Diversity of enteroviruses in cerebrospinal fluid specimens collected from hospitalised patients in the private and public sector in South Africa.

Enteroviruses cause a wide range of neurological illnesses such as encephalitis, meningitis, and acute flaccid paralysis. Two types of enteroviruses, echovirus E4 and E9, have recently been detected in South Africa and are known to be associated with meningitis and encephalitis. The objective of this study was to characterize enterovirus strains detected in cerebrospinal fluid specimens of hospitalized patients in the private and public sector to identify genotypes associated with meningitis and encephalitis. From January 2019 to June 2021 enterovirus positive nucleic acid samples were obtained from a private (n = 116) and a public sector (n = 101) laboratory. These enteroviruses were typed using a nested set of primers targeting the VP1 region of the enterovirus genome, followed by Sanger sequencing and BLASTn analysis. Forty-two percent (91/217) of the strains could be genotyped. Enterovirus B species was the major species detected in 95% (86/91) of the specimens, followed by species C in 3% (3/91) and species A in 2% (2/91) of the specimens. Echovirus E4 and E9 were the two major types identified in this study and were detected in 70% (64/91) and in 10% (9/91) of specimens, respectively. Echovirus E11 has previously been identified in sewage samples from South Africa, but this study is the first to report Echovirus E11 in cerebrospinal fluid specimens from South African patients. The genotypes identified during this study are known to be associated with encephalitis and meningitis. The predominant detection of echovirus E4 followed by E9 corresponds with other studies conducted in South Africa.

Impact of the COVID-19 related border restrictions on influenza and other common respiratory viral infections in New Zealand.

BACKGROUND: New Zealand's (NZ) complete absence of community transmission of influenza and respiratory syncytial virus (RSV) after May 2020, likely due to COVID-19 elimination measures, provided a rare opportunity to assess the impact of border restrictions on common respiratory viral infections over the ensuing 2 years. METHODS: We collected the data from multiple surveillance systems, including hospital-based severe acute respiratory infection surveillance, SHIVERS-II, -III and -IV community cohorts for acute respiratory infection (ARI) surveillance, HealthStat sentinel general practice (GP) based influenza-like illness surveillance and SHIVERS-V sentinel GP-based ARI surveillance, SHIVERS-V traveller ARI surveillance and laboratory-based surveillance. We described the data on influenza, RSV and other respiratory viral infections in NZ before, during and after various stages of the COVID related border restrictions. RESULTS: We observed that border closure to most people, and mandatory government-managed isolation and quarantine on arrival for those allowed to enter, appeared to be effective in keeping influenza and RSV infections out of the NZ community. Border restrictions did not affect community transmission of other respiratory viruses such as rhinovirus and parainfluenza virus type-1. Partial border relaxations through quarantine-free travel with Australia and other countries were quickly followed by importation of RSV in 2021 and influenza in 2022. CONCLUSION: Our findings inform future pandemic preparedness and strategies to model and manage the impact of influenza and other respiratory viral threats.

Clinical staff knowledge and awareness of point-of-care-testing best practices at Tygerberg Hospital, South Africa.

BACKGROUND: Point-of-care testing (POCT) is defined as testing done near or at the site of patient care with the goal of providing rapid information and improving patient outcomes. Point-of-care testing has many advantages and some limitations which affect its use and implementation. OBJECTIVE: The aim of the audit was to determine the current practices, staff attitudes and training provided to hospital clinical staff. METHODS: The audit was conducted with the use of a questionnaire containing 30 questions. One hundred and sixty questionnaires were delivered to 55 sites at Tygerberg Academic Hospital in Cape Town, South Africa, from 21 June 2016 to 15 July 2016. A total of 68 questionnaires were completed and returned (42.5% response rate). RESULTS: Most participants were nursing staff (62/68, 91%), and the rest were medical doctors (6/68, 9%). Most participants (66/68, 97%) performed glucose testing, 16/68 (24%) performed blood gas testing and 17/68 (25%) performed urine dipstick testing. Many participants (35/68, 51%) reported having had some formal training in one or more of the tests and 25/68 (37%) reported having never had any formal training in the respective tests. Many participants (46/68, 68%) reported that they never had formal assessment of competency in performing the respective tests. CONCLUSION: Participants indicated a lack of adequate training in POCT and, thus, limited knowledge of quality control measures. This audit gives an indication of the current state of the POCT programme at a tertiary hospital and highlights areas where intervention is needed to improve patient care and management.

Clinical staff knowledge and awareness of point-of-care-testing best practices at Tygerberg Hospital, South Africa

Background: Point-of-care testing (POCT) is defined as testing done near or at the site of patient care with the goal of providing rapid information and improving patient outcomes. Point-of-care testing has many advantages and some limitations which affect its use and implementation. Objective: The aim of the audit was to determine the current practices, staff attitudes and training provided to hospital clinical staff. Methods: The audit was conducted with the use of a questionnaire containing 30 questions. One hundred and sixty questionnaires were delivered to 55 sites at Tygerberg Academic Hospital in Cape Town, South Africa, from 21 June 2016 to 15 July 2016. A total of 68 questionnaires were completed and returned (42.5% response rate). Results: Most participants were nursing staff (62/68, 91%), and the rest were medical doctors (6/68, 9%). Most participants (66/68, 97%) performed glucose testing, 16/68 (24%) performed blood gas testing and 17/68 (25%) performed urine dipstick testing. Many participants (35/68, 51%) reported having had some formal training in one or more of the tests and 25/68 (37%) reported having never had any formal training in the respective tests. Many participants (46/68, 68%) reported that they never had formal assessment of competency in performing the respective tests. Conclusion: Participants indicated a lack of adequate training in POCT and, thus, limited knowledge of quality control measures. This audit gives an indication of the current state of the POCT programme at a Southand highlights areas where intervention is needed to improve patient care and management

Illicit drug use and violence in acute psychosis among acute adult admissions at a South African psychiatric hospital.

BACKGROUND AND OBJECTIVE: The prevalence of mental illness and illicit substance use has increased markedly in South Africa's Western Cape Province, over the last 2 decades; potentially increasing demand for psychiatric care. This paper describes the demographic and substance use profile of patients admitted to Lentegeur (LGH), the largest of the four psychiatric hospitals in the Province. METHODS: Medical records, patient interviews and other clinical notes were used to collect data on demographics, illicit substance use, violent behaviour and utilization of rehabilitative services for patients (n=535) admitted to LGH between 1 August 2012 and 31 January 2013. RESULTS: Majority of admissions were male (65.6%) and younger (69.8% < 35 years) compared to females (62.6% >35 years). Overall, 255 (49%) used an illicit substance, (24% females and 63% males). Majority of substance users were youth (18-35 years) in both males (83.1%) and females (73.8%). Cannabis and methamphetamine were the most popular drugs in males (56.3% and 34.9%) and females (17.9% and 16.2%) with the highest rates being among the youth. Violence was common among both men (60.7%) and women (40.8%); among the violent, 67% of males and 35.6% of female used substances. Only 5.5% of drug users utilized formal drug rehabilitation services. CONCLUSION: Substance use and violence were high, yet only a small proportion of the patients utilised available drug rehabilitation services. This may have implications on psychotic relapses, morbidity and subsequent pressure on financial resources within the health care system. Efforts are needed to maximise utilisation of existing rehabilitative resources for these patients.

Esomeprazole to treat women with preterm preeclampsia: a randomized placebo controlled trial.

BACKGROUND: Preterm preeclampsia has a high rate of fetal death or disability. There is no treatment to slow the disease, except delivery. Preclinical studies have identified proton pump inhibitors as a possible treatment. OBJECTIVE: The purpose of this study was to examine whether esomeprazole could prolong pregnancy in women who have received a diagnosis of preterm preeclampsia. STUDY DESIGN: We performed a double-blind, randomized controlled trial at Tygerberg Hospital in South Africa. Women with preterm preeclampsia (gestational age 26 weeks+0 days to 31 weeks+6 days) were assigned randomly to 40-mg daily esomeprazole or placebo. The primary outcome was a prolongation of gestation of 5 days. Secondary outcomes were maternal and neonatal outcomes. We compared circulating markers of endothelial dysfunction that was associated with preeclampsia and performed pharmacokinetic studies. RESULTS: Between January 2016 and April 2017, we recruited 120 participants. One participant was excluded because of incorrect randomization, which left 59 participants in the esomeprazole and 60 participants in the placebo group. Median gestational age at enrolment was 29+4 weeks gestation. There were no between-group differences in median time from randomization to delivery: 11.4 days (interquartile range, 3.6-19.7 days) in the esomeprazole group and 8.3 days (interquartile range, 3.8-19.6 days) in the placebo group (3 days longer in the esomeprazole arm; 95% confidence interval, -2.9-8.8; P=.31). There were no placental abruptions in the esomeprazole group and 6 (10%) in the placebo group (P=.01, P=.14 adjusted). There were no differences in other maternal or neonatal outcomes or markers of endothelial dysfunction. Esomeprazole and its metabolites were detected in maternal blood among those treated with esomeprazole, but only trace amounts in the umbilical cord blood. CONCLUSION: Daily esomeprazole (40 mg) did not prolong gestation in pregnancies with preterm preeclampsia or decrease circulating soluble fms-like tyrosine kinase 1 concentrations. Higher levels in the maternal circulation may be needed for clinical effect.

Gitelman syndrome in a South African family presenting with hypokalaemia and unusual food cravings.

BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive renal tubular disorder characterised by renal salt wasting with hypokalaemia, metabolic alkalosis, hypomagnesaemia and hypocalciuria. It is caused by mutations in SLC12A3 encoding the sodium-chloride cotransporter on the apical membrane of the distal convoluted tubule. We report a South African family with five affected individuals presenting with hypokalaemia and unusual food cravings. METHODS: The affected individuals and two unaffected first degree relatives were enrolled into the study. Phenotypes were evaluated through history, physical examination and biochemical analysis of blood and urine. Mutation screening was performed by sequencing of SLC12A3, and determining the allele frequencies of the sequence variants found in this family in 117 ethnically matched controls. RESULTS: The index patient, her sister, father and two aunts had a history of severe salt cravings, fatigue and tetanic episodes, leading to consumption of large quantities of salt and vinegar. All affected individuals demonstrated hypokalaemia with renal potassium wasting. Genetic analysis revealed that the pseudo-dominant pattern of inheritance was due to compound heterozygosity with two novel mutations: a S546G substitution in exon 13, and insertion of AGCCCC at c.1930 in exon 16. These variants were present in the five affected individuals, but only one variant each in the unaffected family members. Neither variant was found in any of the controls. CONCLUSIONS: The diagnosis of GS was established in five members of a South African family through clinical assessment, biochemical analysis and mutation screening of the SLC12A3 gene, which identified two novel putative pathogenic mutations.

The influence of storage time and temperature on the measurement of serum, plasma and urine osmolality.

BACKGROUND: Many clinical laboratories require that specimens for serum and urine osmolality determination be processed within 3 h of sampling or need to arrive at the laboratory on ice. This protocol is based on the World Health Organization report on sample storage and stability, but the recommendation lacks good supporting data. We studied the effect of storage temperature and time on osmolality measurements. METHODS: Blood and urine samples were obtained from 16 patients and 25 healthy volunteers. Baseline serum, plasma and urine osmolality measurements were performed within 30 min. Measurements were then made at 3, 6, 12, 24 and 36 h on samples stored at 4-8℃ and room temperature. We compared baseline values with subsequent measurements and used difference plots to illustrate changes in osmolality. RESULTS: At 4-8℃, serum and plasma osmolality were stable for up to 36 h. At room temperature, serum and plasma osmolality were very stable for up to 12 h. At 24 and 36 h, changes from baseline osmolality were statistically significant and exceeded the total allowable error of 1.5% but not the reference change value of 4.1%. Urine osmolality was extremely stable at room temperature with a mean change of less than 1 mosmol/kg at 36 h. CONCLUSIONS: Serum and plasma samples can be stored at room temperature for up to 36 h before measuring osmolality. Cooling samples to 4-8℃ may be useful when delays in measurement beyond 12 h are anticipated. Urine osmolality is extremely stable for up to 36 h at room temperature.

Serum free light chains in patients with HIV infection: their association with markers of disease severity and antiretroviral use.

AIM: Serum free light chain measurements are used to follow-up and manage patients with monoclonal gammopathies, and abnormal ratios are associated with risk of progression in certain diseases. B cell dysfunction is well described in HIV and patients are at risk of developing B cell lymphomas. This study investigated whether HIV is associated with abnormal free light chain levels and the impact of antiretroviral treatment (ART) on these. METHODS: κ And λ free light chain concentrations and ratios, serum albumin and immunoglobulin G (IgG) were measured in 366 HIV positive subjects and correlated with CD4+ counts, viral loads, IgG, albumin and ART use. RESULTS: 66% were women and most were black Africans (66%), 26% were of mixed ethnicity and 8% were Caucasian or of unknown or other race. 89% were on ART. κ Free light chain values ranged from 5.59 to 357.0 mg/L (median 19.6 mg/L) and λ free light chain values ranged from 9.28 to 286 mg/L (median 22.3 mg/L). Both correlated positively with viral load and IgG and negatively with CD4+ counts and albumin concentrations. The ratio only correlated with IgG concentrations. Patients on ART had significantly lower free light chain concentrations, but the ratio was not significantly affected. CONCLUSIONS: This study demonstrated that free light chain concentrations were significantly correlated with markers of HIV disease severity, suggesting ongoing B cell dysfunction despite ART use. Free light chain ratio was not significantly affected.

Bolus administration of intravenous glucose in the treatment of hyperkalemia: a randomized controlled trial.

BACKGROUND: Hyperkalemia is a common medical emergency that may result in serious cardiac arrhythmias. Standard therapy with insulin plus glucose reliably lowers the serum potassium concentration ([K(+)]) but carries the risk of hypoglycemia. This study examined whether an intravenous glucose-only bolus lowers serum [K(+)] in stable, nondiabetic, hyperkalemic patients and compared this intervention with insulin-plus-glucose therapy. METHODS: A randomized, crossover study was conducted in 10 chronic hemodialysis patients who were prone to hyperkalemia. Administration of 10 units of insulin with 100 ml of 50% glucose (50 g) was compared with the administration of 100 ml of 50% glucose only. Serum [K(+)] was measured up to 60 min. Patients were monitored for hypoglycemia and EKG changes. RESULTS: Baseline serum [K(+)] was 6.01 ± 0.87 and 6.23 ± 1.20 mmol/l in the insulin and glucose-only groups, respectively (p = 0.45). At 60 min, the glucose-only group had a fall in [K(+)] of 0.50 ± 0.31 mmol/l (p < 0.001). In the insulin group, there was a fall of 0.83 ± 0.53 mmol/l at 60 min (p < 0.001) and a lower serum [K(+)] at that time compared to the glucose-only group (5.18 ± 0.76 vs. 5.73 ± 1.12 mmol/l, respectively; p = 0.01). In the glucose-only group, the glucose area under the curve (AUC) was greater and the insulin AUC was smaller. Two patients in the insulin group developed hypoglycemia. CONCLUSION: Infusion of a glucose-only bolus caused a clinically significant decrease in serum [K(+)] without any episodes of hypoglycemia.

Verification of serum reference intervals for free light chains in a local South African population.

Monoclonal serum free light chain measurements are used to follow up and manage patients with monoclonal gammopathies, and abnormal serum free light chain ratios are associated with risk of progression in certain diseases. We aimed to validate the reference intervals in our population. Reference intervals for κ and λ free light chains were established on 120 healthy adults. Creatinine levels were measured to exclude renal dysfunction and serum protein electrophoresis was performed. All creatinine values were within normal limits. After exclusion of subjects with abnormal serum protein electrophoreses, 113 subjects were available for analysis. The 95% reference interval was 6.3-20.6 mg/L for κ free light chains, 8.7-25.9 mg/L for λ free light chains and 0.46-1.23 for free light chain ratio. Most of the values fell within the manufacturer's recommended limits and therefore could be used for our population.

Chronic kidney diseases in mixed ancestry south African populations: prevalence, determinants and concordance between kidney function estimators.

BACKGROUND: Population-based data on the burden of chronic kidney disease (CKD) in sub-Saharan Africa is still very limited. We assessed the prevalence and determinants of CKD, and evaluated the concordance of commonly advocated estimators of glomerular filtration rate (eGFR) in a mixed ancestry population from South Africa. METHODS: Participants were a population-based sample of adults selected from the Bellville-South community in the metropolitan city of Cape Town. eGFR was based on the Cockroft-Gault (CG), Modification of Diet in Kidney Disease (MDRD) and CKD Epidemiology Collaboration (CKD-EPI) equations (with and without adjustment for ethnicity). Kidney function staging used the Kidney Disease Outcome Quality Initiative (KDOQI) classification. Logistic regressions and kappa statistic were used to investigate determinants of CKD and assess the agreement between different estimators. RESULTS: The crude prevalence of CKD stage 3-5 was 14.8% for Cockcroft-Gault, 7.6% and 23.9% respectively for the MDRD with and without ethnicity correction, and 7.4% and 17.3% for the CKD-EPI equations with and without ethnicity correction. The highest agreement between GFR estimators was between MDRD and CKD-EPI equations, both with ethnicity correction, Kappa 0.91 (95% CI: 0.86-0.95), correlation coefficient 0.95 (95% CI: 0.94-0.96). In multivariable logistic regression models, sex, age and known hypertension were consistently associated with CKD stage 3-5 across the 5 estimators. CONCLUSIONS: The prevalence of CKD stages greater than 3 is the highest reported in Africa. This study provides evidence for support of the CKD-EPI equation for eGFR reporting and CKD classification.

Distribution and association of hs-CRP with cardiovascular risk variables of metabolic syndrome in adolescent learners.

OBJECTIVE: Metabolic syndrome (MetS) and its associated cardiovascular risk are on the increase in children. High-sensitivity C-reactive protein (hs-CRP) has emerged as a useful marker for inflammation associated with atherosclerosis and cardiovascular disease. Our aim was to determine the distribution of hs-CRP in an effort to identify the MetS variable that is critical in modulating plasma CRP levels in a population of South African adolescents. DESIGN: A cross-sectional analytical study design was used for this investigation, where the dependent and independent variables were measured simultaneously. METHODS: Anthropometric variables, blood pressure, fasting blood glucose and lipids were performed on 324 consenting learners aged 15-18 years from three different ethnic groups (Black, White and Coloured). The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) for ages 15-18 year olds was used to define MetS. RESULTS: The prevalence of MetS and obesity was 3.7% and 7.1%, respectively. The hs-CRP levels were significantly higher in subjects with a waist-circumference greater than the 90th percentile (p < 0.01) and in obese learners with MetS, but was lower in adolescents with normal weight and MetS. Median hs-CRP levels increased with an increasing number of metabolic abnormalities and exceeded 3 mg/L in 19% of adolescents. Gender and ethnic differences were observed. CONCLUSION: Our findings suggest that obesity and waist circumference appear to be major mediators of hs-CRP levels in South African adolescents.

Stability of red blood cell folate in whole blood and haemolysate.

BACKGROUND: Folate, a water soluble B vitamin, is necessary for normal cell growth and DNA synthesis. A deficiency leads to megaloblastic anaemia and possible neurological sequelae. Since we receive samples from distant clinics and experience problems due to the long transit times to our laboratory, we carried out a folate stability study. METHODS: Fasting blood samples were drawn from 40 healthy volunteers. We determined the baseline red blood cell (RBC) folate in duplicate on each sample. Half the sample was then stored at various temperatures prior to haemolysate formation and RBC folate was determined regularly to determine sample stability. The other half was haemolysed, the haemolysate stored at various temperatures and analysed regularly to determine haemolysate stability. A statistical test of equivalence was applied using 18% as a pre-defined limit. RESULTS: We found that whole blood was stable at 4 degrees C up to 72 hours. At room temperature stability has been proven up to 24 hours. Results of additional experiments with haemolysate support stability under all conditions for 12 hours. CONCLUSIONS: Samples for RBC folate determination transported from distant clinics are stable for up to 72 hours at 4 degrees C or at room temperature for at least 24 hours. The prepared haemolysates may be stored at -20 degrees C. Our experiments show that sample transportation at higher temperature does not affect folate stability within our predefined limits.

Iron status in children with recurrent episodes of tumefactive cerebral demyelination.

Iron is a vital element in the multifactorial initiation of myelination. It is required for cholesterol and lipid biosynthesis, both key components of myelin. Iron also plays an important role in energy production by mitochondrial oxidative metabolism which occurs in myelin-producing oligodentrocytes at a higher rate than in any other cell. Iron deficiency can, therefore, result in decreased oligodendrocyte survival and defective myelination. This led us to investigate iron status in 2 consecutive children with multiple sclerosis who presented with recurrent episodes of tumefactive demyelination. Testing revealed nonanemic iron deficiency in both patients. Discontinuation of iron supplementation in both children resulted in recurrent decreased iron parameters which can indicate mutations in proteins responsible for regulation of iron uptake. Further studies are warranted to explore the association of low iron in children presenting with recurrent episodes of tumefactive demyelination.

An audit on the reporting of critical results in a tertiary institute.

BACKGROUND: Critical result reporting is a requirement for accreditation by accreditation bodies worldwide. Accurate, prompt communication of results to the clinician by the laboratory is of extreme importance. Repeating of the critical result by the recipient has been used as a means to improve the accuracy of notification. Our objective was to assess the accuracy of notification of critical chemical pathology laboratory results telephoned out to clinicians/clinical areas. We hypothesize that read-back of telephoned critical laboratory results by the recipient may improve the accuracy of the notification. METHODS: This was a prospective study, where all critical results telephoned by chemical pathologists and registrars at Tygerberg Hospital were monitored for one month. The recipient was required to repeat the result (patient name, folder number and test results). Any error, as well as the designation of the recipient was logged. RESULTS: Of 472 outgoing telephone calls, 51 errors were detected (error rate 10.8%). Most errors were made when recording the folder number (64.7%), with incorrect patient name being the lowest (5.9%). Calls to the clinicians had the highest error rate (20%), most of them being the omission of recording folder numbers. CONCLUSION: Our audit highlights the potential errors during the post-analytical phase of laboratory testing. The importance of critical result reporting is still poorly recognized in South Africa. Implementation of a uniform accredited practice for communication of critical results can reduce error and improve patient safety.