Characteristics of SARS-CoV-2 Omicron BA.5 variants in Shanghai after ending the zero-COVID policy in December 2022: a clinical and genomic analysis.

Introduction: An unprecedented surge of Omicron infections appeared nationwide in China in December 2022 after the adjustment of the COVID-19 response policy. Here, we report the clinical and genomic characteristics of SARS-CoV-2 infections among children in Shanghai during this outbreak. Methods: A total of 64 children with symptomatic COVID-19 were enrolled. SARS-CoV-2 whole genome sequences were obtained using next-generation sequencing (NGS) technology. Patient demographics and clinical characteristics were compared between variants. Phylogenetic tree, mutation spectrum, and the impact of unique mutations on SARS-CoV-2 proteins were analysed in silico. Results: The genomic monitoring revealed that the emerging BA.5.2.48 and BF.7.14 were the dominant variants. The BA.5.2.48 infections were more frequently observed to experience vomiting/diarrhea and less frequently present cough compared to the BF.7.14 infections among patients without comorbidities in the study. The high-frequency unique non-synonymous mutations were present in BA.5.2.48 (N:Q241K) and BF.7.14 (nsp2:V94L, nsp12:L247F, S:C1243F, ORF7a:H47Y) with respect to their parental lineages. Of these mutations, S:C1243F, nsp12:L247F, and ORF7a:H47Y protein were predicted to have a deleterious effect on the protein function. Besides, nsp2:V94L and nsp12:L247F were predicted to destabilize the proteins. Discussion: Further in vitro to in vivo studies are needed to verify the role of these specific mutations in viral fitness. In addition, continuous genomic monitoring and clinical manifestation assessments of the emerging variants will still be crucial for the effective responses to the ongoing COVID-19 pandemic.

Safety of Immunization for Children with Immune Thrombocytopenia.

Vaccine hesitancy is a common issue for children with immune thrombocytopenia (ITP) in China. The objective of this paper is to assess the immunization statuses of children with ITP, analyze the possible relationship between immunization and thrombocytopenia, and evaluate the safety of immunization after ITP remission. We included 186 children with an ITP history and followed up with them for two years after receiving re-immunization recommendations. The participants had an overall age-appropriate vaccine coverage of 57.9%. Vaccine-associated thrombocytopenia occurred in 99 (53.2%, 95% CI = 46.06-60.26) children ranging from 0 to 34 days following immunization, with 14 vaccines involved. One hundred and fifty-four (82.3%, 95% CI = 76.72-87.54) children were advised to restart immunization, whereas 32 (17.2%, 95% CI = 12.46-23.28) were advised to postpone partial or full vaccination. Following the follow-up, 150 (80.6%, 95% CI = 74.37-85.68) children completed the catch-up immunization, whereas 27 (14.5%, 95% CI = 10.17-20.30) partially completed it. Four patients with thrombocytopenia relapsed following the re-immunization. Incomplete catch-up immunization was related to the factors of chronic thrombocytopenia, vaccine-associated thrombocytopenia, and the relapse of ITP following re-immunization. ITP may occur after immunization with vaccines other than measles-containing vaccines. Re-immunization in children with ITP generally does not result in a relapse, regardless of whether the previous thrombocytopenia was vaccine-associated.

The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A.

Lung epithelial cells and fibroblasts poorly express angiotensin-converting enzyme 2, and the study aimed to investigate the role of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on inflammation and epithelial-mesenchymal transition (EMT) in two lung cell lines and to understand the potential mechanism. Lung epithelial cells (BEAS-2B) and fibroblasts (MRC-5) were treated with the spike protein, then inflammatory and EMT phenotypes were detected by enzyme-linked immunosorbent assay, Transwell, and western blot assays. RNA-sequence and bioinformatic analyses were performed to identify dysregulated genes. The roles of the candidate genes were further investigated. The results showed that treatment with 1,000 ng/mL of spike protein in two lung cell lines caused increased levels of IL-6, TNF-α, CXCL1, and CXCL3, and the occurrence of EMT. RNA-sequence identified 4,238 dysregulated genes in the spike group, and 18 candidate genes were involved in both inflammation- and EMT-related processes. GADD45A had the highest verified fold change (abs), and overexpression of GADD45A promoted the secretion of cytokines and EMT in the two lung cell lines. In conclusion, the spike protein induces inflammation and EMT in lung epithelial cells and fibroblasts by upregulating GADD45A, providing a new target to inhibit inflammation and EMT.

Effectiveness of Pentavalent Rotavirus Vaccine in Shanghai, China: A Test-Negative Design Study.

OBJECTIVE: To evaluate vaccine effectiveness (VE) of a live oral pentavalent rotavirus vaccine (RotaTeq, RV5) among young children in Shanghai, China, via a test-negative design study. STUDY DESIGN: We consecutively recruited children visiting a tertiary children's hospital for acute diarrhea from November 2021 to February 2022. Information on clinical data and rotavirus vaccination was collected. Fresh fecal samples were obtained for rotavirus detection and genotyping. To evaluate VE of RV5 against rotavirus gastroenteritis among young children, unconditional logistic regression models were conducted to compare ORs for vaccination between rotavirus-positive cases and test-negative controls. RESULTS: A total of 390 eligible children with acute diarrhea were enrolled, including 45 (11.54%) rotavirus-positive cases and 345 (88.46%) test-negative controls. After excluding 4 cases (8.89%) and 55 controls (15.94%) who had received the Lanzhou lamb rotavirus vaccine, 41 cases (12.39%) and 290 controls (87.61%) were included for the evaluation of RV5 VE. After adjustment for potential confounders, the 3-dose RV5 vaccination showed 85% (95% CI, 50%-95%) VE against mild to moderate rotavirus gastroenteritis among children aged 14 weeks to ≤4 years and 97% (95% CI, 83%-100%) VE among children aged 14 weeks to ≤2 years with genotypes G8P8, G9P8, and G2P4 represented 78.95%, 18.42%, and 2.63% of circulation strains, respectively. CONCLUSIONS: A 3-dose vaccination of RV5 is highly protective against rotavirus gastroenteritis among young children in Shanghai. The G8P8 genotype prevailled in Shanghai after RV5 introduction.

Jin-Zhen oral liquid for pediatric coronavirus disease (COVID-19): A randomly controlled, open-label, and non-inferiority trial at multiple clinical centers.

Background: As the coronavirus disease 2019 (COVID-19) pandemic progressed, especially with the emergence of the Omicron variant, the proportion of infected children and adolescents increased significantly. Some treatment such as Chinese herbal medicine has been administered for COVID-19 as a therapeutic option. Jin-Zhen Oral Liquid is widely used for pediatric acute bronchitis, while the efficacy and safety in the treatment of pediatric COVID-19 are unclear. Methods: We conducted a randomized controlled, open-label, multicenter, non-inferiority clinical study involving hospitalized children with mild to moderate COVID-19. Children eligible for enrollment were randomly assigned in a 1:1 ratio to Jin-Zhen Oral Liquid (the treatment group) and Jinhua Qinggan Granules (the positive control group) and received the respective agent for 14 days, followed by a 14-day follow-up after discontinuation of the treatment. The primary efficacy endpoint was the time to first negative viral testing. The secondary endpoints were the time and rate of major symptoms disappearance, duration of hospitalization, and the proportion of symptoms changed from asymptomatic or mild to moderate or severe/critical illness. In addition, the safety end points of any adverse events were observed. Results: A total of 240 child patients were assigned randomly into the Jin-Zhen Oral Liquid (117 patients) and Jinhua Qinggan Granules (123 patients) groups. There was no significant difference of the baselines in terms of the clinical characteristics and initial symptoms between the two groups. After 14-day administration, the time to first negative viral testing in the Jin-Zhen group (median 6.0 days, 95% CI 5.0-6.0) was significantly shorter compared with the positive control Jinhua Qinggan Granules group (median 7.0 days, 95% CI 7.0-8.0). The time and rate of major clinical symptoms disappearance were comparable to the positive control. The symptom disappearance time of pharyngalgia and hospitalization duration were significantly shortened in the Jin-zhen Oral Liquid group. No participants in either group experienced post-treatment exacerbation to severe or critical illness. No adverse events were observed in the Jin-Zhen Oral Liquid treatment group (0.0%) while 1 patient with adverse events occurred in the positive control Jinhua Qinggan granules group (0.8%). No serious adverse events were observed during the study period in both groups. Conclusion: Jin-Zhen Oral Liquid is safe and effective in the treatment of mild to medium COVID-19 in children. It is non-inferior to Jinhua Qinggan granules in shortening the time to first negative viral testing, the time and rate of major clinical symptoms disappearance, and the hospitalization duration. The results suggest that Jin-Zhen Oral Liquid can be a recommended drug for treatment of pediatric COVID-19 patients.

Common issues and improvement solution of vaccine hesitancy in children with underlying neurological conditions: Experience from one National Children's Medical Center in China.

BACKGROUND: Parents and healthcare providers usually defer or avoid immunization for children with neurological conditions. This study was conducted to investigate the common issues of immunization among these special children and the impact of specialists' recommendation on improving immunization practice. METHOD: We included 2,221 children with underlying neurological conditions seeking vaccination consultation at the first Immunization Advisory Clinic in China during 2017-2019. The primary neurological conditions and immunization status were analyzed. All parents were informed to self-report the adverse events following catch-up immunization. For specially concerned children with hereditary disorders, immune-related encephalopathy and epilepsy, we conducted the active follow-up to monitor the compliance with recommendation and the adverse events. RESULT: All counselling children were assessed as not having any contraindication of immunization. A total of 2,019 (90.9%) children with underlying neurological conditions had delayed immunization and 99 (4.5%) had non-immunization. The coverage rate of age-appropriate vaccines was 56.1%. The most concerned vaccines were diphtheria, tetanus and acellular pertussis combined vaccine, diphtheria and tetanus combined vaccine, meningococcal polysaccharide vaccine and Japanese encephalitis vaccine. Resuming immunization was recommended for the 2,048 (92.2%) children. Most of counselling children complied with the specialists' recommendation. Neither progress nor flaring of the neurological medical conditions was reported from parents. CONCLUSION: Vaccine hesitancy was a common issue for Chinese children with all kinds of neurological conditions. Specialized consultation on immunization is helpful to build vaccine confidence for the special children. Immunization for children with underlying neurological conditions is generally safe.

Information technology and artificial intelligence support in management experiences of the pediatric designated hospital during the COVID-19 epidemic in 2022 in Shanghai.

Objective: To describe the information technology and artificial intelligence support in management experiences of the pediatric designated hospital in the wave of COVID-19 in Shanghai. Methods: We retrospectively concluded the management experiences at the largest pediatric designated hospital from March 1st to May 11th in 2022 in Shanghai. We summarized the application of Internet hospital, face recognition technology in outpatient department, critical illness warning system and remote consultation system in the ward and the structed electronic medical record in the inpatient system. We illustrated the role of the information system through the number and prognosis of patients treated. Results: The COVID-19 designated hospitals were built particularly for critical patients requiring high-level medical care, responded quickly and scientifically to prevent and control the epidemic situation. From March 1st to May 11th, 2022, we received and treated 768 children confirmed by positive RT-PCR and treated at our center. In our management, we use Internet Information on the Internet Hospital, face recognition technology in outpatient department, critical illness warning system and remote consultation system in the ward, structed electronic medical record in the inpatient system. No deaths or nosocomial infections occurred. The number of offline outpatient visits dropped, from March to May 2022, 146,106, 48,379, 57,686 respectively. But the outpatient volume on the internet hospital increased significantly (3,347 in March 2022 vs. 372 in March 2021; 4,465 in April 2022 vs. 409 in April 2021; 4,677 in May 2022 vs. 538 in May 2021). Conclusions: Information technology and artificial intelligence has provided significant supports in the management. The system might optimize the admission screening process, increases the communication inside and outside the ward, achieves early detection and diagnosis, timely isolates patients, and timely treatment of various types of children.

Epidemiological and clinical features of SARS-CoV-2 infection in children during the outbreak of Omicron variant in Shanghai, March 7-31, 2022.

OBJECTIVES: This study aimed to understand the epidemiological and clinical characteristics of pediatric SARS-CoV-2 infection during the early stage of Omicron variant outbreak in Shanghai. METHODS: This study included local COVID-19 cases <18 years in Shanghai referred to the exclusively designated hospital from March 7 to March 31, 2022. Clinical data, epidemiological exposure, and COVID-19 vaccination status were collected. Relative risks (RRs) were calculated to assess the effect of vaccination on symptomatic infection and febrile disease. RESULTS: A total of 376 pediatric cases of COVID-19 (median age: 6.0 ± 4.2 years) were referred to the designated hospital, including 257 (68.4%) symptomatic cases and 119 (31.6%) asymptomatic cases. Of the 307 (81.6%) children ≥3 years eligible for COVID-19 vaccination, 110 (35.8%) received two doses of vaccines. The median interval between the completion of two-dose vaccination and infection was 3.5 (interquartile range [IQR]: 3, 4.5) months. Compared with no vaccination, two-dose COVID-19 vaccination reduced the risks of symptomatic infection and febrile disease by 35% (RR 0.65, 95% confidence interval [CI]: 0.53-0.79) and 33% (RR 0.64, 95% CI: 0.51-0.81) among confirmed cases. Eighty-four percent of symptomatic cases had fever (mean duration: 1.7 ± 1.0.8 days), 40.5% had cough, and 16.4% had transient leukopenia. Three hundred and seven (81.6%) had an epidemiological exposure in household (69.1%), school (21.8%), and residential area (8.8%). CONCLUSION: The surge of pediatric COVID-19 cases and multiple transmission model reflect wide dissemination of Omicron variant in the community. Asymptomatic infection is common among Omicron-infected children. COVID-19 vaccination can offer some protection against symptomatic infection and febrile disease.

COVID-19 vaccine counseling and safety assessment in children and teenagers with underlying medical conditions in China: a single center study.

Safety concerns about novel vaccines and necessity of COVID-19 vaccination for children, especially with underlying medical conditions, are the obstacle of COVID-19 vaccination program among pediatric population. The study was conducted to investigate the vaccine hesitancy reasons among the parents, and to monitor the adverse events of inactivated COVID-19 vaccines in children and teenagers with underlying medical conditions in China. Children with underlying medical conditions encountered to the Immunization Advisory Clinic for COVID-19 vaccine counseling were enrolled. They were given immunization recommendation and followed up at 72 h and 28 d after immunization to monitor the immunization compliance after consultation and adverse events. A total of 324 children aged 3-17 y were included. The top three primary medical conditions for counseling were allergy (33.6%), neurological diseases (31.2%) and rheumatic diseases (8.3%). COVID-19 vaccination was promptly recommended for 242 (74.7%) children. Seventy-one (65.7%) children who had allergy issues were recommend to take vaccination, which was significantly lower than that of other medical conditions (p < .05). The follow-up record showed that 180 children received 340 doses of inactivated COVID-19 vaccine after consultation. Overall, 39 (21.6%) children reported at least one adverse event within 28 d of either vaccination. No serious adverse reactions were observed. No difference of adverse effects between the first dose and the second dose of vaccination except fever. Parents' hesitancy in COVID-19 vaccination for children with underling medical conditions are mainly due to the safety concerns. Specialist consultation is helpful to improve the vaccine uptake.

Clinical and molecular characterization of the first culture-confirmed pediatric fulminant meningococcemia case caused by a serogroup Y clonal complex 23 strain in China.

Serogroup Y Neisseria meningitidis (NmY) is rare in China, and only serogroup A and C meningococcal polysaccharide vaccines (MPVs) are included in the national vaccination schedule. We describe a case of fulminant meningococcemia caused by NmY, which occurred in a pediatric patient (2 years old) for the first time in China, confirmed by culture. Although the boy was treated in time, the dry gangrene in his toes and fingers left him with severe sequelae. An NmY isolate was cultured from the blood of the patient, and showed decreased susceptibility to penicillin (minimum inhibitory concentration of 0.125 µg/ml), with sequence type (ST) 1655 assigned to clonal complex (cc) 23. Genomic analysis showed it was clustered with isolates from Italy, UK, Finland, and South Africa, sharing designation of Y:P1.5-1,10-1:F4-1:ST-1655(cc23). The emergence of NmY invasive meningococcal disease cases challenges local immunization strategy and warrants wider usage of MPV-ACYW if there is sustained circulation of NmY.

Comparison of Clinical and Epidemiological Characteristics of Asymptomatic and Symptomatic SARS-CoV-2 Infection in Children.

To understand the epidemiological and clinical features of the symptomatic and asymptomatic pediatric cases of COVID-19, we carried out a prospective study in Shanghai during the period of January 19 to April 30, 2020. A total of 49 children (mean age 11.5 ± 5.12 years) confirmed with SARS-CoV-2 infection were enrolled in the study, including 11 (22.4%) domestic cases and 38 (77.6%) imported cases. Nine (81.8%) local cases and 12 (31.6%) imported cases had a definitive epidemiological exposure. Twenty-eight (57.1%) were symptomatic and 21 (42.9%) were asymptomatic. Neither asymptomatic nor symptomatic cases progressed to severe diseases. The mean duration of viral shedding for SARS-CoV-2 in upper respiratory tract was 14.1 ± 6.4 days in asymptomatic cases and 14.8 ± 8.4 days in symptomatic cases (P > 0.05). Forty-five (91.8%) cases had viral RNA detected in stool. The mean duration of viral shedding in stool was 28.1 ± 13.3 days in asymptomatic cases and 30.8 ± 18.6 days in symptomatic participants (P > 0.05). Children < 7 years shed viral RNA in stool for a longer duration than school-aged children (P < 0.05). Forty-three (87.8%) cases had seropositivity for antibodies against SARS-CoV-2 within 1-3 weeks after confirmation with infection. In conclusion, asymptomatic SARS-CoV-2 infection may be common in children in the community during the COVID-19 pandemic wave. Asymptomatic cases shed viral RNA in a similar pattern as symptomatic cases do. It is of particular concern that asymptomatic individuals are potentially seed transmission of SARS-CoV-2 and pose a challenge to disease control.

Mild Cytokine Elevation, Moderate CD4+ T Cell Response and Abundant Antibody Production in Children with COVID-19.

Children with Coronavirus Disease 2019 (COVID-19) were reported to show milder symptoms and better prognosis than their adult counterparts, but the difference of immune response against SARS-CoV-2 between children and adults hasn't been reported. Therefore we initiated this study to figure out the features of immune response in children with COVID-19. Sera and whole blood cells from 19 children with COVID-19 during different phases after disease onset were collected. The cytokine concentrations, SARS-CoV-2 S-RBD or N-specific antibodies and T cell immune responses were detected respectively. In children with COVID-19, only 3 of 12 cytokines were increased in acute sera, including interferon (IFN)-γ-induced protein 10 (IP10), interleukin (IL)-10 and IL-16. We observed an increase in T helper (Th)-2 cells and a suppression in regulatory T cells (Treg) in patients during acute phase, but no significant response was found in the IFN-γ-producing or tumor necrosis factor (TNF)-α-producing CD8+ T cells in patients. S-RBD and N IgM showed an early induction, while S-RBD and N IgG were prominently induced later in convalescent phase. Potent S-RBD IgA response was observed but N IgA seemed to be inconspicuous. Children with COVID-19 displayed an immunophenotype that is less inflammatory than adults, including unremarkable cytokine elevation, moderate CD4+ T cell response and inactive CD8+ T cell response, but their humoral immunity against SARS-CoV-2 were as strong as adults. Our finding presented immunological characteristics of children with COVID-19 and might give some clues as to why children develop less severe disease than adults.

Dynamic surveillance of SARS-CoV-2 shedding and neutralizing antibody in children with COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and quickly spread globally. In this study, we investigated the characteristics of viral shedding from different sites and the neutralizing antibody (NAb) response during the acute and convalescent phases of nine children with COVID-19. SARS-CoV-2 was detected in their nasopharyngeal swabs (9/9, 100%), stool samples (8/9, 89%), and oropharyngeal swabs (3/9, 33%) but was not detected in their serum and urine samples. The median duration of viral shedding detected in nasopharyngeal swabs, oropharyngeal swabs, and stools was 13, 4, and 43 days respectively, and the maximum duration of viral shedding detected from stools was 46 days after discharge. In children, nasopharyngeal swabs appear to be a more sensitive specimen type for the diagnosis of COVID-19 compared with oropharyngeal swabs. Three of eight patients produced NAbs in the acute phase, and NAbs were detected in all eight patients with convalescent sera. The results of this study provide valuable information for the diagnosis and surveillance of COVID-19 and development of SARS-CoV-2 vaccines for use in children.

Non-polio enterovirus infections in children with central nervous system disorders in Shanghai, 2016-2018: Serotypes and clinical characteristics.

BACKGROUND: Non-polio enrerovirus causes a wide spectrum of neurologic syndromes. The epidemiological and clinical profiles of non-polio enrerovirus-associated central nervous system infections vary by regions and over year. OBJECTIVES: This study aimed to understand the prevalence, serotypes and clinical characteristics of enterovirus-associated aseptic meningitis, encephalitis and meningo-encephalitis in children in Shanghai during 2016-2018. METHODS: We collected the clinical data and the cerebrospinal fluid specimens from the pediatric patients with aseptic meningitis, encephalitis and meningo-encephalitis during 2016-2018. The nested RT-PCR and sequencing were performed to identify enterovirus and serotypes. RESULTS: A total of 424 patients were included in this study and their non-duplicated cerebrospinal fluid specimens were collected during the acute stage of illness. Based on PCR assay, enterovirus was detected in 272 (64.15 %) patients, of whom, the ratio of male to female subjects was 1.99, and the mean age was 5.71 ± 3.55 years (range: 0.03-16 years). There were 17 serotypes identified. Echovirus 30 (24.63 %), Coxsackievirus A10 (20.96 %), Coxsackievirus A6 (18.01 %) accounted for 63.6 %, followed by Coxsackievirus B5 (7.72 %), Echovirus 6 (5.88 %), and other serotypes (22.8 %). Of the 10 (3.68 %) critically severe patients, all had refractory seizure, 8 required mechanical ventilation, 7 survivors had recurrent attacks of epilepsy and 3 abandoned treatment; Coxsackievirus A10, Echovirus 9, Coxsackievirus A2, Coxsackievirus A6 and Echovirus 6 were identified. CONCLUSIONS: Non-polio enterovirus is the major pathogen causing aseptic meningitis, encephalitis and meningo-encephalitis in Chinese children and can cause life-threatening encephalitis and severe sequelae.

A quickly, effectively screening process of novel corona virus disease 2019 (COVID-19) in children in Shanghai, China.

BACKGROUND: A recent cluster of pneumonia cases in China was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the screening and diagnosis of corona virus disease 2019 (COVID-19) in our hospital. METHODS: Developed a procedure for the identification of children cases with COVID-19 in outpatient and emergency department of our hospital, then we observed how this process works. RESULTS: (I) There were 56 cases considered suspected cases, and 10 cases were confirmed as COVID-19. (II) Of the 10 confirmed COVID-19 cases admitted in our hospital, 5 were males and 5 were females, aged from 7 months to 11 years, the average age is 6.0±4.2 years, 6 cases were mild pneumonia, the others were upper respiratory tract infection. (III) We followed up 68 patients in isolation at home until symptoms disappeared. Non were missed in the patient's first visit. The sensitivity of this method is 100% and the specificity is 71.3%. CONCLUSIONS: Our screening process works well, and it is also necessary to establish a screening network in the hospital.

Norovirus Activity and Genotypes in Sporadic Acute Diarrhea in Children in Shanghai During 2014-2018.

BACKGROUND: Based on the impact public health of norovirus and the current progress in norovirus vaccine development, it is necessary to continuously monitor the epidemiology of norovirus infection, especially in children who are more susceptible to norovirus. OBJECTIVES: To monitor the activity and genotypes of norovirus infection in sporadic diarrhea in Shanghainese children during 2014-2018. STUDY DESIGN: Acute diarrheal cases were prospectively enrolled in the outpatient setting. Real-time reverse transcription-polymerase chain reaction was used for screening norovirus GI and GII genogroups. Dual norovirus genotypes were identified based on the partial capsid and polymerase gene sequences. RESULTS: Of the 3422 children with diarrhea, 510 (14.9%) were positive for noroviruses with 13 (2.5%) strains being GI genogroup and 497 (97.5%) strains being GII genogroup. Five distinct capsid GII genotypes were identified, including GII.4-Sydney/2012 (71.8%), GII.3 (13.8%), GII.17 (7.8%), GII.2 (6.0%), GII.6 (0.3%) and GII.8 (0.3%). Seven polymerase GII genotypes were identified, including GII.Pe (77.0%), GII.P12 (11.0%), GII.P17 (9.0%), GII.P16 (2.1%), and GII.P7, GII.P8 and GII.P2 in each (0.3%). Eleven distinct polymerase/capsid genotypes were identified with GII.Pe/GII.4-Sydney/2012 (74.2%), GII.P12/GII.3 (11.7%) and GII.P17/GII.17 (7.7%) being common. GII.P17/GII.17 strains were detected since September 2014. Recombinant GII.P16/GII.2 strains were detected since December 2016. CONCLUSIONS: Norovirus is a major pathogen causing diarrhea in Shanghainese children. GII.Pe/GII.4-Sydney/2012 strains remained the predominant genotype. The emergence of GII.P17/GII.17 and GII.P16/GII.2 strains in sporadic diarrhea was consistent with norovirus-associated outbreaks attributable to these 2 novel variants in China. Continuous monitoring norovirus genotypes circulating in pediatric population is needed for current vaccine development.

Epidemiological surveillance of hand, foot and mouth disease in Shanghai in 2014-2016, prior to the introduction of the enterovirus 71 vaccine.

Hand, foot, and mouth disease (HFMD) is mainly epidemic in China and Southeast Asian countries. A novel enterovirus 71 vaccine has been available in China for preventing severe HFMD since 2016. Knowledge of the dynamic epidemiology of HFMD in different regions is necessary for appropriate intervention strategies. This study focused on the citywide surveillance data on the epidemiology and etiology of HFMD in Shanghai during 2014-2016. In these 3 years, the total numbers of reported HFMD cases were 65,018, 39,702, and 57,548, respectively; the numbers of severe cases (case-severity ratios) were 248 (0.38%), 35 (0.09%), and 59 (0.10%), respectively. Children <6 years old accounted for 86.65% to 89.34% of HFMD cases and 91.53 to 97.14% of severe cases. EV-A71 caused all three fatal cases. In severe cases, the detection rate of EV-A71 was 77.82% in 2014, 100% in 2015 and 98.31% in 2016. In uncomplicated inpatient cases, the detection rates of EV-A71, CV-A16, CV-A6, and CV-A10 were, respectively, 43.40, 22.10, 30.73, and 1.89% in 2014; 28.52, 6.46, 53.61, and 7.98% in 2015; and 31.79, 14.15, 44.55, and 4.64% in 2016. In mild community cases, the detection rates of EV-A71, CV-A16, CV-A6, and CV-A10 were, respectively, 25.78, 41.64, 22.93, and 1.78% in 2014; 17.41, 21.23, 50.99, and 3.15% in 2015; and 18.92, 27.84, 45.11, and 1.64% in 2016. Among the cluster outbreaks, the most common pathogen was CV-A16 in 2014 (50.69%) and 2015 (38.10%) and CV-A6 in 2016 (36.30%). These findings show that HFMD outbreaks remained at a high level in Shanghai during 2014-2016. CV-A6 was emerging as the most common pathogen causing HFMD.

Measles Outbreak in Pediatric Hematology and Oncology Patients in Shanghai, 2015.

BACKGROUND: Despite substantial progress toward measles control are making in China, measles outbreaks in immunocompromised population still pose a challenge to interrupt endemic transmission. This study aimed to investigate the features of measles in pediatric hematology and oncology patients and explore the reasons behind the outbreak. METHODS: We collected demographic, epidemiological, and clinical data of immunocompromised measles children. All suspected measles cases were laboratory-confirmed based on the presence of measles IgM and/or identification of measles RNA. The clinical data were statistically analyzed by t-test for continuous variables and Fisher's exact test for categorical variables. RESULTS: From March 9 to July 25 in 2015, a total of 23 children with malignancies and post hematopoietic stem cell transplantation (post-HSCT) were notified to develop measles in Shanghai. Of these 23 patients with the median age of 5.5 years (range: 11 months-14 years), 20 (87.0%) had received 1-3 doses of measles vaccine previously; all patients had fever with the median fever duration of 8 days; 21 (91.3%) had cough; 18 (78.3%) had rash; 13 (56.5%) had Koplik's spot; 13 (56.5%) had complications including pneumonia and acute liver failure; and five (21.7%) vaccinated patients died from severe pneumonia or acute liver failure. Except the first patient, all patients had hospital visits within 7-21 days before measles onset and 20 patients were likely to be exposed to each other. CONCLUSIONS: The outcome of measles outbreak in previously vaccinated oncology and post-HSCT pediatric patients during chemotherapy and immunosuppressant medication was severe. Complete loss of protective immunity induced by measles vaccine during chemotherapy was the potential reason. Improved infection control practice was critical for the prevention of measles in malignancy patients and transplant recipients.

A Hospital-based Case-control Study of Diarrhea in Children in Shanghai.

BACKGROUND: Prevention and control of childhood diarrhea is a global priority. We conducted a case-control study of childhood diarrhea in Shanghai. METHODS: We prospectively recruited diarrheal children in an outpatient setting. Nondiarrheal controls were individually matched to cases. Rotavirus, norovirus and bacterial pathogens were examined. Clinical and epidemiologic data were obtained at enrollment and follow-up. RESULTS: Potential pathogens identified in 680 diarrheal cases and 680 controls were rotavirus (19.0% vs. 1.3%), norovirus (13.4% vs. 4.7%), nontyphoidal Salmonella (9.3% vs. 1.9%), enteropathogenic Escherichia coli (8.4% vs. 6.9%) and enteroaggregative Escherichia coli (7.2% vs. 6.2%) and Campylobacter (5.1% vs. 1.2%), enterotoxigenic Escherichia coli (1.2% vs. 0.6%), enterohemorrhagic Escherichia coli (0.3% vs. 0%) and Shigella (0.15% vs. 0%), respectively. The specificity and sensitivity of fecal leukocytes >5 per high-power field for the diagnosis of bacterial diarrhea were 94.2% and 22.8%. Salmonella were susceptible to ciprofloxacin, ceftriaxone and amoxicillin-clavulanate and showed low frequency of resistance to azithromycin. Campylobacter showed low frequency of resistance to azithromycin and high frequency of resistance to ciprofloxacin. Diarrheagenic Escherichia coli was highly susceptible to ciprofloxacin and amoxicillin-clavulanate. Contact with diarrheal patients was a risk factor for rotavirus [adjusted odds ratio (aOR): 11.7], norovirus (aOR: 7.5) and Campylobacter (aOR: 27.1) infections. Mother's education was positively associated with Salmonella infection (aOR: 2.1). Good hand hygiene was protective against rotavirus (aOR: 0.6), norovirus (aOR: 0.5) and Salmonella (aOR: 0.3) infections. CONCLUSIONS: Rotavirus, norovirus, nontyphoidal Salmonella and Campylobacter are significantly associated with diarrhea in Chinese children. Fecal leukocytes >5 per high-power field can predict bacterial diarrhea. Target prevention and appropriate treatment of diarrhea should consider the potential pathogen and resistance pattern.