Application of the Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the empiric antibiotic treatment of febrile neutropenia in oncological paediatric patients: experience from two paediatric hospitals in Northern Italy.

BACKGROUND: Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres. METHODS: We included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution. RESULTS: We collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin-tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin-tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens. CONCLUSIONS: The application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics.

Assessing the resilience of HIV healthcare services provided to adolescents and young adults after the COVID-19 pandemic in the city of Beira (Mozambique): an interrupted time series analysis.

BACKGROUND: The COVID-19 pandemic has put the provision of health services globally at risk. In Sub-Saharan Africa, it had a major impact on HIV services. However, there is a lack of data on the post-pandemic period. This study aims to evaluate the resumption of HIV services and retention in care for adolescents and young people in the period following the COVID-19 pandemic. METHODS: A retrospective cohort study was conducted using interrupted time series analysis. Three periods were considered: pre-pandemic (form June 2019 to March 2020), pandemic (form April 2020 to March 2022) post-pandemic (from April 2022 to March 2023). Six outcome measures were considered: number of outpatient visits, HIV tests, HIV positivity ratio, the antiretroviral treatment (ART) non-adherence ratio, recall ratio, and the return ratio for adolescent and young adults on ART. RESULTS: During the study period, 447,515 outpatient visits and 126,096 HIV tests were recorded. After a reduction at the beginning of the pandemic period, both visits and tests increased during the pandemic (p < 0.05) and decreased in the post-pandemic (p < 0.05), recovering the pre-pandemic trends. The HIV positivity ratio slightly decreased from 3.3% to 1.7% during the study period (p < 0.05). The ART non-adherence ratio decreased from 23.4% to 2.4% throughout the study period (p < 0.05), with a drop at the beginning of the post-pandemic period (p < 0.05). The recall ratio increased during the study period (p < 0.05) with a drop at the beginning of the pandemic and post-pandemic periods (p < 0.05). The return ratio decreased at the beginning of the pandemic (p < 0.05) but returned to the pre-pandemic ratio in the post-pandemic period. CONCLUSIONS: The post-pandemic values of the investigated outcomes were comparable to pre-pandemic period, or even improved. Differently from other services, such as the community activities, that have been severely affected by COVID-19 pandemic, the HIV service system has shown resilience following emergency situation.

SARS-CoV-2 seroprevalence and associated factors, based on HIV serostatus, in young people in Sofala province, Mozambique.

INTRODUCTION: In Sofala province (Mozambique), young people living with HIV (YPLHIV) are estimated at 7% among people aged 15-24 years. Even though the COVID-19 pandemic threatened HIV health services, data on the impact of COVID-19 on YPLHIV people are lacking. This study aimed at exploring the seroprevalence of SARS-CoV-2 and associated factors among young people based on their HIV status. METHODS: A cross-sectional study was conducted, including people aged 18-24 attending a visit at one of the adolescent-friendly health services in Sofala province between October and November 2022. People vaccinated against SARS-COV-2 or YPLHIV with WHO stage III-IV were excluded. A SARS-CoV-2 antibodies qualitative test and a questionnaire investigating socio-demographic and clinical characteristics were proposed. SARS-CoV-2 seroprevalence was calculated with Clopper-Pearson method. The odds ratio (OR) of a positive SARS-CoV-2 antibodies test was estimated through multivariable binomial logistic regression. RESULTS: In total, 540 young people including 65.8% women and 16.7% YPLHIV participated in the survey.. The mean age was 20.2 years (SD 2.0). Almost all the sample (96.1%) reported adopting at least one preventive measure for COVID-19. The weighted seroprevalence of SARS-CoV-2 in the whole sample was 46.8% (95%CI 42.6-51.2) and 35.9% (95%CI 25.3-47.5) in YPLHIV. The adjusted OR of testing positive at the SARS-CoV-2 antibodies test was higher in students compared to workers (aOR:2.02[0.95CI 1.01-4.21]) and in those with symptoms (aOR:1.52[0.95CI 1.01-2.30]). There were no differences based on HIV status(aOR:0.663[95%CI 0.406-1.069]). Overall, COVID-19 symptoms were reported by 68 (28.2%) people with a positive serological SARS-CoV-2 test and by 7 (21.7%) YPLHIV (p = 0.527). No one required hospitalization. CONCLUSIONS: SARS-CoV-2 seroprevalence was 46.8% without differences in risk of infection or clinical presentation based on HIV status. This result may be influenced by the exclusion of YPLHIV with advanced disease. The higher risk among students suggests the schools' role in spreading the virus. It's important to continue monitoring the impact of COVID-19 on YPLHIV to better understand its effect on screening and adherence to treatment.

Celiac disease in children.

Celiac disease is a common immune-mediated disease, that may present, after gluten ingestion, with various and heterogeneous symptoms that can vary according to patients' age. The diagnostic screening test is serum anti-tissue transglutaminase IgA level. In doubt cases, antiendomysium IgA and the antideamidated gliadin peptides IgG could be useful to confirm the suspicion, before a biopsy will be perform. Since 2012, guidelines have made it possible to avoid the biopsy in symptomatic pediatric patients with high levels of antitransglutaminase IgA, positivity to antiendomysium IgA, and with HLA DQ2 or DQ8. In all other cases duodenal biopsy is still mandatory to confirm the diagnosis. The therapy of celiac disease is a lifelong gluten free diet. In children prognosis of celiac disease is good, without complications. Here we review and discuss the present literature about celiac disease in childhood.

Assessing the impact of a community-based psychodrama intervention on mental health promotion of adolescents and young adults in Mozambique: A mixed-methods study.

Background: While mental health is an emerging issue in low-income countries, its promotion remains poor, with little context-oriented evidence available. Here we aimed to assess the impact and acceptability/feasibility of a community-based psychodrama intervention involving both adolescents and young adults (AYA) living with HIV (AYALHIV) and without HIV (AYAHIV-). Methods: We used a mixed-methods approach, where the quantitative part was based on pre/post questionnaires and the qualitative one on content analysis of semi-structured interviews. Trained community health care workers delivered psychodrama sessions involving AYAs aged 15-24 years once a week between July and August 2023 in Beira, Mozambique. The baseline assessment involved a sociodemographic and three mental health questionnaires: the Mental Health Knowledge Schedule (MAKS), Community Attitudes toward People with Mental Illness (CAMI27), and the Toronto Alexithymia Scale (TAS). We repeated all questionnaires after the intervention and conducted semi-structured interviews. Results: We enrolled 354 AYAs (50.8% female, 45.5% AYALHIV) at baseline; 315 (89.0%) attended the sessions, with a mean participation rate of 94.4%. Overall, 281 (89.2%) completed the post-intervention assessment. MAKS score improved from 44.5 (95% confidence interval (CI) = 44.0-45.0) to 47.1 (95% CI = 46.4-47.7, P < 0.001). Total CAMI27 score showed no significant variation (P = 0.855). Total TAS score decreased from 57.3 (95% CI = 56.1-58.5) to 54.3 (95% CI = 53.0-55.6, P < 0.001). We found no statistically significant interactions between time and sex, age, or HIV serostatus in all questionnaires. For the qualitative part of the study, we analysed 37 semi-structured interviews (43.2% with females, 40.5% with AYALHIV). We identified four areas of intervention impact: peer-to-peer support (30.3%), social empowerment (24.7%), resilience (23.0%), and emotional skills (21.9%). Regarding acceptability/feasibility, perceived scalability (37.2%) and affective attitude (34.5%) were the sub-areas most frequently retrieved in the SSIs. Conclusions: The community-based psychodrama intervention proved to be an effective tool in AYAs' mental health promotion, increasing knowledge and improving emotional awareness through group experience and interpersonal learning. The intervention also showed good acceptability and feasibility in the context of our study.

Stronger and durable SARS-CoV-2 immune response to mRNA vaccines in 5-11 years old children with prior COVID-19.

BACKGROUND AND OBJECTIVES: mRNA vaccines elicit a durable humoral response to SARS-CoV-2 in adults, whereas evidence in children is scarce. This study aimed to assess the early and long-term immune response to the mRNA vaccine in children with or without previous SARS-CoV-2 infection. METHODS: In a multicentre prospective observational study, we profiled the immune response to the Pfizer BioNTech (BNT162b2) vaccine in 5-11-year-old children attending the University Pediatric Hospital of Padua and Bambino-Gesù Hospital in Rome (Italy) from December-2021 to February-2023. Blood samples were collected pre-, 1-, and 6-months after vaccination. Neutralizing antibodies (NAbs) and anti-spike-receptor-binding-domain (anti-S-RBD) IgG titers were analyzed through Plaque Reduction Neutralization Test (PRNT) and chemiluminescent immune-enzymatic assay (CLIA), respectively. Immune cell phenotypes were analyzed by flow cytometry. RESULTS: Sixty children (26 [43 %] female, median age = 8 years [IQR = 7-10.7]) were enrolled in the study, including 46 children with a laboratory-confirmed previous COVID-19 (SARS-CoV-2-recovered) and 14 SARS-CoV-2-naïve participants defined as the absence of antigen-specific antibodies before vaccination. SARS-CoV-2-recovered participants recorded higher anti-S-RBD IgG and Wild-type and Omicron BA.2 NAbs titers than SARS-CoV-2-naïve participants at both 1- and 6-months after vaccination. Antibody titers correlated with T (Tregs) and B (Bregs) regulatory cell frequencies in SARS-CoV-2-recovered children. Both SARS-CoV-2-recovered and SARS-CoV-2-naïve participants decreased antibody titers by approximately 100 to 250 % from 1 to 6 months. While children with immunocompromising underlying conditions developed immune responses comparable to those of healthy children, solid organ transplant recipients exhibited lower levels of NAbs and anti-S-RBD IgG titers, as well as reduced frequencies of Tregs and Bregs. CONCLUSIONS: mRNA vaccination triggered a higher production of specific anti-SARS-CoV-2 antibodies along with increased levels of regulatory cells in children with previous SARS-CoV-2 infection up to the following 6 months. These findings provide insights into boosting pre-existing immunity.

Clinical features of COVID-19 in Italian outpatient children and adolescents during Parental, Delta, and Omicron waves: a prospective, observational, cohort study.

Introduction: COVID-19 features changed with the Omicron variant of SARS-CoV-2 in adults. This study aims to describe COVID-19 symptoms in children and adolescents during the Parental, Delta, and Omicron eras. Methods: A single-centre, prospective observational study was conducted on individuals aged 0-20 years attending the University Hospital of Padua (Italy) from April 2020 to December 2022. COVID-19 cases were defined by positive SARS-CoV-2 molecular detection and/or serology; patient/family symptoms and virological positivity were considered to determine the infection onset. Variables were summarized and compared using appropriate tests of descriptive statistics. Results: A total of 509 cases [46% female, median age eight years (IQR: 4-12)] were studied. Three-hundred-eighty-seven (76%), 52 (10%), and 70 (14%) subjects experienced COVID-19 during the Parental, Delta, and Omicron waves, respectively. All subjects developed an asymptomatic/mild COVID-19. Overall, the most frequent symptoms were fever (47%) and rhinitis (21%), which showed a significant increasing incidence from the Parental to Omicron waves (p < 0.001). Conversely, diarrhea was most common during the pre-Omicron eras (p = 0.03). Stratifying symptoms according to the age group, fever, rhinitis, and skin rashes were observed more frequently among infants/toddlers; conversely, fatigue was more common in children older than five years. The duration of symptoms was similar across different SARS-CoV-2 variants of concern (VOCs); conversely, the number of symptoms varied according to the age group (p < 0.0001). Discussion: This study showed differences in COVID-19 clinical presentation among infants, children, and adolescents and confirmed Omicron infection is more likely to be associated with upper respiratory symptoms. However, further population-based studies are needed to support these findings. In addition, active surveillance will play a crucial role in assessing the disease severity of future VOCs.

SARS-CoV-2 seroprevalence and associated factors, based on HIV serostatus, in young people in Sofala province, Mozambique

n In Sofala province (Mozambique), young people living with HIV (YPLHIV) are estimated at 7% among people aged 15­24 years. Even though the COVID-19 pandemic threatened HIV health services, data on the impact of COVID-19 on YPLHIV people are lacking. This study aimed at exploring the seroprevalence of SARSCoV-2 and associated factors among young people based on their HIV status. Methods A cross-sectional study was conducted, including people aged 18­24 attending a visit at one of the adolescent-friendly health services in Sofala province between October and November 2022. People vaccinated against SARS-COV-2 or YPLHIV with WHO stage III-IV were excluded. A SARS-CoV-2 antibodies qualitative test and a questionnaire investigating socio-demographic and clinical characteristics were proposed. SARS-CoV-2 seroprevalence was calculated with Clopper-Pearson method. The odds ratio (OR) of a positive SARS-CoV-2 antibodies test was estimated through multivariable binomial logistic regression. Results In total, 540 young people including 65.8% women and 16.7% YPLHIV participated in the survey.. The mean age was 20.2 years (SD 2.0). Almost all the sample (96.1%) reported adopting at least one preventive measure for COVID-19. The weighted seroprevalence of SARS-CoV-2 in the whole sample was 46.8% (95%CI 42.6­51.2) and 35.9% (95%CI 25.3­47.5) in YPLHIV. The adjusted OR of testing positive at the SARS-CoV-2 antibodies test was higher in students compared to workers (aOR:2.02[0.95CI 1.01­4.21]) and in those with symptoms (aOR:1.52[0.95CI 1.01­2.30]). There were no diferences based on HIV status(aOR:0.663[95%CI 0.406­1.069]). Overall, COVID-19 symptoms were reported by 68 (28.2%) people with a positive serological SARS-CoV-2 test and by 7 (21.7%) YPLHIV (p=0.527). No one required hospitalization. Conclusions SARS-CoV-2 seroprevalence was 46.8% without diferences in risk of infection or clinical presentation based on HIV status. This result may be infuenced by the exclusion of YPLHIV with advanced disease. The higher risk among students suggests the schools' role in spreading the virus. It's important to continue monitoring the impact of COVID-19 on YPLHIV to better understand its efect on screening and adherence to treatment.