A rare mutation causing autosomal dominant STAT1 deficiency in a South African multiplex kindred with disseminated BCG infection.

BACKGROUND: Autosomal dominant signal transducer and activator of transcription 1 (STAT1) deficiency, part of the Mendelian susceptibility to mycobacterial disease (MSMD) group, frequently causes disseminated Bacillus Calmette-Guérin (BCG) infections, but has not been reported from Sub-Saharan Africa (SSA) where routine birth BCG vaccination is practiced. CASE PRESENTATION: Two half-siblings presented five years apart, with multifocal osteomyelitis as the dominant feature of disseminated BCG, which was successfully treated with antimycobacterial therapy. Whole exome sequencing demonstrated a novel heterozygous substitution in the splice site between intron 13 and exon 14 of the STAT1 gene, NM_007315: c.1128-1G>A, in the proband and his mother and was later confirmed in his half-brother. CONCLUSIONS: Children with BCG vaccine complications in SSA should be referred for further investigation and particular consideration of MSMD.

SARS-CoV-2 antibodies in adolescents living with perinatally acquired HIV.

Data on children and adolescents with HIV and coronavirus disease 2019 (COVID-19) co-infection are limited. Clinical and antibody data related to COVID-19 infection in adolescents living with perinatally acquired HIV (ALPHIV) and originally enrolled in the Children with HIV Early Antiretroviral Therapy (CHER) study were collected. We present a descriptive analysis of 53 ALPHIV who were tested for anti-SARS-CoV-2 antibodies. Just over half (53%) of the adolescents tested had positive anti-SARS-CoV-2 antibodies with only one participant describing a prior history of possible symptomatic infection. Contribution: The study contributes to the understanding of SARS-CoV-2 infection and vaccination practices in HIV-positive adolescents.

Cardiometabolic Risk Profiles of Adolescents Living With Perinatally Acquired HIV in South Africa.

BACKGROUND: We assessed the Pathological Determinants of Atherosclerosis in Youth (PDAY) score and other potential cardiovascular disease risk factors in adolescents previously enrolled in the Children with HIV Early antiRetroviral (CHER) and International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1060 clinical trials. METHODS: Coronary artery and abdominal aorta (AA) PDAY scores were calculated for 56 participants over 15 years of age using a weighted combination of dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. A PDAY score ≥1 is associated with early atherosclerosis. RESULTS: Fifty-six participants were enrolled: 46 (82.1%) on a single-tablet regimen of tenofovir disoproxil fumarate, lamivudine and dolutegravir. Median time on antiretroviral therapy was 15.8 [interquartile range (IQR): 15.8-16.5] years and median time on dolutegravir was 14 (IQR: 10.0-19.0) months. Fasting median high-density lipoprotein cholesterol was 20.1 mg/dL (IQR: 16.0-23.7) and median non-high-density lipoprotein cholesterol was 38.3 mg/dL (IQR: 30.8-44.3). The median systolic blood pressure was 115 mm Hg (IQR: 107-121). Median body mass index was 21.3 kg/m 2 (IQR: 19.5-24.7) and median fasted serum glucose was 82.0 mg/dL (IQR: 75.7-87.3). Only 1 (2%) participant smoked cigarettes, but 5 (9%) smoked hookah pipe and 26 (46.4%) smoked cannabis. Thirty-one (55.4%) participants had coronary artery PDAY scores ≥1 and 33 (58.9%) had AA PDAY scores ≥1. Age was associated with an AA PDAY score ≥1 ( P = 0.02) with a 0.06 increase in AA PDAY score for every month of age (95% confidence interval: 0.01-0.12, P = 0.01). CONCLUSIONS: Adolescents with perinatally acquired HIV appear at risk for cardiovascular disease. Specific tools for monitoring this risk are needed to institute appropriate preventive interventions.

Interventional bronchoscopy in pediatric pulmonary tuberculosis.

INTRODUCTION: Lymphobronchial tuberculosis (TB) is common in children with primary TB and enlarged lymph nodes can cause airway compression of the large airways. If not treated correctly, airway compression can result in persistent and permanent parenchymal pathology, as well as irreversible lung destruction. Bronchoscopy was originally used to collect diagnostic samples; however, its role has evolved, and it is now used as an interventional tool in the diagnosis and management of complicated airway disease. Endoscopic treatment guidelines for children with TB are scarce. AREAS COVERED: The role of interventional bronchoscopy in the diagnosis and management of complicated pulmonary TB will be discussed. This review will provide practical insights into how and when to perform interventional procedures in children with complicated TB for both diagnostic and therapeutic purposes. This discussion incorporates current scientific evidence and refers to adult literature, as some of the interventions have only been done in adults but may have a role in children. Limitations and future perspectives will be examined. EXPERT OPINION: Pediatric pulmonary TB lends itself to endoscopic interventions as it is a disease with a good outcome if treated correctly. However, interventions must be limited to safeguard the parenchyma and prevent permanent damage.

A descriptive study of vancomycin use at Red Cross War Memorial Children's Hospital, Cape Town.

Background: Antimicrobial stewardship principles guide the clinical use of antimicrobials, including vancomycin, but paediatric vancomycin prescribing practices have not been evaluated in South Africa. Objectives: To document the use, prescribing practices and monitoring of intravenous vancomycin and the spectrum of bacteria isolated on microbiological culture in children treated with intravenous vancomycin during a 12-month period at Red Cross War Memorial Children's Hospital (RCWMCH). Method: A retrospective audit of intravenous vancomycin use in children admitted to RCWMCH during 2019 was performed. Results: All 158 vancomycin prescription episodes for 143 children were included. Overall usage of intravenous vancomycin was 63 days of therapy per 1000 patient days (interquartile range [IQR]: 38-72). The median starting dose was 15 mg/kg per dose (IQR: 14-15) and median daily dose was 45 mg/kg per day (IQR: 43-60). Vancomycin was prescribed as empiric (127/158, 80%) and directed (31/158, 20%) treatment. The median duration of treatment for the directed group (7 days) was longer than the empiric group (4 days) (p = 0.001). Vancomycin serum trough concentrations were performed in 65/98 (66%) episodes where vancomycin treatment exceeded 3 days, with only 16/65 (25%) of these samples obtained before the fourth dose. Prolonged antibiotic treatment of 14 days or more was not associated with Gram-positive bacteria on culture (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 0.17-4.2). Conclusion: Dosing errors, prolonged empiric treatment and inappropriate vancomycin monitoring were problems associated with vancomycin prescriptions. Contribution: The study identified multiple opportunities for improved vancomycin prescribing and monitoring. Further research and implementation of improved prescribing practices could contribute to the preservation of vancomycin as an effective antibiotic.

Descriptive analysis of infections due to New Delhi metallo-ß-lactamase-producing Enterobacterales in children at Red Cross War Memorial Children's Hospital.

The increased incidence and absence of antibiotic treatment options for New Delhi metallo-ß-lactamase (NDM)-producing carbapenem-resistant Enterobacterales (CRE) infection are concerning. Recent reports have highlighted NDM-producing Serratia marcescens, as a specific concern, as it is an organism which is intrinsically resistant to colistin. In this study, a descriptive analysis of NDM-producing CRE infections was performed at the Red Cross War Memorial Children's Hospital.

The Outcome of Accidental Bacille Calmette-Guérin Overdose During Routine Neonatal Immunization.

We report a retrospective study on outcome of 14 newborn infants who received 62.5 times the recommended dose of Bacille Calmette-Guérin for immunization. All infants then received high-dose isoniazid and rifampicin (20 mg/kg/d each) as preventive therapy for 6 months. All had mild local adverse reactions, a third resolving within 16 weeks and all by 6 months.