Evaluation of safety and immunogenicity of hepatitis E vaccine in maintenance hemodialysis patients / 中华预防医学杂志

Objective: To evaluate the safety and immunogenicity of hepatitis E vaccine(HEV)in Maintenance hemodialysis(MHD)patients. Methods: Based on an open-labeled controlled trial, from May 2016 to March 2018, 35 eligible MHD patients were recruited in the Hemodialysis Center of Zhongshan Hospital Affiliated to Xiamen University as the experimental group, and 70 MHD patients with matched age, gender and underlying diseases as the control group. The experimental group received HEV at 0, 1 and 6 months according to the standard vaccination procedures, while the control group received routine diagnosis and treatment without vaccine and placebo injection to observe the safety and immunogenicity of the vaccine. The safety of vaccine in MHD population was evaluated by the incidence of adverse reactions/events in the experimental and control groups. The immunogenicity of HEV in MHD patients was evaluated by comparing the data from the phase Ⅲ clinical trial. Results: The overall incidence of adverse reactions/events was 17.1% (18/105), and there were no grade 3-4 adverse reactions/events related to vaccination. In the experimental group, the incidence of local adverse reactions/events was 20.0% (7/35), and the incidence of systemic adverse reactions/events was 17.1% (6/35).There was no significant difference in the incidence of systemic adverse reactions/events between the experimental group and the control group (P>0.05). There were 23 patients receiving 3 doses with the standard schedule. The positive rate of HEV-IgG antibody was 100% and the GMC was 14.47(95%CI:13.14-15.80) WU/ml, which showed no significant difference compared with the 46 patients in Phase Ⅲ clinical trial (t=-1.04, P>0.05). Conclusion: Recombinant HEV has good safety and immunogenicity in MHD patients.

Epidemiological investigation on the first case of human infection with H7N9 avian influenza in Henan Province / 上海预防医学

[Objective] To investigate and analyze the first case of human infection with highly pathogenic avian influenza virus ( H7N9) so as to provide scientific basis for control of avian influenza infec-tion in humans. [Methods] Epidemiological survey was carried out including the process of morbidity , possible infection source , transmission route and risk factors , etc.Strict observation was made on close con-tacts of the patient .Meanwhile the patient underwent clinical diagnosis , treatment and laboratory tests . [ Results] The patient was confirmed to be infected with highly pathogenic human avian influenza H 7N9 virus as ascertained by expert group of ministry of health ,and was cured and discharged .The patient had definate contact with live poultry , and using H7N9 pharyngeal swab through laboratory tests , avian influenza virus nucleic acid showed positivity results .No abnormalities were found in clinical manifestations in close contacts of the patient.By expanding surveillance on 160 cases of influenza-likeillness(ILI)and 858 cases of professional groups , the samples were not found to be H 7 N9 positive .However , on local live poultry market, two chicken pharyngeal swab specimens were detected to be H 7N9 positive.Positive chickens were from other provinces . [ Conclusion] History of live poultry exposure is believed to be the key risk fac-tors in infection with H7N9 virus.So far there has been no evidence of human-to-human transmission . There has not been subclinical infection or mild cases found in crowd .However ,there is the need to expand monitoring and epidemiological investigation so as to improve the understanding of the disease .

Study and application of transmission tracking analysis technique during incubation period of respiratory infectious diseases / 中华预防医学杂志

<p><b>OBJECTIVE</b>To develop a new transmission tracking analysis technique during incubation period of respiratory infectious diseases, and to discuss its practical value in the field survey of infectious diseases.</p><p><b>METHODS</b>The classical epidemiological theory was integrated with geographic information system. The transmission tracking analysis technique was established based on the modeling platform ArcGIS Engine Developer Kit 9.3, using the techniques of address matching, shortest path analysis and buffer analysis, and programming by Visual C++. Eight serious sever acute respiratory syndrome (SARS) cases in Shanghai in year 2003 were then chose as prototype to set up the test cases A-H. The electronic map and population density data were separately collected from Institute of Surveying and Mapping in Shanghai and Shanghai statistical yearbook 2003, to calculate and explore the parameters as length of transmission path, area of buffer zone and key departments by single and multi case analysis module.</p><p><b>RESULTS</b>The single case transmission tracking analysis showed that the length of transmission track of case A was 129.89 km during April 25th to 29th in 2003, including 12 tracing point and 108 intimate contacts, and the total area of buffer zone was 7.11 km(2) including 81 important institutes, naming 72 schools, 6 kindergartens and 3 gerocomiums. The multi-case transmission tracking analysis showed that the 8 cases shared 5 tracks without any temporal communication. However, there was a spatial communication whose length was 1.42 km and area was 0.60 km(2). There were no important institutes found in this communication area.</p><p><b>CONCLUSION</b>Transmission tracking technique is practicable and efficient to trace the source of infection, analyze the transmission tracks, establish the isolation buffer area and explore the important geographic positions in epidemiological investigation.</p>

Epidemiologic and genetic characteristics of hepatitis E virus in Shanghai, 1997-2012 / 中华流行病学杂志

Objective The aim of this study was to systemically analyze the epidemiologic,serological and genetic characteristics of hepatitis E virus (HEV) in Shanghai from 1997 to 2012.Methods We analyzed the data related to the epidemics of hepatitis E from China Information System for Disease Control and Prevention.We implemented serological surveillance program,based on community healthy population with enzyme-linked immunosorbent assay method and estimated the standardized sero-prevalence.We also obtained nucleotide sequences of hepatitis E patients using the nested RT-PCT assays,together with propotype sequences in the GenBank to construct a HEV genetic database in Shanghai.Results In this paper,we found that the distribution of hepatitis E patients was sporadic in the past 16 years in Shanghai.The morbidity kept declining,but with seasonal and periodical fluctuation.Morbidity in males was significantly higher than in females,with the hard hit population between 30 and 65 year-olds.In total,3979 sera samples were collected through the serological surveillance programs in 2001,2004,2007 and 2012.The standardized sero-prevalence rates of the said years were 22.32％,18.56％,10.22％ and 34.43％ which all showing strong relationship with age groups and the regions where the populations were being monitored.73 nucleotide sequences of hepatitis E patients from hospitals were identified,during 2004 and 2008.Results from phylogenetic analysis revealed that all HEV isolates belonged to genotype Ⅳ and including 4 known subtypes 4a,4d,4h and 4i which sharing 83.09％-97.96％,85.87％-97.26％ and 83.80％-95.10％ nucleotide sequence identities with the swine HEV genotype Ⅳ of GU188851,DQ450072 and EF570133.Meanwhile,59 HEV isolates from different districts shared 99％ nucleotide sequence identities with each other.Conclusion Hepatitis E would still be a challenge for long time and the zoonotic questions that related to hepatitis E,need to be explored and explained in the future.

Study on the epidemiological characteristics and incidence trend of scarlet fever in Shanghai,2005-2012 / 中华流行病学杂志

Objective To systemically analyze the epidemiological characteristics,molecular markers of circulating group A Streptococcus (GAS) isolates and the incidence trend of scarlet fever in Shanghai from 2005 to 2012 as well as to explore the practice of GAS isolates surveillance program and the combined mathematical model in the early warning of scarlet fever.Methods The morbidity series of scarlet fever were retrieved to analyze and fit the combined mathematical model which comprised an autoregressive integrated moving average (ARIMA) model and a neural network.GAS isolates surveillances programs were implemented on community healthy population,using the emm typing and superantigens detecting method in Shanghai during the epidemic period of scarlet fever in 2008,2010 and 2012.The standardized prevalence of GAS isolates was estimated with the demographic data.Results From 2005 to 2012,there were a total of 9410 scarlet fever cases reported in Shanghai including local registered residents and immigrant population,showing that the distribution of patients as sporadic.The morbidity kept rising with seasonal and periodical variations and the peak was in 2011.The average morbidity was 6.012 per 100 000 persons.Morbidity in the the suburban was significantly higher than that in the urban areas.Children at 4 to 8 years old were easy to be involved.The mean error rate of single ARIMA model,ARIMA-GRNN and back propagation artificial neural network combined model were 0.268,0.432 and 0.131 respectively.The predicted incidence of scarlet fever in 2013 would keep fluctuating within a narrow range from 0.446 to 3.467 per 100 000 persons.A total number of 4409 throat swab samples were collected through the GAS isolates surveillance programs in 2008,2010 and 2012.The standardized prevalence of GAS isolates in each year were 0.000％,0.000％ and 1.092％.18 GAS isolates were identified and 15 isolates (83.33％) belonged to emm 12.0.Conclusion The morbidity of scarlet fever would continue to maintain an upward trend in Shanghai and the techniques used in GAS isolates surveillance program and in the combined mathematical model could be applied for the early warning system on scarlet fever.

Study on the status of HBV infection and its determinants among family members with HBV infected persons in Shanghai / 中华流行病学杂志

Objective To understand the status of HBV infection among family members with HBV infected persons in Shanghai and to probe the determinants of HBV infection so as to provide evidence for improving the related strategies on hepatitis B prevention and control.Methods Three hundred and four hepatitis B patients together with 288 HBsAg carriers from 6 districts in Shanghai were randomly sampled in 2010.All the said persons and their families members were asked to fill in questionnaires and to be drawn 5 ml venous blood for HBV serologic indicators detection.The subjects were divided into case group and control group according to their status of HBV infection.Univariate analysis and multivariate logistic regression analysis were carried out to identify the determinants of HBV infection among family members.Results Among 1485 subjects from 592 households,a total of 1137 persons were infected by HBV,with the overall infection rate as 76.57％.Fifteen infection modes were noticed,in which double positive of anti-HBs and anti-HBc,triple positive of HBsAg,anti-HBe and anti-HBc,together with triple positive of anti-HBs,anti-HBe and anti-HBc accounted for the top three,with the proportions as 30.69％,26.65％ and 10.03％ respectively.The differences between the years of carrying HBV and the proportions of numbers that carrying HBV in families,were not statistically significant.The infection rate among children (42.86％) was significantly lower than that of their parents (87.54％)(P＜0.001).Results from both univariate and multivariate analysis showed that gender,age,utensil sharing,histories of receiving hepatitis B vaccines and dental outpatient service were determinants of HBV infection among families members (P＜0.05),with OR values being 9.009 for persons without immunization history of hepatitis B vaccines,3.817 for persons above 40 years old and 2.283 for persons of 21-40 years old,2.222 for families members who sharing utensil,2.124 for persons with history of dental outpatient service and 1.339 for male members,respectively.Conclusion Family clustering of HBV infection in was seen in Shanghai.In order to reduce the number of HBV infection in families,hepatitis B vaccination program need to be carried out.Healthy lifestyle should be emphasized to prevent HBV infection due to close contact.The risk of iatrogenic HBV transmission should also be prevented.

Comparison on the antibody response after primary immunization of 5 μg and 10 μg hepatitis B vaccine made bv recombinant DNA techniques among newborns / 中华流行病学杂志

Objective To compare the antibody response induced by primary immunization with 5 μ g and 10 μ g hepatitis B vaccine made by recombinant DNA techniques among the newborns.Methods Healthy infants who had completed primary immunization with 5 μg hepatitis B vaccine made by recombinant dexyribonucleic acid techniques in Saccharomyces (Hep-SC) or 10 μg hepatitis B vaccine made by recombinant dexyribonucleic acid techniques in Hansenula polymorpha (HepB-HP) were included in the study.Kids under study were 7-12 months of age and had been on 0-1-6 schedule.Standardized questionnaire was used and blood samples were collected.The titer of antibody to hepatitis B surface antigen (anti-HBs) was detected by Chemiluminescence Microparticle Imunoassay (CMIA).If anti-HBs happened to be under 10 mIU/ml,HBV DNA was further detected by nested-PCR to distinguish occult hepatitis B virus infection.Sero-conversion rate and titer of anti-HBs were compared between the two kinds of hepatitis B vaccines.Multivariate analysis was used to find the relationship between the kind of hepatitis B vaccine as well as the antibody response after debugging the other influencing factors including month-age,gender,birth-weight,premature birth and mother' s HBsAg status.Results 8947 infants vaccinated with 5 μg HepB-SC and 4576 infants vaccinated with 10 μg HepB-HP were investigated.In the 5 μg group,the rates of non-,low-,normal- and high-response were 1.88％,15.18％,61.42％ and 21.52％ respectively.In the 10 μg group,the corresponding rates were 0.15％,2.16％,29.42％ and 68.26％ respectively.The non-,low-,normal-response rates were all higher in 5 μg group than in 10 μg group (P＜0.01),while the high-response rate was much higher in 10 μg group than in 5 μ g group (P＜0.01).The geometric mean concentration (GMC) of anti-HBs were 354.81 mIU/ml (95％ CI:338.84-363.08 mIU/ml) and 1778.28 mIU/ml (95％CI:1698.24-1819.70 mIU/ml) in the 5 μg group and 10 μg group respectively.The GMC was statistically higher in the 10 μg group than in the 5 μg group (P＜0.001).The seroconversion rate and GMC were significantly different between the two groups even after debugging the other influencing factors.Conclusion Better anti-HBs response could be achieved by primary immunization with 10 μg HepB-HP than with 5 μg HepB-SC among newborns.

Study on the non-and-low response and its determinants to recombinant yeast-derived hepatitis B vaccines among neonates after primary immunization in Shanghai / 中华流行病学杂志

Objective To evaluate the non-and-low response to primary immunization of recombinant yeast-derived hepatitis B vaccines (YDVs) among neonates and to probe its determinants, in Shanghai. Methods Two thousand and forty-seven infants, born during 2008-2009 in three districts of Shanghai and administered with 3 dosages of YDVs according to 0-1-6 month schedule, were selected as subjects. Anti-HBs titers were evaluated by Chemiluminescence Microparticle Immuno Assay and related information was collected from parents through questionnaires. Univariate analysis and logistic regression model were used to probe the determinants among those infants with non-and-low response. Results The max-titer of anti-HBs in 2047 subjects was 14 982.7 mIU/ml, whereas the min-titer was 0.52 mIU/ml. The GMC was 408.04 mIU/ml after primary immunization of YDVs. The proportion of infants with titers of ＜100 mIU/ml (non-and-low response) was 17％, in which the proportion with titers of ＜ 10 mIU/ml (non response)was 1.86％ and the proportion with titers of 10-99 mIU/ml (low response) was 15.14％. Data from both univariate analysis and Ordinal logistic regression suggested that gender, age, premature labor,type of vaccines, double positive for both HBsAg and HBeAg were determinants of non-and-low response for infants, with the OR value of 1.365 for male infants, 3.133 for infants with 13-18 months old, 2.824 fo r prematured infants, 4.540 for infants administered by 5 μg YDVs and 2.298 for infants whose mother was double positive for both HBsAg and HBeAg. Conclusion Male infants,infants with 13-18 months old, prematured infants, infants administered by 5 μg YDVs and infants whose mother were double positive for both HBsAg and HBeAg had comparatively worse response for YDVs, suggesting that the anti-HBs titer surveillance programs set for these infants should be strengthened.

Establishing and applying of autoregressive integrated moving average model to predict the incidence rate of dysentery in Shanghai / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the feasibility of establishing and applying of autoregressive integrated moving average (ARIMA) model to predict the incidence rate of dysentery in Shanghai, so as to provide the theoretical basis for prevention and control of dysentery.</p><p><b>METHODS</b>ARIMA model was established based on the monthly incidence rate of dysentery of Shanghai from 1990 to 2007. The parameters of model were estimated through unconditional least squares method, the structure was determined according to criteria of residual un-correlation and conclusion, and the model goodness-of-fit was determined through Akaike information criterion (AIC) and Schwarz Bayesian criterion (SBC). The constructed optimal model was applied to predict the incidence rate of dysentery of Shanghai in 2008 and evaluate the validity of model through comparing the difference of predicted incidence rate and actual one. The incidence rate of dysentery in 2010 was predicted by ARIMA model based on the incidence rate from January 1990 to June 2009.</p><p><b>RESULTS</b>The model ARIMA (1, 1, 1) (0, 1, 2)(12) had a good fitness to the incidence rate with both autoregressive coefficient (AR1 = 0.443) during the past time series, moving average coefficient (MA1 = 0.806) and seasonal moving average coefficient (SMA1 = 0.543, SMA2 = 0.321) being statistically significant (P < 0.01). AIC and SBC were 2.878 and 16.131 respectively and predicting error was white noise. The mathematic function was (1-0.443B) (1-B) (1-B(12))Z(t) = (1-0.806B) (1-0.543B(12)) (1-0.321B(2) x 12) micro(t). The predicted incidence rate in 2008 was consistent with the actual one, with the relative error of 6.78%. The predicted incidence rate of dysentery in 2010 based on the incidence rate from January 1990 to June 2009 would be 9.390 per 100 thousand.</p><p><b>CONCLUSION</b>ARIMA model can be used to fit the changes of incidence rate of dysentery and to forecast the future incidence rate in Shanghai. It is a predicted model of high precision for short-time forecast.</p>

Study on the risk factors of HBV infection in children under the age of 15 in Shanghai / 中华流行病学杂志

Objective To identify the risk factors of HBV infection in children under the age of 15 in Shanghai and to further enhance the effectiveness of hepatitis B vaccines among children.Methods Using the data from Shanghai under the national hepatitis B serum epidemiological survey in 2006, 599 children aged 1-15 years old were selected as subjects, the subjects were divided into study group and control group by their status on HBV infection. Univariate analysis and multivariate logistic regression analysis were used to identify the risk factors of HBV infection among children.Results Out of 599 children, 15 of them were infected by HBV with the infection rate as 2.50%.Data from both univariate and multivariate analysis showed that the HBsAg status of their mothers during pregnancy, the history of hepatitis B vaccination and place of birth appeared to be risk factors of hepatitis B infection (P＜ 0.05 ), with the OR value of 5.338 for HBsAg-positive mother, 42.118 for no history of hepatitis B vaccination and 12.239 for home-delivery, respectively. Conclusion In order to further decrease the rate of HBV infection among children in Shanghai, intervention should be focusing on both migrant and HBsAg-postive pregnant women. Also, the condition of hepatitis B vaccine immunization for newborns in some township hospitals should be improved.

Phylogenetic analysis of sporadic hepatitis E virus in Eastern China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand phylogenetic characteristics of sporadic hepatitis E virus (HEV) in eastern China.</p><p><b>METHODS</b>Four hundred and thirteen sera were collected from sporadic hepatitis E cases in 14 second- or first-class hospitals in Eastern China from 2005 to 2008 and detected with a nested RT-PCR assay. Partial nucleotide sequences of the HEV isolates were determined for phylogenetic analysis with prototype sequences in the GenBank.</p><p><b>RESULTS</b>The male-to-female sex ratio of the patients was 1.75:1 with 61.5% of them aged 40 - 69 years old. HEV RNA was detected in 140 out of 413(34%)serum samples. Phylogenetic analysis revealed that all the 140 HEV isolates belonged to genotype IV, sharing 77.9% - 88.3%, 80.8% - 90.6%, 73.4% - 85.2% and 91.0% - 95.4% nucleotide sequence identities with prototype I, II, III and IV HEV isolates respectively.</p><p><b>CONCLUSION</b>It was evident that genotype IV HEV served as the main causative agent of sporadic HEV infection in Eastern China. However the viral origin and evolution needs further clarification.</p>

Application of time series analysis in the prediction of incidence trend of influenza-like illness in Shanghai / 中华预防医学杂志

<p><b>OBJECTIVE</b>To forecast incidence trend of influenza-like illness in Shanghai.</p><p><b>METHODS</b>We collected everyday-report influenza-like illness surveillance information from January, 2004 to April, 2006 and used autoregressive integrated moving average model (ARIMA) to analyze and establish prediction model. 114 weeks preceding information was used to establish model and 9 weeks data to evaluate.</p><p><b>RESULTS</b>Model ARIMA (1,0,0) (1,1,0) 26 from Surveillance information was both with seasonal and non-seasonal features (P < 0.001). White noise analysis show the minimum Box-Ljung value of autocorrelation function was 0.803 (P > 0.1) and the residual was randomized difference. We established prediction model as lgY(t) = 0.879 lgY(t-1) + 0.418 lgY(t-26) - 0.367 lgY(t-27) + 0.582 lgY(t-52) - 0.512 lgY(t-53) and forecasting effect was well. True values were all between 95% CI of predicted ones.</p><p><b>CONCLUSION</b>ARIMA model can be well used to simulate incidence trend of influenza-like illness in Shanghai.</p>

Study on risk factors of sporadic hepatitis E virus cases in some districts of Shanghai / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the risk factors of acute sporadic hepatitis E virus (HEV) cases and to analyze its partial sequence in some districts of Shanghai.</p><p><b>METHODS</b>30 blood samples were collected from the acute sporadic HEV cases in 2003-2004 and the RT-nPCR method was applied to obtain the sequence of HEV in these cases. Meanwhile, a 1:2 case-control study was used to identify risk factors in the process of sporadic HEV infection in these regions of Shanghai.</p><p><b>RESULTS</b>Data from the sequential analysis showed that HEV of the sporadic cases belonged to HEV genotype IV. Finding from the case-control study implicated that the housing condition, outside eating history, especially seafoods (OR = 7.048) played an important role in the infection of HEV. Results from multiple logistic regression showed that eating raw seafoods appeared to be one of the risk factors of HEV infection.</p><p><b>CONCLUSION</b>HEV sequences isolated from the sporadic cases of HEV in some districts of Shanghai belonged to HEV genotype IV. Foods, especially seafood, were the risk factors in the infection of HEV.</p>

Surveillance of hemagglutinin genetic variation of influenza viruses in Shanghai and Wuxi / 中华传染病杂志

Objectives To explore the type and subtype distribution of influenza viruses in influenza-like patients and the hemagglutinin(HA)genetic variation of influenza A viruses in Shang- hai and Wuxi during the influenza prevalent season from 2004 to 2006.Methods Throat swabs were collected from the influenza-like patients in the sentinel hospitals and during the outbreaks,and then inoculated into MDCK cells to isolate influenza viruses,which were subsequently identified by direct immunofluorescence(DIF)and reverse transcription-polymerase chain reaction(RT-PCR).HA seg- ments of influenza A viruses were sequenced to analyze the genetic variation of HA.Results One hundred and twenty-six strains of influenza viruses,including 53 H3N2,43 H1N1 and 30 influenza B viruses were isolated from August 2004 to September 2006,and 7 outbreaks.All these outbreaks oc- curred in February or March The pathogens were identified as H1N1 in one outbreak,H3N2 in two outbreaks,B in two outbreaks and mix infections in two outbreaks(1 H1N1 and B,1 H3N2 and B, respectively).By sequencing the HA segment,the H3 and H1 segments were all homologous to the isolates from different countries in the same period.Conclusion H3N2 and H1N1 are the major strains prevalent in Shanghai and Wuxi,which reach the peak from January to March No HA and NA recom- binant strains and new HA and NA subtypes are found in these areas.The variations of H1 and H3 are similar to those found in other countries.