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New technologies for the prevention of infectious diseases are emerging to address unmet medical needs, in particular, the use of long-acting monoclonal antibodies (mAb) to prevent Respiratory Syncytial Virus (RSV) lower respiratory tract disease in infants during their first RSV season. The lack of precedent for mAbs for broad population protection creates challenges in the assessment of upcoming prophylactic long-acting mAbs for RSV, with associated consequences in legislative and registration categorization, as well as in recommendation, funding, and implementation pathways. We suggest that the legislative and regulatory categorization of preventative solutions should be decided by the effect of the product in terms of its impact on the population and health-care systems rather than by the technology used or its mechanism of action. Immunization can be passive and active, both having the same objective of prevention of infectious diseases. Long-acting prophylactic mAbs work as passive immunization, as such, their recommendations for use should fall under the remit of National Immunization Technical Advisory Groups or other relevant recommending bodies for inclusion into National Immunization Programs. Current regulations, policy, and legislative frameworks need to evolve to embrace such innovative preventative technologies and acknowledge them as one of key immunization and public health tools.

Introduction: According to the latest report from the World Health Organization (WHO), approximately 10.0 million people fell ill with tuberculosis (TB) in 2020, 12% of which were children aged under 15 years. There is very few experience on treatment of multi-drug resistant (MDR)-TB in pediatrics., Areas Covered: The aim of this review is to analyze and summarize therapeutic options available for children experiencing MDR-TB. We also focused on management of MDR-TB prophylaxis., Expert Opinion: The therapeutic management of children with MDR-TB or MDR-TB contacts is complicated by a lack of knowledge, and the fact that many potentially useful drugs are not registered for pediatric use and there are no formulations suitable for children in the first years of life. Furthermore, most of the available drugs are burdened by major adverse events that need to be taken into account, particularly in the case of prolonged therapy. A close follow-up with a standardized timeline and a comprehensive assessment of clinical, laboratory, microbiologic and radiologic data is extremely important in these patients. Due to the complexity of their management, pediatric patients with confirmed or suspected MDR-TB should always be referred to a specialized center.

Skin and soft tissue infections (SSTIs) represent a heterogenous group of pathological conditions involving the skin or the underlying subcutaneous tissues, fascia and muscle, characterised by a considerable variety of clinical presentations, severity and possible aetiological pathogens. Although previous analyses on restricted types of SSTIs and population have already been published, we conducted a large nationwide surveillance program on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients and their management. Twenty-nine Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. We included in our database all cases managed by ID specialists participating to the study, independently from their severity or the setting of consultation. Here, we integrated previous preliminary results analysing and reporting data referring to a 3-year period (October 2016-October 2019). During this period, the study population included 478 adult patients with diagnosis of SSTI. The type of infection diagnosed, the aetiological agent involved and some notes on antimicrobial susceptibilities were collected and reported herein. We also analysed the most common co-morbidities, the type and duration of therapy executed, before and after ID intervention and the length of stay. The results of our study provide information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy.

Recurrent infections of upper and lower respiratory tract have an important clinical and economic impact, which can be reduced through appropriate preventive measures, including the use of immunomodulating agents, such as OM-85, which proved to be effective and safe in both adults and children. Although OM-85 can be useful for the prevention of respiratory tract infections, it is still underused in clinical practice. In order to evaluate the level of awareness of the disease burden of recurrent respiratory infections in adults and children and to assess the level of agreement on the prophylactic and therapeutic approach to the disease, including the use of immunomodulants, a Delphi study was performed. A board of six experts in the field of respiratory infections was appointed to elaborate a series of statements covering four main topics (disease, prevention, OM-85, and future strategies), which were thereafter voted by a panel of 30 experts. Results showed that prevention is unanimously recognized as the most important intervention to reduce disease burden, and the use of immunomodulation to improve the effectiveness of vaccination is gaining increasing favor among clinicians. In this respect, OM-85 is recognized as the most studied immunomodulating agent currently available, whose efficacy and safety make it a valuable tool to optimize the management of recurrent respiratory infections in both adults and children. In particular, the combined use of OM-85 and influenza vaccine was recognized as an effective and safe approach to improve the current prevention strategies in order to reduce the burden of recurrent respiratory infections.

There is limited evidence available on the long-term impact of SARS-CoV-2 infection in children. In this article, the authors analyze the recent evidence on pediatric long Covid and lessons learnt from a pediatric post-Covid unit in Rome, Italy. To gain a better understanding of the concerns raised by parents and physicians in relation to the potential long-term consequences of this novel infection, it is important to recognize that long-term effect of a post-infectious disease is not a new phenomenon.

Introduction: In the last decades, the large use of several effective vaccines has dramatically reduced the incidence of community acquired pneumonia (CAP) in infants and children. Moreover, the availability of new antibiotics effective against emerging resistant strains of bacteria has greatly improved the early and long-term prognosis of this disease., Areas Covered: The aim of this manuscript is to evaluate the burden of complicated CAP in pediatric age and to discuss its appropriate management., Expert Opinion: Complicated CAP remains a problem for children in industrialized and developing countries. A larger use of lung ultrasonography (US) as first diagnostic approach could significantly improve early identification of cases at higher risk of complications. Difficult to solve, is the problem of the use of an antibiotic therapy able to assure adequate control in all the CAP cases, including those at high risk of or with already established complications. All these findings reveal that control of the incidence of complicated CAP remains difficult and will not be significantly changed in the next few years. Any attempt to improve complicated CAP management must be made. Consensus documents on better definition of the use of corticosteroids, fibrinolytic agents, and interventional procedures (including surgery) can allow us to reach this goal.

Introduction : The cornerstone of rheumatoid arthritis (RA) therapy relies on the treat-to-target strategy, which aims at dampening inflammation as soon as possible in order to achieve persistent low disease activity or, ideally, remission, according to validated disease activity measures. Traditional disease-modifying antirheumatic drugs (DMARDs) may be chosen in monotherapy or in combination as first-line therapy; in case of an unsatisfactory response after a 3-6-month trial, biologic therapy may be commenced. Areas covered : Real-life RA patients may present with concomitant comorbidities/complications or be in peculiar physiological states which raise more than one question as to which biotherapy may be more well suited considering the whole clinical picture. Therefore, a thorough literature search was performed to identify the most appropriate biologic therapy in each setting considered in this review. Expert opinion : Here we provide suggestions for the use of biologic drugs having a predictable better outcome in specific real-world conditions, so as to ideally profile the patient to the best of the current knowledge.

Introduction: Prior to implementation of Haemophilus influenzae type b (Hib)-conjugate vaccination programs in the 1990s, Hib was the commonest cause of bacterial meningitis in children aged <5 years. While the burden of all Hib disease has significantly decreased in the post-vaccination era, Hib still accounted for >29,000 deaths worldwide in children aged <5 years in 2015., Areas Covered: We reviewed literature data on the most widely used Hib vaccines and vaccination strategies which led to the global prevention and control of Hib disease and aim to highlight important factors for continued disease control and elimination in the future., Expert Commentary: More than 90% of countries worldwide have implemented Hib-conjugate vaccination in their national immunization programs. Vaccines containing Hib polyribosylribitol phosphate (PRP) conjugated with tetanus toxoid (Hib-TT) are the most commonly used. Neisseria meningitidis outer membrane protein complex of PRP (Hib-OMP) is also used. Although the kinetics of the immune response varies with Hib vaccine and schedule used, high control of Hib disease was observed in all settings/scenarios. Further improving global Hib vaccination coverage may result in disease elimination. Plain language summary What is the context? Haemophilus influenzae is causing a variety of diseases, from otitis media and sinusitis to invasive disease (e.g. meningitis and pneumonia). H. influenzae type b (Hib) was the most common cause of bacterial meningitis in children <5 years of age, and especially among <2-year-olds. Even with appropriate treatment, up to 40% of children with bacterial meningitis can suffer permanent disabilities and up to 5% will die. The development of vaccines to protect against Hib disease has started in the late 1970s and has culminated with the licensure of 4 Hib conjugate vaccines, of which 2 are currently widely used. What is new? In this review, we gathered evidence on the different Hib vaccines and vaccination strategies that have contributed to the global prevention and control of Hib disease. The review indicates: the incidence of Hib disease has decreased considerably due to the introduction of Hib vaccines in national immunization programs worldwide. However, Hib disease is not yet completely eradicated. the vaccines currently used offer protection against Hib over long periods of time. carriage of the pathogen by healthy individuals seem to be less frequent, but data are still needed to fully evaluate the impact of vaccination. other H. influenzae types are now more frequent. Why is this important? Despite the huge success of Hib vaccination, continuous surveillance is needed to anticipate potential re-emergences and devise the best strategies for prevention and control of disease. Hib vaccination should be considered in the few countries who have not yet implemented it, to decrease associated morbidity and mortality.

Introduction: Otitis media (OM) is a spectrum of infectious and inflammatory diseases that involve the middle ear. It includes acute otitis media (AOM), otitis media with effusion (OME) and chronic suppurative otitis media (CSOM)., Areas Covered: This manuscript discusses some of the emerging and unsolved problems regarding OM, and some of the newly developed prophylactic and therapeutic medical measures., Expert Opinion: In recent years, considerable progress in the knowledge of OM physiopathology has been made. However, although extremely common, diseases included under OM have not been adequately studied, and many areas of development, evolution and possible treatments of these pathologies are not defined. It is necessary that these deficiencies be quickly overcome if we want to reduce the total burden of a group of diseases that still have extremely high medical, social and economic relevance.

Introduction : approximately half of Crohn's disease (CD) patients suffer from concomitant extra-intestinal manifestations (EIMs). Moreover, CD patients may suffer from comorbidities or have physiologic characteristics that may influence the outcome of a biologic treatment. Previous guidelines, published when only TNF-α antagonists were available as biological agents, addressed only management of CD patients with the most common EIMs. Areas covered : Because of the recent introduction of new biologics for the treatment of Crohn's disease as well as increased awareness about comorbidities potentially able to affect the impact of biological drugs, here we provide an update on management considering old and new biologics with proven efficacy on both Crohn's disease and associated conditions, in order to ideally profile the patient to the best of the current knowledge. Expert Opinion : While waiting for identification and validation of widely available and reliable biomarkers able to predict which biologic may yield the best response in the individual IBD patient (rigorous precision medicine), the choice of biologic agents in CD patients in order to achieve the best outcome still lies on a thorough assessment of patient-related characteristics as well as deep knowledge of the properties and place in therapy of each biologic drug.

This study was planned to evaluate whether a 3-month treatment with Lactobacillus rhamnosus GG (LGG) can modify immune system functions in children and adolescents with type 1 diabetes (T1D), leading to an increased immune response to an injectable quadrivalent inactivated influenza vaccine (QIV). A total of 87 pediatric patients with T1D were screened, although 34 patients in the Probiotic group and 30 in the Control group accepted to be vaccinated with QIV and completed the study. Vaccine immunogenicity and safety and the inflammatory cytokine response were studied. Results showed that QIV was immunogenic and safe in T1D pediatric patients and pre-administration of LGG for three months did not substantially modify the QIV humoral immunity. The combination of QIV and LGG reduced inflammatory responses (i.e., IFN-γ, IL17A, IL-17F, IL-6, and TNF-α) from activated PBMCs of pediatric patients with T1D, without dampening the production of seroprotective antibodies. In conclusion, QIV is associated with an adequate immunogenicity in children and adolescents with T1D in presence of a good safety profile. Although a systematic administration of LGG did not result in an improvement of humoral responses to an influenza vaccine, the probiotic did induce important anti-inflammatory effects.

Introduction : Neonatal sepsis (NS) is a very severe condition that causes significant morbidity and mortality. Areas covered : To overcome the limits of antibiotic therapy and improve NS outcomes, measures chosen among those theoretically able to improve host defenses or positively interfere with deleterious immune responses could be suggested. This paper discusses the mechanisms of action of these measures, whether their efficacy in prophylaxis justifies use in NS therapy and their impact. Expert opinion : NS remains a relevant problem despite the availability of antibiotics effective against the most common agents and the introduction of effective preventive measures such as group B Streptococcus prenatal screening and intrapartum antibiotic prophylaxis. This explains why attempts to introduce new prophylactic and therapeutic measures have been made. Unfortunately, none of the measures suggested and tested to date can be considered a definitive advance. It is highly likely that in the future, new measures will be proposed according to the increase in the knowledge of the characteristics of immune system function in preterm infants and the methods to modulate unproper immune responses.

Introduction : Antibiotics have saved and are still saving countless human lives from the burden of infectious diseases. However, as with all other drugs, they can cause adverse events. Generally, these are uncommon, mild and spontaneously resolving. However, in some cases, they can cause relevant clinical problems. Compared with adults, children, particularly in the first years of life, have a higher risk of antibiotic-related adverse events for several reasons. Areas covered : In this paper, the conditions that can contribute to the elevated risk of antibiotic-related adverse events in children are discussed. Expert opinion : Antibiotic stewardship can be a solution to limit antibiotic abuse and misuse and consequently the incidence of antibiotic-related adverse events in children. Moreover, most of the antibiotic-associated adverse events can be avoided with more extensive pre-marketing medicine investigations, improved postmarket safety surveillance system, increased transparency throughout the clinical research enterprise, increased training of clinical pharmacologists and paediatric researchers, expanded pool of paediatric patients, and providing additional funding and incentives for paediatric drug development.

Introduction : Acute otitis media (AOM) is a common disease, particularly in infants and young children. Almost all children experience at least one episode of AOM in the first 3 years of age, and approximately 50% experience recurrent episodes in the same period of time. Areas covered : Some new potentially effective preventive or therapeutic approaches to AOM have been identified and are not discussed even in the most updated guidelines. The main aim of this narrative review is to detail what has been recently suggested. Expert opinion : Several new measures have been suggested to reduce systemic antibiotic abuse in AOM therapy and prophylaxis. For therapy, the administration of preparations containing antibiotics, bacteriophages or peptides can allow trans-tympanic passage of effective anti-otopathogen measures and the use of vaccines or immunoglobulins can disrupt biofilm. For AOM prophylaxis, new vaccines and the use of probiotics by nasal spray are in development. However, further advances in the selection of children for whom antimicrobial therapy and/or prophylaxis measures are truly needed could be derived from studies that analyse the association between genetic characteristics of the host and development of AOM with specific characteristics of aetiology or tendency to recur.

Skin and soft tissue infections (SSTIs) represent a wide range of clinical conditions characterized by a considerable variety of clinical presentations and severity. Their aetiology can also vary, with numerous possible causative pathogens. While other authors previously published analyses on several types of SSTI and on restricted types of patients, we conducted a large nationwide surveillance programme on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients. Twenty-five Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. All the cases included in our database, independently from their severity, have been managed by ID specialists joining the study while SSTIs from other wards/clinics have been excluded from this analysis. Here, we report the preliminary results of our study, referring to a 12-month period (October 2016-September 2017). During this period, the study population included 254 adult patients and a total of 291 SSTI diagnoses were posed, with 36 patients presenting more than one SSTIs. The type of infection diagnosed, the aetiological micro-organisms involved and some notes on their antimicrobial susceptibilities were collected and are reported herein. The enrichment of our registry is ongoing, but these preliminary results suggest that further analysis could soon provide useful information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy.

Introduction: Pediatric community-acquired pneumonia (CAP) remains a significant health problem worldwide. Although knowledge in the etiology of CAP is not satisfactory, in most cases, therapy is decided following probability-based criteria that are derived from studies that report the frequency of detection of pathogens in children with CAP. Areas covered: This narrative review discusses the present knowledge on pediatric CAP etiology, the limits of the aetiological studies and the tests for differentiation of viral from bacterial infections. Expert commentary: The type of therapeutic approach in pediatric CAP is chosen considering the risk of bacterial etiology and the pathogens most frequently detected in the different pediatric ages. Fear of the potential negative course of unrecognized and untreated bacterial CAP is the main reason for the large use of antibiotics. Unfortunately, the antibiotic prescription is unnecessary in most of the cases as it can favor the emergence of resistant strains and can increase the number of drug-related adverse events. However, it is likely that a significant reduction of antibiotic prescriptions will occur when point-of-care tests with biomarkers for differentiation viral from bacterial infections become available.

Introduction: Skin and Soft Tissue Infections (SSTIs) are some of the most commonly occurring bacterial infections, with a wide range of possible etiological pathogens and a considerable variety of clinical presentations and severity; from mild to severe life-threatening infections. Several classifications have been proposed based on a specific variable, such as anatomical localization, skin extension, progression rate, clinical presentation, severity, and etiological agent. Areas covered: The last criteria allows the differentiation of SSTIs as monomicrobial and polymicrobial. Among them, especially those infections with a long lasting or chronic course can be sustained by multiple microbial etiology. Most polymicrobial SSTIs can be included in the following: diabetes foot infections (DFIs), pressure ulcers infection, burn infection, and infected chronic ulcers. Expert commentary: The medical management of these infections comprises the administration of wide a spectrum antibiotic, taking into consideration the frequent occurrence of multidrug resistant microorganisms as responsible agents. An appropriate deep tissue specimen for microbiological examination is a very important issue, especially for polymicrobial infections, sometimes permitting the distinction between real pathogens and contaminants avoiding more complex antibiotic treatments. This aspect must be strongly emphasized, as frequently superficial swabs remain the specimen of choice because they are easy to obtain.

Introduction: Chronic hepatitis C virus (HCV) infection has been associated with myriad extrahepatic manifestations, often resulting from aberrant immune responses. Among the most common immune-mediated manifestations of HCV infection, mixed cryoglobulinemia is the best known extra-hepatic complication. Areas covered: Here we review less common extrahepatic manifestations of HCV infection, with ascertained or presumed immune pathogenesis and the role of the new all oral direct-acting antiviral agents. Rheumatologic, dermatologic, ophthalmologic, renal, pulmonary, hematologic, cardiovascular, and neuropsychiatric manifestations of HCV infection have been considered. Expert commentary: Pathogenesis of HCV-induced aberrant immune responses resulting in peculiar clinical manifestations is not restricted to a single mechanism. A sound approach would therefore consider implementation of an etiologic treatment, through use of antiviral medications, to stop upstream in the pathogenic process all the immune mechanisms leading to hepatic and extrahepatic abnormalities. With the recent introduction of interferon-free, direct antiviral agents, capable of warranting cure for nearly all HCV-infected patients subjected to therapy, both common and uncommon extrahepatic manifestations of chronic hepatitis C are expected to no longer constitute a matter of comorbidity in the course of HCV infection.

Introduction: Abuse and misuse of available antimicrobial drugs have increased antimicrobial resistance (AMR), with relevant adverse health and economic impacts. Several factors suggest that the influenza vaccine is a possible effective measure to control AMR through a significant reduction in antibiotic consumption. In this paper, aspects related will be discussed., Areas Covered: Although the effectiveness of influenza immunization can significantly vary according to the study design, the circulating influenza viruses, the type of vaccine, the age of the enrolled subjects, the outcome measured and the season of the study, all experts agree that the influenza vaccine can significantly reduce the risk of contracting influenza in subjects of any age. Consequently, influenza vaccination may reduce the number of bacterial superimposed infections that can complicate influenza and require antibiotic prescriptions, Expert Commentary: Several indirect and direct observations seem to indicate that influenza vaccines can play an important role in reducing influenza-related antibiotic prescriptions. This finding can lead to at least two undeniable advantages, reductions in drug expenditure and limitations of the risk of favoring AMR development. However, only when universal vaccination is accepted and implemented will the true advantages of the influenza vaccine in reducing AMR development be completely known and exploited.

Introduction: Community-acquired pneumonia (CAP) remains one of the most common reasons for paediatric morbidity and accounts for about 16% of all the deaths occurring in children less than 5 years of age. Areas covered: The main aim of this paper is to discuss the emerging problems for CAP treatment in paediatric age. Expert commentary: Official recommendations for therapeutic approaches to paediatric CAP, despite being not very recent, seem still to be the best solution to assure the highest probabilities of cure for children with this disease living in industrialized countries. Amoxicillin remains the drug of choice and use of macrolides alone or in combination does not seem supported by solid evidence. Corticosteroids can be useful in CAP associated with bronco-obstruction, whereas their effectiveness in cases with a severe inflammatory response, although plausible, is not supported by data collected through randomized, placebo-controlled trials. Finally, for the administration of vitamin C and vitamin D, the available data are not adequate to draw firm conclusions regarding the real importance of supplementation. Further studies are needed to evaluate which modifications of presently available recommendations for paediatric CAP treatment can improve final prognosis of this still common disease.

Multiple sclerosis (MS) is a multifactorial, inflammatory, and neurodegenerative disease of the central nervous system, where environmental factors interact with genetic susceptibility. The role of diet on MS has not been comprehensively elucidated; therefore, through an extensive search of relevant literature, this review reports the most significant evidence regarding nutrition as a possible co-factor influencing the inflammatory cascade by acting on both its molecular pathways and gut microbiota. Since nutritional status and dietary habits in MS patients have not been extensively reported, the lack of a scientific-based consensus on dietary recommendation in MS could encourage many patients to experiment alternative dietetic regimens, increasing the risk of malnutrition. This work investigates the health implications of an unbalanced diet in MS, and collects recent findings on nutrients of great interest among MS patients and physicians. The aim of this review is to elucidate the role of an accurate nutritional counseling in MS to move toward a multidisciplinary management of the disease and to encourage future studies demonstrating the role of a healthy diet on the onset and course of MS.

Recently, two vaccines against meningococcal serogroup B (MenB) have been developed. They are prepared according to the reverse vaccinology approach and contain 4 (4CMenB) and 2 (MenB-FHbp) cross-reactive surface proteins. In Italy 4CMenB vaccine has been included in the official vaccination schedule only recently and recommended only for infants and toddlers, whereas MenB-FHbp is not licensed. In order to collect information about the present carriage of Neisseria meningitidis serogroup B (MenB) in Italian adolescents and to evaluate the potential protection offered by the presently available MenB vaccines, 2,560 otherwise healthy, high school students aged 14-21 years (907 males, 35.4%, median age 16.2 years) were enrolled in Milan, Italy. A swab to collect posterior pharynx secretions was collected from each subject and meningococcal identification, serogrouping, multilocus sequence typing analysis, sequence alignments and phylogenetic analysis were performed. A total of 135 (5.3%) adolescents were meningococcal carriers. Strains belonging to serogroup B were the most common (n = 58; 2.3%), followed by MenY (n = 32; 1.2%), MenC (n = 7; 0.3%), MenW (n = 6; 0.3%) and MenX (n = 5; 0.2%). The remaining bacteria were not capsulated. The identified MenB strains belonged to eleven clonal complexes (CCs): ST-162 CC (n = 12; 20.7%), ST-865 CC (n = 12; 20.7%), ST-41/44/Lin.3 CC (n = 11; 19.0%), ST-35 CC (n = 6; 10.3%), ST-32/ET-5 CC (n = 4; 6.9%), ST-269 CC (n = 3; 5.2%), ST-213 CC (n = 2; 3.4%), ST-198 CC (n = 1; 1.7%), ST-461 CC (n = 1; 1.7%), ST-549 CC (n = 1; 1.7%), and ST-750 CC (n = 1; 1.7%). This study showed that MenB was the most commonly carried meningococcal serogroup found in adolescents living in Milan, Italy. The MenB vaccines presently licensed could have theoretically induced the production of antibodies effective against the greatest part of the identified MenB strains (100% in the case of 4CMenB and 95% in case of MenB-FHbp) Monitoring carriage remains essential to evaluate MenB circulation, but further studies are necessary to evaluate the effect on carriage and the final efficacy of both new MenB vaccines.

Staphylococcus aureus is still an important problem in clinical and therapeutic area, worldwide. In Italy, in recent years, methicillin resistance remained stable, yet considerably high, the percentage of strains of MRSA being around 40%. It was deemed interesting and timely to carry out a consensus conference using the RAND/UCLA method to collect the opinion of a group of experts in infectious diseases on the role of glycopeptides in the management of MRSA infections within several clinical scenarios and namely in pneumonia, bacteremia and endocarditis, joint replacement infections, skin and soft tissue infections, diabetic foot, abdominal infections and central nervous system infections. The scenarios proposed by the Scientific Committee have been validated by a group of experts in infectious diseases and then voted in three meetings of infectious disease specialists. The results obtained on each individual condition were analyzed and therapeutic recommendations on each of these were released.

Data regarding the use of technology to improve adolescent knowledge on vaccines are scarce. The main aim of this study was to evaluate whether different web-based educational programmes for adolescents might increase their vaccination coverage. Overall, 917 unvaccinated adolescents (389 males, 42.4%; mean age ± standard deviation, 14.0 ± 2.2 years) were randomized 1:1:1 into the following groups: no intervention (n = 334), website educational program only (n = 281), or website plus face to face lesson (n = 302) groups. The use of the website plus the lesson significantly increased the overall knowledge of various aspects of vaccine-preventable disease and reduced the fear of vaccines (p < 0.001). A significant increase in vaccination coverage was observed for tetanus, diphtheria, acellular pertussis and conjugated meningococcal ACYW vaccines in the 2 groups using the website (p < 0.001), and better results were observed in the group that had also received the lesson; in this last group, significant results were observed in the increase in vaccination coverage for meningococcal B vaccine (p < 0.001). Overall, the majority of the participants liked the experience of the website, although they considered it important to further discuss vaccines with parents, experts and teachers. This study is the first to evaluate website based education of adolescents while considering all of the vaccines recommended for this age group. Our results demonstrate the possibility of increasing vaccination coverage by using a website based educational program with tailored information. However, to be most effective, this program should be supplemented with face-to-face discussions of vaccines at school and at home. Thus, specific education should also include teachers and parents so that they will be prepared to discuss with adolescents what is true and false in the vaccination field.

Background: Acute/subacute haematogenous osteomyelitis (AHOM/SAHOM) are potentially devastating diseases. Updated information about the epidemiology, management and outcome of AHOM/SAHOM is needed to minimize the risk of complications and sequelae., Methods: A multicenter study was performed to evaluate retrospectively the management and outcome of AHOM/SAHOM in Italy. Data from children aged >1 month, and hospitalized between 2010 and 2016, in 19 pediatric centers, were analyzed., Results: 300 children with AHOM and 98 with SAHOM were included. Median age was 6.0 years (IQR: 2.0-11.0). No clinical difference was observed with the exception of fever at onset (63.0% vs. 42.9%; P < 0.0001), and a more common spinal involvement in SAHOM (6.7% vs 20.4%; P < 0.001). Fifty-Eight Staphylococcus aureus strains were isolated; 5 (8.6%) were MRSA. No Kingella kingae infection was documented. No different risk for complication/sequela was observed between AHOM and SAHOM (38.3% vs. 34.7%; OR:0.85; 95%CI: 0.53-1.38; P = 0.518). Duration and type of antibiotic therapy were not associated with risk of complication/sequelae., Conclusion: AHOM and SAHOM displayed some differences, however occurrence and risk factors for complications and sequelae are similar, and the same empiric treatment might be recommended.

Influenza is a common disease and in children it can be severe enough to lead to hospitalization and death. Protection of all children against influenza, particularly the youngest, is strongly recommended by most health authorities. However, available vaccines cannot be used in the first 6 months of age, a period of life characterized by the highest risk of influenza-related complications. Maternal immunization is an attractive possibility to overcome this problem. For years, protection against influenza has been pursued by administering the trivalent inactivated vaccine given intramuscularly (IIV3). More recently, a trivalent live attenuated influenza vaccine (LAIV3) administered intranasally was licensed and adopted in a number of countries as an alternative to IIV3. In recent years, to increase protection and include a second B strain, quadrivalent inactivated (IIV4) and live attenuated vaccines (LAIV4) were prepared and licensed. However, during the 2015-2016 season the effectiveness of LAIVs was debated, and they were withdrawn from the list of recommended influenza vaccines in the USA. This review presents an update on the evidence related to the protection of infants against influenza through maternal immunization and the effectiveness of LAIV. Available data indicates that despite maternal immunization, a number of children have no protective antibody levels at birth, and in the majority of children with antibody protection, it is limited to the first 8 weeks of the postnatal period. Moreover, data on LAIV effectiveness in the pediatric population must be clarified because this vaccine can significantly improve vaccination coverage in children.

Despite the availability of effective prophylactic and therapeutic measures, influenza remains one of the most important infectious disease threats to the human population. Every year, seasonal influenza epidemics infect up to 30% of the population; a relevant portion of the ill are hospitalized, and more than a marginal number die. In an attempt to reduce the medical, social and economic burden of influenza, vaccines are recommended by many health authorities worldwide. However, not all countries have a national program for influenza immunization. The main aim of this paper is to list the differences among influenza immunization policies of various countries, highlighting the most important scientific reasons that may have led health authorities to make different decisions. The manuscript highlights that national influenza immunization policies can vary significantly from country to country. These differences arise from insufficient evidence of the relevance of influenza infection from a clinical, social and economic point of view. The lack of precise data on the true frequency and clinical relevance of influenza infection makes it nearly impossible to establish the economic burden of influenza. Moreover, it remains very difficult to evaluate the efficacy of the different influenza vaccines and whether their use is cost-effective considering the various types of people receiving them and the indirect advantages. Disparities among countries will be overcome only when more reliable data regarding all these aspects of influenza infection, particularly those related to the true impact of the disease, are precisely defined.

Pertussis is a highly contagious respiratory disease caused by Bordetella pertussis. However, after the introduction of the whole-cell pertussis vaccine (wP), the annual incidence rates of the disease progressively declined. Despite this result, the inclusion of wP in the national immunization schedule of infants and young children was debated regarding its safety. Several efforts to produce vaccines based on B. pertussis components capable of evoking protective immunity with no or limited adverse events were made. Of these others, five pertussis antigens were considered possible components of acellular vaccines (aPs): pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and fimbria proteins 2 and 3. However, the introduction of aPs was followed by a slight but progressive increase in the incidence of pertussis. This paper discusses the potential reasons for reduced aPs efficacy. Moreover, it attempts to evaluate the real effectiveness of aPs and the potential differences between available preparations. Data analysis showed that several boosters are needed to maintain protection against pertussis and additional studies are needed to confirm the antigens that should be included in aPs to improve the prevention of pertussis.

Introduction: Although significant improvements in the prevention of pneumococcal infections have been achieved in recent years, Streptococcus pneumoniae remains a leading cause of morbidity and mortality. To prevent S. pneumoniae infections, vaccines have been developed for several years., Areas Covered: In this review, the most important emerging problems regarding pneumococcal conjugate vaccines (PCVs) are discussed in addition to the status of new vaccine design and development. Given the medical, social and economic relevance of pneumococcal diseases, the availability of effective and safe vaccines against S. pneumoniae is a key objective of public health., Expert Opinion: Protein vaccines using agents different from capsular polysaccharides (CPs) or whole-cell vaccines seem to induce a broader immune response than PCVs and theoretically offer definitive solutions, as they can stimulate both humoral and cellular immunity. Moreover, these vaccines, particularly the whole-cell vaccine, are simpler to produce and significantly less expensive. However, the development of these preparations is very far from completion. It is highly likely that for a long time, no new safe and effective pneumococcal vaccines will be available. The best formulation of new pneumococcal vaccines has not been established. Consequently, an effort towards the expanded use of the available vaccines has to be made.

Pneumococcal diseases are associated with a significant clinical and economic burden. The 7-valent pneumococcal conjugate vaccine (PCV-7) has been used for the immunization of newborns against invasive pneumococcal diseases (IPD) in Italy while now, the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) and the 13-valent pneumococcal conjugate vaccine (PCV-13) are available. The aim of this analysis was to compare the estimated health benefits, cost and cost-effectiveness of immunization strategies vs. non-vaccination in Italy using the concept of overall vaccine effectiveness. A published Markov model was adapted using local data wherever available to compare the impact of neonatal pneumococcal vaccination on epidemiological and economic burden of invasive and non-invasive pneumococcal diseases, within a cohort of newborns from the Italian National Health Service (NHS) perspective. A 18-year and a 5-year time horizon were considered for the base-case and scenario analysis, respectively. PHiD-CV and PCV-13 are associated with the most important reduction of the clinical burden, with a potential marginal advantage of PHiD-CV over PCV-13. Compared with no vaccination, PHiD-CV is found on the higher limit of the usually indicated willingness to pay range (30,000 - 50,000€/quality-adjusted life year [QALY] gained), while the incremental cost-effectiveness ratio (ICER) for PCV-13 is slightly above. Compared with PCV-13, PHiD-CV would provide better health outcomes and reduce costs even at parity price, solely due to its differential effect on the incidence of NTHi acute otitis media (AOM). The analysis on a shorter time horizon confirms the direction of the base-case.

Visceral leishmaniasis (VL) is a chronic infectious disease endemic in tropical and sub-tropical areas including the Mediterranean basin, caused by a group of protozoan parasites of the genus Leishmania and transmitted by phlebotomine sandflies. Immunocompromised patients, in particular HIV positive, are considered at risk of VL. They report atypical signs and poor response to treatment due to impairment of T-helper and regulatory cells activity. Laboratory diagnosis is based on microscopy on bone marrow or spleen aspirates. Value of serology remains high in term of sensibility, but a positive test must be confirmed by microscopy or molecular tests. Treatment is based on Liposomal amphotericin B whose administration is associated to lower incidence of side effects, in respect to antimonials and other formulations of AmB. Use of Miltefosine needs further investigation when L. infantum is the causative agent. Frequent relapses are observed in co-infected HIV who can benefit of a second cycle.

Most of the severe cases of acute gastroenteritis in infants and children under 5 globally are caused by rotavirus infection. There are nearly 15,000 rotavirus gastroenteritis (RVGE) hospitalizations in Italy each year, which could be reduced by available rotavirus vaccines. In addition to the economic and societal burden, RVGE hospitalization could impact families negatively. The aim of this survey was to obtain parents' insights after hospitalization of their child for RVGE. Parents, of 500 children aged 0-5 years, were interviewed about their experience of RVGE hospitalization and asked to rate their stress on different items and overall. Most children (32.6%) were hospitalized aged 12-23 months, and 6.8% were <6 months old. Family pediatricians referred 56.2% of cases to hospital, and 25.8% went based on their parents' decision. During hospitalization, mean parental stress scores (out of 10, with 10 as highest stress) ranged from 6.6 to 8.4. The highest scores were for child malaise (8.42, SD 1.00), vomiting/diarrhea (8.07, SD 0.97), stress for the family in general (7.82, SD 0.90), parental stress (7.68, SD 0.93) and child dehydration (7.18, SD 1.02). The overall stress for the family was graded as 'high' by 67.2% of parents. Geographical areas and stress level were related (p = 0.0071), being the "high" stress score not an evenly distributed variable (p < 0.0001). Most children (91.8%) were not vaccinated against rotavirus, as most parents (74.5%) were not aware of vaccination availability. Parental distress due to RVGE hospitalization appears to be significant (93.6% reporting high/medium stress) and there is an important lack of awareness among parents about rotavirus vaccination. More education on RVGE for families in Italy should be warranted.

Skin and soft-tissue infections (SSTIs) are among the most common bacterial infections, posing considerable diagnostic and therapeutic challenges. Fourteen members of the Italian Society of Infectious Diseases, after a careful review of the most recent literature using Medline database and their own clinical experience, updated a previous paper published in 2011 by preparing a draught manuscript of the statements. The manuscript was successively reviewed by all members and ultimately re-formulated the present manuscript during a full day consensus meeting. The microbiological and clinical aspects together with diagnostic features were considered for necrotizing and not necrotizing SSTIs in the light of the most recent guidelines and evidences published in the last five years. The antimicrobial therapy was considered as well - both empirical and targeted to methicillin-resistant Staphylococcus aureus and/or other pathogens, also taking into account the epidemiological and bacterial resistance data and the availability of new antibacterial agents.

Thirty-two patients affected by SSTIs including DFIs were enrolled between 2013 and 2014. Superficial swab was obtained before and after cleansing with sterile saline, and after ultrasonic debridement; deep tissue biopsy was obtained from ulcer base. Samples were diluted with 1 mL of saline, serial 10-fold dilutions to 10 -6 were made and 50 μL of each dilution was plated onto appropriate media. Bacteria were identified by Vitek II system. Microbial load was expressed as CFU/mL. Statistical analysis was performed by χ2. Incidence of Gram positives was higher than Gram negatives (S. aureus and P. aeruginosa being the most frequent); concordance (same bacteria isolated before and after debridement) never exceeded 60%. Ultrasonic debridement significantly reduced bacterial load or even suppressed bacterial growth. While reliability of superficial swab is poor for microbiological diagnosis of SSTIs, swabbing after ultrasonic debridement and biopsy of the ulcer base may be equally reliable.

Background: The number of suspected adverse drug reactions (ADRs) yearly submitted to the Italian Network of Pharmacovigilance (RNF) has progressively increased after the new European Pharmacovigilance legislation (July 2012). These results have mostly reflected the agreements between Italian Medicines Agency (AIFA) and Italian Regions, enabling the implementation of active pharmacovigilance projects. A project was funded by the AIFA in Calabria region (Southern Italy) in 2010 to increase ADRs reporting and promote a safer medicines' use. Based on this background, we investigated the trend of ADRs in Calabria in 2011-2014, trying to analyze the possible entailments of the new law., Methods: Quantitative and descriptive analysis of ADRs submitted by Calabrian healthcare professionals and patients to the RNF database between 2011 and 2014., Results: A sharp rise in regional reporting rate was observed over study period. Calabrian Pharmacovigilance system completely fulfilled the World Health Organization gold standard for ADR reporting rate, both in 2013 and 2014. However, heterogeneity was observed regarding reporting health facilities, healthcare professionals and patients among the study years., Conclusions: These findings reflect the success of the project performed in Calabria. However, this initiative should go on in the next future to obtain better and more homogeneous reporting behavior.

Introduction: The success of the vaccines available on the market has significantly increased interest in vaccine development. Areas covered: The main aim of this paper is to discuss the most important vaccines of pediatric interest that are currently being developed. New pneumococcal vaccines and vaccines against group B Streptococcus, Staphylococcus aureus and respiratory syncytial virus are analyzed in detail. Expert commentary: Advances in understanding human immunology, including human monoclonal antibody identification, sequencing technology, and the ability to solve atomic level structures of vaccine targets have provided tools to guide the rational design of future vaccines. It is likely that some of these vaccines will reach the market in the future and will thus partially contribute to the prevention of very severe diseases that significantly affect the morbidity and mortality of children. However, further studies in animals and several clinical trials in children must be performed before new vaccines become licensed.

Phase II clinical trials indicate that the combination of cysteamine plus epigallocatechin gallate (EGCG) is effective against cystic fibrosis in patients bearing the most frequent etiological mutation (CFTRΔF508). Here, we investigated the interaction between both agents on cultured respiratory epithelia cells from normal and CFTRΔF508-mutated donors. We observed that the combination of both agents affected metabolic circuits (and in particular the tricarboxylic acid cycle) in a unique way and that cysteamine plus EGCG reduced cytoplasmic protein acetylation more than each of the 2 components alone. In a cell-free system, protein cross-linking activity of EGCG was suppressed by cysteamine. Finally, EGCG was able to enhance the conversion of cysteamine into taurine in metabolic flux experiments. Altogether, these results indicate that multiple pharmacological interactions occur between cysteamine and EGCG, suggesting that they contribute to the unique synergy of both agents in restoring the function of mutated CFTRΔF508.

Introduction: The advent of nucleic acid amplification tests has significantly improved the aetiologic diagnosis of respiratory infections. However, multiplex real-time polymerase chain reaction (PCR) can be technologically challenging. Areas covered: This paper reports the results of the main published studies on the NxTAG Respiratory Pathogen Panel (RPP) and discusses the advantages and disadvantages of extensive use of multiplex assays in clinical practice. Expert commentary: Currently available data seem to indicate that routine use of multiplex assays, including NxTAG RPP Assay, should be recommended only when epidemiological data concerning circulation of viruses and bacteria have to be collected. Their use in clinical practice seems debatable. They have limited sensitivity and specificity at least in the identification of some infectious agents or, as in the case of NxTAG RPP, they have not been evaluated in a sufficient number of patients to allow definitive conclusions. In the future, the clinical relevance of multiplex assays, including NxTAG RPP, could significantly increase, mainly because a number of new antiviral agents effective against several respiratory viruses for which no drug is presently available will be marketed. In addition, it is highly likely that the efficiency of multiplex assays will be significantly improved.

The removal of simazine from both pure water and solute-bearing well water was studied by adsorption on two solids: zeolite H-Y from the commercial Na form and porous silica tailored by the sol-gel technique. The pH dependence of the amount adsorbed in a closed system at constant total simazine content as well as the apparent isotherms of adsorption was measured in all four cases. The low ion content of natural water suffices to alter the adsorption features in the case of silica, but not with zeolite H-Y. Iteration of the adsorption process onto constant amounts of solid allowed bringing the residual simazine concentration below 0.05 mg/L, the value allowed by Italian laws in wastewaters.

Introduction: The identification of factors that can predispose to the development of severe influenza is essential to enable the implementation of optimal prevention and control measures for vulnerable populations., Areas Covered: Unfortunately, data in the pediatric age group remain difficult to interpret. However, epidemiological data seem to suggest that the most severe influenza cases, those who are hospitalized, those who are admitted to the intensive care unit, and those who died, occur in children in the first 2 years of life and in school age patients. Expert commentary: Immaturity of the immune system, and in particular of the mechanisms that usually recognize influenza viruses and activate cytokine and chemokine responses to reduce viral replication, might explain the high hospitalization rate observed in the youngest patients. Some underlying chronic conditions favour the development of the severe cases, sometime leading to death, although both admission to the intensive care unit and death can occur in otherwise healthy subjects.

The development of a safe and effective respiratory syncytial virus (RSV) vaccine might be facilitated by knowledge of the natural immune response to this virus. The aims of this study were to evaluate the neutralizing antibody response of a cohort of healthy children <18 months old to RSV infection. During the RSV season, 89 healthy children <18 months old were enrolled and followed up weekly for 12 weeks. At each visit, a nasopharyngeal swab was obtained for RSV detection by real-time polymerase chain reaction (PCR). During the study period, 2 blood samples were drawn and they were used to determine RSV geometric mean neutralizing antibody titres (GMT) against RSV. A total of 35 (39.3%) children had RSV detected during the study period. Among RSV-positive patients, children ≥7 months showed a significantly higher increase in antibody response (p<0.001). A significantly higher number of patients with a ≥4 -fold increase in GMT were ≥7 months old (p = 0.02) and presented lower respiratory tract infections (LRTIs) during the study period (p = 0.01). Viral shedding was longer among children aged ≥7 months (p = 0.06), those with viral load ≥10(6) copies/mL (p = 0.03), and those with LRTIs during the study period (p = 0.03), but it was not associated with the immune response (p = 0.41). In conclusion, natural RSV infection seems to evoke a low immune response in younger children. To be effective in this infant population, which is at highest risk of developing severe LRTIs, vaccines must be able to induce in the first months of life a stronger immune response than that produced by the natural infection.

Rapid population aging has become a major challenge in the industrialized world and progressive aging is a key reason for making improvement in vaccination a cornerstone of public health strategy. An increase in age-related disorders and conditions is likely to be seen in the near future, and these are risk factors for the occurrence of a number of vaccine-preventable diseases. An improvement in infectious diseases prevention specifically aimed at adults and the elderly can therefore also decrease the burden of these chronic conditions by reducing morbidity, disability, hospital admissions, health costs, mortality rates and, perhaps most importantly, by improving the quality of life. Among adults, it is necessary to identify groups at increased risk of vaccine-preventable diseases and highlight the epidemiological impact and benefits of vaccinations using an evidence-based approach. This document provides clinical practice guidance on immunization for adults in order to provide recommendations for decision makers and healthcare workers in Europe. Although immunization is considered one of the most impactful and cost-effective public health measures that can be undertaken, vaccination coverage rates among adults are largely lower than the stated goal of ≥ 95% among adults, and stronger efforts are needed to increase coverage in this population. Active surveillance of adult vaccine-preventable diseases, determining the effectiveness of the vaccines approved for marketing in the last 5 y, the efficacy and safety of vaccines in immunocompromised patients, as well as in pregnant women, represent the priorities for future research.