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Objective:To systematically review the severe risk in common chronic diseases and coronavirus disease 2019 (COVID-19) cases.Methods:PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Biology Medicine disc, medRxiv, SSRN and ChinaXiv were searched for clinical and epidemiological studies that reported chronic diseases in patients with COVID-19. Only studies of severe COVID-19 in comparison with non-severe controls were included. The prevalence rates of chronic diseases including chronic obstructive pulmonary disease (COPD), diabetes mellitus, hypertension, malignant tumor, cardiovascular diseases, cerebrovascular disease, chronic kidney disease, and chronic liver disease were estimated. Pooled odds ratio ( OR) with 95% confidence interval ( CI) between patients with severe COVID-19 and non-severe groups were calculated. R 3.6.3 software was used for meta-analysis. Results:The search yielded 2 455 articles. A total of 19 eligible comparative studies with 4 792 patients were included in a quantitative analysis. Meta-analysis showed that there was a proportion of 55.0% (95% CI 40.0%-80.0%) male among patients with COVID-19, and the overall pooled prevalence of any chronic diseases in COVID-19 cases was 30.4% (95% CI 24.0%-37.0%). The most prevalent comorbidity was hypertension (16.9%(95% CI 14.0%-20.0%)), followed by diabetes mellitus (8.3%(95% CI 8.0%-9.0%)). The proportion of male patients with severe COVID-19 was higher than that of male patients with non-severe COVID-19 (64.4% vs 52.8%, OR=1.49, 95% CI 1.08-2.05, Z=4.63, P<0.01). The prevalence rates of COPD, cerebrovascular disease, diabetes mellitus, chronic kidney disease, hypertension, cardiovascular diseases and malignant tumor in severe COVID-19 patients were higher than those of non-severe patients ( OR=5.77, 95% CI 3.80-8.74; OR=4.47, 95% CI 2.71-7.38; OR=3.55, 95% CI 2.86-4.40; OR=3.05, 95% CI=1.76-5.28; OR=2.82, 95% CI=1.96-3.97; OR=2.39, 95% CI=1.77-3.23; OR=2.15, 95% CI 1.27-3.66, respectively, Z=8.37, 6.01, 11.60, 4.20, 5.46, 5.71, 3.12, all P<0.01). There was no significant difference in the prevalence of chronic liver disease between severe and non-severe patients ( OR=1.35, 95% CI 0.84-2.17, P=0.11). Conclusion:COVID-19 patients with chronic diseases have higher risk of developing severe disease, and the ORs from high to low are COPD, cerebrovascular disease, diabetes mellitus, chronic kidney disease, hypertension, cardiovascular diseases and malignant tumor.
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Objective@#To estimate the immune memory at 12 years after hepatitis B vaccination and its risk factors among adults.@*Methods@#The study was conducted in 20 villages of Qudi town in Jiyang county, Shandong province, China in 2003. Hepatitis B surface antigen (HBsAg), antibody against HBsAg (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were tested for all healthy residents aged 15-40 years in these villages. Those who had no history of hepatitis B vaccination and were negative for all three indicators were divided into two groups randomly. Hepatitis B vaccine (HepB) was administrated to them on 0-6 month schedule or 0-1-6 month schedule respectively. Blood samples were obtained at one month after the last dose for each receipt and were quantitatively detected for anti-HBs. Finally a total of 629 participants completed HepB vaccination and anti-HBs testing, including 288 of two-dose group and 341 of three-dose group respectively. In 2015, an additional dose of HepB (challenge dose) was administrated to those who were negative for anti-HBs at follow-up (anti-HBs <10 mIU/ml) to evaluate the immune memory. A total of 93 blood samples, including 50 of two-dose group and 43 of three-dose group respectively, were drawn at 14 days after the challenge dose and anti-HBs was quantitatively detected. The anti-HBs geometric mean concentrations (GMCs) after the challenge dose were compared between the two groups. Multivariate linear regression model was built to find the independent risk factors associated with immune memory response (anti-HBs GMC after the challenge dose).@*Results@#The challenge dose of HepB and post-challenge anti-HBs detection were completed among 93 participants. Totally 92 (98.92%, 92/93) participants were found holding immune memory (anti-HBs after the challenge dose was ≥10 mIU/ml). The immune memory positive rates were 100% (50/50) and 97.67% (42/43) in the two-dose group and three-dose group respectively and the corresponding anti-HBs GMC after challenge dose were 2 684.30 (95%CI: 1 721.71-4 185.08) mIU/ml and 3 527.48 (95%CI: 2 145.15-5 800.58) mIU/ml (P=0.410). The anti-HBs GMC after the challenge dose were 1 908.33 (95%CI: 1 190.01-3 060.27) mIU/ml, 4 004.20 (95%CI: 2 257.90-7 101.12) mIU/ml and 8 682.16 (95%CI: 5 813.94-12 965.36) mIU/ml among the participants whose anti-HBs titer was<4, 4-6 and 7-9 mIU/ml at follow-up, respectively (P=0.002). There was no correlation between immune schedule and anti-HBs GMC after the challenge dose; β (95%CI) was -0.07 (-0.34-0.20), P=0.601.@*Conclusion@#The immune memory after primary hepatitis B vaccination lasted for at least 12 years among adults. The immune memory response was independently associated with ant-HBs titer at follow-up, but might be similar between 0-6 month schedule and 0-1-6 month schedule.
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Objective To compare the antibody persistence 5 years after primary immunization with 5 μg and 10 μg recombinant hepatitis B vaccine (HepB) among newborns with normal and high response.Methods Newborns who completed three doses of 5 μ g HepB made by recombinant dexyribonucleic acid technique in Saccharomyces (HepB-SC) or 10 μg HepB made by recombinant dexyribonucleic acid technique in Hansenula polymorpha (HepB-HP) were recruited.Standardized questionnaire was used and blood samples were collected 1-6 months (T0) and five years (T1) after the third dose respectively.The titer of anti-HBs was detected by chemiluminescence microparticle imunoassay (CMIA).Those who achieved normal or high antibody response (anti-HBs titer ≥100 mIU/ml) were included in the study and the positive rate (≥ 10 mIU/ml) and titer of anti-HBs at T1 were compared between 5 μg HepB group and 10 μg HepB group.Multivariable analysis was conducted to identify the independent factors associated with the antibody persistence.Results The positive rate of anti-HBs at T1 was 49.92％ (943/1 883) and 75.92％ (1 135/1 495) respectively in 5 μg HepB group and 10 μg HepB group,the difference was significant (x2=237.75,P＜0.001).The anti-IBs geometric mean concentrations at T1 were 10.23 mIU/ml (95％CI:9.38-11.16) and 28.91 mIU/ml (95％CI:26.65-31.35) in the two groups respectively,the difference was also significant (F=280.36,P＜0.001).Among those whose anti-HBs titer was ＜ 10 mIU/ml at T1,the distributions of anti-HBs titer were significantly different between 5 μg HepB group and 10 μg HepB group (x2=39.75,P＜ 0.001).The multivariable analysis showed that dosage of HepB was independently associated with both positive rate and titer of anti-HBs at T1 after excluding the other factors [P＜0.001,OR=1.44(95％ CI:1.20-1.73);P＜0.001,β =0.27 (95％ CI:0.14-0.40)].Conclusion Five year anti-HBs persistence after primary immunization with 10 μg HepB might be better than that after primary immunization with 5 μg HepB among infants who achieved normal or high anti-HBs response after primary HepB immunization.
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Objective@#To analyze the sero-epidemiological characteristics of hepatitis E virus (HEV) in Shandong province, and thereby to provide evidence for the policy-making of hepatitis E prevention and control.@*Methods@#The inhabitants aged between 1-59 years old were randomly selected to participate in the study by two-stage stratified random sampling method from 12 counties in Shandong province in October, 2014. Firstly two townships were selected from each county by probability proportional to size sampling (PPS) method. A total of 5 229 participants aged 1-59 years old were selected by stratified random sampling method. All the participants finished a questionnaire survey and a venous blood sample (3-5 ml) was collected from each to test anti-HEV IgG by enzyme-linked assay (ELISA). The weighted prevalence of anti-HEV IgG with different demographic characteristics was estimated. The variance of the positive rate of anti-HEV IgG was calculated by Taylor series linearization method, as well as its 95%CI. A statistical test was conducted to compare the rate of its 95%CI, and the results in the present study were compared with those in sero-survey in 2006.@*Results@#A total of 5 229 subjects entered the final analysis in 2014. The overall weighed prevalence of anti-HEV IgG was 9.19% (95%CI: 6.18%-12.20%) among natural population in Shandong province, decreased by 19.88% in comparison with that in 2006 sero-survey (11.47%, 95%CI: 8.92%-14.02%). The prevalence increased with age increasing (χ2trend=288.11, P<0.001) in 2014, which was similar to the result in 2006 sero-survey. Except for 1-4 years old group, the prevalence of anti-HEV IgG in the other age groups were lower than it in the corresponding groups in 2006. The prevalence of anti-HEV IgG in urban (8.19%, 95%CI: 0.00-22.23%), rural areas (9.69%, 95%CI: 4.99%-14.38%), eastern areas (12.70%, 95%CI: 0.00-27.72%), central areas (4.74%, 95%CI: 0.00-9.91%) and western areas (9.32%, 95%CI: 0.69%-17.94%) in 2014 were all lower than the corresponding prevalences (11.39%, 95%CI: 8.17%-14.62%; 11.92%, 95%CI: 8.75%-15.08%; 22.77%, 95%CI: 14.99%-30.55%; 7.97%, 95%CI: 4.75%-11.20%; 10.59%, 95%CI: 6.37%-14.82%) in 2006 survey. The prevalence of anti-HEV IgG in coastal areas (16.56%, 95%CI: 12.94%-20.18%) and inland areas (7.63%, 95%CI: 5.16%-10.10%) in 2014 were lower than it in the corresponding areas (28.04%, 95%CI: 20.45%-35.64%; 9.50%, 95%CI: 7.31%-11.70%) in 2006 survey. The prevalence among peasant (11.98%, 95%CI: 8.20%-15.76%), worker (9.68%, 95%CI: 4.48%-14.88%), cadre (13.90%, 95%CI: 7.47%-20.33%), service provider (12.26%, 95%CI: 1.80%-22.73%) in 2014 survey were lower than it among the corresponding populations (13.76%, 95%CI: 10.15%-17.38%; 21.11%, 95%CI: 12.67%-29.55%; 17.81%, 95%CI: 7.63%-28.00%; 21.08%, 95%CI: 0.03%-42.12%) in 2006 survey.@*Conclusion@#The prevalence of anti-HEV IgG has decreased in Shandong province in the recent years, but the epidemiological characteristics found no obvious changes. HEV susceptibility in natural population was generally high. Hepatitis E vaccines were recommended to be used in HEV high-risk population in the province.
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Objective@#Assess the 4-year antibody against hepatitis B surface antigen (anti-HBs) persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responder infants following primary vaccination.@*Methods@#According to stratified cluster sampling, a total of 4 147 infants were enrolled and primarily vaccinated with 5 μg HepB derived in Saccharomyces Cerevisiae (HepB-SC) at 0-1-6 months schedule from 75 towns of Jinan, Weifang, Yantai, Weihai prefectures, Shandong Province, China in Aug and Sep 2009. Blood samples were collected one to six months after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). 717 infants who appeared low response (10 mU/ml ≤ anti-HBs<100 mU/ml) were revaccinated with 3-dose of HepB. Blood samples were collected from a total of 315 infants one month (T0), four years (T1) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected by CMIA. Information about their birth, primary vaccination were collected. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple non-conditional logistic regression analysis and multifactor linear regression model analysis, respectively.@*Results@#Among 315 children, 165 (52.38%) were male and 150 (47.62%) were female. The positive rate was 83.81% (264/315) at T0 and it decreased to 16.51% (149/529) at T1. The corresponding GMC decreased from 473.15 mU/ml to 17.37 mU/ml. The average annual decreasing rate of positive rate and GMC was 33.38% and 56.23% from T0 to T1. Multivariable analysis showed the positive rate and GMC among those whose anti-HBs titer higher at T0 were significantly higher at T1. The positive rate at T1 among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000, ≥1 000 mU/ml at T0 were significantly higher than those whose anti-HBs titer less than 200 mU/ml. The OR (95%CI) of the positive rate was 4.29 (1.03-17.84), 4.53 (1.25-16.47), 4.19 (1.10-15.97) and 9.13 (2.91-28.63), respectively. The GMC at T1 among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000 mU/ml and those whose anti-HBs titer ≥1 000 mU/ml at T0 were higher than those whose anti-HBs titer<200 mU/ml. The b value (95% CI) of GMC was 0.84 (0.06-1.62), 1.13 (0.46-1.79), 1.33 (0.65-2.01) and 1.88 (1.33-2.44), respectively. GMC among full-term infants were significantly higher than premature infants at T1. The b value (95% CI) of GMC was 0.86 (0.04-1.68).@*Conclusion@#Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responder infants, but still kept good protection. The anti-HBs persistence after revaccination was associated with anti-HBs level of titer one month after revaccination.
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Objective@#To evaluate prevalence of hepatitis A antibody (anti-HAV IgG) among population covered by different hepatitis A vaccine immunization strategies in Shandong Province in 2015.@*Methods@#In October 2015, according to the geographical location of Shandong Province, the stratified random sampling method was used to stratify the 17 municipal distrcts, and the random number table method was used for sampling, First, two eastern cites (Qingdao, Rizhao), two western cities (Liaocheng, Zaozhuang) and three central cities (Jinan, Zibo and Laiwu) were selected; secondly, one county was drawn from each city. Finally, the participants were divided into five age groups including ≤7 years (age group covered by free hepatitis A vaccination strategy), 8-11 years (age group who receive hepatitis A vaccination at their own charge), 12-24 years (age group covered by catch-up vaccination of hepatitis A), 25-34 years (age group born before hepatitis A vaccine was used) and ≥35 years (age group born before hepatitis A vaccine was used). After all the paticipants or their guardians asked and registered basic information such as age, gender, home address, blood samples were collected from them and anti-HAV IgG was detected by ELISA method. The positive rate of anti-HAV IgG and 95%CI were calculated.@*Results@#A total of 1 654 participants were involved in the final analysis, including 856 males (51.75%) and 798 females (48.25%) whose mean age was (13.44±13.06) years. The crude positive rate of anti-HAV IgG was 91.41% (1 512/1 654, 95%CI: 89.96%-92.72%) and the age-adjusted rate was 90.93% (95%CI: 90.92%-90.94%). The positive rates of anti-HAV IgG was at the highest level in the age group of ≤7 years (95.90%, 95%CI: 95.88%-95.91%) and was at the lowest level in the age group of 25-34 years (83.23%, 95%CI: 83.21%-83.25%). The age-specific positive rates of anti-HAV IgG in eastern areas (96.79%, 95%CI: 96.78%-96.80%) were higher than those in both middle areas (86.66%, 95%CI: 86.65%-86.67%) and western areas (91.96%, 95%CI: 91.95%-91.97%).@*Conclusion@#The positive rate of anti-HAV IgG was high among the general population in Shandong Province, but relatively low among young and middle-aged adults. Besides the routine immunization of hepatitis A among the children, more efforts should be taken for the prevention and control of hepatitis A among young and middle-aged adults in Shandong Province, especially in central and western areas.
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Objective@#To know the prevalence of hepatitis B virus (HBV) among women in child-bearing age in Shandong Province, China, providing references to the improvement of HBV control strategy.@*Methods@#The participants were randomly selected by two-stage sampling method from 12 counties which were representative for the whole province. Firstly two townships were selected from each county by probability proportional to size sampling (PPS) method. Then participants aged 1-4 years, 5-14 years, 15-29 years and 30-59 years were selected by stratified random sampling method. The women in child-bearing age (20-49 years) were involved in this study. Questionnaire survey and 5 ml blood collection were conducted among all participants. Blood samples were detected for hepatitis B surface antigen (HBsAg), antibody against HBsAg (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc). Those who were positive for HBsAg were further detected for hepatitis e antigen (HBeAg), antibody against HBeAg (anti-HBe) and the load of HBV DNA. The basic information of the participants including age, gender, occupation, nationality and residence place were collected. The prevalence of HBV infection indicators after weight adjustment were calculated and compared between participants with different demographic characteristics.@*Results@#A total of 1 151 women in child-bearing age were involved in this study. Twenty-seven participants were positive for HBsAg and the prevalence rate was 2.10% (95% CI: 0.97%-3.23%). Five participants were positive for both HBsAg and HBeAg and the prevalence rate was 0.36% (95% CI: 0-0.84%). There were 567 and 291 participants who were positive for anti-HBs and anti-HBc respectively and the corresponding prevalence rates were 47.72% (95%CI: 41.68%-53.75%) and 24.40% (95% CI: 18.50%-30.30%). The number of participants susceptible for HBV was 527 and the percentage of HBV susceptible women was 47.55% (95% CI: 41.63%-53.47%).@*Conclusion@#HBV infection among women in child-bearing age has attained very low level in Shandong Province, China. However, the high proportion of women in child-bearing age were still susceptible for HBV and hepatitis B immunization should be improved among them.
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Objective To compare the antibody persistence 5 years after primary immunization with 5 μg and 10 μg recombinant hepatitis B vaccine (HepB) among newborns with normal and high response.Methods Newborns who completed three doses of 5 μ g HepB made by recombinant dexyribonucleic acid technique in Saccharomyces (HepB-SC) or 10 μg HepB made by recombinant dexyribonucleic acid technique in Hansenula polymorpha (HepB-HP) were recruited.Standardized questionnaire was used and blood samples were collected 1-6 months (T0) and five years (T1) after the third dose respectively.The titer of anti-HBs was detected by chemiluminescence microparticle imunoassay (CMIA).Those who achieved normal or high antibody response (anti-HBs titer ≥100 mIU/ml) were included in the study and the positive rate (≥ 10 mIU/ml) and titer of anti-HBs at T1 were compared between 5 μg HepB group and 10 μg HepB group.Multivariable analysis was conducted to identify the independent factors associated with the antibody persistence.Results The positive rate of anti-HBs at T1 was 49.92％ (943/1 883) and 75.92％ (1 135/1 495) respectively in 5 μg HepB group and 10 μg HepB group,the difference was significant (x2=237.75,P＜0.001).The anti-IBs geometric mean concentrations at T1 were 10.23 mIU/ml (95％CI:9.38-11.16) and 28.91 mIU/ml (95％CI:26.65-31.35) in the two groups respectively,the difference was also significant (F=280.36,P＜0.001).Among those whose anti-HBs titer was ＜ 10 mIU/ml at T1,the distributions of anti-HBs titer were significantly different between 5 μg HepB group and 10 μg HepB group (x2=39.75,P＜ 0.001).The multivariable analysis showed that dosage of HepB was independently associated with both positive rate and titer of anti-HBs at T1 after excluding the other factors [P＜0.001,OR=1.44(95％ CI:1.20-1.73);P＜0.001,β =0.27 (95％ CI:0.14-0.40)].Conclusion Five year anti-HBs persistence after primary immunization with 10 μg HepB might be better than that after primary immunization with 5 μg HepB among infants who achieved normal or high anti-HBs response after primary HepB immunization.
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Objective The aim of this study is to analyze the long-time outcome of hepatocellular carcinoma(HCC)patients with micro-vascular invasion underwent liver resection combined with transarterial chemoembolization(TACE).Methods Our database of surgical re-section from January 2009 to September 2015 was retrospectively analyzed.This study was conducted on 296 HCC patients with MVI.Patients were divided into two groups:one group underwent liver resection (n =159)and another for liver resection combined with TACE (n =137). The 5-year overall survival rate (OS)and disease free survival (DFR)were compared.A multivariate Cox proportional hazards regression a-nalysis was performed to assess the prognostic risk factors associated with overall survival rate.Results The 5-year OS and 5-year DFR see significant difference (OS:18% vs.8%,P =0.001;TRF:15% vs.8%,P =0.008).Multivariate analysis revealed that HBsAg(HR 1.596, P =0.002,95% CI 1.194 ~2.131),tumor size >5 cm(HR 0.729,P =0.042,95% CI 0.539 ~0.989)as well as multiple tumors(HR 1.480,P =0.049,95% CI 1.002 ~2.186)were correlated to poor overall survival rate.Conclusion Surgical resection combined TACE for HCC patients with MVI realized a better prognosis than patients merely underwent therapy of resection.
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<p><b>OBJECTIVE</b>To examine the influence of three-booster-doses hepatitis B vaccines on children with normal and high antibody response to primary vaccination.</p><p><b>METHODS</b>Antibody against hepatitis B surface antigen (anti-HBs) were detected after primary vaccination and children with normal or high response to hepatitis B primary vaccination at infancy, were identified. Children who were given three booster doses were selected to form the booster group and who were given no booster dose were 1∶1 matched with the same gender and residence to form the control group. Blood samples were obtained from all the participants and tested for anti-HBs and anti-HBc, 5 years after the primary vaccination.</p><p><b>RESULTS</b>The positive rates of anti-HBs response to primary vaccination were 97.39% (224/230, 95% CI: 94.41%-99.04%) in the booster group and 53.91% (124/230, 95% CI: 47.24%-60.48%) in the control group (P<0.05), 5 years after the primary vaccination. Geometric mean concentration (GMC) of anti-HBs were 1 140.02 (887.46-1 464.46) mIU/ml in the booster group and 11.53 (8.73-15.23) mIU/ml in the control group (P<0.05). The prevalence rates of breakthrough HBV infection were 0.87% (2/230) in the booster group and 2.17%(5/230) in the control group (P>0.05). RESULTS from the multivariable analysis showed that the booster doses (OR=38.75, 95%CI: 16.23-92.54) and the level of anti-HBs after the primary vaccination (OR =3.06, 95%CI:1.51-6.17) were independently associated with the positive rates of anti-HBs, 5 years after the primary vaccination (P<0.05).</p><p><b>CONCLUSION</b>Programs with three booster doses to children that showing normal and high antibody response to primary vaccination could improve the persistence of anti-HBs but possibly would not be able to prevent the HBV infection.</p>
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Child , Humans , Infant , Antibody Formation , Case-Control Studies , Hepatitis B , Hepatitis B Antibodies , Blood , Allergy and Immunology , Hepatitis B Surface Antigens , Allergy and Immunology , Hepatitis B Vaccines , Allergy and Immunology , Hepatitis B virus , Immunization, Secondary , Prevalence , Treatment Outcome , VaccinationABSTRACT
<p><b>OBJECTIVE</b>To access the antibody persistence 24-month after revaccination with 3-dose of hepatitis B vaccine (HepB) among non-response adults.</p><p><b>METHODS</b>A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-, 1-, 6-months schedule: 20 µg HepB derived in Saccharomyces Cerevisiae (HepB-SC), 20 µg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 µg HepB-SC and 10 µg HepB derived in Hansenula Polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The non-responders were revaccinated with three doses of HepB at 0-, 1-, 6-months schedule and the type of HepB was the same as which was used for primary immunization. Blood samples were collected one month (T1) and two years (T24) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface angtigen (HBsAg) (if anti-HBs < 10 mU/ml) were detected by CMIA. χ(2) test was used to compared age, gender and body mass index (BMI) between different groups and the anti-HBs positive rate at T1 and T24; analysis of variance (ANOVA) was used to compare the geometric mean concentration (GMC) of anti-HBs between difference groups. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis respectively.</p><p><b>RESULTS</b>A total of 900 non-responders were identified and 71.7% (645/900) of them completed three-dose revaccination and blood collection after revaccination. 467 (72.4%) non-responsive adults were followed up at T24. The anti-HBs positive rate decreased from 85.65% (95% CI: 82.14%-88.71%) at T1 to 60.60% (95% CI: 56.01%-65.06%) at T24 and the corresponding GMC decreased from 175.62 (95% CI: 139.03-221.84) mU/ml to 21.43 (95% CI: 17.62-26.06) mU/ml. Multivariate analysis showed that positive rate of anti-HBs at T24 was associated with gender, HepB type for revaccination and anti-HBs level at T1, but only anti-HBs level at T1 was associated with the anti-HBs titer at T24. No subject showed HBsAg seroconversion and anti-HBc conversion rate was 3.64% (17/467) at T24.</p><p><b>CONCLUSION</b>Anti-HBs titer decreases rapidly two years after HepB revaccination among non-responsive adults, but more than half non-responderd still kept anti-HBs above protective level. The immunity durability after revaccination was associated with gender, HepB type for revaccination and anti-HBs titer one month after revaccination.</p>
Subject(s)
Adolescent , Adult , Animals , Cricetinae , Female , Humans , Male , Middle Aged , Young Adult , Body Mass Index , CHO Cells , China , Cricetulus , Enzyme-Linked Immunosorbent Assay , Follow-Up Studies , Hepatitis B , Hepatitis B Antibodies , Blood , Hepatitis B Core Antigens , Allergy and Immunology , Hepatitis B Surface Antigens , Allergy and Immunology , Hepatitis B Vaccines , Classification , Immunization, Secondary , Multivariate Analysis , Pichia , Risk Factors , Saccharomyces cerevisiae , Seroconversion , VaccinationABSTRACT
<p><b>OBJECTIVE</b>To examine the immune memory status to hepatitis B vaccine among infants with normal or high antibody response to primary vaccination, 5 years after the primary vaccination and the risk factors associated with the immune memory.</p><p><b>METHODS</b>Titers of the antibody against hepatitis B surface antigen (anti-HBs) were detected, five years after the primary vaccination among children who appeared normal or high response to hepatitis B primary vaccination in infancy. Those whose anti-HBs titers were low than protective level (10 mIU/ml) were given a challenge dose of hepatitis B vaccine and titers of anti-HBs were detected 14 days after the challenge. Positive rate and geometric mean titer (GMT) of anti-HBs were calculated. Level of the anti-HBs titers after primary vaccination, at following-up and after the challenge periods were divided into different levels, respectively. Risk factors associated with the levels of anti-HBs titer after the challenge were examined by univariate analysis that and multivariable analysis.</p><p><b>RESULTS</b>Anti-HBs waned to the level below protective standard among 37.98% of the children with normal or high antibody response to hepatitis B primary vaccination; among those children whose anti-HBs were below the protection standard. The seroconversion rate and GMT of anti-HBs after the challenge dose were 98.95% (757/765) and 2 811.69 mIU/ml [95% Confidence Interval (CI) :2 513.55-3 145.19 mIU/ml] , respectively. Titers and levels of anti-HBs after the challenge, appeared an increase with anti-HBs after primary vaccination and the anti-HBs in the following-up (F=5.46, 10.23 respectively; P<0.000 1 for both) periods. Results from the multivariable analysis showed that gender, premature birth and birth weight were factors insignificantly associated with the anti-HBs titers after the dose of challenge, while the anti-HBs levels were independently associated with the levels of anti-HBs titer after the challenge [OR = 1.001 (95%CI: 1.000-1.002) , P<0.001; OR=1.28 (95%CI: 1.81-1.39) , P<0.001]at the following-up periods.</p><p><b>CONCLUSIONS</b>Strong immune memory could be found among those children with normal or high responses to hepatitis B vaccination, 5 years after the primary vaccination. The intensity of immune memory might be associated with the anti-HBs titer after primary vaccination as well as the anti-HBs titers before the challenge dose was given.</p>
Subject(s)
Child , Humans , Infant , Antibody Formation , Follow-Up Studies , Hepatitis B , Hepatitis B Antibodies , Hepatitis B Surface Antigens , Allergy and Immunology , Hepatitis B Vaccines , Allergy and Immunology , Immunization , Immunologic Memory , Risk Factors , SeroconversionABSTRACT
Objective To compare the antibody response between adults with hepatitis B virus(HBV)core antibody(anti-HBc)single positivity and healthy adults after primary immunization and revaccination of hepatitis B vaccine(HepB). Methods Adults aged from 18 to 49 who were both negative for HBV surface antigen(HBsAg)and antibody to HBsAg(anti-HBs),but positive for anti-HBc and narrated no history of HepB immunization by themselves,were selected as single anti-HBc positive group(‘anti-HBc alone’). Adults who were negative for HBsAg,anti-HBs and anti-HBc,with age differences within 2 years,and same gender under the 1 ∶ 1 matching program, were selected to form the control group. Both groups were vaccinated on 0-1-6 schedule with the same HepB. Those who were non-response to HepB at primary immunization were revaccination on 0-1-6 schedule. Response rates and geometric mean concentrations(GMC)between the two groups were compared. Results In total,the number of anticipants were 228 pairs. Rates on non-response, low-response,normal-response and high-response after the primary immunization were 8.77%, 11.84%,31.14%and 48.25%in the control group respectively. The corresponding rates were 8.33%, 30.70%,35.96%and 25.00%in the‘anti-HBc alone’. The rate of low-response in the control group was lower than that in the‘anti-HBc alone’(χ2=22.28,P<0.01),while the rate of high-response was higher than that in the control group(χ2=24.43,P<0.01). GMC of anti-HBs in the control group (534.07 mIU/ml) was higher than that in the‘anti-HBc alone’(183.99 mIU/ml)(u=4.42,P<0.01). The anti-HBs conversion rates were 82.35% and 41.18% in the control group and in the‘anti-HBc alone’respectively after the first-dose revaccination,but increased to 90.00%and 82.35%after the third-dose revaccination. The anti-HBs conversion rates in the control group were higher than that in the‘anti-HBc alone’ after the first-dose revaccination (P<0.05),while there was no difference seen between the two groups after the third-dose revaccination (P>0.05). Conclusion Immune response in the anti-HBc positive adults after primary immunization was weaker than that in common adults. However,immune response induced by HepB was enough to prevent them from infecting HBV. The rates of response showed an obvious increase after revaccination,hence the same HepB immunization strategy could be used.
ABSTRACT
Objective To compare the antibody response between adults with hepatitis B virus(HBV)core antibody(anti-HBc)single positivity and healthy adults after primary immunization and revaccination of hepatitis B vaccine(HepB). Methods Adults aged from 18 to 49 who were both negative for HBV surface antigen(HBsAg)and antibody to HBsAg(anti-HBs),but positive for anti-HBc and narrated no history of HepB immunization by themselves,were selected as single anti-HBc positive group(‘anti-HBc alone’). Adults who were negative for HBsAg,anti-HBs and anti-HBc,with age differences within 2 years,and same gender under the 1 ∶ 1 matching program, were selected to form the control group. Both groups were vaccinated on 0-1-6 schedule with the same HepB. Those who were non-response to HepB at primary immunization were revaccination on 0-1-6 schedule. Response rates and geometric mean concentrations(GMC)between the two groups were compared. Results In total,the number of anticipants were 228 pairs. Rates on non-response, low-response,normal-response and high-response after the primary immunization were 8.77%, 11.84%,31.14%and 48.25%in the control group respectively. The corresponding rates were 8.33%, 30.70%,35.96%and 25.00%in the‘anti-HBc alone’. The rate of low-response in the control group was lower than that in the‘anti-HBc alone’(χ2=22.28,P<0.01),while the rate of high-response was higher than that in the control group(χ2=24.43,P<0.01). GMC of anti-HBs in the control group (534.07 mIU/ml) was higher than that in the‘anti-HBc alone’(183.99 mIU/ml)(u=4.42,P<0.01). The anti-HBs conversion rates were 82.35% and 41.18% in the control group and in the‘anti-HBc alone’respectively after the first-dose revaccination,but increased to 90.00%and 82.35%after the third-dose revaccination. The anti-HBs conversion rates in the control group were higher than that in the‘anti-HBc alone’ after the first-dose revaccination (P<0.05),while there was no difference seen between the two groups after the third-dose revaccination (P>0.05). Conclusion Immune response in the anti-HBc positive adults after primary immunization was weaker than that in common adults. However,immune response induced by HepB was enough to prevent them from infecting HBV. The rates of response showed an obvious increase after revaccination,hence the same HepB immunization strategy could be used.
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<p><b>OBJECTIVE</b>To assess the 24-month efficacy after booster vaccination with 3 doses of hepatitis B vaccine among low-response adults in Zhangqiu county of Shandong province.</p><p><b>METHODS</b>A total of 24 237 adults aged 18-49 years old, never received HepB vaccination, without HBV infection history, and had been living at 3 towns of Zhangqiu county in Shandong province for more than half a year in september, 2009, were collected blood samples of 3-5 ml. A total of 11 590 adults who were negative for hepatitis B virus (HBV) surface antigen (HBsAg) , antibody to HBsAg (Anti-HBs) and antibody to HBV core antigen (Anti-HBc), were divided into four groups randomly and were vaccinated following the schedule of 0-1-6 with 20 µg hepatitis B vaccine made by recombinant deoxyribonucleic acid techniques in Saccharomyces cerevisiae (HepB-SC), 20 µg hepatitis B vaccine made by Chinese hamster ovary cell (HepB-CHO), 10 µg HepB-SC and 10 µg hepatitis B vaccine made by recombinant deoxyribonucleic acid techniques in Hansenula Polymorpha (HepB-HP), respectively. The adults who were low-response to the primary hepatitis B vaccination (10 mU/ml ≤ anti-HBs<100 mU/ml) were divided into four groups by cluster random sampling. These groups were revaccinated with 3-dose of above-mentioned four kinds of HepB respectively. Blood samples were drawn from 1 month (T1) and 24 month (T24) after the 3 dose revaccination, respectively. Anti-HBs and anti-HBc was detected by Chemiluminescence Microparticle Imunoassay (CMIA).</p><p><b>RESULTS</b>Out of the 8 592 adults who have accepted the primary vaccination of hepatitis B and been collected the blood samples, 1 306 subjects showed low-response. A total of 718 low-response subjects were collected blood samples after T1 and T24 following 3 doses of booster vaccination. The proportion of the four groups was 32.3% (232/718), 25.8% (185/718) , 19.3% (139/718) , 22.6% (162/718) , respectively. The average proportion of anti-HBs ≥ 100 mIU/ml were decreased from 77.58% after T1 to 35.63% after T24 (χ² = 256.87, P < 0.01). The proportion of anti-HBs ≥ 100 mIU/ml in T24 were 38.8% (90/177), 39.5% (73/185), 25.2% (35/139) and 35.8% (58/162) in four groups, respectively. The proportion of anti-HBs>100 mIU/ml in T24 was significantly different among groups (χ² = 8.81, P = 0.032). The average geometric mean concentration (GMC) was significantly reduced from 443.53 mIU/ml after T1 to 48.98 mIU/ml after T24 (F = 439.41, P < 0.01). The GMC was 60.26 (45.71-77.62), 1.29 (38.90-69.18) , 35.48 (25.70-48.98) and 46.77 (33.88-6.07) mIU/ml in four groups, respectively (F = 1.97, P = 0.117) . Compared with vaccinated 20 µg HepB-SC, the proportion of anti-HBs ≥ 100 mIU/ml and GMC was 0.56 (0.35-0.91) and -0.20 (-0.39--0.02) times. The positive of HBsAg was not found and the positive rate of anti-HBc was 2.6% (18/692) in T24.</p><p><b>CONCLUSION</b>Protective antibody following booster vaccination with three doses of hepatitis B vaccines among low-response adults after 2 years fade faster. Antibody level of anti-HBs in T24 was corrected with the booster vaccine type and age. 20 µgHepB-SC seemed better than 10 µg HepB-SC.</p>
Subject(s)
Adult , Animals , Humans , CHO Cells , Cricetulus , Follow-Up Studies , Hepatitis B , Hepatitis B Antibodies , Hepatitis B Surface Antigens , Hepatitis B Vaccines , Hepatitis B virus , Immunization, Secondary , Pichia , VaccinationABSTRACT
<p><b>OBJECTIVE</b>To compare the antibody response between adults with hepatitis B virus (HBV) core antibody (anti-HBc) single positivity and healthy adults after primary immunization and revaccination of hepatitis B vaccine(HepB).</p><p><b>METHODS</b>Adults aged from 18 to 49 who were both negative for HBV surface antigen (HBsAg) and antibody to HBsAg (anti-HBs), but positive for anti-HBc and narrated no history of HepB immunization by themselves, were selected as single anti-HBc positive group ('anti-HBc alone'). Adults who were negative for HBsAg, anti-HBs and anti-HBc, with age differences within 2 years, and same gender under the 1 : 1 matching program, were selected to form the control group. Both groups were vaccinated on 0-1-6 schedule with the same HepB. Those who were non-response to HepB at primary immunization were revaccination on 0-1-6 schedule. Response rates and geometric mean concentrations (GMC) between the two groups were compared.</p><p><b>RESULTS</b>In total, the number of anticipants were 228 pairs. Rates on non-response, low-response, normal-response and high-response after the primary immunization were 8.77% , 11.84%, 31.14% and 48.25% in the control group respectively. The corresponding rates were 8.33%, 30.70%, 35.96% and 25.00% in the 'anti-HBc alone'. The rate of low-response in the control group was lower than that in the 'anti-HBc alone' (χ(2) = 22.28, P < 0.01), while the rate of high-response was higher than that in the control group (χ(2) = 24.43, P < 0.01). GMC of anti-HBs in the control group (534.07 mIU/ml) was higher than that in the 'anti-HBc alone' (183.99 mIU/ml) (u = 4.42, P < 0.01). The anti-HBs conversion rates were 82.35% and 41.18% in the control group and in the 'anti-HBc alone' respectively after the first-dose revaccination, but increased to 90.00% and 82.35% after the third-dose revaccination. The anti-HBs conversion rates in the control group were higher than that in the 'anti-HBc alone' after the first-dose revaccination (P < 0.05), while there was no difference seen between the two groups after the third-dose revaccination (P > 0.05).</p><p><b>CONCLUSION</b>Immune response in the anti-HBc positive adults after primary immunization was weaker than that in common adults. However, immune response induced by HepB was enough to prevent them from infecting HBV. The rates of response showed an obvious increase after revaccination, hence the same HepB immunization strategy could be used.</p>