Background Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children. Data sources The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for “respiratory syncytial virus”, “RSV”, “lower respiratory tract infection”, “bronchiolitis”, “acute”, “viral pneumonia”, “neonatal”, “infant” “children”, and “pediatric”. Results Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out. Conclusions This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

Protein carbonylation by reactive oxygen species (ROS) is an important factor in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Carbonyls are mainly produced by peroxynitrite (ONOO-) and hemin/hydrogen peroxide (H2O2)/sodium nitrite (NaNO2)-mediated reactions. As the main active water-soluble chalcone chemical ingredient derived from Carthamus tinctorius L, hydroxysafflor yellow A (HSYA) has been increasingly applied in the treatment of cerebrovascular disease (CVD). In this study, rats were randomly divided into 3 groups: the sham-surgery group (sham), the CIRI group (CIRI) and the CIRI treated with HSYA group (HSYA). We evaluated the protective properties of HSYA in a CIRI model in vivo, assessed its efficacy against ONOO- and hemin/H2O2/NaNO2-induced oxidative damage to cerebral cortical tissues in vitro, and explored the probable molecular mechanisms underlying its neuroprotective effects. The results showed that HSYA protected rats against CIRI by improving their neurological function score (P < .05), reducing infarct volume (P < .01), decreasing the content of protein carbonyls (P < .01) and elevating the glutathione (GSH) levels (P < .01). Further in vitro investigations found that HSYA pretreatment could inhibit protein carbonylation induced by exogenous ONOO- application in cortical brain tissues in a dose-dependent manner (P < .01). In terms of hemin/H2O2/NaNO2-triggered oxidative damage, HSYA slightly promoted the formation of carbonyl groups (P < .05). In conclusion, this study demonstrates that the neuroprotective capabilities of HSYA in CIRI are attributable, at least in part, to the enhancement in antioxidant capacity and the attenuation of protein oxidation, probably via the combined processes of ONOO- scavenging and the suppression of protein carbonyl formation.

Background:It is unclear whether local pathological pulmonary changes truly reflect the severity of childhood Mycoplasma pneumoniae infection, which is characterized by rapid progress and potential mortality. This study multi-dimensionally analyzed low-dose computed tomography findings to assess the severity of Mycoplasma pneumoniae infection and predict its progress in such patients.Methods:In all, 752 children with Mycoplasma pneumoniae pneumonia (MPP) who underwent low-dose computed tomography examinations from February 2016 to July 2020 were retrospectively enrolled to conduct a cohort study. Clinical and radiological variables were analyzed using univariate analysis, and radiological variables were further analyzed using multivariable logistic regression in severe cases. Then, the correlation between the key computed tomography features and clinical symptoms, laboratory indicators, and medical costs were assessed using the chi-squared and Kruskal-Wallis H tests. Kaplan-Meier curves and Cox regression models were created to evaluate the correlations between the key computed tomography features, fever duration, and the length of hospital stay.Results:Of the 752 included patients, 16.2% (122/752) developed severe MPP. Atelectasis, pleural effusion, and lung consolidation occurred in 9.7% (73/752), 15.8% (119/752), and 90.3% (679/752) of patients, respectively. In addition to pleural effusion, the number of lobes of lung consolidation was the highest risk feature of severe MPP. Patients with consolidation in 2, 3, and 4 lobes had a 1.0-, 3.1-, and 7.5-fold increased risk of severe MPP, compared with patients with consolidation in fewer than 1 lobe. The duration of fever prior to admission had no effect on the proportions of the lobar consolidation (P=0.14) but did have significant effect on the incidence of pleural effusion (P=0.004). Levels of inflammatory markers and medical costs rose consistently with the increase in the number of lobar consolidations (P<0.001). After adjustments for pleural effusion, 1, 2, 3, and 4 lobes of consolidation remained positively associated with fever duration [1 lobe: hazard ratio (HR) =1.55, 95% CI: 1.10-2.18; 2 lobes: HR =1.65, 95% CI: 1.13-2.42l; 3 lobes: HR =1.82, 95% CI: 1.11-2.98; 4 lobes: HR =2.87, 95% CI: 1.25-6.61] compared to 0 lobes of consolidation. Compared to 0 lobes of consolidation, 1, 2, 3, and 4 lobes of consolidation were also positively correlated with the length of hospital stay (1 lobe: HR =2.24, 95% CI: 1.73-2.89; 2 lobes: HR =2.56, 95% CI: 1.91-3.43; 3 lobes: HR =2.87, 95% CI: 1.90-4.32; 4 lobes: HR =4.12, 95% CI: 2.01-8.46).Conclusions:Lobar consolidation is a stable and reliable computed tomography feature that can be used to assess the severity of MPP in children. Quantitative analysis of lobar consolidation can comprehensively and accurately predict the progression of Mycoplasma pneumoniae. Low-dose computed tomography is recommended for children with severe MPP with complicated courses.

Expansion of quinolone-resistant Neisseria meningitidis clone ChinaCC4821-R1-C/B from sequence type (ST) 4821 clonal complex (CC4821) caused a serogroup shift from serogroup A to serogroup C invasive meningococcal disease (IMD) in China. To determine the relationship among globally distributed CC4821 meningococci, we analyzed whole-genome sequence data from 173 CC4821 meningococci isolated from 4 continents during 1972–2019. These meningococci clustered into 4 sublineages (1–4); sublineage 1 primarily comprised of IMD isolates (41/50, 82%). Most isolates from outside China (40/49, 81.6%) formed a distinct sublineage, the Europe–USA cluster, with the typical strain designation B:P1.17-6,23:F3-36:ST-3200(CC4821), harboring mutations in penicillin-binding protein 2. These data show that the quinolone-resistant clone ChinaCC4821-R1-C/B has expanded to other countries. The increasing distribution worldwide of serogroup B CC4821 raises the concern that CC4821 has the potential to cause a pandemic that would be challenging to control, despite indirect evidence that the Trumenba vaccine might afford some protection.

The expansion of quinolone-resistant Neisseria meningitidis clone China CC4821-R1-C/B from ST-4821 clonal complex (cc4821) caused a serogroup shift from serogroup A to C in invasive meningococcal disease (IMD) in China. To establish the relationship among globally distributed cc4821 meningococci, we analysed whole genome sequence data from 173 cc4821 meningococci isolated in four continents from 1972-2019. These meningococci clustered into four sub-lineages (1-4), with sub-lineage 1 primarily comprising serogroup C IMD isolates (82%, 41/50). Most isolates from outside China formed a distinct sub-lineage (81.6%, 40/49, the Europe-USA cluster), with the typical strain designation B:P1.17-6,23:F3-36:ST-3200(cc4821) and harbouring mutations in penicillin-binding protein 2. These data show that the quinolone-resistant clone China CC4821-R1-C/B has expanded to other countries. The increasing global distribution of B:cc4821 meningococci raises concern that cc4821 has the potential to cause a global pandemic and, this would be challenging to control though there is indirect evidence that Trumenba ® vaccine might afford some protection.

Objective: Scarlet fever epidemics caused by group A Streptococcus (GAS) have been ongoing in China since 2011. However, limited data are available on the dynamic molecular characterizations of the epidemic strains. Method: Epidemiological data of scarlet fever in Shanghai were obtained from the National Notifiable Infectious Disease Surveillance System. Throat swabs of patients with scarlet fever and asymptomatic school-age children were cultured. Illumina sequencing was performed on 39emm1 isolates. Results: The annual incidence of scarlet fever was 7.5–19.4/100,000 persons in Shanghai during 2011–2015, with an average GAS carriage rate being 7.6% in school-age children. The proportion ofemm1 GAS strains increased from 3.8% in 2011 to 48.6% in 2014; they harbored a superantigen profile similar to emm12 isolates, except for the speA gene. Two predominant clones, SH001-emm12, and SH002-emm1, circulated in 66.9% of scarlet fever cases and 44.8% of carriers. Genomic analysis showed emm1 isolates throughout China constituted distinct clades, enriched by the presence of mobile genetic elements carrying the multidrug-resistant determinants ermB and tetM and virulence genes speA, speC, and spd1. Conclusion: A significant increase in the proportion ofemm1 strains occurred in the GAS population, causing scarlet fever in China. Ongoing surveillance is warranted to monitor the dynamic changes of GAS clones.

Background: Red-skin root of Asian ginseng (Panax ginseng) significantly reduces the quality and limits the production of ginseng in China. The disease has long been thought to be a noninfectious physiological disease, except one report that proved it was an infectious disease. However, the causal agents have not been successfully determined. In the present study, we were to reveal the pathogens that cause red-skin disease. Methods: Ginseng roots with red-skin root symptoms were collected from commercial fields in Northeast China. Fungi were isolated from the lesion and identified based on morphological characters along with multilocus sequence analyses on internal transcription spacer, beta-tubulin (tub2), histone H3 (his3), and translation elongation factor 1 alpha (tef-1 alpha). Pathogens were confirmed by inoculating the isolates in ginseng roots. Results: A total of 230 isolates were obtained from 209 disease samples. These isolates were classified into 12 species, including Dactylonectria sp., D. hordeicola, Fusarium acuminatum, F. avenaceum, F. solani, F. torulosum, Ilyonectria morn-panacis, I. robusta, Rhexocercosporidium panacis, and three novel species I. changbaiensis, I. communis, and I. qitaiheensis. Among them, I. communis, I. robusta, and F. solani had the highest isolation frequencies, being 36.1%, 20.9%, and 23.9%, respectively. All these species isolated were pathogenic to ginseng roots and caused red-skin root disease under appropriate condition. Conclusion: Fungal complex is the causal agent of red-skin root in P. ginseng. (C) 2019 The Korean Society of Ginseng. Publishing services by Elsevier B.V.

BackgroundLittle is known about the knowledge and attitudes towards human papillomavirus (HPV) and its vaccines among adolescents in mainland China. Also, limited information has been available on how to improve their knowledge and willingness towards HPV and its vaccines to ensure a successful vaccination program in the future.MethodsThis was a school-based interventional follow-up study. One urban and one rural junior middle school in Chengdu were selected by convenience sampling. At baseline, half of the grade one students were randomly selected as controls and the rest were interventions. A set of self-administered questionnaires on HPV and its vaccines were completed by both groups at baseline. After that, only the intervention group received a PowerPoint-oriented health education and finished the post-education questionnaires. One year later, both groups completed the same questionnaires as the follow-up survey.ResultsIn total, 1675 students finished the pre-intervention questionnaires; 751 were from the control group and 924 were from the intervention group. Among them, only 34.3% had heard of cervical cancer/genital warts, while only 15.1% of them had ever heard of HPV. However, 55.2% of students showed their willingness to be vaccinated even before any intervention. Seven variables were found to be associated with the willingness to be vaccinated at baseline. Immediately after the intervention, 88.4% of students were willing to vaccinate themselves. After 1 year, the effectiveness of intervention remained but decreased. Compared with the control group, the intervention group was more aware about cervical cancer, HPV and its vaccines with statistical significance. However, the level of HPV knowledge and willingness to be vaccinated among the intervention group had significantly decreased compared with that immediately after the intervention (P<0.001).ConclusionsThe baseline level of knowledge on HPV, its vaccines, and cervical cancer was very low among junior middle school students in Chengdu, China. However, the willingness to be vaccinated seemed positive. School-based health education is effective and appropriate in increasing the awareness of HPV and willingness towards its vaccines. Regular health education on HPV and cervical cancer prevention at a shorter interval should be guaranteed to ensure continuous effectiveness.

Quinolone resistance is increasing in Neisseria meningitidis , with its prevalence in China being high (>70%), but its origin remains unknown. The aim of this study was to investigate the donors of mutation-harboring gyrA alleles in N. meningitidis . A total of 198 N. meningitidis isolates and 293 commensal Neisseria isolates were collected between 2005 and 2018 in Shanghai, China. The MICs of ciprofloxacin were determined using the agar dilution method.

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Influenza A virus (IAV) infections are a major public health concern, including annual epidemics, epizootic outbreaks, and pandemics. A significant IAV epizootic outbreak was the H7N9 avian influenza A outbreak in China, which was first detected in 2013 and which has spread over 5 waves from 2013 to 2017, causing human infections in many different Chinese provinces. Here, RNA from primary clinical throat swab samples from 20 H7N9-infected local patients with different clinical outcomes, who were admitted and treated at one hospital in Shanghai, China, from April 2013 to April 2015, was analyzed. Whole-transcriptome amplification, with positive enrichment of IAV RNA, was performed, all 20 samples were subjected to deep sequencing, and data from 16 samples were analyzed in detail. Many single-nucleotide polymorphisms, including ones not previously reported, and many non-synonymous changes that could affect hemagglutinin head and stalk antibody binding epitopes were observed. Minor populations representing viral quasispecies, including nonsynonymous hemagglutinin changes shared by antigenically variant H7N9 clades identified in the most recent wave of H7N9 infections in 2016 to 2017, were also identified. IMPORTANCE H7N9 subtype avian influenza viruses caused infections in over 1,400 humans from 2013 to 2017 and resulted in almost 600 deaths. It is important to understand how avian influenza viruses infect and cause disease in humans and to assess their potential for efficient person-to-person transmission. In this study, we used deep sequencing of primary clinical material to assess the evolution and potential for human adaptation of H7N9 influenza viruses.

This study aimed to investigate the carriage of Streptococcus pyogenes in population vulnerable to scarlet fever and to compare their genotypic characterization between different age groups. Pharyngeal swabs were collected from 120 150 students in each of the three districts in Shanghai in May and December during 2015 to 2017, while emm typing and detection of 12 superantigen genes were performed to characterize the isolates. During 2015-2017, the average carriage rate in students was 5.7% (135/2,371), without significant difference between different years or districts. The carriage rate was significantly different between children from the three age groups, with 2.4% in 3 4 years, 5.4% in 5 9 years, and 9.1% in 10 14 years. Eight emm types were found, including emm 1, emm 4, emm 12, emm 22, emm 75, emm 89, emm 70 and emm 241, among which emm 12 accounted for 60%, and emm 1 27.5%. The predominance of emm 12 was found in each year, but the proportion of emm 12 was lower in 10 14 years (43.3%) than in 3 4 years (86.7%) and in 5 9 years (73.3%) (P = 0.002 and 0.003). Superantigen genes of speB, speC, speG, ssa and smeZ were found in almost all the isolates. The average carriage of S. pyogenes in population vulnerable to scarlet fever was 5.7% in Shanghai, highest in 10 14 years (9.1%), while emm 12 was the predominant type.

The expansion of hypervirulent sequence type 4821 clonal complex (CC4821) lineage Neisseria meningitidis bacteria has led to a shift in meningococcal disease epidemiology in China, from serogroup A (MenA) to MenC. Knowledge of the evolution and genetic origin of the emergent MenC strains is limited. In this study, we subjected 76 CC4821 isolates collected across China during 1972-1977 and 2005-2013 to phylogenetic analysis, traditional genotyping, or both. We show that successive recombination events within genes encoding surface antigens and acquisition of quinolone resistance mutations possibly played a role in the emergence of CC4821 as an epidemic clone in China. MenC and MenB CC4821 strains have spread across China and have been detected in several countries in different continents. Capsular switches involving serogroups B and C occurred among epidemic strains, raising concerns regarding possible increases in MenB disease, given that vaccines in use in China do not protect against MenB.

Thromboxane A2 analogue U46619 is conventionally used in platelet-rich plasma aggregometry (optical method) to diagnose platelet disorders. However, a significant proportion of the normal population is nonsensitive to U46619 (~10–20%). Noteworthy, a protocol for the use of U46619 in whole blood aggregometry (impedance method) is yet to be established and published. Herein we aimed to validate the use of U46619 in whole blood aggregometry, and improve its sensitive and specificity to detect secretion problems. Serial doses of U46619 (calculated based on hematocrit adjustment) where tested in whole blood from normal donors. After an optimal concentration was chosen, 45 normal donor samples were tested to establish a reference range. Also, we tested if the addition of the chemiluminescence reagents (luciferase and luciferin) to detect ATP secretion improves the sensitivity and specificity. More than 100 cases were analyzed using U46619 as part of a panel including other common platelet agonists such as ADP, collagen, arachidonic acid, thrombin, and ristocetin. The addition of the chemiluminescence reagents significantly improved the platelet aggregation response in normal donors: in the cohort without chemiluminescence reagents, approximately 10% were nonsensitive (no aggregation detected), whereas in the cohort with chemiluminescence reagents the average aggregation response (as measure in ohms) doubled. Therefore, the specificity is 98%, as determined by the number of cases diagnosed as “normal” or non-clinically significant but showed abnormal platelet aggregation response to U46619. The sensitivity was also high, 92%, as determined by the number cases with abnormal response that were diagnosed with a platelet disorder using further confirmatory testing (platelet electron microscopy or molecular testing). In summary, U46169 in whole blood aggregometry is highly sensitive and specific for detection of platelet disorders, in particular storage pool disorders. Furthermore, U46619 is extremely useful to differentiate aspirin-like defects from secretion problems. Finally, we will present examples of U46619-induced platelet aggregation and ATP secretion in a series of common platelet disorders, including Bernard-Soulier, Glanzmann thrombasthenia, aspirin-like defects, and storage pool disorders, as well as other rare platelet disorders such as Rett syndrome, Paris-Trousseau syndrome, and Noonan syndrome.

Although exhibiting no or low virulence in poultry, avian influenza virus H7N9 has caused around 1400 confirmed human infections in China with a case-fatality rate of 30% since 2013. A highly pathogenic H7N9 virus (HP-H7), with the HA antigenicity distinct from the previous, were recently detected in patients and poultry. Therefore, convenient rapid diagnosis with reliability will allow early antiviral use and management for H7N9 infection. Here, a sandwich ELISA targeting the conserved viral antigen, neuraminidase (NA) was developed. The immunoassay employed mouse monoclonal antibody (mAb) 3C1 to specifically capture the N9 and 3E9 for the detection. Its limit of detection is 6.25ng/ml for N9 protein of A/Anhui/1/2013(H7N9, AH1/2013) and 0.125HAU/50μL for live virus, AH1/2013 and A/Environment/Jiangxi/28/2009 (H11N9), respectively. When applied to test the five clinic throat swabs from H7N9 patients confirmed by nuclear acid testing (NAT) using quantitative reverse-transcriptase polymerase chain reaction (Q-PCR), two samples showed positive result in sandwich ELISA while all were negative using commercial Flu A and H7 subtype rapid antigen tests (RAT). The ELISA using anti-N9 mAbs provided a valuable approach to detect H7N9 virus and quantify the N9 protein.

Ranked among the top10 infectious causes of death worldwide, group A Streptococcus (GAS) causes small- and large-scale outbreaks, depending on the trigger as transmission of a GAS strain or expansion of predominant clones. In China, GAS infections other than scarlet fever are not notifiable. In Shanghai, an epidemiological investigation was initiated after two successive severe pneumonia cases with one death in a digital factory, from where outbreaks are less widely reported. The investigation was performed using emm typing, pulsed-field gel electrophoresis (PFGE) typing, superantigen profiling, and genome analysis. This enabled characterization of relatedness among the outbreak isolates and identification of the mobile genetic elements present. Among 57 patients with respiratory symptoms investigated in the factory, emm5 GAS strains were isolated from 8 patients. The eight GAS infection cases comprising one fatal severe pneumonia case, six influenza-like illness cases, and one pharyngitis case. Two risk factors were identified: adult with an age of 18-20 years and close contact with a GAS patient or carrier. GAS attack rate was 14.0% (8/57), and GAS carriage rate was probably around 2.7% (14/521) based on surveys in two nearby districts. All the 10 outbreak associated isolates were assigned to emm5 and sequence type ST-99 (emm5/ST-99), harbored superantigen genes speC, speG, and smeZ, and were assigned to two similar PFGE patterns (clones). Among the outbreak associated isolates, all carried ermA with resistance to erythromycin and inducible resistance to clindamycin, and eight (80%) carried a tetM gene with resistance to tetracycline. Among the 14 carriage isolates, 12 were emm12/ST-36, and 2 were emm1/ST-28, all with superantigen genes speC, speG, ssa, and smeZ. All the carriage isolates harbored ermB and tetM with resistance to erythromycin, clindamycin, and tetracycline. Genome analysis showed the two outbreak clones were closely related and possessed new prophages carrying virulence gene sdc and antibiotic resistance genes of ermA and tetM, which were not found in the emm5 reference strain Manfredo. This is the first report of a GAS outbreak in this type of workplace. The outbreak was caused by two closely related emm5 clones that differed from the predominant emm types circulating in China.

Epidemics of scarlet fever started in China in 2011 .Most of the cases were represented by the classic type ,while the surgical type was rarely reported .It is unclear whether ICE‐emm12 and ΦHKU .vir , the two mobile genetic elements firstly discovered in the strains leading to scarlet fever outbreak in Hong Kong ,were carried by the strains in Mainland China . Here we reported a scarlet fever case in Zhejiang which was caused by Streptococcus pyogenes .Strains isolated from the pharynx and skin wound all carried ICE‐emm12 and ΦHKU .vir .The result suggests a screening of the two mobile genetic elements in Mainland China for genetic surveillance of scarlet fever .

To evaluate the efficacy and safety of Chinese medicine (CM) plus Western medicine (WM) in the treatment of pediatric patients with severe hand, foot and mouth disease (HFMD) by conducting a prospective, controlled, and randomized trial.

UNLABELLED:A rapid expansion of HFMD with enterovirus 71 infection outbreaks has occurred and caused deaths in recent years in China, but no vaccine or antiviral drug is currently available for EV71 infection. This study aims to provide treatment programs for HFMD patients. We conducted a randomized, double-blind, controlled trial and evaluated clinical efficacy of therapy with rHuIFN-α1b in HFMD patients with EV71 infection. There were statistical differences in outcomes including the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load of the HFMD patients among ultrasonic aerosol inhalation group, intramuscular injection group and control group. rHuIFN-α1b therapy reduced the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load in children with HFMD.TRIAL REGISTRATION:Chinese Clinical Trial Registry ChiCTR-TRC-14005153.

Coxsackievirus A16 (CA16) is one of the major causative agents of hand, foot, and mouth disease worldwide. The non-neutralizing antibody response that targets CA16 VP1 remains poorly elucidated. In the present study, antibody responses against CA16 VP1 in Shanghai blood donors and Shanxi individuals were analyzed by ELISA and inhibitory ELISA using five CA16 VP1 antigens: VP1(1-297), VP1(41-297), VP1(1-60), VP1(45-58) and VP1(61-297). The correlation coefficients for most of the reactions against each of the five antigens and the inhibition of the anti-CA16 VP1 antibody response produced by the various antigens were higher in Shanghai blood donors compared to those in Shanxi individuals. VP1(1-297) and VP1(41-297) strongly inhibited the anti-CA16 VP1 response in serum samples from both populations, while VP1(45-58) and VP1(61-297) intermediately and weakly inhibited the anti-CA16 VP1 response, respectively, in only Shanghai group. A specific type of inhibition (anti-CA16 VP1 was completely inhibited by both VP1(1-60) and VP1(41-297)) characterized by high neutralizing antibody titers was identified and accounted for 71.4% of the strongly reactive samples from the Shanghai group. These results indicate that the Shanghai blood donors exhibited a consistent and specific antibody response, while the Shanxi individuals showed an inconsistent and non-specific antibody response. These findings may improve the understanding of host humoral immunity against CA16 and help to identify an effective approach for seroepide-miological surveillance and specific diagnosis of CA16 infection based on normal and competitive ELISA.