[Etiology and molecular-epidemiological characteristics of viral meningo-encephalitis in Zhejiang province, 2002-2018].

Objective: To understand the pathogens and molecular-epidemiologic characteristics of viral meningo-encephalitis in Zhejiang province during 2002 to 2018. Methods: All the samples were collected from suspected patients admitted to the hospitals under the monitoring program. Of the total samples, 2 173 were cerebrospinal fluids while the other 455 were stool specimens. Cerebrospinal fluid (CSF) samples were subject to real-time qPCR for the detection of Human enterovirus (HEV), Mumps virus (MuV), Herpes simplex virus (HSV), Cytomegalovirus (CMV) and Japanese encephalitis virus (JEV). Stool sample were subject to real-time qPCR for HEV. ELISA was used to detect the IgM antibodies in CSF, in the 5 kinds of virus mentioned above. VP1 genes from all RNA-positive specimen were amplified, sequenced, for typing and for evolution analysis. Results: 871 (40.1%) of the 2 173 samples were detected as HEV nucleic acid positive during 2002 to 2018. 654 (38.1%) of the 1 718 CSF sample were HEV nucleic acid positive while 217 (47.7%) of the 455 stool sample were HEV nucleic acid positive. Among the total positive nucleic acid sample, 670 of them were VP1 sequence positive, including 5 HEV-A and 665 HEV-B. There were 23 HEV serotypes, including Coxsackievirus (CV) CVA4, CVA6, CVA9, CVA10, CVB1-5, Echovirus (EchoV; E) E3, E4, E6,E7, E9, E11, E14, E16, E18, E21, E25, E30, E33 and EV-71. The top three serotypes went to E30, E6 and CVB5. These three serotypes presented enhanced viral activity in every several years. 795 CSF samples were detected as virus nucleic acid positive, including 374 HEV, 6 MuV, 5 HSV and 5 CMV, from 2012 to 2015 and in 2018. 5 kinds of IgM antibodies were detected simultaneously in 368 CSF samples, including 2 HEV positive, 6 JEV positive and 1 MuV positive for 5 viruses, respectively. Except for EV-71, there were 517 EchoV and 152 CV viruses presented, with the ratio of 3.4∶1. These two kinds of viruses alternately changed for each predominant epidemic strains in every 3-5 years. Based on VP1, results from the phylogenetic tree showed that HEV from Zhejiang province clustered into HEV-A and HEV-B clades respectively. E30 developed both h and i sub-genotypes. Conclusions: HEV-B seemed the main pathogen for viral meningo-encephalitis in Zhejiang province. Ratio of positive detection on EchoV was significantly higher than that on CV. These two kinds of virus alternately presented changing tendency in every several years. Predominant epidemic strains E30, CVB5 and E6 were presenting enhanced viral activity, also in every several years. High correlation was found in both HEV viral activity from the surveillance sites and in time line of the viral meningo-encephalitis outbreaks.

[Epidemiological characteristics of COVID-19 family clustering in Zhejiang Province].

Objective: To investigate the epidemiological characteristics for family clusters of COVID-19 in Zhejiang Province. Methods: The data including cases information of asymptomatic infected cases of family clusters of COVID-19 in Zhejiang Province were collected from Public Health Emergencies Reporting System of China Center for Disease Control and Prevention. Calculate the case number of subsequent cases, index cases, asymptomatic infected cases, exposure cases, and then, compute family secondary attack rate (SIR) and serial interval. Results: A total of 389 cases comprised 149 family index cases and 240 subsequent cases. The clinical symptoms between family index cases and subsequent cases (exclude asymptomatic infected cases ) were similar, fever was the most common symptoms in the two groups 115 (77.18%) and 110（48.67%）respectively, the cases with diarrhea symptoms accounted for the least proportion, which were 7 (4.70%) and 6 (2.65%) respectively. The serial interval between the family index cases and the subsequent cases [M (P25, P75)] was 4.00 (2.00, 6.00) days. Family secondary attack rate for subsequent cases was 34.43%, subsequent cases aged between 14 and 60 have the highest SIR (43.42%) compared with other two age groups, the difference was statistically (P<0.001); the family SIR of the spouses of the family index cases is 68.57%, and are higher than that of parents (29.03%), children (25.00%) and other family members (24.21%), the difference was also statistically (P<0.001). Conclusion: 2019 novel coronavirus has shorter serial interval and higher family SIR, the SIR of spouses is higher than other family members.

[Review on the etiology and complications of hand, foot and mouth disease, using data from the national sentinel surveillance program, in China, 2015-2016].

Objective: To understand the characteristics relating to the etiology and complications of hand, foot and mouth disease (HFMD) based on data from the pilot National Sentinel Surveillance (NSS) program so as to explore the feasibility, advantages and disadvantages of the NSS. Methods: Data were extracted from the NSS system, conducted in 11 provinces of China from November 2015 to October 2016. Characteristics regarding the etiology, complications of HFMD and factors related to the positive rates of HFMD specimens were analyzed under the logistic regression method by SPSS 20.0 software. Results: A total of 4 783 specimens were collected, including 3 390 from mild, 1 390 from severe and 3 from death cases. The overall positive rate was 81.43% (3 895/4 783). Other enteroviruses (non EV71/Cox A16 enteroviruses) appeared the major serotype (52.68%, 1 482/2 813) for mild infection of the disease while EV71 was for the severe cases (65.31%, 706/1 081). The serotype spectrum revealed by the pilot NSS was almost identical with the existing surveillance system. Other enteroviruses tended to infect younger children (χ(2)=130.17, P<0.001) than EV71 and Cox A16, in China. The multivariate logistic regression results showed that higher positive rate was associated with specimens which were collected from males, at children' hospitals, in peak seasons, timely and in stools. The positive rates presented downwarding trends with the extension of the onset-sampling interval (χ(2)=14.47, P<0.001 in stool specimen; χ(2)=31.99, P<0.001 in throat swab; χ(2)=24.26, P<0.001 in anal swab). Aseptic meningitis, non-brainstem encephalitis and brainstem encephalitis appeared the top three complications of both EV71-associated and other enteroviruses-associated severe HFMD cases. Conclusions: Factors as gender, season/place/timeliness of specimen collection, and types of hospital all appeared independently influenced the positive rates. NSS seemed feasible to be used as an alternative or supplement tool to the existing surveillance program in China.

[Clinical stages and outcomes of severe cases on hand, foot and mouth disease].

Objective: To understand the characteristics and relation of clinical stage and outcome of severe cases on hand, foot and mouth disease (HFMD) and to establish the evaluation method for understanding severity of this disease. Methods: According to factors as geographical location, economic and epidemic levels, five provinces (Henan, Shandong, Yunnan, Zhejiang and Sichuan provinces) were selected. Reported severe cases of HFMD from the National Notifiable Diseases Reporting System were selected randomly in the five provinces. Basic epidemiological information, clinical data, and pathogen testing results in the involved hospitals were collected. Clinical stages on all the patients were decided in accordance with"the clinical expert consensus on diagnosis and treatment for severe case of enterovirus type 71 (EV71) infections (2011 edition)" . Data were analyzed using SPSS software 18.0 and other epidemiological methods. Results: A total of657 severe HFMD cases were investigated, with 326 cases positive of EV71, accounting for 91.3% (326/357) among all the laboratory-confirmed cases. Of the 657 cases, 542 cases (82.5%, 95%CI: 79.4%-85.3%) were diagnosed as in stage 2 (with nervous system involvement), 99 cases (15.1%, 95%CI: 12.4%-18.0%) in stage 3 (early phase of function failure on heart and lung), and 16 cases (2.4%, 95%CI: 1.4%-3.9%) were in stage 4 (function failure of heart and lung). 11 cases (1.7%, 95%CI: 0.9%-3.0%) were with squeal when discharged from hospital with 8 cases (1.2%, 95%CI: 0.6%-2.3%) died. When comparing the proportions among stage 2, stage 3 and stage 4, significant differences were found between age groups (χ(2)=22.632, P=0.012). The younger the patient was the lower the proportions of stage 2 and the more proportion of stage 3 appeared. When comparing the proportions of clinical stages among the five provinces, significant differences (χ(2)=41.481, P=0.000) were noticed. Proportions of different clinical stages in gender, ethnicity, occupation, place of residence types and the type of pathogen appeared no significant differences, respectively. However, the proportions of squeal and death in stage 2, stage 3 and stage 4 showed significant differences (sequela: χ(2)=12.960, P=0.001; Death: χ(2)=16.850, P=0.001), respectively. Conclusions: The percentage of clinical stages of severe HFMD patients related to the rate of squeal and death. Clinical staging can be used for assessing the clinical severity of complications and the effectiveness of treatment, of HFMD.

[Severe cases with hand, foot and mouth disease: data based on national pilot hand, foot and mouth disease surveillance system].

Objective: To investigate the clinical severity, etiological classification and risk factors of severe cases with hand, foot and mouth disease (HFMD). Methods: A total of 1 489 records on severe and fatal HFMD cases reported to the national pilot surveillance system of HFMD were used to analyze the demographic, medical treatment, etiological classification of the cases. Treatment outcome related risk factors were also studied with multi-variable stepwise logistic regression method. Results: Seven out of the 1 489 severe HFMD cases died of this disease. A total of 960 (72.9%) were under three years old and 62.9% were male and most of the cases (937, 62.9%) resided in rural areas. Among all the cases, 494 (33.2%) went to seek the first medical assistance at the institutions of village or township level. Durations between disease onset and first medical attendance, being diagnosed as the disease or diagnosed as severe cases were 0(0-1) d, 1 (0-2) d and 2 (1-4) d, respectively. In total, 773 (51.9%) of the severe HFMD cases were diagnosed as with aseptic meningitis, 260 (17.5%) with brainstem encephalitis, 377 (25.3%) with non-brainstem encephalitis, 6 (0.4%) with encephalomyelitis, 1 (0.1%) with acute flaccid paralysis, 4 (0.3%) with pulmonary hemorrhage/pulmonary edema and 68 (4.6%) with cardiopulmonary failure. Of the etiologically diagnosed 1 217 severe and fatal HFMD cases, 642 (52.8%) were with EV71, other enterovirus 261 (21.5%), Cox A16 36 (3.0%), 1 (0.1%) with both EV71 and Cox A16. However, 277 (22.8%) showed negative on any pathogenic virus. Complication (Z=3.15, P=0.002) and duration between onset and diagnosed as severe cases (Z=3.95, P<0.001) were shown as key factors related to treatment outcomes. Conclusions: Most severe HFMD cases appeared in boys, especially living in the rural areas. Frequently seen complications would include aseptic meningitis, non-brainstem encephalitis and brainstem encephalitis. EV71 was the dominant etiology for severe and fatal cases. Early diagnosis and complication control were crucial, related to the treatment outcome of HFMD.

Epidemiological investigation of a tap water-mediated hepatitis E virus genotype 4 outbreak in Zhejiang Province, China.

An outbreak of acute hepatitis recently occurred in a nursing home in Zhejiang Province, China. The objectives of this study were to confirm the outbreak and identify the aetiology, source and transmission patterns. All residents and staff in or near the nursing home during the period from 1 October 2014 to 21 May 2015 were investigated regarding hygiene and for epidemiological information including water and food (eating meat especially pork products). Serum and stool specimens were collected for detection of hepatitis E virus (HEV) antibodies using ELISA and RNA using RT-PCR. Samples that were RNA positive were genotyped. Of 185 senior residents and 24 staff in the nursing home, there were 37 laboratory-confirmed cases during the outbreak. Of these cases, 12 patients (three deaths) were symptomatic with jaundice, a common clinical symptom for hepatitis E infection. HEV strains were isolated from three cases and they formed a single cluster within genotype 4d. A case-control study was conducted to investigate potential risk factors for the outbreak and the results revealed that cases more often washed their dishes and rinsed their mouths using tap water than the controls (P < 0·05). Based on hygiene investigation and meteorological information, it is likely that HEV-infected sewage and faeces contaminated the water network on rainy days. Collectively, these results suggest that the outbreak of HEV genotype 4 infection was most likely caused by contaminated tap water rather than food.

[On the rapid population growth during the period of Emperors Qian Long, Jia Qing, and Dao Guang of the Qing dynasty].

PIP: The reasons for the rapid growth of population that occurred during the early-middle period of the Qing dynasty in China are examined. Factors considered include Kan Hsi's tax reforms, the expansion of Chinese borders, increased food production, and socioeconomic changes brought about through contact with the West during the reign of Dao Guang. The consequences of the rapid growth of population for land use and food distribution are also considered.^ieng