High incidence of tuberculosis in young children living with HIV in the Western Cape, South Africa.

Background: Data on tuberculosis (TB) incidence and risk factors among children living with HIV (CLHIV) in the universal ART era are limited.

Methods: We analysed routinely-collected data on TB diagnoses for CLHIV age ≤5 years, born 2018-2022, in the Westen Cape, South Africa. We examined factors associated with TB diagnosis, with death and loss to follow-up as competing events.

The pattern of childhood infections during and after the COVID-19 pandemic.

The rates of most paediatric infectious diseases declined during the initial phase of the COVID-19 pandemic due to the implementation of non-pharmaceutical interventions. However, after the gradual release of these interventions, resurgences of infections occurred with notable variations in incidence, clinical manifestations, pathogen strains, and age distribution. This Review seeks to explore these changes and the rare clinical manifestations that were made evident during the resurgence of known childhood infections.

HIV-associated tuberculosis in infants, children, and adolescents younger than 15 years: an update on the epidemiology, diagnosis, prevention, and treatment.

Purpose Of Review: HIV-associated tuberculosis (TB) remains a major driver of morbidity and mortality in children and adolescents younger than 15 years (CLWH). The purpose of this review is to highlight recent findings in the areas of prevention, diagnosis, and treatment of HIV-associated TB in CLWH and to highlight knowledge and implementation gaps.

Recent Findings: We found that despite access to antiretroviral therapy (ART), high rates of HIV-associated TB are still reported, and with an unacceptably high mortality.

COVID-19 in children: Clinical presentation and hospital course at a district hospital in South Africa.

Unlabelled: Limited data exist on South African children hospitalised with COVID-19 in district hospitals. We describe the presentation and outcomes of children admitted to a level 1 and 2 hospital and compare this with children admitted to a level 2 and 3 hospital.

Contribution: This study highlights that young age is an important risk factor for hospitalisation with severe COVID-19.

The socioeconomic impact of the COVID-19 lockdown on families affected by childhood respiratory illnesses in Cape Town, South Africa.

The COVID-19 pandemic impacted families globally, directly and indirectly. Children presenting with respiratory illnesses are affected by emerging health systems and socioeconomic changes in the COVID-19 era. We explored the socioeconomic impacts of the COVID-19 lockdown on families with a respiratory illness diagnosed in their child in Cape Town, South Africa.

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.

Self-transfers, Hospital Admissions and Mortality Among Children and Adolescents Lost to Follow-up From Antiretroviral Therapy Programs in the Western Cape, South Africa Between 2004 and 2019: Linkage to Provincial Records.

Background: Pediatric programs face a high rate of loss to follow-up (LTFU) among children and adolescents living with HIV (CAHIV). We assessed true outcomes and predictors of these among CAHIV who were LTFU using linkage to the Western Cape Provincial Health Data Centre at Western Cape sites of the International epidemiology Databases to Evaluate AIDS-Southern Africa collaboration.

Methods: We examined factors associated with self-transfer, hospital admission and mortality using competing risks regression in a retrospective cohort of CAHIV initiating antiretroviral therapy <15 years old between 2004 and 2019 and deemed LTFU (no recorded visit at the original facility for ≥180 days from the last visit date before database closure and not known to have officially transferred out or deceased).

Paediatric abacavir-lamivudine fixed-dose dispersible tablets and ritonavir-boosted lopinavir granules in neonates exposed to HIV (PETITE study): an open-label, two-stage, single-arm, phase 1/2, pharmacokinetic and safety trial.

Background: Existing solid antiretroviral fixed-dose combination formulations are preferred over liquid formulations in children, but their suitability for neonates is unknown. We evaluated the pharmacokinetics and safety of paediatric abacavir-lamivudine fixed-dose dispersible tablets and ritonavir-boosted lopinavir granules in neonates.

Methods: In this open-label, two-stage, single-arm, phase 1/2, pharmacokinetic and safety trial, generic abacavir- lamivudine (120:60 mg) double-scored dispersible tablets and lopinavir boosted with ritonavir (40:10 mg) granules were studied.

Safety and Pharmacokinetics of Lopinavir/Ritonavir Oral Solution in Preterm and Term Infants Starting Before 3 Months of Age.

Background: Study of liquid lopinavir/ritonavir (LPV/r) in young infants has been limited by concerns for its safety in neonates.

Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1106 was a phase IV, prospective, trial evaluating the safety and pharmacokinetics of antiretroviral medications administered according to local guidelines to South African preterm and term infants <3 months of age. Safety evaluation through 24-week follow-up included clinical, cardiac and laboratory assessments.

Perinatal tuberculosis-An approach to an under-recognized diagnosis.

Tuberculosis (TB) in young infants (<3 months of age), often referred to as perinatal TB, is underdiagnosed, leading to severe morbidity and high mortality. Perinatal TB includes both congenital and postnatal transmission of . We aimed to increase an awareness of TB in neonates and young infants and to provide guidance on the assessment and management when in contact with mothers with TB during or soon after pregnancy.

Evaluating pediatric tuberculosis dosing guidelines: A model-based individual data pooled analysis.

Background: The current World Health Organization (WHO) pediatric tuberculosis dosing guidelines lead to suboptimal drug exposures. Identifying factors altering the exposure of these drugs in children is essential for dose optimization. Pediatric pharmacokinetic studies are usually small, leading to high variability and uncertainty in pharmacokinetic results between studies.

COVID-19 lockdown effect on healthcare utilization and in-hospital mortality in children under 5 years in Cape Town, South Africa: a cross-sectional study.

Background: COVID-19 pandemic measures resulted in the de-escalation of non-COVID-19 healthcare provision.

Methods: A retrospective cross-sectional study of routinely collected data was done to investigate the effect of COVID-19 policies on the healthcare utilization and mortality of children younger than 5 years in Eastern Cape Town, South Africa. We compared visits to primary and urgent care facilities, hospitalization, in-hospital deaths, and vaccine uptake from 1 January to 31 December 2020 to similar periods in 2018 and 2019.

Resurgence of congenital syphilis: new strategies against an old foe.

Congenital syphilis is a major global cause of fetal loss, stillbirth, neonatal death, and congenital infection. In 2020, the global rate of congenital syphilis was 425 cases per 100 000 livebirths-substantially higher than WHO's elimination target of 50 cases per 100 000 livebirths. Case rates are rising in many high-income countries, but remain low compared with those in low-income and middle-income settings.

Pharmacokinetics, safety, and tolerability of dispersible and immediate-release abacavir, dolutegravir, and lamivudine tablets in children with HIV (IMPAACT 2019): week 24 results of an open-label, multicentre, phase 1-2 dose-confirmation study.

Background: Child-friendly fixed-dose combination (FDC) antiretroviral therapy (ART) options are limited. We evaluated the pharmacokinetics, safety, and tolerability of dispersible and immediate-release FDC abacavir, dolutegravir, and lamivudine taken once per day in children younger than 12 years with HIV.

Methods: IMPAACT 2019 was an international, phase 1-2, multisite, open-label, non-comparative dose-confirmation study of abacavir, dolutegravir, and lamivudine in children younger than 12 years.

Short-term outcomes of South African children with multisystem inflammatory syndrome in children: a prospective cohort study.

Background: Despite the life-threatening presentation of multisystem inflammatory syndrome in children (MIS-C), the overall prognosis is favourable in centres with access to appropriate supportive care. In this study, we investigate the short-term outcomes in children with MIS-C in Cape Town, South Africa.

Methods: This prospective observational cohort study included children <13 years who fulfilled the WHO case definition of MIS-C and were admitted to Tygerberg Hospital in Cape Town, South Africa between 1 June 2020 and 31 October 2021.

Recurrent Tuberculosis Treatment Episodes in Children Presenting With Presumptive Pulmonary Tuberculosis in Cape Town, South Africa.

Background: Limited data are available on tuberculosis (TB) recurrence in children. The aim of this study was to explore the burden of and risk factors for recurrent TB treatment in children.

Methods: A prospective, observational cohort study of children (0-13 years) presenting with presumptive pulmonary TB in Cape Town, South Africa from March 2012 to March 2017.

Clinical Presentation and Outcome of Acute Respiratory Illnesses in South African Children During the COVID-19 Pandemic.

Background: Data from low- and middle-income countries (LMICs) show higher morbidity and mortality in children with acute respiratory illness (ARI) from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, whether SARS-CoV-2 infection is distinct from other causes of ARI in this regard is unclear. We describe clinical characteristics and outcomes of South African children with SARS-CoV-2 and non-SARS-CoV-2 ARIs.