Exploring nasopharyngeal microbiota profile in children affected by SARS-CoV-2 infection.

The relationship between COVID-19 and nasopharyngeal (NP) microbiota has been investigated mainly in the adult population. We explored the NP profile of children affected by COVID-19, compared to healthy controls (CTRLs). NP swabs of children with COVID-19, collected between March and September 2020, were investigated at the admission (T0), 72 h to 7 days (T1), and at the discharge (T2) of the patients. NP microbiota was analyzed by 16S rRNA targeted-metagenomics. Data from sequencing were investigated by QIIME 2.0 and PICRUSt 2. Multiple machine learning (ML) models were exploited to classify patients compared to CTRLs. The NP microbiota of COVID-19 patients (N = 71) was characterized by reduction of α-diversity compared to CTRLs (N = 59). The NP microbiota of COVID-19 cohort appeared significantly enriched in Streptococcus, Haemophilus, Staphylococcus, Veillonella, Enterococcus, Neisseria, Moraxella, Enterobacteriaceae, Gemella, Bacillus, and reduced in Faecalibacterium, Akkermansia, Blautia, Bifidobacterium, Ruminococcus, and Bacteroides, compared to CTRLs (FDR < 0.001). Exploiting ML models, Enterococcus, Pseudomonas, Streptococcus, Capnocytopagha, Tepidiphilus, Porphyromonas, Staphylococcus, and Veillonella resulted as NP microbiota biomarkers, in COVID-19 patients. No statistically significant differences were found comparing the NP microbiota profile of COVID-19 patients during the time-points or grouping patients on the basis of high, medium, and low viral load (VL). This evidence provides specific pathobiont signatures of the NP microbiota in pediatric COVID-19 patients, and the reduction of anaerobic protective commensals. Our data suggest that the NP microbiota may have a specific disease-related signature since infection onset without changes during disease progression, regardless of the SARS-CoV-2 VL. IMPORTANCE: Since the beginning of pandemic, we know that children are less susceptible to severe COVID-19 disease. A potential role of the nasopharyngeal (NP) microbiota has been hypothesized but to date, most of the studies have been focused on adults. We studied the NP microbiota modifications in children affected by SARS-CoV-2 infection showing a specific NP microbiome profile, mainly composed by pathobionts and almost missing protective anaerobic commensals. Moreover, in our study, specific microbial signatures appear since the first days of infection independently from SARS-CoV-2 viral load.

Measles lessons in an anti-vaccination era: public health is a social duty, not a political option.

BACKGROUND: Measles virus, member of the genus Morbillivirus in the family Paramyxoviridae, is a highly contagious human pathogen. An effective live-attenuated vaccine is available and its use has the potential to eradicate the disease from the human population. Although the vaccine was introduced in national vaccination schedules, several measles outbreaks have occurred because of insufficient vaccination coverage. Since early January 2017, a new outbreak of measles in Italy has been observed. METHODS: We analyzed all the patients admitted to the Emergency Department of Bambino Gesù Children Hospital of Rome from the 1st of January 2017 to the end of May 2017 and discharged with diagnosis of suspected or confirmed measles or admitted to the Pediatric and Infectious Disease Unit. For each confirmed case, demographic data, vaccination history, exposure to source case, clinical presentation, date of onset of symptoms, hospitalization, laboratory test results, complications and therapy were collected. RESULTS: From the 1st of January 2017 to the 31st of May 2017, we enrolled 139 patients who were conducted to the Emergency Department of Bambino Gesù Children's Hospital because of measles: 33 patients were discharged with the diagnosis of suspected measles by clinical manifestations; 33 discharged with the diagnosis of confirmed measles by laboratory tests and 73 were admitted to the Pediatric and Infectious Disease Unit. Seven patients, who were exposed to mothers with measles, were admitted to receive treatment with Measles Immune Globulin intravenously. Among the 66 patients admitted to the hospital with measles, 31 cases (47%) occurred in unvaccinated individuals who were age-eligible for measles vaccination; 29 (44%) were infants too young to be vaccinated; only five patients (8%) received one dose of measles-containing vaccine. Out of the 66 patients, 35 (53%) developed complications. Acute respiratory failure was the most reported complications (20%). Death, due to multiorgan failure by measles, occurred in one 9-girl-year-age patient with genetic disorders who was unvaccinated. CONCLUSIONS: Measles still represents a serious public health problem worldwide. Vaccination against measles is safe, effective, and cost-effective. High vaccination coverage (>95%) with two doses of measles vaccine is crucial to elimination. Health care professionals play an important role in vaccination uptake and prevention of measles spread during an outbreak.

Brain abscesses in children: an Italian multicentre study.

Brain abscess is uncommon in paediatric population, but of clinical importance because of significant long-term morbidity and mortality. In this multicentre study, promoted by the Italian Society for Paediatric Infectious Diseases, we retrospectively collected patients aged 0-18 years, with a diagnosis of 'brain abscess'. Seventy-nine children were included; the median age was 8·75 years. As predisposing factor, 44 children had preceding infections. The Gram-positive cocci were mostly isolated (27 cases). Sixty (76%) children underwent a surgical intervention. Intravenous antibiotic therapy was administered in all patients, then switched to oral treatment. Clinical sequelae were recorded in 31 (39·2%) children. Twenty-one of them had a single sequela, of which, the most represented, was epilepsy in nine of them. This study focus the attention on the need to have standardized national guidelines or adequate recommendations on type and duration of antibiotic treatment.

Clostridium difficile infection in children: epidemiology and risk of recurrence in a low-prevalence country.

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 spread of drug-resistant tuberculosis in children: an Italian case series.

Drug-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.

HHV6 meningoencephalitis sequelae in previously healthy children.

INTRODUCTION: 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. PURPOSE: The aim of this study was to evaluate sequelae of HHV6 meningoencephalitis in previously healthy children. RESULTS: 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. CONCLUSION: HHV6 meningoencephalitis can be associated with a wide range of clinical outcomes, from long-term neurological sequelae to a benign post-infectious clinical course.

Central nervous system tuberculosis in non-HIV-positive children: a single-center, 6 year experience.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: We studied ten children, of whom five were boys and five were girls and whose mean age was 4 (range 7 months to 16) 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. CONCLUSIONS: 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.

Prolonged in-hospital exposure to an infant with active pulmonary tuberculosis.

Active 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.

Measles-induced respiratory distress, air-leak and ARDS.

Young infants with measles requiring respiratory support have a significant risk for death and long-term complications. Even in developed countries, the occurrence of spontaneous air-leaks and acute respiratory distress syndrome (ARDS) still represent the most severe clinical presentation in early childhood, with a high fatality rate. A clinical series review from a tertiary university paediatric intensive care unit (PICU) was undertaken. During the 2006-2007 outbreak in Rome, Italy, a young infant presented with ARDS/spontaneous air-leak and needed aggressive ventilatory management and haemodynamic support. Both nebulised iloprost and intravenous pentoxifylline were administered during the acute hypoxaemic phase; the role of this pharmacologic approach in critically ill patients is still under debate. We observed four further cases of respiratory impairment requiring a non-invasive approach. Clinical-radiological findings ranged from interstitial pneumonia to bronchiolitis-like pictures. All patients were imported cases, representing an important epidemiological factor and future medical issue, though they were not malnourished nor affected by chronic diseases. We conclude that early respiratory assessment and timely PICU referral is of mainstem importance in the youngest infants with measles-induced respiratory failure. The protean nature of clinical presentation and the possibility of rapid respiratory deterioration should be highlighted, and infants from immigrant families may represent a susceptible high-risk group.

Visceral leishmaniasis revealing chronic granulomatous disease in a child.

We report the first description of visceral leishmaniasis (VL) infection as a harbinger of chronic granulomatous disease (CGD) in a 3-year old child. Although VL is not frequently suspected in CGD patients, our case emphasises the importance of a complete evaluation of the immune system in children presenting with VL in order to exclude underlying immunodeficiency states. As the prognosis of CGD is poor, with high morbidity and mortality, establishing an early diagnosis has important practical implications in the successful treatment of these patients. Following the diagnosis, the patient received Human Leukocyte Antigen (HLA) identical sibling bone marrow transplantation (BMT). The child is now 2 years post-transplant and is in good general conditions with normal blood counts, and evidence of full-donor chimerism in repeated fluorescence in situ hybridization (FISH) studies.

Chemokine profiles in the cerebrospinal fluid (CSF) during the course of pyogenic and tuberculous meningitis.

The concentrations of the chemokines IL-8, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) 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<0.0001). The highest CSF levels were found for IL-8 (median 2917 pg/ml) and MCP-1 (median 2557 pg/ml), whereas those of MIP-1alpha were less significantly elevated (median 24 pg/ml) (P<0.0001). Patients with pyogenic meningitis had higher levels of IL-8 and MCP-1 than those with TBM (P<0.0001). In serial samples from patients with pyogenic meningitis IL-8 levels declined before MCP-1 and MIP-alpha. In the case of TBM, IL-8, MCP-1 and MIP-1alpha decreased more gradually during treatment and were detectable in the CSF for several weeks, without any characteristic time course of elimination. These data indicate that patients with pyogenic meningitis and TBM show different chemokine profiles in CSF. The distinct chemokine pattern could be responsible for a differential attraction and activation of leucocytes in the CSF which is reflected in differences in the inflammatory response and clinical course of pyogenic meningitis and TBM.

[Haemophilus influenzae type b in meningitis: antibiotic resistance in pediatric patients]. / Haemophilus influenzae tipo b: antibioticoresistenza in una casistica pediatrica di meningiti purulente (1985-1994).

A retrospective study on 357 children admitted to four Pediatric Infectious Disease Centers in Rome, affected by acute meningitis, during 10 years period, between January, 1, 1985 and December, 31, 1994 was carried out. Haemophilus influenzae type b was detected in 110 patients; all children aged between 1 month and 5 years; the maximum incidence (74.5%) was observed in patients under two years. The following diagnostic criteria were utilized: Gram stain of CSF; Latex test on CSF, blood, urine; CSF and blood cultures. The in vitro sensitivity of 65 isolates was tested by using the Kirby-Bauer method. We detected 15.3% of strains resistant to Ampicillin and 1.5% resistant to CAF. We also observed a high number of Hib strains resistant to Erythromycin and Cotrimoxazole. Only one strain Ceftriaxone resistant was isolated, confirming the high in vitro sensibility Hib to III generation cephalosporins that still remain the first choice drugs in Hib meningitis.

[Otomastoiditis caused by Mycobacterium avium: a case report]. / Otomastoidite da Mycobacterium avium: descrizione di un caso.

Non tuberculous Mycobacterial (NTM) Infections mainly affect immunocompromised patients, appearing as disseminated or pulmonary disease. In immunocompetent children the most common form of infection with NTM is cervical adenitis. Ear infection seems to be a rare disease. We present a case of otomastoiditis caused by Mycobacterium avium in a 15 months old child, immunologically normal. Patient was referred for persistent right otitis unresponsive to routine medical therapy. TC scan of the ear and temporal bones revealed: soft tissue in external auditory canal, Eustachian canal, and middle ear overlying ossicles with erosion of tegmen tympani. Tuberculin skin test was positive with 5 units PPD and culture yielded M. avium. The patient undergo timpanomastoidectomy and medical therapy with antituberculous drugs and Steroids, subsequently he was given Clarithromycin and Rifabutin. M. avium is an ubiquitous low grade pathogen found in soil, water, dust and food. There is no evidence of direct transmission. Only a few cases of otomastoiditis due to M. avium have previously been reported. The case presented underlines the importance of microbiological investigations. When a NTM infection is suspected surgeons and infectious diseases specialists should cooperate to find an optimal treatment regimen of this unusual disease.

[Bacterial meningitis and CSF cytokines]. / Meningiti batteriche e citochine liquorali.

Aim of study is the determination of concentrations of two important cytokines: TNF alfa and IL8 in children with bacterial meningitis to establish a correlation between infection, CSF concentration of cytokines and neurological sequelae. TNF alfa and IL8 concentrations in CSF have been measured by quantitative immunometric enzyme assay during the course of the disease. In the purulent meningitis we observed that CSF concentrations of these cytokines decreased to undectable values 24 to 48 hours after beginning of the antibiotic therapy. Conversely, in the 3 patients with mycobacterial meningitis (TBM) the concentrations of IL8 were higher for a longer period, being detectable in the CSF between 4 and 8 weeks after the beginning of the specific treatment. We found no significant differences of the values of IL8 in children with neurological sequelae compared with children without sequelae.