with/without HIV have generally similar test results, reflecting regular screening for kidney function in asymptomatic PLHIV whereas young HIV-negative people are tested only when presenting with renal symptoms. Our analysis suggests we cannot infer the future healthcare requirements of younger PLHIV based on the current ageing population, due to changing ART availability for different generations of PLHIV. Instead, routine health data may be used in an agile way to assess ongoing healthcare requirements of ageing PLHIV, and to reflect implementation of treatment guidelines.

Brain tumours in the Western Cape Province of South Africa: A plea for a dedicated brain tumour registry in Africa

Abstract Background: Epidemiological data on brain tumours provides valuable insight into risk factors, treatment modalities and prognoses of these tumours. Despite abundant epidemiological data from brain tumour registries in high-income countries, a critical data gap persists in low- and middle-income countries. Aim: The aim of this study was to report on the epidemiology of brain tumours in South Africa's Western Cape province. Methods: This retrospective study collected data from the National Health Laboratory Services database housed in the public healthcare sector in the Western Cape Province of South Africa. All pathology reports over 2 years (January 2018 to December 2019) that included the term “brain” or equivalent terms were analyzed to compile the epidemiological dataset. Results: The dataset yielded 505 patients with brain tumours, with a mean age at diagnosis of 44 years (range: 0–82 years). A noteworthy subset (16%) of primary tumours occurred in individuals under 20 years of age. The top three primary tumour diagnoses in the study were gliomas, glioneuronal and neuronal tumours, meningiomas and pituitary tumours. Secondary brain tumours (18%) constituted a significant proportion of brain tumours, with lung and breast being the most common primary sites. Comparison with registries and audits from both high- and low-income countries revealed South Africa's unique landscape; ependymal tumours exhibited a substantial proportion, while nerve sheath tumours displayed a reduced proportion. Conclusion: This study offers a unique perspective on brain tumour epidemiology in South Africa's Western Cape Province. It reports on unique trends and emphasizes the feasibility and necessity of establishing a dedicated brain tumour registry.

National Health Laboratory Service (NHLS) changes the method of LDL-cholesterol calculation in South Africa

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Gaps in the type 2 diabetes care cascade: a national perspective using South Africa’s National Health Laboratory Service (NHLS) database

BackgroundResearch out of South Africa estimates the total unmet need for care for those with type 2 diabetes mellitus (diabetes) at 80%. We evaluated the care cascade using South Africa’s National Health Laboratory Service (NHLS) database and assessed if HIV infection impacts progression through its stages.MethodsThe cohort includes patients from government facilities with their first glycated hemoglobin A1c (HbA1c) or plasma glucose (fasting (FPG); random (RPG)) measured between January 2012 to March 2015 in the NHLS. Lab-diagnosed diabetes was defined as HbA1c ≥ 6.5%, FPG ≥ 7.0mmol/l, or RPG ≥ 11.1mmol/l. Cascade stages post diagnosis were retention-in-care and glycaemic control (defined as an HbA1c < 7.0% or FPG < 8.0mmol/l or RPG < 10.0mmol/l) over 24-months. We estimated gaps at each stage nationally and by people living with HIV (PLWH) and without (PLWOH).ResultsOf the 373,889 patients tested for diabetes, 43.2% had an HbA1c or blood glucose measure indicating a diabetes diagnosis. Amongst those with lab-diagnosed diabetes, 30.9% were retained-in-care (based on diabetes labs) and 8.7% reached glycaemic control by 24-months. Prevalence of lab-diagnosed diabetes in PLWH was 28.6% versus 47.3% in PLWOH. Among those with lab-diagnosed diabetes, 34.3% of PLWH were retained-in-care versus 30.3% PLWOH. Among people retained-in-care, 33.8% of PLWH reached glycaemic control over 24-months versus 28.6% of PLWOH.ConclusionsIn our analysis of South Africa's NHLS database, we observed that 70% of patients diagnosed with diabetes did not maintain in consistent diabetes care, with fewer than 10% reaching glycemic control within 24 months. We noted a disparity in diabetes prevalence between PLWH and PLWOH, potentially linked to different screening methods. These differences underscore the intricacies in care but also emphasize how HIV care practices could guide better management of chronic diseases like diabetes. Our results underscore the imperative for specialized strategies to bolster diabetes care in South Africa.

The prevalence and spectrum of thyroid dysfunction among children with Down syndrome attending the paediatric services at two tertiary hospitals in Pretoria, South Africa

Background. Down syndrome (DS) is the most common chromosomal abnormality in the paediatric setting, and thyroid dysfunction is more commonly encountered in this population than among the general population. The literature shows that the most common type of thyroid dysfunction seen in these children is subclinical hypothyroidism.Objective. The purpose of this study was to establish the prevalence and spectrum of thyroid disease in this population with the aim of establishing easy-to-follow protocols. Method. A retrospective study was conducted in children with DS who were seen at the paediatric genetic clinic at two academic hospitals. Data were collected from the hospital files and the results were extracted from the National Health Laboratory Service database system. Results. A total of 158 children were recruited; 25 children were excluded as they had had no thyroid function tests done. From the total of 133 included children, 70 (52.6%) were male. Babies born in one of the two hospitals numbered 60 (45.1%), whereas 54.9% were born in the other hospital. A total of 77 (57.9%) were found to have thyroid dysfunction; 55.8% of these patients were male. The most common thyroid abnormality was subclinical hypothyroidism in n=66/133 (49.6%), accounting for 85.7% of the causes of the thyroid dysfunction. Most children (n=45/133 (33.8%)) had their first thyroid function test done before the age of 2 months, followed by the age group of 1 - 5 years (n=34/133 (25.56%)). The total number of children started on treatment for their thyroid dysfunction was n=5/77 (6.49%). Conclusion. Thyroid dysfunction is seen more commonly in children with DS compared with the general population, which was very evident in the present study. A standardised protocol will have a significant impact on the early management of these children, to prevent further cognitive impairment, especially in developing countries and at any level of healthcare. The recommendations for thyroid dysfunction screening by the American Academy of Pediatrics can be adjusted and tailored for the South African population. Early diagnosis and referral of children with DS to a secondary- or tertiary-level facility is of utmost benefit for these children for screening and treatment of comorbidities and complications.

Tuberculosis testing patterns in South Africa to identify groups that would benefit from increased investigation

The National Health Laboratory Service (NHLS) collects all public health laboratory test results in South Africa, providing a cohort from which to identify groups, by age, sex, HIV, and viral suppression status, that would benefit from increased tuberculosis (TB) testing. Using NHLS data (2012–2016), we assessed levels and trends over time in TB diagnostic tests performed (count and per capita) and TB test positivity. Estimates were stratified by HIV status, viral suppression, age, sex, and province. We used logistic regression to estimate the odds of testing positive for TB by viral suppression status. Nineteen million TB diagnostic tests were conducted during period 2012–2016. Testing per capita was lower among PLHIV with viral suppression than those with unsuppressed HIV (0.08 vs 0.32) but lowest among people without HIV (0.03). Test positivity was highest among young adults (aged 15–35 years), males of all age groups, and people with unsuppressed HIV. Test positivity was higher for males without laboratory evidence of HIV than those with HIV viral suppression, despite similar individual odds of TB. Our results are an important national baseline characterizing who received TB testing in South Africa. People without evidence of HIV, young adults, and males would benefit from increased TB screening given their lower testing rates and higher test positivity. These high-test positivity groups can be used to guide future expansions of TB screening.

NECROTIZING SOFT-TISSUE INFECTIONS: A RETROSPECTIVE CASE SERIES AT A DISTRICT HOSPITAL IN SOUTH AFRICA

Necrotizing soft tissue infection (NSTI) is a rapidly progressive infection that typically starts in the dermis and epidermis and spreads along soft tissue planes, penetrating subdermal layers and can lead to massive tissue necrosis resulting in severe morbidity and mortality. The aim of this case series was to describe the epidemiology and burden of NSTI's at a District Hospital servicing a South African urban settlement.This retrospective case series was performed at a single centre. Consecutive patients were identified following a clinical diagnosis for NSTI. Further laboratory pre-operative work up was standardized including: use of validated Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC scores) and Human Immunodeficiency Virus (HIV) status. All patients who underwent surgical debridement were captured on the Theatre Database (www.medwebtools.org™). All patients received standardized perioperative, intra-operative and post-operative protocols for antibiotics, debridement and soft tissue closure or cover based on the severity of disease. Medical records, theatre notes, National Health Laboratory Service (NHLS) results and radiological results were captured for every patient.28 patients (14 male, 14 female) presented with NSTI over a 3 year period (2021–2023). The mean age was 39.5 years. The most common organisms cultured were Streptococcus pyogenes (10 patients), Staphylococcus aureus (9 patients), Bacillus cereus (3 patients).This retrospective case series is an important study because it demonstrates some of the highest incidence of NSTI globally; however, the cause of this is yet to be determined. Our results show that having a high clinical index of suspicion; using the LRINEC score to assess severity and using a standardized antibiotic and peri-operative protocol with early soft tissue cover that NSTI's can be managed effectively with a reduction in patient morbidity and overall length of hospital stay.

RSV bronchiolitis in 2018: A descriptive study of children admitted to two Johannesburg tertiary hospitals

Background. Respiratory syncytial virus (RSV) is the most common cause of severe bronchiolitis in children worldwide.Objectives. To describe clinical characteristics and outcomes of children hospitalised with bronchiolitis and to compare those with RSVbronchiolitis with children with other viral causes of bronchiolitis.Methods. A retrospective study of children admitted with virally screened bronchiolitis to Charlotte Maxeke Johannesburg AcademicHospital (CMJAH) and Nelson Mandela Children’s Hospital (NMCH) from 1 February to 31 August 2018 was conducted, where RSVpositive and -negative children were compared. These children were identified by the National Health Laboratory Service as havingundergone respiratory viral multiplex molecular assay analysis and hospital charts were retrospectively reviewed.Results. A total of 131 children admitted with bronchiolitis from CMJAH and NMCH were compared in this study, 58 from CMJAHand 73 from NMCH. In the sample group, 65 (49.6%) children had RSV in comparison with 66 (50.4%) children without RSV. Childrenwith RSV comprised 55 (42%) children with RSV only and 10 (7.6%) children with RSV in combination with another respiratory virus.Rhinovirus was the second most common virus detected in this cohort of children (n=17, 12.9%) followed by adenovirus (n=12, 9.2%)and coronavirus (n=9, 6.9%). A statistically significant risk factor noted in children requiring hospitalisation for RSV bronchiolitis wasage less than six months (p&lt;0.001).Conclusions. Bronchiolitis is a common disease in children. Respiratory syncytial virus is the most common cause of severe bronchiolitis in hospitalised infants less than six months of age.

Nucleated red blood cells in neonates with hypoxic ischaemic encephalopathy treated with hypothermia: A worthwhile prognostic biomarker for clinicians in LMIC?

Background. Neonatal hypoxic ischaemic encephalopathy (HIE) is a leading cause of term neonatal death worldwide, with a higherincidence in low- to middle-income settings.Objective. To investigate whether nucleated red blood cell (nRBC) counts could predict severity of HIE and outcomes in term neonatestreated with therapeutic hypothermia (TH).Methods. We conducted a retrospective sub-study at Tygerberg Hospital in Cape Town, South Africa. The review included all cooledneonates’ clinical records and blood samples from a National Health Laboratory Services database. One experienced neurodevelopmental expert assessed patients over a period of 12 months.Results. Twenty-five files out of a total of 100 were excluded owing to missing data. In accordance with the Thompson HIE score,the cohort was classified as mild (56%), moderate (27%), and severe (17%). All included patients (n=75) had full blood counts within6 hours of delivery. nRBC were detected in 52% of the samples. There was no correlation between nRBC category and HIE severity(p=0.265). Raised nRBCs (≥30 cells/100 white blood cells (WBCs)) were more frequent in infants who died than in those whosurvived (p=0.008). Infants with nRBC counts ≥30 cells/100 WBCs had an increased likelihood of having cerebral palsy or impairedneurodevelopment (p=0.013).Conclusion. The study demonstrated a significant association between an early increase in nRBC counts in HIE infants treated with TH,and both short- and long-term outcomes. A larger multicentre study is required to better understand the relationship between nRBCcounts and HIE in the era of cooling in our local setting.

Using laboratory data to assess the impact of coronavirus (COVID-19) on reflex cryptococcal antigenaemia (CrAg) testing in South Africa.

Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, China. Due to the rapid spread globally, it was declared a pandemic in March 2020. Social distancing and lockdown measures were introduced to limit transmission. These strategies could potentially impact the diagnosis and treatment of patients with advanced HIV who are susceptible to secondary infections like cryptococcal disease. In South Africa, reflexed cryptococcal antigenaemia (CrAg) testing and pre-emptive antifungal treatment are recommended preceding antiretroviral therapy initiation for patients with a CD4<100 cells/μl. This study aimed to assess the impact of COVID-19 on CrAg testing in South Africa. Specimen-level data was extracted for individuals ≥15 years from the National Health Laboratory Services repository for calendar years 2018 to 2021. Test volumes and CrAg positivity were assessed at national and provincial levels, by age category and gender. The percentage change in annual and monthly CrAg test volumes for 2020 and 2021 (during lockdown levels) are compared to data reported for 2018. The monthly median CD4 and the percentage of samples with a count <25, 25-50, 51-75 and >75-<100 cells/μl were assessed. Specimen data of 11 944 929 CD4 results included 1 306 456 CrAg tests. Annual CD4 and CrAg test volumes declined by 22.4% and 27.8% for 2020 and 2021 respectively (relative to 2018). There were 23 670 CrAg positive outcomes in 2018 compared to 21 399 (-9.6%) and 17 847 (-24.6%) in 2020 and 2021 respectively. A monthly test volume reduction of up to 36.6%, 35.5%, 36.1% and 13.3% was reported for infection waves one to four. CrAg detection increased from 6.3% in 2018 to 7.5% in 2020. More testing was offered to males (>56%) with a higher detection rate of 8.1% in 2020. Between 81.0% and 81.8% of testing was for patients aged 20 to 49 years. The monthly percentage of specimens <25 cells/μl ranged from 30.2% (June 2019) to 35.3% (August 2020). Overall, the monthly median CD4 ranged from 39 (IQR: 15-70)(August 2020) to 45 (IQR: 19-72)(March 2019) cells/μl. In 2020, the provincial percentage change in CrAg test volumes ranged from 2.9% to -33.7%. Our findings confirmed the impact of lockdown measures on both the absolute number of CrAg tests performed and detection (increase in 2020). A smaller impact on the median CD4 was noted. The long-term impact on patient management in immune- compromised individuals needs further investigation.

Developing an antibiogram for empiric antibiotic prescribing for adult non-spinal orthopaedic infections in a developing world setting

PurposeEmpiric antibiotic strategies in the treatment of fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis should be based on local microbiological antibiograms. This study aims to describe the microbiology and review the antibiogram profiles of bacterial isolates from patients undergoing surgical treatment for non-spinal orthopaedic infections, to identify the most appropriate empiric antibiotic strategy.MethodsA retrospective review was performed of all cases of non-spinal orthopaedic infections treated surgically from 1 January 2018 to 31 December 2018. The National Health Laboratory Service microbiology database was used to identify all intra-operative microbiological specimens obtained from orthopaedic patients, and data were correlated with the orthopaedic surgical database. Cases were divided into fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis. Antibiotic susceptibility data were used to predict the efficacy of different empiric antibiotic regimens.ResultsA total of 107 cases were included in the study; 184 organisms were cultured. Overall, the most common organism cultured was Staphylococcus aureus (25%) followed by Acinetobacter baumannii (9%), Enterococcus faecalis (7%) and Enterobacter cloacae (5%). Across all categories the oral antibiotic combination with the highest effectiveness (81%) would have been a combination of co-trimoxazole, ciprofloxacin and amoxicillin. The most effective intravenous antibiotic combination would have been either piperacillin–tazobactam, amikacin and vancomycin or meropenem and vancomycin; 90% of tested isolates were susceptible to either of these combinations.ConclusionAntibiogram profiles can serve to guide to empiric antibiotic choice in the management of different categories of non-spinal orthopaedic infections.

HIV Viral Load Testing in the South African Public Health Setting in the Context of Evolving ART Guidelines and Advances in Technology, 2013-2022.

HIV viral load (VL) testing plays a key role in the clinical management of HIV as a marker of adherence and antiretroviral efficacy. To date, national and international antiretroviral treatment recommendations have evolved to endorse routine VL testing. South Africa (SA) has recommended routine VL testing since 2004. Progressively, the centralised HIV VL program managed by its National Health Laboratory Service (NHLS) has undergone expansive growth. Retrospective de-identified VL data from 2013 to 2022 were evaluated to review program performance. Test volumes increased from 1,961,720 performed in 2013 to 45,334,864 in 2022. The median total in-laboratory turnaround time (TAT) ranged from 94 h (2015) to 51 h (2022). Implementation of two new assays improved median TATs in all laboratories. Samples of VL greater than 1000 copies/mL declined steadily. Despite initial increases, samples of fewer than 50 copies/mL stagnated at about 70% from 2019 and declined to 68% in 2022. Some variations between assays were observed. Overall, the SA VL program is successful. The scale of the VL program, the largest of its kind in the world by some margin, provides lessons for future public health programs dependent on laboratories for patient outcome and program performance monitoring.

Eliminating Vertical Transmission of HIV in South Africa: Establishing a Baseline for the Global Alliance to End AIDS in Children.

To gain a detailed overview of vertical transmission in South Africa, we describe insights from the triangulation of data sources used to monitor the national HIV program. HIV PCR results from the National Health Laboratory Service (NHLS) were analysed from the National Institute of Communicable Diseases (NICD) data warehouse to describe HIV testing coverage and positivity among children <2 years old from 2017-2021. NICD data were compared and triangulated with the District Health Information System (DHIS) and the Thembisa 4.6 model. For 2021, Thembisa estimates a third of children living with HIV go undiagnosed, with NICD and DHIS data indicating low HIV testing coverage at 6 months (49%) and 18 months (33%) of age, respectively. As immunisation coverage is reported at 84% and 66% at these time points, better integration of HIV testing services within the Expanded Programme for Immunization is likely to yield improved case findings. Thembisa projects a gradual decrease in vertical transmission to 450 cases per 100,000 live births by 2030. Unless major advances and strengthening of maternal and child health services, including HIV prevention, diagnosis, and care, can be achieved, the goal to end AIDS in children by 2030 in South Africa is unlikely to be realised.

How South Africa Used National Cycle Threshold (Ct) Values to Continuously Monitor SARS-CoV-2 Laboratory Test Quality.

The high demand for SARS-CoV-2 tests but limited supply to South African laboratories early in the COVID-19 pandemic resulted in a heterogenous diagnostic footprint of open and closed molecular testing platforms being implemented. Ongoing monitoring of the performance of these multiple and varied systems required novel approaches, especially during the circulation of variants. The National Health Laboratory Service centrally collected cycle threshold (Ct) values from 1,497,669 test results reported from 6 commonly used PCR assays in 36 months, and visually monitored changes in their median Ct within a 28-day centered moving average for each assays' gene targets. This continuous quality monitoring rapidly identified delayed hybridization of RdRp in the Allplex™ SARS-CoV-2 assay due to the Delta (B.1.617.2) variant; S-gene target failure in the TaqPath™ COVID-19 assay due to B.1.1.7 (Alpha) and the B.1.1.529 (Omicron); and recently E-gene delayed hybridization in the Xpert® Xpress SARS-CoV-2 due to XBB.1.5. This near "real-time" monitoring helped inform the need for sequencing and the importance of multiplex molecular nucleic acid amplification technology designs used in diagnostics for patient care. This continuous quality monitoring approach at the granularity of Ct values should be included in ongoing surveillance and with application to other disease use cases that rely on molecular diagnostics.

Assessing very advanced HIV disease in adolescent girls and young women

Background: South Africa has the largest HIV epidemic globally, with ~7.5 million people living with HIV in 2021. Adolescent girls (AG) and young women (YW), aged 15–19 years and 20–24 years, are twice as likely to be living with HIV as their male counterparts. The national HIV prevalence for young women was 9.1% (2021), with limited data on disease severity.Objectives: This study assessed very advanced HIV disease (CD4 100 cells/μL) in adolescent girls and young women (AGYW) in South Africa.Method: A retrospective descriptive study analysed data collated from the National Health Laboratory Service database for 2017 to 2021 calendar years for AGYW. National and provincial specimen volumes, the percentage of tests with a CD4 100 cells/μL and ≥ 100 cells/μL, and the median and interquartile ranges, were calculated. Logistic regression determined the odds ratio for a CD4 100 cells/μL, controlling for age category.Results: Data for 1 199 010 CD4 specimens indicated a significant decrease in volumes of 34% from 287 410 (2017) to 189 533 (2021). The percentage of samples with a count 100 cells/μL ranged from 4.9% to 5.2% for YW versus 5.6% to 6.1% for AG. Provincial data for a CD4 count 100 cells/μL ranged between 4.5% and 8.3% in AG and 3.6% to 6.3% for YW. Logistic regression indicated a 24% higher likelihood for AG having a CD4 count 100 cells/μL.Conclusion: The study reported a higher proportion of very advanced HIV disease for AG versus YW nationally, with provincial disparity needing further analysis.

Evaluation of tumour marker utilisation and impact of electronic gatekeeping in the province of KwaZulu-Natal, South Africa.

Inappropriate testing remains a high healthcare cost driver. Tumour marker tests are more expensive than routine chemistry testing. Implementing test demand management systems like electronic gatekeeping (EGK) has reportedly decreased test requests. This study aimed to describe the appropriateness of tumour marker tests, carcinoembryonic antigen, alpha foetal protein, prostate-specific antigen, carbohydrate antigen 19-9, cancer antigen 15-3, cancer antigen 125, and human chorionic gonadotropin, and determine the effectiveness of the EGK used in the public health sector in KwaZulu-Natal, South Africa. Tumour marker test data for the KwaZulu-Natal province were extracted from the National Health Laboratory Service Central Data Warehouse for 01 January 2017 - 30 June 2017 (pre-EGK) and 01 January 2018 - 30 June 2018 (post-EGK implementation). Questionnaires were sent to the clinicians in the regional hospitals ordering the most tumour marker tests to assess ordering practices. In addition, we assessed monthly rejection reports to determine the effect of the EGK. The EGK minimally reduced tumour marker requests or associated costs (1.4% average EGK rejection rate). An overall 18% increase in the tumour marker tests occurred in 2018. The data suggest inappropriate tumour marker test utilisation, particularly for screening. The introduction of EGK as a test demand management had little impact on tumour marker test requests and costs. Continuous education and reiteration of indications for tumour marker test use are required. This study demonstrates the ineffectiveness of EGK in tumour marker orders, and provides some insight as to why these markers are being ordered, which is important in trying to decrease inappropriate ordering of these tests.

Decreasing Incidence of Conjunctival Squamous Cell Carcinoma in People with HIV in South Africa.

The main risk factors for squamous cell carcinoma of the conjunctiva (SCCC) are immunodeficiency and exposure to ultraviolet radiation. Little is known about the SCCC epidemiology among people with HIV (PWH) in South Africa. We used data from the South African HIV Cancer Match study, a nation-wide cohort of PWH in South Africa, created through a privacy-preserving probabilistic record linkage of HIV-related laboratory records from the National Health Laboratory Service and cancer records from the National Cancer Registry from 2004-2014. We calculated crude incidence rates, analyzed trends using Joinpoint models and estimated hazard ratios (HR) for different risk factors using Royston-Parmar flexible parametric survival models. Among 5,247,968 PWH, 1,059 incident SCCC were diagnosed for a crude overall SCCC incidence rate of 6.8/100,000 person-years. The SCCC incidence rate decreased between 2004 and 2014 with an annual percentage change of -10.9% (95% CI -13.3 to -8.3). PWH residing within latitudes 30°S-34°S had a 49% lower SCCC risk than those residing at < 25°S (adjusted HR 0.67; 95% CI 0.55-0.82). Other risk factors for SCCC were lower CD4 counts and middle-age. There was no evidence for an association of sex or settlement type with SCCC risk. An increased risk of developing SCCC was associated with lower CD4 counts and residence closer to the equator, indicative of higher ultraviolet exposure. Clinicians and PWH should be educated on known SCCC preventive measures such as maintaining high CD4 counts and protection from ultraviolet radiation through sunglasses and sunhats when outdoors.

Succinate dehydrogenase-deficient renal cell carcinoma: A retrospective study, 1999–2018

Background: Succinate dehydrogenase-deficient (SDH-deficient) renal cell carcinoma (RCC) is a rare subtype of RCC. Approximately 0.05% – 0.2% of RCCs are SDH-deficient. It is usually associated with a pathogenic germline variant of the enzyme. Although the tumour is often indolent, it has a strong association with hereditary disease, most commonly paraganglioma and/or pheochromocytoma, and genetic testing is advised. Succinate dehydrogenase-deficient RCC is diagnosed by immunohistochemical (IHC) staining for SDH subunit B (SDHB), with loss of staining confirming SDHB deficiency. The incidence of SDH-deficient RCC in South Africa is unknown.Aim: To determine the incidence of SDH-deficient RCC in the Free State Province and its correlation with the worldwide incidence of 0.05% – 0.2%.Setting: Department of Anatomical Pathology, Universitas Academic Hospital and National Health Laboratory Service (NHLS) in Bloemfontein, South Africa.Methods: A retrospective descriptive study was performed. All primary RCCs diagnosed over a 20-year period (1999–2018) were included. An SDHB IHC stain was performed on all cases. A diagnosis of SDH-deficient RCC required loss of staining in all tumour cells in the presence of internal positive controls.Results: The study included 187 RCC cases. Two cases of SDH-deficient RCC were identified, representing an incidence of 1.1%. Both patients were male and were 22 and 44 years of age, respectively.Conclusion: The incidence of SDH-deficient RCC in central South Africa is slightly higher than global findings.Contribution: This study provides new data on SDH-deficient RCC in the South African context.

SARS-CoV-2 spike protein diversity at an intra-host level, among SARS-CoV-2 infected individuals in South Africa, 2020 to 2022.

Intra-host diversity studies are used to characterise the mutational heterogeneity of SARS-CoV-2 infections in order to understand the impact of virus-host adaptations. This study investigated the frequency and diversity of the spike (S) protein mutations within SARS-CoV-2 infected South African individuals. The study included SARS-CoV-2 respiratory samples, from individuals of all ages, received at the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic hospital, Gauteng, South Africa, from June 2020 to May 2022. Single nucleotide polymorphism (SNP) assays and whole genome sequencing were performed on a random selection of SARS-CoV-2 positive samples. The allele frequency (AF) was determined using TaqMan Genotyper software for SNP PCR analysis and galaxy.eu for analysis of FASTQ reads from sequencing. The SNP assays identified 5.3% (50/948) of Delta cases with heterogeneity at delY144 (4%; 2/50), E484Q (6%; 3/50), N501Y (2%; 1/50) and P681H (88%; 44/50), however only heterogeneity for E484Q and delY144 were confirmed by sequencing. From sequencing we identified 9% (210/2381) of cases with Beta, Delta, Omicron BA.1, BA.2.15, and BA.4 lineages that had heterogeneity in the S protein. Heterogeneity was primarily identified at positions 19 (1.4%) with T19IR (AF 0.2-0.7), 371 (92.3%) with S371FP (AF 0.1-1.0), and 484 (1.9%) with E484AK (0.2-0.7), E484AQ (AF 0.4-0.5) and E484KQ (AF 0.1-0.4). Mutations at heterozygous amino acid positions 19, 371 and 484 are known antibody escape mutations, however the impact of the combination of multiple substitutions identified at the same position is unknown. Therefore, we hypothesise that intra-host SARS-CoV-2 quasispecies with heterogeneity in the S protein facilitate competitive advantage of variants that can completely/partially evade host's natural and vaccine-induced immune responses.