A multicenter clinical epidemiology of pediatric pneumococcal meningitis in China: results from the Chinese Pediatric Bacterial Meningitis Surveillance (CPBMS) 2019-2020.

Objective: To analyze the clinical epidemiological characteristics including clinical features, disease prognosis of pneumococcal meningitis (PM), and drug sensitivity of S. pneumoniae isolates in Chinese children. Methods: A retrospective analysis was performed on the clinical, laboratory microbiological data of 160 hospitalized children less than 15 years of age with PM from January 2019 to December 2020 in 33 tertiary hospitals in China. Results: A total of 160 PM patients were diagnosed, including 103 males and 57 females The onset age was 15 days to 15 years old, and the median age was 1 year and 3 months. There were 137 cases (85.6%) in the 3 months to <5 years age group, especially in the 3 months to <3 years age group (109 cases, 68.2%); S. pneumoniae was isolated from cerebrospinal fluid (CSF) culture in 95(35.6%), and 57(35.6%) in blood culture. The positive rates of S. pneumoniae detection by CSF metagenomic next-generation sequencing (mNGS)and antigen detection method were 40.2% (35/87) and 26.9% (21/78). Fifty-five cases (34.4%) had one or more predisposing factors of bacterial meningitis; and 113 cases (70.6%) had one or more extracranial infection diseases Fever (147, 91.9%) was the most common clinical symptom, followed by vomiting (61, 38.1%) and altered mental status (47,29.4%). Among 160 children with PM, the main intracranial imaging complications were subdural effusion and (or) empyema in 43 cases (26.9%), hydrocephalus in 24 cases (15.0%), cerebral abscess in 23 cases (14.4%), intracranial hemorrhage in 8 cases (5.0%), and other cerebrovascular diseases in 13 cases (8.1%) including encephalomalacia, cerebral infarction, and encephalatrophy. Subdural effusion and (or) empyema and hydrocephalus mainly occurred in children < 1 years old (90.7% (39/43) and 83.3% (20/24), respectively). 17 cases with PM (39.5%) had more than one intracranial imaging abnormality. S. pneumoniae isolates were completely sensitive to vancomycin (100.0%, 75/75), linezolid (100.0%,56/56), ertapenem (6/6); highly sensitive to levofloxacin (81.5%, 22/27), moxifloxacin (14/17), rifampicin (96.2%, 25/26), and chloramphenicol (91.3%, 21/23); moderately sensitive to cefotaxime (56.1%, 23/41), meropenem (51.1%, 23/45) and ceftriaxone (63.5, 33/52); less sensitive to penicillin (19.6%, 27/138) and clindamycin (1/19); completely resistant to erythromycin (100.0%, 31/31). The cure and improvement rate were 22.5% (36/160)and 66.3% (106/160), respectively. 18 cases (11.3%) had an adverse outcome, including 6 cases withdrawing treatment therapy, 5 cases unhealed, 5 cases died, and 2 recurrences. S. pneumoniae was completely susceptible to vancomycin (100.0%, 75/75), linezolid (100.0%, 56/56), and ertapenem (6/6); susceptible to cefotaxime, meropenem, and ceftriaxone in the order of 56.1% (23/41), 51.1% (23/45), and 63.5 (33/52); completely resistant to erythromycin (100.0%, 31/31). Conclusion: Pediatric PM is more common in children aged 3 months to < 3 years old. Intracranial complications mostly occur in children < 1 year of age with fever being the most common clinical manifestations and subdural effusion and (or) empyema and hydrocephalus being the most common complications, respectively. CSF non-culture methods can facilitate improving the detection rate of pathogenic bacteria. More than 10% of PM children had adverse outcomes. S. pneumoniae strains are susceptible to vancomycin, linezolid, ertapenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

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OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Diagnostic status and epidemiological characteristics of community-acquired bacterial meningitis in children from 2019 to 2020: a multicenter retrospective study.

Community-acquired bacterial meningitis (CABM) is the main cause of morbidity and mortality in children. The epidemiology of CABM is regional and highly dynamic. To clarify the diagnostic status and epidemiological characteristics of children with CABM in this region, and pay attention to the disease burden, so as to provide evidence for the prevention and treatment of CABM. By retrospective case analysis, the clinical data of 918 CABM cases in children aged 0-14 years in Zhejiang Province from January, 2019 to December, 2020 were collected. The etiological diagnosis rate of CABM in children was 23.1%, the annual incidence rate 4.42-6.15/100,000, the annual mortality rate 0.06-0.09/100,000,the cure and improvement rate 94.4%, and the case fatality rate 1.4%. The total incidence of neuroimaging abnormalities was 20.6%. The median length of stay for CABM children was 20(16) days, with an average cost of 21,531(24,835) yuan. In addition, the incidence rate was decreased with age. Escherichia coli(E.coli) and group B Streptococcus agalactiae(GBS) were the principal pathogens in CABM infant<3 months(43.3%, 34.1%), and Streptococcus pneumoniae(S. pneumoniae) was the most common pathogen in children ≥ 3 months(33.9%). In conclusion, the annual incidence and mortality of CABM in children aged 0-14 years in Zhejiang Province are at intermediate and low level. The distribution of CABM incidence and pathogen spectrum are different in age; the incidence of abnormal neuroimaging is high; and the economic burden is heavy.

A Multicenter Epidemiological and Pathogenic Characteristics Study of Community-Acquired Bacterial Meningitis Children in China: Results from the Chinese Pediatric Bacterial Meningitis Surveillance (CPBMS) 2019-2020.

Objective: To explore the epidemiological and pathogenic characteristics of children with community-acquired bacterial meningitis. Methods: A multicenter, retrospective study was conducted among CABM patients under 15 years old from 33 hospitals in China from 2019 to 2020. The medical record, laboratory, and microbiological data were collected and analyzed. Results: A total of 1610 children with CABM were identified and presented at a median onset age of 45 days of whom 955 (59.3%) were males. CABM occurred mostly in infants <1 year of age (84.0%, 1352/1610). In etiology-confirmed cases, the pathogens were isolated from CSF culture in 515 (32.0%), 400 (24.8%) in blood culture, and 186 (11.6%) both in CSF and blood culture. In total, 126 pathogens were identified through CSF mNGS in 330 CABM cases; 21 S. pneumoniae isolates were detected in 83 CABM cases by antigen detection method. Major pathogens were E. coli (195, 24.7%), GBS (170, 21.5%), and S. pneumoniae (157, 19.9%). GBS (29.3%, 22/75) was the first pathogen of CABM in neonates aged 0-6 days old, while E. coli (44.7%, 76/170) in 7 to 28 days of age; S. pneumoniae (96.2%, 151/157) was the most common pathogen in >3 months old cases. About 9.7% (19/195) strains of E. coli produced ultra­broad­spectrum ß­lactamases. The common intracranial imaging complications were subdural effusion and (or) empyema in 349 (21.7%), hydrocephalus in 233 (14.5%), and cerebral abscess in 178 (11.1%). A total of 389 (24.2%) cases were completely cured and 1088 (67.6%) cases improved. Among 166 patients (10.3%) with adverse outcomes, 32 cases (2.0%) died, and 37 cases (2.3%) relapsed. Conclusion: The onset age of CABM in children is usually within 1 year of age, especially <3 months. The primary pathogens in infants less than 3 months old are E. coli and GBS, and the dominant pathogen in children older than 3 months old is S. pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. CABM should not be excluded even if CSF leukocyte counts are within normal range. Due to the low detection rate of pathogens in children with CABM, standardized CSF bacteriological examination should be paid more attention to increase the pathogen detection rate. Non­culture CSF detection methods may facilitate pathogenic diagnosis.

Factors associated with afebrile presentation and delayed defervescence of bacterial meningitis in children under 3 years of age: a multi-centre retrospective analysis.

BACKGROUND: This multi-center study aimed to identify factors affecting fever and delayed defervescence in bacterial meningitis (BM) patients under 3 years of age because of the variability of fever in this patient population. METHODS: Only BM patients under 3 years treated at 49 centers in China from November 2018 to end-April 2021 were included in the study. Univariate and multivariate logistic regression analyses were performed to determine factors associated with afebrile presentation and fever of delayed defervescence. RESULTS: A total of 863 BM patients under 3 years were included in the study. Coagulase negative staphylococcus was associated with afebrile presentation (OR = 1.176), while septicaemia and ear-nose-throat infections were associated with fever (P < 0.05). The patients with fever were assigned into early and delayed defervescence groups based on defervescence time (less than and more than or equal to one week). Furthermore, Streptococcus agalactiae meningitis (OR = 1.124), concomitant gastrointestinal infection (OR = 1.276), encephalomalacia (or = 1.339), and subdural effusion (OR = 1.454) were independently associated with delayed defervescence (all P < 0.05). CONCLUSIONS: The findings can aid in the efficient utilization of fever in auxiliary diagnosis and evaluating the condition of the disease.

Clinical characteristics and antibiotic resistance profile of invasive MRSA infections in newborn inpatients: a retrospective multicenter study from China.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) can cause invasive infections with significant mortality in neonates. This study aimed to analyze the clinical characteristics and antibiotic resistance profiles of invasive MRSA infections and determine risk factors associated with invasive MRSA infections in newborn inpatients. METHODS: This multicenter retrospective study of inpatients from eleven hospitals in the Infectious Diseases Surveillance of Pediatrics (ISPED) group of China was performed over a two-year period (2018-2019). Statistical significance was calculated by applying the χ2 test or by Fisher's exact test in the case of small sample sizes. RESULTS: A total 220 patients were included. Among included cases, 67 (30.45%) were invasive MRSA infections, including two deaths (2.99%), while 153 (69.55%) were noninvasive infections. The invasive infections of MRSA occurred at a median age of 8 days on admission, which was significantly younger compared to 19 days in noninvasive cases. Sepsis (86.6%) was the most common invasive infection, followed by pneumonia (7.4%), bone and joint infections (3.0%), central nervous system infection (1.5%), and peritonitis (1.5%). Congenital heart disease, low birth weight infant (<2500 g), but not preterm neonates, and bronchopulmonary dysplasia, were more commonly found in invasive MRSA infections. All these isolates were susceptible to vancomycin and linezolid and were resistant to penicillin. Additionally, 69.37% were resistant to erythromycin, 57.66% to clindamycin, 7.04% to levofloxacin, 4.62% to sulfamethoxazole-trimethoprim, 4.29% to minocycline, 1.33% to gentamicin, and 3.13% were intermediate to rifampin. CONCLUSION: Low age at admission (≤8 days), congenital heart disease, and low birth weight were associated with invasive MRSA infections in neonates, and no isolates resistant to vancomycin and linezolid were found. Determining these risks in suspected neonates may help identify patients with imminent invasive infections who may require intensive monitoring and therapy.

Antimicrobial resistance profile of methicillin-resistant Staphylococcus aureus isolates in children reported from the ISPED surveillance of bacterial resistance, 2016-2021.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health worldwide. In December 2015, the Infectious Disease Surveillance of Pediatrics (ISPED) program was organized to monitor bacterial epidemiology and resistance trends in children. Methods: This retrospective study was conducted from January 2016-December 2021 on patients at eleven ISPED-group hospitals. Results: From 2016-2021, a total of 13024 MRSA isolates were obtained from children. The most common age group for patients with MRSA infection was less than 3 years old, and newborns were an important group affected by MRSA infection. MRSA was most commonly isolated from the lower respiratory, an abscess, a secretion, or blood in neonates and from the lower respiratory, an abscess, or the upper respiratory in non-neonates. All isolates were susceptible to vancomycin and linezolid and resistant to penicillin; additionally, 76.88%, 54.97%, 22.30%, 5.67%, 5.14%, 3.63%, and 1.42% were resistant to erythromycin, clindamycin, tetracycline, levofloxacin, sulfamethoxazole-trimethoprim (TMP-SMX), gentamicin, and rifampin, respectively. Between 2016 and 2021, a significant increase was seen in the levofloxacin- and TMP-SMX-resistance rates (from 5.45% to 7.14% and from 4.67% to 6.50%, respectively) among MRSA isolates, along with a significant decrease in the rates of resistance to erythromycin (from 82.61% to 68.08%), clindamycin (from 60.95% to 46.82%), tetracycline (from 25.37% to 17.13%), gentamicin (from 4.53% to 2.82%), and rifampin (from 1.89% to 0.41%). Discussion: The antibiotic-resistance rates varied among MRSA isolated from different sources. Because of the high antibiotic resistance rate to clindamycin, this antibiotic is not recommended for empirical treatment of MRSA infections, especially in osteomyelitis.

Diagnosis, treatment, and prevention of severe acute hepatitis of unknown etiology in children.

BACKGROUND: Severe acute hepatitis of unknown etiology in children has recently exhibited a global trend of concentrated occurrence. This review aimed to summarize the current available information regarding the outbreak of severe acute hepatitis and introduce our hospital's previous experiences with the diagnosis and treatment of severe acute hepatitis for reference. DATA SOURCES: Websites including the UK Health Security Agency, European Centre for Disease Prevention and Control, CDC, WHO, and databases including PubMed/Medline, Cochrane Library, Embase and Web of Science were searched for articles on severe acute hepatitis in children. RESULTS: As of May 26, 2022, a total of 650 cases have been reported in 33 countries; at least 38 (6%) children required liver transplantation, and nine (1%) died. Cases are predominantly aged between 3 and 5 years old, and there are no epidemiological links among them. The common manifestations are jaundice, vomiting and pale stools. Adenovirus tested positive in most cases, and SARS-CoV-2 and other viruses were detected in a few cases, but virus particles were not found in liver tissue. Adenovirus immunohistochemistry showed immunoreactivity in the intrasinusoidal lumen from some liver samples. The hierarchical treatment includes symptomatic and supportive therapy, management of coagulation disorders and hepatic encephalopathy, artificial liver support, and liver transplantation (approximately 6%-10% of cases require liver transplant). CONCLUSIONS: The etiology of this severe acute hepatitis in children is not clear. The clinical features are severe acute hepatitis with significantly elevated liver enzymes. Clinicians need to be alert to children with hepatitis.

Improved targeting of the 16S rDNA nanopore sequencing method enables rapid pathogen identification in bacterial pneumonia in children.

Objectives: To develop a rapid and low-cost method for 16S rDNA nanopore sequencing. Methods: This was a prospective study on a 16S rDNA nanopore sequencing method. We developed this nanopore barcoding 16S sequencing method by adding barcodes to the 16S primer to reduce the reagent cost and simplify the experimental procedure. Twenty-one common pulmonary bacteria (7 reference strains, 14 clinical isolates) and 94 samples of bronchoalveolar lavage fluid from children with severe pneumonia were tested. Results indicating low-abundance pathogenic bacteria were verified with the polymerase chain reaction (PCR). Further, the results were compared with those of culture or PCR. Results: The turnaround time was shortened to 6~8 hours and the reagent cost of DNA preparation was reduced by employing a single reaction adding barcodes to the 16S primer in advance. The accuracy rate for the 21 common pulmonary pathogens with an abundance ≥ 99% was 100%. Applying the culture or PCR results as the gold standard, 71 (75.5%) of the 94 patients were positive, including 25 positive cultures (26.6%) and 52 positive quantitative PCRs (55.3%). The median abundance in the positive culture and qPCR samples were 29.9% and 6.7%, respectively. With an abundance threshold increase of 1%, 5%, 10%, 15% and 20%, the test sensitivity decreased gradually to 98.6%, 84.9%, 72.6%, 67.1% and 64.4%, respectively, and the test specificity increased gradually to 33.3%, 71.4%, 81.0%, 90.5% and 100.0%, respectively. Conclusions: The nanopore barcoding 16S sequencing method can rapidly identify the pathogens causing bacterial pneumonia in children.

Multidisciplinary treatment of chronic active Epstein-Barr virus infection with multiple complications: a case report.

Chronic active Epstein-Barr virus (CAEBV) infection is a very rare and potentially life-threatening illness caused by long-term EBV infection. Globally, the prevalence is the highest among young children and adolescents with increased frequency in Asians and Native Americans, whereas it is sporadically encountered in European countries. Typically, patients present with nonspecific symptoms such as fever, lymphadenopathy, hepatosplenomegaly, and liver dysfunction. However, the complications of CAEBV and its treatment are quite complex and require great care. We report a case of a 3-year-old boy with CAEBV infection who was later diagnosed with pancreatic mass and recurrent pancreatitis. A multidisciplinary board was consulted for correct diagnosis and treatment plan making. The treatment included pharmaceutical and surgical (duodenum-preserving pancreatic head resection) approaches. The patient showed tremendous improvement following the third discharge from the hospital and is still free of any symptoms. In this case report, we discuss differential diagnosis and comprehensively examined the possibility of the development of pancreatitis caused by EBV infection, the possibility of autoimmune pancreatitis, and the possibility of hereditary pancreatitis. To confirm or rule out the first two etiologies, laboratory and pathology results were studied. We also performed exon sequencing using Agilent exome capture kit to rule out hereditary pancreatitis. The clinical course of this disease and the way it was handled deserves attention so that similar cases receive prompt treatment.

Bacterial Epidemiology and Antimicrobial Resistance Profiles in Children Reported by the ISPED Program in China, 2016 to 2020.

The Infectious Disease Surveillance of Pediatrics (ISPED) program was established in 2015 to monitor and analyze the trends of bacterial epidemiology and antimicrobial resistance (AMR) in children. Clinical bacterial isolates were collected from 11 tertiary care children's hospitals in China in 2016 to 2020. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer method or automated systems, with interpretation according to the Clinical and Laboratory Standards Institute 2019 breakpoints. A total of 288,377 isolates were collected, and the top 10 predominant bacteria were Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter baumannii. In 2020, the coronavirus disease 2019 (COVID-19) pandemic year, we observed a significant reduction in the proportion of respiratory tract samples (from 56.9% to 44.0%). A comparable reduction was also seen in the primary bacteria mainly isolated from respiratory tract samples, including S. pneumoniae, H. influenzae, and S. pyogenes. Multidrug-resistant organisms (MDROs) in children were commonly observed and presented higher rates of drug resistance than sensitive strains. The proportions of carbapenem-resistant K. pneumoniae (CRKP), carbapenem-resistant A. baumannii (CRAB), carbapenem-resistant P. aeruginosa (CRPA), and methicillin-resistant S. aureus (MRSA) strains were 19.7%, 46.4%%, 12.8%, and 35.0%, respectively. The proportions of CRKP, CRAB, and CRPA strains all showed decreasing trends between 2015 and 2020. Carbapenem-resistant Enterobacteriaceae (CRE) and CRPA gradually decreased with age, while CRAB showed the opposite trend with age. Both CRE and CRPA pose potential threats to neonates. MDROs show very high levels of AMR and have become an urgent threat to children, suggesting that effective monitoring of AMR and antimicrobial stewardship among children in China are required. IMPORTANCE AMR, especially that involving multidrug-resistant organisms (MDROs), is recognized as a global threat to human health; AMR renders infections increasingly difficult to treat, constituting an enormous economic burden and producing tremendous negative impacts on patient morbidity and mortality rates. There are many surveillance programs in the world to address AMR profiles and MDRO prevalence in humans. However, published studies evaluating the overall AMR rates or MDRO distributions in children are very limited or are of mixed quality. In this study, we showed the bacterial epidemiology and resistance profiles of primary pathogens in Chinese children from 2016 to 2020 for the first time, analyzed MDRO distributions with time and with age, and described MDROs' potential threats to children, especially low-immunity neonates. Our study will be very useful to guide antiinfection therapy in Chinese children, as well as worldwide pediatric patients.

Clinical features and epidemiological analysis of respiratory human adenovirus infection in hospitalized children: a cross-sectional study in Zhejiang.

BACKGROUND: HAdV is one of the common pathogens in hospitalized children with acute respiratory infections (ARIs). We aim to describe the clinical and laboratory features, epidemiological characteristics, and HAdV species and/or types of inpatients with HAdV respiratory infections. METHODS: Respiratory samples were gathered from inpatients diagnosed ARIs in Children's Hospital, Zhejiang University School of Medicine, and were detected by using Direct Immunofluorescence Assay from 2018 to 2019. PCR amplification and sequencing of the hypervariable zone of hexon gene were used for genotyping. The clinical and laboratory features, and HAdV genotyping, and epidemiological characteristic analysis were retrospectively performed. RESULTS: Of 7072 samples collected, 488 were identified as HAdV-positive. The overall detection rate was 6.9%. The peaked detection rate was 14.1% in January 2019. HAdV-positive cases with ARIs mainly appeared in winter. The detection rate was highest among children between 6 months and 2 years (8.7%, 123/1408). Clinical diagnosis included pneumonia (70.3%, 343/488), bronchitis (7.0%, 34/488) and acute upper respiratory tract infection (22.7%, 111/488). The common clinical manifestations were fever (93.4%, 456/488), cough (94.7%, 462/488), wheezing (26.2%, 128/488), and shortness of breath (14.8%, 72/488). 213 (43.6%) cases had co-infection and 138 (28.3%) cases had extrapulmonary symptoms. 96(19.7%) cases had intrapulmonary and intrathoracic complications.78 (16.0%) had an underlying condition, most of which were congenital heart diseases (20.5%, 16/78). The proportions of hyperpyrexia, duration of fever > 10 days, severe pneumonia, and wheezing in the co-infection group were remarkably higher than those in HAdV single-infection group (all p < 0.05). The proportions of duration of hospitalization, duration of fever > 10 days, wheezing, shortness of breath, change in level of consciousness, serosal fluids, extrapulmonary symptoms, co-infections and underlying diseases were significantly higher in severe pneumonia group than those in the mild pneumonia group (all p < 0.05). Four HAdV species were successfully identified in 155 cases and presented by 8 genotypes. HAdV-B3 (56.1%, 87/155) and HAdV -B7 (31.0%, 48/155) were the most predominant detected types and occurred commonly in different severity groups (p = 0.000), while, HAdV-B55 was detected only in the severe group. HAdV-B7's detection rate in the severe pneumonia group was significantly higher than the non-severe pneumonia group. CONCLUSION: HAdV detection rate is related to age and season. Bronchopneumonia accounts for about 70% HAdV-positive inpatients. The common clinical manifestations include hyperpyrexia, cough, wheezing, and shortness of breath. HAdV-B3 and HAdV-B7 are the most common types in children diagnosed with respiration infections.

The low contagiousness and new A958D mutation of SARS-CoV-2 in children: An observational cohort study.

AIMS: To explore the contagiousness and new SARS-CoV-2 mutations in pediatric COVID-19. METHODS: This cohort study enrolled all pediatric patients admitted to 8 hospitals in Zhejiang Province of China between 21 January and 29 February 2020, their family members and close-contact classmates. Epidemiological, demographic, clinical and laboratory data were collected. Bioinformatics was used to analyze the features of SARS-CoV-2. Individuals were divided into 3 groups by the first-generation case: Groups 1 (unclear), 2 (adult), and 3 (child). The secondary attack rate (SAR) and R0 were compared among the groups. RESULTS: The infection rate among 211 individuals was 64% (135/211). The SAR in Groups 2 and 3 was 71% (73/103) and 3% (1/30), respectively; the median R0 in Groups 2 and 3 was 2 (range: 1-8) and 0 (range: 0-1), respectively. Compared with adult cases, the SAR and R0 of pediatric cases were significantly lower (p<0.05). We obtained SARS-CoV-2 sequences from the same infant's throat and fecal samples at a two-month interval and found that the new spike protein A958D mutation detected in the stool improved thermostability theoretically. CONCLUSIONS: Children have lower ability to spread SARS-CoV-2. The new A958D mutation is a potential reason for its long residence in the intestine.

PD-L1+ exosomes from bone marrow-derived cells of tumor-bearing mice inhibit antitumor immunity.

Tumors escape immune attack by upregulating the surface expression of PD-L1, which interacts with PD-1 on T cells to activate immune inhibitory signaling. Anti-PD-1 treatments can effectively block this inhibitory signaling and activate antitumor immune responses. However, anti-PD-1 treatment also has a tumor suppressive effect in patients whose tumor cells do not express PD-L1. The underlying mechanisms are poorly defined. Here, we report that exosomes from bone marrow-derived cells (BMDCs) in tumor-bearing mice, but not in healthy mice, carry PD-L1. PD-L1 on these exosomes is biofunctional and can inhibit CD8+ T cell proliferation and activation in vitro and in vivo. The transfer of exogenous exosomes from BMDCs and the inhibition of the production of endogenous exosomes by BMDCs promote and suppress tumor growth, respectively. PD-L1+ exosomes from BMDCs can be found in tumor tissues. In addition, exosomes from BMDCs promote tumor metastasis in a PD-L1-dependent manner. Therefore, our results indicate that exosomes from BMDCs play important roles in tumor immunosuppression via PD-L1.

Enhanced Triacylglycerol Metabolism Contributes to Efficient Oil Utilization and High-Level Production of Salinomycin in Streptomyces albus ZD11.

Streptomyces is well known for biosynthesis of secondary metabolites with diverse bioactivities. Although oils have been employed as carbon sources to produce polyketide antibiotics for several industrial Streptomyces strains, the intrinsic correlation between oil utilization and high production of antibiotics still remains unclear. In this study, we investigated the correlation between oil metabolism and salinomycin biosynthesis in Streptomyces albus ZD11, which employs soybean oil as the main carbon source. Comparative genomic analysis revealed the enrichment of genes related to triacylglycerol (TAG) metabolism in S. albus ZD11. Transcriptomic profiling further confirmed the enhancement of TAG metabolism and acyl coenzyme A biosynthesis in S. albus ZD11. Multiple secreted lipases, which catalyze TAG hydrolysis, were seen to be working in a synergistic and complementary manner in aiding the efficient and stable hydrolyzation of TAGs. Together, our results suggest that enhanced TAG hydrolysis and fatty acid degradation contribute to the high efficiency of oil utilization in S. albus ZD11 in order to provide abundant carbon precursors for cell growth and salinomycin biosynthesis.IMPORTANCE In order to obtain high-level production of antibiotics, oils have been used as the main carbon source for some Streptomyces strains. Based on multiomics analysis, this study provides insight into the relationship between triacylglycerol (TAG) metabolism and antibiotic biosynthesis in S. albus ZD11, an oil-preferring industrial Streptomyces strain. Our investigation into TAG hydrolysis yielded further evidence that this strain utilizes complicated strategies enabling an efficient TAG metabolism. In addition, a novel secreted lipase was identified that exhibited highly hydrolytic activity for medium- and long-chain TAGs. Our findings represent a good start toward clarifying the complicated relationship between TAG catabolism and high-level antibiotic production in the industrial strains.

[Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)].

The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and Mycoplasma pneumoniae infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.

Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus.

Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV (the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children's Regional Medical Center, Children's Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.

Diagnosis and treatment of herpangina: Chinese expert consensus.

BACKGROUND: Herpangina is a common infectious disease in childhood caused by an enterovirus. This consensus is aiming to standardize and improve herpangina prevention and clinical diagnosis. METHODS: The Subspecialty Group of Infectious Diseases, the Society of Pediatric, Chinese Medical Association and Nation Medical Quality Control Center for Infectious Diseases gathered 20 experts to develop the consensus, who are specialized in diagnosis and treatment of herpangina. RESULTS: The main pathogenic serotypes of herpangina include Coxsackievirus-A, Enterovirus-A and Echovirus. Its diagnosis can be rendered on the basis of history of epidemiology, typical symptoms, characteristic pharyngeal damage and virological tests. The treatment is mainly symptomatic, and incorporates topical oral spray with antiviral drugs. The course of herpangina generally lasts 4-6 days with a good prognosis. CONCLUSION: The consensus could provide advices and references for the diagnosis, treatment and management of herpangina in children.

Genome mining and homologous comparison strategy for digging exporters contributing self-resistance in natamycin-producing Streptomyces strains.

As antibiotics are always toxic to the antibiotic-producing strains themselves, most Streptomyces strains have evolved several self-resistance mechanisms, among which the antibiotic efflux system is understood best and is commonly found. Among the efflux systems, the ATP-binding cassette (ABC) transporter superfamily and the major facilitator superfamily (MFS) are two important transporter families. In this work, the ABC transporters and the MFS transporters from the four reported natamycin-producing Streptomyces strains have been investigated in order to clarify whether these Streptomyces strains share similar efflux strategies for natamycin metabolism. Fifty-one groups of homologous exporter genes were identified as shared by four strains. Differential transcriptional analysis between the natamycin-producing strain Streptomyces chattanoogensis L10 and its ΔscnS0 mutant, which produces no natamycin, reveals that the expression levels of 25 of the above groups of genes were observably changed. The production of natamycin declined over 30% after solely knocking out several of these 25 groups of genes in S. chattanoogensis L10. This indicates that these transporters participate in the efflux of molecules related to natamycin biosynthesis. Our study is the first to demonstrate that the exporters participating in a particular antibiotic metabolism can be excavated and identified quickly by the strategy of genome mining and homologous comparison in the antibiotic-producing strains, leading to deeper understanding of the complex self-resistance mechanisms in Streptomycetes.

Fas signaling-mediated TH9 cell differentiation favors bowel inflammation and antitumor functions.

Fas induces apoptosis in activated T cell to maintain immune homeostasis, but the effects of non-apoptotic Fas signaling on T cells remain unclear. Here we show that Fas promotes TH9 cell differentiation by activating NF-κB via Ca2+-dependent PKC-ß activation. In addition, PKC-ß also phosphorylates p38 to inactivate NFAT1 and reduce NFAT1-NF-κB synergy to promote the Fas-induced TH9 transcription program. Fas ligation exacerbates inflammatory bowel disease by increasing TH9 cell differentiation, and promotes antitumor activity in p38 inhibitor-treated TH9 cells. Furthermore, low-dose p38 inhibitor suppresses tumor growth without inducing systemic adverse effects. In patients with tumor, relatively high TH9 cell numbers are associated with good prognosis. Our study thus implicates Fas in CD4+ T cells as a target for inflammatory bowel disease therapy. Furthermore, simultaneous Fas ligation and low-dose p38 inhibition may be an effective approach for TH9 cell induction and cancer therapy.