Uninfected Children Research Articles

Infectivity and immunogenicity of live-attenuated respiratory syncytial virus vaccines in HIV-exposed uninfected children

Abstract Background Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory illness among young children. HIV-exposed uninfected (HEU) children experience a higher burden of RSV disease and have immune abnormalities that may influence their responses to live-attenuated RSV vaccines. Methods In a pooled analysis of clinical trials of seven live-attenuated, intranasal RSV vaccines conducted by the IMPAACT Network among children 6 to <25 months of age with serum RSV-neutralizing titers of <1:40, the infectivity and immunogenicity of these vaccines were compared among HEU and HIV-unexposed uninfected (HUU) children. Nasal washes were collected during the first 28 days after vaccination. Serum RSV-neutralizing and anti-RSV F glycoprotein IgG antibodies were measured prior to and 56 days after vaccination, and before and after the following winter season. Results Of 156 children, 90 (58%) were HUU and 66 (42%) were HEU. Seventy-six (84%) HUU and 63 (95%) HEU participants were infected with vaccine (shed vaccine virus and/or had a ≥4-fold rise in serum RSV antibodies at 56 days after vaccination). HUU children had higher serum RSV-neutralizing and anti-RSV F IgG titers prior to vaccination. Compared to HEU children, lower percentages of HUU children had ≥4-fold rises in RSV-neutralizing (67% vs. 88%) and anti-RSV F IgG (70% vs. 89%) titers at 56 days after vaccination. Conclusions Live-attenuated RSV vaccines are highly immunogenic in HEU children. Given their increased burden of RSV disease and higher early-childhood mortality in some settings, HEU children should be prioritized for vaccination against RSV as these vaccines become available.

Hepatitis A Seroprevalence Among HIV-Exposed and Unexposed Pediatric Populations in South Africa

Background: There is limited evidence comparing hepatitis A seroprevalence among HIV-exposed uninfected (HEU), HIV-infected (HIV), and unexposed uninfected (HUU) children. This compromises rational vaccine decision-making. Methods: This study comprised a retrospective health facility-based population of children aged 1 month–12 years. Archival sera were tested for markers of acute (anti-HAV IgM) or past (total anti-HAV) HAV infection. Subgroup analysis was conducted based on perinatal HIV exposure or infection status. Results: Among 513 children, the median age was 10 (IQR: 4–25) months. The median maternal age was 29 (IQR: 25–34) years. An anti-HAV seropositivity of 95.1% (117/122 [95% CI 90.2–98.4]) was found among those ≤6 months of age, indicative of the rate of transplacental antibody transfer. Among 1–12-year-olds, hepatitis A seroprevalence was 19.3% (37/192 [95% CI 14.1–25.7]), while 1.1% (2/188 [95% CI 0.12–2.76]) had evidence of acute infection. Compared to HIV-exposed subgroups (HIV = 60%, 6/10 [95% CI 27.4–86.3] and HEU = 45%, 9/20 [95% CI 23.8–68]), hepatitis A seroprevalence among HUU children was low (29.2%, 47/161 [95% CI 22.4–37.0]). Conclusions: Natural immunity among HIV-exposed and unexposed children in South Africa is insufficient to protect against severe liver complications associated with HAV infection later in adulthood.

Blood cytokines in children with erosive gastritis

Aim: To evaluate the cytokine profile of blood serum in children with erosive gastritis depending on the activity of the inflammatory process, bacterial invasion of H. pylori and family predisposition to peptic ulcer disease. Gastroscopy was performed with the collection of biopsy material from the gastric mucosa in 168 children aged 7-17 years with gastroenterological complaints. Subsequently, a morphological examination of biopsy specimens confirmed the diagnosis of gastritis in all examined patients and determined H. pylori invasion. The content of cytokines in the blood serum (IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IL-1β, IFNα, TNFα) was determined using the enzyme immunoassay method. When analyzing cytokine levels in schoolchildren infected with H. pylori, there were no differences in cytokine concentrations (p 0.05). While in uninfected children in the presence of erosive changes, a decrease in IL-2 content was noted (p = 0.026). In individuals with a family history of peptic ulcer disease with erosive gastritis, an increase in the content of IL-8 was observed (p = 0.006), which is known to play an important role in maintaining innate immunity. Whereas, in the absence of a family predisposition, schoolchildren with erosive gastritis showed a decrease in IL-2 (p = 0.027), which is similar to the level of IL-2 in schoolchildren with erosive gastritis without H. pylori infection. IL-2 is considered an activator of the antitumor response and this property is being actively studied in patients with gastric cancer. In the context of these data, it can be assumed that in individuals with erosive gastritis, even without a family predisposition and H. pylori infection, inhibition of IL-2 synthesis is observed. What causes this influence is an open question. Thus, the variety of components of the cytokine profile involved in the regulation of the inflammatory process and the influencing negative factors create difficulties in assessing and, even more so, predicting the role and significance of changes in the content of a particular cytokine in the blood serum in children with erosive gastritis.

Expression of CDX2, CK20 and CK7 in the epithelium of the gastric mucosa in schoolchildren with CagA H. pylori-associated gastritis

Aim. To study the association of protein expression CDX2, CK20, CK7 in the epithelium of the gastric mucosa in schoolchildren with CagA H. pylori-associated gastritis. Material and methods. Gastroscopy was performed with the collection of biopsy material from the mucous membrane of the antrum and body of the stomach in 89 schoolchildren (7-17 years old) with gastroenterological complaints. The morphological method confirmed the diagnosis of gastritis and determined the presence of H. pylori. Gastric biopsies were examined immunohistochemically to identify the proteins CDX2, CK20, CK7 in the epithelium. Blood was also collected to determine the CagA strain of H. pylori using enzyme immunoassay. Results. In schoolchildren infected with CagA H. pylori, higher expression of CK7 was found in both parts of the stomach (in the body (p = 0.044), in the antrum (p = 0.014)) compared to uninfected children. Changes in the expression of CDX2 and CK20 in children infected with H. pylori CagA have not been established. CDX2 protein was detected more often among schoolchildren aged 12-17 years with H. pylori infection than in children without H. pylori (p = 0.062) and in children with CagA H. pylori (p = 0.017). In the group of younger children with CagA H. pylori, there were higher levels of CK7 expression in the epithelium of the antrum of the stomach, compared with uninfected children (p = 0.033). They also had higher CK7 in the body than in CagA H. pylori-associated gastritis in children of the older age group (p = 0.001). Boys with CagA H. pylori had the highest expression of CK7 in the gastric body, which was higher than in uninfected boys (p = 0.021). Conclusion. Thus, in children, the features of the association of CDX2, CK20, CK7 with CagA H. pylori-associated gastritis have been established, including depending on the age and gender of the child.

Can SARS-CoV-2 Infection Status in Preschool Children be Predicted by Pandemic-related Attitudes and Concerns of their Parents? Data from the Würzburg Daycare Centre Studies (Wü-KiTa-CoV, 2020-2022)

As part of the Würzburg KiTa-CoV study series, SARS-CoV-2 pandemic-related attitudes/concerns of parents of preschool children attending day care centres were surveyed over a 21-month period. We expected associations between these parental attitudes/concerns and their change over the course of the pandemic, on the one hand, and the SARS-CoV-2 infection status of the children, on the other. Parents of children from nine day-care centres who completed a survey on pandemic-related attitudes/concerns in October 2020, July 2021 and July 2022, were included in the analysis. In July 2022, the children's infection status was determined by measuring nucleocapsid protein antibodies (N-AK) and, in the case of N-AK negative, unvaccinated children, the measurement results of spike protein antibodies (S-AK) against SARS-CoV-2 as indicators of previous infection were also taken into account. Changes in parental attitudes/concerns were analysed using trend tests, and their significance in predicting the child's infection status was analysed using multiple binomial regression analyses. Data were available from parents of 159 children (mean age 3.2 years). The overall group of parents showed an increasingly relaxed attitude towards the pandemic over the study period, although the parents' concerns towards a possible infection of their own increased. The infection status of the children could not be predicted from the initial attitudes and concerns of the parents. However, the subgroup of parents with an uninfected child tended to have a higher level of concerns over the course of the pandemic than the parents with an infected child and did not show the same increasing composure towards the pandemic event. The parents' increasing composure is understandable in the context of the reduced virulence of the virus variants prevailing over time, the increasing availability of testing strategies and vaccinations, and the withdrawal of pandemic-related restrictions. In addition, the mildness of most children's infections may have contributed to their parents' sense of security. The seemingly contradictory increase in parental concerns about infection may be related to the strong increase in the incidence due to omicron variant infections in the population since January 2022. It is possible that the higher level of concerns among parents of uninfected children had a protective effect behaviourally.

School mask policies and SARS-CoV-2 seroprevalence among school-age children-United States, September to December 2021.

During the U.S. Fall 2021 school semester, the estimated proportion of previously uninfected school-aged children who experienced a first infection with SARS-CoV-2 was lower in areas where public school district policies required masks for all staff and students compared with areas where the school districts had no mask requirements. Because children are more likely than adults to experience asymptomatic or mild SARS-CoV-2 infections, the presence of infection-induced antibodies is a more accurate measure of infection history than clinical testing. The proportion of children with these antibodies (i.e., seroprevalence) can improve our understanding of SARS-CoV-2 by detecting more infections and eliminating potential bias due to local testing and reporting practices. Enhanced robustness of surveillance for respiratory infections in children, including records of mitigation policies in communities and schools, as well as seroprevalence data, would establish a better evidence base for policy decisions and response measures during future respiratory outbreaks.

A-310 Neurodevelopmental disorders and hyperlipidemia in HIV-exposed uninfected children in the Bronx, New York

Abstract Background The implementation of combination antiretroviral therapy (cART) for treating human immunodeficiency virus (HIV) has significantly reduced the rates of vertical HIV transmission. With increasing cART coverage, the number of HIV-positive infants has declined, while the number of HIV-exposed uninfected (HEU) infants has risen. This group now comprises a rapidly expanding cohort of HIV-affected individuals, currently totaling 16 million and increasing by 1.6 million annually. However, our understanding of the potential in-utero toxicity of cART remains limited. Numerous studies, primarily from Africa, suggest that HEU children may face heightened risks of adverse health outcomes, including growth restriction, increased susceptibility to infections, and neurobehavioral disorders. It is widely recognized that infants with growth restriction are at a greater risk of developing chronic diseases such as cardiometabolic and neurological disorders later in life, which is accentuated by low socioeconomic status. The objective of this study was to assess the prevalence of neurodevelopmental disorders and hyperlipidemia in HIV-negative children born to HIV-infected mothers in the Bronx, New York, utilizing retrospective medical records information. Methods We conducted a retrospective chart review of HEU and age-matched control (HIV-unexposed and uninfected; HUU) children (age 0-15 years) using clinical data obtained from the electronic medical record (EMR) at the Montefiore Medical Center in the Bronx, New York, between 2015 and 2023. Demographic data and documented diagnostic data were collected. Lipid panel results were also obtained from the EMR and stratified by age and testing date. Neurodevelopmental outcome measures were compared between HEU and HUU children using Chi-square and Student’s t-test was used for continuous variables. Results A total of 127 HEU (46% females, 54% males) children and 157 HUU (46% females, 54% males) children were analyzed. Among the HEU children, 12 (9.5%) were diagnosed with attention-deficit/hyperactivity disorder (ADHD), while only 1 out of 157 (0.6%) HUU children had this diagnosis (p=0.0004). Similarly, a significant number of HEU children were found to have autism spectrum disorder, with 11 (8.7%) affected compared to 2 (1.3%) in the control group (p=0.0036). HEU children also exhibited a higher prevalence of unspecified developmental delay compared to HUU children (14.2% vs 5.1%; p=0.012). However, no significant differences were observed between the two groups regarding speech and language delay or learning difficulties. Abnormal cholesterol levels were detected in 33% of HEU children, while 54.5% had abnormal triglyceride levels. These percentages surpass the prevalence of pediatric hypercholesterolemia (7%) and hypertriglyceridemia (10.2%) in the United States. Conclusions Our findings indicate that HEU children born in areas designated as medically underserved and socioeconomically disadvantaged, such as the Bronx in the United States, face significant risks of neurodevelopmental disorders and hyperlipidemia. Considering the increasing population of HEU children, even minor rises in adverse health effects could lead to significant public health challenges. To support HEU children in achieving their utmost potential, further studies must be encouraged to understand these children's needs. Moreover, it is imperative to enact policies that facilitate equitable distribution of resources, ensuring timely screening and intervention in underprivileged communities.

Campylobacter infection of young children in Colombia and its impact on the gastrointestinal environment.

Campylobacter infections are a leading cause of bacterial-derived gastroenteritis worldwide with particularly profound impacts on pediatric patients in low- and middle-income countries. It remains unclear how Campylobacter impacts these hosts, though it is becoming increasingly evident that it is a multifactorial process that depends on the host immune response, the gastrointestinal microbiota, various bacterial factors, and host nutritional status. Since these factors likely vary between adult and pediatric patients in different regions of the world, it is important that studies define these attributes in well-characterized clinical cohorts in diverse settings. In this study, we analyzed the fecal microbiota and the metabolomic and micronutrient profiles of asymptomatic and symptomatic pediatric patients in Colombia who were either infected or uninfected with Campylobacter during a case-controlled study on acute diarrheal disease. Here, we report that the microbiome of Campylobacter-infected children only changed in their abundance of Campylobacter spp. despite the inclusion of children with or without diarrhea. In addition to increased Campylobacter, computational models were used to identify fecal metabolites that were associated with Campylobacter infection and found that glucose-6-phosphate and homovanillic acid were the strongest predictors of infection in these pediatric patients, which suggests that colonocyte metabolism is impacted during infection. Despite changes to the fecal metabolome, the concentrations of intestinal minerals and trace elements were not significantly impacted by Campylobacter infection but were elevated in uninfected children with diarrhea.IMPORTANCEGastrointestinal infection with pathogenic Campylobacter species has long been recognized as a significant cause of human morbidity. Recently, it has been observed that pediatric populations in low- and middle-income countries are uniquely impacted by these organisms in that infected children can be persistently colonized, develop enteric dysfunction, and exhibit reduced development and growth. While the association of Campylobacter species with these long-term effects continues to emerge, the impact of infection on the gastrointestinal environment of these children remains uncharacterized. To address this knowledge gap, our group leveraged clinical samples collected during a previous study on gastrointestinal infections in pediatric patients to examine the fecal microbiota, metabolome, and micronutrient profiles of those infected with Campylobacter species and found that the metabolome was impacted in a way that suggests gastrointestinal cell metabolism is affected during infection, which is some of the first data indicating how gastrointestinal health in these patients may be affected.

The Negative Impact of Maternal HIV Infection on Birth Outcomes-Myth or Reality?

Human Immunodeficiency Virus (HIV) infection during pregnancy poses significant risks to both maternal and child health, with potential adverse effects on perinatal outcomes. This study aimed to compare perinatal outcomes, including birth weight, length, Apgar scores, and prematurity rates, between HIV-exposed, uninfected (HEU) children and HIV-unexposed, uninfected (HUU) children. A total of 204 neonates were included in the study, comprising 102 born to HIV-positive mothers and 102 born to uninfected mothers. Our findings revealed significant differences in birth weight (p < 0.001), length (p < 0.001), and Apgar scores at both 1 min (p = 0.003) and 5 min (p < 0.001) between HIV-exposed and -unexposed children. The HIV-exposed group exhibited lower birth weights and lengths, along with lower Apgar scores, indicating potential neonatal health challenges. No significant disparities were observed in the prematurity risk between the two groups (OR = 2.58, p = 0.126), but the risk of being born small for gestational age (SGA) in the case of HEU newborns was significantly high (OR = 17.41, p < 0.001). The significant differences in birth weight, length, and Apgar scores underscore the need for tailored healthcare interventions and support for neonates born to HIV-positive mothers. These findings contribute to our understanding of the complex interplay between maternal HIV infection and perinatal outcomes, guiding healthcare professionals in delivering targeted care for this vulnerable population.

Respiratory Syncytial Virus among People Living with HIV: Is There a Case for Rolling Out Prophylaxis? A Viewpoint Based on a Systematic Review.

Respiratory Syncytial Virus (RSV) is responsible for a considerable burden of respiratory disease among children and older adults. Several prophylactic strategies have recently been introduced. We review the available evidence on the interplay between RSV infection and HIV, looking at the specific role of RSV prophylactic strategies in individuals affected by or exposed to HIV. We conducted a systematic review on the association between HIV infection and RSV incidence and severity. We searched in PubMed/MEDLINE for clinical epidemiological studies covering outcomes such as RSV-associated illness, severity, and mortality in individuals affected by or exposed to HIV. A total of 36 studies met the inclusion criteria and were included, the majority conducted in sub-Saharan Africa. There was no compelling evidence suggesting a higher incidence of RSV illness among HIV-infected people. A higher risk of severe disease was consistent among both HIV-positive and HIV-exposed but uninfected (HEU) children. Case fatality rates were also higher for these groups. Evidence on a differing risk among adults was scarce. HIV-positive pregnant women should be given priority for recently approved RSV vaccination, for protection of their newborns. HIV-infected and HEU infants should be considered risk groups for nirsevimab prophylaxis in their first year of life and possibly beyond.

Cohort profile: the Swiss Mother and Child HIV Cohort Study (MoCHiV)

PurposeProspective, multicentric observational cohort study in Switzerland investigating measures to prevent mother-to-child transmission in pregnant women with HIV (WWH) and assessing health and development of their exposed children as well...

Relationships of mitochondrial DNA mutations and select clinical diagnoses in perinatally HIV- and ART-exposed uninfected children

The prevalence of pathogenic mutations within mitochondrial (mt) DNA of youth who were perinatally exposed to HIV and ART but remained uninfected (YHEU) were assessed relative to phenotypic clinical indicators of mitochondrial dysfunction (MtD). This was a cross-sectional, nested case-control study. A total of 144 cases met at least one clinical MtD definition and were matched with up to two controls each (n = 287). At least one risk mutation was present in nearly all YHEU (97 %). No differences in mutation frequencies were observed between metabolic or neurodevelopmental cases and respective controls; however, higher frequencies were found in controls versus respective neurologic or growth cases.

Clinical immunity to malaria involves epigenetic reprogramming of innate immune cells.

The regulation of inflammation is a critical aspect of disease tolerance and naturally acquired clinical immunity to malaria. Here, we demonstrate using RNA sequencing and epigenetic landscape profiling by cytometry by time-of-flight, that the regulation of inflammatory pathways during asymptomatic parasitemia occurs downstream of pathogen sensing-at the epigenetic level. The abundance of certain epigenetic markers (methylation of H3K27 and dimethylation of arginine residues) and decreased prevalence of histone variant H3.3 correlated with suppressed cytokine responses among monocytes of Ugandan children. Such an epigenetic signature was observed across diverse immune cell populations and not only characterized active asymptomatic parasitemia but also correlated with future long-term disease tolerance and clinical immunity when observed in uninfected children. Pseudotime analyses revealed a potential trajectory of epigenetic change that correlated with a child's age and recent parasite exposure and paralleled the acquisition of clinical immunity. Thus, our data support a model whereby exposure to Plasmodium falciparum induces epigenetic changes that regulate excessive inflammation and contribute to naturally acquire clinical immunity to malaria.

Plasmodium falciparum infection status in children less than 10 years old under seasonal malaria chemoprevention and risk of clinical malaria in the Koulikoro health district, Mali.

Seasonal malaria chemoprevention (SMC) with Sulfadoxine pyrimethamine plus amodiaquine (SP + AQ) consist of a monthly administration of therapeutic dose to children under five years of age during the high risk of malaria in area where malaria is highly seasonal. According to SMC recommendation, both non-infected and asymptomatic Plasmodium falciparum infected children will receive similar treatment. The gap in our knowledge is how the effect of asymptomatic infection on the efficacy of SMC in preventing clinical malaria over a four-week period. Thus, this study aimed to assess the risk of clinical malaria and its association with children's infection status when SMC treatment is given. The study was carried out in the Koulikoro health district in Mali and concerned children under 10 years of age. A total of 726 and 1452 children were randomly selected and followed over the SMC campaign in the years 2019 and 2020 respectively. Prevalence of asymptomatic P. falciparum infection was determined each round by microscopy before SMC drugs intake. Children were passively followed over a four-week period to determine incidence of clinical malaria. R-Studio software was used for analysis. The risk of clinical malaria by infection status was estimated using a logistic regression. A Kaplan-Meier curve was used to determine the survival time between infected and uninfected children. The Pearson Chi-square test was used to compare proportions with the significant level at p< 0.05. The average prevalence of asymptomatic infection was 11.0% both years, and it was higher among children aged 5 to 9 years old in 2019 (p<0.001) and 2020 (p=0.016). The risk of clinical malaria was significantly higher among asymptomatic infected children 2019: (RR=3.05, CI [2.04-4.72]) and 2020 (RR=1.43, CI [1.04-1.97]) transmission seasons. Likewise, the time of the first malaria occurrence was statistically lower among infected children regardless the year (p<0.001 in 2019 and p=0.01 in 2020). Results show a high risk of clinical malaria in asymptomatic infected children during SMC delivery. Screening for P. falciparum infection before the SMC treatment could significantly enhance the impact of the strategy on malaria morbidity in endemic areas.

Pediatric Gastrointestinal Outcomes During the Post-Acute Phase of COVID-19: Findings from RECOVER Initiative from 29 Hospitals in the US.

The profile of gastrointestinal (GI) outcomes that may affect children in post-acute and chronic phases of COVID-19 remains unclear. To investigate the risks of GI symptoms and disorders during the post-acute phase (28 days to 179 days after SARS-CoV-2 infection) and the chronic phase (180 days to 729 days after SARS-CoV-2 infection) in the pediatric population. We used a retrospective cohort design from March 2020 to Sept 2023. twenty-nine healthcare institutions. A total of 413,455 patients aged not above 18 with SARS-CoV-2 infection and 1,163,478 patients without SARS-CoV-2 infection. Documented SARS-CoV-2 infection, including positive polymerase chain reaction (PCR), serology, or antigen tests for SARS-CoV-2, or diagnoses of COVID-19 and COVID-related conditions. Prespecified GI symptoms and disorders during two intervals: post-acute phase and chronic phase following the documented SARS-CoV-2 infection. The adjusted risk ratio (aRR) was determined using a stratified Poisson regression model, with strata computed based on the propensity score. Our cohort comprised 1,576,933 patients, with females representing 48.0% of the sample. The analysis revealed that children with SARS-CoV-2 infection had an increased risk of developing at least one GI symptom or disorder in both the post-acute (8.64% vs. 6.85%; aRR 1.25, 95% CI 1.24-1.27) and chronic phases (12.60% vs. 9.47%; aRR 1.28, 95% CI 1.26-1.30) compared to uninfected peers. Specifically, the risk of abdominal pain was higher in COVID-19 positive patients during the post-acute phase (2.54% vs. 2.06%; aRR 1.14, 95% CI 1.11-1.17) and chronic phase (4.57% vs. 3.40%; aRR 1.24, 95% CI 1.22-1.27). In the post-acute phase or chronic phase of COVID-19, the risk of GI symptoms and disorders was increased for COVID-positive patients in the pediatric population.

Cohort study: Neurological and cognitive-behavioral sequelae of acquired Zika virus infection among Nicaraguan children.

ZIKV has neuroinvasive properties, and in utero exposure can cause birth defects, but little is known about the neurological and neurocognitive impacts of acquired ZIKV infection, particularly in children. We assessed neurological symptoms frequency among ZIKV-infected children within one year after ZIKV infection. Three to 5 years post-infection, these children and a matched group of uninfected children were assessed via questionnaires, neurological exams, and neuropsychological testing to evaluate the association between prior ZIKV infection and subsequent neurological symptoms, and cognitive-behavioral function. Among 194 ZIKV-infected children, 3 reported asthenia, 4 reported neck pain, and 10 reported back pain within one year post-infection. At follow-up, clinician-observed cranial nerve abnormalities were significantly more common among ZIKV-infected vs. uninfected children (16 vs. 3; p < 0.01), with vestibulocochlear nerve abnormalities observed most frequently. While ZIKV-infected children scored better than uninfected on cognitive measures, this difference was not clinically meaningful. Neurological signs, including paresthesia and cranial nerve abnormalities, were observed among ZIKV-infected participants in our study. However, we did not observe a meaningful link between acquired ZIKV infection and subsequent neurological, cognitive, or behavioral outcomes in a representative sample. An exception may be hearing impairment and loss, which should be explored further in future studies. Neurological symptoms, though rare, were observed and reported more frequently among ZIKV-infected vs. uninfected children. These included: asthenia, neck pain, back pain, paresthesia, and cranial nerve abnormalities. Neurocognitive and behavioral test scores were similar among ZIKV-infected and uninfected children. Our study suggests that ZIKV-infected children should be monitored for neurological symptoms and cranial neuropathy to better understand the full burden of acquired ZIKV infection among children.

The association between COVID-19 vaccine/infection and new-onset asthma in children - based on the global TriNetX database.

The COVID-19 pandemic has underscored the importance of its potential long-term health effects, including its link to new-onset asthma in children. Asthma significantly impacts children's health, causing adverse outcomes and increased absenteeism. Emerging evidence suggests a potential association between COVID-19 infection and higher rates of new-onset asthma in adults, raising concerns about its impact on children's respiratory health. A retrospective cohort study design was employed, using electronic medical records from the TriNetX database, covering January 1, 2021, to December 31, 2022. Two cohorts of children aged 5 to 18 who underwent SARS-CoV-2 RT-PCR testing were analyzed: unvaccinated children with and without COVID-19 infection, and vaccinated children with and without infection. Propensity score matching was used to mitigate selection bias, and hazard ratio (HR) and 95% CI were calculated to assess the risk of new-onset asthma. Our study found a significantly higher incidence of new-onset asthma in COVID-19 infected children compared to uninfected children, regardless of vaccination status. In Cohort 1, 4.7% of COVID-19 infected children without vaccination developed new-onset asthma, versus 2.0% in their non-COVID-19 counterparts within a year (HR = 2.26; 95% CI = 2.158-2.367). For Cohort 2, COVID-19 infected children with vaccination showed an 8.3% incidence of new-onset asthma, higher than the 3.1% in those not infected (HR = 2.745; 95% CI = 2.521-2.99). Subgroup analyses further identified higher risks in males, children aged 5-12 years, and Black or African American children. Sensitivity analyses confirmed the reliability of these findings. The study highlights a strong link between COVID-19 infection and an increased risk of new-onset asthma in children, which is even more marked in those vaccinated. This emphasizes the critical need for ongoing monitoring and customized healthcare strategies to mitigate the long-term respiratory impacts of COVID-19 in children, advocating for thorough strategies to manage and prevent asthma amidst the pandemic.

Missing microbes in infants and children in the COVID-19 pandemic: a study of 1,126 participants in Beijing, China.

The COVID-19 pandemic has caused many fatalities worldwide and continues to affect the health of the recovered patients in the form of long-COVID. In this study, we compared the gut microbiome of uninfected infants and children before the pandemic began (BEFORE cohort, n=906) to that of after the pandemic (AFTER cohort, n=220) to examine the potential impact of social distancing and life habit changes on infant/children gut microbiome. Based on 16S rRNA sequencing, we found a significant change in microbiome composition after the pandemic, with Bacteroides enterotype increasing to 35.45% from 30.46% before the pandemic. qPCR quantification indicated that the bacterial loads of seven keystone taxa decreased by 91.69%-19.58%. Quantitative microbiome profiling, used to enhance the resolution in detecting microbiome differences, revealed a greater explained variance of pandemic on microbiome compared to gender, as well as a significant decrease in bacterial loads in 15 of the 20 major genera. The random forest age-predictor indicated the gut microbiomes were less mature in the after-pandemic cohort than in the before-pandemic cohort in the children group (3-12 years old) and had features of a significantly younger age (average of 1.86 years). Lastly, body weight and height were significantly lower in the after-pandemic cohort than in the before-pandemic cohort in infants (<1 year of age), which was associated with a decrease in bacterial loads in the fecal microbiome.

Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children

Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent influenza vaccination in children (NCT00792051) conducted at the onset of the 2009 H1N1 pandemic (pH1N1) and monitored for infection. We found that seasonal vaccination increases pH1N1 specific antibodies and FcR effector functions. Furthermore, prospective baseline antibody profiles after seasonal vaccination, prior to pH1N1 infection, show that unvaccinated uninfected children have elevated ADCC effector function, FcγR3a and FcγR2a binding antibodies to multiple pH1N1 proteins, past seasonal and avian (H5, H7 and H9) strains. Whereas, children that became pH1N1 infected after seasonal vaccination have antibodies focussed to seasonal strains without FcR functions, and greater aggregated HA-specific profiles for IgM and IgG3. Modeling to predict infection susceptibility, ranked baseline hemagglutination antibody inhibition as the highest contributor to lack of pH1N1 infection, in combination with features that include pH1-IgG1, H1-stem responses and FcR binding to seasonal vaccine and pH1 proteins. Thus, seasonal vaccination can have benefits against pandemic influenza viruses, and some children already have broadly reactive antibodies with Fc potential without vaccination and may be considered ‘elite influenza controllers’.

Preconception and contraceptive care for women living with HIV/AIDS attending antiretroviral treatment clinics in Lagos State, Nigeria.

Women living with HIV/AIDS possess fertility desires similar to their uninfected counterparts, and with advances in health therapies, these women can realistically have and raise uninfected children. Preconception care (PC) is a specialized form of intervention aimed at the prevention, identification, treatment, and management of biomedical, behavioural, and social conditions that militate against safe motherhood and the delivery of healthy offspring. The study aimed to assess preconception and contraceptive care among women living with HIV and attending Antiretroviral Therapy Clinics in Alimosho, Lagos State, Nigeria. This was a descriptive facility-based cross-sectional study of 383 women of reproductive age living with HIV/AIDS and attending ART clinics in the study area. Probability sampling methods were used in the selection procedures. Data were analyzed using descriptive statistics, Chi-square test, and univariate logistic regression at a 5% level of significance. Stratified and simple random sampling were used in the selection process. Only 37.4% of respondents received optimal PC services. Being 20-29 years old [OR =1.716 (95% CI: 1.664, 1.769), p = 0.020], being 30-39 years [OR =1.514 (95% CI: 0.598, 3.831), p = 0.005], tertiary education [OR =8.43. (95% CI: 1.41, 18.5), p = 0.020], and being single [OR =2.00 (95% CI: 1.928-2.072), p = 0.002] were significantly related to the utilization of contraceptives. There is a need to provide structure and guidelines for optimal streamlined PC and contraceptive services for women living with HIV/AIDS.