Objective:To analyze the epidemiological characteristics and clinical features of pertussis cases reported in Shandong Province of China.Methods:Data on pertussis cases in Shandong Province from 2007 to 2022 were collected from China Information System for Disease Control and Prevention. At the same time, some case information was collected from the database of notifiable pertussis in Shandong Province from 2007 to 2022. The distribution characteristics and clinical features of pertussis were analyzed. A spatial distribution map of pertussis cases in Shandong Province was drawn.Results:A total of 26 122 pertussis cases were reported in Shandong Province during 2007-2022, with an annual incidence rate ranging from 0.11 to 5.77 cases per 100 000 people. Cases occurred throughout the whole year, with a seasonal peak occurring in spring and summer, especially in July and August. In recent years, reported cases were mainly distributed in the central and western regions of Shandong Province, with fewer cases in the eastern region. The hot spots of the disease shifted from Heze and Dezhou City in 2007-2013 to Jinan and Tai′an city in 2014-2022. The age range of onset was from 1 day to 93 years old. The proportion of cases with age≤1 year was the largest (41.81%, 10 922/26 122), and the proportion of cases aged 0-6 months decreased from 32.21% (67/208)-55.67% (157/282) within the period of 2007 to 2013 to 16.78% (883/5 263)-41.97% (444/1 058) within the period of 2014 to 2022, with a statistically significant trend ( χ2 trend=670.01, P<0.001). There were 13 682 male cases and 12 440 female cases, with a male-female ratio of 1.10∶1. The male-female ratio was 1.45∶1 (806∶556) from 2007 to 2013 and 1.08∶1 (12 876∶11 884) from 2014 to 2022. The proportion of women increased from 42.31% (88/208) in 2007 to 47.84% (2 518/5 263) in 2022, and with a significant trend ( χ2 trend=22.25, P<0.001). In pertussis cases, the proportions of scattered children, kindergarten children and students were 71.38% (18 645/26 122), 15.13% (3 951/26 122), and 11.60% (3 031/26 122), respectively. The top five clinical symptoms of pertussis cases were paroxysmal spasmodic cough (86.33%, 21 411 cases), flushing (39.61%, 9 824 cases), restless sleep (34.51%, 8 558 cases), fever (30.80%, 7 638 cases), and crowing (27.53%, 6 829 cases). Among 24 802 cases, there were 15 542 cases (62.66%) with a history of immunization against pertussis vaccine. Conclusion:From 2007 to 2022, the incidence rate of pertussis cases in Shandong Province shows an upward trend, with the majority being young children, and the clinical symptoms are relatively typical.

Objective:Assess the 10-year Immune persistence and the predictors after primary vaccination hepatitis B vaccine (HepB) among normal and high-responder infants.Methods:A total of 1 838 Infants of 7-12 months old located in Jinan, Weifang, Yantai and Weihai of Shandong Province who were induced normal or high antibody response (anti-HBs titer ≥ 100 mIU/ml) after primary vaccination (three dose with 0-1-6 procedure) with 5 μg recombinant HepB among newborns were included in the study, in 2009. 3 ml of venous blood samples were collected at baseline survey (T 0) and antibodies against hepatitis B surface antigen (anti-HBs), antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected using chemiluminescence microparticle immunoassay (CMIA) method. A self-designed questionnaire was used to collect information including the infant′s age, sex, birth weight, premature birth, birth number, delivery location and mother′s HBV infection status. In 2014 (followed up for 5 years) and in 2019 (followed up for 10 years) (T 1), 2 ml of venous blood samples were collected. Anti HBS and anti HBC were detected by CMIA method. Those with anti HBS<10 mIU/ml were detected by CMIA method. Multivariate unconditional logistic and linear regression models were used to analyze the influencing factors of anti-HBs positive rate and geometric mean concentration (GMC) at T 1. Results:After 10 years follow-up, 73.94% of the subjects (1 359/1 835) finished the follow-up. 51.15% of the subjects, a total of 625 were boys. The positive rate of anti-HBs was 100% at T 0 and decreased to 53.44% (95% CI: 50.59%-56.26%) at T 1. The average annual decline rate of anti-HBs positive rate from T 0 to T 1 was 6.07%. The GMC of anti-HBs decreased from 607.89 (95% CI: 579.01-642.62) mIU/ml to 16.44 (95% CI: 15.06-18.00) mIU/ml. The average annual decline rate of anti-HBs GMC in 10-year follow-up was 30.30%. Multivariate logistic analysis showed that the positive rate of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time ( OR=0.25, 95% CI:0.07-0.71). Compared with those with GMC<1 000 mIU/ml at T 0, those with GMC ≥ 1 000 mIU/ml had a higher positive rate of anti-HBs at T 1 ( OR=2.29, 95% CI:1.76-2.97). Multivariate regression analysis showed that the GMC of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time (β=-0.50, 95% CI:-1.24-0.24). Compared with those with GMC<1 000 mIU/ml at T 0, those with GMC ≥ 1 000 mIU/ml had a higher GMC of anti-HBs at T 1 (β=0.81, 95% CI: 0.62-1.05). Conclusion:Anti-HBs GMC decreased in 10 years after primary vaccination of 5 μg recombinant hepatitis B vaccine among normal and high-responders. The anti-HBs persistence was mainly associated with whether the first dose was vaccinated in time and the level of anti-HBs at the end of primary vaccination.

Objective:Assess the 10-year Immune persistence and the predictors after primary vaccination hepatitis B vaccine (HepB) among normal and high-responder infants.Methods:A total of 1 838 Infants of 7-12 months old located in Jinan, Weifang, Yantai and Weihai of Shandong Province who were induced normal or high antibody response (anti-HBs titer ≥ 100 mIU/ml) after primary vaccination (three dose with 0-1-6 procedure) with 5 μg recombinant HepB among newborns were included in the study, in 2009. 3 ml of venous blood samples were collected at baseline survey (T 0) and antibodies against hepatitis B surface antigen (anti-HBs), antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected using chemiluminescence microparticle immunoassay (CMIA) method. A self-designed questionnaire was used to collect information including the infant′s age, sex, birth weight, premature birth, birth number, delivery location and mother′s HBV infection status. In 2014 (followed up for 5 years) and in 2019 (followed up for 10 years) (T 1), 2 ml of venous blood samples were collected. Anti HBS and anti HBC were detected by CMIA method. Those with anti HBS<10 mIU/ml were detected by CMIA method. Multivariate unconditional logistic and linear regression models were used to analyze the influencing factors of anti-HBs positive rate and geometric mean concentration (GMC) at T 1. Results:After 10 years follow-up, 73.94% of the subjects (1 359/1 835) finished the follow-up. 51.15% of the subjects, a total of 625 were boys. The positive rate of anti-HBs was 100% at T 0 and decreased to 53.44% (95% CI: 50.59%-56.26%) at T 1. The average annual decline rate of anti-HBs positive rate from T 0 to T 1 was 6.07%. The GMC of anti-HBs decreased from 607.89 (95% CI: 579.01-642.62) mIU/ml to 16.44 (95% CI: 15.06-18.00) mIU/ml. The average annual decline rate of anti-HBs GMC in 10-year follow-up was 30.30%. Multivariate logistic analysis showed that the positive rate of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time ( OR=0.25, 95% CI:0.07-0.71). Compared with those with GMC<1 000 mIU/ml at T 0, those with GMC ≥ 1 000 mIU/ml had a higher positive rate of anti-HBs at T 1 ( OR=2.29, 95% CI:1.76-2.97). Multivariate regression analysis showed that the GMC of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time (β=-0.50, 95% CI:-1.24-0.24). Compared with those with GMC<1 000 mIU/ml at T 0, those with GMC ≥ 1 000 mIU/ml had a higher GMC of anti-HBs at T 1 (β=0.81, 95% CI: 0.62-1.05). Conclusion:Anti-HBs GMC decreased in 10 years after primary vaccination of 5 μg recombinant hepatitis B vaccine among normal and high-responders. The anti-HBs persistence was mainly associated with whether the first dose was vaccinated in time and the level of anti-HBs at the end of primary vaccination.

Objective:To evaluate the persistence of HBsAg-specific antibodies eight years after revaccination with hepatitis B vaccine (HepB) among adults who were non-responsive to primary immunization.Methods:From August to September 2009, rural communities in Zhangqiu district of Ji'nan city were selected as the study site. The subject's inclusion criteria were 18 to 49 years old, local resident population, without HBV infection history and HepB vaccination history, and good health status. Antibodies against hepatitis B surface antigen (anti-HBs) were detected in adults following the standard primary vaccination. Those who were non-responders (anti-HBs titer <10 mIU/ml) were revaccinated with three doses of HepB and included in the study. Blood samples were collected from all of them at one month (T 1), two years, four years, and eight years after revaccination. The three indexes of anti-HBs, hepatitis B surface antigen (HBsAg), together with antibody against hepatitis B core antigen (anti-HBc), were measured by chemiluminescence microparticle immunoassay (CMIA). Results:The proportion of subjects with anti-HBs titers ≥10 mIU/ml was 85.12% (549/645) at T 1, 60.60% (283/467) at two years, 55.90% (199/356) at four years and 55.09% (222/403) at eight years after revaccination. The first two years' annual decline rates, three to four years and five to eight years, were 15.62%, 3.96%, and 0.36%. The GMC of anti-HBs was 153.92 mIU/ml at T 1, 21.43 mIU/ml at two years, 15.02 mIU/ml at four years, and 13.68 mIU/ml at eight years. In the first two years, three to four years and five to eight years, the annual decline rate of GMC was 62.69%,16.28%, and 2.31%, respectively. Multivariable analysis showed that the titer of anti-HBs at T 1 was independently associated with the persistence of anti-HBs at eight years after revaccination. Compared with anti-HBs titer <100 mIU/ml , those whose anti-HBs titers were 100-mIU/ml and ≥1 000 mIU/ml at T 1 had a higher positive rate of anti-HBs ( OR=14.13, P<0.001; OR= 62.91, P<0.001) and a higher probability of anti-HBs titer ( β=1.88, P<0.001; β=3.24, P<0.001) at 8 years after revaccination. Nobody was found seroconversion of HBsAg, and the anti-HBc positive rate was 14.14% (57/403). Conclusions:Following revaccination with three doses of HepB in adults who were non-responsive to primary immunization, anti-HBs titers declined rapidly within the first four years. They then maintained a stable level after the fifth year. More than half still kept anti-HBs protective titer at eight years after revaccination. The immunity persistence was associated with anti-HBs titer at one month after revaccination.

Objective:To analyze the intensity and epidemiological characteristics of hepatitis B virus (HBV) reactivation among inactive HBsAg carriers (IHC) of rural areas in Ji'nan.Methods:In 2018 and 2020, follow-up investigations were conducted on IHC identified in the population physical examination in Zhangqiu district of Ji'nan. The results of the two follow-up visits were compared to analyze the incidence and distribution characteristics of HBV reactivation in IHC at the community level.Results:A total of 424 IHC completed two follow-up visits, and 47 cases of HBV reactivation were found, the cumulative reactivation rate was 11.08%, and the incidence density was 5.46/100 person-years. Multivariate analysis showed that gender, age, smoking, drinking , family history of liver disease and chronic diseases were not associated with HBV reactivation ( P>0.05), and baseline HBV DNA load was associated with reactivation ( P<0.05), in the HBV DNA level ≥1 000 IU/ml group, the reactivation rate could reach 18.92%. After reactivation, the mean level of ALT increased from baseline and the abnormal rate increased, liver function tended to be abnormal in reactivated patients. 4 (8.51%) reactivators had hepatitis, and 1 (2.13%) had jaundice hepatitis. Conclusions:The incidence of HBV reactivation was higher among IHC in rural communities in Ji'nan. Most of the reactivators were asymptomatic or mildly reactivated. Follow-up of inactive HBsAg patients should be strengthened and changes in ALT and HBV DNA levels should be closely monitored.

Objective:To explore newer enteroviruses (EVs) circulating in China and research their genetic characterization.Methods:Sewage samples were collected in Jinan in January and July of 2018, respectively. PCR amplification of the P1 coding region of EV and next-generation sequencing (NGS) were conducted. Homologous and phylogenetic analyses were performed on the newly identified newer EVs.Results:The EV-A89 (n=2) and EV-C96 (n=1) nucleic acid sequences were detected in the sewage in January and July, respectively and obtained complete P1 coding sequence. The two EV-A89 sequences had 6.1% nucleotide divergence among themselves, and had 88.2%-95.3% homologies with other strains. No close genetic relationship was obtained with the sequences from Xinjiang, China and those from other countries. The EV-C96 sequence in this study had 76.2%-89.4% nucleotide similarities with other isolates throughout the world. Phylogenetic analysis showed that global EV-C96 strains were divided into 5 branches, i. e, A to E. Except for the Shandong 1991 isolate, the other Shandong and domestic strains were all located in branch D.Conclusions:This study added the molecular epidemiologic data of newer enteroviruses EV-A89 and EV-C96, and provides basic data for future research on the epidemic trend of EV-A89 and EV-C96 as well as their association with diseases.

Objective:Investigate and analyze the etiology and serological diagnosis capabilities of pertussis in medical institutions in Shandong Province in 2018.Methods:Using the census method, a questionnaire survey was conducted among 603 second and above level medical institutions in Shandong Province. The deadline for the survey was December 2018, and a total of 543 questionnaires have been recovered, and the validity rate of the questionnaires was 90%. Surveyed the pertussis etiology and serology test items (pertussis IgM and IgG, pertussis nucleic acid and pertussis bacterial culture) and the start time of each test item by questionnaire. The reported cases (confirmed cases and clinically diagnosed cases) between January 1, 2012 and December 31, 2018 were derived from the Chinese Disease Control and Prevention Information System according to the onset date. We used indicators such as fixed-base development speed, chain development speed, and chain growth speed for analysis. The chi test was used to analyze the differences in the composition ratio of medical institutions with detection ability in different levels and regions, and analyze the changes in the number of reported cases before and after the development of pertussis etiology and serology testing.Results:A total of 543 medical institutions accounted for 90.0% (543/603) of all secondary and above level medical institutions in the province, 356 secondary medical institutions (65.6%), and 187 tertiary medical institutions (34.4%). There were 10 medical institutions that carry out pertussis IgM, IgG and nucleic acid testing, accounting for 1.8% (10/543) of the surveyed medical institutions respectively. 2 medical institutions that carried out bacterial culture, accounting for 0.4% of the surveyed medical institutions (2/543). 20 medical institutions have carried out the above tests (8 secondary medical institutions and 12 tertiary medical institutions), accounting for 3.7% (20/543). The proportion of tertiary medical institutions with pertussis IgM, IgG detection and nucleic acid detection capabilities [6.42% (12/187)] was significantly higher than that of secondary medical institutions [2.25% (8/356)] ( χ2=6.01, P=0.014). From 2012 to 2018, the fixed base ratio development speed of reported cases was 3 834.69% in Shandong Province, among which medical institutions with etiology and serological testing capabilities reached 4 533.33%. In 13 medical institutions, the average annual number of reported cases after pertussis etiology and serological testing were higher than that of reported cases before testing. Conclusion:The ability of pertussis etiology and serology diagnosis of secondary and above medical institutions in Shandong Province needs to be improved.

Objective:To analyze the carriage characteristics of Neisseria meningitidis ( Nm) among healthy population of epidemic cerebrospinal meningitis in Shandong province. Methods:From April 2008 to April 2020, a total of 16 848 healthy population were recruited from Lixia District of Jinan City, Gaomi City of Weifang City, Jiaxiang County of Jining City, Wendeng District of Weihai City, Tancheng County of Linyi City and Linyi County of Dezhou City for the investigation.Throat swab samples were collected, Nm was isolated, cultured and identified, and Nm carrying characteristics of healthy population with different characteristics were analyzed. Results:Among the 16 848 healthy population, male accounted for 51.86% (8 737). A total of 136 Nm strains were isolated, and the carriage rate was 0.81%. Among the 136 Nm strains, serogroup B (60.29%) and ungroupable strains (23.53%) were dominant. Analysis of the Nm carriage rate, that were higher in the healthy population of Linyi (1.39%) and Jinan (1.14%), higher in 13-16 years old (1.60%) and 17-19 years old (1.10%) healthy population, and higher in male (1.02%). Conclusion:The Nm carriage rate of healthy population is relatively low in Shandong Province, and the proportion of serogroup B and ungroupable Nm is relatively high.

Objective:Investigate and analyze the etiology and serological diagnosis capabilities of pertussis in medical institutions in Shandong Province in 2018.Methods:Using the census method, a questionnaire survey was conducted among 603 second and above level medical institutions in Shandong Province. The deadline for the survey was December 2018, and a total of 543 questionnaires have been recovered, and the validity rate of the questionnaires was 90%. Surveyed the pertussis etiology and serology test items (pertussis IgM and IgG, pertussis nucleic acid and pertussis bacterial culture) and the start time of each test item by questionnaire. The reported cases (confirmed cases and clinically diagnosed cases) between January 1, 2012 and December 31, 2018 were derived from the Chinese Disease Control and Prevention Information System according to the onset date. We used indicators such as fixed-base development speed, chain development speed, and chain growth speed for analysis. The chi test was used to analyze the differences in the composition ratio of medical institutions with detection ability in different levels and regions, and analyze the changes in the number of reported cases before and after the development of pertussis etiology and serology testing.Results:A total of 543 medical institutions accounted for 90.0% (543/603) of all secondary and above level medical institutions in the province, 356 secondary medical institutions (65.6%), and 187 tertiary medical institutions (34.4%). There were 10 medical institutions that carry out pertussis IgM, IgG and nucleic acid testing, accounting for 1.8% (10/543) of the surveyed medical institutions respectively. 2 medical institutions that carried out bacterial culture, accounting for 0.4% of the surveyed medical institutions (2/543). 20 medical institutions have carried out the above tests (8 secondary medical institutions and 12 tertiary medical institutions), accounting for 3.7% (20/543). The proportion of tertiary medical institutions with pertussis IgM, IgG detection and nucleic acid detection capabilities [6.42% (12/187)] was significantly higher than that of secondary medical institutions [2.25% (8/356)] ( χ2=6.01, P=0.014). From 2012 to 2018, the fixed base ratio development speed of reported cases was 3 834.69% in Shandong Province, among which medical institutions with etiology and serological testing capabilities reached 4 533.33%. In 13 medical institutions, the average annual number of reported cases after pertussis etiology and serological testing were higher than that of reported cases before testing. Conclusion:The ability of pertussis etiology and serology diagnosis of secondary and above medical institutions in Shandong Province needs to be improved.

Objective:To analyze the carriage characteristics of Neisseria meningitidis ( Nm) among healthy population of epidemic cerebrospinal meningitis in Shandong province. Methods:From April 2008 to April 2020, a total of 16 848 healthy population were recruited from Lixia District of Jinan City, Gaomi City of Weifang City, Jiaxiang County of Jining City, Wendeng District of Weihai City, Tancheng County of Linyi City and Linyi County of Dezhou City for the investigation.Throat swab samples were collected, Nm was isolated, cultured and identified, and Nm carrying characteristics of healthy population with different characteristics were analyzed. Results:Among the 16 848 healthy population, male accounted for 51.86% (8 737). A total of 136 Nm strains were isolated, and the carriage rate was 0.81%. Among the 136 Nm strains, serogroup B (60.29%) and ungroupable strains (23.53%) were dominant. Analysis of the Nm carriage rate, that were higher in the healthy population of Linyi (1.39%) and Jinan (1.14%), higher in 13-16 years old (1.60%) and 17-19 years old (1.10%) healthy population, and higher in male (1.02%). Conclusion:The Nm carriage rate of healthy population is relatively low in Shandong Province, and the proportion of serogroup B and ungroupable Nm is relatively high.