Immunogenicity and protective capacity of a CpG ODN adjuvanted alum adsorbed bivalent meningococcal outer membrane vesicle vaccine.

Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis, with the main serogroups responsible for the disease being A, B, C, W, X, and Y. To date, several vaccines targeting N. meningitidis have been developed albeit with a short-lived protection. Given that MenW and MenB are the most common causes of IMD in Europe, Turkey, and the Middle East, we aimed to develop an outer membrane vesicle (OMV) based bivalent vaccine as the heterologous antigen source. Herein, we compared the immunogenicity, and breadth of serum bactericidal activity (SBA) assay-based protective coverage of OMV vaccine to the X serotype with existing commercial meningococcal conjugate and polysaccharide (PS) vaccines in a murine model. BALB/c mice were immunized with preclinical batches of the W + B OMV vaccine, either adjuvanted with Alum, CpG ODN, or their combinations, and compared with a MenACYW conjugate vaccine (NimenrixTM, Pfizer), and a MenB OMV-based vaccine (Bexsero®, GSK), The immune responses were assessed through enzyme-linked immunosorbent assay (ELISA) and SBA assay. Antibody responses and SBA titers were significantly higher in the W + B OMV vaccine when adjuvanted with Alum or CpG ODN, as compared to the control groups. Moreover, the SBA titers were not only significantly higher than those achieved with available conjugated ACYW vaccines but also on par with the 4CMenB vaccines. In conclusion, the W + B OMV vaccine demonstrated the capacity to elicit robust antibody responses, surpassing or matching the levels induced by licensed meningococcal vaccines. Consequently, the W + B OMV vaccine could potentially serve as a viable alternative or supplement to existing meningococcal vaccines.

Plasma Extracellular Vesicles Derived from Pediatric COVID-19 Patients Modulate Monocyte and T Cell Immune Responses Based on Disease Severity.

BACKGROUND: The COVID-19 pandemic has caused significant morbidity and mortality globally. The role of plasma-derived extracellular vesicles (EVs) in pediatric COVID-19 patients remains unclear. METHODS: We isolated EVs from healthy controls (n = 13) and pediatric COVID-19 patients (n = 104) with varying severity during acute and convalescent phases using serial ultracentrifugation. EV effects on healthy PBMCs, naïve CD4+ T cells, and monocytes were assessed through in vitro assays, flow cytometry, and ELISA. RESULTS: Our findings indicate that COVID-19 severity correlates with diverse immune responses. Severe acute cases exhibited increased cytokine levels, decreased IFNγ levels, and lower CD4+ T cell and monocyte counts, suggesting immunosuppression. EVs from severe acute patients stimulated healthy cells to express higher PDL1, increased Th2 and Treg cells, reduced IFNγ secretion, and altered Th1/Th17 ratios. Patient-derived EVs significantly reduced proinflammatory cytokine production by monocytes (p < .001 for mild, p = .0025 for severe cases) and decreased CD4+ T cell (p = .043) and monocyte (p = .033) populations in stimulated healthy PBMCs. CONCLUSION: This study reveals the complex relationship between immunological responses and EV-mediated effects, emphasizing the impact of COVID-19 severity. We highlight the potential role of plasma-derived EVs in early-stage immunosuppression in severe COVID-19 patients.

Clinical Challenge: Standard Versus Extended Meropenem Infusion in Children.

The management of Gram-negative bacterial infections poses a significant challenge due to the emergence of highly effective antibiotic-resistant mechanisms, leading to treatment failures, particularly among hospitalized children. This patient population experiences elevated rates of both mortality and morbidity, and the available antibiotic options against these bacteria are limited. Carbapenems, such as meropenem, represent one of the choices for treatment. While meropenem is highly effective against Gram-negative bacteria, the prevalence of multidrug-resistant infections in hospitals has become a growing concern. In response to this challenge, exploring innovative strategies is crucial. One such strategy is the implementation of high-dose extended meropenem infusion treatment. Researchers propose that extended meropenem treatment may offer a viable solution to combat resistant bacteria. Despite a limited number of studies focusing on the effectiveness of this strategy in children, our comprehensive review of the literature revealed promising findings. Our examination specifically compared extended infusion with standard infusion approaches. The evidence suggests that extended infusion of meropenem provides more benefits compared to standard infusion methods. Researchers consistently reported positive results in their observations, with the exception noted in very low birth weight neonates and children with infections caused by carbapenem-resistant Enterobacteria and Acinetobacter baumannii spp. In conclusion, extended meropenem infusion treatment emerges as a promising option for managing resistant infections. However, it is essential to underscore the need for further studies to robustly support the observed benefits of this treatment regimen.

The role of malnutrition on outcomes of multisystem inflammatory syndrome in children (MIS-C) due to COVID-19.

BACKGROUND: Malnutrition increases the complications and mortality in critically-ill children. We performed a retrospective analysis to define the impact of malnutrition on the outcomes of multisystem inflammatory syndrome in children (MIS-C) due to COVID-19. METHODS: Patients with MIS-C were evaluated for demographic features, anthropometric parameters, clinical findings and outcomes. Patients with z scores of body mass index (> 5 years) and weight-for-age (< 5 years) < -2 were considered malnourished. Sarcopenia was defined by total psoas muscle area (tPMA), calculated on abdominal computed tomography (CT) at the level of L3 and L4 vertebrae. The z scores <- 2 for tPMA were considered sarcopenia. The results of patients with and without malnutrition were compared. RESULTS: Twenty-seven patients were included. Forty-four percent (n=12) of patients had malnutrition. Malnutrition was classified as mild to moderate (1/3), severe (1/3) and overweight (1/3). Eighty-two % of cases had acute malnutrition. Among MIS-C symptom criteria, rash was significantly higher in children with malnutrition (p<0.05). Laboratory investigations showed higher ferritin levels in patients with malnutrition (p<0.05). The median tPMA and sarcopenia were significantly higher in patients with malnutrition when compared to patients without malnutrition (42% vs 7%, p<0.05). The oral feeding time, complication rates, and length of hospital stay were similar in both groups (p>0.05). CONCLUSION: Children with MIS-C already had mild to severe malnutrition at admission. Rash and higher ferritin levels were more common in patients with malnutrition. In addition to anthropometric parameters, sarcopenia calculated using tPMA can be used to predict malnutrition in critically-ill children.

Differentiating Multisystem Inflammatory Syndrome in Children from Kawasaki Disease During the Pandemic.

OBJECTIVE: We aimed to delineate the distinctive characteristics that aid in distinguishing between Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) with KD-like manifestations during the pandemic. MATERIALS AND METHODS: We evaluated KD patients and MIS-C patients with KD-like symptoms admitted during the pandemic (between January 2021 and December 2022). RESULTS: Thirty-three MIS-C patients and 15 KD patients were included. Kawasaki disease patients were younger than MIS-C patients (3.4 vs. 7.6 years). Rash (P = .044, 100% vs. 75.7%), oral mucosal changes (P = .044, 100% vs. 75.7%), and cervical lymphadenopathy (P = .001, 93.3% vs. 42.4%) were more common in KD. Multisystem inflammatory syndrome in children: patients had more hypotension (P = .002, 45.4% vs. 0), gastrointestinal (P .001, 72.7% vs. 13.3%), and respiratory symptoms (P = .044, 24.2% vs. 0). Multisystem inflammatory syndrome in children patients also had low lymphocyte and thrombocyte counts and elevated levels of d-dimer, ferritin, and cardiac parameters, unlike KD patients. Multisystem inflammatory syndrome in children patients exhibited a notable reduction in left ventricular systolic function in echocardiography. Another significant difference with regard to management was the anakinra treatment, which was prescribed for MIS-C patients. CONCLUSION: Although MIS-C patients might display a clinical resemblance to KD, several features could help differentiate between MIS-C and classical KD. Specific clinical (hypotension, gastrointestinal, and respiratory symptoms) and laboratory (low lymphocyte and thrombocyte counts with higher C-reactive protein, ferritin, d-dimer, and cardiac parameters) features are characteristic of MIS-C. In addition, divergence in management strategies is evident between the 2 diseases, as biologic drugs were more prevalently employed in MIS-C patients than in classical KD patients.

Gram-negative bacteremia, the risk factors, and outcome in children.

We aimed to determine the epidemiology and resistance patterns of Gram-negative bacteria, the risk factors and outcome of bloodstream infection (BSI). In all, 412 episodes in children who were hospitalized with the diagnosis of bacteremia were analyzed. The most common microorganisms were Klebsiella spp. (43.9%), Escherichia coli (13.5 %) and Acinetobacter spp. (10.6 %). Among isolates, 41.2 % were multidrug-resistant, 13.5 % were extensively drug-resistant and 0.4 % were pan-drug-resistant. Carbapenem resistance was revealed in 27.6 % of isolates. Carbapenem and colistin resistance increased over the years. The most common risk factors were the presence of a central-venous catheter and pediatric intensive care unit admission. Clinical response and infection-related mortality were significantly different in cases infected with carbapenem-resistant gram-negative (CRGN) vs carbapenem-susceptible gram-negative bacteria. The increase in multi-resistant Klebsiella spp. seems to be the biggest obstacles in fight against nosocomial infections. The increasing number of CRGN infections over the years affects both the clinical response and mortality rate of BSI.

Can procalcitonin be a diagnostic marker for catheter-related blood stream infection in children? / A procalcitonina pode ser um marcador de diagnóstico de infecções de corrente sanguínea relacionadas a cateter em crianças?

Abstract Objective The potential role of procalcitonin (PCT) in the diagnosis of catheter-related bloodstream infection (CRBSIs) is still unclear and requires further research. The diagnostic value of serum PCT for the diagnosis of CRBSI in children is evaluated here. Method This study was conducted between October 2013 and November 2014, and included patients with suspected CRBSI from 1 month to 18 years of age who were febrile, with no focus of infection, and had a central venous catheter. Levels of PCT and other serum markers were measured, and their utility as CRBSI markers was assessed. Additionally, the clinical performance of a new, automated, rapid, and quantitative assay for the detection of PCT was tested. Results Among the 49 patients, 24 were diagnosed with CRBSI. The PCT-Kryptor and PCT-RTA values were significantly higher in proven CRBSI compared to those in unproven CRBSI (p = 0.03 and p = 0.03, respectively). There were no differences in white blood cell count and C-reactive protein (CRP) levels between proven CRBSI and unproven CRBSI. Among the 24 patients with CRBSI, CRP was significantly higher among those with Gram-negative bacterial infection than in those with Gram-positive bacterial infections. PCT-Kryptor was also significantly higher among patients with Gram-negative bacterial infection than in those with Gram-positive bacterial infections (p = 0.01 and p = 0.02, respectively). Conclusions The authors suggest that PCT could be a helpful rapid diagnostic marker in children with suspected CRBSIs.

Resumo Objetivo O possível papel da procalcitonina (PCT) no diagnóstico de infecções de corrente sanguínea relacionadas a cateter (ICSRCs) ainda não está claro e precisa ser mais pesquisado. O valor diagnóstico da PCT sérica para o diagnóstico de ICSRC em crianças é avaliado neste estudo. Método Este estudo foi feito entre outubro de 2013 e novembro de 2014 e incluiu pacientes com suspeita de ICSRC de um mês a 18 anos que estavam febris, não tinham foco de infecção e tinham cateter venoso central. Foram medidos os níveis de PCT e de outros marcadores séricos, cuja utilidade como marcadores de ICSRC foi avaliada. Adicionalmente, foi testado o desempenho clínico de um novo ensaio quantitativo automatizado e rápido para a detecção de PCT. Resultados Dentre 49 pacientes, 24 foram diagnosticados com ICSRC. Os valores de PCT-Kryptor e PCT-RTA foram significativamente maiores em ICSRCs comprovadas do que em ICSRCs não comprovadas (p = 0,03 e p = 0,03, respectivamente). Não houve diferença na contagem de glóbulos brancos e nos níveis de proteína C reativa (PCR) entre ICSRCs comprovadas e ICSRCs não comprovadas. Dentre os 24 pacientes com ICSRC, a PCR era significativamente maior entre aqueles com infecção bacteriana gram-negativa do que naqueles com infecção bacteriana gram-positiva. O PCT-Kryptor também foi significativamente maior entre pacientes com infecção por bactérias gram-negativas do que naqueles com infecção por bactérias gram-positivas (p = 0,01 e p = 0,02, respectivamente). Conclusões Sugerimos que a PCT pode ser um marcador de diagnóstico rápido útil em crianças com suspeita de ICSRCs.

Sarcoidosis del adulto de inicio en la infancia: a proposito de un caso / Pediatric-onset adult type sarcoidosis: A case report

La sarcoidosis, un trastorno multiorgánico de etiología desconocida que afecta varios órganos, es poco frecuente en los niños. Se desconocen la incidencia y la prevalencia reales de la sarcoidosis infantil. Al igual que en los adultos, muchos niños con sarcoidosis tal vez no presentan síntomas y la enfermedad cursa sin diagnosticarse. Es fundamental realizar una evaluación completa y sistemática del paciente para establecer el diagnóstico de sarcoidosis en los niños. Se describe el caso de una nina de 12 años con uveítis y hepatoesplenomegalia de dos años de evolución. Mediante una tomografía computarizada del tórax, se hallaron nódulos pulmonares periféricos dispersos y linfadenopatía hiliar bilateral. La aspiración de médula ósea y la biopsia de hígado no fueron diagnósticas. La biopsia de pulmón mostró granulomas de células epitelioides no necrosantes. A la paciente se le diagnosticó sarcoidosis en virtud del hallazgo de inflamación granulomatosa y de la exclusión de entidades confusoras.

Sarcoidosis, a multisystem disorder of unknown etiology that involves multiple organs, is rare in children. The true incidence and prevalence of childhood sarcoidosis is unknown. As in adults, many children with sarcoidosis may be asymptomatic; the disease may remain undiagnosed. A complete and systematic evaluation of the patient is essential for the sarcoidosis diagnosis in children. Here, we describe a case of 12-year-old female who presented with 2 years history of uveitis and hepatosplenomegaly. A chest computerized tomography revealed scattered peripheral pulmonary nodules and bilateral hiliar lymphadenopathy. Bone marrow aspiration and liver biopsy were not diagnostic. A lung biopsy showed non-necrotizing epithelioid cell granulomas. She was diagnosed with sarcoidosis according to demonstration of granulomatous inflammation and the exclusion of confusable entities