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BackgroundIntercepting earlier suspected TB (Tuberculosis) cases clinically is necessary to reduce TB incidence, so we described signs and symptoms of retrospective cases of pulmonary TB and tried to evaluate which could be early warning signs.MethodsWe conducted a retrospective descriptive study of pulmonary TB cases in children in years 2005–2017; in years 2018–2020 we conducted a cohort prospective study enrolling patients ResultsIn the retrospective analysis, 226 patients with pulmonary TB were studied. The most frequently described items were contact history (53.5%) and having parents from countries at risk (60.2%). Cough was referred in 49.5% of patients at onset, fever in 46%; these symptoms were persistent (lasting ≥ 10 days) in about 20%. Lymphadenopathy is described in 15.9%. The prospective study enrolled 85 patients of whom 14 (16.5%) were confirmed to be TB patients and 71 (83.5%) were non-TB cases. Lymphadenopathy and contact history were the most correlated variables. Fever and cough lasting ≥ 10 days were less frequently described in TB cases compared to non-TB patients (p ConclusionsIn low TB endemic countries, pulmonary TB at onset is characterized by different symptoms, i.e. persistent fever and cough are less described, while more relevant are contact history and lymphadenopathy. It was not possible to create a score because signs/symptoms usually suggestive of pulmonary TB (considered in the questionnaire) were not significant risk factors in our reality, a low TB country.

Pediatric osteomyelitis is an insidious disease that can lead to permanent sequelae, the management of which still relies on lengthy intravenous antibiotic therapy. The purpose of this study is to report and describe the clinical course and outcome of pediatric bacterial osteomyelitis in our experience. We reported the clinical, diagnostic, and treatment characteristics of all cases of osteomyelitis in children younger than 18 years of age who were hospitalized between January 2010 and December 2021 at the Bambino Gesù Children’s Hospital in Rome, Italy, we compared patients with and without complications at follow-up, to identify any predictive factor for sequelae. The study sample included 319 cases of pediatric bacterial osteomyelitis. The median age was 7.77 years. Males (60.8%) were more affected than females. The most affected bones were the femur, tibia, and spine. Etiology was identified in 40.1% of cases, with S.aureus as the most common causative agent. Sequelae were reported in 43 cases (13.5%). The main predictors of sequelae were sepsis on admission and hypergammaglobulinemia. Our results show that a severe presentation with sepsis and hypergammaglobulinemia on admission may be associated with a higher frequency of late sequelae. Early recognition and aggressive treatment of this subgroup of patients may lead to a reduction in complications.

Background Two sequelae of pediatric COVID-19 have been identified, the multisystem inflammatory syndrome in children (MIS-C) and the long COVID. Long COVID is much less precisely defined and includes all the persistent or new clinical manifestations evidenced in subjects previously infected by SARS-CoV-2 beyond the period of the acute infection and that cannot be explained by an alternative diagnosis. In this Intersociety Consensus, present knowledge on pediatric long COVID as well as how to identify and manage children with long COVID are discussed. Main findings Although the true prevalence of long COVID in pediatrics is not exactly determined, it seems appropriate to recommend evaluating the presence of symptoms suggestive of long COVID near the end of the acute phase of the disease, between 4 and 12 weeks from this. Long COVID in children and adolescents should be suspected in presence of persistent headache and fatigue, sleep disturbance, difficulty in concentrating, abdominal pain, myalgia or arthralgia. Persistent chest pain, stomach pain, diarrhea, heart palpitations, and skin lesions should be considered as possible symptoms of long COVID. It is recommended that the primary care pediatrician visits all subjects with a suspected or a proven diagnosis of SARS-CoV-2 infection after 4 weeks to check for the presence of symptoms of previously unknown disease. In any case, a further check-up by the primary care pediatrician should be scheduled 3 months after the diagnosis of SARS-CoV-2 infection to confirm normality or to address emerging problems. The subjects who present symptoms of any organic problem must undergo a thorough evaluation of the same, with a possible request for clinical, laboratory and / or radiological in-depth analysis in case of need. Children and adolescents with clear symptoms of mental stress will need to be followed up by existing local services for problems of this type. Conclusions Pediatric long COVID is a relevant problem that involve a considerable proportion of children and adolescents. Prognosis of these cases is generally good as in most of them symptoms disappear spontaneously. The few children with significant medical problems should be early identified after the acute phase of the infection and adequately managed to assure complete resolution. A relevant psychological support for all the children during COVID-19 pandemic must be organized by health authorities and government that have to treat this as a public health issue.

The primary objective of this study is to report and compare our data with the most relevant literature of the past decade about neonatal osteomyelitis. We retrospectively review the data of 22 subjects aged 35 days or less who were admitted to three different sites in Italy with a radiological diagnosis of osteomyelitis. The inherent literature was searched and reviewed: five studies were considered for comparison with our data. All the neonates, except three (two pre-term and one post-term), were born at term. The male to female ratio was 1.75 (14 males and 8 females). The mean age at presentation was 19.5 days. The most common presenting signs of the infection were local swelling and reduced mobility of the affected segment. The most common sites of infection were the femur, humerus, and tibia. The mean duration of intravenous antibiotic therapy was 29.5 days. In most neonates the diagnosis was prompt and the antibiotic treatment immediate. A low rate of sequelae was reported. All infants survived through follow up. The data from the inherent literature showed a wide variability, probably owing to the setting and the historical period of the different studies. Neonatal osteomyelitis is an alarming yet poorly understood disease. Nonetheless, our report suggests that a quick diagnosis and treatment can be easily achieved, with good outcome on the remarkably plastic structure of neonatal bones.

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one ( Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. Funding ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

Background In Italy, the response to coronavirus disease 2019 (COVID-19) pandemic upgraded from social distancing on February 23, 2020, to national lockdown on March 11, 2020. We described how the pandemic affected a tertiary care children hospital with a dedicated COVID-19 regional center. Methods We analyzed the characteristics of emergency department (ED) visits, urgent hospitalizations and severe acute respiratory syndrome (SARS)-COV-2 reverse transcription-polymerase chain reaction testing, and COVID-19 patients across 3 response phases: before the first Italian case, before national lockdown and during lockdown. Results ED visits decreased from a daily mean of 239.1 before the first COVID-19 Italian case, to 79.6 during lockdown; urgent hospitalizations decreased from 30.6 to 21.2. As of April 20, 2020, 1970 persons were tested for SARS-CoV-2 reverse transcription-polymerase chain reaction and 2.6% were positive. Positive rates were 1.2% in the ED, 21.1% in the COVID center and 0.5% in other wards. The median age of COVID-19 patients (N = 33) was 6.7 years, 27% had coexisting conditions and 79% were related to family clusters. Conclusions The pandemic strongly impacted on the use of hospital services, with a 67% reduction in ED visits and a 31% reduction in urgent hospitalizations. Separating the flows of suspected patients from all other patients, and centralization of suspected and confirmed cases in the COVID center enabled to control the risk of nosocomial SARS-CoV-2 transmission. Delay in hospital use for urgent care must be avoided, and clear communication on infection prevention and control must be provided to families. Further studies are needed to assess how the reduction in hospital use affected children healthcare needs during the pandemic.

AIM: Pertussis continues to be a common worldwide infection in pediatric and adult populations. We aimed to study epidemiological and clinical characteristics of infants and children admitted for pertussis to a tertiary-care hospital and to investigate the risk factors for pediatric intensive care unit (PICU) admission. MATERIALS AND METHODS: With a retrospective study, we analyzed all medical reports of patients admitted to Bambino Gesù Children’s Hospital in Rome from January 2011 to December 2018 with a diagnosis of pertussis. RESULTS: We examined 195 patients. The majority of hospitalized children (66.15%) were

Non-congenital viral infections of the central nervous system in children can represent a severe clinical condition that needs a prompt diagnosis and management. However, the aetiological diagnosis can be challenging because symptoms are often nonspecific and cerebrospinal fluid analysis is not always diagnostic. In this context, neuroimaging represents a helpful tool, even though radiologic patterns sometimes overlap. The purpose of this pictorial essay is to suggest a schematic representation of different radiologic patterns of non-congenital viral encephalomyelitis based on the predominant viral tropism and vulnerability of specific regions: cortical grey matter, deep grey matter, white matter, brainstem, cerebellum and spine.

Background Symptomatic Bartonella henselae infection is considered rare in Europe. Cat fleas transmit the microorganism between cats, but their role in transmission of B. henselae to humans has not been defined. The aim of our study was to perform a retrospective study of detected cases at our Hospital. Methods We retrospectively analyzed data of all children showing lymphadenopathy and a 4-fold increase in specific IgM for B. henselae over the period from June 2010 to May 2015. We therefore examined clinical data, laboratory exams in order to achieve a description of the expression of Bartonella infection in our series: age, geographical area of origin, symptoms, laboratory exams, the seat of the swelling lymph nodes with ultrasound description, and data on biopsy of lymph node when performed. Results We could identify a total of 7 patients (4 females, range of age: mean age 8.75±2.87 SD): three cases in 2011 and 1 case per year in 2010, 2012, 2013 and 2014 with an average distance between one case and the sequent of 246.16±214.54 days. All patients came from small towns with no preference between the inland and coastal areas. The infection was characterized only by lymphadenopathy with nonspecific alterations at blood tests and with no history of cat scratch. Conclusions By our experience, Bartonella infection presents as a seasonal disease with increased incidence in autumn, with peaks in October, and a decrease after spring. In conclusion, infection with B. henselae is an issue to keep in consideration in all cases of lymphadenopathy, especially in children coming from small towns even without a declared cat scratch.

Mild encephalopathy with a reversible splenial lesion (MERS) is an uncommon clinico-radiological entity characterized by magnetic resonance imaging (MRI) findings of a reversible lesion in the splenium of corpus callosum associated with a significant neurological manifestation of encephalopathy. The majority of reported cases involve the Asiatic population and are closely associated with infection. We report the case of an adolescent with an HHV6-related MERS presenting with hyponatremia and urinary and fecal retention. To our knowledge, urinary retention is not a constant aspect of the disease and has rarely been described, while fecal retention has never been reported before. Despite the self-limiting nature of the disease, it is mandatory to suspect it for a faster diagnosis and it might be useful to know its rare occurrences in order to better understand its etiopathogenetic mechanisms.

As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies., Graphical abstract, Cotugno et al. show that neutralizing antibodies affect SARS-CoV-2 viral load in infected children. Antigen-specific B and T cells are positively associated with virus neutralization. This information provides a basis for defining SARS-CoV-2 adaptive responses in children.

The failure of immunization coverage is the primary reason for the transmission and the spread of the diseases in young infants not eligible for vaccination because of age and in immunocompromised individuals. In both these categories measles, pertussis and varicella could be devastating. Pertussis, measles and varicella in the first year of life are responsible to the ED admission, the hospitalization and, exceptionally, the death. The only way to protect very young infants and immunocompromised individuals is to obtain the adequate coverage in all the population.

Background Varicella pneumonia has been studied extensively in adults; it may also affect children and may require hospitalization. Methods We examined pneumonia complications in children hospitalized for varicella, over a 13 year period. Results Pneumonia occurred in 8.2% of children hospitalized for varicella. The median length of hospitalization was 6 days. No statistically significant difference in length of stay was detected between immunodepressed children and previously healthy children. The hospitalization was on average shorter in patients who started antiviral therapy within 24 h of varicella onset. None of the included patients had been previously immunized for varicella. Conclusions Our results support the need for increased awareness of current varicella prevention recommendations among both immunocompetent and immunodepressed individuals. In children affected by varicella, prompt antiviral therapy may be indicated to reduce the number of days of hospitalization.

Background Acute cerebellitis (AC) and acute cerebellar ataxia (ACA) are the principal causes of acute cerebellar dysfunction in childhood. Nevertheless. there is no accepted consensus regarding the best management of children with AC/ACA: the aim of the study is both to assess clinical, neuroimaging and electrophysiologic features of children with AC/ACA and to evaluate the correlation between clinical parameters, therapy and outcome. Methods A multicentric retrospective study was conducted on children ≤ 18 years old admitted to 12 Italian paediatric hospitals for AC/ACA from 01/01/2003 to 31/12/2013. A score based on both cerebellar and extracerebellar signs/symptoms was computed for each patient. One point was given for each sign/symptom reported. Severity was divided in three classes: low, moderate, severe. Results A total of 124 children were included in the study. Of these, 118 children received a final diagnosis of ACA and 6 of AC. The most characteristic finding of AC/ACA was a broad-based gait disturbance. Other common symptoms included balance disturbances, slurred speech, vomiting, headache and fever. Neurological sequelae were reported in 6 cases (5%) There was no correlation among symptoms, cerebrospinal fluid findings, clinical outcome. There was no correlation between clinical manifestations and clinical score on admission and length of hospital stay, sex, age and EEG findings with sequelae (P > 0.05). Children with pathological magnetic resonance imaging (MRI) or computed tomography (CT) had a higher probability of having clinical sequelae. Treatment was decided independently case by case. Patients with a higher clinical score on admission had a higher probability of receiving intravenous steroids. Conclusions We confirmed the literature data about the benign course of AC/ACA in most cases but we also highlighted a considerable rate of patients with neurological sequelae (5%). Pathological MRI or CT findings at admission correlate to neurological sequelae. These findings suggest the indication to perform an instrumental evaluation in all patients with AC/ACA at admission to identify those at higher risk of neurological outcome. These patients may benefit from a more aggressive therapeutic strategy and should have a closer follow-up. Randomized controlled trials are needed to confirm these observations. The ultimate goal of these studies could be to develop a standardized protocol on AC/ACA. The MRI/CT data, associated with the clinical manifestations, may allow us to define the class risk of patients for a neurological outcome.

Clostridium difficile infection (CDI) is increasingly found in children worldwide, but limited data are available from children living in southern Europe. A 6-year retrospective study was performed to investigate the epidemiology, clinical features, treatment, and risk of recurrence in Italy. Data of children with community- and hospital-acquired CDI (CA-CDI and HA-CDI, respectively) seen at seven pediatric referral centers in Italy were recorded retrospectively. Annual infection rates/10,000 hospital admissions were calculated. Logistic regression was used to investigate risk factors for recurrence. A total of 177 CDI episodes was reported in 148 children (83 males, median age 55.3 months), with a cumulative infection rate of 2.25/10,000 admissions, with no significant variability over time. The majority of children (60.8 %) had CA-CDI. Children with HA-CDI (39.2 %) had a longer duration of symptoms and hospitalization (p = 0.003) and a more common previous use of antibiotics (p = 0.0001). Metronidazole was used in 70.7 % of cases (87/123) and vancomycin in 29.3 % (36/123), with similar success rates. Recurrence occurred in 16 children (10.8 %), and 3 (2 %) of them presented a further treatment failure. The use of metronidazole was associated with a 5-fold increase in the risk of recurrence [odds ratio (OR) 5.18, 95 % confidence interval (CI) 1.1-23.8, p = 0.03]. Short bowel syndrome was the only underlying condition associated with treatment failure (OR 5.29, 95 % CI 1.17-23.8, p = 0.03). The incidence of pediatric CDI in Italy is low and substantially stable. In this setting, there is a limited risk of recurrence, which mainly concerns children treated with oral metronidazole and those with short bowel syndrome.

The incidence of tuberculosis is increasing in the developed world and children in particular represent a high-risk group for developing the disease. The aim of this review is to analyse the spectrum of radiological signs as reported in the recent literature, in light of our series over a 15-year period, to pinpoint the most common radiological patterns in a developed country and to determine the role played by the different chest imaging techniques in diagnosis improvement. Lung TB was present in 217 out of 255 patients (85 %): 146 patients were under 5 years of age (76 under 2 years) and 71 over 5 years (41 over 10 years). We describe different patterns differentiating adolescents and young adults from infants and children. Adolescents and young adult tuberculosis are apical and cavitary. Thoracic TB in infants and children is characterized by lymph node and parenchymal disease. In 21 cases with lymphadenopathies without lymph-bronchial diffusion (age range 2 months-7 years), CT identified the Ghon focus in 16/21 cases; chest X-ray never identified the Ghon focus. In our series, pleural TB was present in 8 cases out of 146 under 5 years of age, 5 cases out of 76 under 2 years, and 18 cases out of 71 over 5 years. Radiologists should be aware of typical patterns of tuberculosis, to provide an early diagnosis.

The diagnosis of latent or active tuberculosis in children is often challenging. Recently, interferon-γ release assays have been licensed, but their diagnostic accuracy in young children remains questionable as frequent false-negative or indeterminate results have been reported.We performed a multicenter, retrospective study in children 0-24 months of age who were tested at least once with QuantiFERON-TB Gold-in-tube (QTF-IT) ± tuberculin skin test (TST), to analyze its use and performance in clinical practice.Eight-hundred and twenty-three children (449 males, median age 13.5 months) were enrolled. QTF-IT sensitivity and specificity for active tuberculosis were 92.4% and 98.6%, respectively. Indeterminate tests (4.2 %) were not related to age (P = 0.838) or gender (P = 0.223); 32 children (91.4 %) with an indeterminate QTF-IT ultimately resulted uninfected. In the 616 subjects with valid paired results of QTF-IT and TST, sensitivity and specificity were comparable (91.1% vs. 85.1% and 98.1% vs. 97.9%, respectively). Diagnostic concordance between tests was higher in Bacillus Calmétte-Guerin nonvaccinated children (κ = 0.802). A high rate of discordant tests was observed in latent infections.QTF-IT showed good sensitivity and specificity, and a low rate of indeterminate results in the first 2 years of life, supporting its use at this age. However, considering costs and the similar performance between QTF-IT and TST, it is reasonable to suggest the latter as first-line testing in young children. The complementary use of TST and interferon-γ release assays may be considered in selected cases to improve the accuracy of testing.

SUMMARYDrug-resistant paediatric tuberculosis (TB) is an overlooked global problem. In Italy, the epidemiology of TB has recently changed and data regarding drug-resistant forms in the paediatric setting is scanty. The aim of this case series was to report the cases of drug-resistant TB, diagnosed between June 2006 and July 2010 in four Italian tertiary centres for paediatric infectious diseases, in children and adolescents living in Italy. Twenty-two children were enrolled, of these 17 were resistant to one or more drugs and five had multidrug-resistant TB. All but one child were either foreign born or had at least one foreign parent. Twenty-one patients completed their treatment without clinical or radiological signs of activity at the end of treatment, and one patient was lost to follow up. The outcomes were good, with few adverse effects using second-line anti-TB drugs. Although this series is limited, it might already reflect the worrisome increase of drug-resistant TB, even in childhood.

Background Primary melanocytic neoplasms are rare in the pediatric age. Among them, the pattern of neoplastic meningitis represents a peculiar diagnostic challenge since neuroradiological features may be subtle and cerebrospinal fluid analysis may not be informative. Clinical misdiagnosis of neoplastic meningitis with tuberculous meningitis has been described in few pediatric cases, leading to a significant delay in appropriate management of patients. We describe the case of a child with primary leptomeningeal melanoma (LMM) that was initially misdiagnosed with tuberculous meningitis. We review the clinical and molecular aspects of LMM and discuss on clinical and diagnostic implications. Case presentation A 27-month-old girl with a 1-week history of vomiting with mild intermittent strabismus underwent Magnetic Resonance Imaging, showing diffuse brainstem and spinal leptomeningeal enhancement. Cerebrospinal fluid analysis was unremarkable. Antitubercular treatment was started without any improvement. A spinal intradural biopsy was suggestive for primary leptomeningeal melanomatosis. Chemotherapy was started, but general clinical conditions progressively worsened and patient died 11 months after diagnosis. Molecular investigations were performed post-mortem on tumor tissue and revealed absence of BRAFV600E, GNAQQ209 and GNA11Q209 mutations but the presence of a NRASQ61K mutation. Conclusions Our case adds some information to the limited experience of the literature, confirming the presence of the NRASQ61K mutation in children with melanomatosis. To our knowledge, this is the first case of leptomeningeal melanocytic neoplasms (LMN) without associated skin lesions to harbor this mutation. Isolated LMN presentation might be insidious, mimicking tuberculous meningitis, and should be suspected if no definite diagnosis is possible or if antitubercular treatment does not result in dramatic clinical improvement. Leptomeningeal biopsy should be considered, not only to confirm diagnosis of LMN but also to study molecular profile. Further molecular profiling and preclinical models will be pivotal in testing combination of target therapy to treat this challenging disease.

Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large cohorts. A multicenter study was conducted in 27 pediatric hospitals, pediatric wards, and public health centers in Italy using a standardized form, covering the period of time between 1 January 2010 and 31 December 2012. Children with active TB, latent TB, and those recently exposed to TB or recently adopted/immigrated from a high TB incidence country were enrolled. Overall, 4234 children were included; 554 (13.1%) children had active TB, 594 (14.0%) latent TB and 3086 (72.9%) were uninfected. Among children with active TB, 481 (86.8%) patients had pulmonary TB. The treatment of active TB cases was known for 96.4% (n = 534) of the cases. Overall, 210 (39.3%) out of these 534 children were treated with three and 216 (40.4%) with four first-line drugs. Second-line drugs where used in 87 (16.3%) children with active TB. Drug-resistant strains of Mycobacterium tuberculosis were reported in 39 (7%) children. Improving the surveillance of childhood TB is important for public health care workers and pediatricians. A non-negligible proportion of children had drug-resistant TB and was treated with second-line drugs, most of which are off-label in the pediatric age. Future efforts should concentrate on improving active surveillance, diagnostic tools, and the availability of antitubercular pediatric formulations, also in low-endemic countries.

The Italian Society for Pediatric Infectious Diseases created a registry on children with infective endocarditis (IE) hospitalized in Italy.A cross-sectional survey was conducted on patients hospitalized due to IE in Italian paediatric wards between January 1, 2000, and June 30, 2015.Over the 15-year study period, 47 IE episodes were observed (19 males; age range, 2-17 years). Viridans Streptococci were the most common pathogens among patients with predisposing cardiac conditions and Staphylococcus aureus among those without (37.9% vs. 5.5%, p = 0.018, and 6.9% vs. 27.8%, p = 0.089, respectively). Six of the 7 (85.7%) S. aureus strains were methicillin-resistant. The majority of patients with and without predisposing cardiac conditions recovered without any complications.In Italy, paediatric IE develops without any previous predisposing factors in a number of children, methicillin-resistant S. aureus has emerged as a common causative agent and the therapeutic approach is extremely variable.

Background The clinical diagnosis of pertussis is not easy in early infancy since clinical manifestations can overlap with several different diseases. Many cases are often misclassified and underdiagnosed. We conducted a retrospective study on infants to assess how often physicians suspected pertussis and the actual frequency of Bordetella pertussis infections. Methods We analyzed all infants with age ≤90 days hospitalized from March 2011 until September 2013 for acute respiratory symptoms tested with a Real Time Polymerase Chain Reaction able to detect Bordetella pertussis and with a Real Time Polymerase Chain Reaction for a multipanel respiratory virus. Therefore, we compared patients with pertussis positive aspirate, patients with respiratory virus positive aspirate and patients with negative aspirate to identify symptoms or clinical findings predictive of pertussis. Results Out of 215 patients analyzed, 53 were positive for pertussis (24.7 %), 119 were positive for respiratory virus (55.3 %) and 43 had a negative aspirate (20 %). Pertussis was suspected in 22 patients at admission and 16 of them were confirmed by laboratory tests, while 37 infants with different admission diagnosis resulted positive for pertussis. The sensitivity of clinical diagnosis was 30.2 % and the specificity 96.3 %. Infants with pertussis had more often paroxysmal cough, absence of fever and a higher absolute lymphocyte count than infants without pertussis. Conclusions Pertussis is a serious disease in infants and it is often unrecognized; some features should help pediatricians to suspect pertussis, but clinical suspicion has a low sensitivity. We suggest a systematic use of Real Time Polymerase Chain Reaction to support the clinical suspicion of pertussis in patients with less than 3 months of age hospitalized with acute respiratory symptoms.

Tuberculosis (TB) is still one of the most difficult infectious diseases to treat, and the second most frequent cause of death due to infectious disease throughout the world. The number of cases of multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB), which are characterised by high mortality rates, is increasing. The therapeutic management of children with MDR- and XDR-TB 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. This document describes the recommendations of a group of scientific societies on the therapeutic approach to pediatric MDR- and XDR-TB. On the basis of a systematic literature review and their personal clinical experience, the experts recommend that children with active TB caused by a drug-resistant strain of Mycobacterium tuberculosis should always be referred to a specialised centre because of the complexity of patient management, the paucity of pediatric data, and the high incidence of adverse events due to second-line anti-TB treatment.

BACKGROUND Tuberculosis (TB) is among the top 10 causes of child death worldwide. Nevertheless, childhood disease has been neglected by tuberculosis control programs. METHODS This was a retrospective study of patients < 16 years of age diagnosed with active TB in 2 tertiary hospitals in Rome (Italy), between 1990 and 2009. RESULTS Two hundred fourteen cases of active tuberculosis were identified (132 definite, 82 probable). Pulmonary involvement was the most common form (75.5%), followed by lymphadenopathy (15.4%) and central nervous system TB (11%). Fever (51.86%) and cough (40%) were the most common presenting symptoms. A total of 23.4% of children were asymptomatic on admission. Sensitivities of the tuberculin skin test and the quantiferon test were 93.4% and 97%, respectively. Both tests performed in 52 children agreed in 49 cases (94%). Sensitivities for culture, Ziehl-Neelsen staining and polymerase chain reaction were 58%, 25% and 66.3%, respectively. The adult source case was identified in 28% of cases. History of contact with a patient with active TB was associated with pulmonary TB (P = 0.0014), whereas negative history of contact was associated with lymph node (P = 0.0064) and central nervous system TB (P = 0.05). CONCLUSIONS Our study emphasizes the difficulty in managing children with suspected TB, because the absence of constitutional symptoms cannot exclude TB, and bacteriologic confirmation is the exception. Immunologic diagnosis can be a valuable tool to identify TB-infected children because the quantiferon test showed high sensitivity in all age groups. This is of primary importance because early identification of children with latent tuberculous infection and appropriate chemoprophylaxis represent, to date, the most important tool to reduce the burden of TB.

Human herpes virus 6 (HHV6) infection is a self-limiting illness occurring in early childhood. As with other herpes viruses, the encephalopathy associated with HHV6 is often attributable to the reactivation of a virus previously latent in human brain tissue. Previous reports on HHV6 encephalopathy dealt mainly with virus reactivation in immune-depressed older children and, above all, refer to encephalitis and not to meningoencephalitis. Complications are rare in healthy children. Encephalopathy has rarely been associated with HHV6 infection in children not affected by chronic disease.The aim of this study was to evaluate sequelae of HHV6 meningoencephalitis in previously healthy children.We report three cases of HHV6 meningoencephalitis in previously healthy children followed for a 10-year period. Two of the patients presented invalidating sequelae. In detail, one patient developed speech disturbance and the other persistent hemiplegia and bilateral visual deficit. To our knowledge, this is the first case in which an ocular complication developed in the course of HHV6 meningoencephalitis.HHV6 meningoencephalitis can be associated with a wide range of clinical outcomes, from long-term neurological sequelae to a benign post-infectious clinical course.

Tuberculosis (TB) is a re-emerging health problem in developed countries. This paper is part of large guidelines on the global management of TB in children, by a group of scientific societies. It describes the indications to hospitalization of children with suspected or diagnosed TB, the isolation measures, hospital discharge, and re-admission into the community. Using the Consensus Conference method, relevant publications in English were identified by means of a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception until 31 December 2014. Available data on indications to hospitalization were mainly indirect and largely derived from observational studies. They include: (1) host-related risk factors, the main being age

SUMMARYActive pulmonary tuberculosis was diagnosed in a 4-month-old infant 16 days after hospitalization; 186 exposed individuals were traced and one conversion detected. Although the risk of tuberculosis transmission in paediatric hospitals is low, paediatricians in low-incidence countries should maintain a high level of alert for timely identification of cases.

Tubercular spinal localization is very rare (5%) in paediatric age. We report the unusual case of a child with a history of bacillus Calmette-Guerin vaccination who presented with lymphadenitis in the absence of pulmonary involvement. Despite appropriate anti-tubercular therapy, the patient developed spinal tuberculosis with cord compression. Urgent surgical decompression was performed: laminectomy was done at D3-D5 levels and the higher abscess was then flushed using a catheter, decompressing the cauda equina. Our findings suggest that diagnosis of tuberculosis should be considered even in light of anamnestic vaccination at birth, and that surgical treatment should be rapidly provided in the event of spinal cord compression to avoid devastating sequelae.

Fusobacterium necrophorum is an anaerobic, gram-negative highly virulent bacillus, isolated from the oropharingeal cavity, the gastrointestinal tract, and the female genital tract. It is responsible of several clinical syndromes, mainly in children or adolescents, ranging from localized abscess, usually in the upper respiratory sites, to severe septicemic diseases, including meningitis. We report the fatal case of an immunocompetent male with suppurative otitis media and meningitis. Initial empiric antibiotic treatment was not effective. After the recovery of anaerobic gram-negative bacilli from blood cultures, treatment with metronidazole was started, and a rapid improvement in laboratory parameters was observed. However, the patient's clinical course was incurable because of cerebral hypertensive complications. F. necrophorum was identified as the causative agent of this metastatic and fatal infection. This case has shown the severity of infection due to F. necrophorum and, at the same time, the underestimation of anaerobic bacteria in the spectrum of etiologic agents responsible for meningitis. Only a prompt diagnosis and an adequate treatment can improve the prognosis and avoid a fatal outcome.

OBJECTIVES: Because of the spread of drug-resistant Gram-positive bacteria, the use of linezolid for treating severe infections is increasing. However, clinical experience in the paediatric population is still limited. We undertook a multicentre study to analyse the use of linezolid in children. METHODS: Hospitalized children treated with linezolid for a suspected or proven Gram-positive or mycobacterial infection were analysed retrospectively. Side effects were investigated, focusing on younger children and long-term treatments. RESULTS: Seventy-five patients (mean age 6.8 years, range 7 days to 17 years) were studied. Mean ± SD linezolid treatment duration was 26.13 ± 17 days. Clinical cure was achieved in 74.7% of patients. The most frequent adverse events were diarrhoea and vomiting. Two patients had severe anaemia, two neutropenia and one thrombocytopenia. Two cases of grade 3 liver function test elevation and one case of pancreatitis were reported. The overall frequency of adverse events was similar between patients treated for >28 days and those receiving shorter treatments (30.8% versus 28.6%, P = 0.84). Children aged

A child referred to Infectious Disease Unit for varicella complicated by pneumonia with pleural effusion. Due to not improvement, laboratory search was extended to uncommon pathogens, revealing Nocardia transvalensis infection. It is likely that varicella induced immunodepression, facilitating opportunistic infection in an otherwise healthy and immunocompetent child. To our knowledge, our report is the first case of Nocardia infection in varicella.

We here report an unusual paediatric case of streptococcal osteomyelitis with a severe outcome as a complication of varicella. A 15-month-old girl with a 3-day history of varicella rash was admitted to our Paediatric Department because of high fever, pain and joint immobility of her right elbow and left ankle. Upon admission the patient presented pustules with highly infected lesions on her back, trunk, arms and face. Physical examination revealed marked swelling with diffused tenderness and local warmth at both the right elbow and the left ankle. The patient at admission had a leukocyte count (WBC) of 17,940 ll, C-reactive protein (CRP) of 17.15 mg/dl (normal value \0.5 mg/dl) and erythrocyte sedimentation rate (ERS) of 50 mm/h (normal value \20 mm/h). The humoral immune response was normal [immunoglobulin A (IgA) 107 mg/dl, IgG 925 mg/dl, IgM 182 mg/dl) as were the Tand B-cell subsets (CD3? 74%, CD4? 44%, CD8? 23%, CD19? 18%). Empirical antibiotic therapy with ceftriaxone and amikacin was prescribed. Conventional X-ray revealed swelling at the right elbow, left wrist and feet as well as a fragmented and irregular profile of the right ulna distal metaphysic and the left fibula. Magnetic resonance imaging (MRI) of the elbow revealed massive inflammation of the joint on the left side, with involvement of the surrounding soft tissues (Fig. 1). Bone scintigraphy showed increased activity in the right elbow, left fibula and tibia, consistent with osteomyelitis. Three days after admission, ceftriaxone and amikacin were replaced by ampicillin, owing to a positive blood culture for Group A beta-hemolytic streptococcus(GABSH). Two weeks following the initiation of the ampicillin treatment, laboratory tests revealed the WBC count to be 11,000 ll, CRP 4.63 and ERS 100 mm/h. Due to the lack of improvement in the patient’s clinical condition, ampicillin therapy was changed to treatment with linezolid on the basis of the susceptibility testing. This led to pain relief and a decrease in the swelling. Four weeks after the initiation of linezolid therapy, the patient was discharged with oral administration of linezolid. However, 15 days later, the patient was readmitted due to right elbow pain and swelling. At admission, the WBC was 11,200 ll, CRP 0.08 mg/dl and ERS 10 mm/h. Radiological examinations (X-ray and MRI) revealed bone destruction of the ulna distal metaphysic, compatible with destructive osteomyelitis. The residual proximal stump was diverted externally, and both the lamellar and diaphyseal distal stumps were fragmented (Fig. 2). The orthopaedic physician intraoperatively reduced the anterolateral dislocation of the right radius and put it into a cast. No cultures or other microbiological tests were performed during surgery. One month following the surgery, X-ray examinations showed severe right ulna destructive outcomes, with just a minimal residual proximal and distal fragments. Six months later, an X-ray showed no further radiological modifications. Varicella complications are rare, but in some patients they may be severe, requiring hospitalization [1–3]. The frequency of varicella infection complicated by invasive GABSH disease in children has been documented to be 6–17% [3–5]. Recently, numerous studies have documented an increasing incidence and severity of GABSHS infections [2, 6, 7]. E. Bozzola (&) A. Krzystofiak L. Lancella A. Quondamcarlo A. Villani Department of Paediatrics, Paediatric and Infectious Disease Unit, Children Hospital Bambino Gesu, Rome, Italy e-mail: elenabozzola@libero.it

The aim of this paper is to describe the imaging features of central nervous system (CNS) tuberculosis on computed tomography (CT) and magnetic resonance imaging (MRI) studies in non-HIV-positive children. A retrospective descriptive evaluation was conducted on imaging studies obtained from ten children admitted to our hospital over a 6-year period who fulfilled criteria for a diagnosis of CNS tuberculosis. Data were collected with regard to patients’ clinical, laboratory and demographic characteristics, as well as results of radiological investigation. We studied ten children, of whom five were boys and five were girls and whose mean age was 4 (range 7 months to16) years. Neuroradiological findings on the first imaging study were basal meningeal enhancement (100%), hydrocephalus (70%), infarcts (90%), tuberculomas (40%) and cranial nerve involvement (20%). Follow-up studies revealed basal meningeal enhancement, hydrocephalus, and infarcts in all patients, tuberculomas in 70% and cranial nerve involvement in 50%. Only one patient showed a pattern of miliary tuberculosis. CNS tuberculosis is still an important cause of childhood morbidity and mortality even in nonimmunosuppressed children. Because prompt diagnosis results in earlier treatment, it is crucial to be aware of tuberculous meningitis and its complications at imaging, especially because of the impact on patients’ prognosis.

The aim of this study is to assess the frequency and clinical importance of mediastinal tubercular lymphadenitis and adenobronchial fistulas (TABF) and to evaluate the role of fiberbronchoscopy and surgical bronchoscopy associated with antimicrobical chemotherapy. 136 cases of primary pulmonary TBC, admitted to the Unit of Infectious Diseases, Bambino Gesu Children Hospital in Rome, between 1980 and 2001, were enrolled in the study. We considered 56 patients with clinical and radiological evidence of mediastinal tubercular lymphadenitis and 28 patients with adenobronchial fistulas (TABF). The incidence of TABF was 20,58% of primary pulmonary TBC. All patients were treated by medical therapy combined with local endobronchial surgery. TABF emerges as a complication of pediatric primary pulmonary TBC. We suggest a clinical and radiological survey to decide the utility of a diagnostic and therapeutic surgical bronchoscopy

SUMMARYThe concentrations of the chemokines IL-8, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) were measured in 120 CSF samples from 23 patients with pyogenic meningitis and from 11 patients with tuberculous meningitis (TBM) and in 10 CSF from subjects with non-infectious neurological diseases. The chemokine concentrations in patients with meningitis were significantly higher than in control subjects (P

We report the case of an immunocompetent child with spondylodiscitis as a result of staphylococcal sepsis, which was successfully treated with linezolid. The patient was admitted with fever and circumferential swelling in the paradorsal region, which was evident only in the flexed back position. A chest X-ray showed a pleural effusion with pneumonitis and dorsal kyphosis. Following the yield of Staphylococcus aureus from blood cultures, the initial therapy of ceftriaxone and amikacin was changed to vancomycin. However, the dorsal swelling increased further and imaging investigations showed destruction of the vertebral bodies D8–D10 and surrounding tissue swelling. Vancomycin was changed to linezolid, and the patient began to improve; a full recovery was made. Our case suggests that even if spondylodiscitis is rare in the pediatric age-group, particularly as a complication of staphylococcal sepsis, early diagnosis and prompt and appropriate therapy are important to prevent severe complications.

Tuberculosis (TB) is still the world’s second most frequent cause of death due to infectious diseases after HIV infection, and this has aroused greater interest in identifying and managing exposed subjects, whether they are simply infected or have developed one of the clinical variants of the disease. Unfortunately, not even the latest laboratory techniques are always successful in identifying affected children because they are more likely to have negative cultures and tuberculin skin test results, equivocal chest X-ray findings, and atypical clinical manifestations than adults. Furthermore, they are at greater risk of progressing from infection to active disease, particularly if they are very young. Consequently, pediatricians have to use different diagnostic strategies that specifically address the needs of children. This document describes the recommendations of a group of scientific societies concerning the signs and symptoms suggesting pediatric TB, and the diagnostic approach towards children with suspected disease.

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day–17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered.