Objective: To retrospectively analyze the epidemic characteristics and spatial distribution of vomiting and diarrhea outbreaks in schools and kindergartens in Shanghai from 2015 to 2019, so as to provide the scientific evidence for optimizing prevention and control of vomiting and diarrhea outbreaks in schools and kindergartens. Methods: Data collection and analysis were carried out on the vomiting and diarrhea outbreaks reported to Shanghai Municipal Center for Disease Control and Prevention from 2015 to 2019. Epidemiological characteristics were analyzed and compared. The proportion and incidence of outbreaks in schools and kindergartens were calculated, and the influencing factors of outbreaks were analyzed by multivariate Logistic regression. The index of Moran s I was used for the global and local spatial auto correlation analysis. Results: Among the 344 vomiting and diarrhea outbreaks, 98.26% occurred in kindergartens, primary schools, middle schools and other educational institutions. The median number of cases per outbreak was 15. The number of suspected outbreaks and the percentage of cases involved peaked in 2015 ( 60.00% , 84.35%) and then decreased year by year to 16.00% and 38.80% in 2019. About 86.98% of the outbreaks were transmitted by human to human contact. Among the 329 outbreaks with samples collected from cases and/or environments, the main pathogen detected was norovirus ( n =280), and sapovirus was detected in outbreak for the first time in 2016. The outbreaks showed obvious seasonality, with two peaks (November, March) and one trough (July), and the majority of outbreaks occurred in primary schools (44.38%) and kindergartens (32.84%). Compared with kindergartens, the probabilities of suspected epidemic outbreaks in primary schools, combined schools, middle schools and other educational institutions were higher (adjusted OR =6.40, 9.16, 12.64 , 5.58, P <0.01). The proportion and incidence of outbreaks in educational institutions in different districts showed no high-high aggregation areas. Conclusions Primary schools and kindergartens are key places for the prevention and control of vomiting and diarrhea outbreaks. Targeted prevention and control measures should be strengthened at the beginning of each semester and before the peak of the epidemic each year. Timely reporting of symptoms, suspension of school admissions after symptoms appear and standardized disposal of vomit are effective measures to reduce interpersonal transmission and control the scale of an outbreak.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective:To investigate the epidemiological and pathogenic characteristics of children's infectious diarrhea in Shanghai to provide evidence for developing strategies related to the control of the disease .Methods:Diarrhea outpatients were under surveillance at the pediatric intestinal clinic at five sentinel hospitals in Shanghai, with demographic, clinical, and epidemiological information collected. Fecal specimens were collected and detected for 12 bacteria and 5 viruses by district center for disease control and prevention. Characteristics of diarrhea patients were compared and analyzed from 2016 to 2021. Multi-stage systematic sampling method was adopted. The Chi-square test was used for statistical analysis.Results:Of 2 456 infectious diarrhea patients, the positive rate was 45.11% (1 108/2 456), 16.00% (393/2 456), 20.81% (511/2 456), 8.31% (204/2 456), for all pathogens, single bacteria, single virus, and diverse infections respectively. The prevalent detected pathogens were pathogenic Escherichia coli (12.95%, 318/2 456), norovirus (10.91%, 268/2 456), rotavirus (7.49%, 184/2 456), Salmonella (5.82%, 143/2 456) and Campylobacter jejuni (4.68%, 115/2 456). The pathogen spectrum of childhood infectious diarrhea patients showed noticeable seasonal changes, with a prevalent bacterial infection in summer [peaked in June, the positive rate was 34.50% (69/200)] and a prevalent viral infection in winter [peaked in January, the positive rate was 48.10% (101/210)]. The positive rates in different age groups, populations, and seasons were statistically different ( χ2=160.53, P<0.001; χ2=14.80, P=0.003; χ2=27.21, P<0.001). During 2020-2021, the number of cases of infectious diarrhea in children (284 cases/year) dropped significantly compared with the number in 2016-2019 (472 cases/year), the pathogen spectrum changed significantly ( χ2=39.02, P=0.001), and the positive findings of bacteria ( χ2=11.73, P<0.001) and viruses ( χ2=14.22, P<0.001) decreased significantly. However, the positive rate of enteric adenovirus increased. Conclusions:The pathogen spectrum of children's infectious diarrhea patients shows noticeable seasonal changes in Shanghai. Pathogenic Escherichiacoli, norovirus, and rotavirus are the most common diarrheal pathogens. In recent years, the detection of adenovirus in children with infectious diarrhea has increased. The number of children with infectious diarrhea and the positive rate have decreased significantly during 2020-2021. Specific prevention and control measures should be taken for infectious diarrhea of different ages, pathogens, and seasons.

In order to meet the needs of prevention and control of intestinal infectious diseases， a comprehensive surveillance for diarrheal diseases has been innovated and explored in Shanghai since 2012. The surveillance has extensive distribution of sentinel hospitals， systematic sampling， multi-pathogen collection， and hospital information system （HIS） as the basis， which has achieved “One system for surveillance of multiple diseases and one sample for detection of multiple pathogens". Continual active surveillance for the whole population has been conducted， covering demography， clinical information， epidemiology， pathogen detection， and drug sensitivity test for diarrhea cases. The surveillance has obtained preliminary achievements as follows. First， diarrheal diseases and their periodic changes have been characterized， in which the most prevalent pathogen of diarrhea is determined to be norovirus in Shanghai. Second， some rare pathogens and serotypes have been identified that may provide clues to the sources of outbreaks. Third， it facilitates the information sharing between public health institutions and clinical institutions， and provides scientific evidence for clinical diagnosis and treatment. In the future， Shanghai diarrhea comprehensive surveillance will be improved for expanding range and depth of surveillance， artificial intelligence assisted diagnosis and treatment， early warning of outbreaks， prediction of epidemic trends， and application of new detection technologies.

ObjectiveTo conduct on-site epidemiological investigation， emergency response， tracing of infection source and analysis of a confirmed COVID-19 case of a foreign airline cargo service staff member in Shanghai’s international airport， aiming to provide reference for prevention of imported COVID-19 cases under regular prevention and control of COVID-19. MethodsA retrospective field epidemiological investigation was conducted to collect information of basic characteristics， illness onset， diagnosis， treatment， clinical manifestations， exposure history and risk factors within 14 days before onset， close contacts， close contacts of close contacts， and key places related to activity trajectories. Respiratory tract specimens of cases and contacts were collected for detection of SARS-CoV-2 by real time RT-PCR （rRT-PCR）. Emergency response， including infection source analysis and contact management， was conducted. ResultsThe case developed pharyngeal itch on July 28， 2021， and fever on the 30th， and went to the hospital for treatment twice on the 31st. Because his specimen was positive for SARS-CoV-2 by rRT-PCR on August 1， he was isolated and treated on August 2 and diagnosed as a confirmed case of COVID-19. The case was a foreign airline cargo service member at an international airport. The two regular nucleic acid screenings of him as a high-risk occupation on July 21 and 28 were negative. He did not leave Shanghai within 14 days before the onset of illness. During July 22nd and 23rd， he was repeatedly exposed during work to the high-risk environment that may have been contaminated by SARS-CoV-2 and had contact with the crew of foreign airlines， and the personal protection was not standardized. None of the 67 close contacts and 567 close contacts of close contacts in Shanghai showed symptoms during the 14-day medical quarantine， and the specimens of them were all negative for SARS-CoV-2 by rRT-PCR. The results of genome sequencing analysis showed that the genomic homology between the virus of the case and the one of recent domestic local epidemic and the recent imported cases was low， and the homology with the overseas Delta mutant strain was higher than that of the domestic Delta mutant strain. ConclusionThe situation of prevention of COVID-19 import is still serious. It is necessary to conduct regular nucleic acid screening for high-risk occupational groups， strengthen the diagnosis and reporting awareness of medical institutions， effectively implement the prevention and control measures for people， objects， and environment at international airports， and further enhance the public's awareness of personal protection.

Objective:To analyze the epidemiological characteristics of a cluster of 5 confirmed COVID-19 cases related with the transmission in incubation period of initial case, and find out the infection source and transmission chain.Methods:According to "The Prevention and Control Protocol for Coronavirus Disease 2019 (Third Edition)" issued by the National Health Commission, a field epidemiological survey was conducted for the 5 cases in January 2020. Nasopharyngeal swabs and sputum samples were collected from them for the detection of 2019-nCoV by real time RT-PCR. Multi prevention and control measures were taken, such as tracking and screening close contacts, medical isolation observation, investigating the epidemiological link, analyzing transmission chain.Results:Case 1, who had common environmental exposure with other COVID-19 cases, got sick on 20 January, 2020 and was confirmed on 1 February. Case 2 became symptomatic on 22 January and was confirmed on 27 January. Case 3 got sick on 25 January and was confirmed on 30 January. Case 4 had illness onset on 20 January and was confirmed on 1 February. Case 5 got sick on 23 January and was confirmed on 31 January. Among the 5 cases, case 2 died and the illness of other cases were effectively controlled. After exclusion of other common exposure factors, case 1 had a 6-hour meeting with case 2 and case 3 on 19 January. Case 2 and case 3 might be infected by case 1 during the incubation period. It is the key point for epidemiological investigation.Conclusion:The epidemiological investigation indicates that the transmission might occur in the incubation period of COVID-19 case, close attention should be paid to it in future COVID-19 prevention and control.

Objective:To analyze the epidemiological characteristics of imported COVID-19 cases in early phase in Shanghai, introduce measures and provide reference for prevention and control of imported COVID-19 cases.Methods:Data of imported COVID-19 cases in Shanghai reported as of 30 March, 2020 were obtained from National Notifiable Disease Report System of China CDC and field epidemiological investigation reports by CDCs in Shanghai. The information about measures of prevention and control was collected from official websites and platforms of the governments. Data cleaning and statistical analysis were performed with softwares of EpiData 3.1, Excel 2019 and SAS 9.4.Results:A total of 171 imported COVID-19 cases had been reported as of 30 March, 2020 in Shanghai, including 170 confirmed cases and 1 asymptomatic infection case. Among them, cases of Chinese nationality accounted for 71.3% (122/171) and cases of foreign nationality accounted for 28.7% (49/171). The median age of the cases was 23 years ( P 25, P 75: 18, 35 years), and the male to female ratio of the cases was 1.3∶1. Students accounted for 56.6% (97/171). About 45.6% (78/171) of the cases fell ill before arriving in Shanghai. The cases with mild or common clinical manifestation accounted for 96.5% (165/171) and no significant difference in clinical type was observed between overseas Chinese cases and foreign cases. The epidemic curve by diagnosis date reached peak on March 24, and the number of the cases gradually declined due to the closed-loop management process of joint port prevention and control mechanism. The 171 imported COVID-19 cases were mainly from 24 countries and regions, including the United Kingdom (64 cases, 37.3%), the United States (32 cases, 18.6%), France (19 cases, 11.0%) and Italy (16 cases, 9.4%). About 40.4% of the cases (69/171) planned to continue travelling to 21 other provinces and municipalities in China. Customs quarantine and community observation/detection points identified 43.9% (75/171) cases and 31.0% (53/171) cases, respectively. Conclusions:The imported COVID-19 cases in early phase in Shanghai were mainly young population and students accounted for high proportion. The imported risk of COVID-19 was consistent with the severity of the epidemic in foreign countries. The closed-loop management model of the joint port prevention and control mechanism plays an important role in the identification and management of the imported COVID-19 cases.

Objective: To investigate the molecular characterization of adult diarrhea cases caused by enterotoxic Escherichia coli (ETEC) and explore the practical model of epidemiology for laboratory technique and data needs based on the surveillance network. Methods: Epidemiological design and sampling targeted adult cases ETEC caused diarrhea in epidemic season. The enterotoxin type, serogroup, resistance, colonization factor and molecular type of ETEC were identified. Multiple dynamic phenotypic characteristics of ETEC were indicated by multidimensional and multivariable data. Results: From 2016 to 2018, 84 eligible ETEC strains were detected. The dominant serums/toxins were O∶6 (STh), O∶25 (LT), O∶159 (STh), O∶153 (STh). O∶6 (STh+CS21), which replaced O∶25 and O∶159 as the popular clones in 2018. Six cases of O∶153 (STh+CFA/I+CS8+PT34) in outbreak in 2017 were imported ones. The resistance rates of ETEC strains detected in adults to sulfasoxazole, naproxinic acid, ampicillin and azithromycin were more than 30%, multidrug resistance (MDR) reached 58.3%. Serum/toxin types suggested that attenuated strains were more likely to become MDR. Molecular typing confirmed that the genetic similarity of the dominant clone of O∶6 serogroup (PT20-24) was higher than O∶25 and O∶159. There was a high correlation between the minimal inhibitory concentration (MIC) of azithromycin and the resistant gene mphA (87.5%, 28/32). O∶6 (STh+CS21+mphA) resistant clone was first detected in 2016. Conclusion A new epidemic clone in adult ETEC diarrhea cases in Shanghai was O∶6 (STh+CS21+mphA). For the first time the association between azithromycin resistance gene mphA and a serum group of ETEC was observed. Multidimensional and multivariate analysis techniques based on epidemiology can help reveal the potential transmission pattern of ETEC for the accurate surveillance and early warning of outbreaks.

Objective: To investigate the epidemiologic characteristics of Norovirus among adult patients suffering from infectious diarrhea in Shanghai, so as to provide evidence for developing related strategies on prevention and control of the disease. Methods: Diarrheal outpatients were monitored at the 'Intestinal clinic’ from 22 hospitals involved in the sentinel surveillance program in Shanghai. Information on demographic and epidemiologic features of the patients was collected while data and clinical, fecal specimens were collected and sent to the district CDC for Norovirus detection. Positive rates of Norovirus were also compared in various populations and seasons during 2013-2018. Multivariate logistic regression model was adopted to fit into the comparisons between non-Norovirus and Norovirus groups. Results: 19.28% of the 12 083 diarrheal cases were found to have carried the Norovirus, with GⅡgroup the most commonly identified genotype. Rates of detection was seen higher in males (20.78%) than in females (17.73%). 30-44 year-old were found having the highest positive rate (21.51%). The positive rates were found the highest (23.60%) in the year of 2015. All the above shown differences were statistically significant (P<0.05). Diarrheal patients affected with Norovirus would present watery stool (75.94%) and vomiting (35.84%). Data from the multivariate logistic analysis showed that factors as: being males, 30-44 years old, officials/clerks, in winter season and with histories of travelling etc., were related to higher risks on Norovirus infection. Conclusions Infectious diarrhea caused by Norovirus occurred all year round, with seasonal peaks seen in winter and spring, in Shanghai. Specific prevention and control measures should be taken on Norovirus- caused infectious diarrhea, according to the difference on age, gender and season.