Early acute cerebellar ataxia after meningococcal B vaccine: a case report of a 7-month-old infant and a review of the literature.

BACKGROUND: Acute cerebellar ataxia (ACA) and acute cerebellitis represent disorders characterized by a para-infectious, post-infectious, or post-vaccination cerebellar inflammation. They are relatively common neurologic disorders among children, and may follow infections, or, more rarely, vaccinations. Few cases are instead described among infants. Although the immunization with meningococcal group B (MenB) vaccine has been associated with some neurological side effects, suspected ACA has been reported only once in the literature. CASE PRESENTATION: we describe a 7-month-old female that presented ACA within 24 h from the MenB second dose vaccination. Extensive laboratory studies and magnetic resonance imaging excluded other causes. We then conducted an extended review of other vaccine related cases reported in the literature, focusing on the clinical characteristics of ACA and finding that ataxia and cerebellitis of para- or post-infectious cause are very rarely described in the first year of life. We collected 20 articles published in the last 30 years, including an amount of 1663 patients (1-24 years) with ACA. CONCLUSIONS: a very small number of suspected post-vaccinal ataxias has been described in recent years, compared to other causes, and vaccination remains an unquestionable medical need. Further research is needed to clarify the complex pathogenesis of this disorder and its eventual link with vaccinations.

SARS-CoV-2 infection in children: A 24 months experience with focus on risk factors in a pediatric tertiary care hospital in Milan, Italy.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is characterized by a wide variety of expressions ranging from asymptomatic to, rarely, critical illness. The basis of this variability is not yet fully understood. The aim of this study was to identify clinical and genetic risk factors predisposing to disease susceptibility and progression in children. Methods: We enrolled 181 consecutive children aged less than 18 years hospitalized with or for SARS-CoV-2 infection during a period of 24 months. Demographic, clinical, laboratory, and microbiological data were collected. The development of coronavirus disease 2019 (COVID-19)-related complications and their specific therapies were assessed. In a subset of 79 children, a genetic analysis was carried out to evaluate the role of common COVID-19 genetic risk factors (chromosome 3 cluster; ABO-blood group system; FUT2, IFNAR2, OAS1/2/3, and DPP9 loci). Results: The mean age of hospitalized children was 5.7 years, 30.9% of them being under 1 year of age. The majority of children (63%) were hospitalized for reasons different than COVID-19 and incidentally tested positive for SARS-CoV-2, while 37% were admitted for SARS-CoV-2 infection. Chronic underlying diseases were reported in 29.8% of children. The majority of children were asymptomatic or mildly symptomatic; only 12.7% developed a moderate to critical disease. A concomitant pathogen, mainly respiratory viruses, was isolated in 53.3%. Complications were reported in 7% of children admitted for other reasons and in 28.3% of those hospitalized for COVID-19. The respiratory system was most frequently involved, and the C-reactive protein was the laboratory test most related to the development of critical clinical complications. The main risk factors for complication development were prematurity [relative risk (RR) 3.8, 95% confidence interval (CI) 2.4-6.1], comorbidities (RR 4.5, 95% CI 3.3-5.6), and the presence of coinfections (RR 2.5, 95% CI 1.1-5.75). The OAS1/2/3 risk variant was the main genetic risk factor for pneumonia development [Odds ratio (OR) 3.28, 95% CI 1-10.7; p value 0.049]. Conclusion: Our study confirmed that COVID-19 is generally less severe in children, although complications can develop, especially in those with comorbidities (chronic diseases or prematurity) and coinfections. Variation at the OAS1/2/3 genes cluster is the main genetic risk factor predisposing to COVID-19 pneumonia in children.

Corrigendum: Disappearance of seasonal respiratory viruses in children under two years old during COVID-19 pandemic: A monocentric retrospective study in Milan, Italy.

[This corrects the article DOI: 10.3389/fped.2021.721005.].

Epidemiology and antimicrobial susceptibility of Staphylococcus aureus in children in a tertiary care pediatric hospital in Milan, Italy, 2017-2021.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent worldwide and can cause severe diseases. MRSA is associated with other antibiotic resistance. COVID-19 pandemic increased antimicrobial resistance in adult patients. Only a few data report the antimicrobial susceptibility of S. aureus in the Italian pediatric population, before and during the COVID-19 pandemic. METHODS: We included all the S. aureus positive samples with an available antibiogram isolated from pediatric patients (< 18 years old) in a tertiary care hospital in Milan, Italy, from January 2017 to December 2021. We collected data on demographics, antimicrobial susceptibility, and clinical history. We compared methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA strains. We calculated the frequency of isolation by year. The incidence of isolates during 2020 was compared with the average year isolation frequency using the univariate Poisson test. We compared the proportion of MRSA isolates during 2020 to the average proportion of other years with the Chi-squared test. RESULTS: Our dataset included a total of 255 S. aureus isolated from 226 patients, 120 (53%) males, and 106 (47%) females, with a median age of 3.4 years (IQR 0.8 - 10.5). The mean isolation frequency per year was 51. We observed a significant decrease of isolations during 2020 (p = 0.02), but after adjusting for the total number of hospitalization per year there was no evidence that the incidence changed. Seventy-six (30%) S. aureus were MRSA. Twenty (26%) MRSA vs 23 (13%) MSSA (p = 0.02) were hospital-acquired. MRSA strains showed higher resistance to cotrimoxazole, clindamycin, macrolides, levofloxacin, gentamicin, and tetracyclin than MSSA strains. None of MRSA were resistant to linezolid and vancomycin, one was resistant to daptomycin. The proportion of MRSA did not change during the COVID-19 pandemic. The overall clindamycin resistance was high (17%). Recent antibiotic therapy was related to MRSA infection. CONCLUSION: The proportion of MRSA did not change during the COVID-19 pandemic and remained high. Clindamycin should not be used as an empirical MRSA treatment due to its high resistance.

Meningococcal Disease in Pediatric Age: A Focus on Epidemiology and Prevention.

Meningococcal disease is caused by Neisseria meningitidis; 13 serogroups have been identified and differentiated from each other through their capsular polysaccharide. Serotypes A, B, C, W, X, and Y are responsible for nearly all infections worldwide. The most common clinical manifestations are meningitis and invasive meningococcal disease, both characterized by high mortality and long-term sequelae. The infection rate is higher in children younger than 1 year and in adolescents, who are frequently asymptomatic carriers. Vaccination is the most effective method of preventing infection and transmission. Currently, both monovalent meningococcal vaccines (against A, B, and C serotypes) and quadrivalent meningococcal vaccines (against serogroups ACYW) are available and recommended according to local epidemiology. The purpose of this article is to describe the meningococcal vaccines and to identify instruments that are useful for reducing transmission and implementing the vaccination coverage. This aim could be reached by switching from the monovalent to the quadrivalent vaccine in the first year of life, increasing vaccine promotion against ACYW serotypes among adolescents, and extending the free offer of the anti-meningococcal B vaccine to teens, co-administering it with others proposed in the same age group. Greater awareness of the severity of the disease and increased health education through web and social networks could represent the best strategies for promoting adhesion and active participation in the vaccination campaign. Finally, the development of a licensed universal meningococcal vaccine should be another important objective.

Incidental occurrence of neutropenia in children hospitalised for COVID-19.

BACKGROUND: Investigations on haematological alterations in paediatric COVID-19 have been focused mostly on lymphocytes and clotting profiles. Neutropenia has been occasionally reported and its course and impact on the disease have not been elucidated. The aim of this study was to describe the epidemiology, course, and impact of neutropenia in children with COVID-19 hospitalised in a tertiary care referral paediatric ward. METHODS: A single-centre retrospective study was conducted. Hospitalised children between 1 month and 18 years with confirmed COVID-19 and neutropenia were included and compared to non neutropenic patients. Complete blood picture with differential blood count, serum biochemistry, clotting profiles were performed; clinical data, length of hospitalisation, and prescription of drugs were collected. RESULTS: Twelve out of 95 patients (12.63%) with documented SARS-CoV-2 infection were neutropenic and met the inclusion criteria. The mean age was 161 days (range 38-490 days). The mean duration of symptoms in neutropenic children was 3.82 days, while the mean length of hospitalisation was 7.67 days. These findings were not significantly different in the two study groups. All patients had mild clinical manifestations and were discharged without sequelae. CONCLUSIONS: We provided the first comprehensive study on neutropenia in mild paediatric COVID-19 infection. Our findings show that the main features of this haematological disorder in COVID-19 are analogous to the well-known transient benign neutropenia associated with other common viral infections. In our setting, neutropenia does not emerge as a potential negative prognostic factor in paediatric COVID-19.

Management of upper retropharyngeal abscesses in children: Two case reports of a troublesome situation.

Management of upper retropharyngeal abscesses in children is challenging. In surgical cases, ultrasound-assisted intra-operative procedures may be helpful to reach peculiar locations, thus reducing surgical morbidity and complications rate.

Disappearance of Seasonal Respiratory Viruses in Children Under Two Years Old During COVID-19 Pandemic: A Monocentric Retrospective Study in Milan, Italy.

Background: The containment measures adopted during COVID-19 pandemic have influenced the epidemiology of other respiratory viruses. Aim: We analyzed the modification of the incidence and etiology of lower respiratory tract infections (LRTIs) in young children during COVID-19 pandemic. Methods: Case series of all children under 2 years old hospitalized at a tertiary care Hospital in the Center of Milan, Italy diagnosed with LRTIs in three consecutive winter seasons (from the 1st of November to the last day of February in 2018/2019, 2019/2020 and 2020/2021). We compared the number of hospitalizations and viral detections in the 2020/2021 with the average of 2018/2019 and 2019/2020 (pre-COVID-19) using the Poisson distribution. Results: we enrolled 178 patients (66 from 2018/2019, 96 from 2019/2020, 16 from 2020/2021) 94 males (53%) and 84 females (47%), with a median (IQR) age of 5 (2-13) months. The number of hospitalizations during the 2020/2021 season was 80% lower than the average of the pre-COVID-19 seasons (16 vs. 81, p<0.001). Overall, 171 (96%) patient's nasopharyngeal aspirate (NPA) detected at least one virus (110, 64%, single-detection, 61, 36%, co-detections). In 2020/2021 we observed the disappearance of Respiratory Syncytial virus (0 vs. 54, p < 0.001), Influenza virus (0 vs. 6.5, p = 0.002), Metapneumovirus (0 vs. 8, p < 0.001), Parainfluenza viruses (0 vs. 3.5, p = 0.03) and a significant reduction of Adenovirus (2 vs. 7, p = 0.03), Bocavirus (2 vs. 7.5, p = 0.02) and Enterovirus (1 vs. 5, p = 0.04). No significant difference was found for Rhinoviruses (14 cases vs. 17, p = 0.2), other Coronaviruses (0 vs. 2, p = 0.1), and Cytomegalovirus (1 vs. 1, p = 0.7). Conclusions: We observed a striking reduction in hospitalizations due to LRTIs and a modification of the etiology, with enveloped viruses mainly affected.

Panton-valentine leukocidin Staphylococcus aureus severe infection in an infant: a case report and a review of the literature.

BACKGROUND: Panton-Valentine leukocidin (PVL) is one of the major virulence factor of Staphylococcus aureus (SA) that might be associated with invasive life-threating infections. A prompt diagnosis and adequate treatment are essential in achieving the best outcome and avoiding serious sequelae. We describe a case of severe invasive PVL-SA infection in an infant. A literature review starting from 2010 was also performed in order to discuss clinical presentations, radiological findings, treatment and outcome. CASE PRESENTATION: This is a case of a 6-month-old boy who rapidly developed high fever and poor general condition. He was diagnosed as having multiple muscular abscesses, multiple foci of osteomyelitis and bloodstream infections caused by Panton-Valentine leukocidin Methicillin-resistant Staphylococcus aureus. He received intravenous antibiotics and surgical drainage of the abscess with progressive recovery. CONCLUSION: Our report highlights the importance of improving awareness of this severe infection, as a prompt diagnosis and adequate manage is essential in order to save life and to prevent serious complications.

Bronchiolitis and SARS-CoV-2.

BACKGROUND: It has been speculated that the SARS-CoV-2 was already widespread in western countries before February 2020. METHODS: We gauged this hypothesis by analysing the nasal swab of infants with either bronchiolitis or a non-infectious disease admitted to the Ospedale Maggiore, Milan (one of the first epicentres of SARS-CoV-2 outbreak in Europe) from November 2019. RESULTS: The SARS-CoV-2 RNA was never detected in 218 infants with bronchiolitis (95 females, median age 4.9 months) and 49 infants (22 females, median age 5.6 months) with a non-infectious disease between November 2019 and February 2020. On the contrary, two infants hospitalised for bronchiolitis between March and April 2020 tested positive for SARS-CoV-2. CONCLUSIONS: This study does not support the hypothesis that SARS-CoV-2 was already circulating among infants before the official outbreak of SARS-CoV-2 infection. However, it shows for the first time that SARS-CoV-2 might cause bronchiolitis requiring hospitalisation.

SARS-COV-2 Infection and Kawasaki Disease: Case Report of a Hitherto Unrecognized Association.

Coronavirus-associated disease (COVID-19) was firstly reported at the end of 2019. Generally, COVID-19 seems to be a less severe disease in children than in adults. According to the current literature, children account approximately for 2% of diagnosed COVID-19 cases. Northern Italy is one of the geographical areas mainly affected by the ongoing COVID-19 pandemic. We describe a pediatric patient diagnosed and treated for atypical/incomplete Kawasaki Disease (KD) complicated with paralytic ileus, who also resulted positive for SARS-COV-2.

Autoimmune rhomboencephalitis: A pediatric case report.

Rhomboencephalitis is a potentially life-threatening condition due to inflammation of the hindbrain with an unpredictable outcome depending on the wide spectrum of etiologies and the promptness of diagnosis and treatment. A 23-month-old Caucasian male presented with fever, clouding of consciousness, and trunk ataxia. Three weeks earlier he received active immunization against varicella-zoster virus. Routine laboratory tests were unremarkable. Cerebrospinal fluid showed might elevation of leukocytes. The infection panel was negative. Brain magnetic resonance showed signal hyperintensity in the dorsal portion of the pons, which was consistent with a rhomboencephalitis. Autoimmune pathogenesis was supposed and a high dose of steroids was started. The patient's neurologic status progressively improved till full recovery and complete regression of previous magnetic resonance lesions after 1 year. Nevertheless, longer follow-up is needed in order not to miss any possible signs of an underlying autoimmune neurologic disorder.

Otogenic temporomandibular septic arthritis in a child: a case report and a review of the literature.

BACKGROUND: Acute otitis media is one of the most common infectious diseases in the paediatric age and although its complications such as acute mastoiditis have become rare thanks to improvements in therapeutic approaches, possible serious complications such as septic arthritis of the temporomandibular joint may develop. A prompt diagnosis and adequate treatment are essential to achieving the best outcome and avoiding serious sequelae. We describe a case occurring in a previously healthy 6-year-old female and review the literature currently available on this topic. CASE PRESENTATION: The patient presented a right temporomandibular septic arthritis with initial mandibular bone involvement secondary to acute otitis media. She presented with torcicollis, trismus, right preauricular swelling over the temporomandibular joint and was successfully treated with antibiotic treatment alone. CONCLUSIONS: Septic arthritis of the temporomandibular joint is a rare complication of acute otitis media or acute mastoiditis in children. It should be suspected in patients presenting with trismus, preauricular swelling or fever. No guidelines on the diagnosis and treatment of this infectious disease are currently available.

Kikuchi-Fujimoto disease in children: two case reports and a review of the literature.

BACKGROUND: Kikuchi-Fujimoto disease is a rare, idiopathic and generally self-limiting cause of lymphadenitis of unknow etiology with a low recurrence rate. The typical clinical signs are cervical lymphadenopathy, fever, and symptoms of respiratory infection, and less frequently chills, night sweats, arthralgia, rash, and weight loss. CASE PRESENTATION: Here we describe two case reports of Kikuchi Fujimoto disease presenting in Milan within the space of a few months. The first involved the recurrence of KFD in a young boy from Sri Lanka; the second was a rare case of severe KFD complicated by HLH. CONCLUSIONS: Pediatricians must consider KFD in the differential diagnosis of fever of unknown origin in children, even in western countries. Although rare, recurrence and severe complications are possible. Where symptoms suggest KFD, a systematic diagnostic approach is key. Since no guidelines on the management of KFD are available, further studies should be conducted to investigate the therapeutic options and long term outcome in children.

Role of High-Resolution Chest Computed Tomography in a Child with Persistent Tachypnoea and Intercostal Retractions: A Case Report of Neuroendocrine Cell Hyperplasia.

Background: Chronic interstitial lung diseases in children (chILD) are a heterogeneous group of disorders that can represent a clinical challenge for pediatric pneumologists. Among them, neuroendocrine cell hyperplasia of infancy (NEHI) is a diffuse lung disease prevalent in the first years of life that spontaneously improves over time. The clinical presentation of NEHI is indistinguishable from other interstitial lung diseases, so a correct and non-invasive diagnosis by chest computed tomography (CT) without lung biopsy might not be simple. Case presentation: An 8-month-old male infant presented with a history of chronic tachypnoea and dyspnoea since 6 months of age. The patient was born at term, with APGAR scores of 9 and 10 at 1 and 5 min, respectively. Since his second month of life, the patient suffered from abnormal breathing, which was characterized by mild tachypnoea and costal retractions that worsened during breastfeeding, crying, and respiratory infections. Bilateral inspiratory crackles, preferential to the lung bases, without oxygen desaturation were detected. A chest X-ray showed a diffuse over-inflation of the lungs, but laboratory tests did not reveal any abnormalities. High-resolution chest CT documented patchy areas of ground-glass opacity involving the right upper lobe, middle lobe, and lingula, and showed mosaic areas of air-trapping, suggesting a diagnosis of NEHI. The infant was discharged without therapy and gradually improved over time. At 1 year of age, the patient was eupnoeic and chest auscultation had normalized. Conclusions: NEHI is an interstitial disease of infancy characterized by tachypnoea from the first months of life, with a good prognosis and for which a rational diagnostic approach is crucial for making a specific, early diagnosis. Initially, clinical suspicions can be confirmed with reasonable accuracy by a CT scan of the chest. Other more invasive and more expensive investigations should be reserved for selected cases that do not show a spontaneous, favourable clinical evolution.

A young infant with transient severe hypertriglyceridemia temporarily associated with meropenem administration: A case report and review of the literature.

BACKGROUND: Slight changes in the lipid profile can be observed over the acute phase of infectious diseases. Moreover, some anti-infective drugs can modify serum lipid concentrations, although antibiotics do not seem to have a relevant, direct, or acute effect on the lipid profile. METHODS: A 75-day-old breastfed Caucasian female, born at term after a regular pregnancy, was hospitalized for osteomyelitis. She was immediately treated with intravenous meropenem and vancomycin. Therapy was effective, but after 22 days of treatment, her blood was found to be viscous with a purple shade. RESULTS: A fasting blood sample showed serum triglycerides of 966 mg/dL, total cholesterol of 258 mg/dL, and high-density lipoprotein cholesterol of 15 mg/dL. Secondary causes of hyperlipidemia and primary hereditary disorders were ruled out. Thereafter, the possibility that antibiotics may have had a role in the hypertriglyceridemia was considered, and meropenem was discontinued. After 72 hours of meropenem discontinuation, a sharp modification of lipid variables was observed, and further testing showed a complete normalization of the lipid profile. CONCLUSION: In this child with osteomyelitis, the increase in serum triglycerides appeared suddenly after 3 weeks of meropenem treatment and resolved quickly after meropenem discontinuation, thus highlighting the possible association between meropenem and lipid profile alterations. Monitoring the lipid profile should be considered in cases of long-term treatment with meropenem, and further studies on meropenem safety should include evaluation of the lipid profile.

Abdominal mass hiding rib osteomyelitis.

BACKGROUND: Rib osteomyelitis is a rare entity, occurring in approximately 1 % or less of all cases of haematogenous osteomyelitis. Given its rarity and clinical heterogeneity, the diagnosis of rib osteomyelitis can be challenging and requires a high index of suspicion. We present a case of acute osteomyelitis of the rib due to community-acquired methicillin-resistant Staphylococcus aureus (MRSA), which occurred in an otherwise healthy 3-month-old infant and mimicked an epigastric hernia at first. CASE PRESENTATION: An otherwise healthy 3-month-old female infant was sent by her primary care paediatrician to the paediatric emergency department for possible incarcerated epigastric hernia because for 2 days, she had suffered from mild to moderate fever, irritability, poor feeding, and tender epigastric swelling. Ultrasonographic imaging excluded epigastric hernia, and transthoracic echocardiography ruled out endocarditis. However, clinical assessment combined with laboratory criteria classified the child into the high-risk group for having severe bacterial infection. Consequently, awaiting the definitive diagnosis, she was immediately treated with a broad-spectrum regimen of intravenous antibiotic therapy based on vancomycin (40 mg/kg/die in 3 doses) and meropenem (100 mg/kg/die in 3 doses). Three days after admission, the blood culture result was positive for methicillin-resistant Staphylococcus aureus, and vancomycin remained as antibiotic therapy. On day 3, a second swelling appeared at the level of the seventh left rib, 2 cm-wide, non-erythematous, mildly painful. Ultrasonography of the left chest wall on this occasion showed an image consistent with an acute osteomyelitis of the anterior osteo-chondral region of the 7th rib and associated adjacent periosteal and soft tissue collection and magnetic resonance imaging confirmed the osteomyelitis of the anterior middle-distal part of the 7th left rib, near the costochondral junction. Vancomycin was continued up to a total of 6 weeks of therapy, and at the end, the child was discharged in good condition with no relapse during the follow-up. CONCLUSION: This is one of the few reported cases of paediatric rib osteomyelitis caused by community-acquired MRSA. Timely identification associated with prompt and targeted antibiotic therapy may allow full recovery.

Characteristics and Their Clinical Relevance of Respiratory Syncytial Virus Types and Genotypes Circulating in Northern Italy in Five Consecutive Winter Seasons.

In order to investigate the genetic diversity and patterns of the co-circulating genotypes of respiratory syncytial virus (RSV) and their possible relationships with the severity of RSV infection, we studied all of the RSV-positive nasopharyngeal samples collected from children during five consecutive winters (2009-2010, 2010-2011, 2011-2012, 2012-2013 and 2013-2014). The RSVs were detected using the respiratory virus panel fast assay and single-tube RT-PCR, their nucleotides were sequenced, and they were tested for positive selection. Of the 165 positive samples, 131 (79.4%) carried RSV-A and 34 (20.6%) RSV-B; both groups co-circulated in all of the study periods, with RSV-A predominating in all the seasons except for winter 2010-2011, which had a predominance of RSV-B. Phylogenetic analysis of the RSV-A sequences identified genotypes NA1 and ON1, the second replacing the first during the last two years of the study period. The RSV-B belonged to genotypes BA9 and BA10. BA9 was detected in all the years of the study whereas BA only desultorily. Comparison of the subjects infected by RSV-A and RSV-B types did not reveal any significant differences, but the children infected by genotype A/NA1 more frequently had lower respiratory tract infections (p<0.0001) and required hospitalisation (p = 0.007) more often than those infected by genotype A/ON1. These findings show that RSV has complex patterns of circulation characterised by the periodical replacement of the predominant genotypes, and indicate that the circulation and pathogenic role of the different RSV strains should be investigated as each may have a different impact on the host. A knowledge of the correlations between types, genotypes and disease severity may also be important in order to be able to include the more virulent strains in future vaccines.