Fc Glycan-Mediated Regulation of Placental Antibody Transfer.

Despite the worldwide success of vaccination, newborns remain vulnerable to infections. While neonatal vaccination has been hampered by maternal antibody-mediated dampening of immune responses, enhanced regulatory and tolerogenic mechanisms, and immune system immaturity, maternal pre-natal immunization aims to boost neonatal immunity via antibody transfer to the fetus. However, emerging data suggest that antibodies are not transferred equally across the placenta. To understand this, we used systems serology to define Fc features associated with antibody transfer. The Fc-profile of neonatal and maternal antibodies differed, skewed toward natural killer (NK) cell-activating antibodies. This selective transfer was linked to digalactosylated Fc-glycans that selectively bind FcRn and FCGR3A, resulting in transfer of antibodies able to efficiently leverage innate immune cells present at birth. Given emerging data that vaccination may direct antibody glycosylation, our study provides insights for the development of next-generation maternal vaccines designed to elicit antibodies that will most effectively aid neonates.

Standardized Definitions of In Utero Human Immunodeficiency Virus and Antiretroviral Drug Exposure Among Children.

In countries with high human immunodeficiency virus (HIV) prevalence, up to 30% of pregnant women are living with HIV, with fetal exposure to both HIV and antiretroviral therapy during pregnancy. In addition, pregnant women without HIV but at high risk of HIV acquisition are increasingly receiving HIV preexposure antiretroviral prophylaxis (PrEP). Investments are being made to establish and follow cohorts of children to evaluate the long-term effects of in utero HIV and antiretroviral exposure. Agreement on a key set of definitions for relevant exposures and outcomes is important both for interpreting individual study results and for comparisons across cohorts. Harmonized definitions of in utero HIV and antiretroviral drug (maternal treatment or PrEP) exposure will also facilitate improved classification of these exposures in future observational studies and clinical trials. The proposed definitions offer a uniform approach to facilitate the consistent description and estimation of effects of HIV and antiretroviral exposures on key child health outcomes.

Children living with HIV in Europe: do migrants have worse treatment outcomes?

OBJECTIVES: To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe. METHODS: Children aged < 18 years at the start of antiretroviral therapy (ART) in European paediatric HIV observational cohorts where ≥ 5% of children were migrants (defined as born abroad) were included. Three outcomes were considered: (i) severe immunosuppression-for-age; (ii) viraemic viral load (≥ 400 copies/mL) at 1 year after ART initiation; and (iii) AIDS/death after ART initiation. The effect of migrant status was assessed using univariable and multivariable logistic and Cox models. RESULTS: Of 2620 children included across 12 European countries, 56% were migrants. At ART initiation, migrant children were older than domestic-born children (median 6.1 vs. 0.9 years, p < 0.001), with slightly higher proportions being severely immunocompromised (35% vs. 33%) and with active tuberculosis (2% vs. 1%), but a lower proportion with an AIDS diagnosis (14% vs. 19%) (all p < 0.001). At 1 year after beginning ART, a lower proportion of migrant children were viraemic (18% vs. 24%) but there was no difference in multivariable analysis (p = 0.702), and no difference in severe immunosuppression (p = 0.409). However, there was a trend towards higher risk of AIDS/death in migrant children (adjusted hazard ratio = 1.51, 95% confidence interval: 0.96-2.38, p = 0.072). CONCLUSIONS: After adjusting for characteristics at ART initiation, migrant children have virological and immunological outcomes at 1 year of ART that are comparable to those who are domestic-born, possibly indicating equity in access to healthcare in Europe. However, there was some evidence of a difference in AIDS-free survival, which warrants further monitoring.

Innate Immune Responses and Gut Microbiomes Distinguish HIV-Exposed from HIV-Unexposed Children in a Population-Specific Manner.

In both high- and low-income countries, HIV-negative children born to HIV-positive mothers (HIV exposed, uninfected [HEU]) are more susceptible to severe infection than HIV-unexposed, uninfected (HUU) children, with altered innate immunity hypothesized to be a cause. Both the gut microbiome and systemic innate immunity differ across biogeographically distinct settings, and the two are known to influence each other. And although the gut microbiome is influenced by HIV infection and may contribute to altered immunity, the biogeography of immune-microbiome correlations among HEU children have not been investigated. To address this, we compared the innate response and the stool microbiome of 2-y-old HEU and HUU children from Belgium, Canada, and South Africa to test the hypothesis that region-specific immune alterations directly correlate to differences in their stool microbiomes. We did not detect a universal immune or microbiome signature underlying differences between HEU versus HUU that was applicable to all children. But as hypothesized, population-specific differences in stool microbiomes were readily detected and included reduced abundances of short-chain fatty acid-producing bacteria in Canadian HEU children. Furthermore, we did not identify innate immune-microbiome associations that distinguished HEU from HUU children in any population. These findings suggest that maternal HIV infection is independently associated with differences in both innate immunity and the stool microbiome in a biogeographical population-specific way.

Neurological development of children who are HIV-exposed and uninfected.

Widespread use of antiretroviral drugs for pregnant/breastfeeding females with human immunodeficiency virus (HIV) has led to declining vertical transmission. Despite being HIV-uninfected, the increasing number of children who are HIV-exposed and uninfected (CHEU) often present with developmental alterations. We review seminal and recent evidence on the neurological development of CHEU and associations with early life HIV/antiretroviral exposure. Our conceptual model highlights the numerous exposures and universal risk factors for CHEU developmental disorders. Early studies suggest a significant association between HIV exposure and neurological abnormalities, varying according to the burden of HIV-specific exposures and other risk factors. More recent observations from the modern era are inconsistent, although some studies suggest specific antiretrovirals may adversely affect neurological development of CHEU. As the CHEU population continues to grow, alongside simultaneous increases in types and combinations of antiretrovirals used in pregnancy, long-term monitoring of CHEU is necessary for understanding the effects of HIV/antiretroviral exposure on CHEU developmental outcomes. What this paper adds Evidence on the neurological development of children who are human immunodeficiency virus (HIV)-exposed and uninfected (CHEU) is synthesized. Comparisons are made to children who are HIV-unexposed, across treatment eras and settings, and by antiretroviral drug regimens and drug classes. CHEU exposures are complex and include HIV-specific and universal risk factors which may affect development during the early years of life.

Initiation of Antiretroviral Therapy Before Pregnancy Reduces the Risk of Infection-related Hospitalization in Human Immunodeficiency Virus-exposed Uninfected Infants Born in a High-income Country.

BACKGROUND: Epidemiological studies conducted in low- and high-income countries showed that infants exposed to maternal human immunodeficiency virus (HIV) have a high risk of severe infections. Immune alterations during fetal life have been proposed as a possible mechanism. METHODS: This prospective study assessed the relative risk of hospitalization for infection in HIV-exposed uninfected (HEU) infants as compared to HIV-unexposed (HU) infants born in a high-income country (HIC). Markers of monocyte activation and levels of pathogen-specific antibodies were measured at birth to identify correlates of infant susceptibility. RESULTS: There were 27 of 132 HEU infants and 14 of 123 HU infants hospitalized for infection during the first year of life (adjusted hazard ratio [aHR] 2.33, 95% confidence interval [CI] 1.10-4.97). Most of this increased risk was associated with the time of initiation of maternal antiretroviral therapy (ART). As compared to HU infants, the risk of hospitalization for infection of HEU infants was 4-fold higher when mothers initiated ART during pregnancy (aHR 3.84, 95% CI 1.69-8.71) and was not significantly increased when ART was initiated before pregnancy (aHR 1.42, 95% CI 0.58-3.48). The activation of newborn monocytes and the reduced transfer of maternal antibodies were most intense following ART initiation during pregnancy, and predicted the risk of infant hospitalization. CONCLUSIONS: These observations indicate that initiation of maternal ART before pregnancy reduces the susceptibility of HEU infants born in a HIC to severe infections, and that this effect could be related to the prevention of immune alterations during fetal life.

Long-term trends in mortality and AIDS-defining events after combination ART initiation among children and adolescents with perinatal HIV infection in 17 middle- and high-income countries in Europe and Thailand: A cohort study.

BACKGROUND: Published estimates of mortality and progression to AIDS as children with HIV approach adulthood are limited. We describe rates and risk factors for death and AIDS-defining events in children and adolescents after initiation of combination antiretroviral therapy (cART) in 17 middle- and high-income countries, including some in Western and Central Europe (W&CE), Eastern Europe (Russia and Ukraine), and Thailand. METHODS AND FINDINGS: Children with perinatal HIV aged <18 years initiating cART were followed until their 21st birthday, transfer to adult care, death, loss to follow-up, or last visit up until 31 December 2013. Rates of death and first AIDS-defining events were calculated. Baseline and time-updated risk factors for early/late (≤/>6 months of cART) death and progression to AIDS were assessed. Of 3,526 children included, 32% were from the United Kingdom or Ireland, 30% from elsewhere in W&CE, 18% from Russia or Ukraine, and 20% from Thailand. At cART initiation, median age was 5.2 (IQR 1.4-9.3) years; 35% of children aged <5 years had a CD4 lymphocyte percentage <15% in 1997-2003, which fell to 15% of children in 2011 onwards (p < 0.001). Similarly, 53% and 18% of children ≥5 years had a CD4 count <200 cells/mm3 in 1997-2003 and in 2011 onwards, respectively (p < 0.001). Median follow-up was 5.6 (2.9-8.7) years. Of 94 deaths and 237 first AIDS-defining events, 43 (46%) and 100 (42%) were within 6 months of initiating cART, respectively. Multivariable predictors of early death were: being in the first year of life; residence in Russia, Ukraine, or Thailand; AIDS at cART start; initiating cART on a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen; severe immune suppression; and low BMI-for-age z-score. Current severe immune suppression, low current BMI-for-age z-score, and current viral load >400 c/mL predicted late death. Predictors of early and late progression to AIDS were similar. Study limitations include incomplete recording of US Centers for Disease Control (CDC) disease stage B events and serious adverse events in some countries; events that were distributed over a long time period, and that we lacked power to analyse trends in patterns and causes of death over time. CONCLUSIONS: In our study, 3,526 children and adolescents with perinatal HIV infection initiated antiretroviral therapy (ART) in countries in Europe and Thailand. We observed that over 40% of deaths occurred ≤6 months after cART initiation. Greater early mortality risk in infants, as compared to older children, and in Russia, Ukraine, or Thailand as compared to W&CE, raises concern. Current severe immune suppression, being underweight, and unsuppressed viral load were associated with a higher risk of death at >6 months after initiation of cART.

The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis.

BACKGROUND: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in "real-life" settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. METHODS AND FINDINGS: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5-5.2) years for the total cohort and 6.4 (3.6-8.0) years in Europe, 3.7 (2.0-5.4) years in North America, 2.5 (1.2-4.4) years in South and Southeast Asia, 5.0 (2.7-7.5) years in South America and the Caribbean, and 2.1 (0.9-3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3-2.1) years in North America to 7.1 (5.3-8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4-2.6) years in North America to 7.9 (6.0-9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%-2.8%), 15.6% (15.1%-16.0%), and 11.3% (10.9%-11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%-1.1%]) and highest in South America and the Caribbean (4.4% [3.1%-6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%-6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%-13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. CONCLUSION: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses.

Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children - a EuroCoord-CHAIN-EPPICC joint project.

BACKGROUND: Few studies have evaluated the impact of pre-treatment drug resistance (PDR) on response to combination antiretroviral treatment (cART) in children. The objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the prevalence of PDR mutations and their association with virological outcome in the first year of cART in children. METHODS: HIV-infected children <18 years initiating cART between 1998 and 2008 were included if having at least one genotypic resistance test prior to cART initiation. We used the World Health Organization 2009 resistance mutation list and Stanford algorithm to infer resistance to prescribed drugs. Time to virological failure (VF) was defined as the first of two consecutive HIV-RNA > 500 copies/mL after 6 months cART and was assessed by Cox proportional hazards models. All models were adjusted for baseline demographic, clinical, immunology and virology characteristics and calendar period of cART start and initial cART regimen. RESULTS: Of 476 children, 88 % were vertically infected. At cART initiation, median (interquartile range) age was 6.6 years (2.1-10.1), CD4 cell count 297 cells/mm3 (98-639), and HIV-RNA 5.2 log10copies/mL (4.7-5.7). Of 37 children (7.8 %, 95 % confidence interval (CI), 5.5-10.6) harboring a virus with ≥1 PDR mutations, 30 children had a virus resistant to ≥1 of the prescribed drugs. Overall, the cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 %CI, 16.4-23.9). Cumulative risk for VF tended to be higher among children harboring a virus with PDR and resistant to ≥1 drug prescribed than among those receiving fully active cART: 32.1 % (17.2-54.8) versus 19.4 % (15.9-23.6) (P = 0.095). In multivariable analysis, age was associated with a higher risk of VF with a 12 % reduced risk per additional year (HR 0.88; 95 %CI, 0.82-0.95; P < 0.001). CONCLUSIONS: PDR was not significantly associated with a higher risk of VF in children in the first year of cART. The risk of VF decreased by 12 % per additional year at treatment initiation which may be due to fading of PDR mutations over time. Lack of appropriate formulations, in particular for the younger age group, may be an important determinant of virological failure.

Pattern recognition receptor-mediated cytokine response in infants across 4 continents.

BACKGROUND: Susceptibility to infection as well as response to vaccination varies among populations. To date, the underlying mechanisms responsible for these clinical observations have not been fully delineated. Because innate immunity instructs adaptive immunity, we hypothesized that differences between populations in innate immune responses may represent a mechanistic link to variation in susceptibility to infection or response to vaccination. OBJECTIVE: Determine whether differences in innate immune responses exist among infants from different continents of the world. METHODS: We determined the innate cytokine response following pattern recognition receptor (PRR) stimulation of whole blood from 2-year-old infants across 4 continents (Africa, North America, South America, and Europe). RESULTS: We found that despite the many possible genetic and environmental exposure differences in infants across 4 continents, innate cytokine responses were similar for infants from North America, South America, and Europe. However, cells from South African infants secreted significantly lower levels of cytokines than did cells from infants from the 3 other sites, and did so following stimulation of extracellular and endosomal but not cytosolic PRRs. CONCLUSIONS: Substantial differences in innate cytokine responses to PRR stimulation exist among different populations of infants that could not have been predicted. Delineating the underlying mechanism(s) for these differences will not only aid in improving vaccine-mediated protection but possibly also provide clues for the susceptibility to infection in different regions of the world.

Increased risk of serious bacterial infections due to maternal immunosuppression in HIV-exposed uninfected infants in a European country.

BACKGROUND: Morbidity and mortality are higher among human immunodeficiency virus (HIV) exposed but uninfected (HEU) infants than unexposed infants, particularly if the mother had a low CD4 count. We investigated the possible association between maternal immune depression during pregnancy and the risk of infection in HEU infants in the national French Perinatal Cohort (EPF). METHODS: All neonates, born alive, to HIV-1-infected women enrolled in the EPF between 2002 and 2010 were included. The primary outcome was the first serious (hospitalization or death) infection during the first year of life. The main exposure variable was maternal CD4 cell count near delivery. The Kaplan-Meier method and multivariate Cox models were applied, with the different types of infections managed as competing events. RESULTS: Among 7638 HEU neonates, 699 had at least 1 serious infection (of which 159 were bacterial) with a Kaplan-Meier probability of 9.3% (95% confidence interval, 8.7-10.0) at 1 year. The risk of serious bacterial infection during the first year of life significantly increased with lower maternal CD4 cell count, before and after adjustment for maternal CD4 cell count <350 and 350-499 CD4/mm(3) (adjusted hazard ratio = 1.7 [1.2-2.6] and 1.2 [0.8-1.9], respectively; P = .03). This association mainly concerned infections involving encapsulated bacteria (P = .03). The risk of serious viral infection was, by contrast, independent of the mother's CD4 cell count. CONCLUSIONS: Maternal CD4 count is significantly and specifically associated with the risk of serious infections with encapsulated bacteria in HEU infants.

Post-licensing safety of fosamprenavir in HIV-infected children in Europe.

PURPOSE: Fosamprenavir, combined with low-dose ritonavir (FPV/r), is indicated for treatment of HIV-infected children aged ≥ 6 years in Europe. Our purpose was to assess the safety of licensed use of FPV/r in HIV-infected children reported to six cohorts in the European Pregnancy and Paediatric HIV Cohort Collaboration. METHODS: Retrospective analysis of individual patient data for all children aged 6-18 years taking the licensed dose of FPV up to 31/12/10. Adverse events (clinical events and absolute neutrophil counts, total cholesterol and triglycerides, and alanine transaminase) were summarised and DAIDS gradings characterised severity. RESULTS: Ninety-two HIV-infected children aged 6-18 years took the licensed dose, comprising 3% of the total number of children in follow-up in participating cohorts. Median age at antiretroviral therapy initiation was 6 years (interquartile range 1-11 years), and median age at start of FPV/r was 15 years (12-17 years). Estimated median time on an FPV-containing regimen was 52 months, with a total of 266.9 patient years of exposure overall. Half (54%) were on an FPV-containing regimen at last follow-up. Rates of grade 3/4 events were generally low for all biochemical toxicity markers, and no serious adverse events considered to be causally related to FPV/r were reported. CONCLUSIONS: Results suggest that long-term licensed dose FPV-containing regimens appear to be generally well tolerated with few reported toxicities in HIV-infected children in Europe, although relatively infrequently prescribed. No serious events were reported

Maternal immunization in women living with HIV.

Thanks to widespread use of antiretroviral therapy worldwide, women living with HIV (WLWH) are becoming pregnant and giving birth to HIV-exposed but uninfected (HEU) newborns. Both pregnancy and HIV infection-related factors such as low CD4+ T-cell count or uncontrolled viral load increase the risk of severe infections such as influenza, COVID-19, and others, making maternal immunization a valuable tool to decrease maternal morbidity among WLWH. Vaccines administered during pregnancy may also benefit the health of HEU infants. Indeed, HEU infants suffer from higher risk of morbidity of infectious origin, including respiratory syncytial virus (RSV), group B streptococcus (GBS), pneumococcus and pertussis infections. Maternal pertussis immunization is recommended in various high-income countries but not in many low-middle income countries where HIV prevalence is higher. GBS and RSV vaccines to be administered during pregnancy are currently in late-phase clinical trials in HIV-uninfected women and could represent a valuable tool to decrease morbidity during infancy. Decreased transfer of vaccine-specific IgG, accelerated waning of vaccine-induced antibody responses, linked to persistent maternal immune activation, and blunting of infant immune response to vaccines could hamper vaccine effectiveness among WLWH and HEU infants. Vaccine hesitancy could limit benefits of maternal immunization and strategies to tackle vaccine hesitancy should be part of HIV routine care. The aim of this review is to summarize the current knowledge regarding the immunogenicity and efficacy of available and upcoming vaccines recommended during pregnancy of WLWH.

Immunovirological status in people with perinatal and adult-acquired HIV-1 infection: a multi-cohort analysis from France.

Background: No study has compared the virological and immunological status of young people with perinatally-acquired HIV infection (P-HIV) with that of people with HIV adulthood (A-HIV) having a similar duration of infection. Methods: 5 French cohorts of P-HIV and A-HIV patients with a known date of HIV-infection and receiving antiretroviral treatment (ART), were used to compare the following proportions of: virological failure (VF) defined as plasma HIV RNA ≥ 50 copies/mL, CD4 cell percentages and CD4:CD8 ratios, at the time of the most recent visit since 2012. The analysis was stratified on time since infection, and multivariate models were adjusted for demographics and treatment history. Findings: 310 P-HIV were compared to 1515 A-HIV (median current ages 20.9 [IQR:14.4-25.5] and 45.9 [IQR:37.9-53.5] respectively). VF at the time of the most recent evaluation was significantly higher among P-HIV (22.6%, 69/306) than A-HIV (3.3%, 50/1514); p ≤ 0.0001. The risk of VF was particularly high among the youngest children (2-5 years), adolescents (13-17 years) and young adults (18-24 years), compared to A-HIV with a similar duration of infection: adjusted Odds-Ratio (aOR) 7.0 [95% CI: 1.7; 30.0], 11.4 [4.2; 31.2] and 3.3 [1.0; 10.8] respectively. The level of CD4 cell percentages did not differ between P-HIV and A-HIV. P-HIV aged 6-12 and 13-17 were more likely than A-HIV to have a CD4:CD8 ratio ≥ 1: 84.1% vs. 58.8% (aOR = 3.5 [1.5; 8.3]), and 60.9% vs. 54.7% (aOR = 1.9 [0.9; 4.2]) respectively. Interpretation: P-HIV were at a higher risk of VF than A-HIV with a similar duration of infection, even after adjusting for treatment history, whereas they were not at a higher risk of immunological impairment. Exposure to viral replication among young patients living with HIV since birth or a very early age, probably because of lower adherence, could have an impact on health, raising major concerns about the selection of resistance mutations and the risk of HIV transmission. Funding: Inserm - ANRS MIE.

SARS-CoV-2 Infection in Children Less Than Forty Days Hospitalized in Belgium Between 2020 and 2022.

Our study aimed to assess the severity of severe acute respiratory syndrome coronavirus 2 infection in hospitalized infants under 40 days old, across 21 Belgian hospitals between 2020 and 2022. Of the 365 infants studied, 14.2% needed respiratory support. The median hospital stay was 3 days (interquartile range, 2-4), and there were no deaths. Infection severity was similar during the Omicron and Alpha/Delta periods.

Retrospective comparison of respiratory syncytial virus and metapneumovirus clinical presentation in hospitalized children.

Respiratory syncytial virus (RSV) and Human metapneumovirus (hMPV), members of Pneumoviridae family are common causes of acute respiratory tract infections (ARTI) among children. Study material includes routine nasopharyngeal samples obtained during 8-year period for hMPV and one single season for RSV in children hospitalized for ARTI between 0 and 15 years at the Center Hospitalier Universitaire (CHU) Saint Pierre in Brussels. Positive samples for RSV or hMPV identified by viral culture, lateral flow chromatography test for RSV or direct fluorescent assay for hMPV were selected retrospectively. Characteristics of children hospitalized for RSV or hMPV infections were compared. Children hospitalized for RSV infection were significantly younger and requiring more respiratory support, longer hospital stay and transfers in Pediatric intensive Care Units than those hospitalized for hMPV infection. Pneumonia diagnostic and antibiotics therapies were more significantly associated with hMPV infections. In conclusion, despite their genetic similarities, RSV, and hMPV present epidemiological and clinical differences in pediatric infections. Our results should be confirmed prospectively.

Imported Malaria in Children: A Study Over an 11-Year Period in Brussels.

BACKGROUND: Malaria is a major global public health concern in endemic countries and imported childhood malaria is increasing in malaria non-endemic countries. METHODS: This was a retrospective case review of all laboratory-confirmed malaria cases in children 0-16 years admitted between 2009 and 2019 in 2 large university teaching Hospitals in Brussels. RESULTS: A total of 160 children with a median age of 6.8 years (range 5-191 months) were included. We identified 109 (68%) children living in Belgium who had acquired malaria during their visit to malaria-endemic countries to visiting friends and relatives (VFRs), 49 children (31%) visitors or newly installed migrants, and 2 Belgian tourists. Peak seasonal incidence occurred between August and September. Plasmodium falciparum was responsible for 89% of all malaria cases. Almost 80% of children living in Belgium visited a travel clinic for advice, but only one-third reported having taken the prophylaxis schedule according to the recommendations. Based on WHO criteria, 31 children (19.3%) developed severe malaria; most of the patients with severe malaria were VFR travelers and were significantly younger, had higher leukocytosis, had more thrombocytopenia, higher CRP, and lower natremia compared with patients with an uncomplicated course. All children recovered fully. CONCLUSIONS: Malaria is a significant cause of morbidity among returning travelers and newly arrived immigrants to Belgium. Most of the children had an uncomplicated disease course. Physicians should educate families about traveling to malaria-endemic areas to correct malaria preventive measures and prophylaxis.

Gen Z and HIV-Strategies for Optimizing the Care of the Next Generation of Adolescents Living with HIV.

The management of adolescents living with HIV represents a particular challenge in the global response to HIV. The challenges specific to this age group include difficulties engaging and maintaining them in care, challenges with transition to adult care, and limited therapeutic options for treatment-experienced patients, all of which have been jeopardized by the COVID-19 pandemic. This paper summarizes some of the challenges in managing adolescents living with HIV, as well as some of the most recent and innovative therapeutic approaches in this population.