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Background and purposeConsiderable overlap exists in the MR imaging features of hypoglycemic injury and hypoxic-ischemic brain injury, with similar predilections for the occipital and parietal lobes. In partial, prolonged hypoxia-ischemia, there is cortical destruction at the interarterial watershed zones, and in concomitant hypoglycemia and hypoxia-ischemia, an exaggerated final common pathway injury occurs. We interrogated secondary white matter tract-based thalamic injury as a tool to separate pure injuries in each group.Materials and methodsA retrospective observational study of the MRIs of 320 children with a history of hypoxia-ischemia and/or hypoglycemia was undertaken with 3 major subgroups: 1) watershed-type hypoxic-ischemic injury, 2) neonatal hypoglycemia, and 3) both perinatal hypoxia-ischemia and proved hypoglycemia. Cerebral and thalamic injuries were assessed, particularly hyperintensity of the posterolateral margin of the thalami. A modified Poisson regression model was used to assess factors associated with such thalamic injury.ResultsParieto-occipital injuries occurred commonly in patients with hypoglycemia and/or hypoxia-ischemia. Eighty-five of 99 (86%) patients with partial, prolonged hypoxia-ischemia exhibited the thalamus L-sign. This sign was also observed in patients who had both hypoglycemia and hypoxia-ischemia, predominantly attributable to the latter. Notably, the risk of a thalamus L-sign injury was 2.79 times higher when both the parietal and occipital lobes were injured compared with when they were not involved (95% CI, 1.25-6.23; P = .012). The thalamus L-sign was not depicted in patients with pure hypoglycemia.ConclusionsWe propose the thalamus L-sign as a biomarker of partial, prolonged hypoxia-ischemia, which is exaggerated in combined hypoglycemic/hypoxic-ischemic injury.

Background: There is limited research that describes the growth trajectories of African children. The development of World Health Organization (WHO) growth standards considered a sample of children who lived in environments optimum for human growth. Aim: This study aimed to develop weight-for-age and height-for-age growth curves from the Zimbabwean 2018 National Nutrition Survey and compare them with the WHO growth standards. Setting: Study participants were recruited from all districts in Zimbabwe. Methods: Height-for-age and weight-for-age data collected from 32 248 children were used to develop the Zimbabwean references. Smooth growth curves (height, weight and body mass index [BMI]-for-age) were estimated with the Lambda Mu Sigma (LMS) method and compared with the WHO growth standards. Results: Zimbabwean children were shorter and weighed less in comparison with the WHO growth standards. The –2 standard deviation (s.d.) Z-score curves (height-for-age) for Zimbabwean children (boys and girls) were below the –1 s.d. Z-score curves of the WHO growth standards. The Zimbabwean Z-scores (BMI-for-age) values above –1 s.d. were significantly higher in comparison with the corresponding WHO growth standards. Conclusion: Utilising the WHO growth standards would diagnose a higher proportion of Zimbabwean children as stunted whilst underestimating the proportion at risk of obesity. The WHO growth standards lack a consideration of the geographical, economic, political and environmental constraints existing between countries.

Background. The co-occurrence of HIV infection and severe malnutrition contributes to high rates of morbidity and mortality among children in resource-limited settings. Lactose-free, ready-to-use therapeutic feeds (RUTFs) may be most appropriate in this population because of underlying mucosal damage secondary to inflammation and infection. Objectives. To describe the effect of lactose-free RUTFs on the growth parameters of severely malnourished HIV-infected children in Durban, South Africa (SA). Methods. This was a prospective, observational study of nutritional recovery in HIV-infected, severely malnourished children, aged 6 months to 5 years, who received lactose-free RUTFs following admission to King Edward VIII Hospital in Durban, SA. The primary outcome was nutritional recovery, defined as 15% weight gain from enrolment to end of study. Secondary outcomes included z-scores for weight-for-height, weight-for-age, height-for-age, triceps skinfold thickness (SFT) and subscapular SFT calculated at baseline and 7, 14, 30 and 45 days after admission. Univariate analysis was done to compare outcomes among antiretroviral therapy (ART)-naive and ART-experienced children; the effect of ART on nutritional recovery was evaluated in a logistic regression model. Results. A significant improvement in most nutritional parameters was found at 45 days; 59% of children attained nutritional recovery. There was no significant difference in the proportion of children reaching recovery based on ART status at admission (p=0.08). Conclusion. Lactose-free formula feeds may be an effective strategy for nutritional rehabilitation of severely malnourished and HIV-infected children in resource-limited settings. It remains to be determined how ART initiation affects nutritional recovery in these children. [ABSTRACT FROM AUTHOR]

Neisseria meningitidis is a rare cause of meningitis and septicaemia in the neonatal population. Meningococcal septicaemia in neonates is divided into early-onset infection (symptoms within seven days of life) and late-onset infection (8-30 days of life). Early-onset meningococcal infection is extremely rare. We report on a case of early-onset meningitis with septicaemia in a term male infant and provide a review of the literature. This case report highlights the importance of maintaining a high index of suspicion of sepsis in the neonate. [ABSTRACT FROM AUTHOR]

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1-2 trial involving healthy adults, the NVX-CoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARS-CoV-2 transmission.Methods: In this phase 2a-b trial in South Africa, we randomly assigned human immunodeficiency virus (HIV)-negative adults between the ages of 18 and 84 years or medically stable HIV-positive participants between the ages of 18 and 64 years in a 1:1 ratio to receive two doses of either the NVX-CoV2373 vaccine (5 μg of recombinant spike protein with 50 μg of Matrix-M1 adjuvant) or placebo. The primary end points were safety and vaccine efficacy against laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants without previous SARS-CoV-2 infection.Results: Of 6324 participants who underwent screening, 4387 received at least one injection of vaccine or placebo. Approximately 30% of the participants were seropositive for SARS-CoV-2 at baseline. Among 2684 baseline seronegative participants (94% HIV-negative and 6% HIV-positive), predominantly mild-to-moderate Covid-19 developed in 15 participants in the vaccine group and in 29 in the placebo group (vaccine efficacy, 49.4%; 95% confidence interval [CI], 6.1 to 72.8). Vaccine efficacy among HIV-negative participants was 60.1% (95% CI, 19.9 to 80.1). Of 41 sequenced isolates, 38 (92.7%) were the B.1.351 variant. Post hoc vaccine efficacy against B.1.351 was 51.0% (95% CI, -0.6 to 76.2) among the HIV-negative participants. Preliminary local and systemic reactogenicity events were more common in the vaccine group; serious adverse events were rare in both groups.Conclusions: The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, with higher vaccine efficacy observed among HIV-negative participants. Most infections were caused by the B.1.351 variant. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT04533399.). [ABSTRACT FROM AUTHOR]

Dolutegravir (DTG) is primarily metabolized by uridine diphosphate glucuronosyltransferases, forming the pharmacologically inactive DTG glucuronide (DTG-gluc). We described the dolutegravir metabolic ratio (DTG-MR; DTG-gluc AUC 0-24h divided by DTG AUC 0-24h ) in 85 children with HIV aged 3 months to 18 years receiving DTG in the CHAPAS-4 (ISRCTN22964075) and ODYSSEY (NCT02259127) trials. Additionally, we assessed the influence of age, body weight, nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbone, rifampicin use and kidney function on DTG-MR. The overall geometric mean (CV%) DTG-MR was 0.054 (52%). Rifampicin use was the only significant factor associated with DTG-MR (P < .001) in multiple linear regression. DTG-MR geometric mean ratio was 1.81 (95% CI: 1.57-2.08) for children while on vs. off rifampicin. This study showed that overall DTG-MR in children was similar to adults, unaffected by age or NRTI backbone, and increased with rifampicin co-administration. These findings support future paediatric pharmacokinetic modelling and extrapolation from adult data., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Antimicrobial resistance is a global threat in children, and the emergence of multi-drug-resistant organisms is of concern. This secondary analysis of an antimicrobial point prevalence survey (PPS) in children evaluates the impact of age on antimicrobial use. The mean antimicrobial prescriptions were assessed in neonates, infants, young children (1-5 years), school-going children (6-12 years), and adolescents (13-15 years) from a cross-sectional PPS at three academic hospitals between September 2021 and January 2022. Primary and secondary diagnoses, antibiotic type (World Health Organization AWaRe and Anatomical Therapeutic Chemical classifications), and the incidence of healthcare-associated infections (HAI) were evaluated per age category. Multiple regression models were used to analyse age-related risk factors for HAI. The number of antimicrobials per child (1.7-1.9 per patient) was higher in neonates and infants compared to children 6-12 years old (1.4 per patient). Watch antibiotics, especially carbapenems, were commonly prescribed in neonates (32.5%) and infants (42.2%). Reserve antimicrobial use was notable in neonates (4.7%) and infants (4.1%). The incidence risk ratio (IRR) of HAI was higher in neonates and infants (IRR 2.13; 95% CI 1.23-3.70, IRR 2.20; 95% CI 1.40-3.45, respectively) compared to 6- to 12-year-olds. On multivariate analysis of participants according to age, being HIV infected, length of stay >6 days, high McCabe severity score, having surgery and receipt of blood transfusion were associated with an increased risk of HAI (P < .001 for all) while on univariate analysis only, being premature and/or underweight was associated with an increased risk of HAI in infants (P < .001 for both). Infants with risk factors for HAI significantly influenced antimicrobial prescribing, underscoring the necessity for tailored antimicrobial stewardship and enhanced surveillance. The increased use of Watch antibiotics, particularly carbapenems, in infants warrants closer scrutiny. Further research is required to identify inappropriate antimicrobial use in high-risk hospitalized young children., (© The Author(s) [2024]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Analytical treatment interruption (ATI) is widely acknowledged as an essential component of studies to advance our understanding of HIV cure, but discussion has largely been focused on adults. To address this gap, we reviewed evidence related to the safety and utility of ATI in paediatric populations. Three randomised ATI trials using CD4 T-cell and clinical criteria to guide restart of antiretroviral therapy (ART) have been conducted. These trials found low risks associated with ATI in children, including reassuring findings pertaining to neurocognitive outcomes. Similar to adults treated during acute infection, infants treated early in life have shifts in virological and immunological parameters that increase their likelihood of achieving ART-free viral control. Early ART limits the size and diversity of the viral reservoir and shapes effective innate and HIV-specific humoral and cellular responses. Several cases of durable ART-free viral control in early treated children have been reported. We recommend that, where appropriate for the study question and where adequate monitoring is available, ATI should be integrated into ART-free viral control research in children living with HIV. Paediatric participants have the greatest likelihood of benefiting and potentially the most years to prospectively realise those benefits. Excluding children from ATI trials limits the evidence base and delays access to interventions., Competing Interests: Declaration of interests DP reports support from the National Institutes of Health (NIH), being the recipient of the 2023 Jonathan Lax Lectureship sponsored by the BEAT Martin Delaney Collaboratory and Wistar Institute in Philadelphia, and being on the scientific advisory board of ViiV Healthcare and the Elizabeth Glaser Pediatric AIDS Foundation. PP reports grant support from the NIH-Pediatric Adolescent Virus Elimination project (May, 2020, to May, 2025) and the National Institute of Allergy and Infectious Diseases ([NIAID] grant U01AI135941, Targeting HIV reservoirs in children with HIVIS-DNA and MVA-CMDR vaccines) and being a founder of Probiomics (Tor Vergata University of Rome). PRos reports consulting fees from Achilles Vaccines and being on the board of directors of the PENTA Foundation. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

After sporadic reports of post-treatment control of HIV in children who initiated combination anti-retroviral therapy (cART) early, we prospectively studied 284 very-early-cART-treated children from KwaZulu-Natal, South Africa, after vertical HIV transmission to assess control of viremia. Eighty-four percent of the children achieved aviremia on cART, but aviremia persisting to 36 or more months was observed in only 32%. We observed that male infants have lower baseline plasma viral loads (P = 0.01). Unexpectedly, a subset (n = 5) of males maintained aviremia despite unscheduled complete discontinuation of cART lasting 3-10 months (n = 4) or intermittent cART adherence during 17-month loss to follow-up (n = 1). We further observed, in vertically transmitted viruses, a negative correlation between type I interferon (IFN-I) resistance and viral replication capacity (VRC) (P < 0.0001) that was markedly stronger for males than for females (r = -0.51 versus r = -0.07 for IFN-α). Although viruses transmitted to male fetuses were more IFN-I sensitive and of higher VRC than those transmitted to females in the full cohort (P < 0.0001 and P = 0.0003, respectively), the viruses transmitted to the five males maintaining cART-free aviremia had significantly lower replication capacity (P < 0.0001). These data suggest that viremic control can occur in some infants with in utero-acquired HIV infection after early cART initiation and may be associated with innate immune sex differences., (© 2024. The Author(s).)

Vulnerable children from poor communities with high HIV and Tuberculosis(TB) burdens were impacted by COVID-19 lockdowns. Concern was raised about the extent of this impact and anticipated post-pandemic surges in mortality. Interrupted time series segmented regression analyses were done using routinely collected facility-level data of children admitted for medical conditions at four South African referral hospitals. Monthly admission and mortality data over 60 months from 01 April 2018 to 31 January 2023 was analysed using models which included dummy lockdown level variables, a dummy post-COVID period variable, Fourier terms to account for seasonality, and excess mortality as a proxy for healthcare burden. Of the 45 015 admissions analysed, 1237(2·75%) demised with significant decreases in admissions during all the lockdown levels, with the most significant mean monthly decrease of 450(95%, CI = 657·3, -244·3) p<0·001 in level 5 (the most severe) lockdown. There was evidence of loss of seasonality on a six-month scale during the COVID periods for all admissions (p = 0·002), including under-one-year-olds (p = 0·034) and under-five-year-olds (p = 0·004). No decreases in mortality accompanied decreased admissions. Post-pandemic surges in admissions or mortality were not identified in children with acute gastroenteritis, acute pneumonia and severe acute malnutrition.During the COVID-19 pandemic, paediatric admissions in 4 hospitals serving communities with high levels of HIV, TB and poverty decreased, similar to global experiences; however, there was no change in in-hospital mortality. No post-pandemic surge in admissions or mortality was documented. Differences in the impact of pandemic control measures on the transmission of childhood infections and access to health care may account for differing outcomes seen in our setting compared to the global experiences. Further studies are needed to understand the impact of pandemic control measures on healthcare provision and transmission dynamics and to better inform future responses amongst vulnerable child populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Naidoo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite advances in human immunodeficiency virus (HIV) prevention, new pediatric HIV infections continue, necessitating optimized and simplified antiretroviral treatment (ART) regimens tailored for children. Advances in treatment options have been made possible by the availability of child-friendly fixed-dose formulations with decreased dosing frequency, especially in low- and middle-income countries. Ongoing work to improve ART options for neonates and supporting the shift toward long-acting ART for children and adolescents remains a priority. Achieving the UNAIDS goal of 95:95:95 for children will require a comprehensive and holistic approach that addresses both the biomedical and social challenges of managing children with HIV., Competing Interests: Disclosure We wish to confirm that there are no known conflicts of interest associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Diphtheria is a life-threatening respiratory tract infection that causes outbreaks in susceptible populations. Between April and May 2018, an outbreak of diphtheria occurred in the eThekwini district. A school-based outbreak vaccination response was initiated to target vulnerable children and adolescents., Contribution: This study adds to the limited data describing a school-based vaccination in an outbreak response and highlights successes and challenges. School-based outbreak vaccination response can rapidly increase vaccine coverage; however, additional community engagement may be required in vaccine-hesitant populations., Competing Interests: The authors have declared that no competing interest exists., (© 2024. The Authors.)

Background: There is increasing interest in utilising two-drug regimens for HIV treatment with the goal of reducing toxicity and improve acceptability. The D3 trial evaluates the efficacy and safety of DTG/3TC in children and adolescents and includes a nested pharmacokinetics(PK) substudy for paediatric drug licensing., Methods: D3 is an ongoing open-label, phase III, 96-week non-inferiority randomised controlled trial(RCT) conducted in South Africa, Spain, Thailand, Uganda and the United Kingdom. D3 has enrolled 386 children aged 2- < 15 years, virologically suppressed for ≥6 months, with no prior treatment failure. Participants were randomised 1:1 to receive DTG/3TC or DTG plus two nucleoside reverse transcriptase inhibitors(NRTIs), stratified by region, age (2- < 6, 6- < 12, 12- < 15 years) and DTG use at enrolment (participants permitted to start DTG at enrolment). The primary outcome is confirmed HIV-1 RNA viral rebound ≥50 copies/mL by 96-weeks. The trial employs the Smooth Away From Expected(SAFE) non-inferiority frontier, which specifies the non-inferiority margin and significance level based on the observed event risk in the control arm. The nested PK substudy evaluates WHO weight-band-aligned dosing in the DTG/3TC arm., Discussion: D3 is the first comparative trial evaluating DTG/3TC in children and adolescents. Implications of integrating a PK substudy and supplying data for prompt regulatory submission, were carefully considered to ensure the integrity of the ongoing trial. The trial uses an innovative non-inferiority frontier for the primary analysis to allow for a lower-than-expected confirmed viral rebound risk in the control arm, while ensuring interpretability of results and maintaining the planned sample size in an already funded trial., Trial Registration: International Standard Randomised Clinical Trial Number Register: ISRCTN17157458. European Clinical Trials Database: 2020-001426-57., Clinicaltrials: gov: NCT04337450., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

We describe the results of a pilot randomized clinical trial of a mobile phone-based intervention, InTSHA: Interactive Transition Support for Adolescents with HIV, compared to standard care. Encrypted, closed group chats delivered via WhatsApp provided peer support and improved communication between adolescents with HIV, their caregivers, and healthcare providers. We randomized 80 South African adolescents ages 15 to 19 years with perinatally-acquired HIV to receive either the intervention (n=40) or standard of care (n=40). We measured acceptability (Acceptability of Intervention Measure [AIM]) and feasibility (Feasibility of Intervention Measure [FIM]) as primary outcomes. We evaluated impact on retention in care and viral suppression six months after randomization as secondary endpoints. We performed bivariable and multivariable analyses using logistic regression models to assess the effect of the InTSHA intervention compared to standard of care. Among the adolescents randomized to the InTSHA intervention, the median AIM was 4.1/5.0 (82%) and median FIM was 3.9/5.0 (78%). We found no difference in retention in care or in viral suppression comparing intervention and control groups. Among adolescents who attended three or more sessions, retention in care was 100% at 6 months. InTSHA is an acceptable and feasible mHealth intervention warranting further study in a larger population.

Antimicrobial resistance (AMR) poses a global threat, partly fueled by antimicrobial overuse. Paediatric inpatients are particularly vulnerable to infections, leading to high antimicrobial consumption. In low-to-middle income countries (LMICs) like South Africa, research on antimicrobial usage for neonatal and paediatric healthcare-associated infections (HAI) is limited. This cross-sectional study evaluated antimicrobial usage in three academic public sector hospitals in South Africa to improve appropriateness. 22.9% of hospitalised children received at least one prescribed antimicrobial, with neonates, infants, and adolescents having higher prescription rates for HAIs. Common antimicrobials prescribed included beta-lactamase sensitive penicillin, aminoglycosides, and carbapenems. Antimicrobial selection aligned with the WHO AWaRe classification system. HIV infection did not emerge as a risk factor for HAIs or excessive antimicrobial usage. The policy brief recommends several strategies, summarized by the acronym 'PRACTICE,' to optimize antimicrobial prescribing practices. These include implementing standardized policies for empiric antimicrobial use, routine review of antimicrobial therapy, age-specific antimicrobial stewardship programs, and continued collaborative efforts and research. Individualized treatment plans, improved infection prevention and control measures, ongoing surveillance, and exploring electronic technology for antimicrobial stewardship are also crucial. Addressing antimicrobial usage is imperative to combat the growing threat of AMR and improve patient outcomes in LMICs like South Africa.

Patterns of neonatal hypoxic-ischaemic brain injury (HIBI) are fairly well known. There are, however, other diagnoses with imaging patterns that may mimic HIBI. A review of MRI studies was conducted for children with suspected cerebral palsy, correlated with prior imaging, clinical details and laboratory tests where available. In the 63 identified cases, imaging features were, in many cases, very similar to the known patterns of HIBI. The alternative diagnoses can be classified as developmental, vascular, chromosomal, infections, metabolic disorders, and congenital syndromes. These findings are described in this pictorial essay. The potential mimickers of HIBI described in this essay can demonstrate similar imaging appearances to HIBI., Contribution: There are multiple possible causes of neonatal encephalopathy other than hypoxic-ischaemic encephalopathy. Many conditions may mimic HIBI, each of which can be associated with significant morbidity. It is prudent for the reporting radiologist to be aware of these alternate clinico-radiological diagnoses., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

Background: Injury patterns in hypoxic-ischaemic brain injury (HIBI) are well recognised but there are few studies evaluating cerebral injury using neuroquantification models., Objectives: Quantification of brain volumes in a group of patients with clinically determined cerebral palsy., Method: In this retrospective study, 297 children with cerebral palsy were imaged for suspected HIBI with analysis of various cerebral substrates. Of these, 96 children over the age of 3 years with a clinical diagnosis of cerebral palsy and abnormal MRI findings underwent volumetric analyses using the NeuroQuant ® software solution. The spectrum of volumetric changes and the differences between the various subtypes (and individual subgroups) of HIBI were compared., Results: Compared with the available normative NeuroQuant ® database, the average intracranial volume was reduced to the 1st percentile in all patient groups ( p < 0.001). Statistically significant differences were observed among the types and subgroups of HIBI. Further substrate volume reductions were identified and described involving the thalami, brainstem, hippocampi, putamina and amygdala. The combined volumes of five regions of interest (frontal pole, putamen, hippocampus, brainstem and paracentral lobule) were consistently reduced in the Rolandic basal ganglia-thalamus (RBGT) subtype., Conclusion: This study determined a quantifiable reduction of intracranial volume in all subtypes of HIBI and predictable selective cerebral substrate volume reduction in subtypes and subgroups. In the RBGT subtype, a key combination of five substrate injuries was consistently noted, and thalamic, occipital lobe and brainstem volume reduction was also significant when compared to the watershed subtype., Contribution: This study demonstrates the value of integrating an artificial intelligence programme into the radiologists' armamentarium serving to quantify brain injuries more accurately in HIBI. Going forward this will be an inevitable evolution of daily radiology practice in many fields of medicine, and it would be beneficial for radiologists to embrace these technological innovations., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2023. The Authors.)

Objectives: South Africa implemented a National Strategic Framework to optimise antimicrobial stewardship in 2014; however, there is limited data on how this has affected prescribing, especially to children treated in academic centres., Methods: We conducted a point prevalence survey using the World Health Organization (WHO) methodology to evaluate antibiotic and antifungal prescribing practices in paediatric departments at three academic hospitals in South Africa., Results: We recorded 1946 antimicrobial prescriptions in 1191 children, with 55.2% and 39.2% of the antibiotics classified as WHO AWaRe Access and Watch drugs, respectively. There were significant differences in prescription of Reserve antibiotics and antifungals between institutions. Receipt of WHO Watch and Reserve antibiotics was independently associated with infancy (<12 months) and adolescents (13-17 years) (adjusted relative risk [aRR]: 2.09-9.95); prolonged hospitalisation (aRR: 3.29-30.08); rapidly or ultimately fatal illness (aRR: 1.94 to 5.52); and blood transfusion (aRR: 3.28-5.70). Antifungal prescribing was associated with treatment of hospital-associated infection (aRR: 2.90), medical prophylaxis (aRR: 3.30), and treatment in intensive care units (aRR: 2.15-2.27)., Conclusions: Guidance on optimisation of infection prevention and control practice and strengthening of antimicrobial stewardship would impact positively on the care of sick children in our setting., Competing Interests: DPM was, in part, supported by a grant awarded by the Carnegie Corporation of New York. For the remaining authors none were declared., (© 2023 The Author(s).)

Background: The prevalence of antimicrobial prescriptions for healthcare-associated infections (HAI) in South Africa is largely unknown. This study aimed to estimate the point prevalence of pediatric antibiotic and antifungal usage in 3 South African academic hospitals., Methods: This cross-sectional study included hospitalized neonates and children (0-15 years). We used the World Health Organization methodology for antimicrobial point prevalence studies, with weekly surveys to achieve a sample size of ~400 at each site., Results: Overall, 1,946 antimicrobials were prescribed to 1,191 patients. At least 1 antimicrobial was prescribed for 22.9% [95% confidence interval (CI): 15.5-32.5%] of patients. The prevalence of antimicrobial prescribing for HAI was 45.6%. In the multivariable analysis, relative to children 6-12 years, neonates [adjusted relative risk (aRR): 1.64; 95% CI: 1.06-2.53], infants (aRR: 1.57; 95% CI: 1.12-2.21) and adolescents (aRR: 2.18; 95% CI: 1.45-3.29) had significantly increased risk of prescriptions for HAI. Being preterm (aRR: 1.33; 95% CI: 1.04-1.70) and underweight (aRR: 1.25; 95% CI: 1.01-1.54) was predictive of antimicrobial usage for HAI. Having an indwelling device, surgery since admission, blood transfusions and classification as rapidly fatal on McCabe score also increased the risk of prescriptions for HAI., Conclusions: The high prevalence of antimicrobial prescribing for HAI to treat children with recognized risk factors in academic hospitals in South Africa is concerning. Concerted efforts need to be made to strengthen hospital-level infection prevention and control measures, with a critical review of antimicrobial usage through functional antibiotic stewardship programs to preserve the available antimicrobial armamentarium at the hospital level., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

South Africa has the highest burden of adolescents living with HIV (ALHIV) in the world. The transition from pediatric to adult centered HIV care is a vulnerable period during which many clinical outcomes of ALHIV suffer. Transition readiness assessments may help ALHIV transition from pediatric to adult care to improve their health outcomes. Here, we evaluated the perceived acceptability and feasibility of a mobile health (mHealth) application, eHARTS, to determine transition readiness for ALHIV in South Africa. We conducted in-depth interviews with adolescents (n = 15) and healthcare providers (n = 15) at three government-supported hospitals in KwaZulu-Natal, South Africa. We used a semi-structured interview guide comprising of open-ended questions based on the unified theory of acceptance and use of technology. We did a thematic analysis of the data using an iterative, team-based coding approach to develop themes that were representative of the participants' perspectives on the acceptability and feasibility of eHARTS. We found that most participants found eHARTS to be acceptable because of its simplicity and lack of stigma. Participants believed eHARTS was feasible as it could easily be administered within a hospital setting and integrated into regular clinic activity without disrupting patient care. Additionally, eHARTS was found to have great utility for adolescents and healthcare providers. Clinicians saw it as a valuable tool to engage adolescents and prepare them for transition. Despite concerns that eHARTS may give adolescents a wrong impression about immediate transition, participants suggested that eHARTS be framed in an empowering way as they prepare for transition to adult care. Our data showed that eHARTS is a simple, mobile transition assessment tool with perceived acceptability and feasibility for use in HIV clinics in South Africa for ALHIV. It is particularly useful for ALHIV and transitioning to adult care as it can help identify gaps in readiness for transition., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fomo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Intramuscular injection of long-acting cabotegravir and rilpivirine is a novel, long-acting antiretroviral therapy (ART) combination approved for use as a fully suppressive regimen for people living with HIV. Long-acting cabotegravir with rilpivirine ART has reduced required dosing frequency from once daily to once every month or every 2 months injections. This new era of long-acting ART, which includes other antiretrovirals and formulations in various stages of clinical development, holds tremendous promise to change the standard of HIV treatment. Although long-acting ART has high potential to be revolutionary in the landscape of HIV care, prevention, and treatment cascade, more data are needed to substantiate its efficacy and cost-effectiveness among patients at risk of non-adherence and across age groups, pregnancy, and post partum. Advocacy efforts and policy changes to optimise a sustained, high-quality, equitable reach of long-acting ART, especially in low-income and middle-income countries where most people living with HIV reside, are needed to realise the full benefits of long-acting ART., Competing Interests: Declaration of interests RKS reports investigator-sponsored research awards from Gilead Science and ViiV Healthcare; and awards managed by MedStar Health Research Institute. KKS reports investigator-initiated research funding paid to her institution from Organon. LMM reports funding from ViiV Healthcare provided to the Elizabeth Glaser Pediatric AIDS Foundation for a birth outcomes surveillance project in Eswatini; and serving as a paid consultant to WHO on the safety of antiretroviral drugs in pregnancy. JWM is a consultant to Gilead Sciences and a grant recipient from Gilead Sciences to the University of Pittsburgh. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Adolescents and young adults (AYA) in low to middle income countries (LMIC) have poorer outcomes along each step in the HIV continuum of prevention and care compared to younger children or older adults. The use of mHealth technology provides a potentially promising implementation strategy for interventions to remedy these disparities. We therefore conducted a systematic review of the English literature and conference proceedings from January 1, 2000 to April 1, 2021 evaluating mHealth interventions targeting AYA along each step of the HIV continuum of care in LMIC. We identified 27 mHealth interventions across the HIV continuum, with no interventions addressing transition from pediatric to adult care. The majority of studies were single arm, uncontrolled or underpowered, with few randomized trials resulting in mixed and inconclusive outcomes. mHealth interventions have potential to remedy disparities along the HIV continuum of care for AYA in LMIC but larger, powered randomized trials are needed., (© 2022. The Author(s).)

Introduction: Maternal antiretroviral therapy (ART) with viral suppression prior to conception, during pregnancy and throughout the breastfeeding period accompanied by infant postnatal prophylaxis (PNP) forms the foundation of current approaches to preventing vertical HIV transmission. Unfortunately, infants continue to acquire HIV infections, with half of these infections occurring during breastfeeding. A consultative meeting of stakeholders was held to review the current state of PNP globally, including the implementation of WHO PNP guidelines in different settings and identifying the key factors affecting PNP uptake and impact, with an aim to optimize future innovative strategies., Discussion: WHO PNP guidelines have been widely implemented with adaptations to the programme context. Some programmes with low rates of antenatal care attendance, maternal HIV testing, maternal ART coverage and viral load testing capacity have opted against risk-stratification and provide an enhanced PNP regimen for all infants exposed to HIV, while other programmes provide infant daily nevirapine antiretroviral (ARV) prophylaxis for an extended duration to cover transmission risk throughout the breastfeeding period. A simplified risk stratification approach may be more relevant for high-performing vertical transmission prevention programmes, while a simplified non-risk stratified approach may be more appropriate for sub-optimally performing programmes given implementation challenges. In settings with concentrated epidemics, where the epidemic is often driven by key populations, infants who are found to be exposed to HIV should be considered at high risk for HIV acquisition. All settings could benefit from newer technologies that promote retention during pregnancy and throughout the breastfeeding period. There are several challenges in enhanced and extended PNP implementation, including ARV stockouts, lack of appropriate formulations, lack of guidance on alternative ARV options for prophylaxis, poor adherence, poor documentation, inconsistent infant feeding practices and in inadequate retention throughout the duration of breastfeeding., Conclusions: Tailoring PNP strategies to a programmatic context may improve access, adherence, retention and HIV-free outcomes of infants exposed to HIV. Newer ARV options and technologies that enable simplification of regimens, non-toxic potent agents and convenient administration, including longer-acting formulations, should be prioritized to optimize the effect of PNP in the prevention of vertical HIV transmission., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Objective: Stunted children have an increased risk of diminished cognitive development, diabetes, degenerative and CVD later in life. Numerous modifiable factors decrease the risk of stunting in children. This study aimed to assess the role of the individual, household and social factors on stunting in Zimbabwean children., Design: A 1:2 unmatched case-control study., Setting: This study was conducted in two predominantly rural provinces (one with the highest national prevalence of stunting and one with the lowest prevalence) in Zimbabwe., Participants: Data were obtained from the caregivers of 150 children aged between 6 and 59 months with stunting and from the caregivers of 300 children without stunting., Results: Multiple (39) correlates of stunting were identified. Child's age, birth length, birth weight, and weight-for-age outcome (child-related factors), caregiver's age, maternal HIV status, occupation, and education (parental factors), breast-feeding status, number of meals, and dietary quality (dietary factors), child's appetite, diarrhoeal and worm infection (childhood illnesses), income status, access to safe water, access to a toilet, health clubs and maternal support in infant feeding (household, socio-cultural factors) were all found to be significant predictors of childhood stunting., Conclusion: Nearly all aspects under review from the individual-, household- to social-level factors were significantly associated with childhood stunting. These findings add to the growing body of evidence supporting the WHO stunting framework and strengthen the need to focus interventions on a multi-sectoral approach to effectively address stunting in high prevalence countries.