Background Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. Methods We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. Results During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. Conclusion The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously.

ABSTRACT Background Rotavirus infections, prevalent in human populations, are caused mostly by group A viruses. Immunization against rotaviruses in infancy is currently the most effective and economical strategy to prevent rotavirus infection. This study evaluated the safety of a novel hexavalent rotavirus vaccine and analyzed its dose and immunogenicity. Methods This randomized, double-blinded, placebo-controlled phase I clinical trial enrolled healthy adults, toddlers, and infants in Zhengding County, Hebei Province, northern China. 40 adults and 40 children were assigned in a 2:1:1 ratio to receive one vaccine dose, placebo 1, and placebo 2, respectively. 120 6–12 week old infants were assigned equivalently into 3 groups. The infants in each group were assigned in a 2:1:1 ratio to receive three doses of vaccine, placebo 1, and placebo 2, at a 28-day interval. Adverse events (AEs) until 28 days after each dose and serious adverse events (SAEs) until 6 months after the third dose were reported. Virus shedding until 14 days after each dose in infants was tested. Geometric mean concentrations (GMCs) and seroconversion rates were measured for anti-rotavirus IgA by using an enzyme-linked immunosorbent assay (ELISA). Results The solicited and unsolicited AE frequencies and laboratory indexes were similar among the treatment groups. No vaccine-related SAEs were reported. The average percentage of rotavirus vaccine shedding in the infant vaccine groups was 5.00%. The post-3rd dose anti-rotavirus IgA antibody geometric mean concentrations (GMC) and seroconversion rate were higher in the vaccine groups than in the placebo groups. Conclusions The novel oral hexavalent rotavirus vaccine was generally well-tolerated in all adults, toddlers and infants, and the vaccine was immunogenic in infants.

In 1996, 3,515 susceptible children aged one to 12 years were recruited in a randomized, open trial to assess the efficacy of a live-attenuated HA vaccine. A comprehensive and systematic assessment of long-term persistence of anti-HAV antibodies, as well as protection against infection conferred by vaccine was performed based on this cohort. During the 17-year follow-up, the sero-positive rate and the geometric mean concentrations declined from 94.9% and 131.3 mIU/mL (91.5-188.4mIU/mL) at the peak to 55.6% and 41.1 mIU/mL (95% CI: 27.8-61.0 mIU/mL) respectively, with a similar natural infection rate in both groups. These results suggest that a booster dose is currently not necessary.

Rotaviruses (RVs) are the leading cause of acute gastroenteritis in children, while histo-blood group antigens (HBGAs) are believed to be host attachment and susceptibility factors of RVs. A large case–control study nested in a population-based diarrhea surveillance targeting children <5 y of age was performed in rural Hebei province, north China. Saliva and serum samples were collected from all participants to determine HBGA phenotyping, FUT2 mutations, and RV IgG antibody titers. A logistic model was employed to assess the association between host HBGA secretor status and risk of RV infection. Among 235 RV cases and 680 non-diarrhea controls studied, 82.4% of participants were IgG positive by an average age of 77 months. Out of the 235 RV cases, 216 (91.9%) were secretors, whereas the secretor rate was 76.3% in the non-diarrhea controls, resulted in an adjusted OR of 3.0 (95%CI: 1.9–4.7, P < .0001) between the two groups. Our population-based case–control study indicated a strong association between host HBGA secretor status and risk of RV infection in Chinese children. The high prevalence of Lewis-positive secretor status strongly suggests that Chinese children may be genetically susceptible to current co-circulating RV strains, and thus, a universal childhood immunization program against RV disease should be successful in China.

Objective: To assess the immune effect of different types of hepatitis B vaccine (HepB) booster doses 2-32 years after primary immunization, explore the influencing factors, and offer guidance regarding the necessity and timing of boosters. Methods: In total, 1163 participants who were born from 1986 to 2015, received the HepB full-course primary vaccination, were hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) negative, and had hepatitis B surface antibody (anti-HBs) <10 mIU/mL were enrolled. Individuals were randomly divided into two groups and received a booster dose of HepB. Venous blood samples were collected 30 days later and tested for anti-HBs. Results: In total, 595 and 568 individuals received a single dose of HepB (CHO) and HepB (SC), respectively. Venous blood samples were obtained from 1079 vaccinees (CHO: 554, SC: 525). The seroconversion rates were 93.68% (519/554) and 86.67% (455/525) (p < 0.05), with geometric mean concentrations (GMCs) of 426.58 mIU/ml and 223.8 mIU/ml, respectively. This result indicated that BMI, smoking status, vaccine types of booster and prebooster anti-HBs concentration significantly influenced anti-HBs levels. Only BMI, prebooster anti-HBs concentrations and booster types were different between the anti-HBs positive and negative groups. Conclusions: Participants boostered with HepB (CHO) had a relatively higher seroconversion rate than those boostered with HepB (SC). The high seroconversion rates in the two groups suggested that the subjects remained protected despite low circulating antibodies, so there is currently no urgent need for booster immunization. Factors including BMI > 25 and prebooster anti-HBs concentration <2.5 mIU/mL, which contributed to lower responses to a booster dose, might indicate a greater risk of breakthrough infection. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Background: Despite the considerable disease burden caused by the disease, rotavirus vaccine has not been introduced into routine national immunization schedule, and norovirus vaccines are being developed without a comprehensive understanding of gastroenteritis epidemiology. To bridge this knowledge gap, we investigated the disease burden of viral gastroenteritis in rural China. Methods: Between October 2011 and December 2013, population-based surveillance was conducted in Zhengding and Sanjiang counties in China. Stool samples were collected from children <5 years of age with diarrhea. All specimens were tested for rotaviruses, noroviruses, sapoviruses, enteric adenoviruses, and astroviruses. Results: The most common pathogen causing diarrhea was rotavirus (54.7 vs 45.6 cases/1,000 children/year in Zhengding and Sanjiang, respectively), followed by norovirus (28.4 vs 19.3 cases/1,000 children/year in Zhengding and Sanjiang, respectively). The highest incidence of these viruses was observed in children 6-18 months of age. Among the 5 viral pathogens, rotaviruses caused the most severe illness, followed by noroviruses. Conclusion: Rotavirus and norovirus are the 2 most important viral pathogens causing childhood diarrhea in both northern and southern China; they should be the major targets for viral gastroenteritis prevention strategies among children in China. (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Objective: Aanalysis the effect of booster one dose of hepatitis B vaccine after 21-32 years of primary immunization in Zhengding Country of Hebei Province. Methods: A total of 322 participants who were born between 1986 and 1996, received a full course of primary vaccination with plasma-derived hepatitis B vaccine (HepB), had no experience with booster vaccination, were HBsAg, anti-HBcnegative, had anti-HBs<10 mIU/ml, completed the booster and had laboratory results were enrolled between August 2017 to February 2018. A simple random method was uesd to randomly assigned 322 subjects to two groups, receiving a booster dose of HepB derived from either Saccharomyces cerevisiae ［HepB (SC), (151 cases)］ or Chinese hamster ovary-derived HepB ［HepB (CHO), (171 cases)］, the dose was 20 μg. Blood samples were collected 30 days after boosting and quantitatively tested for the geometric mean concentration (GMC) of anti-HBs to assess immunological effect. The related influencing factors of GMC and seroconversion rates of anti-HBs were analyzed by multiple linear regression and multivariate logistic regression models. Results: The 266 subjects (82.61%) had anti-HBs≥ 10 mIU/ml, and GMC was (131.63±12.94) mIU/ml.The seroconversion rates of anti-HBs in the anti-HBs<2.5 mIU/ml group and 2.5-10 mIU/ml group were 74.54% (161 cases) and 99.06% (105 cases), respectively (P<0.001).The seroconversion rates of anti-HBs after one dose of HepB (CHO) was higher than that of one dose of HepB (SC), the seroconversion rates were 87.13% (149 cases) and 77.48% (117 cases), respectively (P=0.023). Participants boostered with HepB (CHO) was the factor influencing the effect of strengthening immunization compared with boostered with HepB (SC), and OR (95%CI) was 1.91 (1.02-3.56) (P=0.042).Compared with anti-HBs<2.5 mIU/ml, prebooster anti-HBs was between 2.5 mIU/ml and 10 mIU/ml was the related factor of seroconversion rates of anti-HBs after booster immunization, and OR (95%CI) was 36.15 (4.91-266.02) (P<0.001). Conclusion: Participants boostered withone dose of HepB had a good immune response. Pre-booster anti-HBs concentration and a variety of vaccine were related factors of immune response.

目的 观察新生儿重组乙型肝炎疫苗(CHO细胞)(HepB-CHO)基础免疫后3-6年血清学效果.方法 于2018年选择河北省正定县4个乡2011-2014年出生且已按0-1-6月免疫程序接种3剂次10μg HepB-CHO的儿童,检测免疫后3-6年血清乙肝表面抗体(HBsAb)、乙肝表面抗原(HBsAg)和乙肝核心抗体(HBcAb).结果 观察对象HepB-CHO基础免疫后HBsAb总阳性率为69.3％ (739/1 067),其中2011年、2012年、2013年、2014年出生儿童HBsAb阳性率分别为64.0％(155/242)、68.8％(179/260)、70.1％(213/304)、73.6％(192/261);HBcAb总阳性率为0.19％(2/1 067),其中2011年、2012年、2013年、2014年出生儿童HBcAb阳性率分别为0.00％(0/242)、0.00％(0/260)、0.33％(1/304)、0.38％ (1/261);HBsAg总阳性率为0.00％ (0/1 067).结论 本研究重组HepB-CHO新生儿免疫后3-6年血清学效果良好.

To assess the immune persistence conferred by a Chinese hamster ovary (CHO)-derived hepatitis B vaccine (HepB) 17 to 20 years after primary immunization during early life. Participants born between 1997 and 1999 who received a full course of primary vaccination with HepB (CHO) and who had no experience with booster vaccination were enrolled. Blood samples were required from each participant for measurement of hepatitis B surface antibody (anti-HBs), surface antigen and core antibody levels. For those who possessed an anti-HBs antibody < 10 mIU/mL, a single dose of HepB was administered, and 30 days later, serum specimens were collected to assess the booster effects. A total of 1352 participants were included in this study. Of these, 1007 (74.5%) participants could retain an anti-HBs antibody ≥10 mIU/mL, with a geometric mean concentration (GMC) of 57.4 mIU/mL. HBsAg was detected in six participants, resulting in a HBsAg carrier rate of 0.4% (6/1352). Of those participants with anti-HBs antibodies < 10 mIU/mL, after a challenge dose, 231 (93.1%) presented an anti-HBs antibody ≥10 mIU/mL, with a GMC of 368.7 mIU/mL. A significant increase in the anti-HBs positive rate (≥ 10 mIU/mL) after challenge was observed in participants with anti-HBs antibodies between 2.5 and 10 mIU/mL and participants boosted with HepB (CHO), rather than those with anti-HBs antibodies < 2.5 mIU/mL and those boosted with HepB (SC). Since satisfactory immune protection against HBV infection conferred by primary vaccination administered 17–20 years ago was demonstrated, there is currently no urgent need for booster immunization.

Background: In recent years, hepatitis A virus (HAV) infection has declined considerably in China, associated with wide deployment of HAV vaccines and improvement in socio-economic indicators. Towards the elimination of HA in the country, we assessed the duration and characteristics of immunity conferred by the widely used, locally manufactured HAV vaccine. Methods: This is a longitudinal cohort study that followed recipients of a live attenuated HAV vaccine 17 years after the initial administration. Blood samples were collected from participants pre- and two-week post-booster HAV vaccine dose. Serum anti-HAV antibody was measured by ELISA method. Memory B and T cells were determined by ELISPOT and Flow Cytometry assays, respectively. Results: A robust anamnestic response was observed two-week post-challenge. Both HAV-specific memory B cell and T cells remained, and responded quickly when re-encountering HAV. The magnitude of recall responses was present, regardless of the status of the serum anti-HAV antibody pre-booster. Conclusions: We demonstrated long-term immunity from the live attenuated HAV vaccine, including antibody persistence and immunological memory. Considering the conditions that make elimination of infectious diseases feasible, following polio, hepatitis A could be targeted for elimination in China. (C) 2017 Elsevier Ltd. All rights reserved.

To understand the distribution of genotyping, as well as evolution of norovirus circulating among children<5yrs., a population-based diarrhea surveillance targeted children<5yrs. was conducted in rural Zhengding County, Hebei Province, China between October 2011 and March 2012. RT-PCR was used to amplify the capsid-encoding region of GI and GII norovirus to identify norovirus infection. All PCR products were sequenced and analyzed for genotyping and constructing phylogenetic tree. Dynamic distribution network was constructed by TempNet to illustrate the genetic relationships at two different time points. Bayesian evolutionary inference techniques were applied by BEAST software to study the norovirus evolution rate. During the 6-month surveillance period, 1091 episodes of diarrhea were reported from 5633 children under 5years of age lived in catchment area. 115 of 1091 stool specimens were detected as norovirus positive (10.54%). Five genotypes based on capsid gene sequences were identified, including GII.2 (11), GII.3 (52), GII.4 (47), GII.6 (4) and GII.7 (1). An identical haplotype of GII.4 circulated between 2006 and 2011 in Hebei Province. A mean rate of 6.29×10−2 nucleotide substitutions/site/year (s/s/y) was obtained for GII.3 viruses in Hebei, while the GII.4 viruses evolved at a mean rate of 3.67×10−2s/s/y. In conclusions, GII.3 (45.22%) and GII. 4(40.87%) are the predominant strain in Hebei Province in the winter season of 2011 and 2012. Different from the current consensus, our study shows that GII.3 noroviruses in Hebei Province evolved at a faster rate than GII.4 viruses.

[目的]观察正定县粉尘作业工人肺功能检查结果,探讨影响当地粉尘作业工人肺功能结果的主要影响因素.[方法]选取2015年1月-12月在正定县疾病预防控制中心进行在岗期间职业健康检查的1 014例接触粉尘作业的工人,按照粉尘类型、接尘工龄、车间空气中粉尘浓度、是否采取防护措施等方式分成不同组别,观察并比较不同组别肺功能检查结果.[结果]接触不同类型粉尘工人的肺功能异常检出率比较,差异有统计学意义(P＜0.05),其中以接触煤尘工人的异常检出率(23.1％)最高,接触木粉尘工人(9.5％)最低.接触无机粉尘作业者肺功能异常检出率(19.51％)高于有机粉尘(9.51％),差异有统计学意义(P＜0.05).随着接尘工龄的增加、车间空气粉尘浓度增加,接触工人的肺功能异常检出率均有逐渐增加趋势(P＜0.05).经常佩戴防护用品的工人肺功能异常检出率(7.85％)低于不经常佩戴防护用品的工人(32.40％),差异有统计学意义(P＜0.05).[结论]粉尘作业工人应当按照粉尘作业体检周期进行职业健康检查,了解自身肺功能状况,平时要加强自我防护意识,养成佩戴防护用品的习惯,避免长时间在粉尘环境中工作,主动预防尘肺病.

Objective: To evaluate the long-term efficacy of Chinese hamster ovary (CHO) cell derived hepatitis B vaccine after being used for 14-16 years in country community in Hebei province in China.Method: A cross-sectional investigation was carried out in 3 of 7 randomly selected rural communities in Zhengding County in 2013. The children who were born between 1997 and 1999 and were vaccinated with three doses of CHO-derived hepatitis B vaccine were eligible to participate in the study. Their sera samples were tested for HBV serological markers. For HBsAg positive children, their historical results were compared, in order to see whether these were new infections.Results: Among the 920 participating children, the prevalence of HBsAg, anti-HBs and anti-HBc were 0.65%, 73.15% and 1.20% respectively. The differences between birth-year groups were not significant. When compared with baseline, the vaccine efficacy was 94.2% and the anti-HBs titers of 668 children with sole anti-HBs positivity were 178.8 mIU/ml. By comparing with historical data, no new infection was found in this latest survey. Among 6 mothers of HBsAg positive children, 4 were HBsAg positive, 1 was negative and 1 was unknown.Conclusion: The long-term efficacy of the CHO derived hepatitis vaccine is good and stable for 14-16 years after vaccination. A booster dose seems not necessary. Implementing mother-newborn blocking measures for newborns from HBsAg carrier mothers is urgently needed in the future. (C) 2014 Elsevier Ltd. All rights reserved.

A universal rotavirus (RV) immunization program is a potentially cost-effective measure for preventing RV infection in China. However, the efficacy of the only licensed RV vaccine (Lanzhou lamb rotavirus vaccine, LLR), which is made by a domestic manufacturer, has not been proven by a properly designed clinical trial. In October 2011 to March 2012, to measure the potential protection provided by LLR, a case-control study nested in a population-based active diarrhea surveillance study of children <5 years of age was conducted in rural Zhengding county. During the study period, 308 episodes of diarrhea were identified as being caused by RV infection, resulting in an incidence rate of 48.0/1000 people/year. The predominant RV serotype was G3 (61.5%), followed by G1 (15.2%), and G9 (6.5%). Overall, a protection of 35.0% (95% confidence interval (CI), 13.0%-52.0%) was identified, and higher protection was found among moderate RV gastroenteritis cases caused by the serotype G3 (52.0% 95% CI: 2.0%-76.1%). A concurrently conducted case-control study comparing non-RV viral diarrheal cases with non-diarrheal controls in the same population found that the RV vaccine offered no protection against non-RV diarrhea. Even under a less ideal immunization schedule, the oral LLR conferred a certain level of protection against RV gastroenteritis. However, further studies are needed to understand the full characteristics of the LLR, including its efficacy when administered following the optimal regimen, the potential risk of inducing intussusception, and the direct and indirect protective effects of LLR.

Objective: To study the epidemiological patterns of hepatitis A, and immunity of entire population in Shijiazhuang prefecture, Hebei province, a former hyper-endemic area in north China.Methods: Cross-sectional, seroprevalence surveys with two-stage cluster sampling were conducted among population older than 2-year between 1992 and 2011. During the 2011 serological survey, blood samples from infants <18 months without hepatitis A immunization history were also collected to determine maternal anti-HAV antibody. Serum samples were tested for anti-HAV antibody by domestic reagent or Abbott reagent Viral hepatitis incidence rates and gross domestic product data were derived from local governmental statistics.Results: Concomitant with the reduction of reported hepatitis A cases between 1992 and 1996 was a significant decline of HAV infections. The average prevalence decreased from 93.6% to 41.9%, and the average age at new infection was postponed from infancy to adolescence. This was attributed to improved socio-economic conditions. With intensive vaccination, a return of new seroconversion rate and seroprevalence was observed. A well fitted exponential regression equation (R-2 = 0.96, p < 0.0001) modeled that the maternal antibody would wane to <20 mIU/mL at 13 months.Conclusion: Benefiting from the booming economy, rapid improvement in sanitation, safe water supply, and implementation of hepatitis A vaccines, the epidemiological pattern of hepatitis A moved from high to intermediate endemicity in Shijiazhuang. Policy makers should be aware of the waning of immunity in entire population, and adapt immunization strategy timely, to ensure a lifelong protection against hepatitis A virus. (C) 2014 Elsevier Ltd. All rights reserved.

Objective To study the HBeAg spontaneous seroconversion among chronic HBV infection.Methods A chronic HBV infection cohort with 172 HBsAg/HBeAg positive carriers was set up through the cross-sectional serological survey in 8 villages of Zhengding county,Hebei province in 1999,2005 and 2006.Serum specimens were collected from all carriers during the follow-up at 2010 and 2012,and were tested for anti-HBs,HBsAg,anti-HBe,HBeAg,HBV DNA,as well as ALT.Results Loss of HBeAg were detected from 32 carriers,the annual rate was 2％ (95％ CI:1.4％-2.8％).Of these,HBeAg seroconversion occurred in 26 carriers,the annual spontaneous HBeAg seroconversion rate was 1.6％ (95％CI:1.1％-2.4％).Conclusion Spontaneous HBeAg seroconversion could be observed in rare cases among chronic HBV carriers,coming along with the significant decrease of HBV DNA and HBsAg level.

OBJECTIVE:To understand the long-term immunological effects of a recombined hepatitis B vaccine [HepB made by recombinant deoxyribonucleic acid (DNA) techniques in Chinese hamster ovary (CHO) cell, HepB (CHO)].METHOD:from 1997 to 1999 all newborns in Zhengding County were administered to HepB (CHO)at birth. Children in 3 of all 7 towns in the county were selected as study objects to check their hepatitis B vaccination history and test for HBV markers.RESULTS:Children who aged 10, 11 and 12 years after immunization, the anti-HBs positive rates were 71.0%, 72.1% and 68.2% respectively, and the geometric mean concentration (GMCs)were 197.9 mIU/ml, 296.0 mIU/ml and 158.0 mIU/ml respectively; Anti-HBs GMCs were 197.9 mIU/ml, 296.0 mIU/ml and 158.0 mIU/ml respectively. The Average GMC was 207.9 mIU/ml. HBsAg and anti-HBc positive rates were 0.50% and 2.26% respectively.CONCLUSION:The long-term immunological effects of HepB (CHO) are excellent.

甲型病毒性肝炎(甲肝)疫苗的问世为预防和控制甲肝的流行提供了有效的预防措施.尤其是国产甲肝减毒活疫苗的诞生,因其价格低廉、有效,更适于在经济尚不发达的农村地区推广使用.甲肝减毒活疫苗免疫的持久性、是否需要加强免疫以及如何加强免疫,一直是人们非常关心的问题.本研究在甲肝减毒活疫苗1针法免疫的基础上,尝试了2针法加强免疫,并对免疫后2组的抗体持久性进行了观察比较,以期对加强甲肝减毒活疫苗的免疫效果提供科学依据.

OBJECTIVE:To observe the immunological effects of three doses of H2 strain live attenuated hepatitis A vaccine 8 years after the administration and to compare with that of one dose of the vaccine.METHODS:In a country area, 110 children of 1 to 7 years old susceptible to HAV were screened and administered with one dose of the vaccine, as group B; Group A were 42 children from one of the villages and administered with 3 doses of the vaccine according to 0, 2, 6 month schedule. Blood samples were taken for the children 1, 2, 6, 7, 8, 12, 24, 36 and 96 months after the administrations respectively and detected for anti-HAV antibody.RESULTS:For group B, the sero conversion rate of anti-HAV and GMC reached peak at 92.2% and 126.2 mIU/ml respectively, and then, began to drop with time; For group A, after 2 dose of the vaccine, the sero-conversion rate reached 100%, and the GMC reached peak of 2 739 mIU/ml one month after the third dose at 7 months. So that, group A has a better short-term immunological effects than that of group B. During 36 through 96 months, the anti-HAV positive rate in group B was 75%-71% and 80-89 mIU/ml respectively, and comparatively in group A were 100% and 918.2-480.6 mIU/ml respectively. The differences between group A and B were significantly important.CONCLUSION:A 3-dose schedule administration of H2 strain live attenuated hepatitis A vaccine has better immunological effects than 1-dose schedule in 8years and further observations are needed.