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Introduction: People living with HIV (PLWH) have higher rates of non-infectious comorbid diseases (NCDs) than individuals without HIV. We characterized the risk of NCDs among PLWH with undetectable viral load and persistent low-level viraemia (pLLV) in the African Cohort Study (AFRICOS). We secondarily quantified the role of immune activation in the association between LLV and NCDs., Methods: AFRICOS enrols participants in 12 clinics in Uganda, Kenya, Tanzania and Nigeria. Participants on antiretroviral therapy ≥ 6 months without an NCD at enrolment were included. PLLV was defined as at least two consecutive visits with a detectable viral load <1000 copies/ml. We examined elevated blood pressure, hypercholesterolemia, hyperglycaemia, renal insufficiency and a composite variable of any NCD. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard modelling. Among a subset of participants with biomarker data, we assessed the interaction between viral load and 13 biomarkers in the association with any NCD., Results: From 23 January 2013 to 1 December 2022, 1755 participants met the inclusion criteria for these analyses. At the first eligible visit, the majority of participants had an undetectable viral load (n = 1375, 78.35%). Participants with pLLV had an increased rate of developing any NCD (aHR: 1.22, 95% CI: 1.02-1.47) compared to participants with an undetectable viral load. There was a statistically significant interaction between LLV and TNF-α, CCL2/MCP-1 and TNF-RII in the association with any NCD., Conclusions: PLLV was significantly associated with NCDs and immune inflammation in this population. Aggressive management of LLV may positively impact NCDs in PLWH., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Background and Objectives: Parents and siblings of very low birth weight, premature infants are at risk for poor mental health outcomes with increased mental health care usage. Knowledge regarding mental health care use patterns could guide interventions., Methods: This retrospective cohort study included US families with commercial insurance coverage from a single carrier. Neonates born at ≤30 weeks' gestational age or with a birth weight <1500 g were identified by insurance claim data between July 1, 2015, and June 30, 2016. Each case neonate family was matched with up to 4 control families., Results: The study included 1209 case and 1884 control neonates (with 134 deaths among only the case neonates [11.1% of cases]); 2003 case and 3336 control parents (mean [SD] age, 34.6 [5.4] years; 2858 [53.5%] female); and 884 case and 1878 control siblings (mean [SD] age, 6.8 [5.5] years; 1375 [49.8%] female). Compared with controls, more case parents used mental health care over the first year after birth hospitalization discharge. Higher usage was observed for bereaved case parents soon after their child's death. A smaller proportion of bereaved case siblings received mental health care compared with controls. Although nonbereaved case parents returned toward the proportion of use observed in controls, nonbereaved case female siblings, bereaved case female and male siblings, and bereaved male parents experienced continued differences., Conclusions: Understanding and meeting the mental health care needs of parents and siblings of very low birth weight premature neonates can be guided by these findings, including elevated and prolonged needs of bereaved parents and siblings., (Copyright © 2024 by the American Academy of Pediatrics.)

Prenatal exposure to inflammation is related to the risk for cognitive impairment in offspring. However, mechanisms underlying the link between inflammatory cytokines at the maternal-fetal interface and human cognitive development are largely unknown. This study addressed this research gap by examining whether i) cytokines within the placenta are associated with different domains of neurocognitive development during infancy, and ii) if DHEA-S in cord blood mediates these associations. We also explored the role of early-life socioeconomic status (SES) in moderating the effect of fetal adrenal steroids on cognitive development in low- and middle-income country contexts. A cohort of 242 mother-infant dyads in Leyte, the Philippines participated in the study and all of them were followed from early pregnancy until 12-months. Concentrations of pro- and anti-inflammatory cytokines in the placenta, and DHEA-S in cord blood collected at delivery were evaluated. The multifactorial aspects of the infant's cognitive functioning were assessed based on the Bayley Scales of Infant Development, third edition (BSID-III). We used Structural Equation Modelling (SEM) with an orthogonal rotation to examine associated paths among latent variables of pro- and anti-inflammatory cytokines in the placenta, fetal neuroendocrine factors, and cognitive development. Pathway analyses showed that both pro- and anti-inflammatory cytokines in the placenta were indirectly related to cognitive (p < 0.05) and language developmental outcomes (p < 0.1) via DHEA-S in cord blood among the low SES group. Yet, we found no statistically significant indirect effect of pro- or anti-inflammatory cytokines on neurocognitive development among the high SES sub-sample. This study extends our understanding of how early-life socioeconomic conditions modify biological pathways underlying the relationship between prenatal factors and postpartum cognitive development., 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 © 2024 Elsevier Inc. All rights reserved.)

Objective: Poor intrauterine growth has negative impacts for child growth and development and disproportionately affects children living in low-resource settings. In the present study, we investigated relationships between placental pathologies and indicators of poor intrauterine growth., Methods: We enrolled a longitudinal cohort of 279 mother-infant pairs from Leyte, the Philippines. Placental measures included characteristics, pathological findings, and immunohistochemistry. At birth, intrauterine growth was assessed using anthropometric measures, weight-for-gestational age, and the clinical assessment of nutritional status score (CANSCORE) for determining fetal malnutrition. Multivariate linear regression and log-binomial regression models were applied, controlling for potential confounding factors., Results: Maternal vascular malperfusion (MVM) was related to reduced birthweight (P < 0.0001), birth length (P = 0.002), head circumference (P = 0.001), and weight-to-length ratio (P = 0.016). MVM increased the risk for preterm delivery (P = 0.0005) and small for gestational age (SGA) (P = 0.016). Acute chorioamnionitis (P = 0.013) and MVM (P = 0.021) both led to an increased risk for fetal malnutrition defined by CANSORE<25. Villous tissue activated caspase-3 was associated with lower birth length (P = 0.0006), higher weight-to-length ratio (P = 0.004), reduced risks for SGA (P = 0.011) and low weight-to-length ratio for gestational age (P = 0.004)., Conclusion: The present study applied comprehensive measures for intrauterine growth and demonstrates that low placental weight and placental pathology, chiefly MVM, contribute to poor intrauterine growth. A better understanding of the mechanistic role of specific placental pathologies on adverse newborn outcomes will provide opportunities for reducing incidence of poor intrauterine growth and associated long-term morbidities., (© 2023 International Federation of Gynecology and Obstetrics.)

In a cross-sectional analysis of 354 Ugandan children (age 12-48 months) infected with Schistosoma mansoni, we assessed relationships between infection intensity and nutritional morbidities. Higher intensity was associated with an increased risk for anemia (RR = 1.05, 95% confidence interval [CI] 1.01-1.10) yet not associated with risk for underweight, stunting, or wasting., Competing Interests: Potential conflicts of interest. A. L. B. reports grants from UKRI Future Leaders Fellowship in Global Health (grant number MR/T041900/1) and Wellcome Trust Biomedical Facilities Grant (Schistosomiasis Snail Resource Facilities—SSR). S. C. reports receipt of the Thrasher Early Career Award. J. F. F. reports a Midcareer Investigator Award in Patient Oriented Research from US National Institutes of Health/NIAID (award number K24 AI112964-06). E. L. W. reports grants from UK Medical Research Council (MRC), UK National Institute for Health and Care Research (NIHR), and European and Developing Countries Clinical Trial Partnership—European Union (EDCTP). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Periportal fibrosis is a late-stage manifestation of chronic infection with Schistosoma mansoni . Praziquantel (PZQ), the only drug available for the treatment of schistosomiasis, has limited effect in treating established morbidity. Preschool-age children (PSAC) are not considered to be an at-risk population for severe morbidity. However, the prevalence of periportal fibrosis in PSAC in S. mansoni endemic settings is unknown., Methods: As part of a phase II clinical trial comparing different dosing regimens of PZQ in children age 12-47 months infected with S. mansoni in Uganda ("praziquantel in preschoolers" trial), we present baseline results assessing liver ultrasound (US) findings as per the WHO Niamey Protocol., Results: A total of 7/347 (2%) PSAC had Image Pattern C with pipe stems and echogenic rings suggestive of periportal fibrosis, 29/347 (8%) had Image Pattern B and 58 (17%) had evidence of periportal thickening There were higher adjusted odds of periportal thickening with older age [odds ratio (OR): 1.04; 95% confidence interval (CI): 1.00-1.07], primary maternal education (OR: 1.04; 95% CI: 1.00-1.07) and being taken to the lake weekly (OR: 3.02; 95% CI: 1.19-7.63). A further 44/347 children (13%) had a rounded caudal liver edge which was associated with high S. mansoni infection intensity (adjusted OR: 3.31; 95% CI: 1.46-7.51)., Conclusions: Incipient schistosomiasis-related liver morbidity was detected in young children enrolled in the praziquantel in preschoolers trial. Adequate age-adjusted reference measurements for liver ultrasound findings in very small children are lacking but urgently needed. Schistosomiasis-related fibrosis may be delayed or averted with early and repeated PZQ treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Studies have implicated schistosomiasis as a cause of intestinal barrier disruption, a salient feature of environmental enteric dysfunction (EED), as eggs translocate from the sterile bloodstream through the gut wall. We examined the longitudinal impact of praziquantel (PZQ) treatment on a) EED biomarkers and b) Insulin growth factor I (IGF-1), a key driver of childhood linear growth, since EED has been implicated in linear growth stunting., Methodology: 290 children infected with S. mansoni in Brazil were treated with PZQ at baseline. EED biomarkers lipopolysaccharide (LPS) and intestinal fatty acid binding-protein (I-FABP) were measured, as well as IGF-1 at baseline, 6 and 12-months. Multivariate regression analysis was applied to assess associations between S. mansoni intensity and plasma biomarkers (LPS, I-FABP, and IGF-1), controlling for potential confounding variables., Principal Findings: At baseline, S. mansoni infection intensities were 27.2% light, 46.9% moderate, and 25.9% heavy. LPS concentrations were significantly reduced at the 12-month visit compared to baseline (p = 0.0002). No longitudinal changes were observed for I-FABP or IGF-1 in the 6- or 12-month periods following baseline treatment. After 6-months, I-FABP concentration was significantly higher in high vs low intensity (p = 0.0017). IGF-1 concentrations were significantly lower among children with high and moderate vs low intensity infections at each study visit., Conclusions/significance: We report that S. mansoni infection impacts LPS, I-FABP and IGF-1. These findings suggest a mechanistic role for EED in schistosomiasis-related morbidities, particularly linear growth., Competing Interests: The authors have declared that no competing interests exist.

Hookworm infection is associated with poor nutritional outcomes, anemia, and impaired cognitive performance. We examined the association between maternal hookworm infection and birth outcomes in a cohort of women in Leyte, Philippines. We observed poor intrauterine growth characteristics associated with maternal hookworm only among male offspring, with lower birth weight, head circumference, and placental surface area. Male neonates also had higher insulin-like growth factor 2 (IGF-2) and lower adiponectin in cord blood. These data intriguingly suggest nutritional impacts of maternal hookworm infection during pregnancy may be divergent based on sex of the offspring., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)