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Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in infants. RSV infection is a self-limiting condition and does not require antibiotics. However hospitalized infants with clinical bronchiolitis often receive antibiotics for fear of bacteria coinfection, especially when chest radiography is performed due to similar radiographic appearance of infiltrate and atelectasis. This may lead to unnecessary antibiotic prescription, additional cost, and increased risk of development of resistance. Despite the considerable burden of RSV bronchiolitis, to date, only symptomatic treatment is available, and there are no commercially available vaccines. The only licensed passive immunoprophylaxis is palivizumab. The high cost of this monoclonal antibody (mAb) has led to limiting its prescription only for high-risk children: infants with chronic lung disease, congenital heart disease, neuromuscular disorders, immunodeficiencies, and extreme preterm birth. Nevertheless, it has been shown that the majority of hospitalized RSV-infected children do not fully meet the criteria for immune prophylaxis. While waiting for an effective vaccine, passive immune prophylaxis in children is mandatory. There are a growing number of RSV passive immunization candidates under development intended for RSV prevention in all infants. In this review, we describe the state-of-the-art of palivizumab's usage and summarize the clinical and preclinical trials regarding the development of mAbs with a better cost-effectiveness ratio.
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Antivirais/uso terapêutico , Palivizumab/uso terapêutico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sinciciais Respiratórios/imunologia , Humanos , LactenteRESUMO
Minor head trauma (MHT) is very frequent in children and post-traumatic headache (PTH) is one of its most common complications; however, its management is still a challenge. We aimed to assess the incidence and clinical characteristics of, and risk factors for, PTH among children referred to our pediatric emergency department (PED) for MHT. A total of 193 patients aged 3-14 years evaluated for MTH were enrolled and followed up for 6 months through phone calls and/or visits. PTH occurred in 25/193 patients (13%). PTH prevalence was significantly higher in school-aged (≥6 years) than in pre-school-aged children (21.6% vs. 4.9%, respectively, p < 0.009). Females were found to be more affected. The median time of onset was 4.6 days after MHT; resolution occurred in a median of 7 weeks. In 83.3% of patients, PTH subsided in <3 months, while in 16.7% it persisted longer. A total of 25% of children exhibited the migraine and 75% the tension-type variant. Our analysis indicates the presence of headache upon arrival in PED, isolated or associated with nausea and dizziness, as a factor predisposing the patient to the development of PTH. Our findings could be useful to identify children at risk for PTH for specific follow-up, family counseling, and treatment.
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Visceral Leishmaniasis (VL) is a vector-borne disease caused by an intracellular protozoa of the genus Leishmania that can be lethal if not treated. VL is caused by Leishmania donovani in Asia and in Eastern Africa, where the pathogens' reservoir is represented by humans, and by Leishmania infantum in Latin America and in the Mediterranean area, where VL is a zoonotic disease and dog is the main reservoir. A part of the infected individuals become symptomatic, with irregular fever, splenomegaly, anemia or pancytopenia, and weakness, whereas others are asymptomatic. VL treatment has made progress in the last decades with the use of new drugs such as liposomal amphotericin B, and with new therapeutic regimens including monotherapy or a combination of drugs, aiming at shorter treatment duration and avoiding the development of resistance. However, the same treatment protocol may not be effective all over the world, due to differences in the infecting Leishmania species, so depending on the geographical area. This narrative review presents a comprehensive description of the clinical picture of VL, especially in children, the diagnostic approach, and some insight into the most used pharmacological therapies available worldwide.
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Introduction: Anaphylaxis is one of the most frequent and misdiagnosed emergencies in the pediatric emergency department (PED). We aimed to assess which factors play a major role for a correct diagnosis and an appropriate therapy. Methods: We reviewed the records of children discharged with a diagnosis of anaphylaxis or an allergic reaction over 11 years from 3 hospitals in the Bologna city area. Results: One hundred and sixteen cases matched the criteria (0.03% of the total admittances) and were divided according to the patients' symptoms at arrival: active acute patients [AP], n = 50, or non-acute patients ([NAP], n = 66). At the patients' discharge, anaphylaxis was diagnosed in 39 patients (33.6%). Some features seemed to favor a correct diagnosis: active symptoms at arrival (AP vs. NAP, p < 0.01), high-priority triage code (p < 0.01), and upper airway involvement (p < 0.01). Only 14 patients (12.1%), all in the AP group, received epinephrine, that was more likely administered to patients recognized to have anaphylaxis (p < 0.01) and with cardiovascular, respiratory, or persistent gastrointestinal symptoms (p < 0.02), as confirmed by logistic regression analysis. Conclusions: Anaphylaxis is still under-recognized and under-treated. Correct triage coding and a proper diagnosis seem to foster an appropriate treatment. Physicians often prefer third-line interventions. Specific training for nurses and physicians might improve the management of this disease.
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Human cytomegalovirus (hCMV) is one of the most common causes of congenital infection in the post-rubella era, representing a major public health concern. Although most cases are asymptomatic in the neonatal period, congenital CMV (cCMV) disease can result in permanent impairment of cognitive development and represents the leading cause of non-genetic sensorineural hearing loss. Moreover, even if hCMV mostly causes asymptomatic or pauci-symptomatic infections in immunocompetent hosts, it may lead to severe and life-threatening disease in immunocompromised patients. Since immunity reduces the severity of disease, in the last years, the development of an effective and safe hCMV vaccine has been of great interest to pharmacologic researchers. Both hCMV live vaccines-e.g., live-attenuated, chimeric, viral-based-and non-living ones-subunit, RNA-based, virus-like particles, plasmid-based DNA-have been investigated. Encouraging data are emerging from clinical trials, but a hCMV vaccine has not been licensed yet. Major difficulties in the development of a satisfactory vaccine include hCMV's capacity to evade the immune response, unclear immune correlates for protection, low number of available animal models, and insufficient general awareness. Moreover, there is a need to determine which may be the best target populations for vaccine administration. The aim of the present paper is to examine the status of hCMV vaccines undergoing clinical trials and understand barriers limiting their development.
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Human Adenoviruses (HAdV) are known to be potentially associated with strong inflammatory responses and morbidity in pediatric patients. Although most of the primary infections are self-limiting, the severity of clinical presentation, the elevation of the white blood cell count and inflammatory markers often mimic a bacterial infection and lead to an inappropriate use of antibiotics. In infections caused by HAdV, rapid antigen detection kits are advisable but not employed routinely; costs and feasibility of rapid syndromic molecular diagnosis may limit its use in the in-hospital setting; lymphocyte cultures and two-sampled serology are time consuming and impractical when considering the use of antibiotics. In this review, we aim to describe the principal diagnostic tools and the immune response in HAdV infections and evaluate whether markers based on the response of the host may help early recognition of HAdV and avoid inappropriate antimicrobial prescriptions in acute airway infections.
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Infecções por Adenovirus Humanos/diagnóstico , Infecções Respiratórias/diagnóstico , Infecções por Adenovirus Humanos/imunologia , Infecções por Adenovirus Humanos/terapia , Biomarcadores/sangue , Criança , Pré-Escolar , Humanos , Lactente , Prognóstico , Infecções Respiratórias/imunologia , Infecções Respiratórias/terapia , Adulto JovemRESUMO
Bronchiolitis is the most common lower respiratory tract infection in infants. According to evidence-based guidelines, diagnosis is clinical, there is no need for routine use of laboratory or instrumental tests and therapy is primarily supportive, based on oxygen and adequate fluid supplementation. Nevertheless, unnecessary diagnostic tests and pharmacological treatments are still very common. The aim of this retrospective cohort study was to evaluate how the management of bronchiolitis has changed in the last ten years in a Tertiary Care Center in Italy, assessing adherence to national guidelines. Considering the publication of the Italian inter-society consensus document in 2014, we compared patients admitted in the prior four epidemic seasons with patients admitted in the latter six epidemic seasons. The comparison between the two groups showed a significant reduction in the prescription of systemic corticosteroids (58.9% vs. 41.8%, p < 0.001), nebulized epinephrine (73.8% vs. 38.3%, p < 0.001) and antibiotics (59.5% vs. 42.3%, p < 0.001), together with a drastic decrease in the use of chest X-ray (92.2% vs. 54.4%, p < 0.001). On the contrary, the use of inhaled salbutamol remained substantially stable over time (39.4% vs. 37.6%, p = 0.505). Despite the encouraging results, further efforts are needed to limit the prescription of ineffective therapies like antibiotics and inhaled salbutamol.
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Respiratory syncytial virus (RSV) is the main cause of acute respiratory tract infections in infants and it also induces significant disease in the elderly. The clinical course may be severe, especially in high-risk populations (infants and elderly), with a large number of deaths in developing countries and of intensive care hospitalizations worldwide. To date, prevention strategies against RSV infection is based on hygienic measures and passive immunization with humanized monoclonal antibodies, limited to selected high-risk children due to their high costs. The development of a safe and effective vaccine is a global health need and an important objective of research in this field. A growing number of RSV vaccine candidates in different formats (particle-based vaccines, vector-based vaccines, subunit vaccines and live-attenuated vaccines) are being developed and are now at different stages, many of them already being in the clinical stage. While waiting for commercially available safe and effective vaccines, immune prophylaxis in selected groups of high-risk populations is still mandatory. This review summarizes the state-of-the-art of the RSV vaccine research and its implications for clinical practice, focusing on the characteristics of the vaccines that reached the clinical stage of development.