A 6-year review of acute post-streptococcal glomerulonephritis at a public children's hospital in Cape Town, South Africa.

BACKGROUND: Acute post-streptococcal glomerulonephritis (APSGN) is the most common cause of acute nephritis in children globally and, in some cases, may be associated with progressive kidney injury and failure, cumulating in the need for long-term dialysis and/or kidney transplantation. METHODS: Our retrospective study describes the occurrence of APSGN among children (< 14 years) admitted to a tertiary children's hospital in Cape Town, South Africa, from January 2015 to December 2020. RESULTS: Of 161 children who presented with acute nephritis (haematuria, oedema, oliguria, and hypertension), 100 met the inclusion criteria. Demographic, clinical features, laboratory findings, management, and outcome data were collected. APSGN was defined by the clinical presentation of at least two clinical signs of acute nephritis, and low serum complement 3 (C3) level or evidence of a recent streptococcal infection. Most cases of APSGN were associated with streptococcal skin infections: 55/100 (55%); 10/100 (10%) children presented with hypertensive seizures; C3 levels were low in 86/92 (93.5%) children; 94/94 (100%) children had elevated anti-deoxyribonuclease-B (anti-DNase-B) levels; and 80/94 (85%) also had elevated anti-streptolysin O titre (ASOT) at presentation. Eleven (11%) children had a percutaneous kidney biopsy; 4/11 (36%) showed histological features of post-infectious nephritis, and 7/11(64%) also had crescentic glomerulonephritis with immune complex deposits. Sixty-two (62%) children confirmed recovered, and five (5%) progressed to kidney failure, but 29 presumed recovered as they did not return for follow-up to our institution. CONCLUSIONS: Childhood APSGN remains an important health problem in South Africa (SA) with favourable outcomes in most, apart from those with crescentic glomerulonephritis who progressed to kidney failure.

Association of full blood count findings with risk of mortality in children with Klebsiella pneumoniae bloodstream infection at a south african children's hospital.

BACKGROUND: Bloodstream infection (BSI) caused by Klebsiella pneumoniae (KP), is a leading cause of hospital-associated childhood mortality. There are limited data on how poor outcomes of KPBSI can be predicted in poorly resourced areas. This study aimed to assess if the profile of differential counts from full blood counts (FBC) taken at two time points in children with KPBSI could be used to predict the risk of death. METHODS: We conducted a retrospective study of a cohort of children admitted to hospital between 2006 and 2011 with KPBSI. FBC collected within 48 h (T1) of blood culture and 5-14 days later (T2), were reviewed. Differential counts were classified as abnormal if they were higher or lower than laboratory ranges for normal results. The risk of death was assessed for each category of differential counts. Risk ratios adjusted (aRR) for potential confounders were used to estimate the effect of cell counts on risk of death using multivariable analysis. Data were stratified by HIV status. RESULTS: Of 296 children, median age 5 (IQR:2-13) months, 82 were HIV -infected. Ninety-five (32%) children with KPBSI died. Mortality in HIV-infected and uninfected children was 39/82 (48%) and 56/214 (26%), respectively (p < 0.001). Independent associations with mortality were observed with leucopenia, neutropenia and thrombocytopenia. Risk of mortality in HIV-uninfected children with thrombocytopenia at T1 and T2 was aRR 2.5 (95% CI: 1.34-4.64) and 3.18 (95% CI: 1.31-7.73) respectively, whereas the mortality risk in the HIV-infected group with thrombocytopaenia at T1 and T2 was aRR 1.99 (95% CI: 0.94-4.19) and 2.01 (95% CI: 0.65-5.99) respectively. Neutropenia in the HIV-uninfected group at T1 and T2, showed aRR 2.17 (95% CI: 1.22-3.88) and aRR 3.70 (95% CI 1.30-10.51) respectively, while in the HIV-infected group, they were aRR 1.18 (95% CI 0.69-2.03) and aRR 2.05 (95% CI 0.87-4.85) at similar time points. Leucopenia at T2 was associated with mortality in HIV-uninfected and HIV-infected patients, aRR 3.22 (95%CI 1.22-8.51) and aRR 2.34 (95% CI 1.09-5.04) respectively. Persistent high band cell percentage at T2 in HIV-infected children indicated a risk of mortality of aRR 2.91 (95% CI 1.20-7.06). CONCLUSION: Abnormal neutrophil counts and thrombocytopenia are independently associated with mortality in children with KPBSI. In resource-limited countries haematological markers have the potential to predict KPBSI mortality.

The prevalence of liquid chromatography-tandem mass spectrometry confirmed paediatric poisoning at Red Cross War Memorial Children's Hospital, Cape Town, South Africa.

BACKGROUND: Paediatric poisoning is a common presentation to emergency departments worldwide. There is a paucity of data on the role of liquid chromatography-tandem mass spectrometry (LC-MS/MS), in the management of paediatric poisoning in low-and middle-income countries (LMICs). In high-income countries, most studies are retrospective, and few include children. OBJECTIVE: The study describes the prevalence of liquid chromatography-tandem mass spectrometry confirmed paediatric poisoning at Red Cross War Memorial Children's Hospital, Cape Town, South Africa. METHODS: Children admitted with suspected poisoning between 1 January 2017 and 31 December 2017, were recruited. All patients had a urine and/or blood sample sent for LC-MS/MS toxicology. Data collected included demographic data, clinical features, investigations, management, outcome and social interventions. RESULTS: One hundred fifty-two children, with median age of 39 (IQR 25-61) months were enrolled of which 128 (84%) were poisoning cases. Of the 128 poisoning cases, 88 (69%) presented with a history of ingesting a known substance, 16 (12%) an unknown substance and 24 (19%) were cases of occult poisoning. LC-MS/MS was able to identify a substance in 92% of the cases of occult poisoning. In those who had presented with a seemingly known substance, LC-MS/MS found a different substance in 15 cases. LC-MS/MS was also able to detect multiple drugs in 40 patients. Of the poisoning cases, six (5%) cases were attempted homicide cases and 5 (4%) cases were attempted suicide cases. No children died. Individualized social interventions were instituted in poisoning cases. Emergency placement safety reasons was required in 6 children. CONCLUSION: When the limitations are known, LC-MS/MS is useful in identifying cases of occult poisoning, identifying patients who have ingested multiple substances and/or an unknown substance and when targeted towards child protection. As LC-MS/MS is an expensive test, it should be used judiciously in LMICs.

Klebsiella pneumoniae bloodstream infections at a South African children's hospital 2006-2011, a cross-sectional study.

BACKGROUND: Klebsiella pneumoniae (KP) is a significant paediatric bloodstream pathogen in children. There is little data from Africa. In this study we describe the epidemiology of multi-drug resistant Klebsiella pneumoniae bloodstream infection (KPBSI) at Red Cross War Memorial Children's Hospital, Cape Town, South Africa. METHODS: We conducted a retrospective cross-sectional study of KPBSI from 1 January 2006 to 31 December 2011 using conventional descriptive and inferential statistical methods. RESULTS: Of 410 hospitalised children with laboratory confirmed KPBSI, 339 (83 %) were caused by extended-spectrum ß-lactamase (ESBL) producing isolates. The median age (IQR) was 5.0 (2-16) months, 212 (51.7 %) were male, 82 (20 %) were HIV-infected, and 241 (58.8 %) were moderately or severely underweight. The infection was hospital-acquired or healthcare-associated in 389 (95 %) children and community-acquired in 21 (5 %) children. Significant risk factors for ESBL-KPBSI included cephalosporin exposure in the 12 months prior to the KPBSI, adjusted risk ratio (aRR) 1.18 (95 % CI: 1.06-1.31); HIV infection, aRR 1.14 (1.04-1.25), and intravenous infusions for more than 3 days before the KPBSI, aRR 1.15 (95 % CI: 1.04-1.28). A total of 109 (26.6 %) children died within 30 days of the KPBSI, their median age was four (IQR 1-11) months. The median (IQR) time between KPBSI and death was three (1-9) days. HIV-infection, aRR 2.44(95 % CI: 1.59-3.74); skin erosions at the time of KPBSI, aRR 2.15 (95 % CI: 1.54-3.00); being in PICU at the time of the KPBSI, aRR 1.64 (95 % CI: 1.03-2.61) or needing PICU admission after developing KPBSI, aRR 1.72 (95 % CI: 1.10-2.70) were significant risk factors for death. CONCLUSION: ESBL-producing KP is an important cause of laboratory confirmed bloodstream infection in hospitalised children and is associated with high mortality.

RSV infection in children hospitalised with severe lower respiratory tract infection in a low-middle-income setting: A cross-sectional observational study.

INTRODUCTION: Low- and middle-income countries carry the largest burden of Respiratory syncytial virus (RSV) disease, with most deaths occurring in these settings. This study aimed to investigate the burden of RSV disease in South African children hospitalised with lower respiratory tract infection (LRTI), with specific reference to incidence, risk factors, and co-infections. METHODS: A database from a previous prospective study containing demographic, laboratory and clinical data on children hospitalised with LRTIs in Cape Town, South Africa, was used. A nasopharyngeal swab (NP) and induced sputum (IS) were tested for RSV PCR. Descriptive statistics were used to characterise the study population, and a multivariable analysis of risk factors and co-infections was done. RESULTS: RSV was detected in 142 (30.9%; 95% CI 26.7-35.3) of the included 460 study children with LRTI. The median age of RSV-positive children was 4.6 (IQR 2.4-9.7) months compared to RSV-negative children of 10.5 (IQR 4.4-21.3) months, P = <0.001. Most cases occurred in autumn and winter with 126 (89%) cases over this period. IS demonstrated greater sensitivity for RSV diagnosis with 135 cases (95.1%) detected on IS and 57 cases (40.1%) identified on NP; P<0.001. The median length of hospital stay was 3.3 (SD 4.2) days in the RSV positive group and 2.7 (SD 3.3) days in the RSV negative group; P<0.001. The median number of detected viral pathogens was 1 (IQR 0-2) in RSV-positive children (when RSV was excluded from the count) compared to 2 (IQR 2-3) in RSV negative children; P<0.001. The presence of RSV was independently associated with a reduction in the frequency of most viruses tested for on PCR. CONCLUSIONS: RSV is common in children hospitalised with LRTI and mainly affects younger children. There is an urgent need to find an effective vaccine to prevent RSV pneumonia in children worldwide, especially in LMICs that carry the greatest burden of disease.

Doing more with less: The use of non-invasive ventilatory support in a resource-limited setting.

OBJECTIVES: Bubble CPAP (bCPAP), a non-invasive ventilation modality, has emerged as an intervention that is able to reduce pneumonia-related mortality in children in low resourced settings. Our study primarily aimed to describe a cohort of children who were started on CPAP in the Medical Emergency Unit (MEU) of Red Cross War Memorial Children's Hospital 2016-2018. METHODS: A retrospective review of a randomly selected sample of paper-based folders was conducted. Children started on bCPAP at MEU were eligible for inclusion. Demographic and clinical data, management, and outcomes regarding admission to PICU, need for invasive ventilation and mortality were documented. Descriptive statistical data were generated for all relevant variables. Percentages depicted frequencies of categorical data while medians with interquartile ranges (IQR) were used to summarise continuous data. RESULTS: Of 500 children started on bCPAP, 266 (53%) were male; their median age was 3.7 (IQR 1.7-11.3) months and 169 (34%) were moderately to severely underweight-for-age. There were 12 (2%) HIV-infected children; 403 (81%) had received appropriate immunisations for their age; and 119 (24%) were exposed to tobacco smoke at home. The five most common primary reasons for admission were acute respiratory illness, acute gastroenteritis, congestive cardiac failure, sepsis and seizures. Most children, 409 (82%), had no underlying medical condition. Most children, 411 (82%), were managed in high care areas of the general medical wards while 126 (25%) went to PICU. The median time on CPAP was 1.7 (IQR 0.9-2.8) days. The median hospitalisation time was 6 (IQR 4-9) days. Overall, 38 (8%) children required invasive ventilatory support. Overall, 12 (2%) children with a median age of 7.5 (IQR 0.7-14.5) months died, six of whom had an underlying medical condition. CONCLUSIONS: Seventy-five percent of children initiated on bCPAP did not require PICU admission. This form of non-invasive ventilatory support should be considered more widely in the context of limited access to paediatric intensive care units in other African settings.

Clinical use and indications for head computed tomography in children presenting with acute medical illness in a low- and middle-income setting.

BACKGROUND: Computed tomography (CT) imaging is an indispensable tool in the management of acute paediatric neurological illness providing rapid answers that facilitate timely decisions and interventions that may be lifesaving. While clear guidelines exist for use of CT in trauma to maximise individual benefits against the risk of radiation exposure and the cost to the healthcare system, the same is not the case for medical emergency. AIMS: The study primarily aimed to retrospectively describe indications for non-trauma head CT and the findings at a tertiary paediatric hospital. METHODS: Records of children presenting with acute illness to the medical emergency unit of Red Cross War Children's Hospital, Cape Town, over one year (2013) were retrospectively reviewed. Participants were included if they underwent head CT scan within 24 hours of presentation with a non-trauma event. Clinical data and reports of CT findings were extracted. RESULTS: Inclusion criteria were met by 311 patients; 188 (60.5%) were boys. The median age was 39.2 (IQR 12.6-84.0) months. Most common indications for head CT were seizures (n = 169; 54.3%), reduced level of consciousness (n = 140;45.0%), headache (n = 74;23.8%) and suspected ventriculoperitoneal shunt (VPS) malfunction (n = 61;19.7%). In 217 (69.8%) patients CT showed no abnormal findings. In the 94 (30.2%) with abnormal CT results the predominant findings were hydrocephalus (n = 54;57.4%) and cerebral oedema (n = 29;30.9%). Papilloedema was more common in patients with abnormal CT (3/56; 5.4%) compared with none in those with normal CT; P = 0.015; while long tract signs were found in 42/169 (24.9%) and 23/56 (41.1%) of patients with normal and abnormal CT findings, respectively; P = 0.020. Post-CT surgery was required by 47(15.1%) of which 40 (85.1%) needed a ventricular drainage. A larger proportion of patients with VPS (25/62; 40.3%) required surgery compared to patients without VPS (22/249; 8.8%; P<0.001). CONCLUSION: A majority of head CT scans in children with medical emergency with acute neurological illness were normal. Patients with VPS constituted the majority of patients with abnormal CT scans that required subsequent neurosurgical intervention. Evidence-based guidelines are required to guide the best use of head CT in the management of children without head trauma.

A Comparison of Parenteral Phenobarbital vs. Parenteral Phenytoin as Second-Line Management for Pediatric Convulsive Status Epilepticus in a Resource-Limited Setting.

Introduction: Pediatric convulsive status epilepticus (CSE) which is refractory to first-line benzodiazepines is a significant clinical challenge, especially within resource-limited countries. Parenteral phenobarbital is widely used in Africa as second-line agent for pediatric CSE, however evidence to support its use is limited. Purpose: This study aimed to compare the use of parenteral phenobarbital against parenteral phenytoin as a second-line agent in the management of pediatric CSE. Methodology: An open-labeled single-center randomized parallel clinical trial was undertaken which included all children (between ages of 1 month and 15 years) who presented with CSE. Children were allocated to receive either parenteral phenobarbital or parenteral phenytoin if they did not respond to first-line benzodiazepines. An intention-to-treat analysis was performed with the investigators blinded to the treatment arms. The primary outcome measure was the success of terminating CSE. Secondary outcomes included the need for admission to the pediatric intensive care unit (PICU) and breakthrough seizures during the admission. In addition, local epidemiological data was collected on the burden of pediatric CSE. Results: Between 2015 and 2018, 193 episodes of CSE from 111 children were enrolled in the study of which 144 met the study requirements. Forty-two percent had a prior history of epilepsy mostly from structural brain pathology (53%). The most common presentation was generalized CSE (65%) caused by acute injuries or infections of the central nervous system (59%), with 19% of children having febrile status epilepticus. Thirty-five percent of children required second-line management. More patients who received parenteral phenobarbital were at a significantly reduced risk of failing second-line treatment compared to those who received parenteral phenytoin (RR = 0.3, p = 0.0003). Phenobarbital also terminated refractory CSE faster (p < 0.0001). Furthermore, patients who received parenteral phenobarbital were less likely to need admission to the PICU. There was no difference between the two groups in the number of breakthrough seizures that occurred during admission. Conclusion: Overall this study supports anecdotal evidence that phenobarbital is a safe and effective second-line treatment for the management of pediatric CSE. These results advocate for parenteral phenobarbital to remain available to health care providers managing pediatric CSE in resource-limited settings. Attachments: CONSORT 2010 checklist Trial registration: NCT03650270 Full trial protocol available: https://clinicaltrials.gov/ct2/show/NCT03650270?recrs=e&type=Intr&cond=Status+Epilepticus&age=0&rank=1.

Effects of saline or albumin fluid bolus in resuscitation: evidence from re-analysis of the FEAST trial.

BACKGROUND: Fluid resuscitation is the recommended management of shock, but increased mortality in febrile African children in the FEAST trial. We hypothesised that fluid bolus-induced deaths in FEAST would be associated with detectable changes in cardiovascular, neurological, or respiratory function, oxygen carrying capacity, and blood biochemistry. METHODS: We developed composite scores for respiratory, cardiovascular, and neurological function using vital sign data from the FEAST trial, and used them to compare participants from FEAST with those from four other cohorts and to identify differences between the bolus (n=2097) and no bolus (n=1044) groups of FEAST. We calculated the odds of adverse outcome for each ten-unit increase in baseline score using logistic regression for each cohort. Within FEAST participants, we also compared haemoglobin and plasma biochemistry between bolus and non-bolus patients, assessed the effects of these factors along with the vital sign scores on the contribution of bolus to mortality using Cox proportional hazard models, and used Bayesian clustering to identify subgroups that differed in response to bolus. The FEAST trial is registered with ISRCTN, number ISRCTN69856593. FINDINGS: Increasing respiratory (odds ratio 1·09, 95% CI 1·07-1·11), neurological (1·26, 1·21-1·31), and cardiovascular scores (1·09, 1·05-1·14) were associated with death in FEAST (all p<0·0001), and with adverse outcomes for specific scores in the four other cohorts. In FEAST, fluid bolus increased respiratory and neurological scores and decreased cardiovascular score at 1 h after commencement of the infusion. Fluid bolus recipients had mean 0·33 g/dL (95% CI 0·20-0·46) reduction in haemoglobin concentration after 8 h (p<0·0001), and at 24 h had a decrease of 1·41 mEq/L (95% CI 0·76-2·06; p=0·0002) in mean base excess and increase of 1·65 mmol/L (0·47-2·8; p=0·0070) in mean chloride, and a decrease of 0·96 mmol/L (0·45 to 1·47; p=0·0003) in bicarbonate. There were similar effects of fluid bolus in three patient subgroups, identified on the basis of their baseline characteristics. Hyperchloraemic acidosis and respiratory and neurological dysfunction induced by saline or albumin bolus explained the excess mortality due to bolus in Cox survival models. INTERPRETATION: In the resuscitation of febrile children, albumin and saline boluses can cause respiratory and neurological dysfunction, hyperchloraemic acidosis, and reduction in haemoglobin concentration. The findings support the notion that fluid resuscitation with unbuffered electrolyte solutions may cause harm and their use should be cautioned. The effects of lower volumes of buffered solutions should be evaluated further. FUNDING: Medical Research Council, Department for International Development, National Institute for Health Research, Imperial College Biomedical Research Centre.

Antiretroviral treatment for children.

OBJECTIVE: To describe the response of children during their first year on highly active antiretroviral therapy (HAART). DESIGN: Retrospective, descriptive. SETTING: Tertiary, referral hospital. SUBJECTS: All HIV-infected children commenced on HAART from 1 August 2002 until 31 December 2004. OUTCOME MEASURES: Children were retrospectively restaged using the WHO 4-stage clinical classification and CDC immunological staging system. After commencing HAART, patients were assessed at monthly intervals for the first 6 months and thereafter mostly 3-monthly. Baseline and 6- monthly CD4 counts and viral loads were performed. RESULTS: Of 409 children commenced on HAART, 50.6% were < 2 years old, 62.7% had severe clinical disease and 76.6% had severe immune suppression. After 1 year, 65.8% were alive and continued HAART at the hospital, 11.2% had been transferred to another antiretroviral site, 15.4% had died, 4.6% were lost to follow-up and treatment had been discontinued in 2.9%. Kaplan-Meier survival estimate for 407 children at 1 year was 84% (95% confidence interval (CI) 80 - 87%). On multivariate analysis, survival was adversely affected in children with WHO stage 4 v. stage 2 and 3 disease (adjusted hazard ratio (HR): 5.26 (95% CI 2.25 - 12.32), p = 0.000), age < 12 months (adjusted HR: 2.46 (95% CI 1.48 - 4.09), p = 0.001) and CD4 absolute count (per 100 cell increase) (adjusted HR: 0.93 (95% CI 0.88 - 0.98), p = 0.013). In a separate multivariate model including only children with an initial viral load (N = 367), viral load > or = 1 million copies/ml (adjusted HR: 1.84 (95% CI 1.03 - 3.29)) and taking a protease inhibitor (PI)-based regimen (adjusted HR: 2.25 (95% CI 1.10 - 4.61)) were additionally independently associated with poorer survival; however, young age was not a significant predictor of mortality, after adjusting for viral load (p = 0.119). After 1 year of HAART 184/264 (69.7%) of children had a viral load < 400 copies/ml. Comparative analysis showed significant improvements in growth, immunological status and virological control. CONCLUSION: HAART can improve the health of many HIV-infected children with advanced disease, including those aged less than 2 years in resource-limited settings.

Initial experience of a public sector antiretroviral treatment programme for HIV-infected children and their infected parents.

OBJECTIVE: To describe the initial experience of treating HIV-infected children and their infected parents with antiretroviral therapy. DESIGN: Prospective, cohort study. SETTING: Tertiary, referral hospital. PATIENTS: HIV-infected children and their parents. METHODS: This report focuses on the early response of children to highly active antiretroviral therapy (HAART). Children were followed up at 4-weekly intervals. Monitoring included initial and yearly viral load measurements, baseline and 6-monthly CD4 counts and 4-weekly adherence checks. RESULTS: Between August 2002 and June 2003, 80 children were enrolled in the programme, representing a follow-up period of 23.9 patient-years. Seventy-five children had severe clinical disease, severe immune suppression, or a combination of the two. The response of children who had received HAART for > or = 6 months (N = 17) was assessed. There was no change in mass z-score (p = 0.11) or length z-score (p = 0.37), but a significant increase in CD4 percentage (p < 0.0001) during the first 6 months of therapy. Six-month viral loads were available for 12 children. There was a significant drop in viral load (p = 0.001) and 9 achieved undetectable levels by 6 months. Most children achieved > or = 85% adherence. By June 2002, 67 children (84%) were relatively well, 1 had B-cell lymphoma, 7 (8.8%) had died, 4 (5%) were lost to follow-up and 1 was withdrawn from the programme. Of 57 children who completed 3 months of HAART, 12 were admitted a total of 17 times for infectious complications. There were no severe drug reactions. Three of 7 mothers on HAART received treatment through the programme. CONCLUSION: These initial results suggest that many HIV-infected children in the public sector will benefit from antiretroviral therapy. However, both ambulatory and inpatient facilities are required to manage children on HAART comprehensively.