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Background: Infancy is an important developmental period when the microbiome is shaped. We hypothesized that earlier antiretroviral therapy (ART) initiation would attenuate HIV effects on microbiota in the mouth., Methods: Oral swabs were collected from 477 children with HIV (CWH) and 123 children without (controls) at two sites in Johannesburg, South Africa. CWH had started ART less than 3 years of age; 63% less than 6 months of age. Most were well controlled on ART at median age 11 years when the swab was collected. Controls were age-matched and recruited from the same communities. Sequencing of V4 amplicon of 16S rRNA was done. Differences in microbial diversity and relative abundances of taxa were compared between the groups., Results: CWH had lower alpha diversity than controls. Genus-level abundances of Granulicatella, Streptococcus, and Gemella were greater and Neisseria and Haemophilus less abundant among CWH than controls. Associations were stronger among boys. Associations were not attenuated with earlier ART initiation. Shifts in genus-level taxa abundances in CWH relative to controls were most marked in children on lopinavir/ritonavir regimens, with fewer shifts seen if on efavirenz ART regimens., Conclusion: A distinct profile of less diverse oral bacterial taxa was observed in school-aged CWH on ART compared with uninfected controls suggesting modulation of microbiota in the mouth by HIV and/or its treatments. Earlier ART initiation was not associated with microbiota profile. Proximal factors, including current ART regimen, were associated with contemporaneous profile of oral microbiota and may have masked associations with distal factors such as age at ART initiation., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: This study aimed to investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell responses 14 days after single-dose ChAdOx1 nCoV-19 (AZD1222) vaccination in black Africans with and without HIV in South Africa, as well as determine the effect of AZD1222 vaccination on cell-mediated immune responses in people with HIV (PWH) with prior SARS-CoV-2 infection., Methods: A total of 70 HIV-uninfected people and 104 PWH were prospectively enrolled in the multicentre, randomized, double-blinded, placebo-controlled, phase Ib/IIa trial (COV005). Peripheral blood mononuclear cells (PBMCs) were collected from trial participants 14 days after receipt of first dose of study treatment (placebo or AZD1222 vaccine). T-cell responses against the full-length spike (FLS) glycoprotein of wild-type SARS-CoV-2 and mutated S-protein regions found in the Alpha, Beta and Delta variants were assessed using an ex-vivo ELISpot assay., Results: Among AZD1222 recipients without preceding SARS-CoV-2 infection, T-cell responses to FLS of wild-type SARS-CoV-2 were similarly common in PWH and HIV-uninfected people (30/33, 90.9% vs. 16/21, 76.2%; P = 0.138); and magnitude of response was similar among responders (78 vs. 56 SFCs/106 PBMCs; P = 0.255). Among PWH, AZD1222 vaccinees with prior SARS-CoV-2 infection, displayed a heightened T-cell response magnitude compared with those without prior infection (186 vs. 78 SFCs/106 PBMCs; P = 0.001); and similar response rate (14/14, 100% vs. 30/33, 90.9%; P = 0.244)., Conclusion: Our results indicate comparable T-cell responses following AZD1222 vaccination in HIV-uninfected people and PWH on stable antiretroviral therapy. Our results additionally show that hybrid immunity acquired through SARS-CoV-2 infection and AZD1222 vaccination, induce a heightened T-cell response., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: This study aimed to describe changes in pediatric emergency department (ED) mental and behavioral health (MBH) visits before and during the early COVID-19 pandemic., Methods: We retrospectively reviewed medical records of patients aged from 5 to 17 years presenting to the pediatric ED of a major tertiary care hospital with MBH-related concerns from March 2017 to September 2020. We evaluated trends in MBH ED visits over the study period, specifically comparing patient demographics, diagnosis categories, and ED disposition between the pre-COVID (2019) and COVID (2020) periods using pairwise Pearson χ 2 analyses with reported odds ratios (ORs) in SAS statistical software version 9.4 (SAS Institute Inc, Cary, NC)., Results: Of 8093 MBH-related visits, 58.5% were females, 85.4% were adolescents, and 62.7% self-identified as non-Hispanic. The proportion of MBH-related ED visits increased from 3.8% to 7.5% over the study period ( P < 0.0001). Although total MBH visits decreased by 17.3% from 2019 to 2020, there was a proportionate increase in MBH-to-total-ED visits, representing a 42.8% increase through 2019. Compared with 2019, there was a proportionate increase in MBH-related ED visits by females (10.6%, P < 0.0001), older adolescents (18.2%, P < 0.0001), and non-Hispanic patients (6.1%, P = 0.017) in 2020. The MBH visits in 2020 were more likely related to suicidality/self-harm (OR, 1.2; confidence interval [CI], 1.1-1.4) or substance use (OR, 1.4; CI, 1.1-1.9). Compared with 2019, there were significantly higher odds of admission (OR, 1.6; CI, 1.3-2.1) or transfer for inpatient psychiatric care (OR, 1.8; CI, 1.6-2.1) in 2020., Conclusions: Our data suggest that the early COVID-19 pandemic had a significant impact on MBH-related ED visits. Compared with 2019, we observed a significant increase in the proportion of MBH-to-total-ED visits primarily affecting older adolescent, non-Hispanic girls with suicidality/self-harm and substance-related disorders in 2020, despite an overall decrease in the number of MBH visits during this period. There was also an increase in the proportion of visits resulting in admission or transfer for inpatient psychiatric care in 2020., Competing Interests: Disclosure: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Summary: Brain injury resulting in coma may evolve into a prolonged disorder of consciousness, including the vegetative and minimally conscious states. Early detection of emerging consciousness has positive prognostic significance, and improvement in consciousness at any point may indicate the potential for meaningful communication and environmental control. Despite the importance of accurate assessment of consciousness, research indicates that as many as 40% of patients with a disorder of consciousness may be assessed incorrectly. Assessment of consciousness is challenging for many reasons, including the fact that consciousness cannot be measured directly but must be inferred from patterns of behavioral activity, that many patients have confounding deficits and treatments that may mask consciousness, and that patient performance may be highly variable over time. In this manuscript, we discuss strategies for optimizing patient status during assessment and review a number of structured assessment approaches that can be used. The available assessment techniques vary in their length and cost, and the expertise required to use them. Which of these approaches is most applicable to a given acute or subacute setting will vary with the volume of patients with a disorder of consciousness and the available resources. Importantly, lack of consciousness in the acute setting should not be used to justify the withdrawal of care or denial of rehabilitation services., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Objective: We evaluated longitudinal trends and associations between bone mass, bone turnover and inflammatory markers among South African children living with HIV (CLHIV) and controls., Design: We previously reported decreased bone mass among CLHIV independent of marked inflammation and increased bone turnover. The goal of this study was to evaluate longitudinal changes in bone mass, bone turnover and inflammation over 2 years., Methods: Longitudinal analyses were conducted among 220 CLHIV and 220 controls. Anthropometric measurements, physical activity, antiretroviral regimen, virologic and immunologic status, whole body (WB) and lumbar spine (LS) bone mineral content (BMC) and bone mineral density (BMD) were collected (enrollment, 12 and 24 months). Bone turnover markers including C-telopeptide of type I collagen (CTx) and procollagen type I N-terminal propeptide (P1NP) and inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble CD14 and high-sensitivity C-reactive protein (hsCRP) were collected at enrollment and 24 months., Results: Compared with controls, CLHIV had significantly lower mean WB-BMC, WB-BMD, WB-BMC z scores, LS-BMC and LS-BMD as well as lower bone formation (P1NP) and resorption (CTx), and higher hsCRP and soluble CD14 over 24 months. CLHIV on efavirenz (EFV) had consistently lower TNF-alpha and IL-6 compared with those on ritonavir-boosted lopinavir (LPV/r) at all time points., Conclusion: Over 2 years of follow-up, South African CLHIV had persistently lower bone mass, bone turnover, and macrophage activation. Lower bone mass and higher pro-inflammatory cytokine profiles were consistently observed among those on LPV/r-based compared with EFV-based regimens., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Children with HIV (CHIV) have lifetime exposure to antiretrovirals (ART); therefore, optimizing their regimens to have the least impact on fat redistribution is a priority., Methods: This is a cross-sectional study of 219 perinatally infected CHIV and 219 HIV-uninfected controls from similar socioeconomic backgrounds in Johannesburg, South Africa. We compared total body and regional fat distribution in CHIV on suppressive ART regimens with controls and, among CHIV, between ritonavir-boosted lopinavir (LPV/r)-based and efavirenz (EFV)-based regimens., Results: The mean age of the 219 uninfected children (45% girls) and the 219 CHIV (48% girls) was 7.0 and 6.4 years, respectively. CHIV had lower adjusted total body fat (P = 0.005) and lower percentage fat at the trunk (P = 0.020), arms (P = 0.001), and legs (P < 0.001) than uninfected children. CHIV on LPV/r had similar body composition as those on EFV, except for arm fat mass (P = 0.030). When stratified by sex, girls with HIV on LPV/r had lower adjusted total (P = 0.007), trunk (P = 0.002), arms (P = 0.008), legs (P = 0.048) fat mass; trunk-to-total body fat (P = 0.044); and higher legs-to-total body fat (P = 0.011) than those on EFV., Conclusions: South African CHIV receiving ART had lower global and partial fat mass and percentage fat than healthy controls. In girls with HIV with sustained virologic suppression on ART, switching from LPV/r to EFV could attenuate fat mass loss, indicating that EFV-based regimen may be a better option in this group of individuals., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Kawasaki disease is an acute vasculitis syndrome that typically occurs in children aged 1 to 4 years. Because there is no specific diagnostic test for Kawasaki disease, the diagnosis is made clinically based on specific characteristic signs and symptoms. Cases in which patients fall outside of the typical age range are uncommon and often challenging to diagnose because they have atypical presentations. This is especially true in infants, who rarely meet all the clinical criteria required for diagnosis. Patients at the extremes of ages often have a delayed diagnosis, which can lead to worse cardiac outcomes. We describe the cases of a young infant and an older adolescent who present with Kawasaki disease. These cases illustrate the challenge of diagnosing Kawasaki disease in patients beyond the typical age range. Both patients were return visits to the emergency department after inpatient stays. When fever persists longer than 5 days, clinicians must have a high index of suspicion for Kawasaki disease in all pediatric age groups to prevent treatment delay and disease sequelae.

Background: Prompt initiation of antiretroviral therapy (ART) for HIV-infected infants is strongly recommended but diagnostic confirmation is important as committing children to life-long ART carries serious health and social implications., Methods: Two HIV-exposed infants in Johannesburg, South Africa were identified presenting with unusual trajectories of diagnostic nucleic acid amplification tests (NAAT) and viral load results., Results: Case 1 had repeat indeterminate NAAT results during the first 3 weeks of life; repeat testing thereafter was negative with undetectable viral load including after daily nevirapine prophylaxis ended. ART was not initiated at this time. Case 2 had a single positive NAAT result at 1 month of age that prompted initiation of ART. Subsequent results were negative and ART was discontinued. Repeat negative NAAT with viral load below the limit of quantification or undetectable continued to be obtained. Shortly after and around weaning, positive NAAT results with high viral load (7.1 and 6.03 log10 copies/ml for Cases 1 and 2, respectively) were observed in both children. Both mothers were treated with tenofovir, emtricitabine and efavirenz during breastfeeding. Testing with ultrasensitive assays on early samples conclusively revealed HIV-1 proviral DNA in Case 1. Testing with ultrasensitive assays after the early period but prior to weaning did not detect HIV in either infant., Conclusion: We hypothesize that breast milk from the mothers of these two rare cases had HIV-specific or nonspecific factors that led to the undetectable results in already infected infants until breastfeeding ended. Our results raise the importance of repeat testing of HIV-exposed breast-fed infants after complete cessation of all breastfeeding.

Objectives: The World Health Organization recommends that human immunodeficiency virus (HIV)-infected children increase energy intake and maintain a balanced macronutrient distribution for optimal growth and nutrition. Few studies have evaluated dietary intake of HIV-infected children in resource-limited settings., Methods: We conducted a cross-sectional analysis of the dietary intake of 220 perinatally HIV-infected children and 220 HIV-uninfected controls ages 5 to 9 years in Johannesburg, South Africa. A standardized 24-hour recall questionnaire and software developed specifically for the South African population were used to estimate intake of energy, macronutrients, and micronutrients. Intake was categorized based on recommendations by the World Health Organization and Acceptable Macronutrient Distribution Ranges established by the IOM., Results: The overall mean age was 6.7 years and 51.8% were boys. Total energy intake was higher in HIV-infected than HIV-uninfected children (1341 vs 1196 kcal/day, P = 0.002), but proportions below the recommended energy requirement were similar in the 2 groups (82.5% vs 85.2%, P = 0.45). Overall, 51.8% of the macronutrient energy intake was from carbohydrates, 13.2% from protein, and 30.8% from fat. The HIV-infected group had a higher percentage of their energy intake from carbohydrates and lower percentage from protein compared with the HIV-uninfected group. Intakes of folate, vitamin A, vitamin D, calcium, iodine, and selenium were suboptimal for both groups., Conclusions: Our findings suggest that the typical diet of HIV-infected children and uninfected children in Johannesburg, South Africa, does not meet energy or micronutrient requirements. There appear to be opportunities for interventions to improve dietary intake for both groups.

Objective: The report of the 'Mississippi baby' who was initiated on antiretroviral therapy (ART) within 30 h of birth and maintained viral suppression off ART for 27 months has increased interest in the timing of ART initiation early in life. We examined associations between age at ART initiation and virologic outcomes in five cohorts of HIV-infected infants and young children who initiated ART before 2 years of age in Johannesburg, South Africa., Methods: We compared those who initiated ART early (<6 months of age) and those who started ART late (6-24 months of age). Two primary outcomes were examined: initial response to ART in three cohorts and later sustained virologic control after achieving suppression on ART in two cohorts., Results: We did not observe consistent differences in initial viral suppression rates by age at ART initiation. Overall, initial viral suppression rates were low. Only 31, 40.1, and 26.5% of early-treated infants (<6 months of age) in the three cohorts, respectively, were suppressed less than 50 copies/ml of HIV RNA 6 months after starting ART. We did observe better sustained virologic control after achieving suppression on ART among infants starting ART early compared with late. Children who started ART early were less likely to experience viral rebound (>50 copies/ml or >1000 copies/ml) than children who started late in both cohorts., Conclusion: These findings provide additional support for early initiation of ART in HIV-infected infants., Competing Interests: The authors have no conflicts of interest to report.

Background: We investigate if switching from a ritonavir-boosted lopinavir (LPV/r)-based to an efavirenz-based antiretroviral therapy (ART) regimen is associated with beneficial bone development., Methods: The CHANGES Bone Study follows HIV-infected children who participated in a noninferiority randomized trial in Johannesburg, South Africa evaluating the safety and efficacy of preemptive switching to efavirenz (n = 106) compared with remaining on LPV/r (n = 113). HIV-uninfected children were also recruited. Whole-body and lumbar spine bone mineral content (BMC) were assessed by dual-energy X-ray absorptiometry at a cross-sectional visit. BMC Z-scores adjusted for sex, age, and height were generated. Physical activity and dietary intake were assessed. CD4 percentage and viral load were measured. We compared bone indices of HIV-infected with HIV-uninfected children and LPV/r with efavirenz by intent-to-treat., Results: The 219 HIV-infected (52% boys) and 219 HIV-uninfected (55% boys) children were 6.4 and 7.0 years of age, respectively. Mean ART duration for HIV-infected children was 5.7 years. Whole-body BMC Z-score was 0.17 lower for HIV-infected children compared with HIV-uninfected children after adjustment for physical activity, dietary vitamin D and calcium (P = 0.03). Whole-body BMC Z-score was 0.55 higher for HIV-infected children switched to efavirenz compared with those remaining on LPV/r after adjustment for physical activity, dietary vitamin D and calcium, CD4 percentage, and viral load (P < 0.0001)., Conclusion: South African HIV-infected children receiving ART have lower bone mass compared with HIV-uninfected controls. Accrued bone mass is positively associated with switching to efavirenz-based ART compared with remaining on LPV/r, providing additional rationale for limiting LPV/r exposure once viral suppression has been achieved.

A case of congenital defect in an abortus is described and the forensic implications of unawareness of childhood artefactual abnormalities which may appear to have a cryptogenic criminal etiology are reiterated. This is apparently the first case reported in which gastroschisis had been misconceived to be criminal abortion.