[Analysis on infectivity of COVID-19 patients before and after last negative nucleic acid test].

Objective: To investigate the infection rate in close contacts of COVID-19 patients before and after the last negative nucleic acid test, evaluate the effect of dynamic nucleic acid test in determining the infectivity of COVID-19 patients. Methods: Dynamic nucleic acid test results of COVID-19 cases were collected in a retrospective cohort study. COVID-19 cases with negative nucleic acid test results before their first positive nucleic acid tests were selected as study subjects. Close contacts of the index cases and the secondary close contacts were kept isolation for medical observation to assess their risk of infection. Results: This study included 89 confirmed cases from two local COVID-19 epidemics in Ningbo. A total of 5 609 close contacts were surveyed, the overall infection rate was 0.20%. No close contacts of the COVID-19 cases before the last negative nucleic acid test were infected, and the infection rate in the close contacts of the COVID-19 cases after the last negative nucleic acid test was 1.33%, all of these close contacts lived together with the index cases. No secondary close contacts were infected. Conclusion: COVID-19 patient becomes infectious after the last nucleic acid is negative, and has no infectivity before the last nucleic acid negative.

[Research progress on immune efficacy, safety, vaccination intention and immunization strategy of domestic enterovirus 71 vaccine after its marketing].

Enterovirus 71 (EV71) is one of the main pathogens of hand, foot and mouth disease (HFMD) and the main pathogen of severe HFMD. In 2015, three EV71 vaccines were successively marketed in China as powerful prevention and control tools for HFMD caused by EV71. To understand the efficacy, immunogenicity, safety and quality stability of the domestic EV71 vaccine after entering into the market and analyze potential problems in its application, this article incorporates research regarding the immune effect, population effect, safety, quality testing and evaluation results, vaccination willingness and vaccination behavior survey to explore the vaccination strategies for the donll stic EV71 vaccine. EV71 vaccine has good immunogenicity, safety, protective efficacy, and good quality stability after entering into the market, however, only a few study focused on its safety when inoculating with other immunization planning vaccines simultaneously. Strengthen safety monitoring and discuss the safety of the EV71 vaccine especially when simultaneously inoculate with other immunization program vaccines are still necessary. Enterovirus evolution and recombination, whilst the probable impact of the EV71 vaccine can be the reason for future changes of HFMD epidemic strains, hence continuous monitoring of antigenic mutations and genetic evolution of enterovirus should be responded to. Encouraging the R&D of polyvalent vaccines against HFMD is also necessary. Parents' lack of HFMD and EV71 vaccine knowledge was common, therefore HFMD knowledge should be strengthened at the same time when introducing the EV71 vaccine to the public. Also, it should be emphasized that the EV71 vaccine can only prevent HFMD caused by EV71.

[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.

Characterization of antibody and memory T-cell response in H7N9 survivors: a cross-sectional analysis.

OBJECTIVES: Despite the importance of immunological memory for protective immunity against viral infection, whether H7N9-specific antibodies and memory T-cell responses remain detectable years after the original infection is unknown. METHODS: A cross-sectional study was conducted to investigate the immune memory responses of H7N9 patients who contracted the disease and survived during the 2013-2016 epidemics in China. Sustainability of antibodies and T-cell memory to H7N9 virus were examined. Healthy individuals receiving routine medical examinations in a physical examination centre were recruited as control. RESULTS: A total of 75 survivors were enrolled and classified into four groups based on the time elapsed from illness onset to specimen collection: 3 months (n = 14), 14 months (n = 14), 26 months (n = 28) and 36 months (n = 19). Approximately 36 months after infection, the geometric mean titres of virus-specific antibodies were significantly lower than titres in patients 3 months after infection, but 16 of 19 (84.2%) survivors in the 36-month interval had microneutralization (MN) titres ≥40. Despite the overall declining trend, the percentages of virus-specific cytokine-secreting memory CD4+ and CD8+ T cells remained higher in survivors at nearly all time-points in comparison with control individuals. Linear regression analysis showed that severe disease (mean titre ratio 2.77, 95% CI 1.17-6.49) was associated with higher haemagglutination inhibition (HI) titre and female sex for both HI (1.92, 1.02-3.57) and MN (3.33, 1.26-9.09) antibody, whereas female sex (mean percentage ratio 1.69, 95% CI 1.08-2.63), underlying medical conditions (1.94, 95% CI 1.09-3.46) and lack of antiviral therapy (2.08, 95% CI 1.04-4.17) were predictors for higher T-cell responses. CONCLUSIONS: Survivors of H7N9 virus infection produced long-term antibodies and memory T-cell responses. Our findings warrant further serological investigation in general and high-risk populations and have important implications for vaccine design and development.

[Advances on epidemiological research of human infections with novel avian influenza A (H7N9) virus].

Human infections with novel avian influenza A(H7N9)virus was an emerging infectious disease discovered in March, 2013. As of June30, 2016, 770 cases of H7N9 were reported in worldwide including 315 deaths with 40.9% of high case fatality rate. Yangtze River Delta and Pearl River Delta were the high-prevalence area. Formerly, the cases of H7N9 were concentrated on the municipalities. However, most of the case-patients were from smaller cities or rural areas nowadays. The H7N9 human infections mainly occurred in winter and spring every waves as similar as seasonal and H5N1 human infections. Middle aged and old (the median age was 61 years) male patients were occupied the large proportion among the cases of H7N9. In addition, the phenomenon of the limited and unsustained human-to-human transmission were existed. At present, the 4 major epidemic waves had happened and human infections with novel avian influenza A (H7N9) virus could be outbreak regularly in China. In this paper, the pathogenic characteristics and disease distribution of H7N9 influenza A viruses were elaborated, with both transmission factors and control measures, which were helpful to provide the scientific evidence for prevention and control in H7N9avian influenza epidemic.

Quantitative risk analysis of the novel H7N9 virus in environments associated with H9 avian influenza virus, Zhejiang province, China.

H9 avian influenza virus played a key role during generation of the novel H7N9 virus. A surveillance programme was conducted to assess the H9 virus in relation to the risk of H7N9 virus contamination in the environment. Risk of H7N9 virus contamination in the presence of H9 virus was higher than without (adjusted odds ratio 4·49, 95% confidence interval 3·79-5·31). Adjusted odds ratios of the H7N9 virus associated with co-presence of H9 virus and interacting factors were 4·93 (rural vs. urban area), 46·80 (live poultry markets vs. other premises), 6·86 (Huzhou vs. Hangzhou prefecture), 40·67 (year 2015 vs. 2013), and 9·63 (sewage from cleaning poultry vs. poultry faeces). Regular surveillance on gene variability of H7N9 and H9 viruses should be conducted and extra measures are needed to reduce co-circulation of H7N9 and H9 viruses in the environment.

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.

Seroprevalence of severe fever with thrombocytopenia syndrome virus in southeastern China and analysis of risk factors.

Severe fever with thrombocytopenia syndrome virus (SFTSV) has been prevalent for some time in China and it was first identified in 2010. However, the seroprevalence of SFTSV in the general population in southeastern China and risk factors associated with the infection are currently unclear. Blood samples were collected from seven counties across Zhejiang province and tested for the presence of SFTSV-specific IgG antibodies by ELISA. A total of 1380 blood samples were collected of which 5·51% were seropositive for SFTSV with seroprevalence varying significantly between sites. Seroprevalence of SFTSV in people who were family members of the patient, lived in the same village as the patient, or lived in a different village than the patient varied significantly. There was significant difference in seroprevalence between participants who bred domestic animals and participants who did not. Domestic animals are probably potential reservoir hosts and contact with domestic animals may be a transmission route of SFTSV.

Clinical and epidemiological survey and analysis of the first case of human infection with avian influenza A(H7N9) virus in Hangzhou, China.

To investigate and report on the clinical and epidemiological characteristics of the first case of human infection with avian influenza A(H7N9) virus in Hangzhou, China. A field epidemiological survey was used to study the first case in Hangzhou. The patient was a 39-year-old male chef with a history of exposure to a farm product market and to poultry prior to the onset of disease on 15 March 2013. He had diarrhea, chills, pyrexia, and intermittent cough with freshly red foamy bloody sputum early in his disease. His fever > 39 °C continued for a week with rapid progression. Computed tomography findings showed extensive bilateral consolidation, followed by multiorgan failure. The patient died on the morning of 27 March. His infection was eventually confirmed 1 week later on 3 April. Flu-like symptoms including fever and cough were found in 46 of his 138 close contacts. This was the first case of human infection with avian influenza A(H7N9) virus in Hangzhou. None of the close contacts had onset of the disease. The case patient's condition progressed rapidly. The source of infection might be his exposure to the farm product market, but the mode of exposure remains unclear.

Delayed administration of the K+ channel activator cromakalim attenuates cerebral vasospasm after experimental subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral vasospasm remains an unpredictable and inadequately treated complication of aneurysmal subarachnoid hemorrhage (SAH). Recent evidence indicates that the potassium channel activator cromakalim is capable of limiting cerebral vasospasm in rabbits when administered immediately after experimental SAH (i.e. before spastic constriction has been initiated). However, the ultimate clinical value of cromakalim for treating vasospasm will depend in part on its effectiveness when administered after SAH-induced constriction has already been initiated. The present study examined the effects of cromakalim on vasospasm when treatment was initiated after SAH-induced constriction was underway. METHODS: New Zealand white rabbits were subjected to experimental SAH by injecting autologous blood into the cisterna magna. Cromakalim (0.03, 0.1 or 0.3 mg/kg) or vehicle was injected intravenously at 8 hour intervals beginning 24 hours post-SAH. Animals were killed by perfusion fixation 48 hours after SAH. Basilar arteries were removed and sectioned, and cross-sectional area was measured. FINDINGS: The average cross sectional areas of basilar arteries were reduced by 64% and 68% in the SAH-only and SAH + vehicle groups, respectively. Treatment with cromakalim dose-dependently attenuated SAH-induced constriction. The groups treated with 0.03, 0. 1, and 0.3 mg/kg cromakalim exhibited average decreases in cross-sectional area of 57%, 42%, and 19%, respectively. INTERPRETATION: These findings indicate that cromakalim dose-dependently attenuates cerebral vasospasm when administered 24 hours after experimental SAH in the rabbit. The results suggest K(ATP) channel activators, such as cromakalim. could be of benefit for reversing cerebral vasospasm after aneurysmal SAH.